Setting and data collection
This study was performed using a database from the Division of Thyroid Surgery, China-Japan Union Hospital of Jilin University. The patients in this study were diagnosed with PTC at our institute between June 2008 and December 2017.
Ethics statement
This study was approved by the Health Care Ethics Committee of the China-Japan Union Hospital of Jilin University (No. 2019040806).
Participants
This study is a retrospective analysis of patients with operable PTC. All the patients eligible for this analysis received central neck node dissection. Patients were aged ≥ 18 years, pathologically-confirmed to have PTC, and normal weight or obese (according to WHO standards). The exclusion criteria included: non-PTC patients, other thyroid cancer subtypes, different types of cancer, and patients requiring reoperations (Fig. 1).
Treatments
Oncological treatment, which ranged from surgery to radioactive iodine (RAI), was standardized for all patients and in accordance with the multidisciplinary tumor board consensus. The histological subtype was assessed according to the WHO classification. According to the Chinese guidelines for diagnosis and treatment of differentiated thyroid, all patients with thyroid cancer routinely underwent prophylactic central neck dissection (CND) (14). For those LNs suggested to be malignant by ultrasonography, fine needle aspiration cytology (FNAC) was used to confirm the diagnosis. Patients with cervical lymph node metastasis were confirmed by preoperative FNAC or intraoperative frozen pathological examinations. These patients underwent therapeutic cervical lymph node dissection. Prophylactic cervical lymph node dissection was not recommended. The upper bound of the range of CND is the lower hyoid bone, the lower bound is the superior sternum fossa, the outside is the common carotid artery, and the inside is the inside of the trachea. The lateral LN dissection minimum ranged from the IIa, III, IV, and Vb area, while other areas were treated according to the results of the FNAC.
Definitions
Body-mass index. According to the WHO-BMI standard, BMI is between 18.5 ≤ BMI < 25 kg/m2, which was defined as normal-weight. Obesity is defined as BMI ≥ 30 kg/m2 (15). Height and weight measurements used to calculate the BMI were retrieved from electronic registration databases. BMI was calculated as weight divided by height squared. Upon the first admission, the demographics and clinical data, including height and weight, were recorded.
Pattern of metastatic LNs. The pattern of metastatic LNs included the rate of metastatic LNs, the number of metastatic LNs, the number of dissected LNs, the lymph node ratio (LNR), the maximum diameter of positive LNs, and the rate of LN skip metastasis.
Maximum diameter of positive LNs. The maximal tumor diameter of the largest metastatic LN using the concept of micro-metastases in breast cancer (16).
Lymph node ratio (LNR). LNR was defined as the number of nodes involved by the tumor divided by the total number of resected lymph nodes during the surgical treatment.
LN skip metastasis. Defined as a lateral lymph node metastasis without central lymph node involvement.
Pathological examination
Specimens removed during the operation were submitted for histological analysis to determine the presence and size of metastatic LNs. For this study, an experienced pathologist reviewed the pathological slides and measured the properties of each LN.
Outcomes and covariates
We used BMI as an index and further correlated it with the presence and pattern of LN metastases. Patients were identified as LN positive if they had a pathologic LN status of pN1a or pN1b. Based on prior studies, we included important predictors of LN status in multivariable models (17). For example, information regarding the following thyroid tumor characteristics was obtained from medical records: age, weight, height, tumor size (mm), multifocality, extrathyroidal extension, rate of metastatic LNs (%), number of metastatic LNs, number of LN dissections, LNR (%), maximum diameter of positive LNs (mm), and LN skip metastasis (%).
Statistical analysis
All data were collected using Microsoft Excel (Microsoft Corporation, Redmond, WA, USA). Continuous variables were expressed as mean (standard deviation), and categorical variables were expressed as a percentage (frequency). Continuous variables were analyzed by the t-test or one-way analysis of variance (ANOVA). Categorical variables were examined using the χ2-test or Fischer’s exact test. P < 0.05 was considered statistically significant. Statistical analysis was performed using SPSS 22.0 software (IBM, Chicago, IL, USA).