The diagnostic value of GICA used for intraoperative lymph node FNA-Tg measurement to evaluate thyroid cancer metastases

in European Thyroid Journal
Authors:
Shaodong Hou Department of Breast and Thyroid Surgery, Chongqing General Hospital, Chongqing, China
Clinical Medical College, North Sichuan Medical College, Nanchong, Sichuan, China

Search for other papers by Shaodong Hou in
Current site
Google Scholar
PubMed
Close
,
Yiceng Sun Department of Breast and Thyroid Surgery, Chongqing General Hospital, Chongqing, China

Search for other papers by Yiceng Sun in
Current site
Google Scholar
PubMed
Close
,
Zeyu Yang Department of Breast and Thyroid Surgery, Chongqing General Hospital, Chongqing, China

Search for other papers by Zeyu Yang in
Current site
Google Scholar
PubMed
Close
,
Mi Tang Department of Breast and Thyroid Surgery, Chongqing General Hospital, Chongqing, China

Search for other papers by Mi Tang in
Current site
Google Scholar
PubMed
Close
,
Tingjie Yin Department of Breast and Thyroid Surgery, Chongqing General Hospital, Chongqing, China

Search for other papers by Tingjie Yin in
Current site
Google Scholar
PubMed
Close
,
Cong Shao Department of Breast and Thyroid Surgery, Chongqing General Hospital, Chongqing, China

Search for other papers by Cong Shao in
Current site
Google Scholar
PubMed
Close
,
Cunye Yan Department of Breast and Thyroid Surgery, Chongqing General Hospital, Chongqing, China

Search for other papers by Cunye Yan in
Current site
Google Scholar
PubMed
Close
,
Linlong Mo Department of Breast and Thyroid Surgery, Chongqing General Hospital, Chongqing, China

Search for other papers by Linlong Mo in
Current site
Google Scholar
PubMed
Close
,
Yuquan Yuan Department of Breast and Thyroid Surgery, Chongqing General Hospital, Chongqing, China

Search for other papers by Yuquan Yuan in
Current site
Google Scholar
PubMed
Close
,
Supeng Yin Department of Breast and Thyroid Surgery, Chongqing General Hospital, Chongqing, China

Search for other papers by Supeng Yin in
Current site
Google Scholar
PubMed
Close
, and
Fan Zhang Department of Breast and Thyroid Surgery, Chongqing General Hospital, Chongqing, China
Clinical Medical College, North Sichuan Medical College, Nanchong, Sichuan, China

Search for other papers by Fan Zhang in
Current site
Google Scholar
PubMed
Close
https://orcid.org/0000-0002-6758-2856

Correspondence should be addressed to S Yin or F Zhang: yinsupeng@163.com or zhangfancgh@163.com

*(S Hou and Y Sun contributed equally to this work)

Open access

Sign up for journal news

Objective

It is crucial to diagnose lymph node (LN) metastases (LNM) before or during thyroid carcinoma surgery. Measurement of thyroglobulin (Tg) in the fine needle aspirate washout (FNA-Tg) is useful to assist in the diagnosis of LNM for papillary thyroid carcinoma (PTC). This study aimed to assess the diagnostic performance of a new technique based on a colloidal gold-based immunochromatographic assay (GICA) for intraoperative FNA-Tg in diagnosing LNM.

Clinical trial information

This study is registered with chictr.org.cn, ID: ChiCTR2200063561 (registered 11 September, 2022).

Methods

This prospective study enrolled 51 PTC patients who underwent cervical LN dissection. A total of 150 LNs dissected from the central and lateral compartments were evaluated by FNA-Tg-GICA at three different time points and compared with frozen sections and the conventional Tg measurement method electrochemiluminescence immunoassay (ECLIA). Receiver operating characteristic curve (ROC) and area under the curve (AUC), cutoff value to discriminate benign and malignant LNs, sensitivity, specificity, and accuracy were provided.

Results

The cutoff value of FNA-Tg to predict LNM was 110.83 ng/mL for ECLIA and 13.19 ng/mL, 38.69 ng/mL, and 77.17 ng/mL for GICA at 3, 10, and 15 min, respectively. There was no significant difference between the AUCs of GICA at different time points compared to using ECLIA and frozen sections. Besides, the diagnostic performance of GICA and ECLIA showed no significant difference in evaluating LNM from central and lateral compartments or between the TgAb-positive subgroup and TgAb-negative subgroup.

Conclusion

GICA is a promising method for intraoperative FNA-Tg measurement and has high value in predicting LNM. It may be a novel alternative or supplementary method to frozen section or ECLIA.

Abstract

Objective

It is crucial to diagnose lymph node (LN) metastases (LNM) before or during thyroid carcinoma surgery. Measurement of thyroglobulin (Tg) in the fine needle aspirate washout (FNA-Tg) is useful to assist in the diagnosis of LNM for papillary thyroid carcinoma (PTC). This study aimed to assess the diagnostic performance of a new technique based on a colloidal gold-based immunochromatographic assay (GICA) for intraoperative FNA-Tg in diagnosing LNM.

Clinical trial information

This study is registered with chictr.org.cn, ID: ChiCTR2200063561 (registered 11 September, 2022).

Methods

This prospective study enrolled 51 PTC patients who underwent cervical LN dissection. A total of 150 LNs dissected from the central and lateral compartments were evaluated by FNA-Tg-GICA at three different time points and compared with frozen sections and the conventional Tg measurement method electrochemiluminescence immunoassay (ECLIA). Receiver operating characteristic curve (ROC) and area under the curve (AUC), cutoff value to discriminate benign and malignant LNs, sensitivity, specificity, and accuracy were provided.

Results

The cutoff value of FNA-Tg to predict LNM was 110.83 ng/mL for ECLIA and 13.19 ng/mL, 38.69 ng/mL, and 77.17 ng/mL for GICA at 3, 10, and 15 min, respectively. There was no significant difference between the AUCs of GICA at different time points compared to using ECLIA and frozen sections. Besides, the diagnostic performance of GICA and ECLIA showed no significant difference in evaluating LNM from central and lateral compartments or between the TgAb-positive subgroup and TgAb-negative subgroup.

Conclusion

GICA is a promising method for intraoperative FNA-Tg measurement and has high value in predicting LNM. It may be a novel alternative or supplementary method to frozen section or ECLIA.

Introduction

By 2020, thyroid cancer had ranked as the fifth most prevalent cancer in women and the 11th most common cancer overall, with a sharp increase in its frequency worldwide (1). Papillary thyroid carcinoma (PTC) is the most common subtype of thyroid cancer, accounting for 85% of all cases (2). It is estimated that 30–80% of individuals with PTC have cervical lymph node (LN) metastases (LNM) at initial diagnosis (3). Thus, it is crucial to distinguish metastatic LNs from benign LNs before or during surgery, which would help surgeons choose the appropriate surgical scope and prevent over- or undertreatment.

Neck ultrasonography (US) and US-guided fine needle aspiration cytology (FNAC) are routinely used for LNM screening preoperatively. However, the sensitivity and specificity of US in the diagnosis of LNM are limited and rely on the experience of the radiologist to a large extent. It has been reported that preoperative US can only identify malignant central compartment LNs in 20–30% of cases (4, 5). LNs that are suspicious for metastases on US would undergo FNAC. However, the sensitivity of FNAC varies from 75% to 85% with a high rate of nondiagnostic samples (6). The diagnostic efficacy of FNAC may be affected by the tiny size, necrosis, lack of epithelial component in cyst aspirates, or inaccessible position of the LNs (7, 8). During the operation, intraoperative frozen section pathology is usually used for the diagnosis of suspicious LNs. Although the accuracy of frozen sections is relatively high, this approach still has some drawbacks, such as the requirement of some advanced equipment and experienced pathologists.

Thyroglobulin (Tg) is a macromolecular tetrameric glycoprotein with a molecular weight of 600 kDa and is produced and released by thyroid follicular epithelial cells (9). In 1992, Pacini et al. first suggested that elevated concentrations of Tg in fine needle aspirate washout (FNA-Tg) of nonthyroidal neck nodes could assist in the diagnosis of metastases from differentiated thyroid cancer (DTC) (6). Since then, a variety of studies have demonstrated the high sensitivity (92–95%) and specificity (91–93%) of this method in the diagnosis of LNM (3, 8, 10, 11, 12, 13).

Electrochemiluminescence immunoassay (ECLIA) is the most common approach used for Tg measurement because of its high reproducibility, sensitivity, and stability (14). However, this assay for Tg testing requires expensive equipment and specially trained technical staff, is generally carried out in the laboratory, and takes several hours. Currently, a new technique based on colloidal gold-based immunochromatographic assay (GICA) for Tg measurement has been developed. The device used by GICA is portable and can be placed in the operating room. This novel method for Tg measurement is quantitative, easy to operate, and time-saving, as it works within a few minutes.

In this study, we used GICA to measure FNA-Tg intraoperatively and evaluated its efficacy in diagnosing LNM of PTC by comparison with ECLIA and frozen section. We also explored the cutoff value of FNA-Tg and the optimum timing of GICA to diagnose LNM. It may provide a novel, accurate, convenient, and rapid method for LNM diagnosis during thyroidectomy.

Materials and methods

Patients

This study enrolled 51 PTC patients who underwent therapeutic or prophylactic cervical LN dissection between September 2022 and January 2023 in the Department of Breast and Thyroid Surgery of Chongqing General Hospital. The LNs were divided into two groups: the central compartment group and the lateral compartment group. The study was approved by the ethics committee of Chongqing General Hospital (Chongqing, China) and was registered with the Chinese Clinical Trial Register (www.chictr.org.cn, identifier ChiCTR2200063561). Written informed consent was obtained from all individual participants included in the study.

FNA procedure

During the operation, after the LNs of the central compartment or lateral compartment were dissected, an experienced surgeon selected one or two macroscopically abnormal and one or two apparently normal LNs in every patient. FNA was performed using a 23G needle with a 5 mL syringe. The needle was repeatedly moved four to six times inside each LN along its major axis until the needle hub was filled with LN tissue. Immediately after aspiration, the needle and syringe were washed with 1 mL of saline solution. Then, 80 μL of washout fluid were pipetted for Tg measurement by GICA (Fig. 1A and B). The remaining washout was sent to the laboratory for Tg measurement by ECLIA using a commercially available kit (Roche E170 Modular Immunoassay Analyzer). The Tg-ECLIA method was registered by the vendor exclusively for serum samples. Based on previous studies (15, 16, 17), our clinical practice data consistently confirm that ECLIA is an effective tool for the detection of FNA-Tg, the assay’s quantification range for Tg concentration spans from 0 to 481 ng/mL.

Figure 1
Figure 1

The detection procedure for GICA assay. A. A lymph node is aspirated along its long axis using a thin 23G needle. B andC. The washout sample is then deposited into the hole of a test strip. Through capillary action, the Tg in the sample flows along the strip and reacts with anti-Tg antibodies embedded on the strip’s membrane. D. The reaction in the test zone on the membrane. If Tg is present in the sample, the test zone turns red (bottom strip), while a negative sample leaves it blank (upper strip). E. The intensity of the color is measured by an instrument to quantify the concentration of Tg.

Citation: European Thyroid Journal 13, 1; 10.1530/ETJ-23-0182

GICA for Tg measurement

The Tg-GICA rapid test kit was developed by Suzhou Dongni Biotechnology Co., Ltd (Suzhou, Jiangsu Province, China). The principle of GICA is to use colloidal gold as a tracer marker in antigen–antibody reactions. The Tg detection kit consists of plastic boxes and test strips installed in the box. Each test strip mainly consists of a sample pad, a conjugate pad, an absorbent pad, a test line, and a control line on a nitrocellulose membrane. An existing gold-labeled antibody on the nitrocellulose membrane is the pre-coating of mouse anti-human Tg monoclonal antibody within the test zone (T). Pre-embedded in the control zone (C) is the goat anti-mouse IgG polyclonal antibody. At the time of testing, 80 μL of FNA washout fluid were added to the sample pad and was allowed to flow toward the absorption pad through the capillary effect. Tg in the sample first binds to the colloidal gold–antibody conjugates that are precoated on the conjugate pad, and then the complexes are captured by the Tg antibody located in the test line and form a pink or red ribbon, and the degree of coloration of the ribbon is proportional to the Tg level in the sample tested within a certain range. The control line is precoated with anti-streptavidin antibody and should always become red. Our pre-experiments and previous studies of qualitative protein detection using GICA methods can yield stable results between 3 and 15 min (18, 19). We thus selected 3, 10, and 15 min as three time points for our experiments. The test strips were quantitatively analyzed using an instrument (Ma'anshan Ruiheng Technology Co., China) at each of the selected time points following sample addition. This instrument comprises a motherboard, a connecting plate, a serial port, an optical system, a touch screen, and a software suite. The image acquisition module captures an image of the test area and converts the image into a photoelectric signal by recognizing the difference in depth between the C and T zones on the gold-labeled strip to garner sample data. The concentration of Tg measured by this instrument ranges from 0.05 to 500 ng/mL (Fig. 1C, D, and E).

Histopathological diagnosis

Each LN that underwent FNA was separately sent for intraoperative frozen sectioning and finally diagnosed by paraffin sectioning, which is the gold standard for diagnosing LNM.

Statistical analysis

The value of FNA-Tg determined by ECLIA and GICA at different time points, the preoperative level of serum TgAb, and the pathology of frozen and paraffin sections of each patient were recorded. The data were analyzed and plotted using MedCalc program version 15.2 (MedCalc Software, Ostend, Belgium) and R software (v4.2.1). Continuous data were recorded as the mean and standard deviation. Categorical data were recorded as counts and percentages. The ROC curve and the AUC of the two tests are displayed. McNemar’s test was used to determine the sensitivity and specificity. The DeLong test was used to compare diagnostic performance, and the Jorden index was calculated to find the best diagnostic cutoff value for the diagnosis of LNM by FNA-Tg. The consistency between the GICA-Tg and ECLIA-Tg methods was examined by linear regression analysis. In all analyses, a two-sided P value < 0.05 was considered to be statistically significant.

Results

Patient characteristics

Fifty-one PTC patients were included in this study with a mean age of 39.15 years (±10.96 years), of whom 34 (66.67%) were female. In total, 10 patients had undergone reoperation, while 41 were receiving their first thyroid surgery. The mean body mass index of all the patients was 23.92 (± 3.36). According to the 8th American Joint Committee on Cancer (AJCC) tumor, node, and metastases (TNM) system, there were 35 pT1, 14 pT2, and 2 pT3 patients. Forty-five patients were classified as stage I, and six patients were classified as stage II. None had received prior radioactive iodine therapy.

A total of 150 LNs from the 51 patients were analyzed, including 72 (48.00%) metastatic LNs and 78 (52.00%) benign LNs that were diagnosed by paraffin section, with mean sizes of 0.88 cm (±0.38 cm) and 0.63 cm (±0.31 cm), respectively. Among the 150 LNs, 59 were dissected from the central compartment, and 91 were dissected from the lateral compartment (The basic information of patients and LNs is detailed in Supplementary Table 1, see the section on supplementary materials given at the end of this article.).

Diagnostic performance of intraoperative FNA-Tg-GICA and FNA-Tg-ECLIA for the total group LNs

When using GICA, according to the level of FNA-Tg measured after adding samples at 3, 10, and 15 min, the AUCs of the ROC curves of this method to identify LNM were 0.878 (95% CI: 0.815–0.926), 0.892 (95% CI: 0.831–0.936), and 0.899 (95% CI: 0.839–0.942), respectively. The AUC of the ROC curve of ECLIA to identify LNM was 0.899 (95% CI: 0.839–0.942) (Table 1). The AUCs of GICA at different time points and ECLIA were compared by the DeLong test, and the results showed that there was no significant difference between these groups (P = 0.196) (Fig. 2). To validate the GICA-Tg assay, Spearman correlation analysis was conducted between GICA-Tg and ECLIA-Tg measurements at 3, 10, and 15 min. Spearman’s correlation analysis showed the relationship between the Tg measurement results detected by GICA at different time points and ECLIA methods, revealed a robust positive correlation between the two methods (Fig. 3). These results indicate that both GICA and ECLIA can efficiently diagnose LNM intraoperatively, with 3 min being enough to achieve an ideal diagnostic performance for GICA. Therefore, we mainly used the data of GICA-3 min for the next analyses. In addition, according to the ROC curves (Fig. 2), the optimal cutoff value of FNA-Tg to predict LNM was 110.83 ng/mL for ECLIA and 13.19 ng/mL, 38.69 ng/mL, and 77.17 ng/mL for GICA at 3, 10, and 15 min, respectively (Table 1). Scatter plots were generated by comparing GICA-Tg and ECLIA-Tg measurements against each LN proven by paraffin, with the diagnostic cutoff marked by dotted lines (Fig. 4).

Figure 2
Figure 2

ROC curves of GICA at different time points, ECLIA, and frozen section for the total group lymph nodes. The DeLong test showed no significant differences between GICA at different time points and ECLIA (P = 0.196), between GICA-3 min and frozen section (P = 0.051), and between ECLIA and frozen section (P = 0.198).

Citation: European Thyroid Journal 13, 1; 10.1530/ETJ-23-0182

Figure 3
Figure 3

Consistency between GICA at different time points and ECLIA. The Spearman’s correlation analysis showed a linear relationship between the Tg measurement results detected by GICA and ECLIA. The upper reading of the ECLIA was 481 ng/mL.

Citation: European Thyroid Journal 13, 1; 10.1530/ETJ-23-0182

Figure 4
Figure 4

Tg values of each LN measured by GICA at different time points and ECLIA. Pathologically proven metastatic lymph nodes are denoted by red dots, and benign lymph nodes are represented by blue dots. The dotted line indicates the diagnostic cutoff value for each method.

Citation: European Thyroid Journal 13, 1; 10.1530/ETJ-23-0182

Table 1

Comparison of diagnostic performance of intraoperative FNA-Tg-GICA and FNA-Tg-ECLIA for the total group LNs.

Cutoff value (ng/mL) Sensitivitya Specificitya Accuracya AUCa P
GICA 0.196b
 3 min 13.19 0.90 (0.81–0.96) 0.82 (0.72–0.90) 0.85 (0.79–0.90) 0.878 (0.815–0.926)
 10 min 38.69 0.89 (0.79–0.95) 0.83 (0.73–0.91) 0.86 (0.79–0.90) 0.892 (0.831–0.936)
 15 min 77.17 0.89 (0.79–0.95) 0.85 (0.75–0.92) 0.86 (0.80–0.91) 0.899 (0.839–0.942)
ECLIA 110.83 0.92 (0.83–0.97) 0.86 (0.76–0.93) 0.88 (0.82–0.93) 0.899 (0.839–0.942)

aValues in parentheses are 95% CI; bP value for the comparison of AUCs between GICA at different time points and ECLIA.

AUC, area under the curve; ECLIA, electrochemiluminescence immunoassay; GICA, colloidal gold-based immunochromatographic assay.

Diagnostic performance of FNA-Tg-GICA, FNA-Tg-ECLIA, and intraoperative frozen section

All LNs subjected to FNA were sent for intraoperative frozen sectioning and finally analyzed by paraffin sectioning. The final histopathological diagnosis of the LNs showed that there were 72 metastatic LNs and 78 benign LNs, and the frozen section results showed 73 metastatic LNs and 77 benign LNs. The sensitivity, specificity, and accuracy of frozen sections were 0.93 (95% CI: 0.85–0.98), 0.92 (95% CI: 0.84–0.97), and 0.92 (95% CI: 0.87–0.96), respectively. The diagnostic performance of FNA-Tg-GICA, FNA-Tg-ECLIA, and intraoperative frozen section was compared by DeLong’s test. The results showed that there was no significant difference among the three methods to diagnose LNM intraoperatively (Table 2 and Fig. 2), suggesting that FNA-Tg-GICA and FNA-Tg-ECLIA are as accurate as frozen sections in diagnosing LNM.

Table 2

Comparison of diagnostic performance of FNA-Tg.-GICA, FNA-Tg-ECLIA, and intraoperative frozen section. Data are presented as value (95% CI).

Sensitivity Specificity Accuracy AUC P
GICA-3 min 0.90 (0.81–0.96) 0.82 (0.72–0.90) 0.85 (0.79–0.90) 0.878 (0.815–0.926)
ECLIA 0.92 (0.83–0.97) 0.86 (0.76–0.93) 0.88 (0.82–0.93) 0.899 (0.839–0.942)
Frozen section 0.93 (0.85–0.98) 0.92 (0.84–0.97) 0.92 (0.87–0.96) 0.927 (0.873–0.963) 0.051a 0.198b

aValue for the comparison of AUCs between GICA-3 min and frozen section. bValue for the comparison of AUCs between ECLIA and frozen section.;

AUC, area under the curve; ECLIA, electrochemiluminescence immunoassay; GICA, colloidal gold-based immunochromatographic assay.

Diagnostic performance of intraoperative FNA-Tg-GICA and FNA-Tg-ECLIA for the central and lateral compartment LNs

In the treatment of thyroid carcinoma, surgeons decide the surgical scope of LN dissection based on pathologically diagnosed or suspicious LNM in the different regions, which mainly include the central compartment and lateral compartment. Therefore, we explored whether the diagnostic performance of GICA and ECLIA is different for LNs from these two regions. Overall, the diagnostic performance of both Tg measurement methods showed no significant difference in evaluating LNM in the central and lateral compartment group (Table 3), implying that FNA-Tg-GICA and FNA-Tg-ECLIA are efficient in diagnosing LNM in both the central and lateral compartment.

Table 3

Diagnostic performance of FNA-Tg-GICA and FNA-Tg-ECLIA for the central compartment and lateral compartment LNs. Data are presented as value (95% CI).

Sensitivity Specificity Accuracy AUC P
GICA-3 min 0.559a
 Central compartment 0.88 (0.62–0.98) 0.79 (0.63–0.89) 0.81 (0.69–0.89) 0.834 (0.714–0.918)
 Lateral compartment 0.91 (0.79–0.97) 0.83 (0.67–0.93) 0.88 (0.79–0.93) 0.871 (0.785–0.932)
ECLIA 0.968b
 Central compartment 0.94 (0.69–1.00) 0.83 (0.68–0.92) 0.86 (0.75–0.93) 0.887 (0.778–0.955)
 Lateral compartment 0.91 (0.79–0.97) 0.86 (0.70–0.95) 0.89 (0.81–0.94) 0.885 (0.801–0.942)

aP value for the comparison of AUCs of GICA-3 min between LNs from central compartment and lateral compartment. bP value for the comparison of AUCs of ECLIA between LNs from central compartment and lateral compartment.

AUC, area under the curve; ECLIA, electrochemiluminescence immunoassay; GICA, colloidal gold-based immunochromatographic assay.

Serum TgAb levels and the diagnostic performance of FNA-Tg

Of the 51 patients, 18 were TgAb positive, and 33 were TgAb negative. Fifty-two LNs were from TgAb-positive patients, and 98 LNs were from TgAb-negative patients. In the TgAb-positive subgroup, a diagnosis based on GICA had a sensitivity of 0.88 (95% CI: 0.69–0.97), a specificity of 0.81 (95% CI: 0.60–0.93), and an accuracy of 0.85 (95% CI: 0.72–0.92). The corresponding values in the TgAb-negative subgroup were 0.91 (95% CI: 0.78–0.97), 0.81 (95% CI: 0.67–0.90), and 0.86 (95% CI: 0.77–0.91), respectively. For ECLIA, the sensitivity, specificity, and accuracy were 0.88 (95% CI: 0.69–0.97), 0.88 (95% CI: 0.69–0.97), and 0.88 (95% CI: 0.77–0.95) in the TgAb-positive subgroup and 0.93 (95% CI: 0.81–0.98), 0.83 (95% CI: 0.69–0.91), and 0.88 (95% CI: 0.80–0.93) in the TgAb-negative subgroup, respectively (Table 4). The AUCs of both methods showed no significant difference between the TgAb-positive subgroup and the TgAb-negative subgroup (Table 4), suggesting that the presence of serum TgAb does not affect the diagnostic performance of GICA and ECLIA.

Table 4

Diagnostic performance of intraoperative FNA-Tg in the presence and absence of TgAb. Data are presented as value (95% CI).

Sensitivity Specificity Accuracy AUC P
GICA-3 min 0.818a
 TgAb-negative 0.91 (0.78–0.97) 0.81 (0.67–0.90) 0.86 (0.77–0.91) 0.860 (0.776–0.922)
 TgAb-positive 0.88 (0.69–0.97) 0.81 (0.60–0.93) 0.85 (0.72–0.92) 0.846 (0.719–0.931)
ECLIA 0.946b
 TgAb-negative 0.93 (0.81–0.98) 0.83 (0.69–0.91) 0.88 (0.80–0.93) 0.881 (0.800–0.938)
 TgAb-positive 0.88 (0.69–0.97) 0.88 (0.69–0.97) 0.88 (0.77–0.95) 0.885 (0.766–0.956)

aP value for the comparison of AUCs of GICA-3 min between LNs from TgAb-negative and TgAb-positive patients. bP value for the comparison of AUCs of ECLIA between LNs from TgAb-negative and TgAb-positive patients.

AUC, area under the curve; ECLIA, electrochemiluminescence immunoassay; GICA, colloidal gold-based immunochromatographic assay.

Discussion

Cervical LNM is an independent risk factor for local recurrence of thyroid carcinoma (20). For patients with PTC, the accurate assessment of LNM preoperatively or intraoperatively is vital to determine the appropriate surgical scope and help the surgeon decide whether to perform a therapeutic cervical LN dissection. Recently, FNA-Tg has been shown to be an efficient technique that can improve the diagnostic accuracy of US and FNAC in evaluating LNM in PTC. It is recommended in both the American Thyroid Association and European Thyroid Association thyroid cancer treatment guidelines (3, 13). However, most of the previous studies performed FNA-Tg preoperatively or postoperatively. Only a few studies have assessed its diagnostic value for LNM intraoperatively (21).

In this study, we have introduced a novel method based on GICA to measure FNA-Tg and assist in the diagnosis of LNM intraoperatively. The results demonstrated that GICA is a rapid, easy-to-operate, and accurate method to diagnose TNM compared with the conventional approach of ECLIA and frozen sections. Although without significant difference, the P value for the comparison of AUCs between GICA-3 min and frozen section was close to 0.05, and the specificity of frozen section also seems higher, which indicates that the diagnostic performance of FNA-Tg tested by GICA may be slightly inferior to the frozen section. However, frozen sections require specialized equipment and experienced pathologists and often take a relatively longer time. The advantages of GICA may make it a novel alternative or supplementary method for LNM diagnosis intraoperatively, especially for hospitals that are unable to perform ECLIA or frozen section.

Some meta-analyses showed that the pooled sensitivity and specificity of FNA-Tg preoperatively or postoperatively were approximately 93–95% and 92–94.5%, respectively (8, 12). However, in this study, the diagnostic performance of FNA-Tg-GICA and FNA-Tg-ECLIA intraoperatively seemed poorer than that of FNA-Tg preoperatively or postoperatively, especially for specificity. This discrepancy may be attributed to the following reasons. On the one hand, all of the LNs in this study were subjected to paraffin sectioning to obtain the final histological diagnosis, but many previous reports diagnosed benign LNs only by FNAC without histology (10, 22, 23, 24, 25). As FNAC is less accurate than paraffin section, this may misclassify some false-negative cases as true-negative cases. On the other hand, previous studies focused more on the lateral compartment LNs (26, 27). However, in this study, central compartment LNs accounted for approximately 40% of the total, and these LNs were more likely to be contaminated by thyroid tissue during a puncture, leading to more false-positive cases.

It is widely recognized that TgAb negatively affects the immunoassay measurement of serum Tg, but it is still controversial whether TgAb affects the results of FNA-Tg. Baskin first proposed that FNA-Tg was not influenced by positive serum TgAb, possibly because intracellular Tg is not exposed to circulating TgAb (28). Marta et al. reported that the values of FNA-Tg in patients with LNM did not differ between those with positive and those with negative TgAb (29). In contrast, Jeon et al. discovered that FNA-Tg levels in the LNs of serum TgAb-positive patients were significantly lower than those of TgAb-negative patients, and the sensitivity and negative predictive value of FNA-Tg diagnosis were lower in the TgAb-positive group than in the TgAb-negative group (30). In agreement with most previous studies, our results demonstrated that the presence of serum TgAb does not affect the diagnostic performance of GICA and ECLIA, suggesting that GICA is as stable as other immunoassays for Tg measurement.

There are some limitations of our study. First, a selection bias may have existed, and the number of LNs from the lateral compartment was much greater than that from the central compartment. In addition, most of the values of Tg detected by GICA were much lower than those detected by ECLIA for the same LN. This implies that GICA may not be so precise in Tg quantification analysis but can still be used as a semiquantitative or qualitative method to evaluate LNM intraoperatively. When the Tg levels in washout fluid exceeded the highest limit of 481 ng/mL measured by ECLIA, we did not dilute the samples. This led to limited correlation between GICA and ECLIA.

In conclusion, our results support that GICA is a promising method for intraoperative FNA-Tg measurement to predict LNM. It may be a novel alternative or supplementary method to frozen section or ECLIA for LNM diagnosis intraoperatively.

Supplementary materials

This is linked to the online version of the paper at https://doi.org/10.1530/ETJ-23-0182.

Declaration of interest

The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the study reported.

Funding

This work was supported by the Chongqing Medical Scientific Research Project (Joint Project of Chongqing Health Commission and Science and Technology Bureau) (Grant no. 2023QNXM017) and Key Special Project for Technological Innovation and Application Development of Chongqing (Grant no. CSTB2022TIAD-KPX0177).

Author contribution statement

The authors have made the following declarations about their contributions: FZ and YS conceived and designed this study; SY, ZY, MT, TY, CS, CY, LM, and YY performed the trial and collected the data; SY, YS, and SH analyzed the data; and FZ, SH, and YS drafted the manuscript.

References

  • 1

    Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, & Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. A Cancer Journal for Clinicians 2018 68 394424. (https://doi.org/10.3322/caac.21492)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2

    Siegel RL, Miller KD, & Jemal A. Cancer statistics, 2020. A Cancer Journal for Clinicians 2020 70 730. (https://doi.org/10.3322/caac.21590)

  • 3

    Leenhardt L, Erdogan MF, Hegedus L, Mandel SJ, Paschke R, Rago T, & Russ G. 2013 European Thyroid Association guidelines for cervical ultrasound scan and ultrasound-guided techniques in the postoperative management of patients with thyroid cancer. European Thyroid Journal 2013 2 147159. (https://doi.org/10.1159/000354537)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4

    Solorzano CC, Carneiro DM, Ramirez M, Lee TM, & Irvin GL 3rd. Surgeon-performed ultrasound in the management of thyroid malignancy. American Surgeon 2004 70 576580. (https://doi.org/10.1177/000313480407000703)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5

    Khokhar MT, Day KM, Sangal RB, Ahmedli NN, Pisharodi LR, Beland MD, & Monchik JM. Preoperative high-resolution ultrasound for the assessment of malignant central compartment lymph nodes in papillary thyroid cancer. Thyroid 2015 25 13511354. (https://doi.org/10.1089/thy.2015.0176)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6

    Pacini F, Fugazzola L, Lippi F, Ceccarelli C, Centoni R, Miccoli P, Elisei R, & Pinchera A. Detection of thyroglobulin in fine needle aspirates of nonthyroidal neck masses: a clue to the diagnosis of metastatic differentiated thyroid cancer. Journal of Clinical Endocrinology and Metabolism 1992 74 14011404. (https://doi.org/10.1210/jcem.74.6.1592886)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7

    Jiang HJ, & Hsiao PJ. Clinical application of the ultrasound-guided fine needle aspiration for thyroglobulin measurement to diagnose lymph node metastasis from differentiated thyroid carcinoma-literature review. Kaohsiung Journal of Medical Sciences 2020 36 236243. (https://doi.org/10.1002/kjm2.12173)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8

    Liu RB, Zhou DL, Xu BH, Yang XH, Liu Q, Zhang X, Tang T, Ye ZL, & Li Y. Comparison of the diagnostic performances of US-guided fine needle aspiration cytology and thyroglobulin measurement for lymph node metastases in patients with differentiated thyroid carcinoma: a meta-analysis. European Radiology 2021 31 29032914. (https://doi.org/10.1007/s00330-020-07400-9)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9

    Coscia F, Taler-Verčič A, Chang VT, Sinn L, O'Reilly FJ, Izoré T, Renko M, Berger I, Rappsilber J, Turk D, et al.The structure of human thyroglobulin. Nature 2020 578 627630. (https://doi.org/10.1038/s41586-020-1995-4)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10

    Uruno T, Miyauchi A, Shimizu K, Tomoda C, Takamura Y, Ito Y, Miya A, Kobayashi K, Matsuzuka F, Amino N, et al.Usefulness of thyroglobulin measurement in fine-needle aspiration biopsy specimens for diagnosing cervical lymph node metastasis in patients with papillary thyroid cancer. World Journal of Surgery 2005 29 483485. (https://doi.org/10.1007/s00268-004-7701-0)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11

    Moon JH, Kim YI, Lim JA, Choi HS, Cho SW, Kim KW, Park HJ, Paeng JC, Park YJ, Yi KH, et al.Thyroglobulin in washout fluid from lymph node fine-needle aspiration biopsy in papillary thyroid cancer: large-scale validation of the cutoff value to determine malignancy and evaluation of discrepant results. Journal of Clinical Endocrinology and Metabolism 2013 98 10611068. (https://doi.org/10.1210/jc.2012-3291)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12

    Grani G, & Fumarola A. Thyroglobulin in lymph node fine-needle aspiration washout: a systematic review and meta-analysis of diagnostic accuracy. Journal of Clinical Endocrinology and Metabolism 2014 99 19701982. (https://doi.org/10.1210/jc.2014-1098)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13

    Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, Pacini F, Randolph GW, Sawka AM, Schlumberger M, 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. Thyroid 2016 26 1133. (https://doi.org/10.1089/thy.2015.0020)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14

    Giovanella L, Feldt-Rasmussen U, Verburg FA, Grebe SK, Plebani M, & Clark PM. Thyroglobulin measurement by highly sensitive assays: focus on laboratory challenges. Clinical Chemistry and Laboratory Medicine 2015 53 13011314. (https://doi.org/10.1515/cclm-2014-0813)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15

    Wang J, Jiang X, Xiao G, Zhou W, & Hu Y. Excellent diagnostic performance of FNA-Tg in detecting lymph nodes metastases from papillary thyroid cancer. Future Oncology 2020 16 27352746. (https://doi.org/10.2217/fon-2020-0213)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16

    Xiao J, Meng S, Zhang M, Li Y, Yan L, Li X, Yang Z, Zhang Y, & Luo Y. Optimal method for detecting cervical lymph node metastasis from papillary thyroid cancer. Endocrine 2023 79 342348. (https://doi.org/10.1007/s12020-022-03213-6)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17

    Liu Q, Mao L, Zhang Z, Li G, & Song H. Diagnostic efficacy of FNA-Tg in DTC cervical LN metastasis and its impact factors: a large retrospective study. Journal of Clinical Endocrinology and Metabolism 2023 108 33113319. (https://doi.org/10.1210/clinem/dgad335)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18

    Tanaka R, Yuhi T, Nagatani N, Endo T, Kerman K, Takamura Y, & Tamiya E. A novel enhancement assay for immunochromatographic test strips using gold nanoparticles. Analytical and Bioanalytical Chemistry 2006 385 14141420. (https://doi.org/10.1007/s00216-006-0549-4)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19

    Guo L, Wu X, Liu L, Kuang H, & Xu C. Gold immunochromatographic assay for rapid on-site detection of lincosamide residues in milk, egg, beef, and honey samples. Biotechnology Journal 2020 15 e1900174. (https://doi.org/10.1002/biot.201900174)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20

    Yu J, Deng Y, Liu T, Zhou J, Jia X, Xiao T, Zhou S, Li J, Guo Y, Wang Y, et al.Lymph node metastasis prediction of papillary thyroid carcinoma based on transfer learning radiomics. Nature Communications 2020 11 4807. (https://doi.org/10.1038/s41467-020-18497-3)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21

    Wang Y, Liu Y, Wang X, Li X, Jiang R, & He X. Intraoperative measurement of thyroglobulin in lymph node aspirates for the detection of metastatic papillary thyroid carcinoma. OncoTargets and Therapy 2017 10 44354441. (https://doi.org/10.2147/OTT.S140643)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22

    Borel AL, Boizel R, Faure P, Barbe G, Boutonnat J, Sturm N, Seigneurin D, Bricault I, Caravel JP, Chaffanjon P, et al.Significance of low levels of thyroglobulin in fine needle aspirates from cervical lymph nodes of patients with a history of differentiated thyroid cancer. European Journal of Endocrinology 2008 158 691698. (https://doi.org/10.1530/EJE-07-0749)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23

    Baloch ZW, Barroeta JE, Walsh J, Gupta PK, Livolsi VA, Langer JE, & Mandel SJ. Utility of thyroglobulin measurement in fine-needle aspiration biopsy specimens of lymph nodes in the diagnosis of recurrent thyroid carcinoma. CytoJournal 2008 5 1. (https://doi.org/10.1186/1742-6413-5-1)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24

    Lee YH, Seo HS, Suh SI, Lee NJ, Kim JH, Seol HY, Lee JH, Kwon SY, Kim NH, Seo JA, et al.Cut-off value for needle washout thyroglobulin in athyrotropic patients. Laryngoscope 2010 120 11201124. (https://doi.org/10.1002/lary.20893)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25

    Chung J, Kim EK, Lim H, Son EJ, Yoon JH, Youk JH, Kim JA, Moon HJ, & Kwak JY. Optimal indication of thyroglobulin measurement in fine-needle aspiration for detecting lateral metastatic lymph nodes in patients with papillary thyroid carcinoma. Head and Neck 2014 36 795801. (https://doi.org/10.1002/hed.23371)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 26

    Song Y, Xu G, Wang T, & Zhang B. Lateral neck multilevel fine-needle aspiration cytology and thyroglobulin estimation in papillary thyroid carcinoma. Laryngoscope Investigative Otolaryngology 2021 6 570575. (https://doi.org/10.1002/lio2.570)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 27

    Kim K, Bae JS, & Kim JS. Measurement of thyroglobulin level in lateral neck lymph node fine needle aspiration washout fluid in papillary thyroid cancer. Gland Surgery 2021 10 26862694. (https://doi.org/10.21037/gs-21-366)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 28

    Baskin HJ. Detection of recurrent papillary thyroid carcinoma by thyroglobulin assessment in the needle washout after fine-needle aspiration of suspicious lymph nodes. Thyroid 2004 14 959963. (https://doi.org/10.1089/thy.2004.14.959)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 29

    Duval MADS, Zanella AB, Cristo AP, Faccin CS, Graudenz MS, & Maia AL. Impact of serum TSH and anti-thyroglobulin antibody levels on lymph node fine-needle aspiration thyroglobulin measurements in differentiated thyroid cancer patients. European Thyroid Journal 2017 6 292297. (https://doi.org/10.1159/000479682)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 30

    Jeon MJ, Park JW, Han JM, Yim JH, Song DE, Gong G, Kim TY, Baek JH, Lee JH, Shong YK, et al.Serum antithyroglobulin antibodies interfere with thyroglobulin detection in fine-needle aspirates of metastatic neck nodes in papillary thyroid carcinoma. Journal of Clinical Endocrinology and Metabolism 2013 98 153160. (https://doi.org/10.1210/jc.2012-2369)

    • PubMed
    • Search Google Scholar
    • Export Citation

Supplementary Materials

 

  • Collapse
  • Expand
  • Figure 1

    The detection procedure for GICA assay. A. A lymph node is aspirated along its long axis using a thin 23G needle. B andC. The washout sample is then deposited into the hole of a test strip. Through capillary action, the Tg in the sample flows along the strip and reacts with anti-Tg antibodies embedded on the strip’s membrane. D. The reaction in the test zone on the membrane. If Tg is present in the sample, the test zone turns red (bottom strip), while a negative sample leaves it blank (upper strip). E. The intensity of the color is measured by an instrument to quantify the concentration of Tg.

  • Figure 2

    ROC curves of GICA at different time points, ECLIA, and frozen section for the total group lymph nodes. The DeLong test showed no significant differences between GICA at different time points and ECLIA (P = 0.196), between GICA-3 min and frozen section (P = 0.051), and between ECLIA and frozen section (P = 0.198).

  • Figure 3

    Consistency between GICA at different time points and ECLIA. The Spearman’s correlation analysis showed a linear relationship between the Tg measurement results detected by GICA and ECLIA. The upper reading of the ECLIA was 481 ng/mL.

  • Figure 4

    Tg values of each LN measured by GICA at different time points and ECLIA. Pathologically proven metastatic lymph nodes are denoted by red dots, and benign lymph nodes are represented by blue dots. The dotted line indicates the diagnostic cutoff value for each method.

  • 1

    Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, & Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. A Cancer Journal for Clinicians 2018 68 394424. (https://doi.org/10.3322/caac.21492)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2

    Siegel RL, Miller KD, & Jemal A. Cancer statistics, 2020. A Cancer Journal for Clinicians 2020 70 730. (https://doi.org/10.3322/caac.21590)

  • 3

    Leenhardt L, Erdogan MF, Hegedus L, Mandel SJ, Paschke R, Rago T, & Russ G. 2013 European Thyroid Association guidelines for cervical ultrasound scan and ultrasound-guided techniques in the postoperative management of patients with thyroid cancer. European Thyroid Journal 2013 2 147159. (https://doi.org/10.1159/000354537)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4

    Solorzano CC, Carneiro DM, Ramirez M, Lee TM, & Irvin GL 3rd. Surgeon-performed ultrasound in the management of thyroid malignancy. American Surgeon 2004 70 576580. (https://doi.org/10.1177/000313480407000703)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5

    Khokhar MT, Day KM, Sangal RB, Ahmedli NN, Pisharodi LR, Beland MD, & Monchik JM. Preoperative high-resolution ultrasound for the assessment of malignant central compartment lymph nodes in papillary thyroid cancer. Thyroid 2015 25 13511354. (https://doi.org/10.1089/thy.2015.0176)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6

    Pacini F, Fugazzola L, Lippi F, Ceccarelli C, Centoni R, Miccoli P, Elisei R, & Pinchera A. Detection of thyroglobulin in fine needle aspirates of nonthyroidal neck masses: a clue to the diagnosis of metastatic differentiated thyroid cancer. Journal of Clinical Endocrinology and Metabolism 1992 74 14011404. (https://doi.org/10.1210/jcem.74.6.1592886)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7

    Jiang HJ, & Hsiao PJ. Clinical application of the ultrasound-guided fine needle aspiration for thyroglobulin measurement to diagnose lymph node metastasis from differentiated thyroid carcinoma-literature review. Kaohsiung Journal of Medical Sciences 2020 36 236243. (https://doi.org/10.1002/kjm2.12173)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8

    Liu RB, Zhou DL, Xu BH, Yang XH, Liu Q, Zhang X, Tang T, Ye ZL, & Li Y. Comparison of the diagnostic performances of US-guided fine needle aspiration cytology and thyroglobulin measurement for lymph node metastases in patients with differentiated thyroid carcinoma: a meta-analysis. European Radiology 2021 31 29032914. (https://doi.org/10.1007/s00330-020-07400-9)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9

    Coscia F, Taler-Verčič A, Chang VT, Sinn L, O'Reilly FJ, Izoré T, Renko M, Berger I, Rappsilber J, Turk D, et al.The structure of human thyroglobulin. Nature 2020 578 627630. (https://doi.org/10.1038/s41586-020-1995-4)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10

    Uruno T, Miyauchi A, Shimizu K, Tomoda C, Takamura Y, Ito Y, Miya A, Kobayashi K, Matsuzuka F, Amino N, et al.Usefulness of thyroglobulin measurement in fine-needle aspiration biopsy specimens for diagnosing cervical lymph node metastasis in patients with papillary thyroid cancer. World Journal of Surgery 2005 29 483485. (https://doi.org/10.1007/s00268-004-7701-0)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11

    Moon JH, Kim YI, Lim JA, Choi HS, Cho SW, Kim KW, Park HJ, Paeng JC, Park YJ, Yi KH, et al.Thyroglobulin in washout fluid from lymph node fine-needle aspiration biopsy in papillary thyroid cancer: large-scale validation of the cutoff value to determine malignancy and evaluation of discrepant results. Journal of Clinical Endocrinology and Metabolism 2013 98 10611068. (https://doi.org/10.1210/jc.2012-3291)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12

    Grani G, & Fumarola A. Thyroglobulin in lymph node fine-needle aspiration washout: a systematic review and meta-analysis of diagnostic accuracy. Journal of Clinical Endocrinology and Metabolism 2014 99 19701982. (https://doi.org/10.1210/jc.2014-1098)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13

    Haugen BR, Alexander EK, Bible KC, Doherty GM, Mandel SJ, Nikiforov YE, Pacini F, Randolph GW, Sawka AM, Schlumberger M, 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. Thyroid 2016 26 1133. (https://doi.org/10.1089/thy.2015.0020)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14

    Giovanella L, Feldt-Rasmussen U, Verburg FA, Grebe SK, Plebani M, & Clark PM. Thyroglobulin measurement by highly sensitive assays: focus on laboratory challenges. Clinical Chemistry and Laboratory Medicine 2015 53 13011314. (https://doi.org/10.1515/cclm-2014-0813)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15

    Wang J, Jiang X, Xiao G, Zhou W, & Hu Y. Excellent diagnostic performance of FNA-Tg in detecting lymph nodes metastases from papillary thyroid cancer. Future Oncology 2020 16 27352746. (https://doi.org/10.2217/fon-2020-0213)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16

    Xiao J, Meng S, Zhang M, Li Y, Yan L, Li X, Yang Z, Zhang Y, & Luo Y. Optimal method for detecting cervical lymph node metastasis from papillary thyroid cancer. Endocrine 2023 79 342348. (https://doi.org/10.1007/s12020-022-03213-6)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 17

    Liu Q, Mao L, Zhang Z, Li G, & Song H. Diagnostic efficacy of FNA-Tg in DTC cervical LN metastasis and its impact factors: a large retrospective study. Journal of Clinical Endocrinology and Metabolism 2023 108 33113319. (https://doi.org/10.1210/clinem/dgad335)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 18

    Tanaka R, Yuhi T, Nagatani N, Endo T, Kerman K, Takamura Y, & Tamiya E. A novel enhancement assay for immunochromatographic test strips using gold nanoparticles. Analytical and Bioanalytical Chemistry 2006 385 14141420. (https://doi.org/10.1007/s00216-006-0549-4)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19

    Guo L, Wu X, Liu L, Kuang H, & Xu C. Gold immunochromatographic assay for rapid on-site detection of lincosamide residues in milk, egg, beef, and honey samples. Biotechnology Journal 2020 15 e1900174. (https://doi.org/10.1002/biot.201900174)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 20

    Yu J, Deng Y, Liu T, Zhou J, Jia X, Xiao T, Zhou S, Li J, Guo Y, Wang Y, et al.Lymph node metastasis prediction of papillary thyroid carcinoma based on transfer learning radiomics. Nature Communications 2020 11 4807. (https://doi.org/10.1038/s41467-020-18497-3)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21

    Wang Y, Liu Y, Wang X, Li X, Jiang R, & He X. Intraoperative measurement of thyroglobulin in lymph node aspirates for the detection of metastatic papillary thyroid carcinoma. OncoTargets and Therapy 2017 10 44354441. (https://doi.org/10.2147/OTT.S140643)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22

    Borel AL, Boizel R, Faure P, Barbe G, Boutonnat J, Sturm N, Seigneurin D, Bricault I, Caravel JP, Chaffanjon P, et al.Significance of low levels of thyroglobulin in fine needle aspirates from cervical lymph nodes of patients with a history of differentiated thyroid cancer. European Journal of Endocrinology 2008 158 691698. (https://doi.org/10.1530/EJE-07-0749)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 23

    Baloch ZW, Barroeta JE, Walsh J, Gupta PK, Livolsi VA, Langer JE, & Mandel SJ. Utility of thyroglobulin measurement in fine-needle aspiration biopsy specimens of lymph nodes in the diagnosis of recurrent thyroid carcinoma. CytoJournal 2008 5 1. (https://doi.org/10.1186/1742-6413-5-1)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 24

    Lee YH, Seo HS, Suh SI, Lee NJ, Kim JH, Seol HY, Lee JH, Kwon SY, Kim NH, Seo JA, et al.Cut-off value for needle washout thyroglobulin in athyrotropic patients. Laryngoscope 2010 120 11201124. (https://doi.org/10.1002/lary.20893)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 25

    Chung J, Kim EK, Lim H, Son EJ, Yoon JH, Youk JH, Kim JA, Moon HJ, & Kwak JY. Optimal indication of thyroglobulin measurement in fine-needle aspiration for detecting lateral metastatic lymph nodes in patients with papillary thyroid carcinoma. Head and Neck 2014 36 795801. (https://doi.org/10.1002/hed.23371)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 26

    Song Y, Xu G, Wang T, & Zhang B. Lateral neck multilevel fine-needle aspiration cytology and thyroglobulin estimation in papillary thyroid carcinoma. Laryngoscope Investigative Otolaryngology 2021 6 570575. (https://doi.org/10.1002/lio2.570)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 27

    Kim K, Bae JS, & Kim JS. Measurement of thyroglobulin level in lateral neck lymph node fine needle aspiration washout fluid in papillary thyroid cancer. Gland Surgery 2021 10 26862694. (https://doi.org/10.21037/gs-21-366)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 28

    Baskin HJ. Detection of recurrent papillary thyroid carcinoma by thyroglobulin assessment in the needle washout after fine-needle aspiration of suspicious lymph nodes. Thyroid 2004 14 959963. (https://doi.org/10.1089/thy.2004.14.959)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 29

    Duval MADS, Zanella AB, Cristo AP, Faccin CS, Graudenz MS, & Maia AL. Impact of serum TSH and anti-thyroglobulin antibody levels on lymph node fine-needle aspiration thyroglobulin measurements in differentiated thyroid cancer patients. European Thyroid Journal 2017 6 292297. (https://doi.org/10.1159/000479682)

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 30

    Jeon MJ, Park JW, Han JM, Yim JH, Song DE, Gong G, Kim TY, Baek JH, Lee JH, Shong YK, et al.Serum antithyroglobulin antibodies interfere with thyroglobulin detection in fine-needle aspirates of metastatic neck nodes in papillary thyroid carcinoma. Journal of Clinical Endocrinology and Metabolism 2013 98 153160. (https://doi.org/10.1210/jc.2012-2369)

    • PubMed
    • Search Google Scholar
    • Export Citation