Significance of Dynamic Risk Assessment in the Follow-up of Non-distant Metastatic Differentiated Thyroid Cancer Patients with Intermediate and High Risk / 中国医学科学院学报

To tailor the subsequent treatment and follow-up strategy,this study dynamically assessed the response to initial therapy in non-distant metastatic differentiated thyroid cancer (DTC) patients with intermediate and high risk. A total of 184 non-distant metastatic DTC patients (intermediate-risk 111 cases and high-risk 73 cases) were retrospectively enrolled in this study. Based on the results of initial response assessment (6-12 months after initial therapy),patients were divided into two groups:excellent response (ER) group (=113) and non-excellent response (non-ER) group (=71). We compared the differences in clinicopathological features between these 2 groups and evaluated the changes of dynamic response to therapy at the initial and final assessments after initial therapy in all patients. Compared with the ER group,the non-ER group showed a larger tumor size (=2771.500,=0.000),higher proportion of extrathyroidal invasion (=4.070,=0.044),and higher preablative-stimulated thyroglobulin levels (=1367.500,=0.000). ER was achieved in 31% of patients in the initial non-ER group [including indeterminate response (IDR) and biochemical incomplete response (BIR)] at the final follow-up only by thyroid stimulating hormone (TSH) suppression therapy,among which 63.6% were with intermediate risk (especially the patients with IDR) and 36.4% at high risk. In addition,5.2%(6/113) of patients in the initial ER group were reassessed as IDR,BIR,or even structural incomplete response at the end of the follow-up (among which one patient developed into cervical lymph node recurrence,as confirmed by pathology);the TSH level in these patients fluctuated at 0.56-10.35 μIU/ml and was not corrected in time during the follow-up after initial therapy. Some of non-distant metastatic DTC patients with intermediate and high risks who presented initial non-ER may achieve ER only by TSH suppression therapy over time;in contrast,the patients presented initial ER may develop into non-ER without normalized TSH suppression therapy. The dynamic risk assessment system may provide a real-time assessment of recurrence risk and tailor the subsequent treatment and follow-up strategies.

Identification of Radioactive Iodine Refractory Differentiated Thyroid Cancer / 전남의대학술지

Most differentiated thyroid cancer (DTC) patients have an excellent prognosis. However, about one-third of DTC patients with recurrent or metastatic disease lose the hallmark of specific iodine uptake initially or gradually and acquire radioactive iodine-refractory DTC (RAIR-DTC) with poor prognosis. Due to the potentially severe complications from unnecessarily repeated RAI therapy and encouraging progress of multiple targeted drugs for advanced RAIR-DTC patients, it has become crucial to identify RAIR-DTC early. In this review, we focus on the progress and controversies regarding the defining of RAIR-DTC, further with subsistent approaches and promising molecular nuclear medicine imaging in identifying RAIR-DTC, which may shed light on the proper management methodsof such patients.

Emerging management and its impact on radioiodine refractory differentiated thyroid cancer / 中国实用外科杂志

Differentiated thyroid cancer(DTC) generally carries good prognosis through standard treatment. While,it could dedifferentiate into radioiodine refractory differentiated thyroid cancer(RAIR-DTC),which progresses rapidly with high mortality and limited treatment methods. Recently,along with the increasing of studies on genetic features,signal transduction pathways and immune microenvironment of RAIR-DTC,as well as the development of new radionuclide tracers,more theoretical bases have been provided for the targeted therapy of RAIR-DTC.

Effect of Lymph Node Metastasis on Change of Positive Thyroglobulin Antibody in Differentiated Thyroid Carcinoma after Initial Treatment / 中国医学科学院学报

Objective To investigate the influence of lymph node metastasis on the change of positive thyroglobulin antibody(TgAb)in differentiated thyroid carcinoma after initial treatment.Methods We retrospectively analyzed the clinical data of 98 differentiated thyroid carcinoma patients with positive TgAb(≥115 IU/ml)before radioiodine(RAI)therapy.All of whom underwent total or near total thyroidectomy,neck lymph node dissection,and subsequent RAI therapy.Patients were divided into negative group(n=83)and non-negative group(n=15)according to the disappearance of positive TgAb or not after a mean follow-up of 21.0 months.Analysis of variance,χtest,and Mann-Whitney rank-sum test were applied to compare the basic clinical features including number of metastatic lymph nodes,lymph node metastasis rate and node stage,and dose of RAI ablation.The receiver operating characteristic curves were employed to evaluate the predictive values of TgAb levels(negative or positive)and optimal cut-off points.Multivariate analyses were further performed to explore the independent indicators for persistent positive TgAb. Results Compared with the negative group,the proportions of N1a and N1b in the non-negative group were significantly higher,with no N0 in the non-negative group(Fisher's Exact Test,P=0.032).The median metastatic lymph node rate was also significantly higher in the non-negative group(Mann-Whitney U=-3.498,P=0.000).The cut-off value for metastatic lymph node rate to predicting disappearance of positive TgAb was 24%,and its sensitivity was 71.4%.The multivariate analysis showed that only lymph node stage(OR=3.183,P=0.038)was the independent indicator for persistent positive TgAb. Conclusions Lymph node stage was an independent indicator for the disappearance of positive TgAb.A metastatic lymph node rate of higher than 24% may be predictive for the disappearance of positive TgAb.

Response to (131)I Therapy in Non-metastatic Differentiated Thyroid CancerPatients with Preablative Stimulated Thyroglobulin above 10 ng/ml / 中国医学科学院学报

<p><b>OBJECTIVE</b>To evaluate the response of (131)I therapy and to explore the influencing factors in non-metastatic differentiated thyroid cancer (DTC) patients with preablative stimulated thyroglobulin (ps-Tg) above 10 ng/ml.</p><p><b>METHODS</b>The study included 157 DTC patients who had undergone total or near total thyroidectomy and subsequent (131)I therapy with ps-Tg>10 ng/ml, and they were divided into 3 groups as excellent response (ER, 49 cases), acceptable response (AR, 36 cases), and incomplete response (IR, 72 cases) according to the response to (131)I therapy. We compared the clinicopathologic features and ps-Tg levels among 3 groups, as well as ps-Tg levels between IR and non-IR groups. The ROC curve was employed to evaluate the predictive value of ps-Tg levels in (131)I therapy responses.</p><p><b>RESULTS</b>The three groups showed significant difference in ps-Tg levels (H=35.142, P<0.001), gender (χ(2)=6.82, P=0.033), extrathyroid invasion (H=31.380, P<0.001), and lymph metastases (H=14.375, P=0.001). The ps-Tg level in IR is higher than that in non-IR (U=1384.5, P<0.001), while it was not significantly different between ER and AR (U=771.5, P=0.326). The diagnostic critical point (DCP) of ps-Tg to differentiate IR and non-IR was 28.3 ng/ml (sensitivity 57.5%, specificity 87.1%), with a corresponding area under the ROC curve (AUC) of 0.774 (95%CI: 0.701-0.847).</p><p><b>CONCLUSIONS</b>Near-half (45.86%) non-metastatic DTC patients with ps-Tg above 10 ng/ml are more susceptible to IR. The level of ps-Tg>28.3 ng/ml may be a useful and sensitive diagnostic marker for predicting incomplete response.</p>

Clinical Outcome of (131)I Therapy in Differentiated Thyroid Cancer with Preablative Thyroglobulin below 10 ng/ml / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the clinical outcome of (131)I therapy in differentiated thyroid cancer (DTC) with preablative stimulated thyroglobulin (ps-Tg) below 10 ng/ml and the value of ps-Tg for predicting clinical outcome.</p><p><b>METHODS</b>Totally 167 DTC patients with ps-Tg below 10 ng/ml were included and divided into three groups [excellent response (ER, n=131), acceptable response (AR, n=34), and incomplete response (IR, n=2)] according to the response to initial (131)I therapy. One-way analysis of variance, χ(2) test, and Kruskal-Wallis test were used to evaluate the statistical differences of clinicopathological features, recurrence risk, and ps-Tg value among the three groups. The ps-Tg value between ER group and non-ER group were compared by Mann-Whitney rank-sum test. The ROC curve and optimal cut-off point were analyzed to evaluate the clinical value of ps-Tg for predicting disease-free status.</p><p><b>RESULTS</b>There was significant difference in ps-Tg level (H=14.305, P=0.001) among three groups but not in age (F=0.831, P=0.755), sex (χ(2)=0.178, P=0.915), cervical lymph node metastases (χ(2)=1.475, P=0.478), TNM stage (H=1.063, P=0.588), and recurrence risk (H=2.947, P=0.229). The median level of ps-Tg in ER group was 2.20 ng/ml (1.10, 4.40), which was significantly lower than 4.40 ng/ml (2.70, 5.90) of non-ER groups (U=1424.50, P=0.000). Area under the ROC curve was 0.717. The cut-off value of ps-Tg was 2.35 ng/ml,with a sensitivity of 83.33%, specificity of 53.43%, and negative predictive value of 92.11%.</p><p><b>CONCLUSION</b>The serum ps-Tg value is a sensitive marker for predicting the disease-free status in DTC patients with ps-Tg below 10 ng/ml.</p>

Serial Thyroglobulin Variation Trend Shortly after Radioiodine Therapy in Poorly to Moderately Differentiated Recurrent Thyroid Cancer / 中国医学科学院学报

Objective To dynamically observe the early change of thyroglobulin(Tg) levels after (131)I therapy in differentiated thyroid cancer(DTC) patients. Methods The study enrolled 22 post-total-thyroidectomy DTC patients and they were stratified as low to intermediate recurrence according to the 2009 American Thyroid Association Guidelines. The clinical data including pre-ablation stimulated Tg (ps-Tg),corresponding thyroid stimulating hormone(TSH),anti-thyroglobulin (TgAb) values,and the afterwards parameters were dynamically measured each week in the first month after (131)I therapy. Values collected at the first time were defined as Tg 0 and TSH0,while Tg1 and TSH1 were collected at the first week after (131)I therapy respectively. Then the variation trend curves of Tg were drawn,and factors influencing the variation of Tg were analyzed. Two groups were divided according to Tg levels:G1 (Tg≤0.1 ng/ml,n=9) and G2(Tg>0.1 ng/ml,n=13). Results The rates of negative Tg were 4.5%,18.0%,27.0%,36.0%,and 41.0%,respectively,exactly before (131)I therapy and the 1(st),2(nd),3(rd),and 4(th) week after the therapy. One-way analysis of variance showed that the two groups statistically differed in age (F=3.182,P=0.04) and remnant thyroid (U=4.849,P=0.026). Multivariate logistic regression analysis showed that early negative Tg was related to remnant thyroid tissue (OR:2.132;95%Cl:1.418- 6.532,P=0.009). Conclusions Negative Tg can be achieved in nearly half of DTC patients by the end of first month after (131)I therapy. The negative conversion is closely related with the volume of remnant thyroid tissue.

Clinical Outcome of Radioiodine Therapy in Low-intermediate Risk Papillary Thyroid Carcinoma with BRAF(V600E) Mutation / 中国医学科学院学报

Objective To evaluate the impact of BRAF(V600E) gene status on clinical outcome of radioiodine((131)I) therapy in low-intermediate risk recurrent papillary thyroid carcinoma (PTC). Methods Totally 135 PTC patients were enrolled and divided into two groups according to BRAF(V600E) gene status:BRAF(V600E) mutation group(n=105) and BRAF(V600E) wild group(n=30). The median follow-up time was 2.16 years(1.03-4.06 years),and clinical outcome after initial (131)I ablation therapy was divided into excellent response(ER),acceptable response(AR),and incomplete response(IR) according to the serological and imageological follow-up results. The cinical outcomes were then compared between these two groups. Results There was no significant difference in clinicopathological features and initial radioactive iodine dose between BRAF(V600E) mutation and wild groups (P>0.05). ER,AR,and IR after (131)I ablation therapy accounted for 74.3%,20.0%,and 5.7% in BRAF(V600E) mutation group and 73.3%,20.0%,and 6.7% in BRAF(V600E) wild group,and no statistical difference was found (P=0.891). Conclusion For low-intermediate risk recurrent PTC,BRAF(V600E) gene status may have no impact on the response to (131)I ablation therapy,and thus this molecular feature should not be used as an independent weighting factor for risk assessment in this population.

Postoperative stimulated thyroglobulin level and recurrence risk stratification in differentiated thyroid cancer / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Postoperative preablative stimulated thyroglobulin (ps-Tg) has been evaluated in predicting prognosis and success of ablation regarding differentiated thyroid cancer (DTC); however, its relationship with recurrence risk and radioiodine decision-making remains uncertain, especially in Chinese DTC patients. We aimed to evaluate the association between ps-Tg and recurrence risk stratification in DTC, to provide incremental values for ps-Tg in postoperative assessment and radioiodine management.</p><p><b>METHODS</b>Seven hundred and seven patients with DTC were included; low-risk (L; n = 90), intermediate-risk (I; n = 283), and high-risk (H; n = 334, 117 with distant metastasis [M1]) patients were divided according to recurrence risk stratification. The M1 group was further analyzed regarding evidence of metastasis. Cut-off values of ps-Tg were obtained using receiver operating characteristic analysis.</p><p><b>RESULTS</b>Patients with more advanced disease at initial risk stratification were more likely to have higher ps-Tg levels (I vs. L: P < 0.05; H vs. I: P < 0.001; H vs. L: P < 0.001). The corresponding cut-off value of ps-Tg for distinguishing sensitivity and specificity in each of the two groups was 2.95 ng/ml (I vs. L: 61.5%, 63.3%), 29.5 ng/ml (H vs. I: 41.9%, 92.6%), 47.1 ng/ml (M1 vs. M0 in the H group: 79.5%, 88.9%) and 47.1 ng/ml (M1 vs. M0 in all patients: 79.5%, 93.7%). With the cut-off value at 47.1 ng/ml, ps-Tg was the only factor that could be used to identify distant metastases, and consequently if measured before radioiodine therapy would prevent 10.26% of patients with M1 from undertreatment.</p><p><b>CONCLUSIONS</b>Ps-Tg, as an ongoing reassessment marker, favors differential recurrence risk grading and provides incremental values for radioiodine treatment decision-making.</p>

Effect of Selenious Yeast Tablets on the Thyroglobulin Antibody Level in ThyroglobulinAntibody-positive Patients with Differentiated Thyroid Cancer / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the change of thyroglobulin antibodies (TgAb) after the application of selenious yeast tablet (SYT) in differentiated thyroid cancer (DTC) patients with positive TgAb (>115 U/ml).</p><p><b>METHODS</b>We enrolled 41 DTC patients with positive TgAb who had undergone total thyroidectomy and subsequent ¹³¹I therapy as well as applied SYT in group 1 (G1). Patients with an interval of more than 6 months between SYT use and ¹³¹I therapy or with repeated TgAb measurements before the use of SYTs were divided into group 2 (G2) and group 3 (G3), respectively. Changes in TgAb after application of SYT in both G1 and G2 were observed and analyzed by rank sum test. Comparison of TgAb gradient over certain time before and after the application was analyzed by t-test.</p><p><b>RESULTS</b>The proportions of patients with decreased or elevated TgAb were 85.4% and 14.6% in G1 and 90.9% and 9.1% in G2, respectively. Compared with the previous TgAb levels, TgAb decreased significantly after the application of SYT in either G1 (P=0.000) or G2(P=0.003). In G3, the TgAb level rose by 5.6% every month before applying SYT and fell 8.3% every month after the application (P=0.086).</p><p><b>CONCLUSION</b>Application of SYT in DTC patients with positive TgAb can effectively decrease the TgAb level.</p>

Low-dose Radioiodine for Ablation in Non-metastatic High-risk Thyroid Cancer / 中国医学科学院学报

<p><b>OBJECTIVE</b>To evaluate the role of low-dose radioiodine in the treatment of non-metastatic high-risk differentiated thyroid cancer (DTC) patients with macroscopic extra-thyroidal extension (MAEE).</p><p><b>METHODS</b>Totally 103 DTC patients with total/near-total thyroidectomy and selective lymph node resection, and with MAEE, any N stage,preablative stimulated thyroglobulin (ps-Tg) ≤ 5 ng/ml when thyroglobulin antibodies (TgAb) ≤ 46 U/ml and no evidence of distant metastasis were retrospectively analyzed in this study. Fifty-two received low dose RAI (1110 MBq) and 51 received high dose (≥ 3700 MBq). The successful ablation rate and disease-free survival rate were compared between these two groups.</p><p><b>RESULTS</b>The successful ablative rate was 86.5% (45/52) in low-dose group and 86.3% (44/51) in high-dose group (P=0.9688), and the disease-free survival was 97.4% (38/39) in low-dose group and 97.5% (39/40) in high-dose group.</p><p><b>CONCLUSION</b>The ablation success and medium-term clinical outcome with low-dose RAI is proved to be non-inferior to high dose in non-metastatic patients with MAEE when ps-Tg level is less than 5 ng/ml.</p>

Changes in thyroglobulin antibodies after treatment of differentiated thyroid cancer and its influencing factors / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the changes in thyroglobulin antibodies (TgAb) and its influencing factors in differentiated thyroid cancer (DTC) patients with positive TgAb (>115 U/ml) after total thyroidectomy and radioiodine (¹³¹I) therapy.</p><p><b>METHODS</b>We collected the clinical data of 118 DTC patients with positive TgAb and analyzed their TgAb levels before surgery, before ¹³¹I therapy, and after ¹³¹I therapy with a median follow-up of 2.3 months and 5.2 months. Multiple linear regression (MLR) was applied to analyze the time of TgAb concentration decreased by more than 50% (T₅₀) and its influencing factors.</p><p><b>RESULTS</b>Compared with the previous TgAb levels, TgAb decreased significantly 2.3 months and 5.2 months after surgery or after ¹³¹I therapy, respectively (both P=0.000). The proportions of patients with TgAb decreased by more than 50% in each stage were 28.6%,33.3%, and 37.2%,respectively. The negative conversion ratios were 23.4%,48.9%, and 62.8%,respectively. MLR showed that only the interval between surgery and ¹³¹I therapy was correlated with T₅₀ (B=1.125, P=0.000).</p><p><b>CONCLUSIONS</b>The TgAb levels in DTC patients remarkably decrease after surgery and after ¹³¹I therapy. The interval between surgery and ¹³¹I therapy remarkably influences the lowering speed of TgAb levels. Prompt application of ¹³¹I therapy after surgery helps to lower TgAb levels.</p>

Relationship between Variation of Pre-ablation Stimulated Thyroglobulin and Distant Metastasis in Patients with Differentiated Thyroid Cancer / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the relationship between the dynamic variation of pre-ablation stimulated thyroglobulin(sTg)and distant metastasis in patietns with differentiated thyroid cancer(DTC).</p><p><b>METHODS</b>DTC patients after total or near total thyroidectomy were divided into two groups as M1 group(n=38)and M0 group(n=130)according to the presence of distant metastases or not. Clinical data including pre-ablation sTg and the corresponding thyrotropin(TSH)values were dynamically measured. The pre-ablation sTg and corresponding TSH collected at the first time were defined as Tg1 and TSH1,while as Tg2 and TSH2 at the last time. χ(2) test was used to compare the variation tendency of sTg between these two groups. Tg1,Tg2,pre-ablation sTg variation(∆Tg),and ∆Tg/∆TSH ratio between M0 and M1 were compared by Mann-Whitney rank-sum test. The receiver operating characteristic(ROC)curves and diagnostic critical point(DCP)were employed to evaluate the predictive values of the above indicators.</p><p><b>RESULTS</b>Both Tg1 and Tg2 of M1 were significantly higher than those of M0(the Mann-Whitney rank-sum test:Tg1 P<0.001,Tg2 P<0.001). The corresponding areas under the ROC curve(AUC)to differentiate the two groups were 0.921 and 0.942,respectively. The cut-off value of Tg2,which was more accurate in predicting distant metastasis,was 24.3 ng/ml with a sensitivity of 92.11% and a specificity of 83.85%. Both ∆Tg and ∆Tg/∆TSH between these two groups were significantly different(the Mann-Whitney rank-sum test:∆Tg P=0.002,∆Tg/∆TSH P<0.001). ∆Tg/∆TSH worked better than Tg2 in predicting distant metastasis with both higher accuracy(87.50%)and higher specificity(86.92%).</p><p><b>CONCLUSIONS</b>Dynamically tracing pre-ablation sTg may improve the accuracy and specificity of distant metastases prediction in DTC patients. ∆Tg/∆TSH,which means the ratio of sTg variation to TSH variation,may be a useful diagnostic marker for predicting distant metastases in DTC.</p>

Influence of (99m)Tc-pertechnetate thyroid imaging on radioactive iodine uptake / 中国医学科学院学报

<p><b>OBJECTIVE</b>To observe the influence of (99m)Tc-pertechnetate on radioactive iodine uptake (RAIU) in patients with Graves' disease (GD) hyperthyroidism after thyroid scintigraphy.</p><p><b>METHODS</b>Totally 40 patients in whom thyrotoxicosis was diagnosed at Peking Union Medical College Hospital from 2013 March to May were recruited, and RAIU were performed in all patients. Gamma-count rates at 1 h,25 h,49 h,73 h and 169 h were examined respectively after intravenous injection of 185 MBq (5mCi)of (99m)Tc-pertechnetate. The counts of (99m)Tc and (131)I as well as effective half-life of (99m)Tc (Teff (99m)Tc) were calculated respectively according to the half-life formula. The ratio of (99m)Tc to background counts (1200) was calculated as a reference value to evaluate biokinetics of (99m)Tc.The relationship between the effective half-life of (99m)Tc(Teff (99m)Tc) and the level of free triiodothyronine (FT3), free thyroxine (FT4), and effective half-life of (131)I (Teff (131)I)were also evaluated.</p><p><b>RESULTS</b>After intravenous injection of (99m)Tc-pertechnetate, (99m)Tc counts at 1h, 25h, 49h, 73h and 169h was (440.16±247.35)×10(4), (11.37±10.67)×10(4), (0.13±0.36)×10(4), (-0.1±0.19)×10(4), respectively, and the ratio of (99m)Tc to background at 1h, 25 h, and 49 h was 3668, 94.75, and 1.08, respectively. The Teff (99m)Tc was (4.41±0.49)h. Inverse correlations were noted between the effective half-life of Teff (131)I and level of FT3 (r=-0.503, P=0.003) and FT4 (r=-0.516, P=0.002), while no significant correlation was found between the Teff (99m)Tc and FT3, FT4 as well as the Teff (131)I.</p><p><b>CONCLUSIONS</b>Teff (99m)Tc is 4.41h, (99m)Tc-pertechnetate thyroid imaging does not influence RAIU three days after injection of (99m)Tc-pertechnetate. Teff (99m)Tc shows no correlation with the thyroid hormone level and RAIU of Graves's hyperthyroidism.</p>

Correlations between cellular immunity and invasiveness in differentiated thyroid cancer / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the relationship between the immunity and invasiveness in differentiated thyroid cancer (DTC).</p><p><b>METHODS</b>Totally 74 DTC who were treated in Peking Union Medical College Hospital from September 2012 to December 2012 were enrolled in this study. These 74 patients were divided into membrane invasion group (n=36) and without membrane invasion group (n=38); also, they were divided into distant metastasis group (n=18) and without distant metastasis group (n=56). Natural killer (NK) cells and T-cell subsets were chosen as indicators for cellular immunity to investigate the correlation between cellular immunity and invasiveness in DTC.</p><p><b>RESULTS</b>Univariate analysis showed that the membrane invasion (Χ(2)=12.175, P=0.000) and distant metastasis (Χ(2)=8.139, P=0.006) correlated with cell immunity, whereas distant metastasis correlated with lymphocytic thyroiditis (Χ(2)=7.094, P=0.008). Further investigation shows that distant metastasis was associated with the percentage of CD8+T cell subgroup (Χ(2)=5.429, P=0.020), and membrane invasion was significantly associated with NK cells (Χ(2)=2.445, P=0.018) and CD4/CD8 disorder subgroup (Χ(2)=8.079, P=0.002). Multivariate analysis showed that cell immunity disorder was a risk factor for membrane invasion [OR=5.701,95%CI(2.075~15.666), P=0.001] and distant metastasis [OR=5.063,95%CI (1.571~16.320), P=0.008]. Further analysis showed that CD8+T cell was a risk factor for metastasis [OR=2.236,95%CI( 1.084~4.613), P=0.029], and CD4/CD8 disorders were the risk factors for membrane invasion [OR=2.802,95%CI(1.257~6.244), P=0.012].</p><p><b>CONCLUSION</b>Cell immunity in thyroid cancer has close relationship with membrane invasion and distant metastasis, especially when the percentage of CD8+T cells decreases and when the NK cells and CD4/CD8 are abnormal, which may lead to membrane invasion and distant metastasis.</p>

Postoperative treatment of differentiated thyroid carcinoma with intermediate recurrence risk / 中国医学科学院学报

The three-level recurrence stratification of differentiated thyroid carcinoma (DTC) has attracted wide attention since its introduction in 2009 American Thyroid Association guidelines. Among these three levels, the postoperative treatment of DTC with intermediate recurrence risk is highly controversial. This article summarizes the relevant advances and controversies in this field.

Invasiveness of papillary thyroid microcarcinoma with BRAF mutation / 中国医学科学院学报

<p><b>OBJECTIVE</b>To explore the invasiveness of papillary thyroid microcarcinoma(PTMC)with BRAF mutation.</p><p><b>METHODS</b>Totally 99 patients with PTMC with BRAF mutation were enrolled in this study, meanwhile another 97 patients with papillary thyroid carcinoma (PTC) (tumor size>1 cm)with BRAF mutation were included as controls. The clinicopathologic factors including extrathyroidal invasion, multifocality, and distant metastasis were analyzed.</p><p><b>RESULTS</b>The rates of extrathyroidal invasion and nodal metastasis in PTMC group were as high as 16.10% and 71.74%, respectively. In the PTMC group and PTC group,the extrathyroidal invasion rate was 16.10% and 39.18%, cervical lymph node metastasis rate was 71.74% and 91.75%, and distant metastasis rate was 1.01% and 9.28%, respectively. In the PTMC subgroups with tumor sizes ≤0.3 cm, 0.3-0.6 cm, and 0.6-1.0 cm, the cervical lymph node invasion rate was 60.00%, 72.50%, and 73.81%, the extrathyroidal invasion rate was 10.00%, 9.09%, and 24.44%, and the multifocality rate was 60.00%, 38.64%, and 57.78%, respectively. Univariate analysis showed that the tumor size was not significantly correlated with multifocality (Χ (2)=3.752, P=0.153), cervical lymph node metastasis (Χ (2) = 0.780,P = 0.677), extrathyroidal invasion (Χ (2) = 4.182, P = 0.124), and distant metastasis (Χ (2)=1.212, P = 0.545). While the BRAF group and PTC group were not significantly different in multifocality (Χ (2) = 1.742, P=0.187), they were significantly different in terms of extrathyroidal invasion (Χ (2) = 13.000, P = 0.000), nodal involvement (Χ (2) = 12.819, P = 0.000), and distant metastasis (Χ (2) = 5.316, P = 0.021). Multivariate analysis showed that nodal metastasis was independently associated with size>1 cm (P=0.001) and extrathyroidal invasion (P=0.003).</p><p><b>CONCLUSIONS</b>BRAF mutant PTMC manifests relative high extrathyroidal involvement and nodal metastasis, and the similar multifocality as BRAF mutant PTC. Radioactive iodine should be considered in PTMC with the presence of BRAF mutation combined with extrathyroidal invasion or nodal metastasis.</p>

Invasive properties of papillary thyroid cancer with concurrent BRAF(V600E) mutation and rearranged during transfection proto-oncogene protein expression / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the aggressive properties of papillary thyroid cancer (PTC) with concurrent BRAF(V600E) mutation and rearranged during transfection (RET) proto-oncogene protein expression.</p><p><b>METHODS</b>Fifty pathologically confirmed PTC patients who had received thyroidectomy were enrolled in this study. BRAF(V600E) mutation was detected by real time polymerase chain reaction (RT-PCR), while RET protein expression was measured by immunohistochemical SP method. Clinical and pathological features were compared between the concurrent BRAF(V600E) mutation and RET protein expression group (n=24) and BRAF(V600E) mutation or RET protein expression alone group (n=19). Seven patients were ruled out from the final analysis due to the absence of either BRAF(V600E) mutation or RET protein expression.</p><p><b>RESULTS</b>Of these 50 patients, BRAF(V600E) mutation and RET protein expression were detected in 38 patients (76%) and 28 patients (56%), respectively. Concurrent BRAF(V600E) mutation and RET expression was detected in 24 patients (48%). Compared with the concurrent BRAF(V600E) mutation and RET protein expression group, the BRAF(V600E) mutation or RET protein expression alone group had relatively poorer tissue differentiation and higher prognostic score (P=0.011, P=0.022).</p><p><b>CONCLUSION</b>PTC patients with concurrent BRAF(V600E) mutation and RET expression present poorer differentiation, more highly aggressive variant in carcinoma tissues, and higher cancer-related mortality risk.</p>

Invasive capacity of differentiated thyroid carcinoma in pediatric and adolescent patients / 中国医学科学院学报

<p><b>OBJECTIVE</b>To summarize the invasion features of differentiated thyroid carcinoma (DTC) in pediatric and adolescent patients.</p><p><b>METHODS</b>The clinical data of 32 DTC cases (≤18 years old) were retrospectively analyzed for the invasive capacity of DTC in terms of age and gender.</p><p><b>RESULTS</b>Bilateral (P=0.023), multifoci (P=0.037), and extrathyroid invasions (P=0.041) were more often in patients younger than 12 years old.</p><p><b>CONCLUSION</b>DTC in pediatric and adolescent patients tend to have a more aggressive pattern, especially in patients younger than 12 years.</p>

Efficacy of iodine-131 in treating hyperthyroid heart disease / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the value of iodine-131 therapy for hyperthyroidism complicated hyperthyroid heart disease(HHD) induced by Graves' disease or Plummer disease.</p><p><b>METHODS</b>Totally 40 HHD cases who were confirmed in our department from 2009 to 2010 were enrolled in this study. All patients received serum thyroid hormones and associated antibodies tests, 12-lead electrocardiogram, and/or thyroid imaging before and after iodine-131 therapy to access the treatment effectiveness.</p><p><b>RESULTS</b>Among 31 patients with HHD due to Graves' disease and 9 due to Plummer disease, iodine-131 treatment resulted in euthyroidism in 15 and 5 patients and hypothyroid in 7 and 2 patients, while 9 and 2 remain hyperthyroid, respectively.Serum free triiodothyronine, free thyroxine, and thyroid-stimulating hormone were statistically significant(P<0.05) before and after iodine-131 therapy, while no significant difference for serum thyrotrophin receptor antibody, antithyroid peroxidase autoantibody, and anti-thyroglobulin antibody.Atrial fibrillation was the most common cardiac complication of hyperthyroidism(n=25, 62.5%) .The remission rate after iodine-131 treatment was 76.0%.</p><p><b>CONCLUSION</b>Iodine-131 therapy can effectively and timely control hyperthyroid in HHD patients.</p>