Studies on surgical methods for sporadic micromedullary thyroid carcinoma

Background:To observe the changes in serum calcitonin levels after application of different surgical methods for primary medullary thyroid microcarcinoma(MTMC)and explore a more reasonable surgical method.Methods:A retrospective analysis of 36 patients with MTMC,16 in group A and 20 in group B,was performed.In group A,tumors were single and confined to the thyroid lobe,and thyroid lobectomy with isthmusectomy was performed.In group B,tumors were in the isthmus or invaded the thyroid gland,or there were multiple foci in bilateral lobes,and patients with primary foci underwent total thyroidectomy.The median follow-up time was 3.6 years.Clinical and pathological characteristics and changes in serum calcitonin(CTn)and carcinoembryonic antigen levels after the surgery were compared between the 2 groups.Results:The difference in the biochemical cure rate after surgery was statistically significant between patients with preoperative serum calcitonin levels<150 pg/mL and≥150 pg/mL(P<0.01).No significant differences in the biochemical cure rates and serum calcitonin levels were noted at different time points after surgery between group A and group B(P>0.05).One recurrence and metastasis were observed in each group after surgery.Conclusions:After performing different surgical methods for the primary foci of MTMC,the changes in serum calcitonin and carcinoembryonic antigen levels are similar.Especially for patients with single foci confined to the thyroid lobe without lateral cervical lymph node metastasis and with serum calcitonin levels<150 pg/mL,the unilateral thyroid lobectomy with isthmectomy can achieve the same therapeutic effect and biochemical cure rate as total thyroidectomy.

2016 Chinese expert consensus and guidelines for the diagnosis and treatment of papillary thyroid microcarcinoma

The incidence of papillary thyroid carcinoma(PTC)has exponentially increased in recent years.Papillary thyroid microcarcinoma(PTMC)accounts for the majority of the reported cases of PTC.The debates and crucial issues in PTMC management have received researchers'attention.To further improve the clinical management of PTMC in China,

2017 Chinese expert consensus on the clinical application ofserum marker for thyroid cancer

In recent years, the clinical incidence of thyroid cancer has been increasing year by year, and its risk assessment and clinical management methods have also been accordingly modified and constantly improved. There are great differences between the clinical diagnostic and therapeutic modes and disease management of thyroid cancer employed by various medical institutions in China, particularly with regard to the clinical application of serum marker of thyroid cancer. To this end, the China Anti-Cancer Association Thyroid Cancer Specialized Committee Chinese Association of Thyroid Oncology organized this compilation of ExpertConsensus on Clinical Application of Serum Marker of Thyroid Cancer to help and impel relevant clinical institutions and professionals to standardize clinical diagnosis, treatment, and long-term management of thyroid cancer, and to properly utilize the serum marker for scientific auxiliary clinical diagnosis and assessment of thyroid cancer before and after operation.

Factors influencing the presence of circulating differentiated thyroid cancer cells in the thyroidectomy perioperative period

Objective The aim of the study was to detect circulating differentiated thyroid cancer （DTC） micrometas-tasis and to investigate the factors influencing their presence in the perioperative thyroiclectomy period. Methods DTC micrometastases in the peripheral blood were detected with flow cytometry, and patient clinical and pathological factors were analyzed in 327 DTC patients. Results Circulating blood micrometastases were present in the peripheral circulation at a higher rate 1 week postoperatively than preoperatively and at 4 weeks postoperatively （P 〈 0.05）. The preoperative pres- ence of circulating micrometastasis was associated with the size of the tumor and the presence of lymph node metastasis （P 〈 0.05）, but was not related to the degree of tumor differentiation （P 〉 0.05）. At 4 weeks postoperatively, the presence of circulating micrometastasis was not associated with tumor size or lymph node stage （P 〉 0.05）, but was associated with poorly differentiated tumors （P 〈 0.05）. Conclusion The presence of circulating DTC micrometastases correlates to tumor size, lymph node stage, and operative manipulation. The differentiation degree of the tumors were associated with the persistent presence of micrometastasis in the circulating blood.

Correlation between sodium-iodide symporter expression and circulating tumor cell positivity in differentiated thyroid carcinoma

Objective We investigated the correlation between the expression of the sodium-iodide symporter(NIS) and the detection of circulating tumor cells(CTCs) in differentiated thyroid carcinoma(DTC).Methods NIS expression in differentiated thyroid and the positive rate of CTCs in the peripheral blood were determined by immunohistochemistry S-P and flow cytometry from the records of 172 cases of differentiated thyroid carcinoma.Results Seventy-six cases(44.2%) expressed NIS in the differentiated thyroid and 63 cases(36.6%) were positive for CTCs in the peripheral blood. There was a significant difference between N0 and N1 in the expression of NIS(χ~2 = 6.015, P = 0.014) and the positive rate of CTCs(χ~2 = 14.035, P = 0.001). N0 and N1 also differed significantly in the expression of NIS(r =-0.383,-0.610, P = 0.002, < 0.001). The differences in the NIS expression, but not in the positive rate of CTCs, were significant among the different pathological subtypes(χ~2 = 7.897, P = 0.005; χ~2 = 1.455, P = 0.228, respectively). There was a significant negative correlation between the highly differentiated type and intermediate differentiation type both in the expression of NIS and positive rate of CTCs(r =-0.591,-0.443, P < 0.001, P = 0.002). Conclusion There was a significant negative correlation between the expression of tissue NIS and positive rate of CTCs in the peripheral blood in DTC. The malignancy level and lymph node metastasis in differentiated thyroid carcinoma were negatively correlated with NIS expression and positively correlated with the positive rate of CTC.

BRAF V600E/TERT promoter mutations and NIS/TSHR expression in differentiated thyroid carcinomaand their clinical significance

Objective Telomerase reverse transcriptase(TERT) promoter mutations have recently been described in thyroid carcinoma.The purpose of this study was to investigate the clinical significance of(v-raf murine sarcoma viral oncogene homolog B1) BRAF V600 E and TERT promoter mutations in differentiated thyroid carcinoma(DTC).The relationship between the two mutations and NIS/TSHR expression was also analyzed.Methods We have detected BRAF V600 E and TERT promoter mutations by direct sequencing and NIS/TSHR expression by immunohistochemistry in 229 cases of DTC,52 cases of benign nodular goiter,and 31 cases of normal thyroid tissue.Results The BRAF V600 E mutation was detected in 142(62.0%) of 229 cases of DTC [141 cases of papillary thyroid carcinoma(PTC) and 1 case of follicular thyroid carcinoma(FTC)].TERT promoter mutations were detected in 18(7.9%) of 229 cases of DTC(14 cases of PTC and 4 cases of FTC),including the mutations C228T(0.9%) and C250T(7.0%),which were mutually exclusive.Moreover,11(61.1%) cases also harbored the BRAF V600 E mutation,which was not associated with gender,age,tumor size,lymph node metastasis,and recurrence risk stratification(P >0.05).The rate of TERT promoter mutation was higher in males,age ≥45,and in the middle/high-risk group(P <0.05),and the rate of simultaneous BRAF V600 E and TERT promoter mutations were higher in the middle/high-risk group(P <0.05).In addition,NIS positive rate in the concurrent BRAF V600 E and TERT promoter mutation group(45.5 %) was lower than in other groups(that is,the DTC group with BRAF V600 E or TERT promoter mutations(55.1%),the DTC group with no BRAF V600 E or TERT promoter mutation(57.5%),the nodules and normal group(75.9%);| r | = 0.171,P = 0.002).Conclusion TERT promoter mutations were lower in patients with DTC,with the C250 T mutation being the most common.The detection of BRAF V600 E mutation combined with TERT promoter mutations was instructive for the prognosis assessment and treatment of DTC.

Effect of parathyroid hormone on apoptosis of human medullary thyroid carcinoma cells

Objective The aim of the study was to investigate the effect of parathyroid hormone(PTH) on the apoptosis of human medullary thyroid carcinoma(MTC) cells.Methods In vitro cultured medullary thyroid carcinoma cell lines were treated with parathyroid hormone and parathyroid hormone receptor-monoclonal antibody,and the apoptosis of cells was detected by flow cytometry.Results The cell morphology changed significantly after treatment based on the observation using the inverted phase-contrast microscope.Various concentrations of parathyroid hormone and parathyroid hormone receptor-monoclonal antibody effectively induced apoptosis in a time-and concentrationdependent manner.When the concentration of parathyroid hormone was 2.0 μmol/L and that of parathyroid hormone receptor-monoclonal antibody was 1.0 μmol/L,the apoptotic rate was 13.24% and 20.78%,respectively,representing a statistically significant difference from that of the control cells(P < 0.05).Conclusion PTH plays a role in inducing apoptosis of human MTC cells.

Inhibition effects of parathyroid hormone on human medullary thyroid carcinoma cells

Objective： The purpose of the study was to investigate the effects of parathyroid hormone and parathyroid hormone receptor monoclonal antibody on in vitro growth and proliferation of human medullary thyroid carcinoma cell lines. Methods： The medullary thyroid carcinoma cell line was cultured in vitro, with parathyroid hormone and parathyroid hormone receptor monoclonal antibody treatment intervention, the growth of the cells was observed under an inverted contrast micro scope, the MTT assay was used to detect the cell growth inhibition rate. Results： Under the inverted contrast microscope, the cells changed significantly, the parathyroid hormone and parathyroid hormone receptor monoclonal antibodies can effectively inhibit the proliferation of medullary thyroid cancer cells in a time and dose dependent. When parathyroid hormone concentra tion reached a concentration of 2.0 IJmol/L, the parathyroid hormone receptor monoclonal antibody reached a concentration of 1.0 μmol/L, the cell growth was most significantly inhibited （P 〈 0.05）. Conclusion： Parathyroid hormone and parathyroid hormone receptor monoclonal antibody were able to inhibit the proliferation of medullary thyroid carcinoma cells and signifi cantly reduce the proliferation index.

Effects of rearranged during transfection mutation on calcitonin and procalcitonin expression in sporadic medullary thyroid carcinoma

Objective The aim of this study was to investigate the effects of rearranged during transfection(RET)mutation on the expressions of calcitonin(CTn)and procalcitonin(PCT)in sporadic medullary thyroid carcinoma(SMTC).Methods RET mutation was detected by polymerase chain reaction direct sequencing in 64 cases of SMTC,and the expression levels of CTn and PCT in SMTC tissues were detected using the immunohistochemical streptavidin-perosidase(SP)method.The effect of RET mutations on the expression of CTn and PCT along with its relationship with clinicopathological parameters were analyzed.Results The expression rates of CTn and PCT in SMTC tissues were 90.6%(58/64)and 67.2%(43/64),respectively.CTn and PCT expression were found to be associated with tumor size and lymph node metastasis(P<0.05)but not with gender,age,or tumor capsule invasion(P>0.05).There was a significant correlation between CTn and PCT expression(r=0.269,P=0.041),and the intensity of positive CTn expression was positively correlated with RET mutation(r=0.507,P=0.000).However,PCT expression was not associated with RET mutation(r=0.188,P=0.136).Conclusion High expression of CTn and PCT was associated with the progression of medullary carcinoma,and the intensity of CTn expression was associated with RET mutation.PCT may provide valuable information for the diagnosis and prognosis of SMTC.

Clinical value of cancer cells joint detection in peripheral blood plasma of thyroid cancer patients

We aimed to detect cytokeratin 19 （CK19） and polymorphic epithelial mucin 1 （MUC1） expression in peripheral blood of thyroid cancer patients, and investigate the clinical value of it as a diagnostic marker for circulating blood micrometastases. Methods： The flow cytometry （FCM） was used to detect and analyze CK19 and MUC1-expressing cells in peripheral blood of 491 thyroid cancer patients. Results： CK19 and MUC1 expression showed no statistically significant difference with gender and age in thyroid cancer patients （P 〉 0.05）, while had statistically significant difference with tumor size, lymph node stage and distant metastasis （P 〈 0.01）. The expression of CK19 and MUC1 were positively correlated （r = 0.628, P = 0.00）. Conclusion： CK19 is closely related to MUC1 expression, tumor size, extent of invasion and distant metastasis in peripheral blood of thyroid cancer patients. The circulating blood CK19 and MUC1 tests can help predict thyroid cancer micrometastases and prognosis.

Scabrous patrinia root inhibits circulating tumor cells in differentiated thyroid carcinoma–a clinical observation

Objective To observe the clinical inhibition of circulating tumor cells(CTCs) in differentiated thyroid carcinoma(DTC) by the extract of scabrous patrinia root(Huikangling).Methods Eighty-seven DTC patients tested positive for CTCs were randomly divided into two groups; all patients were treated with oral levothyroxine sodium in accordance with the DTC endocrine inhibition treatment criteria. Patients(n = 45) in the treatment group were provided the standard endocrine therapy along with oral Huikangling(0.4 g/tablet, 0.4 g × 3/time, 3 times/day, 12 weeks). Patients(n = 42) in the control group were only provided the standard therapy. After 4 and 12 weeks, CTCs in the blood were detected by flow cytometry.Results After 4 weeks of oral Huikangling treatment, CTCs were detected in 18(40%) and 29(69%) patients in the treatment and control groups, respectively; the difference was statistically significant(χ2 = 8.49, P < 0.05). After 12 weeks, CTCs were detected in 7(15.6%) and 17(44.7%) patients in the treatment and control groups, respectively; the difference was statistically significant(χ2 = 5.68, P < 0.05). Follow-up evaluation revealed two patients with lung metastasis and one patient with bone metastasis in the control group; one patient showed lateral neck lymph node metastasis without local recurrence in the treatment group.Conclusion Huikangling treatment reduces the number of CTC-positive DTC cases; however, further studies are needed to elucidate the underlying mechanisms.

Clinical significance of BRAF^(V600E) and TERT promoter mutation in papillary thyroid microcarcinoma

Objective The objective of this study was to analyze the correlation between BRAF^(V600E) and TERT promoter mutations and papillary thyroid microcarcinoma (PTMC) risk factors, and their importance in the risk assessment of papillary thyroid microcarcinoma.Methods This study retrospectively analyzed 107 cases of PTMC, which were diagnosed after the surgery in the department of head and neck surgery in Gansu Province Tumor Hospital from October 2014to June 2016. The mutations of BRAFV^(600E) and TERT promoter were detected by PCR direct sequencing.We analyzed the data usingχ~2 test and binary Logistic regression analysis.Results Among 107 patients with PTMC, the BRAFV^(600E) and TERT promoter mutation rates were 68.2%and 11.2%, respectively. Single factor analysis showed that there was a significant difference between the presence of membrane invasion, lymph node metastasis, and BRAFV^(600E) mutations (P<0.01). The age,gender, thyroid capsular invasion, poor pathologic subtype, and lymph node metastasis of patients, was significantly associated with the TERT promoter mutation (P<0.05) and the coexistence of the BRAF^(V600E)and TERT promotor mutations; although, there was a difference between the association of these factors with the TERT promoter mutation and the association of these factors with the coexistence of the BRAF^(V600E)and TERT promotor mutations. The multifactorial analysis showed that the factors closely related to the BRAFV^(600E) mutation included capsular invasion (P=0.012) and lymph node metastasis (P=0.000). The following factors were closely associated with the TERT promoter mutant:male (P=0.004), aged <45 years(P=0.026), capsular invasion (P=0.004), pathological subtype (P=0.030), and lymph node metastasis (P=0.043). The following factors were closely related to the simultaneous mutation of BRAFV^(600E) and TERT:male (P=0.022), capsular invasion (P=0.023), poor pathological subtype (P=0.041), and lymph node metastasis (P=0.030).Conclusion The risk of recurrence increases significantly when mutations in BRAFV^(600E) and TERT promoters occur simultaneously in PTMC and may have adverse outcomes. Combined detection of BRAFV^(600E) and TERT promoter mutations is of great value in risk assessment of PTMC.

Correlation between thyroid function and nodular goiter accompanied with gallstone

Objective： The purpose of the study wass to explore the correlation between thyroid function and nodular goiter accompanied with gallstone. Methods： We collected 120 cases about nodular goiter accompanied with gallstone and 128 cases about nodular goiter and establish 50 healthy control groups. Detected t level of hyrotropic hormone （TSH）, total triio- dothyronine （TT3）, total thyroxine in the peripheral venous blood of these cases in the three groups by using electrochemilu- minescenca immunoassay, measure level of total cholesterol （TC）, high-density tipoprotein cholesterol（HDL-C）, low-density lipoprotein cholesterol （LDL-C） and total bile acid （TBA） levels by using enzymic method, and observed the changes of thyroid function and blood lipid among the three groups. Results： The serum TT3 level in nodular goiter accompanied with gallstone group and the nodular goiter group was significantly lower than that in control group （P 〈 0.01）, and TSH level in the nodular goiter accompanied with gallstone group is significantly higher than that in control group （P 〈 0.01）, There were no statistical significance about difference of TT4 level among the three groups （P 〉 0.05）. Accordingly, TC and LDL-C level in nodular goiter accompanied with gallstone group was significantly higher than that in nodular goiter and control group （P 〈 0.01）, while TBA level in nodular goiter accompanied with gallstone group was significantly lower than that in simple nodular goiter group and control group （P 〈 0.01）. There was no statistical significance about difference of TC and LDL-C level between simple nodular goiter group and control group （P 〉 0.05）. The HDL-C level in nodular goiter accompanied with gallstone group and control group was higher than that in simple nodular goiter group （P 〈 0.01）. Conclusion： The originating etiologic factor of nodular goiter accompanied with gallstone may be related to that the decreased TT3 induced sub-clinical hypothyroidism.

Correlation analysis between serum β2-MG and sodium/iodide symporter in patients with thyroid carcinoma

Objective： The aim of our study was to investigate the correlation between the expression of sodium/iodide symporter, serum levels of β2-MG and prognosis of thyroid carcinoma patients. Methods： Ninty-five cases with thyroid carcinoma, using enzyme-linked immunosorbent assay with double-antibody sandwich to detect the serum β2-MG levels and immunehistochemistry to detect NIS expression of thyroid cancer tissue. Results： Thirty-seven cases showed positive expression of sodium/iodide symporter （38.9%） and 30 cases showed positive expression of β2-MG （31.57%）. There were significant differences of NIS expression （X2 = 8.207, P = 0.017） and β2-MG expression （X2 = 10.121, P = 0.006） between different pathological types of thyroid carcinoma, but there was no correlation between the positive rate of the two research groups （r = -0.546, P = 0.633）. The significant differences was observed in expression of sodium/iodide symporter （X2 = 9.272, P=0.002） and expression of β2-MG （X2 = 4.441, P = 0.035） between the group with neck lymph node metastasis and the group without neck lymph node metastasis and both positive rate was significantly negatively correlated （r = -1.000, P = 0.000）. The significant differences was observed in expression of sodium/iodide symporter （X2 = 9.272, P = 0.002） and expression of β2-MG （X2 = 3.867, P = 0.043） between the group with distant organ metastasis and the group without distant organ metastasis （X2 = 11.985, P = 0.001） and both positive rate was significantly negatively correlated （r = -1.000, P = 0.000）. Conclusion： There are significantly negatively correlated between neck lymph node metastasis, distant organ metastasis and expression of sodium/iodide symporter and expression of β2-MG. Thyroid cancer lymph node and distant organ metastasis, the tumor tissue NIS expression and serum levels of β2-MG is significantly negatively correlated. The detection of serum β2-MG provides clinical reference value for the effects on radionuclide therapy and prognosis assessment of thyroid carcinoma. Serum β2-MG levels is negatively correlated with prognosis in thyroid cancer patients.

Radiofrequency induction on sodium/iodide symporter expression of thyroid cancer

Objective; The aim of this study was to investigate the effects of radiofrequency treatment on sodium/iodide symporter expression of thyroid cancer ceils. Methods： In 29 thyroid cancer patients with low or no expression of soda ／ iodide symporter, the radio frequency combined 1311 therapy was used, the whole-body scintigraphy and serum Ig were detected before and after the radiofrequency treatment. Results： The whole-body scintigraphy showed that 4 cases （4/29） before radiofrequenc_y treatment had positive iodine uptake, 19 cases （19/29） two weeks after radiofrequency treatment had the positive iodine uptake, 12 cases （12/29） four weeks after radiofrequency treatment had the positive iodine uptake. Four weeks after radiofrequency treatment, 5 cases had increased serum Ig levels, 17 cases had decreased serum Ig levels, 7 cases showed no change. 25 cases （25/29） were effective, 15 cases （15/29） were cured. Conclusion： The radiofrequency induced the non-expressed the sodium/iodide symporter of thyroid cancer cells regain the iodine intake ability, it improved the clinical efficacy of 131I therapy in dedifferentiated thyroid cancer.

The clinical significance evaluation of serum β_2-microglobulin for thyroid cancer patients

Objective： The aim of this study was to investigate the clinical value and relevance on the serum β2-microglobulin （β2-MG） of patients with thyroid cancer. Methods： One thousand and two normal cases, 95 thyroid cancer patients and 243 nodular goiter patients were selected to measure serum β2-MG levels using double-antibody sandwich enzyme-linked immunosorbent assay （ELISA）. Results： The positive rate of 7.78% in normal population （78/1002） and 31.57% in thyroid cancer patients （30/95）. There were significant differences between the normal population and thyroid cancer patients （X2 = 55.352; P = 0.000）. The positive rate of 7.81% in nodular goiter patients （19/243） and there were no significant differences between the normal population and nodular goiter patients （X2 = 0.0004; P = 0.986）, but significant differences between nodular goiter patients and thyroid cancer patients （x2 = 31.106; P = 0.000）. Meanwhile, the significant difference of the positive rate existed in between the various pathological types of thyroid cancer （X2 = 10.015; P = 0.007）, anaplastic thyroid cancer patients with the highest positive rate and The significant difference was found between the positive lymph node metastasis groups and negative lymph node metastasis groups （x2 = 4.441; P = 0.035）, the presence of distant metastasis group and absence of distant metastasis group （X2 = 9.795; P = 0.002）. Conclusion： Serum β2-MG levels and prognosis of thyroid cancer patients was negatively correlated. It showed important clinical value to detect the level of β2-MG in the early diagnosis, prognosis and the clinical observation for thyroid cancer patients.