Risk stratification for radioactive iodine refractoriness using molecular alterations in distant metastatic differentiated thyroid cancer

Objective: Patients with radioactive iodine-refractory differentiated thyroid cancer(RAIR-DTC) are often diagnosed with delay and constrained to limited treatment options. The correlation between RAI refractoriness and the underlying genetic characteristics has not been extensively studied.Methods: Adult patients with distant metastatic DTC were enrolled and assigned to undergo next-generation sequencing of a customized 26-gene panel(Thyro Lead). Patients were classified into RAIR-DTC or non-RAIR groups to determine the differences in clinicopathological and molecular characteristics. Molecular risk stratification(MRS) was constructed based on the association between molecular alterations identified and RAI refractoriness, and the results were classified as high, intermediate or low MRS.Results: A total of 220 patients with distant metastases were included, 63.2% of whom were identified as RAIRDTC. Genetic alterations were identified in 90% of all the patients, with BRAF(59.7% vs. 17.3%), TERT promoter(43.9% vs. 7.4%), and TP53 mutations(11.5% vs. 3.7%) being more prevalent in the RAIR-DTC group than in the non-RAIR group, except for RET fusions(15.8% vs. 39.5%), which had the opposite pattern. BRAF and TERT promoter are independent predictors of RAIR-DTC, accounting for 67.6% of patients with RAIR-DTC. MRS was strongly associated with RAI refractoriness(P<0.001), with an odds ratio(OR) of high to low MRS of 7.52 [95%confidence interval(95% CI), 3.96-14.28;P<0.001] and an OR of intermediate to low MRS of 3.20(95% CI,1.01-10.14;P=0.041).Conclusions: Molecular alterations were associated with RAI refractoriness, with BRAF and TERT promoter mutations being the predominant contributors, followed by TP53 and DICER1 mutations. MRS might serve as a valuable tool for both prognosticating clinical outcomes and directing precision-based therapeutic interventions.

Role of TSH Inhibition Therapy in the Postoperative Management of Patients with Differentiated Thyroid Cancer

Objective:To investigate the effect of TSH inhibition therapy in the postoperative management of patients with differentiated thyroid cancer.Methods:Seventy patients diagnosed with differentiated thyroid cancer were selected for the study.TSH inhibition therapy was administered to the research group,while thyroxine replacement therapy was provided to the control group during the postoperative management phase.This allowed for a comparative analysis between the two groups.Results:In comparison with the control group,the research group exhibited significant decreases in serum TSH,T3,and T4 levels after treatment,while FT4 and FT3 levels significantly increased(P<0.05).Additionally,significant decreases in Tg,VEGF,TSGF,CD44V6,and sIL-2R levels were observed in the research group after treatment(P<0.05).No significant differences were found in pre-treatment thyroid function between the two groups(P>0.05).Conclusion:The application of TSH inhibition therapy in the postoperative management of patients with differentiated thyroid cancer demonstrates promising outcomes.

Characteristics of Persistent or Recurrent Differentiated Thyroid Cancer

Introduction: The differentiated thyroid cancer has generally an excellent prognosis after the treatment. The aim of this study is to describe the characteristics of persistent or recurrent differentiated thyroid cancers. Patients/ Methods: It is about a descriptive and retrospective study conducted from 392 patients followed for differentiated thyroid cancer. The data concerning the persistent or recurrent differentiated thyroid cancer have been collected from 1986 to 2015 in endocrinology service in Ibn Rochd CHU. Results: In total, twenty-four patients have shown the relapse or the persistency of their tumor, corresponding to the prevalence of 6.12 percent. The papillary carcinoma was dominant in 79 percent of cases and the follicular carcinoma in 21 percent of cases. The metastases were cerebral (two cases), lung (3 cases), bones (3 cases, Figure 1), and lymph nodes (9 cases). In our series, eighteen cases of persistent differentiated thyroid cancer have been found against six cases of recurrent differentiated thyroid cancer. Two cases of death at least three years of followed in our series and concerned the two cases of cerebral metastasis. Conclusion: The persistent or recurrent differentiated thyroid cancer rate is low in our series. The discovery of the relapse t is late.

Impact of Thyroglobulin on Survival and Prognosis of Differentiated Thyroid Cancer

Proper assessment of risk factors contributes to the principle management of differentiated thyroid carcinoma post operatively. Aim of the study: to investigate the effect of Thyroglobulin (Tg) levels on prognosis together with other risk factors for Differentiated Thyroid Cancer (DTC). Patients and methods: Medical records of all patients with DTC presented to Clinical Oncology and Nuclear Medicine Department referred from Diabetes & Endocrine unit (Internal Medicine Hospital) and Surgery Department Mansoura University from 2011-2016 were retrospectively reviewed. Patients with distant metastasis or who lost follow-up were excluded. So data of 220 patients were analyzed. Data collected included pre-surgical assessment, also surgical interference either total or near total thyroidectomy with or without lymph node neck dissection were reviewed. Different prognostic factors that affect progression free survival (PFS) include age, umorsize, ymph node status, ex, multifocality, capsular infiltration, vascular invasion and Tg level were evaluated through multivariate analysis. Results: Most of the patients included were <45 years (69.1%). Incidence of the disease was higher in female (80%) with papillary type predominance (80.9%). About 59.5% of cases presented with tumor size ≤ 2 cm and multifocality was reported in 13.6%. While 30% had lymph node metastasis, 11% had vascular invasion. Capsular infiltration was observed in 15% and most of them showed Tg level ≤ 10 ng/ml (68.2%). About 70% received ablative radioiodine. The 5-year Progression Free Survival (PFS) was 85%. On multivariate analysis of variable prognostic factors on PFS, we found that tumor size, age, lymph node status, capsular infiltration, Tg level and vascular invasion significantly affected PFS (P = 0.01, 0.005, 0.004, 0.005, 0.02, 0.003) respectively. While sex, pathological type and multifocality were not (P = 0.9, 0.4, 0.6) respectively. Conclusion: Postoperative Tg level is a statistically significant prognostic factor together with other risk factors.

Differentiated Thyroid Cancer with Thyroglobulin Elevation and Negative Iodine Scintigraphy (TENIS Syndrome)

Background and Objectives: Following the initial management, some patients with differentiated thyroid cancer (DTC) develop a state of high thyroglobulin (Tg) and Negative Iodine Scintigraphy. The predisposing factors and outcome of this condition are unclear. In this study, our objectives were to analyze the characteristics of patients with high Tg level and negative Iodine scintigraphy and to determine the predictive factors for development of high Tg and negative scintigraphy. Patients and Methods: Retrospective study of 34 patients undergoing treatment for DTC, followed in the Nuclear Medicine department of the University Hospital—Sahloul Sousse between 1990 and 2006 and having a high Tg and negative Iodine scintigraphy. Fourteen patients had Tg between 2 and 10 ng/ml, 16 had Tg between 11 and 100 ng/ml and 4 patients had Tg more than 100 ng/ml. Results: There were 25 women and 9 men. The mean age was 51.65 years. In 94.1% of cases, the tumor was papillary carcinoma. Follicular tumors accounted for only 5.9%. The mean nodule size was3.26 cm. Capsular invasion was seen in 47.1% cases. The locoregional invasion was found in 35.3%. The lymph node extension was found in 84.8% of patients having lymph node surgery. Lymph node involvement was observed in 92.8% of patients with papillary cancer but it was found in 7.2% of patients with follicular cancers. Lymph node invasion was unilateral in 28.6% (N1a) and bilateral, contralateral or mediastinal in 71.4% (N1b). Initial level of Tg was as follows: 7 patients had Tg between 2 and 10 ng/ml, 14 patients had Tg between 11 and 100 ng/ml and 12 had Tg more than 100 ng/ml. The mean number of radioactive Iodine cure was 11.08 for patients with Tg more than 100 ng/ml with a significant difference (P = 0.001). Conclusion: Among epidemiological, pathological and clinical characteristics, lymph node invasion is the most frequent parameter found in patients with a DTC with high Tg level and negative Iodine scintigraphy.

Changes in percentage of lymphocyte subsets after ^(131)I treatment in patients with differentiated thyroid cancer

To monitor the extent and the duration of lymphocyte subset changes in patients with thyroid carcinoma undergoing therapeutic 131I administration, the percentage of lymphocyte subsets were serially analyzed before and after 131I treatment. In patients who received 1850 MBq of 131I for ablation of thyroid remnants, only for NK cells and B cells showed a significant reduction. In patients received 3700 MBq of 131I for treatment of local lymph node me-tastases, NK cells, B cells and CD4+ were found decreased. In patients received 7400 MBq of 131I for treatment of distant metastases, NK cells, B cells and CD4+ and CD8+ were all affected. However, there is no significant reduc-tion compared to the baseline in the percentage of all lymphocyte subsets three months after 131I treatment. The re-sults show that the sensitivity of lymphocytes to 131I internal radiation depends upon lymphocyte phenotype and 131I activity. The immunosuppression effects are temporary and reversible.

ANALYSIS OF EFFICACY IN TREATMENT OF LOW-RISK WELL-DIFFERENTIATED THYROID CANCER WITHOUT CERVICAL LYMPH NODE INVOLVEMENT: 42 CASES REPORT

Objective To assess the more appropriate surgical treatment for low-risk group differentiated thyroid cancer. Methods A total of 42 low-risk patients with DTC, according to the AMES system (male, n = 6; female, n = 36) , were chosen for total thyroidectomy or subtotal thyroidectomy with center compartment lympha-dectomy. Results Nineteen patients had cervical lymph node involvement. Two patients had recurrent nerve injured. One patient had hypoparathyroidism. There were no mortality or local lymph recurrent up to present. Conclusion Total thyroidectomy or subtotal thyroidectomy with prophylactic center compartment lymphadectomy is an appropriate approach for the treatment of low-risk group differentiated thyroed cancer, to prevent recurrent and improve life quality.

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.

甲状腺全切术治疗对DTC患者炎性反应、神经营养因子的影响及其与喉返神经损伤的相关性

目的:探究甲状腺全切术治疗对分化型甲状腺癌(DTC)患者炎性反应、神经营养因子的影响及其与喉返神经(RLN)损伤的相关性。方法:选取285例DTC患者为研究对象。所有患者均行甲状腺全切术治疗。记录患者围术期指标、RLN损伤情况。比较患者术前、术后12、24 h及3、7、30 d的炎性反应指标[白细胞介素6(IL-6)、C反应蛋白(CRP)、肿瘤坏死因子α(TNF-α)]、神经营养因子[脑源性神经营养因子(BDNF)、神经生长因子(NGF)]水平,同时比较有无RLN损伤患者术后12 h的上述指标水平。采用Pearson法分析炎性反应指标、神经营养因子水平之间的相关性。结果:手术时间(88.35±7.64)min;术中出血量(23.24±6.98)mL;术后引流量(97.41±14.23)mL;术后住院时间(7.56±3.54)d。患者IL-6、CRP及TNF-α水平均随时间发展而呈先升高后降低的趋势(P<0.05)。患者BDNF、NGF水平均随时间发展而呈先降低后升高的趋势(P<0.05)。患者RLN损伤发生率为13.68%。RLN损伤组术后12 h的IL-6、CRP及TNF-α水平高于无RLN损伤组(P<0.05),BDNF、NGF水平低于无RLN损伤组(P<0.05)。RLN损伤组患者IL-6、CRP、TNF-α水平均随时间发展而呈先升高后降低的趋势(P<0.05),而BDNF、NGF水平均随时间发展而呈先降低后升高的趋势(P<0.05)。IL-6、CRP、TNF-α水平之间及BDNF、NGF之间均呈正相关关系(P<0.05),IL-6、CRP、TNF-α水平与BDNF、NGF水平均呈负相关关系(P<0.05)。结论:甲状腺全切术治疗DTC患者具有手术时间短、创伤小、术后恢复快的优点,对炎性反应、神经营养因子的影响较为轻微;但该手术会引起一定的RLN损伤,且炎性反应和神经营养因子均与RLN损伤有密切联系。

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.

Analysis of the incidence and influencing factors of hyponatremia before ^(131)I treatment of differentiated thyroid carcinoma

BACKGROUND Hyponatremia is a common clinical electrolyte disorder.However,the association between hyponatremia and acute hypothyroidism is unclear.Acute hypothyroidism is usually seen in patients who undergo preparation for radioactive iodine therapy.AIM To analyze the incidence and influencing factors of hyponatremia in a condition of iatrogenic acute hypothyroidism in patients with differentiated thyroid cancer(DTC)before ^(131)I treatment.METHODS The study group consisted of 903 DTC patients who received ^(131)I treatment.The clinical data before and after surgery,as well as on the day of ^(131)I treatment were analyzed.According to the blood sodium level before ^(131)I treatment,patients were divided into the non-hyponatremia group and hyponatremia group.Correlations between serum sodium levels before ^(131)I treatment and baseline data were analyzed.Univariate analysis and binary logistic regression were performed to identify the influencing factors of hyponatremia.RESULTS A total of 903 patients with DTC,including 283(31.3%)males and 620(68.7%)females,with an average age of 43.8±12.7 years,were included in this study.The serum sodium levels before surgery and ^(131)I treatment were 141.3±2.3 and 140.5±2.1 mmol/L,respectively(P=0.001).However,the serum sodium levels in males and females before ^(131)I treatment were lower than those before surgery.Patients aged more than 60 years and less than 60 years also showed decreased serum sodium levels before ^(131)I treatment.In addition,the estimated glomerular filtration rate(eGFR)in males and females decreased before ^(131)I treatment compared with those before surgery(P=0.001).Moreover,eGFR in patients over 60 years and under 60 years decreased before ^(131)I treatment,when compared with that before surgery.There were no significant differences in serum potassium,calcium,albumin,hemoglobin,and blood glucose in patients before surgery and ^(131)I treatment(P>0.05).Among the 903 patients,23(2.5%)were diagnosed with hyponatremia before ^(131)I treatment,including 21 cases(91.3%)of mild hyponatremia and 2 cases(8.7%)of moderate hyponatremia.Clinical data showed that patients with mild hyponatremia had no specific clinical manifestations,while moderate hyponatremia cases were mainly characterized by fatigue and dizziness,which were similar to neurological symptoms caused by hypothyroidism and were difficult to distinguish.Correlation analysis showed a correlation between serum sodium before ^(131)I treatment and the preoperative level(r=0.395,P=0.001).There was no significant correlation between blood sodium and thyroid-stimulating hormone(TSH)levels and urine iodine before ^(131)I treatment(r=0.045,P=0.174;r=0.013,P=0.697).Univariate analysis showed that there were significant differences in age,sex,history of diuretic use,distant metastasis,preoperative blood sodium,blood urea nitrogen(BUN),eGFR,TSH and urinary iodine between the two groups(all P<0.05).Logistic regression analysis showed that factors such as history of diuretic use,distant metastases,preoperative sodium and BUN were all influencing factors of hyponatremia.The Hosmer and Lemeshow test(c2=2.841,P=0.944)suggested a high fit of the model.Omnibus tests of model coefficients indicated the overall significance of the model in this fitted model(P<0.05).Preoperative serum sodium was a significant factor associated with pre-^(131)I therapy hyponatremia(OR=0.763;95%CI:0.627-0.928;P=0.007).CONCLUSION The incidence of hyponatremia induced by ^(131)I treatment preparation was not high.Preparation for radioactive iodine therapy was not a risk factor for the development of hyponatremia in thyroid cancer patients.

Short-term overt hypothyroidism affect on lipids after thyroxine-withdrawal in patients with differentiated thyroid carcinoma

Objective: The aim of the study was to investigate the effects of short-term overt hypothyroidism on lipids after thyroxine-withdrawal in patients with iatrogenically induced hypothyroidism before radioiodine treatment for differentiated thyroid carcinoma (DTC). Methods: Thirty patients with a history of differentiated thyroid carcinoma on thyroid-stimulating hormone (TSH)-suppressive thyroxine replacement therapy were studied. Blood sample were taken before and 4 weeks after withdrawal of thyroxine substitution. Venous blood was drawn after an overnight fast and analyzed for serum free T4 (FT4), free T3 (FT3), thyroid-stimulating hormone (TSH), total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB). Fifty healthy people matched for age and gender were controls. Their blood samples were taken only once. Results: After thyroxine-withdrawal, the patients presented with increased serum TSH and low serum FT4 and FT3 levels compared with controls. Serum TG, TC, LDL, HDL, ApoB and Lp(a) increased after thyroxine withdrawal, reaching statistical significant differences with previous evaluation. However, when compared to euthyroid controls, only TC, LDL and ApoB were increased when patients were hypothyroidism. No changes were observed in ApoA1 in patients during thyroxine withdrawal, or when comparing the values observed in patients to those of euthyroid controls. Conclusion: TG, TC, LDL, HDL, ApoB and Lp(a) were increased during short-term overt hypothyroidism.

Expression and significance of ER and PR in differentiated thyroid carcinoma

Objective： The aim of the study was to investigate the relationship between expressions of estrogen receptor （ER）, progesterone receptor （PR） and gender, age, tumor size, lymph node metastasis, capsular invasion and histological type of differentiated thyroid carcinoma （DTC）. Methods： Seventy cases of DTC who received surgery in our hospital （No. 401 Hospital of People＇s Liberation Army, Qingdao, China） between January 2008 and December 2011 were selected. Among them, 61 cases were papillary carcinoma and 9 cases were follicular carcinoma. Twenty cases were normal thyroid tissue adjacent to the tumor which was used as control. Immunohistochemical SP method was employed to detect the expression of ER and PR. Results： The positive rates of ER and PR in tumor tissues of DTC patients were 21.4% （15/70） and 31.4% （22/70）, respectively, and no expression of ER or PR were founded in normal thyroid tissue （P 〈 0.01）. The expressions of ER and PR were related to the lymph node metastasis and capsular invasion （X2 = 16.913 and 6.327, P 〈 0.05; x2 = 7.516 and 12.727, P 〈 0.05）. No relationship was observed between the expressions of EPJPR and gender, age, and histological type （P 〉 0.05） of DTC patients. Conclusion： The expression levels of ER and PR in the tumor tissue of DTC patients were higher than those in the normal thyroid tissue nearby the tumor. Therefore, ER and PR expression might be clinical markers for DTC and its prognosis.

早期积极心理干预对DTC患者负性情绪和癌因性疲乏的影响

目的 探讨在分化型甲状腺癌(DTC)患者的治疗中,采用早期积极心理进行干预,对患者负性情绪和癌因性疲乏的影响。方法 抽取2021年6月—2023年1月平煤神马医疗集团总医院收治的160例DTC癌患者,随机分为对照组(常规护理)和研究组(常规护理+早期积极心理干预),每组各80例,评估患者干预前后的心理状态、癌因性疲乏、生活质量、护理工作满意度。结果 护理干预1~4周后,两组患者汉密尔顿抑郁量表(HAMD)评分、汉密尔顿焦虑量表(HAMA)评分均降低,并且研究组患者评分更低(P<0.05);干预后,两组患者的癌因性疲乏评分均升高,但是研究组患者的以上指标升高幅度小于对照组(P<0.05);此外,两组患者的护士观察量表(NOSIE)评分均明显改善,并且研究组变化幅度大于对照组(P<0.05);研究组患者的护理满意度高于对照组(95.00%vs 82.50%,P<0.05)。结论 对DTC患者开展早期积极心理干预,能够帮助患者改善负性情绪,减轻癌因性疲乏,提高患者的生活质量和护理满意度。

New approaches for patients with advanced radioiodine-refractory thyroid cancer

The cumulative evidence over the past decades has shown that the incidence of differentiated thyroid carcinoma(DTC)has exponentially increased.Approximately 10%of patients with DTC exhibit recurrent or metastatic disease,and about two-thirds of the latter will be defined as refractory to radioactive iodine(RAIR)treatment.Since this condition implies 10-year survival rates less than 10% after detection,using available treatments,such as systemic and targeted therapies,have become increasingly relevant.The initiation of these treatments aims to reach stabilization,tumor volume reduction,and/or symptom improvement and it should be decided by highly specialized endocrinologists/oncologists on the basis of patient’s features.Considering that despite enlarged progression-free survival was proven,multikinase inhibitors remain non-curative,their benefits last for a limited time and the side effects potentially cause harm and quality of life reduction.In this context,molecular testing of cancer cells provides a promising spectrum of targeted therapies that offer increased compatibility with individual patient needs by improving efficacy,progression free survival,overall survival and adverse events profile.This review article aims to provide a summary of the current therapeutic strategies in advanced RAIR-DTC,including approved target therapies as well as those for off-label use,RAI resensitization agents,and immunotherapy.

Stem cell biology in thyroid cancer: Insights for novel therapies

Currently, thyroid cancer is one of the most common endocrine cancer in the United States. A recent involvement of sub-population of stem cells, cancer stem cells, has been proposed in different histological types of thyroid cancer. Because of their ability of self-renewal and differentiation into various specialized cells in the body, these putative cells drive tumor genesis, metastatic activity and are responsible to provide chemo- and radioresistant nature to the cancer cells in the thyroid gland. Our Review was conducted from previously published literature to provide latest apprises to investigate the role of embryonic, somatic and cancer stem cells, and discusses the hypothesis of epithelial-mesenchymal transition. Different methods for their identification and isolation through stemness markers using various in vivo and in vitro methods such as flow cytometry, thyrosphere formation assay, aldehyde dehydrogenase activity and ATP-binding cassette sub-family G member 2 efflux-pump mediated Hoechst 33342 dye exclusion have been discussed. The review also outlines various setbacks that still remain to target these tumor initiating cells. Future perspectives of therapeutic strategies and their potential to treat advanced stages of thyroid cancer are also disclosed in this review.

DTC术后残留/复发转移性淋巴结^(18)F-FDG和^(131)I代谢与临床病理和^(131)I疗效的相关性

目的分析分化型甲状腺癌(differentiated thyroid cancer,DTC)术后伴残留/复发转移性淋巴结的^(18)F-FDG PET/CT和^(131)I显像特点及其与临床病理特征和^(131)I治疗效果的相关性。方法回顾性纳入分析DTC术后伴残留/复发转移性淋巴结、并在^(131)I治疗前行^(18)F-FDG PET/CT显像和^(131)I治疗后扫描(^(131)I-WBS)患者,根据2种显像结果将转移淋巴结分为^(18)F-FDG PET/CT阳性(^(18)F+)和阴性(^(18)F-)组,以及^(131)I-WBS阳性(^(131)I+)和阴性(^(131)I-)组。采用2015 ATA指南将^(131)I治疗疗效分为疗效满意(excellent response,ER)组和非ER组。采用卡方检验和非参数检验进行数据比较,采用受试者工作特征曲线评估^(131)I治疗前刺激性甲状腺球蛋白(stimulated thyroglobulin,sTg)对治疗效果的预测价值。结果纳入DTC术后伴残留/复发转移性淋巴结患者80例,其中男28例、女52例,年龄(43.25±13.59)岁。^(18)F+和^(18)F-患者分别为64(80.0%)和16(20.0%)例;^(131)I+和^(131)I-患者分别为29(36.3%)和51(63.7%)例。^(18)F+和^(131)I-患者多伴原发灶BRAF基因突变,差异有统计学意义(χ^(2)=4.267、11.025,P=0.039、0.001)。DTC术后转移淋巴结^(131)I治疗后,ER和非ER组患者分别为14/80(17.5%)和66/80(82.5%),与ER组比较,非ER组淋巴结转移患者往往表现为^(18)F+和^(131)I-,且sTg水平较高,差异有统计学意义(χ^(2)=3.945、13.152,Z=-3.141,P=0.047、<0.001、0.002)。sTg预测^(131)I治疗效果的最佳阈值为23.52μg/L、曲线下面积为0.793(95%CI:0.680.88)、灵敏度为85.7%、特异度为72.7%。结论DTC术后FDG代谢增高、^(131)I摄取不佳的残留/复发转移性淋巴结多见于原发灶伴BRAF基因突变的患者;FDG和^(131)I这种代谢特点、BRAF基因突变以及高sTg血症是DTC残留/复发转移性淋巴结^(131)I治疗效果欠佳的影响因素。

Optimal Threshold of Stimulated Serum Thyroglobulin Level for ^(18)F-FDG PET/CT imaging in Patients with Thyroid Cancer

This study was to explore the optimal threshold of thyroid-stimulating hormone(TSH)-stimulated serum thyroglobulin(s-Tg) for patients who were to receive18F-fluorodeoxyglucose(18F-FDG) PET/CT scan owing to clinical suspicion of differentiated thyroid cancer(DTC) recurrence but negative post-therapeutic 131I whole-body scan(131I-WBS). A total of 60 qualified patients underwent PET/CT scanning from October 2010 to July 2014. The receiver operating characteristic(ROC) curve analyses showed that s-Tg levels over 49 μg/L led to the highest diagnostic accuracy of PET/CT to detect recurrence, with a sensitivity of 89.5% and a specificity of 90.9%. Besides, bivariate correlation analysis showed positive correlation between s-Tg levels and the maximum standardized uptake values(SUVmax) of18F-FDG in patients with positive PET/CT scanning, suggesting a significant influence of TSH both on Tg release and uptake of18F-FDG. So, positive PET/CT imaging is expected when patients have negative 131I-WBS but s-Tg levels over 49 μg/L.

Role of prophylactic central neck lymph node dissection for papillary thyroid carcinoma in the era of de-escalation

Thyroid cancer is the most common endocrine malignancy.While there has been no appreciable increase in the observed mortality of well-differentiated thyroid cancer,there has been an overall rise in its incidence worldwide over the last few decades.Patients with papillary thyroid carcinoma(PTC)and clinical evidence of central(cN1)and/or lateral lymph node metastases require total thyroidectomy plus central and/or lateral neck dissection as the initial surgical treatment.Nodal status in PTC patients plays a crucial role in the prognostic evaluation of the recurrence risk.The 2015 guidelines of the American Thyroid Association(ATA)have more accurately determined the indications for therapeutic central and lateral lymph node dissection.However,prophylactic central neck lymph node dissection(pCND)in negative lymph node(cN0)PTC patients is controversial,as the 2009 ATA guidelines recommended that CND“should be considered”routinely in patients who underwent total thyroidectomy for PTC.Although the current guidelines show clear indications for therapeutic CND,the role of pCND in cN0 patients with PTC is still debated.In small solitary papillary carcinoma(T1,T2),pCND is not recommended unless there are high-risk prediction factors for recurrence and diffuse nodal spread(extrathyroid extension,mutation in the BRAF gene).pCND can be considered in cN0 disease with advanced primary tumors(T3 or T4)or clinical lateral neck disease(cN1b)or for staging and treatment planning purposes.The role of the preoperative evaluation is fundamental to minimizing the possible detrimental effect of overtreatment of the types of patients who are associated with low disease-related morbidity and mortality.On the other hand,it determines the choice of appropriate treatment and determines if close monitoring of patients at a higher risk is needed.Thus,pCND is currently recommended for T3 and T4 tumors but not for T1 and T2 tumors without high-risk prediction factors of recurrence.

Screening and bioinformatics analysis of thyroid cancer-related hub genes

Objective:To identify the thyroid cancer-related hub genes and pathways by bioinformatics initially in order to lay the foundation for further study.Methods:The expression profile chips and data of thyroid cancer were screened and downloaded from the gene expression omnibus(GEO).The GEO2R was applied to identify the differential expressed genes between thyroid cancer tissues and normal thyroid tissues.And the Metascape online website was used for pathway and function enrichment.With the usage of STRING and Cytoscape,the protein-protein interaction network was constructed,and the plug-in app cytoHubba in Cytoscape was applied to screen hub genes.Kaplan-Meier Plotter was implemented to conduct survival analysis of hub genes for further screening and discussion.Results:A total of 304 differential expressed genes were screened,and were mainly enriched in the biological processes of extracellular matrix,cell-substrate adhesion,response to wounding,muscle structure development and hormone metabolic process etc.by Metascape.Protein-protein interaction network visualized 284 nodes;the top ten scores of Maximal Clique Centrality algorithm were taken as the criteria to screen out the hub genes with high connectivity in the gene expression network.The KM plotter analysis confirmed that 5 of 9 hub genes were correlated with the prognosis of thyroid cancer patients.Conclusion:FN1,SPP1,TIMP1,VCAN,COL1A1,COL1A2,MMP1,DCN,COMP and FMOD may play a significant role in the development of thyroid cancer.Genes which have prognostic significance in survival analyses were found to be relevant to the composition and regulation of extracellular matrix.