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.

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.

Correlation between Central and Lateral Neck Dissection in Differentiated Thyroid Carcinoma

Objective: To determine the histopathological correlation between central and lateral neck metastasis in differentiated thyroid carcinoma, and its potential therapeutic impact. Although the central neck dissection (CND) is recommended in differentiated thyroid carcinoma, the indication for lateral neck dissection (LND) remains controversial. Design: Retrospective study. Methods and Main Outcome Measures: Pathological analysis of systematic ipsilateral central neck dissection (CND) and LND performed with total thyroidectomy in differentiated thyroid carcinoma was retrospectively reviewed according to “side” and to “patient”. Results: A total of 56 sides (46 patients) were suitable for analysis. Analysis by “side” revealed that CND and LND dissection samples were both negative in 15 cases, both positive in 32, CND was positive and LND was negative for 8 cases and CND was negative and LND was positive in 1 case. The combined presence of positive LND and positive CND was therefore observed in 32/40 “sides” and 26/46 “patients”. Analysis by “side” of the impact of the treatment decision to perform ipsilateral LND only in patients with positive CND and vice versa demonstrated a sensitivity, specificity, and accuracy of 97%, 65%, and 84%, respectively. Conclusions: In most cases, the presence of positive LND was associated with positive ipsilateral CND. The very low prevalence of positive LND in patients with negative CND may justify LND as a second step procedure only in patients with positive CND, except in the case of documented lateral neck metastasis.

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.

The launch of a special issue on “Neck Dissection in Differentiated Thyroid Carcinoma” in Gland Surgery

Given the high incidence of cervical lymph node metastasis in differentiated thyroid cancer （DTC） and the rapidly increased importance of neck dissection in DTC, the journal of Gland Surgery is launching a special issue on ＂Neck Dissection in Differentiated Thyroid Carcinoma＂ in November Issue of 2013, inviting Dr. Xinying Li from Xiangya Hospital, China, as the guest editor.

^(131)I-chTNT-mediated radioimmunotherapy for non-uptaking ^(131)I pulmonary metastases from differentiated thyroid carcinoma

In this paper,the safety and efficacy of 131I-labeled mouse/human chimeric monoclonal antibody(131I-chTNT)-mediated radioimmunotherapy are evaluated because the patients have non-uptaking 131I pulmonary metastases from differentiated thyroid carcinoma(DTC).The 16 patients were injected intravenously by 29.6±3.7MBq·kg–1 using 131I-chTNT.The chest computer tomography was performed before treatment,as well as 28 and 70days after treatment.Responses and safety were assessed during the treatment.The results show that the 131I-chTNT infusion was well tolerated with the 12.5%complete response,18.8%partial response,25.0%progressive disease,and the 43.8%stable disease,indicating that most treatment-related adverse effects are mild transient and reversible.The131I-chTNT is promising for patients with non-uptaking the 131I pulmonary metastases from DTC.

两种不同剂量碘-131对非远处转移性高危分化型甲状腺癌全切术后患者DTC的应用效果

目的探讨两种不同剂量碘-131对非远处转移性高危分化型甲状腺癌(DTC)全切术后患者的应用效果。方法回顾性分析86例非远处转移性高危DTC患者的临床资料,所有患者均行DTC全切术,并按照碘-131治疗剂量的不同分成低剂量组(100~150 mCi)和高剂量组(150~200 mCi),前者为45例,后者为41例,治疗3个月,随访1年。比较两组相关临床治疗指标(清甲成功率、无病生存率、住院隔离时间)、甲状腺癌特异性生命质量量表(THYCA-QoL)和不良反应发生情况的差异。结果治疗及随访结束后,两组的清甲成功率无明显差异(P<0.05),低剂量组的无病生存率(95.56%)高于高剂量组(80.49%),且住院隔离时间短于高剂量组(P<0.05);两组生理功能和活动、心理功能、症状或对生活影响评分均高于同组治疗前,且低剂量组THYCA-QoL评分均高于高剂量组(P<0.05);低剂量组不良反应发生率(8.89%)低于高剂量组(29.27%)(P<0.05)。结论低剂量和高剂量碘-131对于非远处转移性高危DTC全切术后患者的治疗效果相当,但前者更有利于缩短住院隔离时间,提高无病生存率,减少不良反应的发生,进而提高生存质量。

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.

Papillary thyroid carcinoma with nodular fasciitis-like stroma-an unusual variant with distinctive histopathology:A case report

BACKGROUND Papillary thyroid carcinoma(PTC)is regarded as a fairly common endocrine malignancy,which can be divided into different multiple variants due to wide morphologic differences.The majority of PTC variants have been reported,but PTC with nodular fasciitis-like stroma(NFS)is a rare pathological variant and has been infrequently reported in the relevant literature.This condition involves abundant reactive stromal components rich in spindle cells,which may account for 60%-80%of the tumor along with a typical papillary carcinoma.CASE SUMMARY A 44-year-old man presented with a 4-mo history of a palpable mass over the anterior aspect of the left neck,the tumor demonstrated gradual enlargement but was painless during the 4 mo prior to discovery.Thyroid function test results were normal.Physical examination showed an enormous and firm nodular mass in the left lobe of the thyroid gland extending to the level of the hyoid bone.Ultrasonography of the neck revealed a well-defined heterogeneous lesion measuring around 5.0 cm×4.0 cm with a hypoechoic complex nodule,decreased vascularity and speckles of microcalcification.The patient underwent left thyroidectomy with central compartment lymph node dissection.Final histopathological examination confirmed the diagnosis of PTC with extensive fibromatosis-like stroma combined with typical PTC.The patient was asymptomatic at the 3-mo follow-up.CONCLUSION PTC-NFS is a rare pathological variant and its diagnosis and prognosis may be similar to typical papillary carcinoma.

Papillary Thyroid Carcinoma and Pregnancy: What Impact on Prognosis?

Introduction: The impact of pregnancy on the prognosis of papillary thyroid carcinoma (PTC) has been debated for several decades;however, no definitive conclusions have been reached. The main objective of this study is to demonstrate the short-term influence of pregnancy on the evolution and prognosis of PTC. Materials and Methods: A prospective descriptive and analytical study was conducted in the Endocrinology and Diabetology Department at the Hassan II University Hospital in Fez, including patients followed for papillary thyroid carcinoma presenting with a pregnancy during the year 2019 and 2020. The follow-up of these patients was continued until 1 year postpartum. We studied the clinical, paraclinical and therapeutic factors that could influence the prognosis of the disease. Results: We included 26 patients. Our study showed a significant correlation between recurrence and the presence of unfavorable histological signs (p = 0.02) as well as the initial Tg level (0.01). However, pregnancy was not an influencing factor (p = 0.41). Conclusion: Pregnancy does not seem to be a factor aggravating the prognosis of differentiated thyroid cancers.

Prevalence and Clinical Significance of Preoperative Thyroglobulin Antibodies in Differentiated Thyroid Cancer Patients

Thyroglobulin antibody (TgAb) has been used as a surrogate tumor marker of differentiated thyroid carcinoma (DTC) patients. Preoperative TgAb (PreopTgAb) is thought to affect the prevalence, disease severity, and outcome of DTC. The objective of the present study was to retrospectively analyze the prevalence of PreopTgAb in patients diagnosed with DTC and its relation to thyroid cancer characteristics, staging, and disease outcome. A retrospective analysis of 109 DTC patients with reports of PreopTgAb was carried out. Clinicopathological parameters, including patient demographics (age and gender), TNM staging, histopathologic characteristics (type of pathology, vascular invasion, extrathyroid extension, carcinoma variant, multifocality), treatment (surgery, radioactive iodine), and outcome were recorded. The association of PreopTgAb was compared with the study variables and outcome of the disease using the Chi-square test and Mann-Whitney tests. The prevalence of PreopTgAb was 59.6%. Among the 54 PreopTgAb positive patients, 34 patients had an excellent response and 15 patients had an indeterminate response, while biochemically and structurally incomplete response was observed in 3 and 2 patients, respectively. PreopTgAb was not significantly associated with age (p = 0.919), sex (p = 0.650), pathology (p = 0.079), stage at diagnosis (p = 0.513), vascular invasion (p = 0.211), extra thyroid extension (p = 0.734), histologic variant (p = 0.877), multifocality (p = 0.361), and outcome (p = 0.360). Although we did not find a significant association between positive PreopTgAb and clinical characteristics and outcome of DTC, it can still be considered as a surrogate marker of DTC during follow-up.

EFFECTS OF LEVOTHYROXINE ON BONE METABOLISM IN PATIENTS WITH DIFFERENTIATED THYROID CANCER AFTER OPERATION AND ^(131)I ABLATION

Objective To investigate the effects of substitutive and suppressive doses of levothyroxine on bone metabolism in patients with differentiated thyroid carcinoma after surgery and 131I ablation. Methods The patients, who had received levothyroxine(L-T4) for at least 3 years for treating their differentiated thyroid carcinoma after surgery and 131I therapy, were classified into substitutive group and suppressive group according to the levels of serum free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH). We compared the levels of FT3, FT4, TSH, serum parathyroid hormone (PTH), serum calcium (Ca), serum phosphate (P), serum alkaline phosphates (ALP) and Bone mineral density (BMD) to those of healthy volunteers well matched for sex, age, menopausal status, and body mass index (BMI). Results No significant differences were found in the bone density and biochemical parameters of bone metabolism of the subjects treated with substitutive or suppressive doses of L-T4 compared with the control subgroup. No significant differences were observed among the subgroups according to accumulative doses of 131I. No bone fracture was found in all the patients. Conclusion The substitutive and suppressive doses of L-T4 are safe and necessary for patients with differentiated thyroid carcinoma after surgery and 131I therapy. Such treatment for 3 years is not associated with increased risk of osteoporosis. Much longer term of follow up is still needed in patients receiving substitutive and suppressive doses of L-T4.

我国新旧版《甲状腺结节和分化型甲状腺癌诊治指南》——外科视角的比较

我国2023年发布的《甲状腺结节和分化型甲状腺癌诊治指南》(第二版)是在第一版(2012年版)的基础上由7个国家级学会、近百位内分泌科、甲状腺外科、肿瘤科、核医学科、超声医学科和病理科专家历时一年联合修订。新版《指南》仍分为甲状腺结节和分化型甲状腺癌两大部分,采用提出临床问题、进行解释、给出推荐意见的撰写模式,共给出了117条推荐意见。本文从外科视角比较新版和旧版《指南》中甲状腺结节的良恶性鉴别、分化型甲状腺癌的手术治疗等重点内容差异,并浅谈一些理解和体会。

^(131)I+TSH抑制治疗对分化型甲状腺癌术后患者甲状腺功能、免疫功能及复发转移的影响

目的研究分化型甲状腺癌(DTC)术后采用^(131)I+促甲状腺激素(TSH)抑制治疗的临床疗效及对患者甲状腺功能、免疫功能及复发转移的影响。方法回顾性选取2018年1月至2019年12月于该院就诊并接受治疗的97例DTC患者为研究对象,根据术后治疗方案不同分为对照组57例(采用TSH抑制治疗)和观察组40例(在对照组基础上联合^(131)I治疗)。观察两组清除残余甲状腺组织(清甲)的效果,以及甲状腺功能指标[游离三碘甲状腺原氨酸(FT3)、游离甲状腺素(FT4)、促甲状腺激素(TSH)及甲状腺球蛋白(Tg)]、甲状腺抗体指标[促甲状腺素受体抗体(TRAb)、甲状腺球蛋白抗体(TgAb)、抗甲状腺过氧化物酶抗体(TPOAb)]水平和免疫功能指标(CD3^(+)、CD4^(+)、CD8^(+)T淋巴细胞细胞亚群比例)变化。随访统计两组术后1、3年复发和转移情况。结果观察组完全清除率为72.5%,明显高于对照组的52.6%,差异有统计学意义(P<0.05)。治疗后,两组FT3、FT4水平明显升高(P<0.05),TSH和Tg水平明显降低(P<0.05);治疗后,观察组FT3、FT4、TSH水平与对照组比较,差异无统计学意义(P>0.05),Tg水平显著低于对照组,差异有统计学意义(P<0.05)。治疗后,两组TRAb、TgAb、TPOAb水平及CD8^(+)比例较治疗前明显降低,CD3^(+)、CD4^(+)比例较治疗前明显升高,且观察组水平优于对照组,差异有统计学意义(P<0.05)。观察组术后1、3年复发率分别为0、7.5%,转移率分别为2.5%、10.0%;对照组术后1、3年复发率分别为14.4%、22.8%,转移率分别为15.8%、28.1%,两组比较,差异均有统计学意义(P<0.05)。结论^(131)I+TSH抑制治疗能够提高清甲效果,降低TSH、Tg水平,维持甲状腺功能及改善患者免疫功能,抑制肿瘤复发、转移,提高患者预后。

血清E2、25(OH)D3及尿碘水平对分化型甲状腺癌的预测价值

目的分析血清雌二醇(E2)、25-羟基维生素D3[25(OH)D3]及尿碘水平对分化型甲状腺癌(DTC)的预测价值。方法选取2021年9月至2022年9月雅安市人民医院收治的并经病理组织学确诊的190例DTC患者作为恶性组,并选取本院同期收治的125例甲状腺良性病变患者作为良性组,另选取甲状腺形态正常的健康体检者100名作为健康对照组,比较三组血清E2、25(OH)D3及尿碘水平,并比较不同临床特征的DTC患者血清E2、25(OH)D3及尿碘水平,采用ROC曲线分析血清E2、25(OH)D3及尿碘水平对DTC的预测价值。结果血清E2、尿碘水平:恶性组>良性组>健康对照组,25(OH)D3水平:恶性组<良性组<健康对照组,差异均有统计学意义(P<0.05)。血清E2、尿碘水平:肿瘤低分化程度患者>肿瘤中分化程度患者>肿瘤高分化程度患者;尿碘水平:T3-T4浸润深度患者>T1-T2浸润深度患者,淋巴结转移患者>无淋巴结转移患者;血清25(OH)D3水平:肿瘤低分化程度患者<肿瘤中分化程度患者<肿瘤高分化程度患者,T3-T4浸润深度患者<T1-T2浸润深度患者,淋巴结转移患者<无淋巴结转移患者,差异均有统计学意义(P<0.05)。ROC曲线分析显示,血清E2、25(OH)D3及尿碘水平联合预测DTC的敏感度、特异度、AUC为94.74%、92.80%、0.978,高于三指标单独检测(P<0.05)。结论血清E2、25(OH)D3及尿碘水平与DTC发生及病情进展有关,且三者联合对DTC的预测价值更高。

血清TgAb水平对预测DTC术后转移/复发的临床价值

目的:探讨血清Tg Ab(抗甲状腺球蛋白抗体)水平对预测DTC(分化型甲状腺癌)术后转移/复发的临床价值。方法:选择50例血清Tg(甲状腺球蛋白)阴性、Tg Ab阳性的DTC术后患者,将其分为转移/复发组(M组)35例和无转移/复发组(N组)15例,观察其Tg Ab水平;根据Tg Ab水平分为低水平组(100-2000IU/ml)和高水平组(>2000IU/ml),研究Tg Ab不同水平组DTC患者的转移率、转移部位。结果:转移/复发组Tg Ab值明显高于无转移/复发组,两组Tg Ab值分布差别显著(U=120.500,P=0.002)。血清Tg Ab高水平组转移率明显高于低水平组,两组转移率差别显著(P=0.011),进一步分析,高水平组发生淋巴结、肺转移高于低水平组,有明显统计学差异(P<0.05)。结论:血清Tg阴性时,Tg Ab可作为DTC术后转移/复发的监测指标。Tg Ab值越高,发生转移/复发可能性越大。

彩色多普勒超声结合血小板与淋巴细胞比值在分化型甲状腺癌术前诊断中的价值分析

目的分析彩色多普勒超声结合血小板与淋巴细胞比值(PLR)在分化型甲状腺癌术前诊断中的价值。方法回顾性分析2020年2月至2023年8月池州市第二人民医院收诊的95例分化型甲状腺癌患者的病历资料,另选取95例诊断为甲状腺良性结节且具备彩超检查结果的同期病历作为对照。收集并整理所有受试者术前的彩色多普勒超声检查、PLR检查资料,比较两组甲状腺结节患者的超声影像学特征及PLR水平,评估彩色多普勒超声及PLR对分化型甲状腺癌的诊断效能。结果分化型甲状腺癌患者中单发结节、结节最大径≤1cm及存在钙化灶的所占比例高于甲状腺良性结节患者(P<0.05)。术前彩色多普勒超声、PLR以及二者联合诊断分化型甲状腺癌与术后病理诊断的一致性Kappa值分别为0.679、0.640和0.723。分化型甲状腺癌患者的PLR水平高于甲状腺良性结节患者(P<0.05)。彩色多普勒超声及PLR单一及联合诊断分化型甲状腺癌的灵敏度分别为84.21%、82.10%、86.32%,特异性分别为71.58%、73.68%、74.74%,曲线下面积(AUC)分别为0.767、0.810、0.881,且Delong检验表明二者联合诊断性能显著优于单一诊断方法(P<0.05)。结论彩色多普勒超声结合PLR在分化型甲状腺癌术前诊断中的效能表现良好。

血清TgAb评价DTC术后^(131)Ⅰ治疗疗效及预后的临床价值

目的:探讨抗甲状腺球蛋白抗体(Tg Ab)评价分化型甲状腺癌(DTC)术后131Ⅰ治疗疗效及预后的临床价值。方法:对血清甲状腺球蛋白(Tg)阴性、Tg Ab阳性且行二次131Ⅰ治疗的25例DTC转移患者进行回顾性分析,研究其131Ⅰ治疗前、治疗后6个月、治疗后1年Tg Ab水平的变化及病情发展趋势。结果:25例DTC转移患者131Ⅰ治疗不同随访时间,Tg Ab水平不同,三者差异显著(统计值:20.582,P=0.000)。治疗前水平最高,治疗后1年水平最低。有效组和无效组患者131Ⅰ治疗前Tg Ab水平差异无统计学意义(U=53.500,P=0.406);131Ⅰ治疗后1年Tg Ab水平差异显著(U=8.000,P=0.000)。治疗后有效组Tg Ab水平明显低于无效组。结论:血清Tg阴性时,Tg Ab水平可作为DTC转移患者131Ⅰ治疗疗效及预后的监测指标。

甲状腺癌碘-131治疗抵抗发生的分子机制研究进展

甲状腺癌是内分泌系统最常见的恶性肿瘤,其中分化型甲状腺癌(differentiated thyroid carcinoma,DTC)占90%以上。多数DTC患者经过系统治疗后预后良好,但少数患者肿瘤原发灶或转移灶出现失分化现象,进展为放射性碘难治性DTC(radioiodine-refractory DTC,RAIR-DTC),预后明显变差,是甲状腺癌致死的主要原因。钠碘转运体(sodium iodide symporter,NIS)的表达和功能异常,是导致甲状腺癌碘-131治疗抵抗的主要原因,其发生受遗传学改变、表观遗传学改变、肿瘤微环境作用、自噬作用等多因素影响。遗传学改变如BRAF基因的V600E位点突变、RET/PTC基因重排等导致致癌信号通路的激活,直接或间接地影响NIS的表达及其在细胞膜上的正常定位。表观遗传学调控特定基因的表达模式,调节NIS的表达水平,进而影响甲状腺细胞的碘摄取功能。肿瘤微环境中的免疫细胞、细胞因子和细胞外基质等成分也可能通过降低NIS的表达水平和/或干扰其在细胞膜上的正常功能导致细胞碘摄取障碍。此外,自噬作为一种细胞内部的代谢调节机制,也可以调节NIS的表达及其在细胞内的分布,从而影响碘的摄取和碘-131治疗的敏感性。通过综述以上因素在甲状腺癌失分化中的作用机制,可以更全面地理解RAIR-DTC的发生和发展过程,有助于探寻新的治疗靶点,改善预后,并为患者提供更有效的个体化治疗策略。

血清Tg检测联合^(131)I-WBS在DTC术后的临床价值

目的探讨分化型甲状腺癌(DTC)甲状腺清除术后血清甲状腺球蛋白(Tg)联合131I全身显像(131I-WBS),为判定甲状腺癌的复发及转移提供参考依据。方法 56例DTC患者,甲状腺全切或次全切术后4~6周,均行131I清除残余甲状腺治疗,3~6个月后重复治疗,治疗前停用甲状腺激素3~6周,同时忌碘饮食,治疗中检测血清Tg和口服碘化钠(131I)治疗剂量3.70~7.40 GBq后5~7天行131I-WBS。结果在首次清除残留甲状腺组织治疗时,显像发现淋巴结、肺及骨转移8例,其余转移灶于3~6个月后二次治疗时发现,有11例DTC患者(19.6%)Tg测定在正常范围,而131I-WBS出现转移灶;有7例患者(12.5%)Tg测定异常,而131I-WBS正常。结论 Tg测定和131I-WBS可作为诊断DTC术后复发及转移的重要指标,二者应联合应用、互相补充,具有重要的临床价值。