131I联合甲磺酸阿帕替尼对难治性甲状腺癌细胞的抑制作用及机制研究

目的 探讨¹³¹I联合血管生成抑制剂甲磺酸阿帕替尼对难治性甲状腺癌细胞的抑制作用及其机制。方法 将难治性甲状腺癌细胞分为对照组、¹³¹I组、阿帕替尼组及¹³¹I联合阿帕替尼治疗组(联合组),使用噻唑蓝(MTT)法检测各组肿瘤细胞治疗24 h、48 h后的增殖率;采用免疫荧光方法及蛋白印迹法检测各组细胞凋亡蛋白Caspase-3和血管生成蛋白VEGF的表达。结果 联合组处理后细胞的增殖率明显低于其它各组,差异具有统计学意义(P＜0.05)。联合组Caspase-3蛋白的表达含量明显高于其它各组(P＜0.01),联合组VEGF蛋白的相对表达量显著低于其它各组(P＜0.01)。结论 ¹³¹I联合甲磺酸阿帕替尼作用于难治性甲状腺癌细胞时具有协同增效作用,¹³¹I联合甲磺酸阿帕替尼通过上调促凋亡蛋白Caspase-3,下调VEGF的表达水平以达到增强¹³¹I抑制难治性甲状腺癌的增殖作用,从而为难治性甲状腺癌的临床治疗提供较好的策略。     

非远处转移性甲状腺乳头状癌131I疗效预测模型的分析

目的 分析影响非远处转移性甲状腺乳头状癌¹³¹I治疗疗效的危险因素,构建疗效预测模型。方法 回顾性分析我院2016年1月—2020年12月期间行甲状腺癌切除术和¹³¹I治疗的422例患者临床资料,采用多因素logistic回归分析筛选影响¹³¹I治疗疗效的独立危险因素,构建疗效预测模型,并对模型进行评价和验证。结果 选取75%的患者作为训练集(n=319),25%的患者作为验证集(n=103),训练集经多因素logistic回归分析后,非远处转移性甲状腺乳头状癌¹³¹I治疗疗效不满意的独立危险因素为BRAF^V600E突变阳性、sTg/TSH≥0.05 ng/μIU、sTg/TgAb≥0.60 ng/IU、病灶最大径≥1.05 cm、淋巴结分期N1b、淋巴结转移率≥34.58%(P＜0.05)。构建诺莫图模型,其在训练集和验证集中的ROC曲线下面积分别为0.90(95% CI:0.87~0.94,P＜0.001)和0.86(95% CI:0.78~0.94,P＜0.001)。结论 本研究基于非远处转移性甲状腺乳头状癌¹³¹I治疗疗效不满意的危险因素构建的疗效预测模型具有良好的预测效能。     

131I联合甲磺酸阿帕替尼治疗分化型甲状腺癌肺转移的短期疗效及安全性研究

目的 探讨¹³¹I联合甲磺酸阿帕替尼治疗分化型甲状腺癌肺转移的短期疗效及安全性。方法 回顾分析2018年10月—2020年10月于我院就诊治疗的分化型甲状腺癌肺转移患者57例,分为对照组(n=30)和联合治疗组(n=27),对照组单纯使用¹³¹I治疗,联合治疗组行¹³¹I联合阿帕替尼治疗。每半年观察并记录两组患者的甲状腺球蛋白(Thyroglobulin,Tg)水平、靶病灶(Target lesions,TL)的基线直径变化情况及靶病灶浓聚放射性灶计数/本底计数(Concentration range count/background count,C/B)的变化情况,同时记录两组患者的不良反应情况。结果 随访结束后联合治疗组Tg水平(36.34±19.72 μg/L)较对照组(122.18±22.98 μg/L)明显降低,差异具有统计学意义(P＜0.001);联合治疗组TL的直径均值(3.55±0.39 mm)较对照组(14.01±1.44 mm)明显缩小,差异具有统计学意义(P＜0.001)。24个月后,联合治疗组DCR和ORR高于对照组(P＜0.01)。联合治疗组C/B值(2.98±0.54)较对照组(25.45±3.00)明显降低,差异具有统计学意义(P＜0.001)。联合治疗组阿帕替尼常见的不良反应为手足综合征6例,高血压4例,皮疹2例,未观察到与阿帕替尼相关的Ⅲ级以上严重不良反应。结论 ¹³¹I联合甲磺酸阿帕替尼治疗分化型甲状腺癌肺转移疗效确切,具有明显的缩瘤效果,达到较高的生化缓解率,同时副作用轻微可控,安全性较高。     

可疑甲状腺球蛋白增高性分化型甲状腺癌患者经131I治疗后的临床转归

背景与目的： 分化型甲状腺癌（differentiated thyroid cancer,DTC）中可疑甲状腺球蛋白（thyroglobulin,Tg）水平增高但无明确结构性病灶者预后差异大,临床治疗决策存在较大争议,本研究拟探究¹³¹I治疗及不同治疗剂量对于这类患者临床转归的影响。方法： 回顾并分析2007—2021年就诊于北京协和医院核医学科的138例DTC全切术后可疑Tg水平增高的患者,依据首次¹³¹I治疗剂量分为低（剂量为1.11 GBq）、中（1.11 GBq<剂量≤3.70 GBq）、高（3.70 GBq<剂量≤7.40 GBq）3组,观察不同剂量¹³¹I治疗后6个月的短期及后续未再行其他干预患者的长期疗效,并进一步观察经初始治疗评估为生化疗效不佳（biochemical incomplete response,BIR）患者的临床转归。采用受试者工作特征（receiver operating characteristic,ROC）曲线评估预测结构性疗效不佳（structural incomplete response,SIR）和远处转移的刺激性Tg（stimulated Tg,sTg）的最佳界值点。结果： 低、中、高3个剂量组中分别有6.7%、13.5%、7.0%的患者短期疗效达到疗效满意（excellent response,ER）,3组间总体疗效差异无统计学意义（H=1.02,P=0.60）。常规随访下3组患者的长期疗效同样差异无统计学意义（H=2.94,P=0.23）。经初始治疗评估为BIR的患者经常规随访和再次¹³¹I治疗后的临床转归差异无统计学意义（U=324.5,P=0.15）。预测SIR和远处转移的sTg最佳界值点分别为27.5和61.7 ng/mL。结论： 可疑Tg水平增高的DTC患者复发率较高,以27.5 ng/mL为sTg界值点有助于尽早识别这部分患者。¹³¹I治疗有助于术后可疑Tg水平增高患者快速达到ER,但高剂量¹³¹I治疗未对患者的预后产生增益效应;再次¹³¹I治疗对于BIR患者未显示出进一步获益。     

CRT+ARC技术在局部晚期肺癌患者中临床应用的初步研究

目的 研究CRT+ARC技术在局部晚期肺癌中临床应用情况。方法 选择2016年3月1日—2017年3月1日在我院放疗科放疗的100例局部晚期肺癌患者,随机分为实验组和对照组,每组各50例患者,实验组制定CRT+ARC计划,对照组制定三维适形放射治疗技术+调强放射治疗技术(Intensity-modulated radiotherapy,IMRT)(CRT+IMRT)计划。根据世界卫生组织(World health organization,WHO)标准评估患者的近期疗效,根据影像学检查及放射治疗肿瘤学组(Radiaton therapy ognization group,RTOG)标准明确放疗主要副反应放射性肺炎发生情况。结果 实验组治疗有效率为82%,对照组治疗有效率为76%,两组差异无统计学意义(χ²=0.542,P=0.461)。实验组肺炎发生率为22%,对照组肺炎发生率18%,两组差异无统计学意义(χ²=0.250,P=0.617)。结论 CRT+ARC技术在局部晚期肺癌临床应用中,与CRT+IMRT相比,近期疗效和主要的副反应放射性肺炎都没有统计学差异。     

不同年龄儿童及青少年分化型甲状腺癌患者的临床病理学特征与131I治疗分析

背景与目的： 既往研究已发现18岁以下的儿童及青少年分化型甲状腺癌（differentiated thyroid carcinoma,DTC）与成人DTC在临床病理学特征、远期预后等方面存在差异,但对其内部不同年龄段之间,特别是青春期前、围青春期和青春期之间的特征研究较少,因此本研究旨在探讨不同年龄组儿童及青少年DTC的临床病理学特征及首次¹³¹I治疗效果的差异。方法： 回顾性分析四川大学华西医院2006年7月—2022年1月收治的156例儿童及青少年DTC患者。根据年龄分为青春期前（0岁<年龄≤10岁）、围青春期（10岁<年龄≤14岁）及青春期（14岁<年龄≤18岁）3组,比较3组的临床病理学特征、初始复发危险度分层、首次¹³¹I治疗后动态风险评估及刺激性甲状腺球蛋白（stimulated thyroglobulin,sTg）水平在首次¹³¹I治疗后的变化。结果： 3组患者的性别、原发肿瘤最大直径、包膜侵犯、T分期、N分期及切除淋巴结阳性转移比例差异无统计学意义（P>0.05）。3组患者的远处转移率分别为63.2%、42.1%和20.2%（χ²=16.839,P=0.000）,高危患者分别占88.9%、60.5%和46.4%（χ²=12.447,P=0.009）。3组患者首次¹³¹I治疗后动态风险评估的差异有统计学意义（χ²=21.744,P=0.001）,其中3组患者的疗效满意（excellent response,ER）比例分别为10.5%、25.0%和38.1%;结构性疗效不佳（structural incomplete response,SIR）比例分别为68.4%、52.8%和25.8%;生化疗效不佳（biochemical incomplete response,BIR）比例分别为21.1%、13.9%和14.4%。63例患者接受了第2次¹³¹I治疗且TgAb低于40 U/mL,首次¹³¹I治疗后3组的中位sTg降幅分别为41.31%、38.02%和60.38%（H=4.642,P=0.098）。结论： 儿童及青少年DTC中0~10岁组患者的远处转移率和高危复发风险最高,首次¹³¹I治疗后ER的结局最少,青春期前儿童DTC的发生、发展机制和治疗值得进一步研究。     

甲状腺乳头状癌18F-FDG PET/CT显像葡萄糖代谢与BRAF突变的相关性研究

目的 评估甲状腺乳头状癌(Papillary thyroid carcinoma,PTC)患者¹⁸F-FDG PET/CT的最大标准摄取值(SUV_max)与BRAF突变的相关性。方法 回顾性分析我院在甲状腺切除术前接受¹⁸F-FDG PET/CT显像和活检的患者51例(平均年龄为49.3±12.9岁),病理诊断为PTC 48例,甲状腺滤泡状癌(Follicular thyroid carcinoma,FTC)3例。采用基因检测法检测BRAF V600E突变状态,半定量分析法测定甲状腺结节灶的SUV_max,分析患者临床资料包括性别、年龄、肿瘤大小和甲状腺球蛋白浓度与SUV_max之间的相关性;将患者分为BRAF V600E突变组和未突变组,分析比较两组间SUV_max值的差异。结果 在PTC患者中,33例患者肿瘤发生BRAF V600E突变,15例患者肿瘤未发生突变,BRAF V600E突变组的SUV_max显著高于未突变组(5.5±3.9 vs. 2.2±1.2,P=0.002);肿瘤直径≥1cm的患者的SUV_max明显高于肿瘤＜1cm(P＜0.05);甲状腺球蛋白浓度升高患者的SUV_max高于正常甲状腺球蛋白浓度的患者(P＜0.05);FTC组中未观察到BRAF V600E突变。结论 PTC患者携带BRAF V600E突变基因相对于未携带者具有更高的SUV_max值,不同肿瘤大小、血清甲状腺球蛋浓度的PTC患者SUV_max值存在统计学差异。     

摄碘阳性的分化型甲状腺癌淋巴结转移灶131I疗效分析

背景与目的：淋巴结转移（lymph node metastasis,LNM）是分化型甲状腺癌（differentiated thyroid carcinoma,DTC）最常见的转移,而¹³¹I对LNM的疗效存在争议,本研究旨在明确¹³¹I对摄碘良好的LNM的疗效及影响因素。方法：纳入2015年1月—2019年6月在上海交通大学医学院附属新华医院接受¹³¹I治疗的90例DTC患者,共计161个摄碘阳性的转移淋巴结。分析患者的临床及影像学资料,应用SPSS 24.0软件进行统计分析。计量资料按照正态分布,进行独立样本t检验比较,计数资料的比较采用χ²检验,用logistic回归进行多因素分析,建立多个定量指标与结局为¹³¹I治疗无效的关系间的受试者工作特征（receiver operating characteristic,ROC）曲线,并得到最佳诊断阈值。结果：161个摄碘阳性的转移淋巴结中,有效组为71个（44.10%）,无效组为90个（55.90%）。单因素分析提示,两组患者在年龄、性别、病理学类型、原发病灶数量、原发病灶位置、有无远处转移及血清甲状腺球蛋白（thyroglobulin,Tg）水平等方面差异均有统计学意义（P <0.05）。多变量logistic回归分析显示,病理学类型（OR = 11.827,95% CI：1.128 ~ 123.978,P = 0.039）、有无远处转移（OR = 0.220,95% CI：0.093 ~ 0.522,P = 0.001）和原发病灶数量（OR = 0.421,95% CI：0.212 ~ 0.837,P = 0.014）与治疗后的转归密切相关。结论：原发病灶多灶、病理学类型为甲状腺乳头状癌（papillary thyroid carcinoma,PTC）、远处转移、血清Tg高于43.51 ng/mL及转移淋巴结的最大径大于16.8 mm是摄碘阳性淋巴结¹³¹I治疗无效的危险因素,建议对此类患者加大治疗剂量或尽早选择手术切除。     

盐酸帕洛诺司琼与托烷司琼预防含大剂量顺铂方案化疗所致呕吐的疗效

  目的  探讨注射用盐酸帕洛诺司琼在骨肉瘤患者大剂量化疗中预防恶心、呕吐的疗效, 及其不良反应。  方法  80例骨肉瘤患者接受大剂量顺铂(100 mg/m²)联合阿霉素(60~80 mg/m²)化疗方案, 随机分为试验组(盐酸帕洛诺司琼组)和对照组(盐酸昂丹司琼组), 每组各40例。比较两组预防化疗急性期的呕吐总有效率、延迟期的呕吐完全缓解率以及用药后不同时间恶心的完全控制率, 同时对不良反应进行评价。  结果  试验组对于预防急性期呕吐的总有效率为80%, 与对照组77.5%比较差异无统计学意义(P=0.785)。延迟期(分别观察化疗后第3天、第5天和第7天)的呕吐完全缓解率, 试验组均高于对照组(P < 0.05)。用药后第5天和第7天试验组恶心的完全控制率明显高于对照组, 差异有统计学意义(P=0.039, P=0.034)。两组不良反应比较差异无统计学意义(P > 0.05)。  结论  盐酸帕洛诺司琼注射液能更好的预防骨肉瘤大剂量化疗引起的延迟性恶心和呕吐, 对青少年患者使用有较好的安全性。     

ZCCHC12对甲状腺细胞恶性转化的影响与作用机制

目的 分析含CCHC结构域的锌指蛋白12(ZCCHC12)在甲状腺癌组织与甲状腺癌细胞系中的表达,并探讨其对甲状腺细胞恶性转化的影响与机制。方法 采用RT-PCR与Western blot检测30例甲状腺癌患者肿瘤组织和10例良性甲状腺组织以及甲状腺癌细胞系中ZCCHC12的表达。以ZCCHC12腺病毒载体或siRNA转染法处理甲状腺癌细胞,检测细胞增殖、侵袭能力以及相应分子的表达变化情况。结果 与良性甲状腺组织相比,甲状腺癌肿瘤组织中ZCCHC12的mRNA和蛋白表达水平均升高(P＜0.05);同时与甲状腺滤泡上皮细胞HUM-CELL-0097相比,甲状腺癌细胞中ZCCHC12的MRNA和蛋白表达也明显升高(P＜0.05)。ZCCHC12过表达后甲状腺癌细胞增殖与侵袭能力显著上升(P＜0.05),相反,ZCCHC12沉默后其增殖和侵袭能力受到抑制(P＜0.05)。与对照组相比,ZCCHC12过表达后细胞周期蛋白D(cyclin D)及基质金属蛋白酶2(MMP-2)、基质金属蛋白酶9(MMP-9)的表达水平增加;ZCCHC12沉默后则降低(P＜0.05)。结论 ZCCHC12在甲状腺癌组织及细胞中表达升高,其过表达后甲状腺癌细胞增殖活力与侵袭能力上升。ZCCHC12异常表达可激活细胞周期相关蛋白及胞外基质相关酶的表达,加剧甲状腺细胞的恶性转化。     

Recombinant human thyrotropin (rhTSH) in the follow-up and treatment of patients with thyroid cancer

The follow-up of thyroid cancer is based on the detection of residual and recurrent thyroid carcinoma. This is traditionally done by means of measurements of serum thyroglobulin (Tg) combined with various imaging techniques (131I-whole body scan, ultrasound and other modalities). Tg serum levels and the uptake of 131I on a whole body scan (WBS) depend on TSH stimulation, which in thyroidectomized patients can be obtained either by withdrawal of thyroid hormone treatment (thyroxine) or by administration of exogenous TSH. At present exogenous human TSH is obtained by means of recombinant DNA technology, (recombinant human TSH (rhTSH), Thyrogen). Even if the administration of rhTSH and withdrawal of thyroid hormone are not completely equivalent, the use of rhTSH has already entered the clinical routine (rhTSH Tg test and rhTSH WBS) because with rhTSH the morbidity and discomfort associated with the withdrawal of thyroid hormone can be avoided. At a recent International Consensus Conference on the follow-up of differentiated thyroid carcinoma it was proposed to carry out only Tg measurement after rhTSH stimulation; moreover, it was stated that 131I whole body scan has to be discouraged in patients submitted to radical surgery and radioiodine ablation with no clinical evidence of residual tumor and with undetectable levels of Tg during hormonal suppression of TSH. Similar strategies in this respect tend to eliminate the 131I WBS and propose only the rhTSH Tg test combined with head and neck ultrasound (US). This is still a matter of debate, also because it is not valid for all risk groups and not all patients undergo the same clinical management (radical surgery or not, thyroid ablation with 131I or not). However, the availability of rhTSH will definitely change the management of papillary and follicular thyroid carcinoma, also with regard to iodine treatment. In fact, rhTSH can be used during radioiodine treatment to enhance the 131I uptake by the cancer cells in particular groups of patients. Patients who could benefit from this approach can be divided into three subgroups: 1) patients in whom thyroxine withdrawal may be dangerous because of the effects of long-term TSH stimulation on the tumor mass (brain metastases, vertebral metastases, presence of neurological signs, heart diseases); 2) patients affected by tumors with marked biological aggressiveness and a low iodine uptake (variants of follicular carcinoma, insular carcinoma, tall and columnar cell variants of papillary thyroid carcinoma, Hürthle cell carcinoma); 3) patients with hypothalamic-pituitary alterations. The potential efficiency of rhTSH in radiometabolic treatment is an important issue that has been studied in a limited number of patients, but is worthy of further investigations in large perspective. A recent clinical prospective trial has been proposed by the Thyroid Cancer Study Group of the Istituto Nazionale Tumori and is now ongoing.     

Predictive value of thyroglobulin changes for the efficacy of thyroid remnant ablation.

The aim of this case-control study was to determine the utility of the evaluation of changes in serum thyroglobulin (Tg) levels before and after 1311 diagnostic total body scan (TBS) in patients with thyroid cancer to predict the efficacy of radioiodine ablation. Among 134 consecutive patients with differentiated thyroid carcinoma (DTC) who had undergone a thyroidectomy and TBS prior to radioiodine ablation, we selected those subjects with no evidence of distant metastases and with two consecutive assessments of Tg before TBS and radioiodine ablation within a period of four weeks. With this selection procedure 27 patients (22 with papillary and five with follicular carcinomas) were included in our evaluation. The ablation therapy was considered successful when the TBS performed one year after treatment did not show any or less than 1% cervical 131I uptake, Tg levels remained below 3 ng/mL, and clinical and instrumental examinations were negative for the presence of relapses. These criteria divided the selected patients into two subsets: patients with successful radioiodine ablation and patients with residual thyroid tissue. The majority of patients with unsuccessful ablation showed an increase in serum Tg levels, while most of the patients with successful ablation showed a steady decrease in Tg concentrations. Statistical analysis evidenced that the increase in Tg levels after TBS was related to unsuccessful ablation (P > or = 0.01). By contrast, the rate of thyroid remnants with 131I uptake did not show any relationship with the outcome of ablation therapy. The group of patients with increasing Tg levels after TBS had a relative risk of 3.3 of unsuccessful ablative therapy compared to the group with stable or decreasing Tg levels. This study supports the concept that by monitoring Tg levels in patients who undergo diagnostic TBS before radioiodine ablation it is possible to obtain useful information about the efficacy of 131I therapy.     

分化型甲状腺癌术后首次不同剂量131I清除残留甲状腺组织的临床观察

目的 探讨分化型甲状腺癌术后首次不同剂量131 I清除残留甲状腺组织(清甲)的临床效果.方法 将84例分化型甲状腺癌患者随机分为观察组(131I清甲剂量>100 mCi)和对照组(131I清甲剂量≤100 mCi)各42例.观察组空腹一次性口服131 I 100~120 mCi,对照组空腹一次性口服131 I 30~40 mCi.清甲半年后行131 I甲状腺显像检查,对两组清甲成功率进行评价,并检测促甲状腺激素(TSH)、甲状旁腺素(PTH)和甲状腺球蛋白(TG)水平,以及两组不良反应发生情况.结果 观察组乳头状癌与滤泡状癌清甲成功率与对照组比较,差异无统计学意义(P>0.05).同组内乳头状癌与滤泡状癌清甲成功率比较,差异无统计学意义(P>0.05).清甲前血清TSH浓度≥30 mIU/mL与血清TSH浓度﹤30 mIU/mL比较,差异具有统计学意义(P<0.05).清甲前血清Tg值﹤30 ng/mL与血清Tg值≥30 ng/mL比较,差异具有统计学意义(P<0.05).清甲6个月后,观察组TSH和PTH水平均显著高于对照组,Tg水平显著低于对照组,差异具有统计学意义(P<0.05).对照组胃肠道反应及泪腺功能紊乱发生率均低于观察组,差异具有统计学意义(P<0.05).对照组唾液腺功能紊乱及颈部疼痛发生率与观察组比较,差异无统计学意义(P>0.05).结论 分化型甲状腺癌术后首次应用131 I与剂量无太大关系,且低剂量的不良反应少于高剂量,低剂量131 I方案值得推广.     

100例分化型甲状腺癌术后131I治疗的疗效及安全性评价

目的：探讨131I在分化型甲状腺癌（differentiated thyroid cancer,DTC）术后清除残留甲状腺组织（清甲）和转移灶（清灶）治疗中的疗效及安全性。方法随机选取100例进行131I清甲及清灶治疗的DTC患者。所有患者治疗前3～4周均停服L-T4,并予以131I（2.96～5.55）×103 MBq清甲治疗;治疗后口服L-T4替代治疗,6个月后复查,根据颈部超声、全身显像及血清甲状腺球蛋白（thyroglobulin,Tg）水平评价131I治疗的效果。结果所有的患者均接受1～3次的131I治疗,共140个疗程,平均每次治疗剂量为4.03×103 MBq,1次131I治疗成功率为67%,2次131I治疗成功率为92%,经131I治疗后患者的Tg转阴率为53.3％;治疗后5例患者出现一过性白细胞下降,治疗前后肝肾功能无明显改变。结论 DTC患者术后尽早进行规范化的131I治疗,具有治疗次数少、清甲成功率高且不良反应少的特点,对预防甲状腺癌的复发有重要的作用。     

Importance of Postoperative Stimulated Thyroglobulin Level at the Time of 131I Ablation Therapy for Differentiated Thyroid Cancer

Background: Serum thyroglobulin detection plays an essential role during the follow-up of thyroid cancerpatients treated with total/near total thyroidectomy and radioiodine ablation. The aim of this retrospective studywas to evaluate the relationship between stimulated serum thyroglobulin (Tg) level at the time of high dose 131Iablation and risk of recurrence, using a three-level classification in patients with differentiated thyroid cancer(DTC) according to the ATA guidelines. Also we investigated the relationship between postoperative stimulatedTg at the time of ablation and DxWBS results at 8-10 months thereafter. Materials and Methods: Patientswith radioiodine accumulation were regarded as scan positive (scan+). If there was no relevant pathologicalradioiodine accumulation or minimal local accumulation in the thyroid bed region, this were regarded as scannegative (scan-) at the time of DxWBS. We classified patients in 3 groups as low, intermediate and high riskgroup for assessment of risk of recurrence according to the revised ATA guidelines. Also, we divided patients into3 groups based on the stimulated serum Tg levels at the time of 131I ablation therapy. Groups 1-3 consisted ofpatients who had Tg levels of ≤2 ng/ml, 2-10 ng/ml, and ≥10 ng/ml, respectively. Results: A total of 221 consecutivepatients were included. In the high risk group according to the ATA guideline, while 45.5% of demonstratedScan(+) Tg(+), 27.3% of patients demonstrated Scan(-) Tg(-); in the intermediate group, the figures were 2.3%and 90.0% while in the low risk group, they were 0.6% and 96.4%. In 9 of 11 patients with metastases (81.8%),stimulated serum Tg level at the time of radioiodine ablation therapy was over 10, however in 1 patient (9.1%)it was <2ng/mL and in one patient it was 2-10ng/mL (p=0.005). Aggressive subtypes of DTC were found in 8 of221 patients and serum Tg levels were ≤2ng/ml in 4 of these 8. Conclusions: We conclude that TSH-stimulatedserum thyroglobulin level at the time of ablation may not determine risk of recurrence. Therefore, DxWBSshould be performed at 8-12 months after ablation therapy.     

经验性 131 I治疗对甲状腺乳头状癌不摄碘肺转移患者价值存疑

背景与目的：甲状腺乳头状癌（papillary thyroid cancer,PTC）肺转移但 ¹³¹ I 全身显像（whole body scan,WBS）阴性的患者是否可从经验性 ¹³¹ I 治疗中获益仍存在争议。探究经验性¹³¹ I 治疗对PTC伴不摄碘性肺转移患者的必要性。方法：经筛选纳入回顾性分析2008年—2019年就诊于北京协和医院核医学科的45例PTC仅伴肺转移患者,比较清甲成功后再行清灶治疗后全身显像（post-treated whole body scan,RxWBS）提示肺转移灶未摄碘的“经验性 ¹³¹ I治疗”前后的血清甲状腺球蛋白（thyroglobulin,Tg）水平变化,以及同一例患者在经验性 ¹³¹ I治疗和仅促甲状腺激素（thyroid-stimulating hormone,TSH）抑制治疗两阶段血清Tg变化速度及影像学改变。据影像学改变,观察这部分患者在仅TSH抑制治疗时的无进展生存期（progression-free survival,PFS）。结果：45例PTC患者在经验性 ¹³¹ I治疗后血清Tg水平较治疗前升高（P=0.001）。经验性 ¹³¹ I治疗和仅TSH抑制治疗两阶段患者的血清Tg变化速度（P=0.123）及影像学改变（P=1.000）差异均无统计学意义。仅TSH抑制治疗时患者的中位PFS可达到54.4（46.5,66.2）个月。结论：经验性 ¹³¹ I治疗对于PTC伴不摄碘性肺转移患者的疗效甚微,并可能适得其反,宜及时终止经验性 ¹³¹ I治疗。     

Radioiodine ablation of post-surgical thyroid remnants after preparation with recombinant human TSH: why, how and when.

AIMS: The use of recombinant human TSH (rhTSH) represents one of the most exciting innovations in the field of differentiated thyroid cancer (DTC) management, but the use of rhTSH for radioiodine post-surgical thyroid remnant ablation is still controversial. The aim of this review is to provide the reader with an analysis of the literature regarding the use of rhTSH for the radioiodine ablation of post-surgical thyroid remnants. METHODS: We performed a literature search of the most relevant papers in the PubMed database. FINDINGS AND CONCLUSIONS: To date, five prospective studies have been published regarding this topic and there is strong evidence of the effectiveness of rhTSH, at least when high doses of 131I are used. Vice-versa, data regarding the outcome of ablation using low doses (30 mCi) are quite different in the studies published. So the problem of the amount of 131I to be administered and the influence of iodine intake is still open. In fact, the results of some studies suggest that 131I uptake could be particularly dependent on iodine intake during the euthyroid state and when low doses of 131I are used. This could be the reason for the reduced radioiodine uptake observed in other studies. However, also when rhTSH stimulation had produced a reduced iodine uptake, this was at least partially compensated for by an increased half-time in thyroid cells. So rhTSH stimulation appears to have pathophysiological bases which all lead to a powerful destructive effect by 131I on thyroid cells. All the data in the literature appear concordant that rhTSH is safe and associated to a good quality of life and the problem of costs appears negligible when compared to the benefits for the patient. In most cases, the use of rhTSH, for radioiodine ablation of post-surgical thyroid remnants can represent the best therapeutic option that we can offer to the patient.     

Clinical experience with recombinant human thyrotrophin (rhTSH) in the management of patients with differentiated thyroid cancer

The purpose of this work was to gain clinical experience with and to identify the optimal conditions for the use of recombinant human TSH (rhTSH, commercially available as Thyrogen) in the management of patients with differentiated thyroid cancer (DTC). The study involved 22 patients for a total of 27 administration cycles of rhTSH, for either diagnostic (in 19 instances) and/or therapeutic purposes (in 8 instances). There were 19 patients with papillary cancer (follicular variant in 4, columnar variant in 1) and 3 patients with follicular cancer (1 Hurtle cell variant). All patients had previously undergone total thyroidectomy and 1-5 cycles of 131I-therapy. Thyrogen was administered i.m. according to the suggested protocol: 0.9 mg i.m. on days 1 and 2, radioiodine on day 3. Peak serum TSH levels between 68-237 microIU/mL were observed after rhTSH administration; these were on average 65% higher, on a patient-by-patient basis, than peak serum TSH observed after conventional withdrawal of thyroxine treatment in 19 patients, while in 3 patients they were 28% lower, but still in the potent stimulation range (86-94 microIU/mL). There was general agreement between imaging results obtained under rhTSH stimulation and those obtained on prior occasions during thyroxine withdrawal, although radioiodine uptake was interpreted as less intense following Thyrogen administration. Of 18 patients undergoing rhTSH administration for diagnostic purposes, 11 patients had a negative radioiodine whole-body scan (WBS) and 7 had a positive WBS. Three of the WBS-negative patients were shown to be actually affected by tumor recurrence, respectively by PET with [18F]FDG (in 2 cases) and by post-131I therapy scan. Serum thyroglobulin (hTg) increased to abnormal levels following rhTSH stimulation in 3/7 of the WBS-positive patients as well as in 1/11 WBS-negative patients. In 3/7 WBS-positive as well as in 3/11 WBS-negative patients, serum hTg progressively rose under rhTSH stimulation, yet still remaining below 3 ng/mL. Post-131I therapy scans following Thyrogen administration showed good radioiodine uptake in 7/8 patients, the single unsuccessful case being most likely due to expansion of the iodine pool because of recent use of an iodinated contrast medium. The overall results show the feasibility and practical advantages of employing rhTSH stimulation in the general clinical setting rather than thyroxine withdrawal in the management of DTC patients. Caution should be raised on the interpretation of the serum hTg response to such potent but short-lived TSH stimulation.     

甲状腺球蛋白抗体对甲状腺乳头状癌131I清甲疗效的影响

背景与目的：甲状腺球蛋白抗体(thyroglobulin antibody,TgAb)在甲状腺乳头状癌(papillary thyroid carcinoma,PTC)中较为常见。该研究旨在探讨PTC患者术后TgAb对¹³¹I清甲疗效的影响。方法：纳入329例非远处转移性PTC患者,根据¹³¹I清甲前TgAb水平分为G1组(大于115 U/mL,n=84)和G2组(<115 U/mL,n=245),G2组再以40 U/mL为界分为S1(大于40 U/mL,n=31)和S2(小于40 U/mL,n=214)两个亚组,中位随访时间24个月,比较两组患者清甲疗效并分析其影响因素,观察¹³¹I清甲剂量对患者疗效的影响。结果：G1组女性居多,年龄更小(P=0.000,P=0.004),其余临床病理基线资料差异均无统计学意义(P均>0.05)。G1组清甲成功率为35.7%,G2组为72.7%,差异有统计学意义(P=0.000);S1和S2两个亚组清甲成功率分别为54.8%和75.2%,差异有统计学意义(P=0.017);G1组高、低剂量¹³¹I清甲后成功率分别为34.1%、37.2%,与G2组的71.9%、73.2%差异均有统计学意义(P均=0.000);G1组与G2组内分别采用低剂量¹³¹I与高剂量¹³¹I清甲的成功率差异均无统计学意义(P均>0.05)。多因素分析显示,清甲疗效仅与清甲前TgAb值有关(P=0.018)。结论：TgAb可以影响PTC患者的¹³¹I清甲疗效,TgAb越高者清甲疗效越差。增加¹³¹I治疗剂量未能进一步提高患者的清甲成功率。     

Correlation of thyroglobulin measurements and radioiodine scans in the follow-up of patients with differentiated thyroid cancer

Correlation of radioiodine (131I) scans and serum thyroglobulin (Tg) concentrations were performed in the follow-up of 85 differentiated thyroid cancer patients who had undergone total thyroidectomy. Tg results were also compared with the control group of 33 thyroidectomized patients with no evidence of thyroid carcinoma and normal values for Tg established. Excellent correlation between Tg and scans was noted in patients with scan evidence of metastasis distant from the neck. Poor correlation was present in patients with scan evidence of local neck metastasis only, thyroid bed activity, and those with mediastinal activity. In addition, in 8% of the patients, the Tg assay could not be performed because of interfering antibodies. The conclusion is that elevated Tg concentration is a good indicator of metastasis outside of the neck as detected by 131I scans. Caution should be used when Tg alone is used in evaluating local neck metastasis demonstrated on scans. The significance of mediastinal activity warrants further investigation.