分化型甲状腺癌肺转移的研究进展

分化型甲状腺癌（DTC）的发病率呈逐年上升趋势,当发生远处转移时患者的生存质量变差、生存率明显降低。肺是DTC最常见的远处转移部位,占DTC远处转移的55%~85%。DTC肺转移是造成甲状腺癌患者病死的主要因素。故针对此类患者的早期诊断、评估以及治疗决策的制定尤为重要,同时这也是缩短我国与发达国家甲状腺癌诊治的差距、提高患者生存质量的关键。笔者就近年来有关DTC肺转移的流行病学及临床病理特征、诊断与动态评估以及治疗方法等研究进展作一综述。     

甲状腺癌骨转移模型的研究

甲状腺癌是内分泌系统最常见的恶性肿瘤,其发病率逐年上升,虽然该病预后较好,但若发生骨转移,患者10年生存率将明显降低。目前,甲状腺癌发生骨转移的机制尚不明确,对甲状腺癌骨转移的研究不仅具有重要的临床价值,也有很重要的科研价值。甲状腺癌骨转移动物模型的建立是研究甲状腺癌骨转移机制和治疗的基础,根据其建立方法可分为自发性、化学诱导性、转基因诱导性和移植性4种。     

^131I治疗分化型甲状腺癌骨转移的疗效评价和生存分析

目的评价^131I治疗DTC骨转移的疗效及影响因素,评估生存率及其影响因素。方法回顾分析经^131I治疗的106例DTC骨转移患者的临床资料,分别基于^131I治疗后血清Tg的变化、骨痛缓解情况和影像学变化评价^131I治疗疗效,并对影响^131I疗效的因素进行单因素分析;采用寿命表法评估DTC骨转移患者的^131I治疗后总生存率;采用Kaplan—Meier法对影响生存率的因素进行分析,应用Log-rank法比较各组间差异。结果经^131I治疗后血Tg显著下降者37例,有效率34．9％。骨转移伴疼痛的61例DTC经^131I治疗后疼痛明显缓解者39例,有效率63．9％。患者年龄、病理类型、是否合并其他非骨性远端转移等因素对^131I治疗后血Tg的变化有影响（x2=6．443,11．455和6．756,P均〈0．05）,但对^131I治疗后骨痛缓解的影响无统计学意义（x2=0,0,0．060,P均〉0．05）。^131I治疗后77．4％的患者骨转移灶无明显影像学变化。该组DTC骨转移患者5年和10年生存率分别为86．47％和57．90％;骨转移灶数目、是否合并其他远端脏器转移、^131I治疗前是否行手术治疗对患者的10年生存率影响差异有统计学意义（Log-rank值为4．05,5．98和4．22,P均〈0．05）;患者的性别、年龄、病理类型、是否以骨转移症状首诊等因素对10年生存率无明显影响（Log—rank值为0．01,1．56,2．59和0．04,P均〉0．05）。结论^131I治疗可使DTC骨转移患者血清Tg下降、骨痛缓解、病灶保持稳定或缩小,是治疗DTC骨转移的有效手段;单发病灶、单纯骨转移、手术＋^131I治疗患者预后较好。     

131 I治疗分化型甲状腺癌脑转移

目的：探讨131I治疗分化型甲状腺癌（DTC）脑转移的临床价值。方法：随访8例经131I治疗的DTC脑转移患者，通过临床症状，影像学检查及生存率分析，观察DTC脑转移131I治疗效果。结果：（1）131I一生存期2－35年，2001年底随访时均存活；（2）I期患者131I治疗5次（20．65GBq)，后CT示右小脑占位灶缩小，6次（23．61GBq)后CT示占位灶消失。（3）甲状腺双侧切除者，术后剩余甲状腺平均131I清除次数为2次，平均总清除剂量8．87GBq;单侧切除者，平均清除次数5．7次，平均总清除剂量29．98GBq，后者的清除次数和剂量均明显高于前者（P＜0．01）。（4）合并有肺和（或）骨转移灶仍见131I提取。结论：合并有肺和（或）骨转移的DTC脑转移者治疗难度增加，但术后131I治疗仍有效。     

甲状腺癌骨转移模型的研究

甲状腺癌是内分泌系统最常见的恶性肿瘤,其发病率逐年上升,虽然该病预后较好,但若发生骨转移,患者10年生存率将明显降低.目前,甲状腺癌发生骨转移的机制尚不明确,对甲状腺癌骨转移的研究不仅具有重要的临床价值,也有很重要的科研价值.甲状腺癌骨转移动物模型的建立是研究甲状腺癌骨转移机制和治疗的基础,根据其建立方法可分为自发性、化学诱导性、转基因诱导性和移植性4种.     

甲状腺球蛋白与分化型甲状腺癌

甲状腺球蛋白(Tg)检测对分化型甲状腺癌(DTC)的诊治具有重要价值,尽管其测量受诸多因素影响,但手术及131I清除残留甲状腺后,Tg仍是监测DTC复发或转移的一项灵敏而又特异的肿瘤标志物.Tg检测与131I扫描的价值互为补充.此外,Tg免疫组化分析、Tg mRNA及Tg抗体等在DTC的诊治与随访中也具有一定价值.     

血清midkine测定在分化型甲状腺癌诊断和预后评价中的价值

目的 探讨血清midkine(MK)能否鉴别甲状腺结节良恶性及131I治疗前血清MK能否预测DTC患者是否存在转移灶.方法 在鉴别甲状腺结节良恶性的研究中,有162例患者(其中DTC 70例、良性甲状腺结节92例)入组,同时有75名健康者作为对照.通过ROC曲线研究术前MK和Tg水平对甲状腺结节良恶性的鉴别诊断价值.在预测是否存在转移灶的研究中,有214例DTC患者入组.通过ROC曲线研究131 I治疗前血清MK和Tg水平对是否存在摄131I转移灶的预测价值.组间比较采用两样本t检验或Mann-Whitney u检验,对MK和Tg间的相关性行Pearson分析,对无转移灶生存率采用Kaplan-Meier法进行分析.结果 Pearson分析显示MK和Tg呈显著正相关(r=0.917,P＜0.05).手术前,DTC患者血清MK和Tg水平显著高于良性甲状腺结节患者(z=-7.283和-3.191,均P＜0.05),也显著高于健康对照者(z=-7.328和-4.384,均P＜0.05).对于术前甲状腺结节良恶性的鉴别,MK的最佳切点值为323.12 ng/L,此时的诊断准确性为75.31％(122/162),高于Tg的60.49％(98/162).对于DTC的鉴别,MK和Tg的诊断准确性均为77.93％ (113/145).对于预测是否存在转移灶,Tg的最佳切点值为19.50 μg/L,诊断准确性为96.73％ (207/214);MK的最佳切点值为504.71 ng/L,诊断准确性为89.25％ (191/214).Kaplan-Meier分析显示对于DTC患者,当MK或Tg水平高于阈值(分别为500 ng/L和20μg/L)时无转移灶生存率较低于阈值时低(x2=118.539和209.823,均P＜0.05).结论 术前MK水平不但可用于鉴别甲状腺结节的良恶性,也可用来预测DTC患者是否存在转移灶,是良好的DTC血清标志物.     

肝癌骨转移的特点及核素骨显像的价值

目的 :探讨肝癌骨转移的特点及核素骨显像的价值。方法 :回顾性分析 2 76例经CT或病理学证实的肝癌病例的临床资料及骨显像表现。结果 :①肝癌骨转移率为 2 0 .3 % ( 5 6/2 76) ,最常累及部位为椎体 ( 2 8/5 6) ,依次是肋骨、肩胛骨及四肢、骨盆、颅骨和胸骨 ,其中多发性转移 67.9% ( 3 8/5 6) ;②相同部位CT或X线平片检出的病灶数较骨显像少 ,均表现为溶骨性 ,核素骨显像对溶骨性转移灶的检出率为 95 .5 % ( 4 4/4 6) ;③ 3 5 .7% ( 2 0 /5 6)的患者以骨转移为首发症状 ,其中80 % ( 16/2 0 )伴有骨痛 ,15例骨痛患者骨转移灶数在 2个或以上。结论 :晚期肝癌骨转移常见 ,好发部位为椎体 ,常多发转移 ,肝癌术前分期检查应常规包括放射性核素骨显像。     

颈部超声在分化型甲状腺癌131I治疗中的应用进展

分化型甲状腺癌是内分泌系统最常见的恶性肿瘤,其发病率呈逐年上升的趋势.其中,乳头状癌易发生颈部淋巴结转移.超声和超声引导下细针穿刺在颈部淋巴结转移检测方面具有很高的灵敏度和特异度.准确判断颈部淋巴结的性质对决定是否再次手术或131I治疗,以及131I治疗后的随访均有重要意义.     

大剂量131I治疗312例分化型甲状腺癌转移灶的临床分析

目的：评价甲状腺癌（简称甲癌）转移灶患者多次大剂量^131I治疗疗效及其副作用。方法：①治疗方法：肺、骨转移乾每次口服^131I7.4GBq，淋巴结转移者每次口服^131I5.55GBq，2次治疗间隔4个月。②疗效判断：分治愈：为^131I显像阴性，血甲状腺球蛋白（Tg）降至正常水平；有效：血Tg转阴，^1321I显像仅见病灶缩小或减少或病灶吸^131I率下降；无效：血Tg高水平，^131I显像有新病灶出现或患者死亡。③副作用观察为对甲状旁腺功能及染色体畸变的影响。结果：①疗效：312例甲癌转移灶患者治愈35.9％（112例），有效60.2％（188例），无效3.8％（12例）。②副作用：8.6％的患者有甲状旁腺素（PTH）一过性下降，但无1例甲状旁腺减退症发生。治疗后外周淋巴细胞染色体出现多种畸变，部分患者的辐射耐受增强。结论：采用^131I多次大剂量治疗甲癌转移灶疗效佳，副作用小，不会发生甲状旁腺功能减退症等并发症。^131I治疗的适应证应扩大至手术病理检查发现淋巴结转移者。     

Usefulness of technetium-99m hydroxymethylene diphosphonate scans in localizing bone metastases of differentiated thyroid carcinoma

Iodine-131 is uniquely able to demonstrate iodine uptake of differentiated thyroid carcinoma (DTC), but precise localization may be difficult, especially in the thorax, due to the quality of image resolution with 1311 and the lack of anatomical landmarks. When bone metastases do not show radioiodine uptake, bone scintigraphy can be used to detect them. We studied two groups of patients. In group 1, 15 patients with known bone metastases of DTC were treated with 3.7 GBq ¹³¹I. After 4 or 5 days, technetium-99m hydroxymethylene diphosphonate (HMDP; 740 MBq) was injected and a whole-body scan with simultaneous acquisition of ¹³¹I and ^99mTc-HMDP images was carried out using a large field of view gamma camera fitted with a high-energy collimator. Technetium uptake was abnormal in 47 of 63 localizations, being increased in 29 foci, decreased in 7 and heterogeneous in 11. The superimposition of ¹³¹I and ^99mTc-HMDP scans permitted an accurate localization in 80% of spine metastases and in 46% of osseous thoracic localizations, even in the presence of lung metastases. In group 2, 9 patients, who had bone pain, neurological signs or elevated serum thyroglobulin, had DTC bone metastases without iodine uptake. They received a diagnostic dose of ^99mTc-HMDP 3h prior to scintigraphy with a large field of view gamma camera fitted with a low-energy collimator. Technetium uptake was abnormal in 37 of 38 localizations, being increased in 34 foci and decreased in 3. One false-negative was found in a skull metastasis. In both groups of patients, ^99mTc-HMDP scans were useful. The procedure allows accurate localization of bone metastases and can be used as a guide for subsequent radiological investigations.     

Distant metastases of differentiated thyroid cancer: diagnosis, treatment and outcome

The remarkably good prognosis and long-term survival in differentiated thyroid cancer (DTC) are significantly reduced in patients with distant metastasis (DM). Multi-site metastases are associated with a high mortality rate reaching 92% at 5 years necessitating early diagnosis and treatment. The most common site of metastases are the lungs, followed by the bone, with the former having better prognosis than the latter due to late detection. A number of factors contribute to the development of DM including large and multifocal primary tumour, extrathyroidal extension, aggressive histology and advanced age. In patients with good (131)I uptake, (131)I therapy appears highly effective and should be offered up to a cumulative activity of 22 GBq. Other measures such as surgery, radiotherapy, arterial embolisation and cementoplasty may be required. If there is low or no (131)I uptake, FDG-PET should be obtained due to its prognostic impact. It may help in selecting patients for other modalities such as cytotoxic chemotherapy and redifferentiation therapy by 13-cis retinoic acid. The development of tyrosine kinase inhibitors has raised hopes in providing alternative therapy for bone metastasis, especially in older age groups with poorly differentiated tumours with no (131)I uptake but good uptake of FDG.     

Acute effects of recombinant human TSH on bone markers in differentiated thyroid cancer

Patients suffering from differentiated thyroid cancer receive suppressive of TSH thyroxine treatment of long duration. This study was undertaken to determine changes on bone serum markers after administration of recombinant human TSH in differentiated thyroid cancer patients on thyroxine treatment. Forty-five patients undergoing diagnostic evaluation of their disease and 48 matched controls were investigated: two injections of 0.9 mg of recombinant human TSH were given to the patients (on days 1 and 2). Blood samples were collected the day before first injection (day 0) and days 3, 5 and 10 after recombinant human TSH administration. Blood samples were obtained for serum TSH, bone alkaline phosphatase, osteocalcin, osteoprotegerin, receptor activator of nuclear factor kB ligand and bone tartrate resistant acid phosphatase. Recombinant human TSH induced a significant increase in bone alkaline phosphatase on day 3 up to day 10 in postmenopausal women. A statistically significant increase was also observed in serum receptor activator of nuclear factor kB ligand in both men and postmenopausal women on day 3 while on day 10 these values returned to baseline levels. No significant effects were seen in other parameters at any time of the investigation. In conclusion, we demonstrated significant increases in receptor activator of nuclear factor kB ligand and bone alkaline phosphatase after TSH stimulation. The changes in these bone indices were more prominent in the group of postmenopausal women.     

Value of the first serum thyroglobulin level after total thyroidectomy for the diagnosis of metastases from differentiated thyroid carcinoma

The aim of this study was to evaluate the diagnostic significance of the first serum thyroglobulin (Tg) measurement, performed 40 days after total thyroidectomy for differentiated thyroid carcinoma and prior to the ablation of residual thyroid tissue by means of iodine-131 therapy. In a retrospective study we examined 334 consecutive patients followed up for 4–16 years by means of regular Tg measurements, ¹³¹I whole-body scans (WBS) and other diagnostic techniques, if necessary. In 79 patients metastases were discovered (32 lymph node and 47 distant metastases) within 18 months following thyroidectomy. Mean values of first Tg were significantly higher in patients with than in patients without metastases (258.9±310.6 vs 15.9±19.6 ng/ml; P<0.0001). Receiver operating characteristic (ROC) curve analysis of data revealed that for first Tg values higher than 69.7 ng/ml, the positive predictive value for the presence of metastases exceeded 90%. No statistically significant correlation was found between first Tg value and either thyroid-stimulating hormone (TSH) value or percentage of ¹³¹I uptake by residual thyroid tissue. No other parameter (age, histological type, site of metastases, ¹³¹I uptake by metastases) was significantly related to the first Tg value. We conclude that the first Tg measurement after total thyroidectomy provides a useful early diagnostic indication of metastatic disease in spite of the presence of a post-surgical thyroid remnant, and that this holds true regardless of the TSH value and WBS result. This early information is of clinical relevance for patient follow-up. Received 26 October 1998 and in revised form 12 June 1999     

Value of the first serum thyroglobulin level after total thyroidectomy for the diagnosis of metastases from differentiated thyroid carcinoma.

The aim of this study was to evaluate the diagnostic significance of the first serum thyroglobulin (Tg) measurement, performed 40 days after total thyroidectomy for differentiated thyroid carcinoma and prior to the ablation of residual thyroid tissue by means of iodine-131 therapy. In a retrospective study we examined 334 consecutive patients followed up for 4-16 years by means of regular Tg measurements, (131)I whole-body scans (WBS) and other diagnostic techniques, if necessary. In 79 patients metastases were discovered (32 lymph node and 47 distant metastases) within 18 months following thyroidectomy. Mean values of first Tg were significantly higher in patients with than in patients without metastases (258.9+/-310.6 vs 15.9+/-19.6 ng/ml; P<0.0001). Receiver operating characteristic (ROC) curve analysis of data revealed that for first Tg values higher than 69.7 ng/ml, the positive predictive value for the presence of metastases exceeded 90%. No statistically significant correlation was found between first Tg value and either thyroid-stimulating hormone (TSH) value or percentage of (131)I uptake by residual thyroid tissue. No other parameter (age, histological type, site of metastases, (131)I uptake by metastases) was significantly related to the first Tg value. We conclude that the first Tg measurement after total thyroidectomy provides a useful early diagnostic indication of metastatic disease in spite of the presence of a post-surgical thyroid remnant, and that this holds true regardless of the TSH value and WBS result. This early information is of clinical relevance for patient follow-up.     

PET/CT在分化型甲状腺癌复发和转移诊断中的应用进展

分化型甲状腺癌（DTC）的发病率呈逐年上升趋势,大部分患者预后良好,但当DTC发生复发和转移时,患者生存率明显下降,因此,对DTC患者复发和转移的诊断、评估以及治疗显得尤为重要。随着PET/CT在肿瘤学领域研究的不断开展,其在DTC复发和转移患者中的应用越来越受到重视,可为其精准诊疗提供重要信息。笔者就PET/CT在DTC复发和转移诊断中的应用进展进行综述。