Thyroid cancer review 3: management of medullary and undifferentiated thyroid cancer

This is the last of the three review articles dealing with thyroid cancer. Over 90% of thyroid cancer is of the differentiated type associated with a very good 10-year disease-free survival rate. In contrast, the rare forms of thyroid cancer which comprise medullary thyroid cancer arising from parafollicluar C cells, Hurthle cell carcinoma, anaplastic carcinoma, thyroid lymphoma and squamous cell carcinoma are typically associated with a poorer survival rate. Management is based upon small retrospective cohort studies.     

甲状腺微小乳头状癌的诊断与治疗

目的 探讨甲状腺微小乳头状癌（PTMC）的诊断和外科治疗方法.方法 回顾性分析2008年1月至2012年12月我院收治的138例PTMC患者诊断和治疗的临床资料.结果 138例患者术前均无临床不适症状,为查体时超声波检查所发现.所有病例甲状腺超声显示结节直径≤1.0 cm,结节内有钙化122例,血流丰富84例,边界不清53例.其中术前通过甲状腺结节细针穿刺和细胞学检查54例,明确为微小癌46例,假阴性8例.其余均为术后病理证实.所有病例中单侧单发甲状腺微小癌96例,单侧多发甲状腺微小癌20例,双侧多发甲状腺微小癌22例.采用患侧＋峡部切除＋对侧腺叶次全切除64例;患侧＋峡部腺叶切除35例;双侧甲状腺切除18例;双侧甲状腺次全切除25例.行颈部淋巴结清扫76例,未行颈部淋巴结清扫62例.其中合并淋巴结转移26例,无淋巴结转移112例.术后随访1～6年,出现喉返神经损伤4例,喉上神经损伤2例,一过性甲状旁腺损伤2例.局部复发4例,无远处转移和死亡病例.结论 甲状腺高频超声波检查是发现PTMC的重要手段.术前甲状腺结节细针穿刺和细胞学检查是及时判定结节性质的最可靠方法.手术是治疗PTMC的最佳治疗方式.而选择合理的手术方式是提升治疗效果、较少并发症的关键.     

甲状腺包膜内滤泡型乳头状癌的超声表现及误诊分析

目的探讨甲状腺包膜内滤泡型乳头状癌(EFVPTC)的超声表现,分析其超声误诊原因。方法回顾分析31例经手术及病理证实的EFVPTC患者的超声表现,结合病理结果进行对照分析。结果 31例EFVPTC患者的超声表现可分为两种:①Ⅰ型15例(48.4%),表现为境界较清晰的等回声或低回声结节,其形态不规则,边缘可见成角或分叶,微小钙化较少见;②Ⅱ型16例(51.6%),表现为形似腺瘤,结节边界清晰且边缘光整,内部为均匀中等回声。31例中有6例(19.4%)发现颈部淋巴结转移,超声表现为高回声,内可见微小钙化及囊性变。超声提示甲状腺恶性肿瘤9例,误诊22例,诊断符合率为29%。结论甲状腺内单发的分叶状病灶及典型甲状腺乳头状癌转移淋巴结对提示诊断EFVPTC有较高价值。     

Serum thyroglobulin in the monitoring of differentiated thyroid cancer

Abstract

Patients with differentiated thyroid cancer (DTC) usually have an excellent prognosis. Following surgical and radioiodine treatment to remove the cancer cells and suppressive doses of levothyroxine, long-term follow-up, including measurement of serum thyroglobulin (Tg) using a sensitive assay is required to detect recurrence. To interpret Tg results clinicians need to know the corresponding serum TSH concentration, have an appreciation of the clearance of Tg from patient serum following various interventions and the limitations of its measurement. The limitations of Tg immunoassay are well described and include potential interference from TgAb. For the majority of patients with DTC who are TgAb-negative, Tg measurement remains the most useful method of follow-up. For the TgAb-positive minority, interference and the possibility of producing erroneous results is a concern. Some assays are less badly affected than others and laboratories are advised to choose their assays carefully. Laboratories have sought to identify interferences using measurement of TgAb, lack of concordance between RIAs and immunometric assays and recovery of added Tg. More recently LC-MSMS assays to quantify Tg have been developed. They are not currently as sensitive as Tg immunoassays and it is likely these assays will, like immunoassays, be limited by Tg heterogeneity and standardization issues, although initial evaluations indicate that they may have value in the clinical setting as a second line test in antibody-positive DTC patients in whom Tg is unmeasurable by immunoassay.     

TSH对分化型甲状腺癌病人血Tg的影响

目的对分化型甲状腺癌行双侧甲状腺全切术后停用内分泌治疗前后所测得的Tg进行对比分析。方法采用化学发光法对2003～2006年我院收治的83例分化型甲状腺癌的血TSH和Tg水平进行检测，在停用左旋T4前1天以及”。I内照射治疗前1天各测1次。结果在内分泌治疗期间Tg水平≤30μg／L时，停用内分泌治疗后Tg水平没有明显升高（P〉0．05）；但内分泌治疗期间Tg水平〉30μg／L时，停用内分泌治疗后Tg水平出现明显升高（P〈0．05）。结论风是分化型甲状腺癌较好的随诊指标．监测血Tg不必停用内分泌治疗．     

Thyroid cancer review 1: presentation and investigation of thyroid cancer

Thyroid cancer is uncommon with an estimated lifetime risk of 0.8% for women and 0.3% for men. The incidence appears to be increasing by 4% per year and is currently the eighth commonest cancer in women. Managing thyroid cancer is challenging, as no prospective randomised trials exist. Most of the information is derived from large patient cohorts in which therapy has not been randomly assigned. This is the first of the three review papers we have written on the management of thyroid cancer.     

Identification of a four-miRNA signature predicts the prognosis of papillary thyroid cancer

BACKGROUNDIn recently diagnosed patients with thyroid cancer, papillary thyroid cancer (PTC), as the most common histological subtype, accounts for 90% of all cases. Although PTC is known as a relatively adolescent malignant disease, there still is a high possibility of recurrence in PTC patients with a poor prognosis. Therefore, new biomarkers are necessary to guide more effective stratification of PTC patients and personalize therapy to avoid overtreatment or inadequate treatment. Accumulating evidence demonstrates that microRNAs (miRNAs) have broad application prospects as diagnostic biomarkers in cancer.AIMTo explore novel markers consisting of miRNA-associated signatures for PTC prognostication.METHODSWe obtained and analyzed the data of 497 PTC patients from The Cancer Genome Atlas. The patients were randomly assigned to either a training or testing cohort.RESULTSWe discovered 237 differentially expressed miRNAs in tumorous thyroid tissues compared with normal tissues, which contained 172 up-regulated and 65 down-regulated miRNAs. The evaluation of differently expressed miRNAs was conducted using our risk score model. We then successfully generated a four-miRNA potential prognostic signature [risk score = (-0.001 × hsa-miR-181a-2-3p) + (0.003 × hsa-miR-138-5p) + (-0.018 × hsa-miR-424-3p) + (0.284 × hsa-miR-612)], which reliably distinguished patients from high and low risk with a significant difference in the overall survival (P < 0.01) and was effective in predicting the five-year disease survival rate with the area under the receiver operating characteristic curve of 0.937 and 0.812 in the training and testing cohorts, respectively. Additionally, there was a trend indicated that high-risk patients had shorter relapse-free survival, although statistical significance was not reached (P = 0.082) in our sequencing cohort.CONCLUSIONOur results indicated a four-miRNA signature that has a robust predictive effect on the prognosis of PTC. Accordingly, we would recommend more radical therapy and closer follow-ups for high-risk groups.     

分化型甲状腺癌再次手术46例临床分析

目的 探讨分化型甲状腺癌再次手术的原因和选择合理的手术方式.方法 对甲状腺癌再次手术46例的资料进行回顾性分析并结合文献进行讨论.结果 本组病例首次手术前均诊断为良性甲状腺疾病;首次手术方式肿物切除或甲状腺部分切除术28例,甲状腺次全切除术12例,甲状腺叶全切除术3例,甲状腺腺叶全切除＋峡部切除＋颈淋巴结切除3例.再次手术原因主要为甲状腺癌术前诊断率低、首次手术方式不当及肿瘤复发或颈淋巴结转移.结论 由于甲状腺癌的术前误诊或首次手术方式不当,致术后的残癌率高,再次手术是必要的;术中冰冻病理切片检查是避免再次手术的关键;对于甲状腺癌切除术后复发或淋巴结转移者,应积极作合理的再次手术.     

Iodine-131 radio-guided surgery in differentiated thyroid cancer: outcome on 31 patients and review of the literature.

In the present study we investigated the role of radio-guided surgery with Iodine-131 (I-131) in a group of 31 patients with differentiated thyroid cancer (DTC) and loco-regional recurrent disease. The principal inclusion criterion for I-131 radio-guided surgery in our protocol was the presence of an I-131 positive loco-regional disease relapse after previous total thyroidectomy and at least 2 ineffective conventional I-131 treatments. The protocol we used consisted of the following steps. Day 0: all patients were hospitalized and received a therapeutic 3.7 GBq (100 mCi) dose of I-131 after thyroid hormone therapy withdrawal in condition of overt hypothyroidism (serum TSH levels>30 microUI/ml). Day 3: a whole body scan following the therapeutic I-131 dose (TxWBS) administration was acquired. Day 5: neck surgery was performed through a wide bilateral neck exploration using a 15-mm collimated gamma probe, measuring the absolute intra-operative counts and calculating the lesion to background (L/B) ratio. Day 7: post-surgery TxWBS was performed using the remaining radioactivity to evaluate the completeness of tumoral lesions extirpation. The final histologic examination showed the presence of 184 metastatic foci; among them, 98 (53.2%) were evident by both TxWBS and gamma probe evaluation, 76 (41.3%) were demonstrated only by gamma probe, and 10 (5.4%) were negative by both TxWBS and gamma probe evaluation. During follow-up (8 months to 4.9 years, mean 2.8 years), DxWBS, serum Tg levels off l-T4, and US showed absence of loco-regional disease in 25 patients (80.6%) while 6 patients had persistent disease. In conclusion, this protocol allowed us to identify neoplastic foci with high sensitivity and specificity, enabling us to remove loco-regional I-131 disease recurrences resistant to previous conventional I-131 therapies. Furthermore, the gamma probe allowed detection of some additional tumoral foci in sclerotic areas or located behind vascular structures that were not visualized at the pre-surgery TxWBS evaluation.     

Management of medullary carcinoma of the thyroid: a review

Medullary thyroid carcinoma (MTC) is an uncommon malignancy of neuroendocrine origin derived from the parafollicular C cells. Although infrequent, the interest in this cancer exceeds its incidence owing to its distinctive features and its characteristic association with other endocrine tumors. Although the majority of MTCs are sporadic, hereditary varieties occur in isolation or as a part of multiple endocrine neoplasia type 2 syndrome (MEN 2). Currently, complete surgical resection of the tumor and nodal metastases with a curative intent remains the mainstay of therapy. The role of adjuvant therapy is limited, although radiotherapy and newer targeted therapies are routinely used for metastatic disease. The lack of consensus in the available guidance regarding the most appropriate diagnostic, therapeutic and follow-up strategies has caused substantial variability in clinical practice. Therefore, this review summarizes the latest available evidence and guidelines on the management of MTC with an emphasis on diagnosis, surgical treatment and follow-up.     

Management of differentiated thyroid cancer of the follicular epithelium

Abstract

The incidence of thyroid cancer has been increasing in many countries over the last 30 years (from 3.6/100,000 people in 1973 to 8.7/100,000 people in 2002) while mortality has been slowly decreasing (). The increase is mainly represented by papillary thyroid cancer, while follicular and anaplastic histotypes remained stable. It is a general opinion that the increase is attributable to better detection of small papillary carcinomas as a result of improved diagnostic accuracy (neck ultrasound and fine-needle aspiration cytology). Consequently, it is common experience in thyroid cancer referral centers that nearly 60%–80% of thyroid carcinomas detected nowadays are micropapillary thyroid carcinomas (less than 1 cm in size) carrying an excellent long-term prognosis. In view of this change in the presentation of the disease, the objective of thyroid cancer management should be aimed at achieving complete cure using the less aggressive diagnostic and therapeutic procedures.     

分化型甲状腺癌患者促甲状腺激素抑制治疗期间骨质疏松风险筛查及影响因素分析

目的了解分化型甲状腺癌患者术后长期行促甲状腺激素(TSH)抑制治疗期间骨质疏松风险,并探索其相关影响因素。方法选取接受分化型甲状腺癌术后行TSH抑制治疗的300例患者为研究对象,利用国际骨质疏松基金会骨质疏松一分钟测试法和亚洲人骨质疏松自我筛查工具(OSTA)进行骨质疏松风险筛查,并根据结果进行影响因素分析。结果300例接受分化型甲状腺癌术后行TSH抑制治疗的患者中,66.00%的患者存在骨质疏松风险;OSTA显示该组患者骨质疏松低度风险为96.00%,中度风险为1.00%,高度风险为3.00%。患者的服药剂量、性别、绝经、婚姻状况、医保支付类型以及是否知晓甲状腺癌术后激素治疗会增加骨质疏松的发病率是骨质疏松的影响因素。结论大部分分化型甲状腺癌TSH抑制治疗患者都存在患有骨质疏松的风险,但多为低度风险。患者对骨质疏松的防范意识普遍不高。     

甲状腺乳头状癌组织中S-100阳性树突状细胞及淋巴细胞浸润与颈部淋巴结转移关系的研究

目的探讨甲状腺乳头状癌组织中S-100阳性树突状细胞及淋巴细胞浸润与颈部淋巴结转移的关系。方法50例甲状腺乳头状癌行颈部淋巴结清扫术患者,采用免疫组织化学方法检测甲状腺癌组织中S-100阳性树突状细胞及淋巴细胞浸润情况,分为S-100阳性树突状细胞及淋巴细胞阳性浸润者（A组）与单独S-100阳性树突状细胞或淋巴细胞浸润者（B组）,均行术后颈部淋巴结组织病理检查,比较2组颈部淋巴结转移率。结果A组颈部淋巴结转移率（27．78％）低于B组（78．12％）,2组比较差异有统计学意义（P〈O．05）。结论甲状腺乳头癌组织中S-100阳性树突状细胞及淋巴细胞浸润情况与颈部淋巴结转移密切相关。     

PET组合融合成像在分化型甲状腺癌复发和转移中的应用进展

甲状腺癌是最常见的内分泌系统恶性肿瘤之一,其中分化型甲状腺癌约占甲状腺癌发病率的90%以上,预后良好。但中国甲状腺癌患者5年相对生存率与一些发达国家差距较大。早期、准确地发现复发性疾病并应用适当的治疗策略,可改善复发性疾病患者的预后。因此,早期发现这些病人的复发和转移是至关重要的。随着诊断技术从系统向分子水平的过渡,多模态分子成像的作用越来越重要。PET能提供肿瘤细胞的功能学信息,而CT、MRI则能提供肿瘤的解剖学信息。功能成像技术和解剖学成像技术相结合能够实现优势互补,对于疾病复发和转移的诊断意义重大。随着近年来PET-CT在分化型甲状腺癌诊断、分期、疗效及预后评估上都较常规影像学检查更具优势,而PET-MRI是继PET-CT之后又一项优秀的多模态成像技术,因其软组织高分辨率和多序列多参数成像特性,所发挥的作用也愈发重要。因此,本文就PET-CT和PET-MRI在分化型甲状腺癌术后复发/转移中临床应用及未来前景进行综述。      

益气养阴方配合左甲状腺素钠片对分化型甲状腺癌手术患者甲状腺功能的改善效果

目的分析益气养阴方配合左甲状腺素钠片对分化型甲状腺癌手术患者甲状腺功能的改善效果。方法纳入2016年10月至2021年1月于我院诊治的120例分化型甲状腺癌手术患者为研究对象,按照红绿双色球法将其分为对照组(n=60,左甲状腺素钠片)与试验组(n=60,益气养阴方⁺左甲状腺素钠片)。连续治疗8周后,比较两组患者治疗前、后的甲状腺功能指标、白细胞介素-6(IL-6)、β₂-微球蛋白(β₂-MG)、骨代谢指标、免疫功能指标水平及中医证候积分,统计并比较两组患者的不良反应发生情况。结果治疗后,两组的促甲状腺激素(TSH)、甲状腺球蛋白(TG)以及甲状旁腺激素(PTH)水平均降低,且试验组明显低于对照组,差异具有统计学意义(P<0.05)。治疗后,两组的中医证候积分及IL-6、β₂-MG水平均降低,且试验组低于对照组,差异具有统计学意义(P<0.05)。治疗后,两组的碱性磷酸酶(ALP)、骨钙素(BGP)、β-胶原特殊序列(β-CTX)、Ⅰ型前胶原氨基端前肽(PⅠNP)水平均升高,但试验组低于对照组,差异具有统计学意义(P<0.05)。试验组的不良反应总发生率为6.67%,明显低于对照组的26.67%,差异具有统计学意义(P<0.05)。治疗后,两组的CD3⁺、CD4⁺以及CD4⁺/CD8⁺均升高,CD8⁺均降低,且试验组优于对照组,差异具有统计学意义(P<0.05)。结论益气养阴方⁺左甲状腺素钠片用于分化型甲状腺癌术后患者中的治疗效果理想,对于甲状腺功能以及临床症状具有改善效果,有利于减轻患者的炎症反应,优化骨代谢指标水平与免疫功能,且不良反应少,临床可进一步推广应用。