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.     

分化型甲状腺癌再次手术治疗分析

目的 探讨分化型甲状腺癌再次手术的原因、必要性和对策.方法 回顾性分析我院2000-2010年收治的124例分化型甲状腺癌患者再次手术的临床资料.结果 124例甲状腺癌再次手术病例中,75例甲状腺癌误诊为甲状腺良性病变,而行肿瘤局部切除或一侧腺叶次全切除术,手术切除范围不够;39例为首次手术方式选择不当,其中27例已有颈淋巴结转移,未行颈淋巴结清扫术,12例因颈淋巴结转移癌仅行淋巴结活检,忽视甲状腺肿瘤的诊断;10例因为快速病理检查未能诊断甲状腺癌而再次手术.最终病理检查证实肿瘤的残留率为50%(62/124),并发症发生率为4.03%(5/124).结论 甲状腺癌误诊为良性病变是造成再次手术的主要原因;不规范甲状腺癌手术后再次手术是必要的;提高术者对甲状腺癌的认识水平,强调术中快速冰冻切片病检在甲状腺手术中常规应用,选择恰当的手术方式,是避免甲状腺癌再次手术的关键.

Abstract：

Objective To discuss the main causes, necessity and strategy of reoperation in patients with differentiated thyroid cancer. Methods The clinical data of 124 patients with thyroid cancer who needed reoperation from 2000 to 2010 were analyzed retrospectively. Results In the 124 patients with thyroid cancer required for reoperation, 75 cases were misdiagnosed as benign thyroid tumor and previously received local nodulectomy or subtotal lobectomy, in which the extent of resection was not enough; in 39 cases, the first time surgical modality were unsuitable, of which 27 cases with cervical lymph node metastasis were not performed cervical lymph node dissection, and 12 cases with cervical lymph node metastasis cancer were only performed lymph node biopsy, and the diagnosis of thyroid cancer was ignored. 10 cases suffered reoperation because of failure to diagnosis thyroid cancer by quick pathologic diagnosis. The rate of residual cancer was 50% (62/124) by final pathologic diagnosis,and the rate of complication was 4.03% (5/124). Conclusion Misdiagnosis of thyroid cancer as benign thyroid tumor is the main cause of reoperation. Reoperation is necessary for those patients who received nonstandardized operation. The key points of avoiding reoperation are to improve cognitive level of operator for thyroid cancer, to emphasize the routine application of quick pathologic diagnosis during operation of thyroid and select the best suitable surgical modality.     

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.     

Serum thyroglobulin measurements in differentiated thyroid cancer.

In pathological states, the serum thyroglobulin (Tg) concentrations are generally high. Therefore, a serum assay of Tg levels is not useful for the differential diagnosis between benign or malignant disease in the preoperative period. Serum Tg measurements are a suitable marker in the follow-up of patients with differentiated thyroid carcinoma (DTC) during the postoperative period. After total thyroidectomy, serum Tg concentrations were found to be undetectable in subjects without evidence of residual thyroid tissue or metastases; however, detectable serum Tg levels in subjects on and off thyroid hormone suppressive therapy indicate the presence of residual or metastatic thyroid tissue. An increase in serum Tg levels during thyroid stimulating hormone (TSH) suppression indicates that further investigations are necessary.     

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.     

Clinical development of kinase inhibitors for the treatment of differentiated thyroid cancer

The incidence of thyroid cancer is growing at a rapid rate, with the majority of cases being differentiated thyroid cancers. Although a significant number of patients with localized disease are cured, a paucity of effective therapies currently exists for patients with recurrent and/or metastatic disease. The translational bridging of critical biologic insights into the pathogenesis of thyroid cancer and the clinical development of specific kinase inhibitors that disrupt these oncogenic pathways has led to exciting progress in clinical thyroid cancer research. This review will present the scientific rationale and clinical trial data gathered to date with kinase inhibitors in differentiated thyroid cancers.     

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 2: management of differentiated thyroid cancers

This is the second review article on thyroid cancer dealing with the common differentiated types that comprise 90% of thyroid cancers. Despite clinical management guidelines offered by a number of organisations including the British Association of Otolaryngologists and Head and Neck Surgeon, The British Thyroid Association, The American Association Of Endocrinologists, The American Thyroid Association and the National Cancer Centre Network, debate regarding the management of differentiated thyroid cancer continues. This is because of the absence of good quality research evidence as a consequence of the natural history of this disease.     

Autophagy induction of reversine on human follicular thyroid cancer cells

The incurable differentiated thyroid cancer (DTC), poorly differentiated thyroid cancer (PDTC) and anaplastic thyroid cancer (ATC) are the most aggressive in all of the thyroid cancers. Unfortunately, there are almost no effective therapies. A novel and effective treatment is urgently needed to develop. Recently, reversine, a small synthetic purine analogue, has been reported to be effective in human thyroid cancer suppression through cell cycle arrest and apoptosis induction. In this study, we performed an in vitro evaluation of reversine on autophagy activation, one of the programmed cell death, and the related mechanisms in human follicular thyroid cancer cell line WRO. Incubation of WRO cells with reversine induced autophagosome formation in a short time treatment. LC3-II overexpression in a dosage-dependent manner with reversine treatment was demonstrated in the autophagy activation. Moreover, reversine suppressed Akt/mTOR related signaling pathway activation, a major pathway for autophagy activation, was also revealed in WRO cells. Our data demonstrated that reversine is effective to induce autophagy. Moreover, the LC3-II overexpression and the p62 protein were degraded in a time-dependent manner, indicating that the autophagic flux has happened in the reversine treated WRO cells. In addition, the activation of Akt/mTOR/p70S6 K related pathways were shown to be reduced, suggesting these pathways may involve in the reversine mediated autophagy induction. Reversine is therefore worthy of further investigation in clinical therapeutics.     

The role of external beam radiotherapy in the management of differentiated thyroid cancer.

Well differentiated thyroid cancers (DTC), usually having an indolent course, are generally treated by surgery, i.e., total or near total thyroidectomy, followed by radioiodine and TSH suppressive therapy with thyroid hormone. The beneficial effect of external beam radiotherapy (EBRT) in the treatment of selected metastatic sites (i.e., brain and bone) or for palliation in cases of locally advanced inoperable disease is widely accepted. In contrast, its efficacy in improving postoperative locoregional disease control is still controversial. A better definition of subgroups of patients at high risk of local failure is mandatory. At present, patients older than 40-45 years affected by papillary cancers with macro- or microscopic postoperative residual disease and with extensive extrathyroid invasion appear to benefit from EBRT performed in addition to surgery and radioiodine. The role of EBRT in patients with radioiodine non-responsive progressive disease will also be discussed.     

SPECT/CT融合显像在分化型甲状腺癌中的临床应用价值

分化型甲状腺癌（Differentiated thyroid carcinoma,DTC）包括乳头状甲状腺癌和滤泡状甲状腺癌,约占甲状腺恶性肿瘤的94%。影像学检查除了超声、CT、^99mTcO4^-甲状腺显像、^131I全身显像（^131I-WBS）等检查手段外,随着技术的发展SPECT/cT融合显像既能反映甲状腺大小、形态的改变,又能对DTC病灶数目、部位以及摄碘情况进行准确定位和定性,     

分化型甲状腺癌患者停用甲状腺激素后血脂与甲状腺功能的相关性分析

目的研究分化型甲状腺癌患者停用甲状腺激素后血脂与甲状腺功能的相关性。方法选取2014年8月至2015年8月在该院实施手术治疗的130例分化型甲状腺癌患者,患者在停止应用左甲状腺激素钠(L-T4)前、手术前以及停药3周后分别测定血清FT_4、TSH、FT_3、三酰甘油(TG)、总胆固醇(TCHO)、LDL-C、HDL-C等指标,由此分析患者的血脂水平与甲状腺功能的相关性。结果实施手术前HDL-C与TSH水平呈正相关(P0.05),其他指标与甲状腺功能未见明显相关性(P0.05);停药前血脂水平与甲状腺功能未见明显相关性(P0.05);停药后总胆固醇水平与FT_3、FT_4水平呈负相关(P0.05);HDL-C与FT_3、FT_4水平呈负相关(P0.05),与TSH水平呈正相关(P0.05);LDL-C与FT_4呈负相关(P0.05)。结论甲状腺激素暂停应用治疗时,随着TSH水平的升高,HDL-C水平有所提升;总胆固醇、HDL-C以及LDL-C水平均与FT_3、FT_4呈负相关,药物停用后患者血脂代谢异常与甲状腺功能减退密切相关。     

分化型甲状腺癌131Ⅰ治疗后扫描的假阳性分析

目的分析分化型甲状腺癌131Ⅰ治疗后扫描假阳性摄取的常见部位和摄取机制.方法分化型甲状腺癌患者346例,口服治疗剂量131Ⅰ后7天进行全身131Ⅰ扫描,根据临床症状、体征、131Ⅰ全身扫描结果、血清Tg水平和其他影像学检查结果,判断131Ⅰ的摄取是否为假阳性摄取.结果胃肠道假阳性摄取65例,肺部假阳性摄取12例,双侧乳腺假阳性摄取3例,两侧腋下汗腺假阳性摄取1例,肝脏显影253例.结论131Ⅰ治疗后扫描发生假阳性摄取常见部位主要为胃肠道、肺部和肝脏;应注意甄别,避免使患者接受不必要的131Ⅰ治疗.     

Imaging,genetic testing,and biomarker assessment of follicular cell-derived thyroid cancer

Abstract

Thyroid carcinoma is the most common endocrine malignancy worldwide, and its incidence continues to increase. As such the approach to a recently identified thyroid nodule is important to understand. The relevant imaging, examination, and need for fine-needle aspiration biopsy (FNA) are discussed. In approximately 25% of nodules, the diagnosis cannot be established with FNA-based cytology, and surgical excision is necessary for definitive diagnosis. Recent advances in genetic and molecular testing may increase the diagnostic accuracy of FNA in managing thyroid nodules.     

The thyroid "microsomal" antibody revisited. Its paradoxical binding in vivo to the apical surface of the follicular epithelium

We have shown that thyroid monolayers derived from the glands of patients with autoimmune thyroid disease have immunoglobulin (Ig) bound to their surface. This appears to have been deposited in vivo rather than during preparation of the monolayers, a view supported by our finding of such deposits on the apical margin of follicular cells in sections cut from these glands and stained with conjugated anti-immunoglobulin. It is likely that these deposits represent specific binding of so-called "microsomal" autoantibodies to the surface of the thyroid cells in vivo since staining of partially disrupted follicles ("half-melons") with Hashimoto serum containing microsomal autoantibodies in the indirect immunofluorescence (IFL) test, localized the antigen on the apical surface of the cells lining the follicular cavity. Thus, paradoxically, although the antigen is relatively inaccessible, autoantibodies do reach and combine with the thyroid surface in vivo and may therefore play a role in pathogenesis.