Lymph node management in clinically node-negative patients with papillary thyroid carcinoma

Aims

Systematic lymph node dissection in patients with papillary thyroid carcinoma (PTC) remains controversial. The objective of this study was to study the pattern of lymph node spread in patients with PTC clinically node-negative and then to propose a lymph node management strategy.

Methods

We retrospectively reviewed the records of patients who had undergone total thyroidectomy and a systematic central neck dissection (CND) and lateral neck dissection. Ninety patients with PTC without lymph nodes metastases (LNM) detected on preoperative palpation and ultrasonographic examination were included.

Results

Forty-one patients (45.5%) had LNM. Twenty-eight patients (31%) had a central and a lateral involvement. Thirteen patients (14.5%) had only a central involvement. All the patients without LNM in the central compartment were also free in the lateral compartment. There was no correlation between LNM status and TNM staging.The largest LNM in the central compartment was smaller than or equal to 5 mm in 66% of the cases, and that could explain the lack of sensitivity of the preoperative ultrasonographic examination.

Conclusion

CND could be considered at preoperative or intraoperative diagnosis of PTC whereas lateral neck dissection should be performed only in patients with preoperative suspected and/or intraoperatively proven LNM. Systematic CND allows an objective evaluation of lymph node status in this central cervical area where the LNM are particularly small and difficult to detect preoperatively.     

cN0甲状腺乳头状癌74例治疗分析

背景与目的:临床颈淋巴结阴性(cN0)甲状腺乳头状癌是否行颈部淋巴结清扫术、清扫范围以及清扫时机等是国内外学者长期争论的焦点.本研究通过对cN0甲状腺乳头状癌手术治疗结果分析,评价中央区淋巴结清扫的安全性和有效性,探讨cN0甲状腺乳头状癌患者清扫侧颈区淋巴结的必要性.方法:回顾性分析1999年1月-2006年12月间74例cN0甲状腺乳头状癌患者的手术治疗疗效.结果:74例患者均行中央区淋巴结清扫(Ⅵ区),其中32例阳性.32例中央区淋巴结阳性患者同期或分期行侧颈区淋巴结清扫(Ⅱ-Ⅴ区),其中19例阳性.中央区淋巴结转移与原发病灶大小、患者年龄无关,侧颈区淋巴结转移与原发病灶大小有关(χ2=5.96,P<0.05)、与患者年龄无关.当中央区淋巴结转移≥2枚时,侧颈区淋巴结转移率85.71%(χ2=4.61,P<0.05).结论:对cN0甲状腺乳头状癌建议行患侧腺叶和峡部切除加中央区淋巴结清扫术;对中央区淋巴结阳性(≥2枚)的患者可考虑行侧颈区清扫术.     

Total thyroidectomy alone versus ipsilateral versus bilateral prophylactic central neck dissection in clinically node-negative differentiated thyroid carcinoma. A retrospective multicenter study

Background

Central neck dissection (CND) remains controversial in clinically node-negative differentiated thyroid carcinoma (DTC) patients. The aim of this multicenter retrospective study was to determine the rate of central neck metastases, the morbidity and the rate of recurrence in patients treated with total thyroidectomy (TT) alone or in combination with bilateral or ipsilateral CND.

Current management of medullary thyroid cancer

Medullary thyroid cancer accounts for 5%-10% of all thyroid cancers. The majority of medullary thyroid cancers are sporadic, but 20% of cases are a result of a germline mutation in the ret proto-oncogene. Hereditary medullary thyroid cancer can be seen as part of the multiple endocrine neoplasia syndrome type 2A or 2B or as part of familial medullary thyroid cancer. This article discusses the current methods available for the diagnosis and evaluation of a patient with suspected medullary thyroid cancer. The management of medullary thyroid cancer is predominantly surgical excision, consisting of a total thyroidectomy and lymph node dissection. The extent and timing of surgical excision are discussed. Systemic therapeutic options are limited for medullary thyroid cancer, but several therapeutic targets show promise for the development of new therapies in the future.     

Systemic treatment and management approaches for medullary thyroid cancer

Although rare, medullary thyroid cancer (MTC) exemplifies the value that ever-expanding knowledge of molecular pathways and mechanisms brings to managing challenging cancers. Although surgery can be curative for MTC in many patients, a substantial proportion of patients present with locoregional or distant metastatic disease. Once distant disease occurs, treatment options are limited, and conventional cancer treatments such as cytotoxic chemotherapy are of minimal benefit. Biomarkers such as calcitonin and carcinoembryonic antigen are important correlates of disease burden as well as predictors of disease progress, including recurrence and survival. MTC is either sporadic (∼75%) or inherited (∼25%) as an autosomal dominant disease. Regardless, germline and somatic mutations, particularly in the rearranged during transfection (RET) proto-oncogene, are key factors in the neoplastic process. Gain-of-function RET mutations result in overactive proteins that lead to abnormal activation of downstream signal transduction pathways, resulting in ligand-independent growth and resistance to apoptotic stimuli. Specific RET mutation variants have been found to correlate with phenotype and natural history of MTC with some defects portending a more aggressive clinical course. Greater understanding of the consequence of the aberrant signaling pathway has fostered the development of targeted therapies. Two small-molecule tyrosine kinase inhibitors, vandetanib and cabozantinib, are currently available as approved agents for the treatment of advanced or progressive MTC and provide significant increases in progression-free survival. Since there have been no head-to-head comparisons, clinicians often select between these agents on the basis of familiarity, patient characteristics, comorbidities, and toxicity profile.     

甲状腺髓样癌临床病理分析

目的:探讨甲状腺髓样癌(MTC)的临床病理特点、免疫表型及电镜诊断特点。方法:回顾性分析10例甲状腺髓样癌的临床资料,采用免疫组化、组织化学方法研究其病理形态特点,结合文献分析甲状腺髓样癌的电镜诊断特点。结果:散发型甲状腺髓样癌8例,家族型甲状腺髓样癌2例,6例淋巴结转移;9例肿瘤间质刚果红染色( );免疫组化:癌组织中降钙素( )10例、铬粒素A( )10例、突触素( )7例,1例见甲状腺球蛋白阳性细胞,CD44V6在髓样癌中的阳性表达率为60%;电镜下见癌细胞胞质内有大小不一的神经内分泌颗粒。结论:MTC具有多分化肿瘤的特点,可产生多种神经内分泌物质;其诊断依赖于组织病理学、免疫组化和组织化学,电镜在MTC的诊断中有重要价值;降钙素(CT)是其特异性标记物;CD44V6的高表达与MTC的颈部淋巴结转移密切相关。     

95例Ⅰ期舌体鳞癌的颈部处理

背景与目的颈淋巴结的转移与复发是舌癌治疗失败的常见原因,目前对早期舌癌的颈部处理仍有争论,本研究旨在探讨选择性颈清扫术在治疗临床Ⅰ期舌体鳞癌中的作用。方法回顾性分析1988年至1997年间手术治疗的95例临床Ⅰ期舌体鳞癌患者,分为颈部观察和选择性颈清扫两组,总结分析选择性颈清扫对颈部复发率、总体生存率等治疗结果的影响。结果行颈部观察组24例,颈部复发率为25.0%(6/24),由于颈部复发而导致的死亡率为20.8%(5/24);行选择性颈清扫组71例,颈部复发率和由于颈部复发而导致的死亡率分别为7.0%(5/71)和4.2%(3/71)。两组的颈部复发率和由于颈部复发而导致的死亡率差异均有显著性(χ2检验,P<0.05);选择性颈清扫组的总体生存率亦显著高于颈部观察组(log鄄rank检验,P<0.05)。结论对临床Ⅰ期舌体鳞癌行选择性颈清扫不但可以提高患者的颈部控制率,而且能减少因颈部复发导致的死亡率,提高患者的总体生存率。     

甲状腺髓样癌的辅助治疗

目的 评价放射治疗、化学治疗和放射性核素186Re对晚期甲状腺髓样癌的疗效。方法 回顾性分析本院1960年6月～2000年7月间接受放疗、化疗或放射性核素治疗的甲状腺髓样癌患者疗效。结果 放射治疗对术后肉眼残留者3年局控率为33．3％(3／9例)，对镜下残留者3年局控率达63．6％(7／11例)，单用放射治疗无效(3例)。化学治疗疗效不明显(11例)。放射性核素186Re对晚期甲状腺髓样癌肿瘤灶有抑制生长作用。结论 放射治疗对术后镜下残留、肉眼残留者不失为手术治疗的有益补充，能明显提高局控率。放射性核素186Re的治疗价值有待研究。     

甲状腺乳头状癌颈部淋巴结转移规律及其治疗方案选择的研究

目的:探讨临床淋巴结阴性的甲状腺乳头状癌患者的颈部淋巴结转移特点及淋巴结处理方法。方法:回顾性分析107例临床淋巴结阴性甲状腺乳头状癌患者的临床资料。按肿瘤大小及淋巴结的处理不同将患者分为3组,A组:肿瘤长径≤1cm行同侧Ⅵ区淋巴结清除;B组:肿瘤长径>1～3cm行双侧Ⅵ区淋巴结清除及同侧Ⅲ、Ⅳ区淋巴结冷冻病理;C组:肿瘤长径>3cm者行双侧Ⅵ区淋巴结清除及同侧Ⅲ、Ⅳ区淋巴结冷冻病理。B、C组患者中,同侧Ⅲ、Ⅳ区淋巴结冷冻病理转移者行改良性颈淋巴结清除。结果:3组患者同侧Ⅵ区转移率分别为41.1%、61.1%和73.3%,差异有统计学意义,χ2=6.610 9,P=0.036 7;B、C组患者的对侧Ⅵ区淋巴结转移率分别为30.5%和73.3%,差异有统计学意义,χ2=3.851 0,P=0.049 7;B、C组患者的Ⅲ、Ⅳ区转移率分别为19.4%和46.7%,差异有统计学意义,χ2=4.267 4,P=0.038 9。结论:临床淋巴结阴性的甲状腺乳头状癌患者易发生Ⅵ及Ⅲ、Ⅳ区淋巴结转移。肿瘤长径≤1cm者建议行同侧Ⅵ区淋巴结清除,肿瘤长径>1cm者建议行双侧Ⅵ区淋巴结清除及同侧Ⅲ、Ⅳ区淋巴结冷冻,转移者行改良性颈淋巴结清除。     

遗传型甲状腺髓样癌肿瘤休眠现象与RET基因突变

甲状腺髓样癌(medullary thyroid carcinoma,MTC)属于甲状腺癌中恶性程度较高的一类,其10年生存率约为50%.我们报告2例来自同一家系休眠时间超过20年的遗传型甲状腺髓样癌,同时提取其外周血基因组DNA,对RET原癌基因进行检测,探讨其肿瘤休眠现象发生的可能机制.     

Lymph node metastasis in hereditary medullary thyroid cancer is independent of the underlying RET germline mutation

Although the onset of hereditary medullary thyroid cancer (MTC) depends on mutational risk, the impact of that risk on lymph node metastasis is unclear.Included in this investigation were 387 carriers of RET germline mutations with node-negative MTC (201 carriers) or node-positive MTC (186 carriers).Age at thyroidectomy increased significantly from highest (p.Met918Thr; 45 carriers), high (p.Cys634Arg/Gly/Phe/Ser/Trp/Tyr; 138 carriers) and moderate-high risk (p.Cys609/611/618/620Arg/Gly/Phe/Ser/Trp/Tyr; 93 carriers) to low-moderate risk (p.Glu768Asp, p. Leu790Phe, p. Val804Leu/Met, p. Ser891Ala; 111 carriers).In contrast, tumor progression to lymph node metastasis was similar, taking 8.6–9.1 years with moderate risk mutations and 13.6–14.5 years with high and highest risk mutations. Primary tumor size across the mutational risk spectrum changed little, measuring 18.1–22.1 mm with and 2.7–7.3 mm without lymph node metastasis.Because the biological behavior of hereditary MTC is similar after disease onset, equal treatment of comparable tumors is warranted regardless of the underlying RET mutation.     

食管癌219例根治性切除的淋巴结的转移规律

目的研究淋巴结在食管癌转移的规律。方法根治性切除２１９例食管癌患者的癌组织及廓淋巴结１８７９枚并作区域分布的病理分析。结果２１９例根治性切除食管癌患者中６５例有淋巴结转移。其中胸上段食管癌８例中有２例颈深淋巴结转移。胸中段食管癌１８６例中５２例有淋巴结转移,其中伴有隆突淋巴结转移２６例,伴有食管旁、贲门区和胃左动脉旁、左下肺静脉及左下肺韧带淋巴结转移分别为１５、１２、２２、４、５例。胸下段食管癌２５例中有淋巴结转移者１１例,其中伴有食管旁、左下肺韧带、贲门区和胃左动脉旁淋巴结转移分别为１、２、５、８例。左肺动脉淋巴结无１例转移。结论淋巴结在食管癌转移的共性规律是：上段癌向上转移大于向下,下段癌向下转移大于向上,中段癌转移依次隆突区、胃左动脉旁、胸上食管旁、胸下食管旁和贲门区。左肺动脉淋巴结甚少转移。     

Ultrasound features of medullary thyroid carcinoma correlate with cancer aggressiveness: a retrospective multicenter study

Background

Poor prognosis of medullary thyroid cancer (MTC) with suspicious ultrasound (US) features has been reported. The aim of the study was to investigate the association between preoperative US presentation and aggressiveness features of MTC. Also, US features of MTC were compared with those previously reported.

Methods

Study group comprised 134 MTC from nine different centers. Based on US presentation the nodules were stratified in “at risk for malignancy” (m-MTC) or “probably benign” (b-MTC) lesions.

Results

Eighty nine (66.4%) m-MTC and 45 (33.6%) b-MTC were found. Metastatic lymph nodes (p = 0.0001) and extrathyroid invasiveness (p < 0.0001) were more frequent in m-MTC. There was statistically significant correlation (p = 0.0002) between advanced TNM stage and m-MTC with an Odds Ratio 5.5 (95% CI 2.1–14.4). Mean postsurgical calcitonin values were 224 ± 64 pg/ml in m-MTC and 51 ± 21 in b-MTC (p = 0.003).

Conclusions

This study showed that sonographically suspicious MTC is frequently associated with features of aggressiveness, suggesting that careful preoperative US of MTC patients may better plan their surgical approach.     

Individual prediction of lateral neck metastasis risk in patients with unifocal papillary thyroid carcinoma

IntroductionMuch controversy exists over whether to perform lateral neck dissection (LND) on patients with papillary thyroid carcinoma (PTC). This study aimed to build predictive nomograms that could individually estimate lateral neck metastasis (LNM) risk and help determine follow up intensity.Patients and methodsUnifocal PTC patients who underwent LND between April 2012 and August 2014 were identified. Clinical and pathological variables were retrospectively evaluated using univariate and stepwise multivariate logistic regression analysis. Variables that had statistical significance in final multivariate logistic models were chosen to build nomograms, which were further corrected using the bootstrap resampling method.ResultsIn all, 505 PTC patients were eligible for analysis. Among these, 178 patients (35.2%) had lateral neck metastasis. Two nomograms were generated: nomogram (c) and nomogram (c + p). Nomogram (c) incorporated four clinical variables: age, tumor size, tumor site, and extrathyroidal extension (ETE). It had a good discriminative ability, with a C-index of 0.79 (bootstrap-corrected, 0.78). Nomogram (c + p) incorporated two clinical variables and two pathological variables: tumor size, tumor site, extranodal extension (ENE), and number of positive nodes in the central compartment. Nomogram (c + p) showed an excellent discriminative ability, with a C-index of 0.86 (bootstrap-corrected, 0.85).ConclusionTwo predictive nomograms were generated. Nomogram (c) is a clinical model, whereas nomogram (c + p) is a clinicopathological model. Each nomogram incorporates only four variables and can give an accurate estimate of LNM risk in unifocal PTC patients, which may assist clinicians in patient counseling and decision making regarding LND.     

食管癌术后颈部和纵隔淋巴结转移放射治疗的意义

为评价食管癌术后颈部和纵隔淋巴结转移局部放射治疗的意义，回顾性分析1989年3月～1994年2月5年间收治的143例病人。其中颈部转移89例，纵隔转移32例，纵隔和颈部同时并有转移22例。60Co局部放射，大多数病人的放射剂量为50～70Gy。随访2年以上或至死亡。结果70％以上的肿瘤获得局部控制。1，2，3，5年生存率分别为43．4％，18．2％，7．4％和6．4％。中位生存期14个月。多数病人死于照射野外转移。转移淋巴结≤3cm者放疗后的局部控制率和生存期优于淋巴结＞3cm者。结果提示：放疗对食管癌术后颈部和纵隔转移淋巴结的局部控制有效，但只有少数病人可获较长时间生存。远处转移是致死的主要原因。     

微波消融治疗甲状腺乳头状癌术后淋巴结转移的临床研究和疗效观察

目的 为了提高对超声引导下经皮微波消融术治疗甲状腺乳头状癌术后颈部淋巴结转移癌的认识,并评价其疗效性和安全性。方法 选择84例甲状腺乳头状癌术后复发的患者,接受微波消融治疗后,通过超声造影增强检查,评估消融区内的肿瘤活性,在1、3、6个月以及12个月对患者进行肿瘤大小、体积和血清甲状腺球蛋白的测量临床评估。结果 103个颈部淋巴结转移癌全部成功接受了微波消融治疗,治疗后超声造影增强检查未检测到不完全消融,在最后一次随访中,平均最大直径从10.5±5.7mm减小到0.8±1.5mm(P＜0.05),平均体积从285.9±245.7mm³减小到4.0±8.0mm³(P＜0.05)。治疗后既未检测到已治疗的肿瘤发生进展,也没有新增可疑的淋巴结。结论 超声引导下经皮微波消融术可能成为某些不适合或拒绝进行手术治疗的甲状腺乳头状癌术后淋巴结转移患者的替代疗法,这种手术安全有效,并发症发生率低。     

Prognostic impact of nuclear DNA content in medullary thyroid carcinoma; a retrospective pilot study

The prognostic significance of DNA content in medullary thyroid carcinoma was studied retrospectively in 16 patients. Five patients died within 3 years of medullary thyroid carcinoma and 11 patients survived for at least 10 years. Clinical data and tumour morphology were studied. DNA measurements on tumour cells in histologic sections were performed with slide cytophotometric technique. The tumours of the survivors had in all but two cases a DNA content comparable to that of normal cells, whereas the tumours of the non-survivors and two of the survivors had higher DNA content. The results indicate that DNA measurements in medullary thyroid carcinoma might be of use in addition to clinical and morphologic data and that further studies are warranted.     

Surgery for lymph node metastases of medullary thyroid carcinoma: A review

Medullary thyroid carcinoma (MTC) is a neuroendocrine malignancy of the thyroid C cells that occurs in hereditary and sporadic clinical settings. Metastatic spread commonly occurs to cervical and mediastinal lymph nodes. MTC cells do not concentrate radioactive iodine and are not sensitive to hormonal manipulation, and therefore surgery is the most effective option for curative therapy, reduction in tumor burden, or effective palliation. In patients undergoing preventative surgery for hereditary MTC, central lymph node dissection should be considered if the calcitonin level is elevated. Preservation of parathyroid function in these young patients is of paramount importance. In patients with established primary tumors, systematic surgical removal of lymph node basins (compartmental dissection) should be guided by ultrasound mapping of lymph node metastases and level of serum calcitonin. A “berry‐picking” approach is discouraged. Newly approved targeted molecular therapies offer wider treatment options for patients with progressive or metastatic disease. Cancer 2016;122:358–366. © 2015 American Cancer Society.