Clinical significance of CCNE2 protein and mRNA expression in thyroid cancer tissues

PurposeThyroid carcinoma (TC) is the most common endocrinal malignancy worldwide. Cyclin E2 (CCNE2), a member of the cyclin family, acts as a regulatory subunit of cyclin-dependent kinases (CDKs). It controls the transition of quiescent cells into the cell cycle, regulates the G1/S transition, promotes DNA replication, and activates CDK2. This study explored the role and potential molecular mechanisms of CCNE2 expression in TC tissues.Material/methodsImmunohistochemistry was used to evaluate the CCNE2 protein expression levels in TC. High-throughput data on CCNE2 in TC were obtained from RNA sequencing (RNA-seq), microarray, and literature data. The CCNE2 expression levels in TC were comprehensively assessed through an integrated analysis. Analyses of Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein–protein interaction (PPIs) data facilitated the investigation of the relative molecular mechanisms of CCNE2 in TC.ResultsThe immunohistochemical experiment showed a significant increase in the expression of CCNE2 in the TC tissues. For 505 TC and 59 non-cancerous samples from RNA-seq data, the area under the curve (AUC) was 0.8016 (95% confidence interval [CI] 0.742–0.8612; p<0.001). With another 14 microarrays, the pool standard mean difference [SMD] was 1.01 (95% CI [0.82–1.19]). The pooled SMD of CCNE2 was 1.12 (95% CI [0.60–1.64]), and the AUC was 0.87 (95% CI [0.84–0.90]) for 1157 TC samples and 366 non-cancerous thyroid samples from all possible sources. Nine hub genes were upregulated in TC.ConclusionsA high expression of CCNE2 may lead to carcinogenesis and the development of TC.     

Clinical Utility of BRAF,NRAS, and TERT Promoter Mutation in Preoperative Thyroid Fine-Needle Aspiration Biopsy: A Diagnostic Study From Dharmais Cancer Hospital

Objective: Molecular testing of thyroid nodules becomes important for improving the accuracy of fine-needle aspiration biopsy (FNAB). This study aimed to investigate the diagnostic utility of BRAF, NRAS, and TERT promoter mutation in thyroid nodules at Dharmais Cancer Hospital.Methods: We performed a prospective diagnostic study involving 50 patients with thyroid nodules who needed surgery between September 2013 and August 2014. Mutational hotspots in BRAF exon 15, NRAS exon 3, and TERT promoter region were analyzed by Sanger sequencing from FNAB specimens. Cytology and molecular data were compared to histopathology results.Result: Of the 50 cases included in the analysis, 39 cases (78%) were thyroid malignancies. Mutations of BRAF, NRAS, and TERT promoter were detected in 31% (12/39), 18% (7/39), and 13% (5/39) cases, respectively. BRAF and NRAS mutations were found mutually exclusive, while all of TERT promoter mutation was found coexistent either with BRAF (40%) or NRAS (60%). The combination of FNAB cytology and molecular testing resulted in 69% sensitivity, 100% specificity, 100% positive predictive value, 48% negative predictive value, and 76% accuracy.Conclusion: Molecular testing of BRAF, NRAS, and TERT mutations improve the sensitivity of thyroid FNAB and is beneficial for more definitive treatment in selective cases. However, the NPV is relatively low to avoid the need for diagnostic surgery. Therefore, further studies to identify more sensitive methods and more comprehensive molecular markers in the diagnosis of thyroid nodules are needed.     

琥珀酰胆碱与罗库溴铵用于麻醉诱导对甲状腺手术患者术中喉返神经监测的影响[论著]

目的　比较常规剂量琥珀酰胆碱与小剂量罗库溴铵用于麻醉诱导对甲状腺手术患者术中喉返神经监测的影响。方法　选取2019年4月至2019年7月本院120例同一外科医师团队甲状腺手术喉返神经监测患者，随机分为A组：麻醉诱导肌松药物为琥珀胆碱1.5 mg/kg；B组：麻醉诱导肌松药物为罗库溴铵0.3 mg/kg。麻醉医师待肌松监测显示到最大抑制后，通过气管插管条件评分评估两组患者气管插管条件。记录各组插管时间、等待时间；迷走神经和喉返神经电信号基础值；以及术中血压波动、术后咽痛、声音嘶哑、低氧血症、苏醒延迟等并发症。外科医师通过神经肌电监测仪进行喉返神经刺激评估两组患者喉返神经监测情况。结果　A组患者气管插管条件优于B组，A组插管时间、肌松监测时间小于B组，两组手术监测时间差异无统计学意义。A组首次神经监测信号值大于B组，A组首次监测例数多于B组，两组患者术中无体动，血压下降差异无统计学意义。麻醉术后并发症，A组咽痛少于B组，A组有少量患者发生肌痛，差异无统计学意义。结论　1.5 mg/kg琥珀酰胆碱用于甲状腺手术患者的麻醉诱导，可以提供较好的插管条件，不影响外科医师术中行喉返神经监测，同时减少患者术后咽痛的发生。     

老年轻度认知障碍患者血清瘦素、甲状腺激素水平与局部脑血流量关系的研究

目的 通过检测老年轻度认知障碍（MCI）患者血清瘦素（LEP）、甲状腺激素水平，分析其与局部脑血流量（rCBF）的关系。方法 选择本院收治的128 例老年MCI 患者，另选健康者128 例作为对照组。检测血清LEP、甲状腺激素、大脑各区域rCBF 水平并分析其相关性。结果 老年MCI 组患者左右侧额叶、右侧颞叶、左侧顶叶、左右侧基底节区域脑血流量[（43.81±8.62）mL/（100 g·min）、（43.24±7.93）mL/（100 g·min）、（45.14±6.98）mL/（100 g·min）、（45.86±6.77）mL/（100 g·min）、（67.95±8.52）mL/（100 g·min）、（68.36±8.34）mL/（100 g·min）]低于对照组[（46.39±8.31）mL/（100 g·min）、（46.52±8.56）mL/（100 g·min）、（47.37±7.04）mL/（100 g·min）、（48.25±6.98）mL/（100 g·min）、（70.34±8.96）mL/（100 g·min）、（70.58±8.57）mL/（100 g·min）]（P＜0.05）。老年MCI 组患者血清LEP、T3、FT3 水平[（4.87±1.56）μg/L、（1.21±0.16）nmol/L、（3.04±0.36）pmol/L]低于对照组[（11.45±3.92）μg/L、（1.68±0.21）nmol/L、（4.82±1.21）pmol/L]（P＜0.05），TSH 水平为（2.78±0.75）IU/mL，高于对照组的（1.13±0.38）IU/mL（P＜0.05）。老年MCI 患者血清LEP 水平与左侧额叶、右侧颞叶、左侧顶叶rCBF 呈正相关（r=0.452、0.537、0.544，P 均＜0.05），T3 水平与左侧额叶、右侧颞叶rCBF 呈正相关（r=0.427、0.521，P 均＜0.05），FT3 水平与右侧颞叶rCBF 呈正相关（r=0.492，P＜0.05），TSH 水平与左侧额叶、右侧颞叶rCBF 呈负相关（r=-0.463、-0.489，P 均＜0.05）。结论 老年MCI 患者血清中LEP、T3、FT3 水平降低，TSH 水平升高，且与不同区域rCBF 有相关性，可通过调控脑血管功能影响rCBF 变化水平。     

甲状腺乳头状癌合并颈部局灶型Castleman病1例

摘要：目的探讨甲状腺乳头状癌(PTC)合并颈部局灶型Castleman病 (UCD)的临床诊治经验。方法回顾性分析1 例PTC合并颈部UCD的临床病例资料，并检索国内外文献。该患者术前行甲状腺结节穿刺细胞学检查(FNA)倾向PTC，合并右颈侧区淋巴结肿大，行甲状腺右侧腺叶合并峡部切除及右颈II、III、IV、VI区淋巴结清扫术。结果术后切口愈合良好，无声音嘶哑及低钙症状，术后 4 d治愈出院。术后随访6个月无复发。术后病理证实颈侧区肿大淋巴结为UCD。结论PTC合并UCD极为罕见，且UCD的术前诊断较为困难，但手术切除多可治愈；PTC合并颈部淋巴结肿大者，临床医生不仅需考虑甲状腺癌转移淋巴结可能，还需警惕UCD的存在。     

Synergistic effect of clinicopathological factors on mortality risk in patients with differentiated thyroid cancer: An analysis using the SEER database

ObjectivesIn this study, we analyzed the effects of histology subtypes, lymph node N-stages, and the presence of extrathyroidal extensions on cancer-specific survival (CSS) and overall survival (OS) in patients with differentiated thyroid cancer.Materials and methodsCox proportional hazards regression analyses were carried out to evaluate the correlations between clinicopathological factors and CSS/OS. The combined effects of these factors on CSS and OS were then analyzed to determine the relative excess risk, attributable proportion, and synergy index. Kaplan-Meier curves were used to evaluate the mortality rate.ResultsA total of 86033 cases were included in the analysis. Histology subtype, N-stage, and extrathyroidal extension were all found to be risk factors for CSS (hazard ratio [HR] = 1.8, 95% confidence intervals [CI]: 1.4–2.3, p < 0.001; HR = 1.9, 95% CI: 1.6–2.3, p < 0.001; HR = 1.4, 95% CI: 1.0–1.9, p = 0.035, respectively). The risk factors for OS were histology subtype and N-stage (HR = 1.3, 95% CI; 1.2–1.5, p < 0.001; HR = 1. 4, 95% CI: 1.3–1.5, p < 0.001, respectively) but not extrathyroidal extension (HR = 1.1, 95% CI: 0.9–1.3, p = 0.228). Furthermore, histology subtype and N-stage, histology subtype and extrathyroidal extension, and N stage and extrathyroidal extension (relative excess risk, attributable proportion, and synergy index: 48.8, 0.9, 7.6; 50.2, 0.7, 3.9; 7.0, 0.3, 1.6; respectively) were found to have significant synergistic effects.ConclusionPatients with follicular thyroid carcinoma (FTC) and extrathyroidal extension or lymph node metastasis are at a higher risk of mortality. Histology subtype, N-stage, and extrathyroidal extension appear to have synergistic effects on the increased risk of poor CSS in patients. This result can in the further development of treatment guidelines to improve the outcome of FTC patients.     

加速康复外科理念应用于甲状腺癌手术100例

目的 观察加速康复外科(ERAS)在甲状腺癌手术患者围手术期的应用效果。 方法 选取行双侧甲状腺癌根治术的患者150例,随机分为ERAS组(100例)、常规手术组(50例)。ERAS组围手术期采取一系列符合加速康复理念的优化措施,非ERAS组采取传统术前准备措施。比较两组术后疼痛评分、术后恶心、术后住院时间、住院费用、并发症等指标。 结果 ERAS组患者术后疼痛评分、恶心发生例数均较低,引流管拔除时间、住院时间短,住院费用减少;其他术后并发症发生例数均较少且差异无统计学意义。 结论 甲状腺癌手术患者围手术期采用ERAS理念处理可明显降低术后疼痛、恶心等不适,缩短住院时间,节省住院费用。     

仝小林教授分类、分期、分证思想在甲状腺结节及甲状腺癌的治疗中的体现

甲状腺结节是指甲状腺细胞在局部异常生长所引起的散在病变。5%～15%的甲状腺结节为恶性。结合现代医疗，仝小林教授在传承传统辨证论治模式，又开启了“分类、分期、分证”的辨证辨病思想，系统阐述甲状腺结节及甲状腺癌的类型、发展及转归等内容，并构建基于甲状腺结节及甲状腺癌分类、分期(根据自然演变过程可以分为郁、瘀、虚3期)、分证思想体系指导下的甲状腺结节及甲状腺癌防治临床实践。分类、分期、分证思想综合考量疾病共性及患者个性，可为现代慢性病中医理论构建提供启示。     

一例分化型甲状腺癌患者健康管理全科医生教学案例分析

甲状腺癌已成为北京市增长较快的恶性肿瘤。本文通过介绍1例由全科医生首诊、术后连续随访4年的分化型甲状腺癌患者的诊疗经过，采用临床案例教学方法，重点关注甲状腺结节良恶性的鉴别，全科医生接诊甲状腺结节患者的诊治流程及对甲状腺癌患者术后长期监测、健康管理的内容，引导患者规范诊治，以期为逐步实现甲状腺癌患者个体化、不同风险分层的高质量管理，提高在职全科医生、全科医学专业住院医师规范化培训的学员对甲状腺结节、分化型甲状腺癌患者的规范诊治水平，提供参考。