The Effects of Hashimoto Thyroiditis on Lymph Node Metastases in Unifocal and Multifocal Papillary Thyroid Carcinoma: A Retrospective Chinese Cohort Study

The purpose of this study was to investigate the risk factors for central and lateral neck lymph node metastases in papillary thyroid carcinoma (PTC) and multifocal papillary thyroid carcinoma (MPTC), particularly when associated with Hashimoto thyroiditis (HT).A retrospective analysis of 763 consecutive patients who underwent total thyroidectomy with bilateral central neck dissection in the First Affiliated Hospital, College of Medicine, Zhejiang University between October 2011 and October 2014 was conducted. All patients had formal histological diagnoses of HT. Multivariable logistic regression analysis was performed to identify risk factors of neck lymph node metastases.Our study identified 277 PTC patients with HT and showed comparatively low rates of central lymph node metastases (CLNM) compared with the PTC patients without HT (37.2% versus 54.7%, P < 0.001). There were no statistically significant differences in lateral lymph node metastases (LLNM) (P = 0.656). Neck lymph node metastases were histologically proven in 127 (45.8%) patients with PTC with HT, including 103 CLNM and 24 LLNM. There were no significant differences in LLNM between the MPTC-associated HT and classic MPTC cases; however, a significantly reduced risk of CLNM was observed in the MPTC-associated HT compared with the MPTC cases (35.7% versus 72.4%, respectively, P < 0.001). In the multivariate analysis, HT was identified as an independent alleviating factor for CLNM in all PTC patients (odds ratio, 0.369; 95% confidence interval (CI), 0.261 to 0.521; P < 0.001) and in MPTC patients (odds ratio, 0.227; 95% CI, 0.126–0.406; P < 0.001). A cut-off of thyroid peroxidase antibody >140 IU/mL was established as the most sensitive and specific level for the prediction of MPTC based on receiver operating characteristic curve analyses. Thyroid peroxidase antibody, age, tumor size, and multifocality exhibited the ability to predict CLNM in PTC with HT patients with an area under the curve of 81.1% based on a multivariate model.Hashimoto thyroiditis was associated with increased prevalences of multifocality and capsular invasion. In contrast, HT was associated with a reduced risk of CLNM in PTC and MPTC patients, which indicated a potential protective effect. We found that the prognostic prediction model was applicable for predicting multifocality and CLNM in PTC patients with HT.     

Coexistence of Papillary Thyroid Carcinoma With Thyroid MALT Lymphoma in a Patient With Hashimoto's Thyroiditis: A Clinical Case Report

Papillary thyroid carcinoma (PTC) is the most common type of thyroid neoplasias; however, primary thyroid gland lymphoma (PTL) is uncommon and their simultaneous occurrence is very rare.Herein, we reported a 25-year-old female patient with Hashimoto''s thyroiditis (HT), who developed a small goiter with a palpable 1.2-cm nodule in the right lobe. A fine-needle aspiration (FNA) biopsy revealed atypical follicular epithelial cells and lymphoid cells in a background of lymphocytic thyroiditis. A total thyroidectomy was performed. The pathology showed multicentric papillary thyroid carcinoma, concomitant thyroid mucosa-associated lymphoid tissue (MALT) lymphoma, and Hashimoto''s thyroiditis. Postoperatively, he received chemotherapy and radioactive iodine ablation treatment. Nowadays the thyroglobulin of the patient is undetectable, without recurrences at 2 years of follow-up.It is concluded that the PTC and MALT lymphoma can exist concomitantly, especially in patients with HT. For the diagnostic workup and optional management of this rare coexistence, a multidisciplinary approach and close surveillance are needed.     

Association Between Genetic Polymorphisms in the Promoter Regions of Let-7 and Risk of Papillary Thyroid Carcinoma: A Case-Control Study

The aim of this study was to investigate the association between 2 polymorphisms (ie, rs10877887 and rs13293512) in the promoter regions of let-7 and the risk of papillary thyroid carcinoma (PTC).A case-control study of 618 PTC patients and 562 controls was conducted. The rs10877887 polymorphism was genotyped by using polymerase chain reaction-restriction fragment length polymorphism and the rs13293512 polymorphism was genotyped by using a TaqMan Genotyping Assay. The results were confirmed by DNA sequencing.The rs10877887 polymorphism had reduced risks of PTC in heterozygous comparison, dominant model, and overdominant model (TC vs TT: adjusted odds ratio [OR] = 0.73, 95% confidence interval [95% CI] = 0.58–0.94, P = 0.01; TC/CC vs TT: adjusted OR = 0.79, 95% CI = 0.63–1.00, P = 0.047; TC vs TT/CC: adjusted OR = 0.73, 95% CI = 0.57–0.92, P = 0.007, respectively). Stratified analyses showed that PTC patients carrying the rs10877887 CC genotype were more likely to have multiple tumors (adjusted OR = 1.71, 95% CI = 1.03–2.86, P = 0.04), and PTC patients carrying the rs13293512 TC + CC or CC were more likely to develop N0 status (TC/CC vs TT: adjusted OR = 0.64, 95% CI = 0.43–0.94, P = 0.02; CC vs TC/TT: adjusted OR = 0.50, 95% CI = 0.33–0.77, P = 0.001, respectively).Our study suggests that the rs10877887 polymorphism may be associated with the risk of PTC and the rs13293512 polymorphism may correlate to lymph node metastasis in PTC.     

Expression Profiles and Clinical Significance of MicroRNAs in Papillary Renal Cell Carcinoma: A STROBE-Compliant Observational Study

Papillary renal cell carcinoma (pRCC) is the second most prevalent subtype of kidney cancers. In the current study, we analyzed the global microRNA (miRNA) expression profiles in pRCC, with the aim to evaluate the relationship of miRNA expression with the progression and prognosis of pRCC.A total of 163 treatment-naïve primary pRCC patients were identified from the Cancer Genome Atlas dataset and included in this retrospective observational study. The miRNA expression profiles were graded by tumor-node-metastasis information, and compared between histologic subtypes. Furthermore, the training-validation approach was applied to identify miRNAs of prognostic values, with the aid of Kaplan–Meier survival, and univariate and multivariate Cox regression analyses. Finally, the online DAVID (Database for Annotation, Visualization, and Integrated Discover) program was applied for the pathway enrichment analysis with the target genes of prognosis-associated miRNAs, which were predicted by 3 computational algorithms (PicTar, TargetScan, and Miranda).In the progression-related miRNA profiles, 26 miRNAs were selected for pathologic stage, 28 for pathologic T, 16 for lymph node status, 3 for metastasis status, and 32 for histologic types, respectively. In the training stage, the expression levels of 12 miRNAs (mir-134, mir-379, mir-127, mir-452, mir-199a, mir-200c, mir-141, mir-3074, mir-1468, mir-181c, mir-1180, and mir-34a) were significantly associated with patient survival, whereas mir-200c, mir-127, mir-34a, and mir-181c were identified by multivariate Cox regression analyses as potential independent prognostic factors in pRCC. Subsequently, mir-200c, mir-127, and mir-34a were confirmed to be significantly correlated with patient survival in the validation stage. Finally, target gene prediction analysis identified a total of 113 target genes for mir-200c, 37 for mir-127, and 180 for mir-34a, which further generated 15 molecular pathways.Our results identified the specific miRNAs associated with the progression and aggressiveness of pRCC, and 3 miRNAs (mir-200c, mir-127, and mir-34a) as promising prognostic factors of pRCC.     

Characterization of Papillary Thyroid Microcarcinomas Using Sonographic Features in Malignant Papillary Thyroid Cancer: A Retrospective Analysis

The diagnosis of malignant thyroid nodules is still a clinical challenge. This study aimed to determine the ultrasonographic characteristics of papillary thyroid carcinoma.The ultrasonographic and pathological data of 2453 thyroid nodules in a cohort of 1895 Chinese patients who underwent thyroidectomy from January 2010 to December 2012 were retrospectively reviewed.Anteroposterior and transversal (AP/TR) diameters ≥1, solid structure, infiltrative margins, hypoechoic appearance, and microcalcifications were more common in malignant nodules than in benign nodules (P < 0.01). These ultrasonographic features were independent risk factors of malignancy (P < 0.01) as determined by logistic regression analysis. Based on multivariate analysis, these characteristics were also present in large nodules (diameter >10 mm). However, in small nodules (diameter ≤10 mm), only AP/TR ≥1 and infiltrative margins were independent risk factors of malignancy (P < 0.01).Ultrasonography is of high diagnostic value for malignant thyroid nodules and may help to improve the differential diagnosis. Small and large nodules have distinct ultrasonographic features.     

Risk of Depression,Chronic Morbidities,and l-Thyroxine Treatment in Hashimoto Thyroiditis in Taiwan: A Nationwide Cohort Study

The aim of this study was to evaluate the risk of depression in and effect of l-thyroxine therapy on patients with Hashimoto thyroiditis (HT) in Taiwan.In this retrospective, nationwide cohort study, we retrieved data from the Longitudinal Health Insurance Database 2000. We collected data of 1220 patients with HT and 4880 patients without HT for the period 2000 to 2011. The mean follow-up period for the HT cohort was 5.77 years. Univariate and multivariate Cox proportional hazards regression models were used to estimate the risk of depression in the HT cohort.In the HT cohort, 89.6% of the patients were women. Compared with the non-HT cohort, the HT cohort exhibited a higher prevalence of diabetes mellitus, hyperlipidemia, and coronary artery disease. Furthermore, the HT cohort showed a higher overall incidence of depression compared with the non-HT cohort (8.67 and 5.49 per 1000 person-year; crude hazard ratio [HR] = 1.58, 95% confidence interval [CI] = 1.18–2.13). The risk of depression decreased after administration of l-thyroxine treatment for more than 1 year (adjusted HR = 1.02; 95% CI = 0.66–1.59).In Taiwan, the overall incidence of depression was greater in the young HT cohort. l-thyroxine treatment reduced the risk of depression.     

99Tc-生长抑素受体显像发现甲状腺乳头状癌1例报道并文献复习

目的:评价生长抑素受体显像在发现甲状腺乳头状癌中的作用。方法:本文报道1例以胰岛素瘤来就诊的女性患者,在诊治过程中,对患者行全身生长抑素受体核素显像。并行131I-甲状腺显像示甲状腺右叶冷结节。结果:全身生长抑素受体核素显像发现甲状腺右叶占位。经甲状腺手术,病理证实为甲状腺乳头状癌。结论:生长抑素受体显像可能对发现甲状腺乳头状癌有一定帮助。     

干燥综合征合并桥本甲状腺炎的临床特点及相关因素分析

目的 分析干燥综合征（SS）合并桥本甲状腺炎（HT）患者的临床表现、特点以及相关因素。方法 回顾性分析32例SS合并HT住院患者和24例随机抽样的SS对照组患者的资料。结果 合并HT的SS患者眼干、甲状腺增大及浆膜腔积液的发病率显著高于SS对照组。与SS对照组相比，SS合并HT患者血清甘油三酯水平显著增高．血清IgA及α1球蛋白比例显著降低。所有SS患者的血清C反应蛋白（CRP）与血清三碘甲状腺原氨酸（T3）、甲状腺素（T4）、游离甲状腺素（FT4）水平呈显著负相关，与促甲状腺激素（TSH）、抗甲状腺球蛋白抗体（ATG）呈显著正相关；血清胆固醇水平与血清游离三碘甲状腺原氨酸（FIB）、FT4水平呈显著负相关，血糖水平与血清TSH、ATG水平呈显著负相关；血清IgG水平与血清T4、FT3水平呈显著正相关，血清C4水平与血清TSH、ATG及抗甲状腺髓过氧化酶抗体（ATM）水平呈显著负相关；血清α2球蛋白比例与血清T4呈显著正相关；血清γ球蛋白比例与血清ATG水平呈显著正相关。结论 SS患者易合并HT，当SS患者临床出现眼干明显、甲状腺增大、浆膜腔积液，CRP、甘油三酯、胆固醇及γ球蛋白升高，血糖、IgA、IgG、C4、cd及以球蛋白水平下降时，需警惕合并HT。     

大肠癌的特殊染色研究

本文以HID／AB（pH2.5)染色，PAT，KOH／PAS染色和CEA染色方法研究了73例大肠组织，其中慢性结肠溃疡14例，肠息肉25例，肠癌17例和正常肠粘膜17例。结果在HID／AB(pH2.5)染色，PAT／KOH／PASivs qc t CEA染色中，肠癌分别表现蓝色，紫色和深棕色，正常肠粘膜分别表现黑色，红色和无棕色，肠息肉特别是伴不典型增生者染色倾向于癌肿，慢性结肠溃疡染色虽异于正常肠粘膜，但与癌肿不同。本文认为三种染色有两种以上阳性者应考虑恶变。     

Clinical Diagnostic Implications of Body Fluid MiRNA in Oral Squamous Cell Carcinoma: A Meta-Analysis

Oral cancer, predominantly oral squamous cell carcinoma (OSCC), is one of the most leading causes of cancers worldwide. Due to a low 5-year survival rate, highly effective methods for the early detection of OSCC are totally needed. MicroRNAs (miRNAs), as promising biomarkers, can bring insights into tumorigenesis of oral cancers. However, studies on the accuracy of miRNAs detection in OSCC have inconsistent conclusions, leading us to conduct this meta-analysis. The aim of this study was to systematically review the articles investigating the diagnostic value of miRNAs in OSCC.The PubMed, Embase, Chinese National Knowledge Infrastructure (CNKI), Web of Science were searched (updated to June 11th, 2015) to identify all articles evaluating the diagnostic yield of miRNAs for OSCC. The pooled sensitivity, specificity, and other diagnostic parameters were used to assess the performance of miRNAs assays on OSCC detection. Statistical analysis was conducted by employing the R software.The present meta-analysis comprised 23 studies from 10 articles, including 598 OSCC patients and 320 healthy individuals, available for analysis. The summary receiver operator characteristic (SROC) curve was plotted. Meanwhile, the pooled diagnostic parameters and the area under curve (AUC) were calculated based on all included studies. The pooled diagnostic parameters calculated from all 23 studies were as follows: pooled sensitivity of 0.759 (95% CI: 0.701–0.809), pooled specificity of 0.773 (95% CI: 0.713–0.823) and AUC of 0.832, which indicates a relatively high diagnostic accuracy of miRNAs in differentiating OSCC patients from healthy controls. Meanwhile, In addition, subgroup analyses were conducted to access the heterogeneity between studies, which is based on specimen (serum/plasma/blood/saliva/ tissue) and ethnicity (Asian/Caucasian).In summary, our meta-analysis suggests that miRNAs might be used in noninvasive screening tests for OSCC, which needs further large-scale studies to be validated.     

食管鳞状细胞癌中转移相关lncRNAs的生物学和临床相关性

食管鳞状细胞癌是世界上最常见的癌症之一,转移快、预后差、死亡人数多。其中主要的死亡原因之一是转移。转移是由一系列细胞信号通路多方面共同作用的过程。长非编码RNA(lncRNAs)作为转录调控因子,可以调控多种基因组过程和细胞过程,如细胞增殖、迁移和侵袭等。lncRNAs也被证明参与/调节与肿瘤转移相关的信号通路。因此,它们在分子肿瘤学研究中越来越受关注。许多研究人员试图揭示lncRNAs在食管癌发生和转移中的生物学和临床相关性,包括诊断、预后和治疗反应。本文就lncRNAs在食管癌转移中的生物学作用以及转移相关的lncRNAs在肿瘤诊断和预后中的临床意义作一综述。     

Annual Average Changes in Adult Obesity as a Risk Factor for Papillary Thyroid Cancer: A Large-Scale Case-Control Study

We evaluated the association between weight change in middle-aged adults and papillary thyroid cancer (PTC) based on a large-scale case-control study.Our study included data from 1551 PTC patients (19.3% men and 80.7% women) who underwent thyroidectomy at the 3 general hospitals in Korea and 15,510 individually matched control subjects. The subjects’ weight history, epidemiologic information, and tumor characteristics confirmed after thyroidectomy were analyzed. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were determined for the annual average changes in weight and obesity indicators (body mass index (BMI), body surface area, and body fat percentage (BF%) in subjects since the age of 35 years.Subjects with a total weight gain ≥10 kg after age 35 years were more likely to have PTC (men, OR, 5.39, 95% CI, 3.88–7.49; women, OR, 3.36, 95% CI, 2.87–3.93) compared with subjects with a stable weight (loss or gain <5 kg). A marked increase in BMI since age 35 years (annual average change of BMI ≥0.3 kg/m²/yr) was related to an elevated PTC risk, and the association was more pronounced for large-sized PTC risks (<1 cm, OR, 2.34, 95% CI, 1.92–2.85; ≥1 cm, OR, 4.00, 95% CI, 2.91–5.49, P heterogeneity = 0.005) compared with low PTC risks.Weight gain and annual increases in obesity indicators in middle-aged adults may increase the risk of developing PTC.     

Long-term Follow-up of a Toddler with Papillary Thyroid Carcinoma: A Case Report with a Literature Review of Patients Under 5 Years of Age

Papillary thyroid cancer (PTC) is extremely rare in children. Herein, we present a case diagnosed with PTC at 15 months of age. We conducted a literature review of the published cases with PTC under five years of age. A 1.25-year-old male patient had initially presented with a complaint of progressively enlarging cervical mass that appeared four months earlier. On physical examination, a mass located in the anterior cervical region with the largest measurements of around 3x3 cm was detected. Cervical and thyroid ultrasonography showed a 50x27 mm solid mass in the right lateral neck. Excisional biopsy revealed a follicular variant of PTC with capsular invasion. Subsequently, he underwent a complementary total thyroidectomy. He was diagnosed with intermediate-risk (T3N0M0) PTC. He developed permanent hypoparathyroidism. In the first year of the operation, he was treated with radioiodine ablation (RAI) since basal and stimulated thyroglobulin (Tg) levels tended to increase. Whole-body scintigraphy was normal in the first year of RAI ablation. On levothyroxine sodium (LT4) treatment, levels of thyroid stimulating hormone (TSH) and Tg were adequately suppressed. He is now 8.5-years-old and disease-free on LT4 replacement therapy for seven years and three months. Pediatric PTC has different biological behavior and an excellent prognosis compared to adults. The optimal treatment strategy for pediatric TC is total thyroidectomy, followed by RAI ablation. Post-operative management should include regular follow-up, TSH suppression by adequate LT4 therapy, serial Tg evaluation, and radioiodine scanning when indicated.     

ⅠⅡ相代谢酶基因多态性与食管癌遗传易感性的病例对照研究

目的研究细胞色素P450（CYP）1A1和谷胱甘肽转硫酶M1（GSTM1）和T1（CSlTrl）基因多态性与食管癌易感性的关系。方法应用PCR—RFLP技术对87例食管癌患者和162例无上消化道肿瘤的健康者的CYP1A1、GSTMl和GSlTrl的基因多态性进行分析。比较两组基因型频率的差异。结果食管癌组CYPlAlIle—Val多态位点各等位基因和基因频率与对照组比较，差别有统计学意义，其中Val／Val基因型在食管癌组的频率（29．9％）显著高于对照组（13．0％）（X^2=10．54，P〈0．01），OR值为3．10，95％CI为（1.57，6．14），而CYPlAl的Ⅱe／Val、Ⅱe／Ⅱe多态位点和GSTMl与GSTTl的缺失多态性的基因型频率与对照组比较，差别无统计学意义（P〉0．05）。结论CYPlAlVal／Val基因型为食管癌的重要易感因素之一，而GSTMl与GSTTl的基因型可能与食管癌的发生无关。