桥本氏甲状腺炎合并甲状腺癌的研究进展

桥本氏甲状腺炎(Hashimoto”s thyroiditis,HT)又称慢性淋巴细胞性甲状腺炎,是一种比较常见的自身免疫性疾病.甲状腺癌是较常见的恶性肿瘤,其中以乳头状癌(papillary thyroid carcinoma,PTC)最为常见.近年来桥本氏甲状腺炎合并甲状腺癌的发病率呈上升趋势.甲状腺癌通常伴随着炎症细胞的浸润,包括淋巴细胞、巨噬细胞、肥大细胞等,但这些细胞在癌症发生中的作用及发挥作用的机制并不完全清楚.然而,大部分实验表明这些细胞有促肿瘤发生的作用.此外,甲状腺乳头状癌患者表达的RET/PTC、RAS、BRAF等癌基因都可以导致甲状腺细胞发生炎症反应.这些证明炎性分子可以作为甲状腺癌治疗的潜在靶点.在本篇综述将集中在甲状腺炎和甲状腺癌的流行病学特点、二者之间的因果关系以及RET/PCT基因和癌基因蛋白信号肽等目前获得较多承认的发病机制理论进行论述.     

甲状腺乳头状癌合并桥本氏甲状腺炎的BRAF基因表达及侵袭性

目的:比较甲状腺乳头状癌合并桥本氏甲状腺炎与不合并桥本氏甲状腺炎的BRAFV600E基因表达以及侵袭性的区别。方法:2011年9月到2013年9月四川大学华西医院手术治疗并有BRAFV600E基因测定的甲状腺乳头状癌患者226名,均有病理证实。其中合并桥本氏甲状腺炎者50例为研究组,同期随机抽取50例不合并桥本氏甲状腺炎者作为对照组。比较两组性别、年龄、肿瘤大小、数量、BRAFV600E基因表达以及甲状腺外侵犯和淋巴结转移与侵袭性相关的因素的区别。结果:甲状腺乳头状癌合并桥本氏甲状腺炎在男女性别,发病年龄、肿瘤大小上和对照组相比无差异(P0.05);BRAFV600E突变率、甲状腺外侵犯和淋巴结转移都较对照组更低(P0.05)。BRAF基因突变阳性组甲状腺外侵犯和淋巴结转移率较BRAFV600E基因突变阴性组更高(P0.05)。结论:BRAFV600E基因突变的甲状腺乳头状癌患者有更高的甲状腺腺外侵犯和淋巴结转移。甲状腺乳头状癌合并桥本氏甲状腺炎较不合并桥本氏甲状腺炎有着更低的BRAFV600E突变率,更低的甲状腺外侵犯和淋巴结转移。     

血清甲状腺过氧化物酶抗体对合并桥本甲状腺炎甲状腺微小癌淋巴结转移影响

目的:探讨合并桥本甲状腺炎的甲状腺微小乳头状癌淋巴结转移的特点,分析血清甲状腺过氧化物酶抗体(Thyroid peroxidase-antibody,TPO-Ab)滴度对该组病例淋巴结转移的影响。方法:回顾性分析武汉同济医院甲状腺乳腺外科2012年1月至2014年5月收治的甲状腺微小癌伴桥本甲状腺炎的病例,运用卡方检验、阈值效应分析、多因素logistic回归方法分析该组病例血清TPO-Ab滴度对淋巴结转移的影响。结果:共收集75例合并桥本甲状腺炎的微小乳头状癌病例,血清TPO-Ab滴度与淋巴结转移相关:抗体滴度对淋巴结转移的影响存在分段特征,有阈值效应,该组病例以212 IU/m L为阈值;多因素logistic回归显示,随着血清TPO-Ab水平升高,淋巴结转移率下降(OR=0.993,95%CL=0.987,0.999,P=0.018)。结论:合并桥本甲状腺炎的甲状腺微小乳头状癌病例,血清TPO-Ab滴度对淋巴结转移的影响可能存在阈值效应,值得深入分析;且高血清TPO-Ab滴度可能是淋巴结转移的保护因素,但两者的相互关系尚需进一步探讨。     

The Epidemiology of Thyroid Cancer in Los Angeles County

More than 300 new cases of thyroid cancer are diagnosed in Los Angeles County every year. The age-adjusted annual incidence rates of this disease for all races combined are 2.4 for males and 6.1 for females. Rates for women are more than twice rates for men in each major ethnic group. Blacks of both sexes have the lowest rates; Japanese, Chinese, other Asians and Spanish-surnamed whites all have rates that are as high as or higher than rates among non-Spanish-surnamed whites. Other demographic patterns include the excess of thyroid cancer among Jewish residents of Los Angeles.There have been an increase in thyroid cancer incidence and a decline in mortality for this disease in the United States over the past several decades. Several possible explanations can be made for these trends. Also, the risk factors for thyroid cancer deserve review.     

The Effects of Chronic Lymphocytic Thyroiditis on Clinicopathologic Factors in Papillary Thyroid Cancer

ObjectiveThis study evaluated the impact of chronic lymphocytic thyroiditis (CLT) on clinicopathologic parameters, prognostic outcome, and initial treatment responses in patients with papillary thyroid cancer (PTC).MethodsA retrospective review was conducted of 1409 patients with PTC, comprising 443 patients with pathology-proven PTC with CLT and 447 patients with PTC without CLT.ResultsThe median follow-up time was 58 months (range, 8-380 months), and the median age at the time of diagnosis was 43 years. The age at diagnosis was significantly lower in patients with CLT than in those without CLT (42 years vs 45 years, respectively; P = .001). The preoperative thyroid-stimulating hormone level was found to be significantly higher in patients with CLT than in those without CLT (1.71 mIU/L vs 1.28 mIU/L, respectively; P < .001). Multifocality and capsular, lymphovascular, and perineural invasion were detected at a higher rate in the group with CLT than in the group without CLT (P = .015, P = .024, P = .004, and P = .039, respectively). No difference was found between the 2 groups in terms of tumor size, bilaterality, extrathyroidal invasion, lymph node metastasis, disease stage, or response to treatment (P > .05).ConclusionThe results of the present study demonstrated that the coexistence of PTC and CLT is very frequent. Patients with the coexistence of PTC and CLT were diagnosed at a younger age, and the thyroid-stimulating hormone level was higher in these patients. Contrary to previous studies, no positive effect of the CLT and PTC combination was detected on any clinicopathologic factor. In addition, lymphovascular and perineural invasions, which had negative effects on prognosis, were more common in the group with CLT.     

Pre-Operative Ultrasound Identification of Thyroiditis Helps Predict the Need for Thyroid Hormone Replacement After Thyroid Lobectomy

ObjectiveTo evaluate whether pre-operative thyroiditis identified by ultrasound (US) could help predict the need for thyroid hormone replacement (THR) following thyroid lobectomy.MethodsData from patients who underwent thyroid lobectomy in 2006-2011, were not taking THR pre-operatively, and had >1 month of follow-up were reviewed retrospectively. THR was prescribed for relatively elevated thyroid-stimulating hormone (TSH) and hypothyroid symptoms. The Kaplan-Meier method was used to estimate the percentage of patients who required THR at 6, 12, 18, and 24 months postoperatively, and Cox proportional hazards regression models were used to evaluate prognostic factors for requiring post-thyroid lobectomy THR.ResultsDuring follow-up, 45 of 98 patients required THR. Median follow-up among patients not requiring THR was 11.6 months (range, 1.2 to 51.3 months). Six months after thyroid lobectomy, 22% of patients were taking THR (95% confidence interval [CI], 15-32%); the proportion increased to 46% at 12 months (95% CI, 36-57%) and 55% at 18 months (95% CI, 43-67%). On univariate analysis, significant prognostic factors for postoperative THR included a pre-operative TSH level >2.5 μ international units [IU]/mL (hazard ratio [HR], 2.8; 95% CI, 1.4-5.5; P = .004) and pathology-identified thyroiditis (HR, 2.4; 95% CI, 1.3-4.3; P = .005). Patients with both pre-operative TSH >2.5 μIU/mL and US-identified thyroiditis had a 5.8fold increased risk of requiring postoperative THR (95% CI, 2.4-13.9; P<.0001).ConclusionA pre-operative TSH level >2.5 μIU/mL significantly increases the risk of requiring THR after thyroid lobectomy. Thyroiditis can add to that prediction and guide pre-operative patient counseling and surgical decision making. US-identified thyroiditis should be reported and post-thyroid lobectomy patients followed long-term (≥18 months). (Endocr Pract. 2013;19:1015-1020)     

Possible Role of the WDR3 Gene on Genome Stability in Thyroid Cancer Patients

The role of the WDR3 gene on genomic instability has been evaluated in a group of 115 differentiated thyroid cancer (DTC) patients. Genomic instability has been measured according to the response of peripheral blood lymphocytes to ionizing radiation (0.5 Gy). The response has been measured with the micronucleus (MN) test evaluating the frequency of binucleated cells with MN (BNMN), both before and after the irradiation. No differences between genotypes, for the BNMN frequencies previous the irradiation, were observed. Nevertheless significant decreases in DNA damage after irradiation were observed in individuals carrying the variant alleles for each of the three genotyped SNPs: rs3754127 [−8.85 (−15.01 to −2.70), P<0.01]; rs3765501 [−8.98 (−15.61 to −2.36), P<0.01]; rs4658973 [−8.70 (−14.94 to −2.46), P<0.01]. These values correspond to those obtained assuming a dominant model. This study shows for the first time that WDR3 can modulate genome stability.     

横县野生种子植物区系及与附近地区的比较研究

为了解广西横县野生种子植物区系特征,对横县野生种子植物进行了调查分析。结果表明,广西横县有野生种子植物1 269种,隶属于163科658属,以被子植物占优势,而裸子植物则贫乏。在科属种组成上,以大科、区域单型属和少型属为主;生活型组成反映亚热带常绿阔叶林群落特征,藤本植物种类丰富。种子植物地理成分均以热带成分为主,兼备亚热带和温带成分。与邻近地区相比较,横县种子植物区系与广东紫金县相似性较高,区系成分组成则与广东新会区、紫金县相近。因此,横县地区野生种子植物种类丰富,热带性质明显,呈热带至亚热带过渡性质,起源古老,具有一定特有现象,与广东地区联系密切。     

Therapeutic Implications of Diffuse Hepatic Uptake Following I-131 Therapy for Differentiated Thyroid Cancer

ObjectiveTo determine if diffuse hepatic uptake (DHU) of radioactive iodine (I-131) following radioactive iodine treatment has prognostic implications in otherwise scan-negative patients.MethodsThis is a retrospective review of patients treated for differentiated thyroid cancer (DTC) at Beth Israel Deaconess Medical Center between January 1990 and June 2006. This group included patients receiving therapy to ablate presumed remnant tissue, as well as treatment for persistent disease as measured by thyroglobulin or imaging. All patients included in the study had no remnant uptake and otherwise negative posttherapy scans. A total of 57 patients with 63 scans met these criteria. The scans were then scored for DHU on a scale of 0 to 5, with 0 being no uptake and 5 being intense uptake relative to background.ResultsSixteen of 63 treatments were remnant ablations. Ten of 57 patients had positive thyroglobulin antibodies. Average DHU was similar in the ablation and therapeutic groups (1.9 vs. 2.3, P = .3). There was no correlation with either I-131 dose or the presence of thyroglobulin antibodies. There was a difference for DHU in the rate of disease-free survival, (undetectable thyroglobulin and no clinical or radiographic evidence of metastasis); 50% of patients with hepatic uptake scores of 0-2 were disease-free compared to 15% with scores of 3-5 (P<.01). The average length of follow-up for disease-free patients was 4.6 years.ConclusionIn patients with DHU with otherwise negative whole-body scans following I-131 treatment, more intense hepatic uptake is associated with lower likelihood of complete response to I-131 treatment. (Endocr Pract. 2013;19:263-267)     

Assessing the Relationship Between Serum Ghrelin Levels and Metabolic Parameters and Autoimmunity in Patients with Euthyroid Hashimoto's Thyroiditis

ObjectivesHashimoto’s thyroiditis (HT) may affect metabolic parameters and increase predisposition to obesity. In this study, we aimed to assess the relationships among serum ghrelin concentrations, metabolic parameters, and thyroid autoimmunity in euthyroid HT patients.MethodsThe study included 48 euthyroid HT patients and 41 age- and sex-matched healthy controls. We assessed serum ghrelin, free triiodothyronine (T3), free thyroxine (T4), thyroid-stimulating hormone (TSH), thyroid peroxidase antibody (anti-TPO), thyroglobulin antibody (anti-Tg), fasting blood glucose (FBG), insulin, lipid levels, and homeostasis model assessment insulin resistance (HOMA-IR) in all subjects.ResultsSex distribution, mean age, and body mass index (BMI) were similar in HT patients and controls (female/male, 42/6 vs. 33/8, 46.8 ± 14.7 vs. 45 ± 12.5 years,28.5 ± 6.1 vs. 28.4 ± 4.9 kg/m², respectively; P>.05 for all). The mean waist circumference (WC) of the HT group was significantly higher than that of the control group (100.6 ± 14.6 vs. 93.2 ± 13.2 cm, P = .015). While FBG, low-density lipoprotein cholesterol (LDL-C), and triglyceride levels in the HT group were significantly higher than in the control group, insulin levels and HOMA-IR were similar. Ghrelin levels were lower in HT patients compared to controls (416.9 ± 224.4 and 689.9 ± 191.6 pg/mL, respectively; P<.001). Ghrelin levels were similar in patients with low and high anti-TPO titers. Negative correlations were observed between ghrelin levels and BMI, WC, and anti-TPO levels. Regression analysis revealed that HT was the most important predictor of ghrelin levels.ConclusionEuthyroid HT is associated with a decrease in plasma ghrelin levels. Altered body fat distribution and increased anti-TPO levels do not seem to be directly involved in lower ghrelin levels in euthyroid HT patients.     

部分国家和地区分级诊疗特点及启示

通过剖析部分国家和地区分级诊疗的特点,即分级诊疗是医疗卫生服务体系健全的自然结果,分级诊疗的实质在于服务整合,合理的支付制度是分级诊疗的重要促进因素;提出以强基层、建机制的原则发展分级诊疗,将医疗机构分工合作、服务功能整合作为分级诊疗的重要路径,增强医保对医疗服务体系的影响力以促进分级诊疗等建议。     

Things We Like: Human Preferences among Similar Organisms and Implications for Conservation

Human preferences will increasingly determine many species’ prospects for survival. However, aside from a small number of survey-based studies of preference among disparate taxa, human species preferences have received little attention. I determined human aesthetic preferences among a relatively homogenous group, the penguins, from representation in all recently published, comprehensive, popular books of photographs of penguins (n = 4 books; 304 photographs). Representation of visually distinguishable types of penguins, measured by total photograph area, was highly skewed and rankings were highly concordant across books, suggesting large and commonly held differences in aesthetic appeal. Multiple regression analysis indicated that amount of warm color was the only significant determinant of representation, and warm color was highly correlated (r ² = 0.96) with mean representation of the penguin types. Body size and neotenic form, traits found to influence human preferences among other animals, were not significant, suggesting that the bases of human species preferences differ by species type. The results of this study indicate that human aesthetic preferences discriminate finely among species and may be based on minor features. Conservationists must be vigilant to the potential for aesthetic responses to influence conservation efforts.     

Increasing Thyroid Cancer Rate and the Extent of Thyroid Surgery in Korea

Background

It is evident that the rate of thyroid cancer is increasing throughout the world. One reason is increased detection of preclinical small cancers. However, it is not clear whether the increase in thyroid cancer rate is reducing the extent of thyroid surgeries. The purpose of this study was to evaluate the thyroid cancer rate and analyze recent changes in the extent of thyroid cancer surgeries in Korea.

Methods

An observational study was conducted using data from Korea’s Health Insurance Review and Assessment Service (HIRAS) for thyroidectomy with/without neck dissection, with 228,051 registered patients between 2007 and 2011. Data were categorized by the extent of surgery: unilateral thyroidectomy without neck dissection (UT), bilateral thyroidectomy or radical thyroidectomy without neck dissection (TT), any thyroidectomy with unilateral selective neck dissection (SND), any thyroidectomy with unilateral modified radical neck dissection (MRND), any thyroidectomy with unilateral radical neck dissection (RND), and any thyroidectomy with bilateral neck dissection (BND). Annual rate difference for each surgery was analyzed with a linear by linear association.

Results

The absolute numbers of total thyroid surgeries (UT+TT+SND+MRND+RND+BND) were increased from 28539 to 61481. The proportion of patients who underwent only thyroidectomy without neck dissection (UT+TT) decreased from 67.30% to 60.50%, whereas the proportion of patients who underwent neck dissection (SND+MRND+RND+BND) increased from 32.70% to 39.50% during the 5-year study period.

Conclusion

Despite the increase in rate of thyroid cancer due to earlier detection, increased rate of neck dissection was noted.     

ABCC1 Is Related to the Protection of the Distal Nephron against Hyperosmolality and High Sodium Environment: Possible Implications for Cancer Chemotherapy

Aims

Glutathione (GSH) plays an important role in protecting cells against oxidative damage. ABCC1 protein transports GSH. Although this protein is largely studied in cancer, due to multidrug resistance phenotype, its role in the tubular cells of the kidney is unknown. The goal of this study was to find out whether ABCC1 has a role in protecting cells from the distal nephron against the stress caused by high medullar osmolality.

Main Methods

MA104 cells were treated with high concentrations of sodium chloride, urea, or both to raise the osmolality of the culture medium. Cell viability was accessed by MTT and trypan blue assays. ABCC1 expression and extrusion of carboxi-fluorescein (CF), a fluorescent ABCC1 substrate, were measured by flow cytometry.

Key Findings

Incubation of MA104 cells in a high sodium concentration medium resulted in changes in cell granularity and altered expression and activity of ABCC1. Urea did not alter ABCC1 expression or activity, but reversed the observed NaCl effects. High sodium concentrations also had a negative effect on cell viability and urea also protected cells against this effect.

Significance

Our findings demonstrate that ABCC1 plays a significant role in the protection of kidney epithelial cells against the stress caused by high sodium environment present in renal medulla.     

Thyroid Cytology and Risk of Thyroid Cancer: Differences Among Indeterminate Specimens

ObjectiveTo assess the potential for stratification of indeterminate cytologic findings on fine-needle aspiration (FNA) of thyroid nodules in an effort to improve therapeutic strategies.MethodsWe attempted to determine the malignant risk associated with various indeterminate FNA cytologic patterns by correlation of specimens with the final histologic diagnosis. For this analysis, we identified 294 computerized medical records of surgically treated thyroid nodules during a 5-year period at our institution with the corresponding FNA cytology reports available.ResultsOf the 294 surgical cases, 162 with a positive or indeterminate cytologic report were selected, reviewed, and classified. Of 52 patients with positive cytologic findings on FNA, 51 (98%) had a final histologic report of a malignant thyroid nodule. Of 110 patients with indeterminate specimens, 30 (27%) had a final histologic diagnosis of thyroid carcinoma. The presence of nuclear atypia was predictive of thyroid carcinoma in 75% of patients, a Hürthle cell cytologic pattern was associated with a malignant thyroid nodule in 33%, and a hypercellular smear was suggestive of malignant involvement in 26% of cases. The lowest rate of malignant potential was associated with cytologic microfollicular and scant colloid alone subtype (6%).ConclusionThe results of this study show that indeterminate thyroid cytologic specimens can be subdivided into groups with different malignant risks. A microfollicular cytologic pattern in the absence of a hypercellular smear or nuclear atypia does not support a recommendation of surgical treatment. A malignant cytologic diagnosis has a high positive predictive value for detection of thyroid cancer. (Endocr Pract. 2004;10:330-334)