甲状腺癌CT、B超诊断与病理诊断对照分析研究

目的探讨CT、B超检查对甲状腺癌的诊断意义。方法回顾性分析286例甲状腺癌的螺旋CT、彩色B超的影像学资料,与病理诊断作对照分析。结果对于病灶直径≤1.0 cm的82例甲状腺微小癌B超诊断符合率为76.8%（63/82）,CT的诊断符合率为31.7%（26/82）,两者比较差异有统计学意义（P〈0.005）,而对于病灶直径≥1.0 cm的204例甲状腺癌B超诊断符合率为79.4%（162/204）,CT的诊断符合率为84.8%（173/204）,两者比较差异无统计学意义（P〉0.05）。结论彩色B超是目前诊断甲状腺微小癌最有效的检查方法 ,对于病灶≥1.0 cm的甲状腺癌,B超和CT检查均是阳性诊断率高的检查方法 。     

环氧化酶和基质金属蛋白酶在甲状腺乳头状癌组织中的增强表达及意义

目的 :研究甲状腺乳头状癌 (PTC)中环氧化酶 -2 (COX 2 )和基质金属蛋白酶-2 (MMP 2 )的表达情况及相互关系。方法 :采用免疫组化 (SP法 )检测 67例PTC组织、15例甲状腺腺瘤组织和 2 0例癌旁组织中COX 2和MMP 2的表达 ,以胞质出现棕黄色颗粒为阳性。结果 :67例PTC组织COX 2和MMP 2的阳性表达率为 82 1%( 5 5 /67)和 74 6% ( 5 0 /67) ,均高于甲状腺腺瘤组织和癌旁正常滤泡组织 ,P <0 0 1。COX 2和MMP 2阳性表达与淋巴结转移和肿瘤侵袭程度呈正相关 ,P <0 0 5。COX 2阳性表达强度与MMP 2的阳性表达强度之间呈明显正相关 ,P <0 0 1。结论 :COX 2和MMP 2在PTC组织中的表达密切相关 ,两者协同作用可促进PTC的恶性发展 ,二者可作为PTC恶性化的分子标志。     

二维超声及彩色多普勒血流显像在甲状腺疾病诊断中的价值

目的 :探讨二维超声与彩色多普勒血流显像 (CDFI)对甲状腺疾病的诊断价值。方法 :分析了15 6例甲状腺疾病的二维超声及CDFI表现和结果并与病理对照。结果 :甲状腺癌的诊断符合率 86 % ,甲状腺腺瘤的诊断符合率 92 % ,结节性甲状腺肿的诊断符合率 93% ,毒性甲状腺肿的诊断符合率10 0 % ,桥本氏甲状腺炎诊断符合率 10 0 %。结论 :病变的边界、形态、内部回声类型、后方回声特征及血流特点对甲状腺病变的病理诊断有重要意义     

Human thyroid tumours, the puzzling lessons from E7 and RET/PTC3 transgenic mice

Human rearranged RET/PTC3 (papillary thyroid carcinoma) proto-oncogene and high-risk human papillomavirus (HPV) type 16 E7 oncogene induces in the mouse a neoplastic transformation of thyroid follicular cells. We present a detailed immuno-histological study (170 mouse thyroids: RET/PTC3, E7, wild type, 2- to 10-month-old) with cell cycle proliferation and signalling pathway indicators. The characteristics of both models are different. There is an 'oncogene dependent' cellular signature, maintained at all studied ages in the E7 model, less in the RET/PTC3 model. During tumour development a large heterogeneity occurred in the Tg-RET/PTC3 model within a same tumour or within a same thyroid lobe. The Tg-E7 model was less heterogeneous, with a dominant goitrous pattern. The solid tumour already described in the RET/PTC3 models associated with cribriform patterns, suggested 'PTC spindle cell changes' as in humans PTC rather than the equivalent of the solid human PTC. Proliferation and apoptosis in the two thyroid models are related to the causal oncogene rather than reflect a general tumorigenic process. The thyroids of RET/PTC3 mice appeared as a partial and transient model of human PTCs, whereas the Tg-E7 mice do not belong to the usual PTC type.     

恶性潜能未定的高分化甲状腺肿瘤中CK19、Galectin-3、HBME-1和TPO的表达及意义

目的 探讨细胞角蛋白19(cytokeratin 19,CK19)、Galectin-3、Hector Battifora mesothelial cell-1(HBME-1)和甲状腺过氧化物酶(thyroid peroxidase,TPO)在恶性潜能未定的高分化甲状腺肿瘤(well-differentiated thyroid tumors of uncertain malignant potential,WDT-UMP)中的表达及意义.方法 用免疫组织化学法检测38例WDT-UMP、80例甲状腺乳头状癌(papillary thyroid carcinoma,PTC)和40例良性甲状腺病变周围正常组织(对照组)中CK19、Galectin-3、HBME-1和TPO的表达情况.结果 WDT-UMP中CK19、Galectin-3、HBME-1和TPO的阳性率分别为55.2%、68.4%、60.5%和86.8%;CK19、Galectin-3和HBME-1以弱阳性或阴性为主,TPO呈弱阳性至强阳性表达.PTC中CK19、Galectin-3、HBME-1和TPO的阳性率分别为100.0%、95.0%、97.5%和7.5%;CK19、Galectin-3和HBME-1以弥漫强阳性表达为主,TPO以阴性表达为主.对照组中CK19、Galectin-3、HBME-1和TPO的阳性率分别为10.0%、7.5%、5.0%和97.5%;CK19、Galectin-3和HBME-1基本不表达或弱阳性表达,TPO以强阳性表达为主.CK19、Galectin-3和HBME-1在PTC中的表达均高于WDT-UMP(均P<0.01).CK19、Galectin-3和HBME-1在PTC和WDT-UMP中的表达均高于对照组(均P<0.01).TPO在PTC中的表达低于WDT-UMP和对照组(均P<0.01).联合应用CK19、Galectin-3、HBME-1和TPO鉴别PTC与WDT-UMP时,可获得较高的敏感度、特异度和诊断准确率,分别为96.2%、50.6%和81.6%.结论 CK19、Galectin-3、HBME-1和TPO可作为鉴别WDT-UMP、PTC和甲状腺良性病变的潜在标志物.     

HTg测定和 131I全身显像检查对甲状腺癌131I治疗后随访的临床意义

目的 :评价血清HTg和 13 1I全身显像联合检查对分化型甲状腺癌 (differentiat edthyvoidcarcinoma ,DTC)患者 13 1I治疗后随访的临床意义。方法 :85例DTC患者停服甲状腺激素 4～ 6周并忌碘饮食 3 0d后 ,双抗体法测定血清HTg ,同时口服 13 1I 185～3 70MBq 2 4h后 ,和 (或 )口服治疗剂量 13 1I 4～ 7d后做全身显像。结果 :61例经临床证实有复发或转移的DTC患者中 ,3 8例(62 3 0 % )HTg高于正常 ,有肺或 (和 )骨转移者 ,血清HTg升高更加明显 ,极端甚至 >2 0 0 μg/L。2 2例肺转移及肺 (骨 )转移患者 ,其血清HTg水平随 13 1I治疗剂量的增加而呈降低趋势。 5 3例 (86 88% ) 13 1I全身显像结果和 (或 )血清HTg有阳性表现 ,只有49 18% (3 0 /61)的患者同时出现 13 1I全身显像有异常浓聚和血清HTg异常升高。 结论 :DTC术后及 13 1I治疗后 ,常规进行血清HTg测定和 13 1I全身显像检查 ,对早期发现复发或有无转移灶、13 1I治疗方案的选择以及评估 13 1I疗效具有重要的临床价值。     

PET/CT在甲状腺癌中的应用

目的:探讨正电子发射型计算机断层成像(PET/CT)在甲状腺癌原发灶、转移灶的诊断,复发检测中的应用价值。方法:回顾性分析应用PET/CT检查的40例甲状腺癌患者的临床资料,将其显像结果与病理,部分与Bus、CT比较。结果:PET/CT显像结果与病理结果符合率极高,对原发灶的诊断灵敏度100%,特异度87.5%,对转移灶的诊断灵敏度92.1%,特异度92.0%,优于CT和彩超。结论:PET/CT对甲状腺癌原发灶、转移灶的诊断,临床分期,甲状腺癌术后观测疗效、监测复发具有明显的优势。     

RET/PTC and PAX8/PPARγ chromosomal rearrangements in post‐Chernobyl thyroid cancer and their association with iodine‐131 radiation dose and other characteristics

BACKGROUND:

Childhood exposure to iodine‐131 from the 1986 nuclear accident in Chernobyl, Ukraine, led to a sharp increase in papillary thyroid carcinoma (PTC) incidence in regions surrounding the reactor. Data concerning the association between genetic mutations in PTCs and individual radiation doses are limited.

METHODS:

Mutational analysis was performed on 62 PTCs diagnosed in a Ukrainian cohort of patients who were < 18 years old in 1986 and received 0.008 to 8.6 Gy of ¹³¹I to the thyroid. Associations between mutation types and ¹³¹I dose and other characteristics were explored.

RESULTS:

RET/PTC (ret proto‐oncogene/papillary thyroid carcinoma) rearrangements were most common (35%), followed by BRAF (15%) and RAS (8%) point mutations. Two tumors carrying PAX8/PPARγ (paired box 8/peroxisome proliferator‐activated receptor gamma) rearrangement were identified. A significant negative association with ¹³¹I dose for BRAF and RAS point mutations and a significant concave association with ¹³¹I dose, with an inflection point at 1.6 Gy and odds ratio of 2.1, based on a linear‐quadratic model for RET/PTC and PAX8/PPARγ rearrangements were found. The trends with dose were significantly different between tumors with point mutations and rearrangements. Compared with point mutations, rearrangements were associated with residence in the relatively iodine‐deficient Zhytomyr region, younger age at exposure or surgery, and male sex.

CONCLUSIONS:

These results provide the first demonstration of PAX8/PPARγ rearrangements in post‐Chernobyl tumors and show different associations for point mutations and chromosomal rearrangements with ¹³¹I dose and other factors. These data support the relationship between chromosomal rearrangements, but not point mutations, and ¹³¹I exposure and point to a possible role of iodine deficiency in generation of RET/PTC rearrangements in these patients. Cancer 2013. © 2013 American Cancer Society.     

Association of PTEN gene methylation with genetic alterations in the phosphatidylinositol 3-kinase/AKT signaling pathway in thyroid tumors

BACKGROUND: The phosphatidylinositol 3-kinase (PI3K)/AKT pathway plays an important role in thyroid tumorigenesis and progression. Genetic alterations, particularly PIK3CA amplification and mutations and ras mutations, are the major cause of aberrant activation of this pathway in thyroid tumors. Epigenetic silencing of the PTEN gene, a negative regulator of the PI3K/AKT pathway, also occurs in thyroid tumors, but its relationship with genetic alterations in this pathway is unclear. METHODS: By using quantitative methylation-specific polymerase chain reaction, the authors examined PTEN methylation and its relationship with genetic alterations in the PI3K/AKT pathway in various types of thyroid tumors. RESULTS: The authors found PTEN methylation to become progressively higher from benign thyroid adenoma to follicular thyroid cancer and to aggressive anaplastic thyroid cancer, which harbored activating genetic alterations in the PI3K/AKT pathway correspondingly with a progressively higher prevalence. The association of PTEN methylation was seen with both overall genetic alterations and individual genetic alterations, particularly PIK3CA alterations and ras mutations, in the PI3K/AKT pathway within each of the 3 types of thyroid tumors. In contrast, no such relationship was observed for the tumor suppressor gene RASSF1A. CONCLUSIONS: The authors found an interesting association of PTEN methylation with the activating genetic alterations in the PI3K/AKT pathway in thyroid tumors. This finding is consistent with a model in which aberrant methylation and hence silencing of the PTEN gene, which coexists with activating genetic alterations of the PI3K/AKT pathway, may enhance the signaling of this pathway aberrantly activated by genetic alterations and hence contribute to the progression of thyroid tumors. Cancer 2008.     

螺旋CT对甲状腺单发结节良恶性鉴别的价值

目的探讨甲状腺单发良、恶性结节的CT表现。方法通过经病理证实的47例甲状腺单发良性结节和21例恶性结节CT影像对比,分析两者间的CT表现差别。结果47例单发良性结节中39例病变边界清晰、8例病灶边界欠清、26例囊变、10例钙化;21例恶性结节有17例病变边界不清、4例病灶边界较清、8例囊变、9例钙化、6例表现强化残圈征、9例肿瘤侵犯周围组织器官和7例颈部淋巴结转移。结论螺旋CT对甲状腺结节的良、恶性鉴别有重要意义。     

Rg3对甲状腺癌血管生成抑制作用的临床观察

为了探讨人参皂甙Rg3对人甲状腺癌血管生成的抑制作用 ,对 18例甲状腺癌患者在术前 2周口服Rg3 ,观察手术切除癌内微血管密度 (microvesseldexsity ,MVD)的变化。结果实验组血管减少明显 ,高倍镜下可见血管内皮细胞支架塌陷、变性、坏死 ;而对照组血管无明显改变。实验组MVD值计数 10 8 69± 2 5 2 4,对照组MVD计数 160 5 2±47 45 ,两组比较差异有统计学意义 ,P <0 0 0 1。初步研究结果提示 ,Rg3具有抑制甲状腺癌血管生成的作用 ,可有效抑制其生长和转移。     

Expression of matrix metalloproteinase-2, but not caspase-3, facilitates distinction between benign and malignant thyroid follicular neoplasms

Purpose: Definite diagnosis of follicular thyroid carcinoma (FTC) is based on the presence of capsularor vascular invasion. To date, no reliable and practical method has been introduced to discriminate thismalignant neoplasm from follicular thyroid adenoma (FTA) in fine needle aspiration biopsy material. Matrixmetalloproteinase-2 (MMP-2), by degrading extracellular matrix, and caspase-3, by induction of apoptosis, havebeen shown to play important roles in carcinogenesis and aggressive behavior in many tumor types. The aim of thisstudy was to examine expression of MMP-2 and caspase-3 in thyroid follicular neoplasms and to determine theirusefulness for differential diagnosis. Method: Sixty FTAs and 41 FTCs were analysed immunohistochemicallyfor MMP-2 and caspase-3. Result: MMP-2 was positive in 4 FTCs (9.8%), but in none of FTAs, with statisticalsignificance (p= 0.025). Caspase-3 was positive in 30 (50%) of FTAs and in 27 (65.9%) of FTCs. Conclusion: Ourresults show MMP-2 expression only in FTCs and suggest that this protein may be a useful marker to confirmdiagnosis of FTC versus FTA with 100% specificity and 100% predictive value of a positive test. We failed toshow any differential diagnostic value for caspase-3 in thyroid follicular neoplasms.     

Naftifme Solution (1%) in the Treatment of Pityriasis versicolor in Zambia/Naftifin 1%ige Lösung in der Behandlung von Pityriasis versicolor in Zambia

Summary: Pityriasis versicolor is a common skin disease among Zambians and of the patients seen at the skin clinic at University Teaching Hospital, Lusaka, during the past 3 years, 7.4% were there primarily because of this superficial fungal infection.
In an open clinical trial, 1% naftifme solution was given in two regimens: 3-day or 6-day therapy. Forty patients received the first regimen and of 30 who were followed for 6 weeks, 9 (30.0%) had a mycological cure. The 6-day regimen was given to 79 patients and of 62 who were followed for 6 weeks, clinical cure was seen in 56 (903%) and mycological cure in 51 (82.3%) with residual hypopigmentation in 55% of patients.
In view of the high prevalence of the disease and good results obtained with 1% naftifine (Exo-deril®) solution, the 6-day regimen is recommended for treatment.
Zusammenfassung: Pityriasis versicolor ist eine häufig vorkommende Hauterkrankung in Zambia. 7.4% der Patienten, die in den letzten drei Jahren an der Universitätshautklinik Lusaka, Zambia, behandelt wurden, leiden an dieser oberflächlichen Pilzinfektion. In einer offenen klinischen Studie erprobten wir eine 1%ige Naftifin Lösung in 3tägiger oder 6tägiger Therapie. 40 Patienten erhielten die 3tägige Therapie, davon wurden 30 Patienten 6 Wochen klinisch überwacht. 9 (30%) hatten eine mykologische Heilung. Dem 6tägigen Therapieschema waren 79 Patienten zugeordnet und 62 wurden durch 6 Wochen beobachtet. Die klinische Heilung lag bei 90,3% (56 Patienten), die mykologische Heilung bei 823% (51 Patienten). 55% der Patienten hatten eine anhaltende Hypopigmentation. In Anbetracht der guten Wirksamkeit gegen Pityriasis versicolor und der erhaltenen guten Resultate mit 1% iger Naftifin-Lösung (Exoderil®) kön-nen wir das 6-tägige Therapieschema gegen Pityriasis versicolor empfehlen.     

甲状腺癌中MCM7和p27的表达及临床意义

目的探讨MCM7和p27蛋白的表达与甲状腺癌发生、发展的关系。方法采用免疫组织化学S-P法检测50例甲状腺癌、30例甲状腺腺瘤、30例结节性甲状腺肿及20例正常甲状腺组织中MCM7和p27蛋白的表达。结果甲状腺癌组织中MCM7蛋白的阳性表达率为100.0%（50/50）,均显著高于甲状腺腺瘤20.0%（6/30）、结节性甲状腺肿23.3%（7/30）及正常甲状腺组织20.0%（4/20）（P〈0.01,P〈0.01,P〈0.01）。甲状腺癌组织中p27蛋白的阳性表达率为22.0%（11/50）,均显著低于甲状腺腺瘤100.0%（30/30）、结节性甲状腺肿100.0%（30/30）及正常甲状腺组织100.0%（20/20）（P〈0.01,P〈0.01,P〈0.01）。甲状腺癌中MCM7与p27蛋白的表达呈负相关关系（r=-0.326,P〈0.05）。结论 MCM7蛋白的高表达和p27蛋白的低表达可能涉及了甲状腺癌的发生过程。二者联合检测,可能可作为临床早期诊断和判断甲状腺肿瘤细胞增殖活性的生物学指标。     

结节性甲状腺肿与甲状腺癌并存的诊断与治疗(附68例临床报告)

目的　探讨结节性甲状腺肿与甲状腺癌并存的临床特点和诊治原则 ,进一步提高对该病诊断和治疗的认识。方法　回顾性分析 6 8例结节性甲状腺肿与甲状腺癌并存的临床资料。结果　本组病史平均 2 6 .6年 ;平均年龄 44.4岁 ;术前诊断率为 2 6 .4% ;伴发甲亢率为 5 .7% ;微小癌占 11.8% :以乳头状癌为主要病理类型。结论　病史长及年龄偏大的结节性甲状腺肿患者应想到合并甲状腺癌的可能性 ,此时结节性甲状腺肿的手术适应证应适当放宽 ;本病术前诊断率低 ,应重视术中对可疑结节的探查 ;并非一定行甲状腺癌根治术 ,根据术中冰冻结果采用相应术式。     

促甲状腺激素水平对18F-FDG PET／CT诊断分化型甲状腺癌失分化后复发及转移灶的影响

目的探讨促甲状腺激素（thyroid stimulating hormone,TSH）水平对18F-氟代脱氧葡萄糖（18F—fluorodeoxyglucose,18F—FDG）正电子发射计算机断层显影术（positron emission tomography／eomputed tomograpby,PET／CT）诊断甲状腺球蛋白（thyroglobalin,TG）阳性而131I-诊断剂量全身显像（131I-diagnos—ticwhole—body scanning,131I-dWBS）阴性的分化型甲状腺癌（differentiated thyroid carcinoma,DTC）失分化后复发和转移灶的影响。方法征得患者同意后,将60例欲行18F-FDG PET／CT检测的分化型甲状腺癌术后患者（TG阳性而131I-dWBS阴性）随机分为低TSH组（30例）和高TSH组（30例）。以术后组织病理学或至少6个月的临床和影像学随访结果为诊断病灶性质的标准,得出其阳性预测值（positive predictive value,PPV）,比较TSH水平高低对18F—FDG PET／CT检测结果的影响;分析TG水平与放射性浓聚病灶的标准摄取值（standardized uptake Value,SUV）间的关系。结果高TSH水平及低TSH水平下18F—FDG PET／CT诊断DTC复发和转移灶的阳性预测值分别为96．7％和80．0％（P〈0．05）;患者TG水平与SUV呈正相关。结论18F—FDG PET／CT对于TG阳性而131I-dWBS阴性DTC患者复发和转移灶的诊断,在高TSH水平下较低TSH水平有更高的敏感性与特异性,此可能与TSH刺激肿瘤组织对18F—FDG的摄取相关。     

分化型甲状腺癌NIS表达与外周血CT C的相关性研究

目的：探讨分化型甲状腺癌钠／碘同向转运体（sodium／iodide symporter,NIS）与外周血循环肿瘤细胞（circulating tumor cell,CTC）的相关性。方法收集分化型甲状腺癌172例。通过免疫组织化学SP法及流式细胞术,对甲状腺癌组织NIS表达及外周血CTC 阳性率进行检测分析。结果分化型甲状腺癌组织NIS 表达76例（44．2％）,外周血CTC阳性63例（36．6％）。淋巴结 N0组 NIS 阳性表达较 N1组多,差异有统计学意义（χ2＝6.015,P＝0.014）,N0组CTC阳性率低于N1组,差异亦有统计学差异（χ2＝14.035,P＝0.001）。在N0组及N1组中NIS表达与CTC阳性率均呈负相关（r＝－0.383,r＝－0.610,均P＜0.01）。各病理亚型之间NIS表达高分化型多于中间分化型,差异有统计学意义（χ2＝7.897,P＝0.005）,CTC阳性率高分化型较中间分化型低,差异无统计学意义（χ2＝1.455,P＝0.228）。高分化型及中间分化型中 NIS 表达与 CTC 阳性率均呈负相关（r＝－0.591,r＝－0.443,均P＜0.01）。结论分化型甲状腺癌组织NIS表达与外周血CTC阳性率呈负相关。     

甲状腺乳头状癌BRAF基因突变及表达的临床意义研究

目的探讨BRAF基因点突变及B-raf蛋白表达在甲状腺乳头状癌发生中的临床意义。方法应用聚合酶链式反应(PCR)技术检测65例甲状腺病变石蜡组织中BRAF点突变,应用免疫组化方法检测112例甲状腺病变组织中B-raf蛋白的表达情况,并比较BRAF基因突变和B-raf蛋白表达的相关性。结果在46例甲状腺乳头状癌中有21例发生BRAF的点突变,突变率为45.7。BRAF基因突变位于第15外显子的1799位点,胸腺嘧啶突变为腺嘌呤(T1799A)。在结节性甲状腺肿和滤泡状癌中未检测到BRAF的突变。乳头状癌BRAF基因突变率与结节性甲状腺肿比较,差异具有统计学意义(P<0.05)。但是与患者的性别、年龄、组织学类型、淋巴结转移和肿瘤分期无相关性(P>0.05)。在乳头状癌、滤泡状癌和结节性甲状腺肿中B-raf蛋白表达阳性率分别为65.1、47.6和15.4。结果显示,乳头状癌B-raf蛋白阳性表达率与良性病变比较,差异具有统计学意义(P<0.05)。在乳头状癌中BRAF基因突变与B-raf蛋白表达水平呈正相关(P<0.05)。乳头状癌与滤泡状癌比较,B-raf蛋白表达水平两组间无统计学意义(P>0.05)。结论甲状腺乳头状癌BRAF基因突变率和蛋白表达水平的增高,提示BRAF基因在乳头状癌发病中可能发挥重要的作用。对甲状腺肿瘤的病理诊断也具有辅助价值。