侵袭性垂体瘤的MRI表现

【目的】通过分析侵袭性垂体瘤（invasive pituitary adenoma，IPA）的MRI表现，以探讨该肿瘤的生长方式、形态及信号特征。【方法】回顾分析经手术及病理证实的33例IPA的MRI表现。33例患者均行MRI平扫及增强检查，其中男15例，女18例，年龄17-67岁，平均46．7岁。【结果】IPA通常体积较大，易向鞍外多个方向侵犯，其中以颅底骨质和海绵窦侵犯为特征。IPA的MRI信号混杂，其中囊变坏死和出血常见。【结论】MRI可清楚反映该肿瘤的侵袭特征，是术前评价垂体瘤侵袭性的重要方法。     

Study on the Expression Levels of CXCR4, CXCL12, CD44, and CD147 and Their Potential Correlation with Invasive Behaviors of Pituitary Adenomas

Objective To evaluate the factors of CXCR4, CXCL12, CD44, and CD147 as early potential diagnostic biomarkers by determining their expression levels in invasive and non-invasive pituitary adenomas. Methods Fresh pituitary adenoma specimens were collected from 35 pituitary adenoma (21 invasive and 14 non-invasive) patients who underwent surgical treatment in our Neurosurgery Department between January and April of 2009. The expression levels of CXCR4, CXCL12, CD44, and CD147 were evaluated firstly by flow cytometry, fluorescence microscopy in single cell suspensions, and then by immunohistochemical staining of paraffin tissue sections. Results Flow cytometric analyses showed that the percentage of CXCR4-and CXCL12-positive cells from invasive pituitary adenomas (IPA) was significantly higher in the single cell suspensions than that from non-invasive pituitary adenomas (nIPA) (P<0.05). Immunohistochemical staining revealed that CXCR4 and CXCL12 staining index scores of the invasive pituitary adenomas were significantly higher than those of the non-invasive pituitary adenomas (P<0.05). In contrast, neither flow cytometry nor immunohistochemical staining demonstrated significant difference between CD44 and CD147 expression levels, respectively. Conclusion Expression levels of CXCR4 and CXCL12 are correlated with the invasiveness of pituitary adenomas. Therefore, rather than CD44 and CD147, CXCR4 and CXCL12 may potentially serve as biomarkers for early detection of pituitary adenomas.     

磁共振成像对侵袭性垂体瘤的诊断价值

目的探讨磁共振成像在侵袭性垂体瘤诊断中的价值及意义。方法全部患者均行MRI平扫及增强检查,测量冠状位上肿瘤的最大直径,记录肿瘤的大小、部位、信号强度特点及向周围组织浸润生长的方式。并同术中医师所见的肿瘤生长范围、周围组织受累情况及术后病理情况做对比分析。结果 MRI检查肿瘤强化后边界更清楚,一般肿瘤成像均匀,出血坏死肿瘤成像不均匀。MRI观察侵袭性垂体瘤所累及周围组织与术中所见基本相符,相符率为94.2%。36例患者术后病理均诊断为侵袭性垂体瘤,同MRI诊断相符率达100%。其中,部位符合率为94.4%,形状符合率为88.9%,出血坏死符合率为91.7%。结论磁共振可清楚反映垂体瘤的侵袭特征,是诊断评价侵袭性垂体瘤的重要方法。     

侵袭性垂体腺瘤MRI表现与MMP-9、MMP-14、VEGF表达的相关性研究

目的:目的:研究侵袭性垂体腺瘤(IPA)MRI特征,探讨其最大径、体积与其侵袭性的关系;研究垂体腺瘤(PA)基质金属蛋白酶(MMP)-9、MMP-14及血管内皮生长因子(VEGF)的蛋白质表达水平与肿瘤侵袭性的相关性。方法:回顾性分析36例IPA,并以44例非侵袭性垂体腺瘤(NIPA)为对照,PA的性质由MRI表现和术中所见共同确定,所有病例术前均行MRI平扫及动态增强扫描,剂量为0.1mmol/kg。IPA的判断标准采用Knosp分级标准,3、4级视为MRI海绵窦侵袭;测量PA轴位、冠状位及矢状位的最大径,用公式(长×宽×高×1/2)计算肿瘤体积;采用SP法检测80例PA组织标本MMP-9、MMP-14及VEGF的表达,分析肿瘤的侵袭性特征与3种蛋白表达之间的相关性。结果:IPA多见于大腺瘤及巨大腺瘤,肿瘤的侵袭性与其最大径及体积呈正相关(P<0.05);IPA的MMP-9、MMP-14及VEGF的表达明显高于NIPA组(P<0.05)。结论:MRI评价IPA侵袭性的准确性较高,其诊断应综合影像学检查、术中所见及病理学检查;MMP-9、MMP-14及VEGF可作为判断IPA的良好生物学指标。     

侵袭性垂体腺瘤MRI表现与Gal-3、MMP-2表达的相关性

目的：探讨垂体腺瘤MRI侵袭特征与半乳糖凝集素3（Gal-3）和基质蛋白金属酶-2（MMP-2）表达的相关性.方法：对43例垂体腺瘤患者术前行MRI检查,收集术后标本并采用免疫组织化学S-P法诊断侵袭性垂体腺瘤（IPA,26例）和非IPA（17例）组织中Gal-3与MMP-2的表达,分析Gal-3和MMP-2之间的关系.结果：IPA组中Gal-3、MMP-2表达的阳性率均高于非IPA组（P＜0.01）.Gal-3和MMP-2在IPA组织的表达中呈正相关关系（P＜0.01）.结论：Gal-3、MMP-2的表达与垂体腺瘤的侵袭性生长密切相关,可作为判断垂体腺瘤有无侵袭性的潜在分子标志物;裂解的Gal-3片段可能在垂体腺瘤的侵袭中起重要作用,并可能为在分子治疗IPA提供有用的治疗靶标.     

CCL17基因在垂体瘤微环境下的表达及其临床意义

目的　探讨肥胖介导的趋化因子CCL17对垂体腺瘤侵袭性的影响及其临床意义。方法　采用免疫组织化学方法检测64例垂体腺瘤（pituitary adenomas, PAs）组织中巨噬细胞浸润情况,分析巨噬细胞浸润与CCL17表达的相关性。通过免疫荧光和qPCR定量检测侵袭性（32例）和非侵袭性（32例）PAs样本中CCL17的表达水平,评估分析CCL17表达对垂体瘤侵袭进展和不良预后的临床意义。结果　侵袭性PAs中巨噬细胞浸润显著高于非侵袭性垂体瘤（P<005）。免疫荧光和qPCR显示,CCL17的表达在侵袭性垂体瘤中显著增高（P<005）,并且与巨噬细胞浸润（r=0307 6,P<005）和肿瘤大小（r=0356 7,P<005）呈显著的正相关性。在CCL17重组蛋白作用下,垂体腺瘤细胞在48和72 h增殖显著增加（P<005）,且在72 h迁移能力显著增强（P<005）。根据临床资料的单因素分析,高表达CCL17的患者呈现肿瘤体积更大(P=0023),侵袭性更强(P=0024),术后复发的易感程度也越高(P=0031);CCL17的表达与患者BMI呈正相关性(P=0003)。结论　肥胖介导的趋化因子CCL17高表达可能与PA的侵袭进展及患者肿瘤复发密切相关,检测CCL17对PA患者的预后判断具有参考价值。     

ELEVATED SOLUBLE EPIDERMAL GROWTH FACTOR RECEPTOR LEVEL IN PITUITARY ADENOMA AND CARCINOMA

Objective To investigate effect of the soluble epidermal growth factor receptor (sEGFR/sErbB1) level in the peripheral blood in development, invasiveness, apoplexy of each type of pituitary tumor.Methods The sEGFR level was determined in peripheral serum from 190 patients with pituitary diseases by enzyme linked immunosobent assay. The sEGFR levels were measured in 10 pituitary Rathke's pouch, 18 pituitary hyperplasia, 161pituitary adenomas including 30 microadenomas, 83 large adenomas, 48 giant adenomas, 1 pituitary carcinoma, and 28 healthy controls.Results In the patients with pituitary hyperplasia, microadenoma, large adenoma, giant adenoma, and pituitary carcinoma, the sEGFR level was 188.92 32.62, 209.83 19.01,333.20 69.33, 405.85 37.38, and 617.45 fmol/mL independently. They were all significantly higher than patients with pituitary Rathke's pouch (156.78 18.24 fmol/mL, P ＜ 0.001)and healthy control group (159.11 40.50 fmol/mL, P ＜ 0.05). The sEGFR level in pituitary carcinoma was higher than pituitary adenoma. In patients with pituitary adenoma, the sEGFR level was positive correlated to the size of pituitary adenomas (r = 0.998), the significant difference was observed for the sEGFR level in each group of the patients with pituitary adenomas (P ＜ 0.001). Furthermore, in patients with pituitary ACTH-secrefing microadenomas, the serum sEGFR levels in invasiveness (295.00 77.80 fmol/mL) was higher than that in non-invasiveness (210.60 16.4 fmol/mL, P ＜ 0.05). In patients with pituitary ACTH-secreting, PRL-secreting, GH-secreting, and non-functioning large adenomas, the serum sEGFR levels in invasiveness (407.86 28.50, 399.25 30.10, 386.00 13.08, and 369.25 36.70 fmol/mL) was higher than that in non-invasiveness (335.25 63.49, 300.64 47.57, 297.00 61.93, and 269.30 25.68 fmol/mL) respectively (P ＜ 0.05). In patients with invasive pituitary PRL-secreting, GH-secreting, and non-functioning giant adenomas, the serum sEGFR levels not significantly different in between invasiveness (417.50 35.94, 409.50 69.14, and 417.50 44.13 fmol/mL) and noninvasiveness (386.00 49.64, 417.50 44.03, and 409.51 35.17 fmol/mL) (P ＞ 0.05). In patients with pituitary large adenomas, the sEGFR levels in pituitary apoplexy (377.48 39.18 fmol/mL) was higher than that in non-pituitary apoplexy(343.18 68.17 fmol/mL, P ＞ 0.05).Conclusions The increased level of peripheral serum sEGFR is concomitant with development, proliferous size of the adenomas in patients with pituitary adenomas. In addition, the elevated levels of serum sEGFR occur in pituitary apoplexy as clinical active tumors, and the non-invasive ACTH secreting adenomas. The sEGFR levels could be differentiated helpfully between pituitary adenomas and non-pituitary adenomas. These data suggest that serum sEGFR could be as a referable marker of the size and activation of proliferation in pituitary adenoma.     

侵袭性垂体瘤的磁共振成像研究进展

磁共振成像(MRI)因其多方位扫描成像及较高的组织分辨率,在诊断垂体瘤并判断其侵袭性方面具有重大价值。由于某些部位解剖结构的特殊性并不能对肿瘤的侵袭性做出明确诊断,并且部分侵袭性垂体瘤向周围侵犯累及鞍上、海绵窦、鞍底、脑实质等或是同时累及多个部位,MRI信号因肿瘤内出血、坏死等也表现复杂。现就侵袭性垂体瘤的MRI研究进展予以综述,为侵袭性垂体瘤的MRI诊断及鉴别诊断提供依据。     

临床诊断侵袭性肺曲霉菌病相关危险因素分析

侵袭性肺曲霉菌病(invasive pulmonary aspergillosis,IPA)是曲霉菌侵入肺组织引起的深部真菌感染性疾病,主要发生在免疫抑制人群,ICU患者是感染的高危群体.近年来,IPA的发病率旱上升趋势,病死率高达56%～88.1%[1].本研究拟通过对临床诊断IPA危险因素分析,为IPA的早期诊断、预防和治疗提供依据.     

单鼻孔经蝶入路显微手术切除垂体瘤后脑脊液鼻漏的相关因素分析及防治

目的探讨单鼻孔经蝶入路显微手术(简称:蝶术)切除垂体瘤后脑脊液鼻漏发生的相关因素及防治。方法回顾性分析单鼻孔经蝶术切除垂体瘤1 641例的临床资料,比较侵袭性垂体瘤、生长激素腺瘤、垂体瘤全切及术后复发再次经蝶术术后脑脊液鼻漏发生率的差异及相关性。结果侵袭性垂体瘤经蝶术后脑脊液鼻漏发生率(17.8%)显著高于非侵袭性垂体瘤(2.99%);生长激素腺瘤经蝶术后脑脊液鼻漏发生率(7.1%)显著高于其他类激素腺瘤(3.5%);垂体瘤经蝶术全切后脑脊液鼻漏发生率(5.6%)显著高于非全切(1.8%);垂体瘤术后复发再次经蝶术脑脊液鼻漏的发生率(24.1%)显著高于首次经蝶术后(3.2%);Logistic多因素回归分析:肿瘤侵袭性生长、再次手术、术中肿瘤全切与脑脊液鼻漏的发生相关(P<0.01),术前生长激素(HGH)的浓度与术后脑脊液鼻漏的发生相关(P<0.05)。结论单鼻孔经蝶术后脑脊液鼻漏的发生与垂体瘤的侵袭性、激素类型、切除程度及肿瘤术后复发再次手术等因素相关,术前对患者全面了解,术中掌握手术操作要点,早期发现及时处理脑脊液鼻漏是防治的关键。     

The Expression of Integrinβ1 and FAK in Pituitary Adenomas and Their Correlation with Invasiveness

The expression and possible role of integrin-focal adhesion kinase signal pathway in invasive pituitary adenomas were explored. Forty-nine human pituitary adenomas were detected for the expression of integrinβ1 (INTβ1) and focal adhesion kinase (FAK) by immunohistochemistry, and their correlation with the invasiveness of pituitary adenomas as well as between themselves was ana- lyzed. The results showed that INTβ1 was expressed in 46 cases (93.9%) and FAK in 36 cases (73.5%), respectively, and their expression levels were highly correlated with tumor invasiveness, but not with the tumor types. It was suggested that the integrin-focal adhesion kinase signal pathway plays a role in the invasiveness of pituitary adenomas.     

MMP-1、PTTG、Cyclin D1在垂体腺瘤中的表达及与侵袭性关系

目的 探讨基质金属蛋白酶-1(matix metalloproteinase-1,MMP-1)、垂体瘤转化基因(pituitary tumor transforming gene,PTTG)及细胞周期素D1(Cyclin D1)蛋白与垂体腺瘤侵袭性之间的关系.方法 60例垂体腺瘤手术标本分为侵袭性和非侵袭性2组,免疫组织化学染色法检测MMP-1、PTTG和Cyclin D1蛋白在2组中的表达差异.结果 侵袭性和非侵袭性2组垂体腺瘤标本MMP-1、PTTG和Cyclin D1蛋白均有阳性表达,非侵袭性垂体腺瘤均呈低表达,侵袭性垂体腺瘤均呈高表达,差异有统计学意义(P均<0.05).结论 MMP-1、PTTG和Cyclin D1均可作为垂体腺瘤侵袭性的评估指标.     

垂体瘤海绵窦侵袭性与CD34和PTTG表达的关系

目的：探讨海绵窦侵袭性垂体腺瘤的CD34和垂体瘤转化基因（pituitary tumor transforming gene,PTTG）表达特点。方法：收集62例手术治疗的垂体大腺瘤患者资料,按照Knosp标准对肿瘤进行分组,对标本行CD34和PTTG免疫组化染色检查,对染色结果进行统计学比较。结果：62例患者中海绵窦侵袭二级以上者共23例,微血管密度(MVD)平均值为44.04,PTTG超过（+结论：海绵窦侵袭超过Ⅱ级的垂体腺瘤其微血管密度大,PTTG表达强度高,肿瘤具有较强的侵袭性,手术全切困难,术后易复发,术后应给予放射治疗或是药物辅助治疗。     

侵袭性垂体瘤治疗方法的研究进展

垂体瘤是最常见的颅内肿瘤,大多数属于良性肿瘤。少数肿瘤呈侵袭性生长,其特点为侵袭周围的解剖结构、对常规治疗抵抗、术后早期复发率高。目前,侵袭性垂体瘤的治疗仍然是一个挑战。本文从三个方面综述侵袭性垂体瘤的治疗进展：(1)标准的治疗方案为再手术治疗或放射治疗,能在一定程度降低激素分泌水平,但不能控制肿瘤进展;(2)替莫唑胺被推荐作为侵袭性垂体瘤的一线化疗药物,但只对部分患者有效;(3)肽受体放射性核素治疗、新的分子靶向药物(mTOR抑制剂和表皮生长因子受体抑制剂)和免疫检查点抑制剂已用于治疗侵袭性垂体瘤的临床研究,并且取得了一定的治疗效果,给侵袭性垂体瘤患者带来了希望。     

The expression of integrinβ1 and FAK in pituitary adenomas and their correlation with invasiveness

The expression and possible role of integrin-focal adhesion kinase signal pathway in invasive pituitary adenomas were explored. Forty-nine human pituitary adenomas were detected for the expression of integrinβ1 （INTβ1） and focal adhesion kinase （FAK） by immunohistochemistry, and their correlation with the invasiveness of pituitary adenomas as well as between themselves was ana- lyzed. The results showed that INTβ1 was expressed in 46 cases （93.9%） and FAK in 36 cases （73.5%）, respectively, and their expression levels were highly correlated with tumor invasiveness, but not with the tumor types. It was suggested that the integrin-focal adhesion kinase signal pathway plays a role in the invasiveness of pituitary adenomas.     

流感相关侵袭性肺曲霉病的早期诊断

侵袭性肺曲霉病(IPA)常发生于粒细胞缺乏症等严重免疫缺陷患者[1],在入住重症加强治疗病房(ICU)的非严重免疫缺陷患者中,IPA病例也在不断增加[2].发生IPA的高危人群也在不断扩大,已从"传统因素"(如接受同种异体干细胞移植,血液系统恶性肿瘤等)扩展到"非特异因素"(如慢性阻塞性肺疾病、PTX3基因突变等)[3...     

烟曲霉菌感染引起脓气胸1例

曲霉孢子在空气中传播,人吸入后可以在气道内定植、致敏、感染,当人体免疫功能低下时可产生危及生命的侵袭性肺曲霉病(invasive pulmonary aspergillosis,IPA)[1].近年来IPA发病率呈上升趋势,本科收治1例少见的曲霉菌感染引起的脓气胸,现报告如下.     

CD105和HIF-la在侵袭性垂体瘤中的表达

目的 研究CD<,105>和缺氧诱导因子-la (HIF-la)在侵袭性垂体瘤中的表达水平,并探讨CD<,105>标记的MVD密度及HIF-la在侵袭性垂体瘤中的生物学意义和作用.方法 收集2005-2010年的侵袭性垂体瘤手术标本25例,非侵袭性垂体瘤15例,用免疫组化方法检测CD<,105>及HIF-la的表达,并对CD<,105>标记的MVD进行计数,结果进行对照分析.结果 所有垂体瘤标本均有CD<,105>表达,40例标本CD<,105>MVD均值为(16.2±6.1),侵袭性组为(21.8±2.8),非侵袭性组为(10.6±2.2);HIF-la表达情况:侵袭性组为14例阳性,11例阴性;非侵袭性组为3例阳性,12例阴性.经统计学分析侵袭性与非侵袭性垂体瘤中CD<,105>和HIF-la的表达存在显著差异,有统计学意义(F<0.05).结论 侵袭性垂体瘤中CD<,105>和HIF-la的表达明显增高,CD<,105>和HIF-la参与侵袭性垂体瘤的发生、发展.CD<,105>和HIF-la可以作为预测垂体瘤侵袭性的免疫检测指标.     

THE ROLE OF CALCIUM ION IN THE PATHOGENESIS OF HUMAN PITUITARY GH-SECRETING ADENOMAS

To study the role of Ca^2 in the pathogenesis of pituitary growth hormone secreting adenornas,the function of Ca^2 in 23 cases of human pituitary GH-secreting adenoma was investigated in monolayer cell culture.It was found that Ca^2- channel blockers nicardipin and nifedipin inhibited hasal and growth hormone releasing hormone (GRH)-stimulated GH secretion in 87.5% and 100.0% of the GH adenomas.respectively,demonstrating that in most human pituitary GH agonist octreotide regulated the processes of GH secretion via Ca^2 had defects in different steps including receptor.postreceptor Ca^2 channel and Ca^2 -GH secreting coupling in 6(66.6%)and 5(55.5%) cases of 9 GH adenomas respectively.Among them,the defects in GRH receptor and SRIF regulated Ca^2 channel are the main causes of the dysfunction of GH adenomas.These defects may be related to GH hypersecretion in GH adenomas.Our data provides advance evidences for intrinsic defects of GH adenomas.