无功能性垂体腺瘤卒中的特点以及对肿瘤侵袭性影响的分析研究

发布时间：2018-03-26 03:02

本文选题：垂体卒中　切入点：无功能性垂体腺瘤　出处：《第二军医大学》2017年硕士论文

【摘要】：垂体腺瘤是一种良性的内分泌肿瘤,发病率约占颅内肿瘤的10%[1]。其中,垂体巨大腺瘤以临床早期就诊率低,治疗不及时、手术切除率较低以及预后不佳为特点。随着近年来内分泌诊断技术、神经影像检测技术的提高,越来越多的报道发现垂体卒中广泛发生于垂体腺瘤中,而其中以巨大垂体腺瘤最为常见[2]。早期关于垂体卒中的研究报道绝大多数集中于急性/临床型垂体卒中病例,随着神经影像学技术近些年飞速的发展,神经外科学者发现亚急性/亚临床型垂体卒中的发生率要远远大于急性/临床型垂体卒中,因此近些年对于亚临床型垂体卒中的报道日趋增多。值得关注的是,由于发生垂体卒中患者的病例的特殊性,大多对于垂体卒中的临床研究局限于回顾性观察研究,缺乏有效的前瞻性研究,仍有不少未知的领域有待探索,可能成为提高此类患者预后的契机[3]。本文拟从垂体卒中患者的症状特点、影像学特征、内分泌激素、肿瘤切除率以及相关基因/蛋白等的表达量进行多方面研究分析,尝试阐述垂体卒中这一生物学行为对于垂体腺瘤诊疗的影响及特点。本文共分为三个部分:第一部分,以临床回顾性观察分析为主要方法,对194例垂体巨大腺瘤患者的基本资料、肿瘤侵袭性范围、影像学特征和预后等多个方面进行研究分析。第二部分,以患者下丘脑-垂体促性腺激素轴为主要研究内容,分别从回顾性分析和横断面研究两种方法对其进行研究,探讨垂体卒中对于性腺激素轴功能的影响。第三部分,根据回顾性观察研究中关于切除率与侵袭范围的研究结果,进一步分析Ki-67、VEGF、CD34基因及相关蛋白在不同垂体卒中类型中的表达量,尝试探讨垂体卒中对于肿瘤侵袭性、切除率之间是否存在相互关系或影响。第一部分无动能性垂体巨大腺瘤瘤内卒中临床特点的研究分析目的:探讨无功能性垂体巨大腺瘤瘤内卒中的临床和影像学特点,及其对手术疗效和预后的影响。方法:回顾性分析上海长征医院自2012年1月至2015年12月收治的194例垂体巨大腺瘤(肿瘤直径1cm)病例的临床资料。将所有病例按不同卒中类型分为:非卒中组、出血性卒中组、缺血性卒中组。所有手术均采用在内镜下经鼻蝶入路的手术方法切除鞍区肿瘤。结果:出血性卒中组患者就诊时间较缺血性卒中组更及时(P0.001);梗阻性卒中组的垂体腺瘤侵袭范围更广(Hardy's分级:P=0.013;Knosp分级:P=0.008)。出血性卒中形态更倾向于团块状聚集发生,而缺血性卒中以多发/散点状分布更为多见(P=0.005);缺血性卒中易发生于鞍隔上区,而出血性卒中于鞍内较多见(P0.001)。缺血性卒中组患者的术后头痛症状改善情况优于出血性卒中组(P=0.05);缺血性卒中组肿瘤切除率优于出血性卒中组及非卒中组(0.031)。结论:出血性垂体卒中就诊相对及时,及时手术治疗能获得较好的预后;缺血性卒中就诊时机较晚,侵袭范围广。根据术前鞍区磁共振的检查,合理区分垂体卒中类型对于制定治疗方案及评价预后有一定的价值。第二部分垂体卒中对于男性患者性腺激素影响的相关性研究目的:探索垂体卒中对于男性患者垂体-性腺激素功能轴的影响以及变化特点,尝试阐述垂体卒中对于性腺激素功能影响的可能机制。方法:回顾性分析男性患者性激素水平(免疫化学发光法)与垂体腺瘤卒中之间的关系,内分泌功能随访至术后1年。采用酶联免疫吸附测定实验法分析男性患者血清中卵泡刺激素、黄体生成素以及游离睾酮水平。统计分析垂体卒中以及肿瘤体积对于患者内分泌激素的影响。结果:回顾性分析在男性非卒中组中,术前血清促性腺激素水平与肿瘤体积成负线性相关(FSH:P0.001;LH:P0.001);在出血性卒中组中,术前/术后卵泡刺激素、黄体生成素、游离睾酮与肿瘤体积大小均成负线性相关(术前:FSH:P=0.006;LH:P=0.001;F-T:P0.001);(术后:FSH:P=0.009;LH:P=0.001;F-T:P=0.008);而在缺血性卒中组中未发现任何相关关系。经酶联免疫吸附测定实验试验分析后发现,在男性非卒中组中,促性腺激素水平与肿瘤体积成负线性相关(FSH:P=0.036;LH:P=0.035);在出血性卒中组中,促性腺激素与肿瘤体积成负线性相关(FSH:P=0.033;LH:P=0.036);而在缺血性卒中组中未见任何相关关系。结论:伴随出血性卒中组或非卒中组垂体腺瘤体积的增大,男性患者促性腺激素水平逐渐下降。但男性性功能障碍的不典型性一定程度上掩盖了促性腺激素下降的事实。垂体性腺激素轴可能是评价患者垂体腺细胞的有效参照,在正确区分卒中类型的前提下,评估促性腺功能水平对于判断患者预后有重要价值。第三部分垂体卒中对垂体腺瘤侵袭性以及切除率影响的研究分析目的:检测Ki67、VEGF、CD34基因及相关蛋白在不同类型垂体卒中的垂体腺瘤组织中的表达情况,结合患者临床影像学等临床资料,分析不同类型的卒中对于垂体腺瘤侵袭性、肿瘤切除率以及肿瘤复发率的影响。方法:共计有36例患者纳入本次研究,使用实时定量PCR实验、免疫组织化学技术(IHC)检测Ki67、VEGF、CD34基因及相关蛋白在各样品中的表达量;利用术前、术后磁共振影像检测结果计算肿瘤体积判断垂体腺瘤的切除率,利用统计学方法分析不同类型垂体卒中对于肿瘤侵袭范围、切除率以及术后复发率的影响。结果:经实时定量PCR实验检测后发现,Ki-67在缺血性卒中组中的表达量显著高于出血性卒中组(P0.05);CD34在非卒中组中的表达量显著高于出血性卒中组(P=0.018);VEGF的表达量在三组间的趋势与CD34表达量相似,但未见显著统计学差异。经免疫组化检测发现,卒中组垂体腺瘤出现散在Ki-67相关蛋白阳性染色,非卒中腺瘤细胞中未见阳性染色;此外,VEGF相关蛋白多见于非卒中腺瘤组织中,而卒中组腺瘤细胞未见阳性结果。结论:缺血性卒中腺瘤侵袭能力强于出血性卒中垂体腺瘤,但这与肿瘤血供、血管新生并无明显的相关性。减少腺瘤血供对于软化腺瘤、提高手术切除率有一定帮助,但对于控制肿瘤复发并没有统计学意义,卒中对预后的影响仍需大样本量的临床研究以及长期的随访。
[Abstract]:Pituitary adenoma is a benign neuroendocrine tumor incidence accounnting 10%[1]. the giant pituitary adenoma to early clinical treatment is low, treatment is not timely, the resection rate is low and the prognosis is poor. In recent years with the characteristics of endocrine diagnostic technology, neural imaging detection technology, more and more reports found pituitary apoplexy occurs widely in pituitary adenomas, which in most of giant pituitary adenoma early reports of pituitary apoplexy [2]. most common focus on acute / clinical cases with pituitary apoplexy, neuroimaging technology rapid development in recent years, scholars have found that the Department of Neurosurgery of subacute / subclinical pituitary apoplexy incidence is far greater than the acute / clinical type of pituitary apoplexy, therefore reports on subclinical pituitary apoplexy is increasing in recent years. The concern is that due to the occurrence of The particularity of patients with pituitary apoplexy cases, mostly for clinical study of pituitary apoplexy is limited to retrospective observational study, the lack of prospective study effectively, there are still many unknown areas to be explored, to improve the prognosis of these patients may become an opportunity to [3]. this paper from the characteristics of the patients with pituitary apoplexy symptoms, radiological features, endocrine analysis of various hormones, tumor resection rate and the expression of related gene / protein, try to elucidate the biological behavior of pituitary apoplexy for diagnosis and treatment of pituitary adenoma and characteristics. This paper is divided into three parts: the first part, based on clinical retrospective observation and analysis is the main method of basic data of 194 cases of pituitary giant adenoma patients, tumor invasive range, many aspects of imaging features and prognosis were analyzed. The second part, in patients with hypothalamic pituitary gonadotropin The shaft as the main research contents, respectively from the retrospective analysis and cross-sectional study of two methods to study the effects of pituitary apoplexy, the gonadal hormone axis function. In the third part, according to the review of research results on resection rate and invasion of the observational study, further analysis of Ki-67, VEGF, CD34 gene expression and related proteins in different types of pituitary apoplexy, attempts to explore for pituitary apoplexy invasive tumor resection, whether there is relationship between the rate of or influence. The first part of the kinetic energy of giant pituitary adenoma in tumor stroke clinical characteristics analysis objective: To investigate the clinical and imaging features of non functional pituitary adenoma apoplexy in great, and its influence on the curative effect and prognosis. Methods: a retrospective analysis of Shanghai Changzheng Hospital from January 2012 to December 2015 were 194 cases of giant pituitary adenoma (direct tumor Size 1cm) clinical data of cases. All the cases of different types of strokes are divided into: non stroke group, hemorrhage stroke group, ischemic stroke group. All underwent surgical methods in endoscopic transsphenoidal approach for resection of sellar tumors. Results: hemorrhagic stroke group patients were ischemic stroke more timely group (P0.001); obstructive stroke group of pituitary adenoma invading a wider range (Hardy's classification: P=0.013; Knosp grade: P=0.008). Hemorrhagic stroke patterns tend to agglomerate aggregation, and ischemic stroke with multiple / punctate distribution is more common (P=0.005); ischemic stroke prone in sellar area, and hemorrhagic stroke were more common in the saddle (P0.001). The improvement of symptoms better than hemorrhagic stroke group headache patients with postoperative ischemic stroke group (P=0.05); ischemic stroke group tumor resection rate better than hemorrhagic stroke group and non stroke group (0.031). Conclusion: hemorrhagic pituitary apoplexy were relatively timely, timely surgical treatment can achieve good prognosis; late treatment of ischemic stroke, a wide range of invasion. According to the operation of a magnetic resonance examination, a reasonable distinction between types of pituitary apoplexy have a certain value for treatment and evaluation of prognosis. The second part for pituitary apoplexy objective to study the effects of gonadal hormones between male patients with pituitary apoplexy: To explore the effect on male patients with pituitary gonadal hormone function axis and characteristics, try to elucidate possible mechanisms affecting gonadal hormone function for pituitary apoplexy. Methods: a retrospective analysis of sex hormone level in male patients (chemiluminescence immunoassay) and the relationship between pituitary apoplexy the endocrine function of up to 1 years after operation. The ELISA test analysis of serum follicle stimulating hormone in male patients, yellow Erythropoietin and body free testosterone level. Statistical analysis and the effect of pituitary apoplexy tumor volume in patients with endocrine hormone. Results: a retrospective analysis in male non stroke group, preoperative serum gonadotropin levels and tumor volume in a negative linear correlation (FSH:P0.001; LH:; P0.001) in hemorrhagic stroke group, preoperative postoperative / follicle stimulating hormone, luteinizing hormone, free testosterone and tumor size were negative linear correlation (before operation: FSH:P=0.006; LH:P=0.001; F-T:P0.001; () after surgery: FSH:P=0.009; LH:P=0.001; F-T:P=0.008); without any correlation found in the ischemic stroke group. The ELISA test the analysis found that in male non stroke group, gonadotropin levels and tumor volume in a negative linear correlation (FSH:P=0.036; LH:P=0.035); in hemorrhagic stroke group, gonadotropin and tumor volume has a negative linear phase Close (FSH:P=0.033; LH:P=0.036); in the ischemic stroke group showed no correlation. Conclusion: with the increase of the volume of bleeding of pituitary adenoma stroke group and non stroke group, male patients with gonadotropin levels gradually decreased. But not typical of a certain degree of male sexual dysfunction conceal the decline in gonadotropin pituitary gonadal hormones. Axis may be effective according to the evaluation of patients with pituitary gland cells, in the premise of distinguishing type of stroke under the correct assessment of gonadal function level to determine the prognosis of patients has important value. The third part of the study of pituitary apoplexy and the invasiveness of pituitary adenoma resection rate analysis objective: to detect the expression of CD34 Ki67 and VEGF. Genes and related proteins in different types of pituitary apoplexy pituitary adenoma tissues, combined with clinical imaging and clinical data analysis for different types of stroke The invasiveness of pituitary adenomas, tumor resection rate and tumor recurrence rate. Methods: a total of 36 patients were included in this study, using real-time quantitative PCR assay, immunohistochemistry (IHC) detection of Ki67, VEGF, CD34 gene expression and related protein in the sample; the use of preoperative, postoperative the results of magnetic resonance imaging to detect the tumor volume was calculated to determine the resection rate of pituitary adenoma, analysis of different types of pituitary apoplexy for tumor invasion by using statistical method, and the effect of the resection rate of postoperative recurrence rate. Results: the quantitative real-time PCR assay showed that the expression of Ki-67 in ischemic stroke group was markedly higher than that of hemorrhage stroke group (P0.05); the expression of CD34 in non stroke group was significantly higher than that in the stroke group (P=0.018); the expression of VEGF between the three groups in the trend and the expression of CD34 is similar, but there was no significant difference with the free. Immunohistochemical detection showed that the stroke group of pituitary adenoma scattered in Ki-67 protein positive staining, non stroke adenoma cells had no positive staining; in addition, VEGF related protein in non tumor tissue in stroke, and stroke group adenoma cells had no positive results. Conclusion: ischemic stroke tumor invasion ability in hemorrhagic stroke pituitary adenoma, but with the blood supply of the tumor, there is no obvious correlation between angiogenesis. For reducing blood for softening adenoma adenoma, improve the resection rate of some help, but for the control of tumor recurrence and no significant influence on the prognosis of stroke, still need large sample clinical study and long-term follow-up.

【学位授予单位】：第二军医大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R736.4

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