本文選題：垂體卒中　切入點：無功能性垂體腺瘤　出處：《第二軍醫(yī)大學(xué)》2017年碩士論文

【摘要】：垂體腺瘤是一種良性的內(nèi)分泌腫瘤,發(fā)病率約占顱內(nèi)腫瘤的10%[1]。其中,垂體巨大腺瘤以臨床早期就診率低,治療不及時、手術(shù)切除率較低以及預(yù)后不佳為特點。隨著近年來內(nèi)分泌診斷技術(shù)、神經(jīng)影像檢測技術(shù)的提高,越來越多的報道發(fā)現(xiàn)垂體卒中廣泛發(fā)生于垂體腺瘤中,而其中以巨大垂體腺瘤最為常見[2]。早期關(guān)于垂體卒中的研究報道絕大多數(shù)集中于急性/臨床型垂體卒中病例,隨著神經(jīng)影像學(xué)技術(shù)近些年飛速的發(fā)展,神經(jīng)外科學(xué)者發(fā)現(xiàn)亞急性/亞臨床型垂體卒中的發(fā)生率要遠(yuǎn)遠(yuǎn)大于急性/臨床型垂體卒中,因此近些年對于亞臨床型垂體卒中的報道日趨增多。值得關(guān)注的是,由于發(fā)生垂體卒中患者的病例的特殊性,大多對于垂體卒中的臨床研究局限于回顧性觀察研究,缺乏有效的前瞻性研究,仍有不少未知的領(lǐng)域有待探索,可能成為提高此類患者預(yù)后的契機[3]。本文擬從垂體卒中患者的癥狀特點、影像學(xué)特征、內(nèi)分泌激素、腫瘤切除率以及相關(guān)基因/蛋白等的表達(dá)量進(jìn)行多方面研究分析,嘗試闡述垂體卒中這一生物學(xué)行為對于垂體腺瘤診療的影響及特點。本文共分為三個部分:第一部分,以臨床回顧性觀察分析為主要方法,對194例垂體巨大腺瘤患者的基本資料、腫瘤侵襲性范圍、影像學(xué)特征和預(yù)后等多個方面進(jìn)行研究分析。第二部分,以患者下丘腦-垂體促性腺激素軸為主要研究內(nèi)容,分別從回顧性分析和橫斷面研究兩種方法對其進(jìn)行研究,探討垂體卒中對于性腺激素軸功能的影響。第三部分,根據(jù)回顧性觀察研究中關(guān)于切除率與侵襲范圍的研究結(jié)果,進(jìn)一步分析Ki-67、VEGF、CD34基因及相關(guān)蛋白在不同垂體卒中類型中的表達(dá)量,嘗試探討垂體卒中對于腫瘤侵襲性、切除率之間是否存在相互關(guān)系或影響。第一部分無動能性垂體巨大腺瘤瘤內(nèi)卒中臨床特點的研究分析目的:探討無功能性垂體巨大腺瘤瘤內(nèi)卒中的臨床和影像學(xué)特點,及其對手術(shù)療效和預(yù)后的影響。方法:回顧性分析上海長征醫(yī)院自2012年1月至2015年12月收治的194例垂體巨大腺瘤(腫瘤直徑1cm)病例的臨床資料。將所有病例按不同卒中類型分為:非卒中組、出血性卒中組、缺血性卒中組。所有手術(shù)均采用在內(nèi)鏡下經(jīng)鼻蝶入路的手術(shù)方法切除鞍區(qū)腫瘤。結(jié)果:出血性卒中組患者就診時間較缺血性卒中組更及時(P0.001);梗阻性卒中組的垂體腺瘤侵襲范圍更廣(Hardy's分級:P=0.013;Knosp分級:P=0.008)。出血性卒中形態(tài)更傾向于團塊狀聚集發(fā)生,而缺血性卒中以多發(fā)/散點狀分布更為多見(P=0.005);缺血性卒中易發(fā)生于鞍隔上區(qū),而出血性卒中于鞍內(nèi)較多見(P0.001)。缺血性卒中組患者的術(shù)后頭痛癥狀改善情況優(yōu)于出血性卒中組(P=0.05);缺血性卒中組腫瘤切除率優(yōu)于出血性卒中組及非卒中組(0.031)。結(jié)論:出血性垂體卒中就診相對及時,及時手術(shù)治療能獲得較好的預(yù)后;缺血性卒中就診時機較晚,侵襲范圍廣。根據(jù)術(shù)前鞍區(qū)磁共振的檢查,合理區(qū)分垂體卒中類型對于制定治療方案及評價預(yù)后有一定的價值。第二部分垂體卒中對于男性患者性腺激素影響的相關(guān)性研究目的:探索垂體卒中對于男性患者垂體-性腺激素功能軸的影響以及變化特點,嘗試闡述垂體卒中對于性腺激素功能影響的可能機制。方法:回顧性分析男性患者性激素水平(免疫化學(xué)發(fā)光法)與垂體腺瘤卒中之間的關(guān)系,內(nèi)分泌功能隨訪至術(shù)后1年。采用酶聯(lián)免疫吸附測定實驗法分析男性患者血清中卵泡刺激素、黃體生成素以及游離睪酮水平。統(tǒng)計分析垂體卒中以及腫瘤體積對于患者內(nèi)分泌激素的影響。結(jié)果:回顧性分析在男性非卒中組中,術(shù)前血清促性腺激素水平與腫瘤體積成負(fù)線性相關(guān)(FSH:P0.001;LH:P0.001);在出血性卒中組中,術(shù)前/術(shù)后卵泡刺激素、黃體生成素、游離睪酮與腫瘤體積大小均成負(fù)線性相關(guān)(術(shù)前:FSH:P=0.006;LH:P=0.001;F-T:P0.001);(術(shù)后:FSH:P=0.009;LH:P=0.001;F-T:P=0.008);而在缺血性卒中組中未發(fā)現(xiàn)任何相關(guān)關(guān)系。經(jīng)酶聯(lián)免疫吸附測定實驗試驗分析后發(fā)現(xiàn),在男性非卒中組中,促性腺激素水平與腫瘤體積成負(fù)線性相關(guān)(FSH:P=0.036;LH:P=0.035);在出血性卒中組中,促性腺激素與腫瘤體積成負(fù)線性相關(guān)(FSH:P=0.033;LH:P=0.036);而在缺血性卒中組中未見任何相關(guān)關(guān)系。結(jié)論:伴隨出血性卒中組或非卒中組垂體腺瘤體積的增大,男性患者促性腺激素水平逐漸下降。但男性性功能障礙的不典型性一定程度上掩蓋了促性腺激素下降的事實。垂體性腺激素軸可能是評價患者垂體腺細(xì)胞的有效參照,在正確區(qū)分卒中類型的前提下,評估促性腺功能水平對于判斷患者預(yù)后有重要價值。第三部分垂體卒中對垂體腺瘤侵襲性以及切除率影響的研究分析目的:檢測Ki67、VEGF、CD34基因及相關(guān)蛋白在不同類型垂體卒中的垂體腺瘤組織中的表達(dá)情況,結(jié)合患者臨床影像學(xué)等臨床資料,分析不同類型的卒中對于垂體腺瘤侵襲性、腫瘤切除率以及腫瘤復(fù)發(fā)率的影響。方法:共計有36例患者納入本次研究,使用實時定量PCR實驗、免疫組織化學(xué)技術(shù)(IHC)檢測Ki67、VEGF、CD34基因及相關(guān)蛋白在各樣品中的表達(dá)量;利用術(shù)前、術(shù)后磁共振影像檢測結(jié)果計算腫瘤體積判斷垂體腺瘤的切除率,利用統(tǒng)計學(xué)方法分析不同類型垂體卒中對于腫瘤侵襲范圍、切除率以及術(shù)后復(fù)發(fā)率的影響。結(jié)果:經(jīng)實時定量PCR實驗檢測后發(fā)現(xiàn),Ki-67在缺血性卒中組中的表達(dá)量顯著高于出血性卒中組(P0.05);CD34在非卒中組中的表達(dá)量顯著高于出血性卒中組(P=0.018);VEGF的表達(dá)量在三組間的趨勢與CD34表達(dá)量相似,但未見顯著統(tǒng)計學(xué)差異。經(jīng)免疫組化檢測發(fā)現(xiàn),卒中組垂體腺瘤出現(xiàn)散在Ki-67相關(guān)蛋白陽性染色,非卒中腺瘤細(xì)胞中未見陽性染色;此外,VEGF相關(guān)蛋白多見于非卒中腺瘤組織中,而卒中組腺瘤細(xì)胞未見陽性結(jié)果。結(jié)論:缺血性卒中腺瘤侵襲能力強于出血性卒中垂體腺瘤,但這與腫瘤血供、血管新生并無明顯的相關(guān)性。減少腺瘤血供對于軟化腺瘤、提高手術(shù)切除率有一定幫助,但對于控制腫瘤復(fù)發(fā)并沒有統(tǒng)計學(xué)意義,卒中對預(yù)后的影響仍需大樣本量的臨床研究以及長期的隨訪。
[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.

【學(xué)位授予單位】：第二軍醫(yī)大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R736.4

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