垂体生长激素腺瘤靶向性基因治疗系统的构建及实验研究

目的构建并评价垂体生长激素腺瘤靶向性基因治疗系统.方法构建GE7系统介导的生长激素启动子调控的基因治疗系统,通过垂体生长激素腺瘤GH3细胞及对照细胞的体外基因转染实验,观察此基因治疗系统对GH3细胞的转染能力和靶向性.结果成功构建基因治疗系统,基因转染后GH3细胞特异性表达报告基因,对照的HO8910PM和U-2OS细胞报告基因的表达不明显.结论应用GE7转染的生长激素启动子调控的基因治疗系统能靶向性地将目的基因转入垂体生长激素腺瘤细胞.     

Osseous metaplasia in a growth hormone-secreting pituitary adenoma.

A case of growth hormone-secreting adenoma of the pituitary gland showing osseous metaplasia is described in a 56-year-old acromegalic female. The tumor was composed of nests of densely granulated cells separated by and intermixed with calcifications, trabeculae of mature bone and fat. Calcifications are seldom found in pituitary adenomas. In rare instances, calcium deposits can be prominent enough to lead to the formation of pituitary stones and bone which replace the entire tumor mass. Analogously with metaplastic meningiomas, we propose using the term metaplastic adenoma to define cases with osseous metaplasia in order to distinguish between lesions containing bone from the more frequently seen calcified adenomas.     

Non-surgical management of cystic prolactinomas

Cystic prolactinomas are considered not amenable to dopamine agonist therapy. We present the results of dopamine agonist therapy in six patients with cystic prolactinomas. The inclusion criteria of patients were: (i) cystic macroadenomas with the cyst occupying more than 50% of the tumour volume; (ii) a serum prolactin value more than 150 ng/mL. All patients were males with a mean age of 35 years. The clinical presentations were erectile dysfunction in 66.6%, visual deficits in 50% and headache in 50% of patients. All patients were treated with bromocriptine only except one who was treated with both bromocriptine and cabergoline. The mean duration of follow up was 57.1 months. At the final follow-up 50% of patients had hormonal cure, 50% had radiological cure and 50% had reduction in the size of the tumour. Hence, it is appropriate to consider dopamine agonist therapy in patients with cystic prolactinomas before considering surgery.     

垂体生长激素腺瘤的临床和病理特征

目的探讨垂体生长激素（GH）腺瘤患者的临床及病理学特征。方法回顾性分析92例垂体GH腺瘤患者的临床资料,均采用经鼻蝶手术治疗。结果本组患者均有典型肢端肥大症状,但只有20例出现其他内分泌症状;共有微腺瘤20例,大腺瘤72例;侵袭性腺瘤19例,非侵袭性73例;术后免疫组织病理学结果示,GH（＋）15例,GH（＋）和泌乳素（＋）38例,GH（＋）和促肾上腺皮质激素（＋）2例,GH（＋）和促卵泡激素（＋）1例,GH（＋）和促黄体激素（＋）1例;包括GH在内的三种及以上激素（＋）35例。术后1周总缓解率为55．4％（51／92）。单纯GH（＋）腺瘤缓解率为66．7％（10／15）,伴其它激素阳性腺瘤缓解率为53．2％（41／77）,两者无统计学差异（P〉0．05）。73例患者术后随访3～52个月,平均30．3个月,肢端肥大症状、月经不调、溢乳、性欲减退和甲状腺功能异常缓解率分别为86．3％（63／73）、71．4％（5／7）、66．7％（4／6）、33．3％（2／6）和42．9％（3／7）。结论多数垂体GH腺瘤组织病理学表现为多激素阳性腺瘤,但是仅有少数患者表现出除肢端肥大症外的其它内分泌症状。     

生长激素型垂体腺瘤伽玛刀治疗的疗效分析

目的 评价leksell伽玛(γ)刀治疗生长激素型垂体腺瘤的疗效.方法 对我院自2005年1月至2008年3月应用伽玛刀治疗41例生长激素型垂体腺瘤患者进行回顾性分析,肿瘤直径4～38.6mm,平均15.2mm.采用1.5T磁共振定位,Ganuna-Plan计划系统规划,等剂量曲线16%～60%,治疗周边剂量9.95～35 Gy,中心剂量31.25～70 Gy.结果 33例获随访,30例(90.9%)患者临床症状改善,16例(48.4%)患者的血清生长激素(GH)值降到正常水平,12例(36.3%)患者GH值下降,4例(12.1%)患者GH值无变化.24例(72.7%)患者肿瘤缩小,9例(27.2%)患者肿瘤无改变.结论 γ刀治疗在控制生长激素型垂体腺瘤生长和改善内分泌症状是安全有效的,是GH微腺瘤首选治疗方法;对肿瘤术后残存或复发,尤其是侵袭海绵窦的患者,γ刀是最好的补充治疗.     

人垂体生长激素腺瘤临床生化特征分析

目的 研究人垂体生长激素（GH）腺瘤临床生化特征及肿瘤Gsp癌基因表达、激素分泌、细胞增殖水平及侵袭性之间的相互关系。方法 垂体GH腺瘤43例，对其中17例分别提取DNA，经多聚酶链反应（PCR）扩增和基因直接序列分析法检测Gsp癌基因的表达；以^125I-VolR DNA聚合酶活性测量法，检测43例患血清DNA聚合酶活性以间接评价肿瘤组织增生活性；用放射免疫法测定患血清GH分泌水平。结果 Gsp癌基因阴性和阳性患在肿瘤大小、GH水平及侵袭性上均无显性差异。侵袭性垂体腺瘤DNA聚合酶活性比非侵袭性垂体腺瘤患高，在统计学上有显性差异（P＜0．05）。结论 侵袭性垂体腺瘤的增殖活性和GH水平明显增高。DNA聚合酶活性和GH水平可作为判断垂体腺瘤侵袭性的有用参考指标。     

激素在垂体生长激素腺瘤预后判断中的意义

垂体生长激素腺瘤是一种相对罕见的疾病，生长激素（growth hormone，GH）高分泌发生在青春期骨骺闭合前表现为巨人症，成年后主要是肢端肥大症，约占垂体腺瘤的20％，总发病率在15．7～75．8／百万。肢端肥大症是个缓慢进展的疾病，临床上主要表现为疲劳感、关节疼痛、头痛、感觉异常及过量出汗。     

Sarcomatous change after sellar irradiation in a growth hormone-secreting pituitary adenoma

BACKGROUND: Although the benefits of radiotherapy for pituitary adenomas are well-documented, post-irradiation sarcomas of the sella are rarely seen, with only 20 cases (mainly of fibrosarcoma) reported in the medical literature. METHOD: We describe a case of post-irradiation sarcoma five years after surgery followed by external-beam irradiation for an extensive and locally invasive growth hormone-secreting tumor. The patient was subsequently given pegvisomant, an antagonist of growth hormone receptor, to control symptoms of growth hormone excess. RESULTS: The patient underwent transsphenoidal resection of the recurrent tumor, followed by adjuvant chemotherapy. This led to significant relief in the patient's symptoms including radiological evidence of tumor shrinkage, but the tumor regrew when, owing to dose-limiting toxicity, chemotherapy was stopped. CONCLUSIONS: Post-irradiation sarcomas of the pituitary are well-recognized but rare. They should be suspected in patients following sellar irradiation who show abrupt onset of new symptoms and appropriate radiological findings, and such tumors may respond to cytotoxic chemotherapy.     

垂体生长激素腺瘤病人术前应用奥曲肽的初步研究

目的前瞻性探讨奥曲肽对生长激素腺瘤病人生长激素水平和瘤体中Ⅰ型、Ⅲ型胶原含量的影响。方法将25例病例随机分为治疗组13例和对照组12例。治疗组术前2周开始皮下注射奥曲肽,对照组直接手术。肿瘤标本行Ⅰ型、Ⅲ型胶原免疫组织化学染色,计算Ⅰ型、Ⅲ型胶原阳性面积百分比。比较两组手术前后生长激素水平、Ⅰ型、Ⅲ型胶原含量等。结果治疗组和对照组中,术后生长激素恢复正常的例数分别为9例和6例;治疗组与对照组Ⅰ型胶原阳性面积分别为(12.75±5.01)%和(36.86±11.27)%(P<0.05),Ⅲ型胶原阳性面积为(11.99±4.13)%和(13.12±5.13)%(P=0.40)。结论术前应用奥曲肽有助于降低生长激素腺瘤病人的生长激素水平,使瘤体中I型胶原含量减少,进而可能软化瘤体,为经蝶手术治疗创造有利条件。     

垂体生长激素大腺瘤和无功能大腺瘤的生长模式分析

目的 通过分析垂体生长激素大腺瘤和无功能大腺瘤的生长特点来比较它们不同的生长模式.方法 回顾分析42例无功能大腺瘤和18例生长激素大腺瘤(微腺瘤和二次手术者除外),采用术前MRI评估两者的生长模式特点.结果 垂体无功能大腺瘤和生长激素大腺瘤的最大肿瘤直径分别为34 mm和26 mm.无功能大腺瘤从垂体窝向外生长的部位如下:蝶鞍下侵犯19例(45.2％),蝶鞍上侵犯37例(88.1％),海绵窦侵犯14例(33.3％).生长激素大腺瘤向外生长的部位如下:蝶鞍下侵犯14例(77.8％),蝶鞍上侵犯4例(22.2％),海绵窦侵犯2例(11.1％).与生长激素大腺瘤相比,无功能大腺瘤更倾向于蝶鞍上侵犯(P＜0.05)、海绵窦侵犯(P＜0.05)和独立蝶鞍上侵犯(P＜0.05);而生长激素大腺瘤则更易于向蝶鞍下生长(P＜0.05)和独立蝶鞍下侵犯(P＜0.05).结论 根据垂体腺瘤不同的组织病理类型来观察它们生长模式的本质区别.生长激素大腺瘤明显表现出优先突破鞍底向蝶鞍下生长的倾向,而无功能大腺瘤则倾向于突破鞍膈向蝶鞍上生长.     

Prolactin-Secreting pituitary tumors

Prolactin secretion was evaluated in 69 patients with pituitary tumors. Among the 47 who were seen prior to treatment, hyperprolactinemia was present in 37 (79%). Excluding patients with galactorrhea, hyperprolactinemia was present in 19 (70%) of those seen before treatment. There was little correlation between tumor size and level of serum prolactin. Both transspheoidal surgery and radiotherapy greatly reduced the hyperprolactinemia, but a more rapid decrease was achieved with microsurgical removal of the secreting adenoma.     

Management of pituitary tumors

Pituitary adenomas represent the only true adenomas of the cranial cavity. In 1000 asymptomatic pituitary glands examined at autopsy, there was a 22.4 per cent incidence of undetected microadenomas. Advances in diagnostic endocrinology, in radiologic imaging, and in surgical and medical treatments have brought many more patients to the attention of the authors. Over the last 10 years, their treatment approaches have evolved to those presented in this article.     

经颅鞍区肿瘤切除术后的处理(附156例分析)

目的探讨经颅鞍区肿瘤切除术后并发症的特点及临床处理。方法分析156例鞍区肿瘤经颅显微手术病例术后并发症的发生情况。结果手术全切除140例(90％)，术后死亡3例(1．9％)；术后并发尿崩症36例(23％)、电解质紊乱28例(18％)、癫痫8例(5．1％)、垂体功能低下5例(3．2％)、术后出血3例(1．9％)；无高热和应激性溃疡。结论鞍区肿瘤经颅术后的并发症以水、电解质紊乱最为常见；制定术后常规处理并进行积极治疗，术后并发症基本上可以恢复。     

影响垂体生长激素腺瘤经蝶手术疗效的因素分析

目的 评价垂体生长激素腺瘤经蝶手术的疗效和分析影响手术疗效的相关因素。方法 回顾性分析62例资料完整经蝶手术治疗的垂体生长激素腺瘤病人的临床资料．根椐肿瘤大小、术前生长激素水平、侵袭性、肿瘤病理类型等进行分类。按肢端肥大症的治愈标准．采用术后激素水平结合影像学复查评价手术疗效。结果 总缓解率为66．1％，微腺瘤、大微腺、巨大腺瘤术后缓解率分别为87．5％、71．8％和40．0%．侵袭性和非侵袭性腺瘤则为36．8％和79．7％。微腺瘤与巨大腺瘤（P〈0．05）、侵袭性与非侵袭性腺瘤术后缓解率有统计学差异（P〈0．001）。结论 微腺瘤和非侵袭性大腺瘤采用经蝶手术可取得满意疗效，侵袭性腺瘤或巨大腺瘤采用经蝶手术治愈率较低。     

经鼻蝶入路显微手术切除垂体生长激素腺瘤的疗效及免疫组化分析

目的观察分析不同临床类型及病理免疫组化分型的垂体生长激素(GH)腺瘤患者经鼻蝶入路显微手术的临床疗效。方法回顾性分析75例经鼻蝶入路手术治疗的垂体GH腺瘤的临床资料。结果术前GH平均值为40.79mIU/L,术后为19.48mIU/L。侵袭性腺瘤40例,非侵袭性腺瘤35例。侵袭性和非侵袭性腺瘤的术后症状缓解率分别为72.5%和88.6%,复发率分别为42.5%和14.3%。结论经鼻蝶入路显微手术对垂体GH腺瘤具有较高的临床症状和内分泌缓解率。侵袭性垂体GH腺瘤,缓解率较低,复发率高,单纯GH腺瘤侵袭性明显高于其他类型GH腺瘤。     

Molecular pathogenesis of pituitary tumors

Pituitary tumors are the result of a monoclonal outgrowth where the intrinsic genetic defects involve oncogenes, tumor suppressor genes (TSG), and most likely genes responsible for differentiation. In addition, hypothalamic and intrapituitary derived growth factors are imposed upon these aberrant cells, contributing to their growth characteristics. While histological examination will not identify those tumors likely to progress toward an invasive phenotype or those destined toward recurrence recent advances in the molecular pathology of these tumors holds significant promise for prediction of recurrence and the design of novel treatment strategies. Moreover, emerging data clearly indicate that different molecular mechanisms are involved in the pathogenesis of the various pituitary tumor subtypes. Until recently the gsp oncogene was the only oncogene significantly associated with pituitary tumors; however, emerging data have describe a role for PTTG and cyclin D1 in pituitary tumorigenesis. For known and putative TSG loci, allelic losses on the long arms of chromosomes 10, 11, and 13 are significantly associated with the transition from the noninvasive to the invasive and metastatic phenotype, while losses on chromosome 9p occur early in pituitary tumorigenesis. Studies of known TSG at these loci, including the menin gene and RB1, would suggest a limited role, if any, in pituitary tumors. However, loss of pRB is evident in a proportion of somatotropinomas but is not associated with allelic loss of an RB1 intragenic marker. The gene encoding p16/CDKN2A is neither deleted nor mutated in pituitary tumors; however, its associated CpG island is frequently methylated and is associated with a loss of p16 protein expression. Allelic losses on chromosome 9p, frequent methylation, and loss of p16 protein appear as early changes in nonfunctional tumors, whereas they are infrequent events in somatotropinomas. The functional consequence of enforced expression of p16/CDKN2A in the mouse corticotroph cell line AtT20 has shown that it is responsible for a profound reduction in cell proliferation and the mechanism is a G(1) arrest, mimicking the in vivo role of this cell cycle regulator in most tissues. The combined data from several groups show that the allelic losses reported at known TSG loci are not accompanied by mutation in the retained allele. However, since abnormal methylation patterns may precede and predispose toward genetic instability this could account for the allelic losses on these chromosomes. Equally, since DNA methylation may lead to reduced expression of a gene it might also account for the reduced expression of as yet unidentified TSGs implicated in pituitary tumorigenesis. Collectively these studies hold significant promise as markers predictive of tumor behavior and point to novel treatment strategies, which may include the reactivation of TSGs that are intact but silenced through epigenetic mechanisms.     

Non-surgical management of intracranial subdural hematoma complicating spinal anesthesia

We report the case of a 29 year-old woman who presented a symptomatic intracranial subdural hematoma developing shortly after spinal anesthesia. The patient was fully conscious at clinical onset, and thus we treated her conservatively with an epidural autologous blood patch and close neurological observation. Given the clinical improvement the possibility of surgery was discauded in agreement with the neurosurgical team. Most cases of subdural hematoma appearing after spinal anesthesia are treated with surgery. In the present case the subdural hemorrhage was detected at our hospital 20 days after the anesthetic procedure, and given the excellent state of consciousness, we choosed a conservative management.