侵袭性垂体腺瘤侵袭性的综合判断及其与临床预后的关系

目的分析经侵袭性垂体腺瘤侵袭性的判断标准及其与临床预后的关系。方法回顾性分析我科自2000年1月至2003年5月行经蝶手术切除的具有完整影像学、病理学和随访资料的侵袭性垂体腺瘤82例,随访时间5～30个月。结果侵袭性垂体腺瘤MR影像学特点为鞍底受侵下陷,部分肿瘤突入蝶窦;颈内动脉包绕;海绵窦受累,鞍隔突破等。病理检查以鞍底硬膜浸润的发生率最高。PRL腺瘤的全切率明显低于无功能腺瘤(P<0.01),无功能腺瘤、GH腺瘤与ACTH腺瘤之间相差不明显。PRL腺瘤的复发率较无功能腺瘤和GH腺瘤高(P<0.05)。结论垂体腺瘤的侵袭性生物学行为导致手术全切几率下降,是术后复发的主要原因。     

垂体生长激素腺瘤经蝶手术预后的影响因素分析

目的 探讨垂体生长激素（GH）腺瘤经蝶手术预后的影响因素。方法 回顾性分析60例经蝶手术治疗垂体GH腺瘤患者的临床资料,术后缓解标准为血清IGF-1水平在年龄校正后的正常范围,以及随机血清GH水平<1.0 μg/L或OGTT-GH谷值<0.4 μg/L。结果 术后总缓解率为60%（36/60）。微腺瘤术后缓解率（90.0%）明显高于大腺瘤（46.0%;P<0.05）,非侵袭性腺瘤术后缓解率（73.2%）明显高于侵袭性腺瘤（31.6%;P<0.05）,术前血清GH≤30 μg/L患者术后缓解率（72.5%）明显高于术前血清GH>30 μg/L患者（35.0%;P<0.05）。术后缓解患者术后1 d血清GH水平明显低于未缓解患者（P<0.05）,根据受试者工作特征（ROC）曲线,术前血清GH水平>1.16 μg/L时,判断术后不缓解的敏感度为80.6%,特异度为100%。术后缓解患者术中GH下降程度明显低于未缓解患者（P<0.05）,根据ROC曲线,术中血清GH水平下降程度<40%时,判断术后不缓解的敏感度为79.4%,特异度为61.9%。结论 术前GH水平>30 μg/L、大腺瘤、侵袭性腺瘤是垂体GH腺瘤术后缓解的不良因素;术后1 d血清GH水平<1.16 μg/L对术后缓解具有良好的预测效果;术中血清GH下降程度>40%对术后缓解具有一定的预测效果。     

Preoperative administration of a slow releasing somatostatin analog (SR-lanreotide, BIM 23014) in patients with acromegaly in the course of GH-releasing adenoma]

To evaluate the therapeutic efficacy of slow releasing analogue of somatostatin (SR-Lanreotide) in the pretreatment for GH-releasing adenomas, especially macroadenomas. During the last four years (between January 1996 and December 1999) the authors carried out 382 transsphenoidal operations for to various lesions. There were 169 acromegalic patients in this group. 82 of them received, as pretreatment, the slow releasing analogue of somatostatin (SR-Lanreotide, BIM 23014) in a dose of 30 mg every 14 days for 3 months (6 injections). There were 55 women and 27 men (range 25-68, mean age 44.8 years, SD +/- 10 years) operated on by one experienced neurosurgeon. The concentrations of serum GH--70.5 micrograms/l (range 5.3-500 micrograms/l, SD +/- 83.9 micrograms/l) and IGF-I--1302 micrograms/l (range 610-2030 micrograms/l, SD +/- 360.7 micrograms/l) were high. Out of these 82 patients 79 had macroadenomas with suprasellar and parasellar extension. The volume of the tumours was calculated according to the formula of Di Chiro-Nelson. The mean volume of the tumour was 4146.9 mm3 (range 213.5-38595.3 mm3, SD +/- 5675.9 mm3). The response to the pretreatment suppression of the serum GH, IGF-I level and shrinkage of the tumours--were evaluated before surgery. Second MR examination was performed in 38 pretreated patients. During the Lanreotide treatment mean serum GH level decreased from 70.5 to 15.6 micrograms/l (p < 0.0001), mean serum IGF-I concentration decreased from 1302 to 787 micrograms/l and mean volume of the tumour decreased from 5662 to 2326 mm3 (p < 0.0001). During surgery, tumours were observed to be softer, had liquid consistency and were easier removed. 57 patient (69.5%) who underwent surgery had GH below 5 micrograms/l and were cured. Transsphenoidal microsurgical resection of pituitary adenomas is the primary treatment for acromegaly. Lanreotide pretreatment significantly decreased mean serum GH and IGF-I level, shrinks the tumour and make it much softer and easier to be removed.     

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。     

120例垂体生长激素腺瘤及多激素腺瘤的临床和病理学特点分析

目的分析120例垂体生长激素（GH）腺瘤及多激素腺瘤患者的临床及病理学特征。方法回顾性分析120例免疫组化证实的垂体GH腺瘤及多激素腺瘤患者的临床资料,包括临床表现、生化改变、病理分型及侵袭性等。结果垂体腺瘤的好发年龄为20~50岁,男女发病比约为1：2,主要的临床表现为肢端肥大、头痛头晕、视力下降、视野缺损,女性患者表现有闭经、泌乳或月经紊乱。本组各种类型的垂体腺瘤的侵袭性比例：GH（＋）腺瘤为59.57%（28/47）、GH（＋）及PRL（＋）二种激素混合性瘤为35.48%（11/31）、GH（＋）和ACTH（＋）为33.33%（1/3）、GH（＋）和TSH（＋）为0（0/4）、GH（＋）和LH（＋）为33.33%（1/3）,以及GH（＋）及其它二种以上激素（＋）的多激素腺瘤34.38%（11/32）。单纯GH垂体腺瘤的侵袭性明显高于GH（＋）伴其它激素（＋）的垂体腺瘤的侵袭性（P0.05）。结论本组病例女性多于男性,单纯GH垂体腺瘤侵袭性明显高于其他类型的垂体腺瘤;病理免疫组化提示GH腺瘤除GH（＋）外,常常伴随其他激素（＋）。     

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。     

Surgical Results of Growth Hormone-Secreting Pituitary Adenoma

Objective

We retrospectively analyzed the surgical outcomes of 42 patients with growth hormone (GH)-secreting pituitary adenoma to evaluate the clinical manifestations and to determine which preoperative factors that significantly influence the remission.

Methods

Forty-two patients with GH-secreting pituitary adenoma underwent transsphenoidal surgery (TSS) between 1995 and 2007. The patient group included 23 women and 19 men, with a mean age of 40.2 (range 13-61) years, and a mean follow-up duration of 49.4 (range 3-178) months after the operation. For comparable radiological criteria, we classified parasellar growth into five grades according to the Knosp classification. We analyzed the surgical results of the patients according to the most recent stringent criteria for cure.

Results

The overall rate of endocrinological remission in the group of 42 patients after primary TSS was 64% (26 of 42). The remission rate was 67% (8 of 12) for microadenoma and 60% (18 of 30) for macroadenoma. The remission rate was 30% (3 of 10) for the group with cavernous sinus invasion and 72% (23 of 32) for the group with intact cavernous sinus. Cavernous sinus invasion in Knosp grade III and IV was significantly correlated with the remission rate. There was a significant relationship between preoperative mean GH concentration and early postoperative outcome, with most patients in remission having a lower preoperative GH concentration.

Conclusion

TSS is thought to be an effective primary treatment for GH-secreting pituitary adenomas according to the most recent criteria of cure. Because the remission rate in cases with cavernous sinus invasion is very low, early detection of the tumor before it extends into the cavernous sinus and a long-term endocrinological and radiological follow-up are necessary in order to improve the remission rate of acromegaly.     

生长激素(GH)水平在垂体GH腺瘤缓解及预后判断中的意义

目的 探讨生长激素(GH)水平的测定在垂体GH腺瘤手术缓解及预后判断中的意义.方法 回顾性分析91例经鼻蝶垂体腺瘤切除术的GH腺瘤的病例.分别测定术前、术后1d及1 w空腹垂体激素水平.结果 手术缓解率为67.0％,微腺瘤与大腺瘤缓解率(P＜0.001)、侵袭性与非侵袭性腺瘤缓解率(P＜0.001)、术前各浓度的术后缓解率(P＜0.05)、术中GH下降大于50％组与GH下降不足30％组缓解率(P＜0.01)均有明显差异.鞍内局限组与鞍外扩展组缓解率无明显差异(P＞0.05).术后1d、1 w、1个月激素缓解率无明显差异(P＞0.05).结论 术前、术后早期(术后1w、1个月)GH水平和术中GH下降程度对预后有重要预测价值;手术疗效与肿瘤大小、是否侵袭性生长和术前激素水平显著相关.     

Significance of leptin expression in invasive potential of pituitary adenomas

We immunohistochemically examined the expression of leptin in pituitary adenomas to investigate the correlation between the invasiveness of tumours and leptin expression. The subjects consisted of 79 patients with pituitary adenoma and were classified into the following groups: (1) non-functioning adenomas; (2) GH-secreting adenomas; (3) prolactinomas; (4) ACTH-secreting adenomas; (5) others (LH, FSH or TSH-secreting adenomas). Thereafter all cases were subdivided according to the size of tumour and the presence of invasion to the surrounding tissue. Among non-functioning adenomas, there was no significant difference between invasive and non-invasive non-functioning adenoma. In functioning adenomas, a significant difference in leptin expression was noted in intrasellar non-invasive adenomas compared to other adenomas. There was also a significant difference in leptin expression between non-invasive and invasive adenomas regardless of size. These results suggest that leptin has a role in the invasive potential of functioning adenomas.     

单鼻孔经蝶入路显微手术治疗垂体微腺瘤

目的探讨垂体微腺瘤的诊断和手术方法。方法回顾性分析经单鼻孔蝶窦入路显微手术切除的48例垂体微腺瘤患者的临床资料。此48例垂体微腺瘤中,PRL腺瘤18例,GH腺瘤9例,ACTH腺瘤6例,无分泌功能腺瘤15例。结果肿瘤全切45例,次全切3例;33例分泌腺瘤中,术后激素水平降至正常22例,下降大于50%的6例,5例变化不明显。结论垂体微腺瘤的诊断应结合临床症状、内分泌检测和MR检查结果考虑,经单鼻孔蝶窦入路显微手术是其治疗的理想方法。     

Comparative assessment of the results of different surgical treatments in patients with pituitary adenomas infiltrating the cavernous sinus

Benign pituitary tumors or adenomas are highly common, occasionally inclined to infiltrate the adjacent structures, the cavernous sinus in particular. Despite the fact that drug and radiation therapy are at present widely used treatments, surgical procedures remain highly topical. Different modifications of two basic surgical methods (transcranial intradural and transsphenoidal) that fail to completely remove a tumor from the cavernous sinus in most cases are mostly frequently used as before. Attempts to improve surgical procedures and introduction of current technologies have led to the emergence of an extradural method for tumor removal from the cavernous sinus and to the introduction of endoscopic monitoring during transsphenoidal operations. A strategy of two-stage removal of pituitary tumors has simultaneously been developed. The paper presents the results of surgical treatment of 297 patients with pituitary adenomas growing into the cavernous sinus, by using currently available procedures: transsphenoidal, transcranial intradural, and intra-extradural, and two-stage ones. The findings have confirmed that transsphenoidal removal of pituitary adenomas is the safest method. However, this method has a number of limitations in cases with tumor being grown into the cavernous sinus especially when there is a medial displacement of the intracavernous segment of the internal carotid artery. Moreover, secondary tumor nodes that may be removed by transcranial intradural access are a contraindication to its use. With this, attempts to remove a tumor from the cavernous sinus fail to ensure the desired completeness of removal from the cavernous sinus. The application of an intra-extradural access is the most adequate procedure for tumor removal from the cavernous sinus. The two-stage removal is the most adequate procedure in cases of simultaneously significant spread of a tumor intracranially and into the structures of the base of the skull.     

Ki—67抗原在侵袭性垂体腺瘤中的表达研究

目的 探讨垂体腺瘤中Ki—67抗原表达与垂体腺瘤侵袭性的关系。方法 采用新一代鼠抗人Ki—67单克隆抗体MIB—1免疫组化LSAB法对52例侵袭性垂体腺瘤和35例非侵袭性垂体腺瘤中的Ki—67抗原表达进行检测，以MIB—1增殖细胞指数(MIB—1PCI)表示。结果 侵袭性垂体腺瘤和非侵袭性垂体腺瘤间、海绵窦侵袭腺瘤和无海绵窦侵袭腺瘤间，Ki—67抗原表达有显性差异。结论 Ki—67抗原表达可以作为反映垂体腺瘤增殖潜能、侵袭性和侵袭程度的标志物，具有较大的临床应用价值。     

微血管密度及血管内皮生长因子表达与垂体瘤侵袭性的关系

目的探索垂体瘤微循环与侵袭性的关系及其临床意义。方法采用免疫组化技术检测了42例垂体瘤中血管内皮生长因子(VEGF)蛋白表达,同时染色VonWillebrand因子显示血管内皮细胞以检测肿瘤内微血管密度MVD,分析VEGF蛋白表达及MVD与垂体瘤海绵窦侵袭性的关系。结果VEGF蛋白表达和MVD与垂体瘤的海绵窦侵袭性均有关(两者均P<0.001)。结论VEGF与新生血管形成在垂体瘤的侵袭性生物学行为中具有重要的作用。     

经蝶手术治疗垂体生长激素腺瘤的长期随访

目的评价垂体生长激素腺瘤经蝶手术的疗效,分析影响手术疗效的相关因素。方法回顾性分析162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,根据术后激素水平评价手术疗效。结果术后总缓解率为46.3％;微腺瘤、大微腺、巨腺瘤术后缓解率分别为76．1％、44.3％和13．5％：侵袭性和非侵袭性腺瘤的缓解率则为37．0％和58．6％。手术治疗效果与肿瘤大小、术前生长激素水平及肿瘤的侵袭性相关。结论微腺瘤和非侵袭性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,术后常需药物治疗或放疗。     

Transsphenoidal adenomectomy for GH-, PRL- and ACTH-secreting pituitary tumours: outcome analysis in a series of 125 patients

Abstract Transsphenoidal surgery (TSS) is a well recognised treatment for secreting pituitary adenomas, however a very wide variation of clinical outcomes and recurrence rates has been reported, depending on the different criteria used to define the cure. We reported the clinical outcome of a large series of patients operated on for a secreting pituitary adenoma according to the most recent stringent criteria of biochemical remission nowadays accepted. One hundred and twenty-five consecutive patients with a secreting pituitary adenoma (42 PRL-, 67 GH- and 16 ACTH-secreting adenomas) who were operated on by the two same neurosurgeons were considered for the study. Biochemical remission of disease was achieved in 56% of patients; 78% for patients with microadenoma and 47% for patients with macroadenomas, respectively. No cases of mortality or major immediate postoperative complications were observed. Tumour size, high hormone levels and dural invasion were significantly correlated to a poor surgical outcome. The recurrence rates ranged between 0 and 24%, being higher for PRL-secreting tumours. In conclusion, TSS is safe and effective in secreting pituitary tumours. It is still the first treatment for GH- and ACTH-secreting adenomas, whereas in patients with prolactinomas, surgery should be reserved for cases of resistance or intolerance to dopamine agonists.     

生长激素测定在垂体生长激素腺瘤手术预后判断中的意义

目的探讨生长激素（GH）测定杠垂体GH腺瘤于术预后或远期结果判断中的意义。方法回顾性分析42例垂体GH腺瘤病人的经蝶手术结果。在术前、术后1d及1周空腹检测垂体各轴激素;2005年起,监测26例经蝶手术中不同阶段GH情况。结果本组总缓解率为54．8％（23例）,侵袭性与非侵袭性腺瘤术后缓解率有统计学差异（P=0．008）。术前GH〉30μg／L组与GH≤30μg／L组、术中GH下降大于50％组与GHF降不足30％组、术后早期与术后远期（半年以上）、术后口服糖耐量试验后GH水平（GH／OGTT）≤2．5μg/L组与GH／OGTT〉2．5μg／L组术后缓解率均具有统计学差异（P〈0．05）。结论术前、术后早期（术后10d以内）GH水平和术中GH监测对判断垂体GH腺瘤手术预后有高度预测价值。在判断术后缓解方面,GH／OGTT比空腹GH更具价值。     

影响垂体促肾上腺皮质激素腺瘤经蝶手术后疗效的危险因素分析

目的研究可能影响垂体促肾上腺皮质激素（ACTH）腺瘤经蝶手术后疗效的危险因素。方法对1999年至2008年收治的垂体ACTH腺瘤经蝶手术的102例患者的临床资料进行回顾性研究。结果垂体ACTH腺瘤经蝶手术后疗效可能与肿瘤切除方式和肿瘤病理类型相关（P〈0.05）,而与肿瘤大小、术前24h尿游离激素水平无关（P〉0.05）。结论肿瘤的切除方式和肿瘤病理类型是影响垂体ACTH腺瘤经蝶手术后疗效的危险因素。     

经硬膜外入路显微切除巨大鞍旁侵袭性垂体瘤

目的 提高巨大鞍旁侵袭性垂体瘤的手术效果。方法 回顾性分析我科自1995年2月～2000年8月间收治的18例巨大鞍旁侵袭性垂体瘤患者。肿瘤直径3．0～65mm(平均4．5cm),均采用前中颅底联合硬膜外入路进行手术。结果 肿瘤全切除、次全切除及大部切除分别为78％(14／18)、17％(3／18)、5％(1／18),并发症以第Ⅱ～Ⅵ颅神经麻痹、尿崩及下丘脑反应多见,无手术死亡。结论 巨大鞍旁侵袭性垂体瘤可经前中颅底联合硬膜外入路一次性全切除,手术成功的关键是充分翻开额底、中颅底及海绵窦外侧壁硬膜,并能从视神经内、外及海绵窦不同解剖间隙内显露和切除肿瘤。     

Secretory granules of pituitary adenomas: quantitative study of hormonal antigenicity

Ultrastructurally, the antigenicity of major pituitary hormones in secretory granules was quantitatively investigated in five growth hormone (GH)-secreting adenomas, five prolactin (PRL)-secreting adenomas and eight clinically non-functioning (CN-F) adenomas. Sparsely granulated cells with a few or several small secretory granules (60–100 nm) exhibiting little or only weak antigenicity of various biochemically unrelated hormones were commonly observed in CN-F adenomas and occasionally in GH- and PRL-secreting adenomas. GH- or PRL-secreting adenomas consisted of many densely granulated cells with medium-sized (200–250 nm) or large (over 250 nm) secretory granules and a few or several sparsely granulated cells with small secretory granules. The densely granulated cells showed intense GH or PRL antigenicity and slight to moderate antigenicity for other hormones in large secretory granules and little or only weak antigenicity for various hormones including GH or PRL in small secretory granules. Their secretory granules larger than 160 nm or 140 nm significantly exhibited intense GH or PRL antigenicity (Fisher’s exact test; P < 0.05 and < 0.01, respectively). Two CN-F adenomas showed sparsely and densely granulated cells as well as intermediate cells. The densely granulated cells closely resembled GH-secreting cells. The intermediate cells simultaneously included small and medium-sized or large secretory granules exhibiting little/slight and intense GH-antigenicity, respectively. This study indicates that sparsely granulated cells of different categories showing slight antigenicity for various hormones, antigenically share the same origin, and that their hormonality, single or multiple, may be selectively activated in the developmental course of secretory granules. Received: 21 January 1999 / Revised, accepted: 13 July 1999     

A further study on the stimulatory effect of peptide histidine methionine on growth hormone secretion in acromegaly: a dose-related study and a comparison with vasoactive intestinal peptide.

We examined whether the GH-releasing effect of peptide histidine methionine (PHM) in acromegaly may be mediated by activation of pituitary receptors for vasoactive intestinal peptide (VIP), which is structurally similar to but more powerful than PHM in stimulating GH secretion in acromegaly. VIP (50 or 100 micrograms) or PHM (50, 100, or 200 micrograms) was given as an i.v. bolus to 11 patients with active acromegaly, and plasma GH levels were measured before and at intervals up to 120 min after the injection. A paradoxical GH response (> 50% and > 6 micrograms/l above the basal) to 50 or 100 micrograms of VIP was observed in 4 (36%) or 5 (45%) patients, respectively. 2 (18%) patients showed paradoxical GH responses to both 50 and 100 micrograms of PHM, and, interestingly, as many as 5 (45%) patients showed positive GH responses to 200 micrograms of PHM. 3 of these 5 responders to 200 micrograms of PHM were also responders to both doses of VIP. To add to, one of the responders to 100 micrograms of VIP did not show a positive GH response to even 200 micrograms of PHM. These results may suggest that in at least some acromegalics the PHM stimulation of GH secretion is mediated by activation of pituitary VIP receptors by PHM and/or by PHM binding to its specific receptors which may have appeared concomitantly with VIP receptors. However, the occasional heterogeneity of the VIP- and PHM-induced GH responses may suggest that on some somatotroph adenomas either VIP or PHM receptors may appear independently.