颅咽管瘤显微外科治疗后的远期疗效与相关因素分析
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摘要
目的本文通过比较颅咽管瘤患者不同治疗结果(术中全切除肿瘤、垂体柄保留与否)在术后远期疗效上的差异,初步探讨颅咽管瘤最佳治疗方案。
方法回顾性分析2003年2月至2012年9月由中南大学湘雅医院袁贤瑞教授连续主刀完成的168例颅咽管瘤患者,同时进行长期随访,记录其生存状况、肿瘤复发情况、内分泌、代谢、视力视野及生活质量,并运用统计学方法进行相关因素分析。
结果本组患者手术全切除率达92.9%(156/168),围手术期死亡率为1.2%(2/168),全切除肿瘤且保留垂体柄32例(19%)。
随访患者151例,平均随访时间为46.4个月,5年总体生存率为90%,Cox模型显示未全切肿瘤患者术后死亡风险为全切除的4.7倍,女性患者术后死亡风险为男性的4.2倍。
至随访截止,有14例患者出现肿瘤复发,在访134例患者的5年肿瘤无复发率为90.2%,151例患者的5年肿瘤无进展生存率为83.1%,Cox模型显示未全切肿瘤患者肿瘤复发风险为全切除的9.4倍,肿瘤起源部位为鞍内的患者复发风险是起源部位为垂体柄的4.2倍。
全切除肿瘤且保留垂体柄的患者5年生存率(100%)明显高于垂体柄未得到保留的患者(86.8%)(P=0.048),但前者的5年肿瘤无复发率(82.5%)与后者的(90.5%)无统计学差异(P=0.325)。
内分泌方面,下丘脑-垂体-肾上腺轴、下丘脑-垂体-甲状腺轴、下丘脑-垂体-性腺轴、生长激素、催乳素的异常率及尿崩率在手术前后不同,受手术的影响也不同,术前异常率为27.6-78.9%,术后远期异常率为51.6-89.2%,新出现异常率为33.3-77.1%,好转率为0-28.9%,术后远期异常率较术前有明显升高的有下丘脑-垂体-肾上腺轴、下丘脑-垂体-甲状腺轴及生长激素(P<0.05)。在术前相应激素轴正常的前提下,垂体柄得到保留的患者术后远期HPA (T)轴正常率高于垂体柄未得到保留的患者。
代谢方面,术后远期有32.5%患者出现超重,10.4%患者存在肥胖。术后远期血糖、甘油三酯及胆固醇较术前有显著升高(P<0.05),重复测量方差分析结果显示“手术切除程度”及“垂体柄保留与否”作为干预主效应无统计学意义(P>0.05)。
视觉方面,术后远期视力异常率(45.6%)与术前(47.1%)相比没有明显改变(P>0.05),而术后远期视野异常率(70.6%)较术前(47.1%)明显升高(P=0.005)。
生活质量方面,KPS (Karnofsky performance scale)分级显示本组患者术后生活质量优良率达82.1%,其中获肿瘤全切除患者术后生活质量(平均76.6分)优于未全切除肿瘤患者(平均41.8分)(P<0.001),垂体柄得到保留与未得到保留的患者之间的术后KPS(分别为82、73.1分)无统计学差异(P>0.05)。
结论：
1、实现颅咽管瘤的全切除是延长术后生存时间、降低肿瘤复发率和提高生活质量的有利因素。
2、根据显微镜下判断,未瘤化的垂体柄的保留并不增加肿瘤复发的风险。在术前内分泌功能正常的前提下,未瘤化垂体柄得到保留的患者在术后远期有较好的内分泌功能。保留未瘤化的垂体柄有利于患者术后的长期生存。
3、垂体柄因根治性治疗需要而切除的患者,其术后机体代谢和生活质量与垂体柄保留的患者无明显差异,且肿瘤复发率低。
Object:The optimal management of craniopharyngioma remains controversial. To explore the optimal operation strategy, this dissertation analyzes the differences in long-term results between different therapeutic outcomes (total resection, preservation of pituitary stalk or not) in a continuous series of patients who have undergone resection of craniopharyngioma.
Methods:A retrospective analysis and long-term follow-up were performed in168consecutive patients who underwent microsurgery of craniopharyngioma performed by the same senior surgeon between2003and2012. The patients' general information and operation data, especially the extent of resection and involvement of pituitary stalk (PS), were recorded. During the follow-up, the status of survival, tumor progression, endocrine, metabolism, visual outcomes and quality of life were noted and the factors related to them were analyzed.
Results:
Among the168patients,156patients (92.9%) received gross-total resection (GTR), including32patients (20.5%) whose pituitary stalks were preserved.2patients died during the perioperative period (1.2%).
17patients were lost to follow-up. Thus, the follow-up data were obtained on151patients. The average follow-up time is46.4months and the five-year overall survival (OS) rate is90.2%. Cox shows that the mortality risk of the patients who didn't receive GTR is4.7times that of the patients who received GTR. Meanwhile, the mortality risk of the female is4.2times that of the male.
By the end of the follow-up,14patients had tumor progression. The five-year progression-free rate is90.2%and the five-year progression-free survival (PFS) rate is83.1%. Cox model reveals that the recurrent risk of the patients who didn't receive GTR is9.4times that of the patients who received GTR. And the recurrent risk of the patients whose tumor originated from intra-seller is4.2times that of the patients whose tumor originated from PS.
In our series, the group with preserved pituitary stalks has a higher long-term survival rate (100%) than the group without (86.8%), but there is not statistical difference in their tumor progression rates (P=0.325).
In endocrine, hypothalamus-pituitary-adrenal (HPA) axis, hypothalamic-pituitary-thyroid (HPT) axis, hypothalamic-pituitary-gonadal (HPG) axis, growth hormone (GH), prolactin (PRL) and diabetes insipidus (DI) had different degrees of abnormities before and after operation, and they were impacted by surgery to different extent. The abnormal rate is27.6-78.9%before operation but51.6-89.2%in the late postoperative period. The rates of new abnormalities range from33.3%to77.1%and the improvement rates are between0and28.9%. Obvious rises in the abnormal rates are detected only in HPA, HPT and GH between the preoperative period and the late postoperative period (P<0.05). With the corresponding hormone axes being normal before the operation, the normal rate of the group with preserved PSs is higher than that of the patients whose PSs were resected.
In terms of metabolic function, overweight occurs in32.5%of the patients, and obesity10.4%. There are significant rises in the laboratory indexes of blood glucose, triglyceride and cholesterol. In repeated measures analysis of variance,"the extent of resection" and "the management of PS" as the main intervention are not statistically significant.
The abnormal rates of visual acuity in the late postoperative period (45.6%) do not change significantly compared with that before operation (47.1%). Meanwhile, the rate of abnormality of visual field in the late postoperative period (70.6%) has a significant increase (P=0.005).
KPS classification reveals that the quality of life after resection of craniopharyngioma was good or excellent in82.1%of the cases; the patients who received GTR (average score:76.6) have better performance than the patients who didn't (average score:41.8)(P<0.001); there is no significant difference (P=0.085) in KPS of the late postoperative period between the patients with their PSs preserved and the ones without (the average scores were82and73.1, respectively).
Conclusions:
1Gross-total resection of craniopharyngioma makes positive contribution to the improvement of long-term survival, tumor progression-free rate and quality of life.
2Preservation of the PS which shows no tumor infiltration under the microscope does not increase the risk of tumor progression. Patients with a preserved pituitary stalk show better neuroendocrine functions to some degree, but the precondition is that the pre-operative endocrine functions are not completely destroyed. Preservation of PS benefits the patients'long-term survival and quality of life after the operation.
3The patients whose PSs were resected for the need of radical treatment, have a low recurrence rate, and show no significant differences in metabolism and quality of life with the patients with their PSs preserved.
方法回顾性分析2003年2月至2012年9月由中南大学湘雅医院袁贤瑞教授连续主刀完成的168例颅咽管瘤患者,同时进行长期随访,记录其生存状况、肿瘤复发情况、内分泌、代谢、视力视野及生活质量,并运用统计学方法进行相关因素分析。
结果本组患者手术全切除率达92.9%(156/168),围手术期死亡率为1.2%(2/168),全切除肿瘤且保留垂体柄32例(19%)。
随访患者151例,平均随访时间为46.4个月,5年总体生存率为90%,Cox模型显示未全切肿瘤患者术后死亡风险为全切除的4.7倍,女性患者术后死亡风险为男性的4.2倍。
至随访截止,有14例患者出现肿瘤复发,在访134例患者的5年肿瘤无复发率为90.2%,151例患者的5年肿瘤无进展生存率为83.1%,Cox模型显示未全切肿瘤患者肿瘤复发风险为全切除的9.4倍,肿瘤起源部位为鞍内的患者复发风险是起源部位为垂体柄的4.2倍。
全切除肿瘤且保留垂体柄的患者5年生存率(100%)明显高于垂体柄未得到保留的患者(86.8%)(P=0.048),但前者的5年肿瘤无复发率(82.5%)与后者的(90.5%)无统计学差异(P=0.325)。
内分泌方面,下丘脑-垂体-肾上腺轴、下丘脑-垂体-甲状腺轴、下丘脑-垂体-性腺轴、生长激素、催乳素的异常率及尿崩率在手术前后不同,受手术的影响也不同,术前异常率为27.6-78.9%,术后远期异常率为51.6-89.2%,新出现异常率为33.3-77.1%,好转率为0-28.9%,术后远期异常率较术前有明显升高的有下丘脑-垂体-肾上腺轴、下丘脑-垂体-甲状腺轴及生长激素(P<0.05)。在术前相应激素轴正常的前提下,垂体柄得到保留的患者术后远期HPA (T)轴正常率高于垂体柄未得到保留的患者。
代谢方面,术后远期有32.5%患者出现超重,10.4%患者存在肥胖。术后远期血糖、甘油三酯及胆固醇较术前有显著升高(P<0.05),重复测量方差分析结果显示“手术切除程度”及“垂体柄保留与否”作为干预主效应无统计学意义(P>0.05)。
视觉方面,术后远期视力异常率(45.6%)与术前(47.1%)相比没有明显改变(P>0.05),而术后远期视野异常率(70.6%)较术前(47.1%)明显升高(P=0.005)。
生活质量方面,KPS (Karnofsky performance scale)分级显示本组患者术后生活质量优良率达82.1%,其中获肿瘤全切除患者术后生活质量(平均76.6分)优于未全切除肿瘤患者(平均41.8分)(P<0.001),垂体柄得到保留与未得到保留的患者之间的术后KPS(分别为82、73.1分)无统计学差异(P>0.05)。
结论：
1、实现颅咽管瘤的全切除是延长术后生存时间、降低肿瘤复发率和提高生活质量的有利因素。
2、根据显微镜下判断,未瘤化的垂体柄的保留并不增加肿瘤复发的风险。在术前内分泌功能正常的前提下,未瘤化垂体柄得到保留的患者在术后远期有较好的内分泌功能。保留未瘤化的垂体柄有利于患者术后的长期生存。
3、垂体柄因根治性治疗需要而切除的患者,其术后机体代谢和生活质量与垂体柄保留的患者无明显差异,且肿瘤复发率低。
Object:The optimal management of craniopharyngioma remains controversial. To explore the optimal operation strategy, this dissertation analyzes the differences in long-term results between different therapeutic outcomes (total resection, preservation of pituitary stalk or not) in a continuous series of patients who have undergone resection of craniopharyngioma.
Methods:A retrospective analysis and long-term follow-up were performed in168consecutive patients who underwent microsurgery of craniopharyngioma performed by the same senior surgeon between2003and2012. The patients' general information and operation data, especially the extent of resection and involvement of pituitary stalk (PS), were recorded. During the follow-up, the status of survival, tumor progression, endocrine, metabolism, visual outcomes and quality of life were noted and the factors related to them were analyzed.
Results:
Among the168patients,156patients (92.9%) received gross-total resection (GTR), including32patients (20.5%) whose pituitary stalks were preserved.2patients died during the perioperative period (1.2%).
17patients were lost to follow-up. Thus, the follow-up data were obtained on151patients. The average follow-up time is46.4months and the five-year overall survival (OS) rate is90.2%. Cox shows that the mortality risk of the patients who didn't receive GTR is4.7times that of the patients who received GTR. Meanwhile, the mortality risk of the female is4.2times that of the male.
By the end of the follow-up,14patients had tumor progression. The five-year progression-free rate is90.2%and the five-year progression-free survival (PFS) rate is83.1%. Cox model reveals that the recurrent risk of the patients who didn't receive GTR is9.4times that of the patients who received GTR. And the recurrent risk of the patients whose tumor originated from intra-seller is4.2times that of the patients whose tumor originated from PS.
In our series, the group with preserved pituitary stalks has a higher long-term survival rate (100%) than the group without (86.8%), but there is not statistical difference in their tumor progression rates (P=0.325).
In endocrine, hypothalamus-pituitary-adrenal (HPA) axis, hypothalamic-pituitary-thyroid (HPT) axis, hypothalamic-pituitary-gonadal (HPG) axis, growth hormone (GH), prolactin (PRL) and diabetes insipidus (DI) had different degrees of abnormities before and after operation, and they were impacted by surgery to different extent. The abnormal rate is27.6-78.9%before operation but51.6-89.2%in the late postoperative period. The rates of new abnormalities range from33.3%to77.1%and the improvement rates are between0and28.9%. Obvious rises in the abnormal rates are detected only in HPA, HPT and GH between the preoperative period and the late postoperative period (P<0.05). With the corresponding hormone axes being normal before the operation, the normal rate of the group with preserved PSs is higher than that of the patients whose PSs were resected.
In terms of metabolic function, overweight occurs in32.5%of the patients, and obesity10.4%. There are significant rises in the laboratory indexes of blood glucose, triglyceride and cholesterol. In repeated measures analysis of variance,"the extent of resection" and "the management of PS" as the main intervention are not statistically significant.
The abnormal rates of visual acuity in the late postoperative period (45.6%) do not change significantly compared with that before operation (47.1%). Meanwhile, the rate of abnormality of visual field in the late postoperative period (70.6%) has a significant increase (P=0.005).
KPS classification reveals that the quality of life after resection of craniopharyngioma was good or excellent in82.1%of the cases; the patients who received GTR (average score:76.6) have better performance than the patients who didn't (average score:41.8)(P<0.001); there is no significant difference (P=0.085) in KPS of the late postoperative period between the patients with their PSs preserved and the ones without (the average scores were82and73.1, respectively).
Conclusions:
1Gross-total resection of craniopharyngioma makes positive contribution to the improvement of long-term survival, tumor progression-free rate and quality of life.
2Preservation of the PS which shows no tumor infiltration under the microscope does not increase the risk of tumor progression. Patients with a preserved pituitary stalk show better neuroendocrine functions to some degree, but the precondition is that the pre-operative endocrine functions are not completely destroyed. Preservation of PS benefits the patients'long-term survival and quality of life after the operation.
3The patients whose PSs were resected for the need of radical treatment, have a low recurrence rate, and show no significant differences in metabolism and quality of life with the patients with their PSs preserved.
引文
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[1]NIELSEN E H, FELDT-RASMUSSEN U, POULSGAARD L, et al. Incidence of craniopharyngioma in Denmark (n= 189) and estimated world incidence of craniopharyngioma in children and adults [J]. Journal of neuro-oncology,2011, 104(3):755-63.
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