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Ectopic Adrenocorticotropic Hormone Syndrome Caused by Thoracic Neuroendocrine Tumors: Surgical Treatment and Prognosis Factors
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摘要:
目的 探讨胸部神经内分泌肿瘤所致异位促肾上腺皮质激素综合征(ectopic adrenocorticotropic hormone syndrome, EAS)的手术诊治经验, 并分析相关预后因素。 方法 1983年12月至2013年12月北京协和医院收治并经手术病理证实的胸部神经内分泌肿瘤引起的EAS 33例, 其中男性20例, 女性13例, 回顾其临床表现、影像学资料、手术为主的综合治疗方案、围手术期并发症及随访情况, 计算生存期并分析相关的预后因素。 结果 33例患者就诊时中位年龄33岁(13~65岁), 中位病程12个月(1~156个月)。所有患者均存在库欣综合征的临床表现, 均由胸部CT定位病变来源。手术治疗后血清皮质醇及促肾上腺皮质激素浓度明显下降(P < 0.05)。围手术期死亡1例(1/33, 3.0%), 术后出现并发症2例(2/33, 6.1%)。33例患者5年存活率为65.8%, 其中病变来源于肺部患者的5年存活率明显优于病变来源于胸腺患者(84.2%比36.3%, P < 0.05)。类癌与不典型类癌5年存活率分别为76.2%和45.7%(P=0.056);Ⅰ-Ⅱ期病变与Ⅲ-Ⅳ期病变5年存活率分别为80.0%和50.5%(P=0.072)。 结论 胸部神经内分泌肿瘤所致EAS早期诊断及治疗存在较大难度, 胸部CT是病变定位的最佳方法, 肺部病变预后明显优于胸腺来源病变, 病理类型及分期可能是影响其预后的因素。 -
关键词:
- 胸腔 /
- 神经内分泌肿瘤 /
- 异位, 促肾上腺皮质激素综合征 /
- 手术治疗 /
- 预后
Abstract:Objective To discuss the surgical management and prognosis factors of ectopic adrenocorticotropic hormone syndrome (EAS) caused by thoracic neuroendocrine tumors(NETs). Methods The clinical manifestations, radiological findings, outcome of surgical treatment and follow-up of consecutive 33 cases(20 males and 13 females) of EAS caused by thoracic NETs from December 1983 to December 2013 in Peking Union Medical College Hospital were retrospectively analyzed. Results The median age was 33 years old (13~65 years)and the median duration of disease was 12 months(1~156 months). Cushing's syndrome was demonstrated in all cases by clinical and biochemical evidences. All the thoracic NETs were located by computed tomography (CT) eventually. The serum cortisol and adrenocorticotropic hormone levels decreased significantly after surgery(both P < 0.05).One patient(3.0%) died after surgery and two patients(6.1%) had postoperative complications.The overall 5-year survival rate was 65.8%.Pulmonary diseases had better survival rate versus thymic diseases(84.2% vs. 36.3%, P < 0.05).The 5-year survival rate was 76.2% in typical carcinoid and 45.7% in atypical carcinoid(P=0.056).The 5-year survival rate was 80.0% in stage Ⅰ and Ⅱ, 50.5% in stage Ⅲ and Ⅳ respectively(P=0.072). Conclusions Due to the varity and atypical clinical features, early diagnosis and therapy in EAS is very challenging for clinicians. CT scan plays a key role in localization of the thoracic NETs. Pulmonary diseases have better prognosis than thymic diseases.Pathological type and stage of tumors might be prognostic factors for this rare syndrome. -
Key words:
- thorax /
- neuroendocrine tumors /
- ectopic adrenocorticotropic hormone syndrome /
- surgery /
- prognosis
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图 3 33例胸部神经内分泌肿瘤所致异位促肾上腺皮质激素综合征患者Kaplan-Meier生存曲线分析图
A.全组患者生存曲线；B.胸腺与肺部来源病变生存曲线比较；C.类癌与不典型类癌生存曲线比较；D.肿瘤分期(Ⅰ-Ⅱ期与Ⅲ-Ⅳ期)生存曲线比较
表 1 33例胸部神经内分泌肿瘤所致异位促肾上腺皮质激素综合征患者主要临床症状(n=33)
临床症状 肺部来源 胸腺来源 P值 性别[男/女(N)] 12/7(19) 8/6(14) 0.50 中位年龄[M(Q), 岁] 37 (30~44) 29 (23~42) 0.14 低钾血症[%(n/N)] 89.5(17/19) 92.8(13/14) 0.62 高血压[%(n/N)] 78.9(15/19) 57.1(8/14) 0.17 血糖异常[%(n/N)] 63.2(12/19) 64.3(9/14) 0.62 多血质面容[%(n/N)] 47.4(9/19) 71.4(10/14) 0.15 向心性肥胖[%(n/N)] 68.4(13/19) 64.3(9/14) 0.55 水牛背[%(n/N)] 73.7(14/19) 71.4 (10/14) 0.60 满月脸[%(n/N)] 73.7(14/19) 71.4 (10/14) 0.60 皮肤痤疮[%(n/N)] 47.4(9/19) 57.1(8/14) 0.42 肢体无力[%(n/N)] 42.1(8/19) 57.1(8/14) 0.31 
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表 2 33例胸部神经内分泌肿瘤所致异位促肾上腺皮质激素综合征患者内分泌检查及病理
项目 肺部来源(n=19) 胸腺来源(n=14) P值 血皮质醇[M(Q), μg/dl] 术前 37.0(22.6~58.3) 41.6(34.0~67.8) 0.27 术后 6.8(2.4~10.1) 8.7(6.9~14.6) 0.10 ACTH[M(Q), pg/ml] 术前 214.5(141.3~340.5) 197.0(143.5~778.0) 0.73 术后 23.8(13.9~37.1) 86.0(20.2~37.3) 0.03 HDDST(被抑制/不被抑制) 5/12 2/12 0.29 奥曲肽显像(阳性/阴性) 4/6 6/1 0.08 肿瘤最大径[M(Q), cm)] 2.0(1.2~2.5) 4.0(3.0~6.2) 0.00 TC/ATC 17/2 4/10 0.00 分期*(Ⅰ-Ⅱ期/Ⅲ-Ⅳ期) 10/4 5/9 0.06 19例肺部来源病变中14例获得TNM分期; ACTH：促肾上腺皮质激素；HDDST：大剂量地塞米松抑制试验; TC:典型类癌；ATC：不典型类癌
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[1] Han B, Sun JM, Ahn JS, et al.Clinical outcomes of atypical carcinoid tumors of the lung and thymus:7-year experience of a rare malignancy at single institute[J]. Med Oncol, 2013, 30:479. doi: 10.1007/s12032-013-0479-x [2] Oberg K, Hellman P, Ferolla P, et al. Neuroendocrine bronchial and thymic tumors:ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up[J]. Ann Oncol, 2012, 23 Suppl 7:120-123. https://academic.oup.com/annonc/article/23/suppl_7/vii120/144890 [3] Yao JC, Hassan M, Phan A, et al.One hundred years after "carcinoid":epidemiology of and prognostic factors for neuroendocrine tumors in 35, 825 cases in the United States[J]. J Clin Oncol, 2008, 26:3063-3072. doi: 10.1200/JCO.2007.15.4377 [4] Phan AT, Oberg K, Choi J, et al.NANETS consensus guideline for the diagnosis and management of neuroendocrine tumors:well-differentiated neuroendocrine tumors of the thorax (includes lung and thymus)[J]. Pancreas, 2010, 39:784-798. doi: 10.1097/MPA.0b013e3181ec1380 [5] Travis WD, Brambilla E, Müller-Hermelink, et al.Pathology and Genetics of Tumours of the Lung, Pleura, Thymus and Heart (WHO Classification of Tumours)[M]. Lyon, France:IARC Press, 2004:145-247. [6] Lacroix A, Feelders RA, Stratakis CA, et al. Cushing's syndrome[J]. Lancet, 2015, 386:913-927. doi: 10.1016/S0140-6736(14)61375-1 [7] Lababede O, Meziane M, Rice T.Seventh edition of the cancer staging manual and stage grouping of lung cancer:quick reference chart and diagrams[J]. Chest, 2011, 139:183-189. doi: 10.1378/chest.10-1099 [8] Detterbeck FC, Nicholson AG, Kondo K, et al.The Masaoka-Koga stage classification for thymic malignancies:clarification and definition of terms[J]. J Thorac Oncol, 2011, 6:S1710-S1716. doi: 10.1097/JTO.0b013e31821e8cff [9] Alexandraki KI, Grossman AB.The ectopic ACTH syndrome[J]. Rev Endocr Metab Disord, 2010, 11:117-126. doi: 10.1007/s11154-010-9139-z [10] Isidori AM, Lenzi A.Ectopic ACTH syndrome[J]. Arq Bras Endocrinol Metabol, 2007, 51:1217-1225. doi: 10.1590/S0004-27302007000800007 [11] Ejaz S, Vassilopoulou-Sellin R, Busaidy NL, et al. Cushing syndrome secondary to ectopic adrenocorticotropic hormone secretion:the University of Texas MD Anderson Cancer Center Experience[J]. Cancer, 2011, 117:4381-4389. doi: 10.1002/cncr.26029 [12] Liddle GW, Nicholson WE, Island DP, et al. Clinical and laboratory studies of ectopic humoral syndromes[J]. Recent Prog Horm Res, 1969, 25:283-314. http://www.ncbi.nlm.nih.gov/pubmed/4310919 [13] Wajchenberg BL, Mendonca B, Liberman B, et al. Ectopic ACTH syndrome[J]. J Steroid Biochem Mol Biol, 1995, 53:139-151. doi: 10.1016/0960-0760(95)00044-Z [14] Isidori AM, Kaltsas GA, Pozza C, et al. The ectopic adrenocorticotropin syndrome:clinical features, diagnosis, management, and long-term follow-up[J]. J Clin Endocrinol Metab, 2006, 91:371-377. doi: 10.1210/jc.2005-1542 [15] Aniszewski JP, Young WF, Thompson GB, et al. Cushing syndrome due to ectopic adrenocorticotropic hormone secretion[J]. World J Surg, 2001, 25:934-940. doi: 10.1007/s00268-001-0032-5 [16] Beuschlein F, Hammer GD.Ectopic pro-opiomelanocortin syndrome[J]. Endocrinol Metab Clin North Am, 2002, 31:191-234. doi: 10.1016/S0889-8529(01)00025-1 [17] 卢琳, 顾锋, 张晓波, 等.岩下窦静脉取血在疑难ACTH依赖性库欣综合征诊断中的应用[J].中华神经外科杂志, 2009, 25:1110-1113. doi: 10.3760/cma.j.issn.1001-2346.2009.012.022 [18] Findling JW, Kehoe ME, Shaker JL, et al. Routine inferior petrosal sinus sampling in the differential diagnosis of adrenocorticotropin (ACTH)-dependent Cushing's syndrome:early recognition of the occult ectopic ACTH syndrome[J]. J Clin Endocrinol Metab, 1991, 73:408-413. doi: 10.1210/jcem-73-2-408 [19] De Herder WW, Lamberts SW.Octapeptide somatostatin-analogue therapy of Cushing's syndrome[J]. Postgrad Med J, 1999, 75:65-66. doi: 10.1136/pgmj.75.880.65 [20] Salgado LR, Fragoso MC, Knoepfelmacher M, et al. Ectopic ACTH syndrome:our experience with 25 cases[J]. Eur J Endocrinol, 2006, 155:725-733. doi: 10.1530/eje.1.02278 [21] Noel-Savina E, Descourt R.Focus on treatment of lung carcinoid tumor[J]. Oncol Targets Ther, 2013, 6:1533-1537. http://www.ncbi.nlm.nih.gov/pubmed/24187503 [22] Crona J, Bjorklund P, Welin S, et al. Treatment, prognostic markers and survival in thymic neuroendocrine tumours. a study from a single tertiary referral centre[J]. Lung Cancer, 2013, 79:289-293. doi: 10.1016/j.lungcan.2012.12.001 [23] 陈野野, 刘洪生, 李单青, 等.胸腺神经内分泌肿瘤手术治疗及预后因素[J].协和医学杂志, 2016, 7:190-194. doi: 10.3969/j.issn.1674-9081.2016.03.006 [24] Neary NM, Lopez-Chavez A, Abel BS, et al. Neuroendocrine ACTH-producing tumor of the thymus-experience with 12 patients over 25 years[J]. J Clin Endocrinol Metab, 2012, 97:2223-2230. doi: 10.1210/jc.2011-3355 [25] Kyriss T, Maier S, Veit S, et al. Carcinoid lung tumors:long-term results from 111 resections[J]. Thorac Surg Sci, 2006, 3:Doc03. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3011338/ [26] Gaur P, Leary C, Yao JC.Thymic neuroendocrine tumors:a SEER database analysis of 160 patients[J]. Ann Surg, 2010, 251:1117-1121. doi: 10.1097/SLA.0b013e3181dd4ec4 [27] Garcia-Yuste M, Matilla JM, Cueto A, et al. Typical and atypical carcinoid tumours:analysis of the experience of the Spanish multi-centric study of neuroendocrine tumours of the lung[J]. Eur J Cardiothorac Surg, 2007, 31:192-197. doi: 10.1016/j.ejcts.2006.11.031 [28] Moran CA, Suster S.Neuroendocrine carcinomas (carcinoid tumor) of the thymus. A clinicopathologic analysis of 80 cases[J]. Am J Clin Pathol, 2000, 114:100-110. http://med.wanfangdata.com.cn/Paper/Detail/PeriodicalPaper_JJ021061893 [29] Cardillo G, Rea F, Lucchi M, et al. Primary neuroendocrine tumors of the thymus:a multicenter experience of 35 patients[J]. Ann Thorac Surg, 2012, 94:241-246. doi: 10.1016/j.athoracsur.2012.03.062 [30] Oberg K. Chemotherapy and biotherapy in the treatment of neuroendocrine tumours[J]. Ann Oncol, 2001, 12 Suppl 2:S111-S114. http://www.ncbi.nlm.nih.gov/pubmed/11762335 -
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