陈野野;李单青;田震寰;周小昀;何嘉;张晔;刘洪生;
CHEN Ye-ye;LI Shan-qing;TIAN Zhen-huan;ZHOU Xiao-yun;HE Jia;ZHANG Ye;LIU Hong-sheng;Department of Thoracic Surgery,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences &Peking Union Medical College;

• 1:中国医学科学院北京协和医学院北京协和医院胸外科

摘要(Abstract)：

目的探讨肺大细胞神经内分泌癌(large cell neuroendocrine carcinoma,LCNEC)的临床特点及手术治疗经验并分析相关预后因素。方法 2000年1月至2014年1月在北京协和医院诊治并经手术病理证实为LCNEC的患者35例,其中男性29例,女性6例,回顾性总结其临床资料,分析以手术为主综合治疗的结局并分析相关预后因素。结果 35例患者就诊时中位年龄为63岁(47~77岁),中位病程为2个月(1~14个月)。临床症状不具特异性,术前活检病理难以明确诊断。手术方法根据肿瘤具体情况采用开胸或胸腔镜下肺叶切除及淋巴结清扫。术后病理分期Ⅰ期12例,Ⅱ期7例,Ⅲ期13例,Ⅳ期3例。23例患者行辅助治疗。患者中位生存期17个月(95%CI:11.4~22.6),1、3、5年生存率分别为60.6%、29.0%、24.8%。肿瘤分期对LCNEC患者生存期存在显著影响(Cox多因素分析HR 2.608,95%CI:1.572~4.327,P=0.000)。结论 LCNEC为一种罕见的侵袭性强、预后差的恶性肿瘤,分期是影响其预后的独立危险因素,对于早期病变尤其是Ⅰ、Ⅱ期病变采用手术为主的综合治疗可获得较好的治疗效果。
Objective To investigate the clinical manifestations,outcomes after surgical management,and prognostic factors of large cell neuroendocrine carcinoma( LCNEC) of the lung. Methods We retrospectively analyzed the data of 35 consecutive cases( 29 males,6 females) of LCNEC of the lung surgically treated and pathologically confirmed in Peking Union Medical College Hospital from January 2000 to January 2014. Their outcomes after receiving surgery-based comprehensive therapy and related prognostic factors were explored.Results The median age of patients was 63( 47- 77) years and the median duration of disease was 2( 1- 14)months. No specific symptom was found and preoperative pathological diagnosis was not definitive. Surgical methods included open or thoracoscopic lobectomy and lymph node dissection based on the specific conditions of tumor in each case. Postoperative pathological staging showed stageⅠin 12 cases,stage Ⅱin 7,stage Ⅲ in 13,and stage Ⅳin 3. Twenty-three patients received adjuvant therapy. Median survival was 17 months [95% confidence interval( CI) : 11. 4-22. 6 months]. The 1-year,3-year,and 5-year survival rates were 60. 6%,29. 0%,and 24. 8%,respectively. Tumor stage was significantly related with the overall survival( Cox regression analysis,hazard ration =2. 608,95% CI: 1. 572- 4. 327,P = 0. 000). Conclusions LCNEC is a rare malignancy with tremendous aggressiveness and poor prognosis. Stage of tumor may be the independent risk factor affecting the prognosis. Surgerybased comprehensive therapy could achieve good survival for patients of early stages,especially stagesⅠand Ⅱ.

关键词(KeyWords)： 神经内分泌癌;肺;手术治疗;预后
neuroendocrine carcinoma;lung;surgery;prognosis

Abstract:

Keywords:

基金项目(Foundation):

作者(Author): 陈野野;李单青;田震寰;周小昀;何嘉;张晔;刘洪生;
CHEN Ye-ye;LI Shan-qing;TIAN Zhen-huan;ZHOU Xiao-yun;HE Jia;ZHANG Ye;LIU Hong-sheng;Department of Thoracic Surgery,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences &Peking Union Medical College;

Email:

DOI:

参考文献(References)：

• [1]Barbareschi M,Mariscotti C,Barberis M,et al.Large cell neuroendocrine carcinoma of the lung[J].Tumori,1989,75:583-588.
• [2]Travis WD,Linnoila RI,Tsokos MG,et al.Neuroendocrine tumors of the lung with proposed criteria for large-cell neuroendocrine carcinoma.An ultrastructural,immunohistochemical,and flow cytometric study of 35 cases[J].Am J Surg Pathol,1991,15:529-553.
• [3]Travis WD,Brambilla BE,Müller-Hermelink,et al.Pathology and Genetics of Tumours of the Lung,Pleura,Thymus and Heart(WHO Classification of Tumours)[M].Lyon:IARC Press,2004:145-247.
• [4]Eichhorn F,Dienemann H,Muley T,et al.Predictors of survival after operation among patients with large cell neuroendocrine carcinoma of the lung[J].Ann Thorac Surg,2015,99:983-989.
• [5]Iyoda A,Makino T,Koezuka S,et al.Treatment options for patients with large cell neuroendocrine carcinoma of the lung[J].Gen Thorac Cardiovasc Surg,2014,62:351-356.
• [6]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.
• [7]Travis WD,Giroux DJ,Chansky K,et al.The IASLC Lung Cancer Staging Project:proposals for the inclusion of bronchopulmonary carcinoid tumors in the forthcoming(seventh)edition of the TNM Classification for Lung Cancer[J].J Thorac Oncol,2008,3:1213-1223.
• [8]Gridelli C,Rossi A,Airoma G,et al.Treatment of pulmonary neuroendocrine tumours:state of the art and future developments[J].Cancer Treat Rev,2013,39:466-472.
• [9]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.
• [10]Travis WD.Advances in neuroendocrine lung tumors[J].Ann Oncol,2010,21 Suppl 7:65-71.
• [11]Sakurai H,Asamura H.Large-cell neuroendocrine carcinoma of the lung:surgical management[J].Thorac Surg Clin,2014,24:305-311.
• [12]Glisson BS,Moran CA.Large-cell neuroendocrine carcinoma:controversies in diagnosis and treatment[J].J Natl Compr Canc Netw,2011,9:1122-1129.
• [13]Paci M,Cavazza A,Annessi V,et al.Large cell neuroendocrine carcinoma of the lung:a 10-year clinicopathologic retrospective study[J].Ann Thorac Surg,2004,77:1163-1167.
• [14]Asamura H,Kameya T,Matsuno Y,et al.Neuroendocrine neoplasms of the lung:a prognostic spectrum[J].J Clin Oncol,2006,24:70-76.
• [15]Grand B,Cazes A,Mordant P,et al.High grade neuroendocrine lung tumors:pathological characteristics,surgical management and prognostic implications[J].Lung Cancer,2013,81:404-409.
• [16]Veronesi G,Morandi U,Alloisio M,et al.Large cell neuroendocrine carcinoma of the lung:a retrospective analysis of 144surgical cases[J].Lung Cancer,2006,53:111-115.
• [17]Sarkaria IS,Iyoda A,Roh MS,et al.Neoadjuvant and adjuvant chemotherapy in resected pulmonary large cell neuroendocrine carcinomas:a single institution experience[J].Ann Thorac Surg,2011,92:1180-1186.
• [18]Iyoda A,Hiroshima K,Moriya Y,et al.Postoperative recurrence and the role of adjuvant chemotherapy in patients with pulmonary large-cell neuroendocrine carcinoma[J].J Thorac Cardiovasc Surg,2009,138:446-453.
• [19]Shin AR,Shin BK,Choi JA,et al.Large cell neuroendocrine carcinoma of the lung:radiologic and pathologic findings[J].J Comput Assist Tomogr,2000,24:567-573.
• [20]Akata S,Okada S,Maeda J,et al.Computed tomographic findings of large cell neuroendocrine carcinoma of the lung[J].Clin Imaging,2007,31:379-384.
• [21]Maleki Z.Diagnostic issues with cytopathologic interpretation of lung neoplasms displaying high-grade basaloid or neuroendocrine morphology[J].Diagn Cytopathol,2011,39:159-167.
• [22]Fernandez FG,Battafarano RJ.Large-cell neuroendocrine carcinoma of the lung:an aggressive neuroendocrine lung cancer[J].Semin Thorac Cardiovasc Surg,2006,18:206-210.
• [23]Faggiano A,Sabourin JC,Ducreux M,et al.Pulmonary andextrapulmonary poorly differentiated large cell neuroendocrine carcinomas:diagnostic and prognostic features[J].Cancer,2007,110:265-274.
• [24]Takei H,Asamura H,Maeshima A,et al.Large cell neuroendocrine carcinoma of the lung:a clinicopathologic study of eighty-seven cases[J].J Thorac Cardiovasc Surg,2002,124:285-292.
• [25]Battafarano RJ,Fernandez FG,Ritter J,et al.Large cell neuroendocrine carcinoma:an aggressive form of non-small cell lung cancer[J].J Thorac Cardiovasc Surg,2005,130:166-172.
• [26]Iyoda A,Travis WD,Sarkaria IS,et al.Expression profiling and identification of potential molecular targets for therapy in pulmonary large-cell neuroendocrine carcinoma[J].Exp Ther Med,2011,2:1041-1045.
• [27]Isaka M,Nakagawa K,Ohde Y,et al.A clinicopathological study of peripheral,small-sized high-grade neuroendocrine tumours of the lung:differences between small-cell lung carcinoma and large-cell neuroendocrine carcinoma[J].Eur J Cardiothorac Surg,2012,41:841-846.
• [28]Kinoshita T,Yoshida J,Ishii G,et al.The differences of biological behavior based on the clinicopathological data between resectable large-cell neuroendocrine carcinoma and small-cell lung carcinoma[J].Clin Lung Cancer,2013,14:535-540.
• [29]Sun JM,Ahn MJ,Ahn JS,et al.Chemotherapy for pulmonary large cell neuroendocrine carcinoma:similar to that for small cell lung cancer or non-small cell lung cancer?[J].Lung Cancer,2012,77:365-370.
• [30]Iyoda A,Hiroshima K,Moriya Y,et al.Prospective study of adjuvant chemotherapy for pulmonary large cell neuroendocrine carcinoma[J].Ann Thorac Surg,2006,82:1802-1807.