【作者】 张军；

【导师】 胡伟；

【作者基本信息】 郑州大学 ， 外科学（胸外科）， 2017， 硕士

【摘要】 背景和目的目前,肺癌已经成为了世界上对人类健康威胁最大的恶性肿瘤之一,这从各个国家的报道的对肺癌的相关报道看出^[3.5.7]。目前仍未有明确的肺癌病因。循证医学表明大量吸烟与肺癌的发生密切相关。随着社会发展,各种精密仪器的不断出现,使医学技术出现有了大幅度提高。而对于无明确禁忌症且能耐受手术的Ⅰ或Ⅱ期肺癌患者来说,外科手术（切除肿瘤源发病灶及系统的淋巴结清扫）是肺癌的首先疗法,尤其适用于非小细胞肺癌（NSCLC）患者。通过常规纤维支气管镜检查或者术后行病理检测,明确肿瘤具体类型,结合资料确定TNM分期,进而评估预后和指导后续治疗。对于非小细胞肺癌患者（NSCLC）临床治疗后预后评估,TNM分期中淋巴结分期（N分期）状态显得尤为关键。目前,国际上应用最广泛的淋巴结分期系统（N分期）是国际抗癌联盟发布的以淋巴结区为基础（pN分期）的解剖学分期TNM。近年来,随着检查手段的提高,以阳性淋巴结数量（MLN）和阳性淋巴结比率（LNR）作为基础的淋巴结分期开始逐渐获得人们关注。长期的临川实践过程中,逐渐发现以现行的TNM分期中的pN分期,及以解剖区域分组的淋巴结分期,在临床实际应用中存在许多不足,淋巴结（N）分期中异质性难以避免。当前的淋巴结分期几乎均有解剖区域分组和阳性的淋巴结数量共同决定,特别是,结肠癌、胃癌和食管癌的最新版的TNM分期,对于这些肿瘤,最新的证据表明,阳性淋巴结数量对于这些肿瘤预后判断更有意义^[5]。另外一些研究也指出,淋巴结阳性率对于非小细胞肺癌患者的预后判断也有预测价值。但是,MLN客观上由切除和检验的淋巴结数量来决定,受手术医师和病理科医师影响较大。在实际应用中发现,通过将MLN和RLN结合起来对很多恶性肿瘤预后更有意义,如胃癌、结肠癌、食管癌等^[9],因此,本实验设计决定应用淋巴结阳性率（LNR）对非小细胞肺癌预后判断进行分析。综述所述,本研究为了探讨LNR作为研究对象,是为非小细胞肺癌术后治疗指导方向做进一步的研究探索。方法:第一部分通过对2010年1月到2012年1月间于郑州大学第一附属医院胸外科783例行肺癌根治术的非小细胞肺癌（NSCLC）患者的病历资料和随访进行回顾性分析。本研究采用COX风险回归模型来确定MLN和RLN的最佳节点,采用K-M法分析单因素（吸烟情况、年龄、性别、手术方式、辅助化疗等）对生存的影响,Log-rank分析比较组间生存率的差异。采用COX风险回归模型对预后因子进行多元分析。第二部分通过对PubMed和中国知网进行检索,到2016年10月25日截止。中文检索词包括:淋巴结阳性率、淋巴结阳性数量、生存率。英文检索词包括:proportion of lymph node,lymph node ratio,survival。手工检索已发表文献,追溯纳入文献中的参考文献。文献内容采取描述性评测,情况允许使用荟萃分析。、本实验设计应用Stata 12.0软件。P值采取双侧检验结果。结果:1.根据COX回归风险模型的X²值,确定3个淋巴结为MLN,35%为LNR的最优节点,从而分别将MLN.划分为0,1-3,>3三组,将LNR划分为0%,0一35%,or>₃5%三组。且MLN与LNR密切相关2.根据COX多元分析确定LNR分期、吸烟和辅助化疗是非小细胞肺癌（NSCLC）预后的独立危险因素。部分PN1患者需要行术后辅助治疗。3.在文献多元分析中显示,LNR是与生存期的相关因子,而pN分期不具有显著意义。LNR比当前pN分期的对生存期的预测更有意义4.在文献多元分析中显示,LNR越高,生存率越低。结论:1、阳性淋巴结率是NSCLC术后患者的独立预后因子,可对NSCLC术后治疗起指导作用。PN1部分患者也应行术后辅助治疗2、本实验为非小细胞肺癌患者术后生存治疗指导提供预测方向。更多还原

【Abstract】 Background and purposeIn recent years,lung cancer has become one of the fastest growing tumors with the highest morbidity and mortality.This can be seen from the incidence and mortality of lung cancer reported in various countries over the last 50 years^[3.5.7].The incidence and mortality of lung cancer in male malignant tumors were the first,and the incidence rate of lung cancer in female malignant tumors accounted for second in the second place,and the mortality rate was only^[4].At present,the etiology of lung cancer is not completely clear,a large number of survey data show that a large number of long-term smoking and lung cancer are closely related.With the development of society,the appearance of all kinds of precision instruments,the medical technology has been greatly improved.The level of diagnosis,surgical instruments,postoperative adjuvant therapy and nursing level have been greatly improved,and there is no clear contraindication and patients with stage I or II lung cancer undergo surgery,surgery（resection of the tumor lesions and source system of lymph node dissection）is the first therapy of lung cancer,especially for in non-small cell lung cancer（NSCLC）patients.As the largest category of lung cancer,the incidence and mortality of non-small cell lung cancer（NSCLC）remain high.The pathological staging of lung cancer is the key to evaluate the prognosis and to make the treatment plan.The ability to accurately assess the status of lymph node staging（N stage）in patients with non-small cell lung cancer（NSCLC）is essential for the selection of treatment and prognosis.At present,the most widely used lymph node staging system（N stage）is the International Anti Cancer Alliance Based on the lymph node region（pN stage）of the anatomical staging TNM.In recent years,with the improvement of inspection methods,the number of positive lymph nodes（MLN）and positive lymph node ratio（LNR）as the basis of the lymph node stage began to get people’s attention.Comorbid illness and adverse medical conditions due to aging is a si ficantconcern to treat elderly patients with lung cancer.Lobectomy is the current standard treatment for early-stage non-small cell lung cancer SCLC)in the general population.Sublobar resection such as wedge resection and segmentectomy could be indicated inpatients with stage I NSCLC,who may tolerate operative intervention but not a lobar orgreater lung resection because of comorbid disease or decreased cardiopulmonaryInternational Union against cancer（UICC）the latest version of the lung cancer TNM staging standards promulgated and implemented in January 2017（Table 1）,which is a major event in the field of lung cancer research and treatment in the world,this standard is an important guiding document to promote the development of a new round of lung cancer diagnosis and treatment[8].The retrospective analysis of the data from the International Lung Cancer Association（IASLC）in 81000 patients with lung cancer between 1990 and 2000 was the basis of the UICC and AJCC version of the TNM staging of lung cancer.At present,the world’s UICC seventh edition of the lung cancer TNM staging standard was promulgated in 2009,has not been revised for8 years.In the past 8 years,the great development and great progress of the research and the diagnosis and treatment of lung cancer,staging old exposed some problems,the urgent need to revise and adopt the new standards by the data from 35 databases in data from 16 countries.Including 94708 cases of lung cancer from 1999-2010.The data source in the database（90014 cases）or through electronic data collection system（EDC）submitted to the cancer research and Biostatistics（CRAB）data（4667 cases）.The revised version of the eighth edition of lung cancer staging standard was published in the 2015 issue of（Journalof Thoracic Oncology）,the research results will be the new version of the UICC standard for staging of lung cancer in early（Eighth Edition）,the main basis.Anatomical factors constitute the cornerstone of TNM staging system for lung cancer.Tumor size（tumor,T）,local lymph node involvement（node,N）and distant metastasis（metastasis,M）is a prognostic factor for characterizing the extent of histologic involvement of the disease,and may also be used to differentiate different clinical outcomes in patients with cancer.The eighth edition of non-small cell lung cancer N staging according to the regional lymph node involvement,N will be divided into four groups:no regional lymph node metastasis（NO）,ipsilateral peripheral bronchi and（or）ipsilateral hilar lymph node and lung lymph node metastasis（N1）,ipsilateral mediastinal and（or）subcarinal lymph node metastasis(（N2）,contralateral mediastinal and contralateral hilar,ipsilateral or contralateral anterior scalene muscle and supraclavicular lymph node metastasis（N3）staging,it follows the basic seventh edition of N staging system,there are no major changes in[7].However,that a large number of clinical practice,is based on anatomy and lymph node staging（pN staging）problems in the practical application stage in non-small cell lung cancer,lymph node anatomy for the same patients with different stages can exist obvious differences in prognosis,known as the heterogeneity of N staging.For the majority of malignant tumors,lymph node staging by anatomical definition and cumulative number of lymph nodes is determined,and in the latest edition of TNM staging in colon cancer,gastric cancer and esophageal cancer lymph node staging for the number of positive lymph nodes（MLN）,decision(the research shows that MLN provides for these tumors the predictive value of[5]more effective.Similarly,many studies have shown that the number of positive lymph nodes in patients with non-small cell lung cancer is also highIt is noteworthy that the number of positive lymph nodes depends on the number of lymph nodes removed and examined,and is largely affected by the surgeon and pathologist.The national comprehensive cancer network（NCCN）recommends a minimum of 6 to 10 lymph nodes or lymph nodes in non-small cell lung cancer（N）for accurate determination of lymph node（node）stage.More and more evidence that the number of positive lymph nodes（MLN）and the number of resected lymph nodes（RLN）are combined in many malignant tumor postoperative follow-up treatment has obvious implications,such as gastric cancer,colorectal cancer,thyroid cancer,breast cancer,colorectal cancer[9],so we use the positive lymph nodes rate（LNR）to describe the number of positive lymph nodes（MLN）and the number of resected lymph node（RLN）ratio,because it contains two important factors,positive lymph MethodsJanuary 2014²016 years in January,683 patients in our hospital were treated with radical resection of lung cancer and regional lymph node dissection.In this study,the following conditions must be met:1.All cases were pathologically confirmed non-small cell lung cancer,lymph node metastasis after operation2.The results showed that the pathological reports were confirmed by the experienced pathologists.3.Pathological diagnosis of patients with Tis or IV stage,pathological stage according to the eighth edition of UICC/AJCC TNMDefinite diagnosis by stages"Preoperative radiotherapy and chemotherapy were excluded.4.The exclusion of a history of lung cancer or other malignant tumors,or lung cancer with tumor shuangyuanfa.Finally,a total of 480 patients were included in the retrospective study.The demographic information and clinical data were collected Pathological data.The clinical study on the positive lymph node ratio of non-small cell lung cancer Quasi pass.Clinical information and survival data.Determination of X2 value in COX risk regression model MLN,Multivariate regression analysis of prognostic factors was performed using the COX risk regression model with the optimal node of LNR.Results:1.According to the X2 value of the COX regression model,the results showed that the of the 3 lymph nodes was MLN9（LNR）MLN.is divided into 0,1-3,>3 three groups,the LNR is divided into 0%,0 a,or>₃5%group three.2,COX multivariate analysis identified LNR stage,smoking status,and adjuvant chemotherapy for non-small cell lung cancer Independent risk factors.3.In the literature in the multivariate analysis,LNR is related to the survival of the factor,and pN stage has significant meaning.LNR animal survival than the current pN stage forecast more meaningful4.In the literature in the multivariate analysis,LNR is higher,the lower the survival rate.Discussion:1.There are many problems in the determination of variable nodes in LNR classification.First,different surgical pathologist and between resection and lymph node number test vary greatly,so that different countries and regions and populations in the LINK value of significant heterogeneity;secondly,LNN is after operation to determine lymph node status,is not conducive to the preoperative staging and determine the treatment plan;in addition,the best classification of nodes LNR still can not reach agreement,the methods and results of selecting nodes are not the same,and the best node classification method has not been a consensus;finally,from a clinical perspective,LNR will increase the complexity of clinical staging,promotion difficult.Future research needs to focus on the uniform surgical and pathological procedures and the best classification.2.our systematic review has many limitations:all the studies are retrospective study,therefore,can not be a unified standard based in standard operation and pathology;in addition,a retrospective study of the majority of individual institutions,the number of cases is limited,relatively low level of evidence;in addition,publication bias is another a problem can not be ignored,the lack of the negative results will increase the value of the estimated bias effect.In summary,summary of our systematic review and evaluate the value of LNR in surgical resection in NSCLC prediction,although LNR is an independent prognostic factor of NSCLC,but at this stage there is not enough evidence to show that LNR can replace pN as the NSCLC lymph node staging clinical guidance,however,pN staging and LNR combination may provide the prognosis the more accurate information for patients.Conclusions1.The positive lymph node rate is an independent prognostic factor for patients with NSCLC surgery,which can be used to guide the treatment of NSCLC.The PN1should also be treated with postoperative adjuvant therapy2.This study provides the prediction direction for postoperative survival therapy for non-small-cell lung cancer patients更多还原