肺癌早期诊断进展
摘要
肺癌是全球最常见的恶性肿瘤之一,其死亡率位居恶性肿瘤首位。近年来肺癌发病率逐步升高,在我国,其发病率已由原恶性肿瘤的第6位跃居为第2位,在城市中死亡率占第一位,严重危害着人类健康。尽管肺癌的治疗手段日新月异,其5年生存率仅14.1%,60%的患者在诊断后1年内死亡。统计资料显示肺癌的预后与诊断时的临床分期密切相关,0期肺癌患者术后的5年生存率可达90%以上,Ia期患者术后5年生存率为60%,而Ⅱ-Ⅳ期患者总的5年生存率则从40%下降到5%以下。由此可见肺癌早期诊断直接影响着患者的预后。然而令人遗憾的是,目前肺癌早期诊断率仅15%,0期患者一般没有任何症状,确诊时还不到肺癌患者总数的0.6%,故提高肺癌早期诊断率争取“早期发现、早期诊断、早期治疗”,是降低死亡率的重要措施。
到目前为止,人们已在肝癌、宫颈癌、前列腺癌、大肠癌等恶性肿瘤建立了筛选和早期诊断的方法,明显降低了其死亡率。但肺癌筛选仍是传统的X线胸片、痰脱落细胞及纤维支气管镜等检查方法,其应用于肺癌的筛查(尤其在高危人群中)并没有降低被筛选人群肺癌的死亡率,同时由于检测敏感性差、过程痛苦、患者耐受性差、不能早期动态监测等而受到限制。因此临床上要求有新的方法进行肺癌早期诊断,近年,肺癌的早期诊断已取得了许多新的进展,如螺旋CT(spiral computed tomography,SCT)和正电子发射体层成像(positron emission tomography,PET)、荧光支气管镜检(fluorescence bronchoscopy)、基因检测、与生物技术相结合的痰液检测、呼吸气体检测、胸部X线计算机辅助图像分析(computer-assisted image analysis of chest radiographs)等,提高了早期肺癌的诊断率,本文就此做一综述。
Lung cancer is one of the most common malignant tumor, which morbility is increasing year by year, the crude mortality is at the first place of all. In China, the morbility has jumped to the second place from the sixth, and the mortality and case fatality are on the first place in towns, which has became the killer of peoples' health. In spite of the prompot new therapy of the lung cancer, the five-year survival rate is mearly 14.1%, 80% of the patients are dying during one year after the diagnosis. The statistics information displays that the prognosis of the lung cancer is closely correlated with the clinical stage which is determined on the time of the diagnosis, the five-year survival rate of the stage 0 patient will up to more then 90%, the stager Ia's is 60%, while the stageⅡ-Ⅳ's descend fleetly from 40% to under 5%. It can be seen that the early diagnosis rate of lung cancer influences the prognosis directly. However, it is regretful that the early diagnosis reate of lung cancer is mearly 15%, the stage 0 patient has no symptom, it only occupys 0.6% of the total sufferers. Therefor, to increase the early diagnosis rate of lung cancer striving for“early discocery, early diagnosis, early treatment”is the significant means of depressing the fatality.
As yet, people has established the screening and early diagnosis ways of liver、cervix、prostate and colon cancer, and cut down theirs mortality obviouslilly. While the screening methords of lung cancer remains traditionary X-ray、cytological examination of sputum、bronchofibroscopy and so on , as the detections procedure are complicated , time-consuming and can’t be monitor dynamically, their using on lung cancer early detection are confined. Previous screening trials on early lung cancer (typically in high-risk group) , such as traditional X-ray、cytological examination of sputum , didn’t lower the fatality of the crowd screened . Therefor, new methods are desired in clinic on lung cancer screening. In recent years , great progress has been made in lung cancer early detction , such as spiral CT, positron emissiontomography , laser-induced fluorescence endoscope, gene detection, cytological examination of sputum based on polymerase chainreaction, respiratial gas dection, computer-assisted image analysis of chest radiographs, they were used on lung cancer early detection and increase the early detection rate of lung cancer, this articles will make a overview based on what mentioned above:
到目前为止,人们已在肝癌、宫颈癌、前列腺癌、大肠癌等恶性肿瘤建立了筛选和早期诊断的方法,明显降低了其死亡率。但肺癌筛选仍是传统的X线胸片、痰脱落细胞及纤维支气管镜等检查方法,其应用于肺癌的筛查(尤其在高危人群中)并没有降低被筛选人群肺癌的死亡率,同时由于检测敏感性差、过程痛苦、患者耐受性差、不能早期动态监测等而受到限制。因此临床上要求有新的方法进行肺癌早期诊断,近年,肺癌的早期诊断已取得了许多新的进展,如螺旋CT(spiral computed tomography,SCT)和正电子发射体层成像(positron emission tomography,PET)、荧光支气管镜检(fluorescence bronchoscopy)、基因检测、与生物技术相结合的痰液检测、呼吸气体检测、胸部X线计算机辅助图像分析(computer-assisted image analysis of chest radiographs)等,提高了早期肺癌的诊断率,本文就此做一综述。
Lung cancer is one of the most common malignant tumor, which morbility is increasing year by year, the crude mortality is at the first place of all. In China, the morbility has jumped to the second place from the sixth, and the mortality and case fatality are on the first place in towns, which has became the killer of peoples' health. In spite of the prompot new therapy of the lung cancer, the five-year survival rate is mearly 14.1%, 80% of the patients are dying during one year after the diagnosis. The statistics information displays that the prognosis of the lung cancer is closely correlated with the clinical stage which is determined on the time of the diagnosis, the five-year survival rate of the stage 0 patient will up to more then 90%, the stager Ia's is 60%, while the stageⅡ-Ⅳ's descend fleetly from 40% to under 5%. It can be seen that the early diagnosis rate of lung cancer influences the prognosis directly. However, it is regretful that the early diagnosis reate of lung cancer is mearly 15%, the stage 0 patient has no symptom, it only occupys 0.6% of the total sufferers. Therefor, to increase the early diagnosis rate of lung cancer striving for“early discocery, early diagnosis, early treatment”is the significant means of depressing the fatality.
As yet, people has established the screening and early diagnosis ways of liver、cervix、prostate and colon cancer, and cut down theirs mortality obviouslilly. While the screening methords of lung cancer remains traditionary X-ray、cytological examination of sputum、bronchofibroscopy and so on , as the detections procedure are complicated , time-consuming and can’t be monitor dynamically, their using on lung cancer early detection are confined. Previous screening trials on early lung cancer (typically in high-risk group) , such as traditional X-ray、cytological examination of sputum , didn’t lower the fatality of the crowd screened . Therefor, new methods are desired in clinic on lung cancer screening. In recent years , great progress has been made in lung cancer early detction , such as spiral CT, positron emissiontomography , laser-induced fluorescence endoscope, gene detection, cytological examination of sputum based on polymerase chainreaction, respiratial gas dection, computer-assisted image analysis of chest radiographs, they were used on lung cancer early detection and increase the early detection rate of lung cancer, this articles will make a overview based on what mentioned above:
引文
1 Ahmedia TL,Talor CA.Cancer [J].Clin 2002,52(1):23-47
2 Wardwell NR,Massion PP. Novel strategies for the early detection and prevention of lung cancer[J]. Semin Oncol, 2005,32(3):259-268
3 Mountain CF. Revisions in the international system for staging lung cancer [J].Chest,1997,111(6):1710-1711
4 Minna JD.Neoplasms of the lung.In: Fauci AS, Braunward E, Isselbacher KJ, et al.Haxrison's principles of internal medicine, New York:McGraw Hill,1 997:1 221
5 邢学忠.肺癌的早期诊断[J].癌症, 2003;22(2):221-223
6 Kaneko M,et al.Radiology,[J].1996;201:798-802
7 Henschke CI, McCauley DI, Yankelevitz DF,et al. Ealy lung Cancer Action Projict: overall design and findings from baseline screening [J]. lancet,1999,354 (9173):99-105
8 Diederich S, Semik M, lentschig MG, et al. Helical CT of pulmonary nodules in patients with extrathoracic malig- nancy: CT-surgical correlation [J].Am J Roentgenol,1999, 172(2):353-360
9 Swensen SJ, Jett JR, Sloan JA, et al. Screening for lung cancer with low-dose spiral computed Tomography[J].Am JRespir Crit Care Med,2002;165(4):508-513
10 Abe Y, Hanai K, Nakano M, et al. A computer-aided diagnosis (CAD)system in lung cancer screening with computed tomography [J]. Anti cancer Res,2005,25 (1B): 483-488
11 Sone S, Takashima S, Li F, et al. Masss creening for lung cancer with mobile spiral computed to mography scanner[J]. lancet, 19 98;351(9111):1242-1245
12 Chong S, Lee KS, Chung MJ, et al. lung cancer screening with low-dose helical CT in Korea: experiences at the Samsung Medical Center[J]. J Korean Med Sci,2005,20(3): 402-408
13 Diederich S,Wormanns D,Semik M,et al. Screening for early lung cancer with low-dose spiral CT: Prevalence in 817 asymptomatic smokers[J].Radiology,2002;222(3):773-781
14 杨栓盈,王双妮.肺癌早期诊断研究进展[J].国外医学呼吸系统分册,2002;22(1):75-77
15 Fischer BM, Mortensen J, Dirksen A,et al. Positronemission tomography of incidentally detected small pulmonary nodules [J]. Nucl Med Commun,2004,25(1):3-9
16 Pieterman R,Vanputten JWG,Meuzelaar JJ,etal.Preoperative staging of non-small-cell lung cancer with l8-fluorodeoxy- glucose positron-emission tomography [J]. Thorax, 2001, 56 (suppl 1):38-44
17 Aquino Sl,Asmuth JC,Alpert NM,et al. Improved radiologicstaging of lung cancer with 2- [18F]-fluoro-2-deoxy-D- glucose-positron emission tomography and computed tomography registration [J]. J Comput AssistTomogr,2003, 27:479-484
18 张红雨,黄岩.CT 扫描融合显像联合肿瘤标志物检测在肺癌早期诊断中的意义[J].临床内科杂志,2006;23(9):625 - 626
19 Woolner LB, Fontana RS, Cortese DA,et al. Roentgeno- graphically occult lung cancer: pathologic findings and frequency of multicentricity during a l0-year period. Mayo Clin Proc,1984, 59(7):453-466
20 Hirsch FR,Prindiville SA,Miller Y,et al. A randomized study of fluorescence bronchoscopy versus white-light broncho- scopy for early detection of lung cancer in high risk patients[J]. lung Cancer,2000;29(suppl 2):244
21 Lam S, MacAulay C, Hung J, et al. Detection of dysplasia and carcinoma in situ with a lung imaging fluorescence endoscope device. [J]. Thorac Cardiovasc Surg,1993,105(6) 1035-1040
22 Kusunoki Y,Imamura F,Uda H ,et al. Early detection of lung cancer with laser-induced fluorescence endoscopy and speetro-fluorometry[J]. Chest,2000;118(6):1776-1782
23 Hirsch FR,Priudiville SA,Miller YE,et al. Fluorescence versus white-light bronchoscopy for detection of preneoplastic lessiions: arandomized study [J]. CancerIst,2001,93(18):1385-1391
24 Saito Y,Nagamoto N,Ota S ,et al. Results of surgical treatment for roentgeno graphically occult brochogenic squamous cell carcinoma. [J].Thorac Cardiovasc Surg, 1992, 104(2);401-407
25 王孟昭,张力.荧光纤维支气管镜在肺癌早期诊断中的应用[J].中国肺癌杂志,2000;3(6):478-480
26 Gary M,Strauss.Randomized population trials and screening of lung cancer [J]. Cancer,2000,89(11):2399-2412
27 Thomas L. Petty MD. The early indertification of lung carcinoma by sputum Cytology[J].Cancer,2000,89(11): 2461 -2463
28 Qiao YL,Tockman M S,Li L,et al. A case-cohort study of early biomarker of lung cancer in a screening cohort of Yunnan tin miners in China[J].Cancer Epidemiol Biomarkers Prey,1997(6);893-900
29 Sueoka E,Goto Y,Sueoka N,et al. Heterogeneous nuclear ribonucleoprotein Bl as a new marker of early detection for human lung cancers [J]. Cancer Res,1999,59(7): 1404-1407
30 Fielding P,Turnbull L,Prime W,et al. Heterogeneous nuclear ribonucleoprotein A2/Bl up regulation in bronchial lavage specimens: A Clinical marker of early lung cancer detection[J].Clin Cancer Res,1999;5(12):4048-4052
31 Belinsky SA,Palmisano WA,Gilliland FD,et al. Aberrant promoter methylation in bronchial epithelium and sputumfrom current and former smokers[J]. Cancer Res,2002,62 (8):2370-2377
32 Mehsch LS,Weller L,Simmons AL,et al. GLUTl antibody staining in thin-layer specimens of benign and malignant body cavity effusions[J]. Aeta Cytol,2002,46 (5):813
33 吴广平,王恩华,李建华等.液基细胞学检查系统在肺癌患者 痰 液 检 查 中 的 临 床 应 用 价 值 [J]. 中 国 肺 癌 杂志,2006,9(2):192-195
34 Payne PW,Sebo TJ,Doudkine A,et al.Sputum screening by quantitative microscopy: A reexamination of a portion of the National Cancer Institute Cooperative Early lung Cancer Study [J]. Mayo Clin Proe,1997;72(8):697-704
35 Lam S,Paleie B,Garner D,et al.lung cancer control strategy in the new millennium[J].lung Cancer,2000;29(suppl 2):145
36 Jahr S,Hentze H,Englisch S et al. DNA fragments in the blood plasma of cancer patients: Quantitation and evidence for their origin from apoptotic and necrotic cell. Cancer Res,2001,61: 1659-1665
37 Coulet F,Blons H,Cabelguenne A et al. Detection of plasma tumor DNA in head and neck squamous cell carcinoma by microsatellite typing and p53 mutation analysis[J]. Cancer Res,2000,60(3):707-711
38 Mayall F, Fairweather S, Wilkins R,et al. Microsatellite abnormalities in plasma of patients with breast carcinoma: concordance with the primary tumour [J]. J Clin Pathol,1999,52(5):363-366
39 易斌杨,杨和平.微卫星 DNA 与肺癌的研究进展.国外医学肿瘤学分册[J].2000;27(5):306-308
40 郭雪君,倪培华,李莉,等.17 号染色体微卫星不稳定性和杂合性丢失与非小细胞肺癌的关系.[J].中华结核于呼吸杂志,1999.22(12):743-745
41 Sozzi G,Musso K,Ratcliffe C,et al. Detection of micro- satellite alterations in plasma DNA of non-small cell lung cancer patients: a prospect for early diagnosis [J].Clin Cancer Res,1999,5(10):2689-2692
42 Zhang JX.Shen H. Mierosatdlite instability and loss of hetemzygosity of fragile histidine triad gene in lung hyperplastie lesions.Di Yi Jun Yi Da Xue Xue Bao,[J]. 2003, 23(4):313-317
43 易斌,杨和平,阮志华.肺癌患者血浆游离性肿瘤 DNA 的研究[J].肿瘤防治研究,2003;30(2):106-108
44 Powell CA,Klares S,Connor G,et al .loss of heterozygosity in epithelial cell obtained by bronchial brushing:Clinical utility in lung cancer. [J].Clin Cancer Res,1999,5:2 025-2 034
45 汪雨来,罗效梅,涂植光.血浆循环 DNA 在肺癌诊断上的应用[J].武警医学,2005;16(8):570-572
46 舒莉,何亚军,田应选等.肺癌早期诊断研究进展[J].中国医学理论与实践,2005;15(7):1023-1024
47 Stieber P,Dienemann H,Schalhorn A,et al. Pro-gastrin-releasing peptide (ProGRP) a useful marker in small cell lung carcinomas[J].Anti cancer Res,1999,9(4A):2673-2678
48 余秉翔,刘庆锋,陈良安.胃泌素释放肽前体作为小细胞肺癌标志物的临床研究[J].中国肺癌杂志,2003,6(3):209-210
49 Molina R. Tumor marker guidelines of the EYGM:how to sensibly use TM in Clinical practice [J]. Tumor Marker Oncol, 2004,19(4):79-80
50 Lamy P,Grenier J,Kramar A,et al. Pro-gastrin-releasing peptide,neuron specific enolase and chromogranin A as serum markers of small cell lung cancer [J]. lung Cancer, 2000,29(3): 197-203
51 吴京,于治方.胃泌素释放肽前体对小细胞肺癌诊断作用的初探[J].中华结核和呼吸杂志,2000,23(3):570-571
52 杨拴盈,张王刚,孙秀珍,等.血清胃泌素释放肽前体和神经元烯醇化酶在小细胞肺癌早期诊断中的价值及其相关性[J].西安交通大学学报(医学版),2005;26(03):247-249
53 Shibayama T,Ueoka H,Nishii K,et al. Complementary roles of pro-gastrin -releasing peptide (ProGRP) and neuron specific enolase(NSE) in diagnosis and prognosis of small cell lung cancer (SCLC)[J]. lung Cancer,2001,32(1):61-69
54 Alatas F,Alatas O,Metintas M. Diagnostic value of CEA, CA15-3,CA19-9,CYFRA21-1,NSE,and TSA assay in pleural effusions[J]. Lung cancer,2001,31(1):9
55 姚群峰,宁勇,张利平. 血清 p16 基因甲基化联合 Cyfra21-1检测在肺癌诊断中的应用[J].微循环学,2006; 16(1):29-34.
56 Ando S,Kimura H,Iwai N,et al. Positive reaction for both Cyfra21-1 and CA125 indicate worst prognosis in non-small cell lung cancer[J].Antican-cer Res,2003,23(3c):2869-2874
57 Reinmuth N,Brandt B,Semik M,et al. Prognostic impact of CyFra21-1 and other serum markers in completely resected non-small cell cancer(1) [J].lung Cancer,2002,36(3):265-270
58 Nakayama M,Satsh H,Ishikawa H,et al. Cytokeratin 19 fragment in patients with nonmalignant respiratory diseases [J]. Chest, 2003,123:2001-2006
59 Belinsky SA,Nikula KJ,Palmisano WA,et al. Aberrant methylation of p16 (INK4a) is an early event in lung cancer and apotential biomarker for early diagnosis [J].Proc Natl Acad Sci USA,1998,95(20):11891-11896
60 Zemaitis M,Pdeger N,Fischer JR,et al.Aberrant promoter methylation of tumor suppressor genes in sernm from lung cancer patients:frequency and correlation with Clinieo Pathological Characteristics[J].Medieina (Kaunas),2005. 41(2):123-131
61 Palmisano WA,Divine KK,Saccomanno G,et al. Predicting lung cancer by detecting aberrant promoter methylation in sputum[J].CancerRes,2000;60(21):5954-5958
62 姚群峰 , 宁勇 , 张利平 . 血清 p16 基因甲基化联合CYFRA21_1 检测在肺癌诊断中的应用[J].微循环学, 2006;16(1):29-34
63 汪洋,邹丽娟,许冠东,等.微流控芯片检测肺癌患者血浆中p16 基因异常甲基化在临床应用的评价[J].生物化学与生物物理进展,2004;31(12):1085-1090
64 Rosenfeld MR,Malat N,Sehramm L,et al.Serum anti p53 antibodies and prognosis of patients with small-cell lung cancer [J].Natl Cancer Inst,1997.89(5):381-385
65 赵峰.肺癌患者血清 p53 抗体的检测及其临床意义[J].华西医学,2002,17(1)23-24
66 薛建平,王先广,朱虎,等.检测血清恶性肿瘤特异性标志物在肺癌早期诊断中的实验研究[J].肿瘤防治研究,2001,28:467-468
67 Schenk T, Ackermann J, Brummer C,et a1.Detection of chromodomal aneuploidy by interphase fluorescence in situ hybridiztion in bronchoscopicaI1y gained cells from lung cancer patients[J].Chest,l997,111:l69l-l696
68 杨国仪,虞敏红,华惠琦,等.DNA 图像分析技术在肺癌良恶性病变诊断中的价值[J].肿瘤研究与临床,2001,13 (1):31-33
69 Gonzalez R, Silva JM, Sanchez A,et al. Microsatellite alterations and TP53 mutations in plasma DNA of small cell lung cancer patients: follow-up study and prognostic significance[J].Ann Oncol,2000.11(9):1097-1104
70 Mao L,Hruban RH,Boyle JO,et al.Detection of oncogene mutation in sputum precedes diagnosis of lung cancer[J]. Cancer Res,1994,54:1634-1637
71 Yoko Kusssonoki M D,Fumio Imamura.Hiroshi Vda,etal.Early detection of lung cancer with laser-induced fluorescence endoscopy and spectrofluorometry [J].Chest, 2000.118(6):1777- 1779
72 Masahiro K, Masahiko K, Toshiaki K,et al.Computed tomography screening for lung carcinomo in Japan[J], Cancer, 2000,89(11):2485-2487
73 Westra WH,Bass IO,Hruban RH,et al.K-ras oncogene activation in a typical alveolar huperplasias of the human lung [J].Cancer Res,1996,56:2224-2228
74 Marx J.New tumor suppressor may rival p53 [J]. Seience, 1994,264(5157):344-345
75 王洁,王曾礼,高沽.癌基因蛋白在肺癌中的表达及其临床意义[J].中华结核和呼吸杂志,1997,20(5):317-321
76 Moriyama S,Nakashima Y,Yano M,et al.Rattio of expression of p16INK4a to p14ARF correlates with the progression of non-small cell lung cancer.Jpn J Cancer Res,2002,93(7):783-788
77 崔旭,张京岚,周奕等.人肺癌端粒酶活性的研究[J].中国肺癌杂志,2000;3:104-106
78 Yashima K,Litzky LA,Kaiser L,et al.Telomerase expression in respiratory epithelium during the multistage pathogenesis of lung carcinomas[J]. Cancer Res,1997,57(12):2373-2377
79 Ahrendt SA, Chow JT, Xu LH, et al. Molecular detection of tumor cells in bronchoalveolar lavage fluid from patients with early stage lung cancer[J]. J Natl Cancer Inst,1999,91(4):332-339
80 Yashima K, Litzky LA, Kaiser L, etal. Telomerase expre- ssionin respiratory epithelium during the multistage patho- genesis of lung carcinomas[J].Cancer Res,1997;57(12): 2373-2377
81 Zhou,Nong L,Wloch M,et al. Expression of early lung cancer detection marker: hnRNP-A2B1 and its relation to microsatellite alteration in non-small cell lung cancer[J].lung Cancer,2001;34(3):341-350
82 Sueoka E,Sueoka N,Goto Y,et al. Heterogeneous nuclear ribonucleoprotein Bl as early cancer biomarker for occult cancer of human lungs and bronchial dysplasia[J].Cancer Res,2001;61 (5):1896-1902
83 Fielding P,Turnbull L,Prime W,et al. Heterogeneous nuclear ribonucleoprotein A2/B1 up regulation in bronchial lavage specimens: A Clinical marker of early lung cancer detection [J].Clin Cancer Res,1999;5(12):4048-4052
84 杨栓盈 王双妮. 肺癌早期诊断研究进展. 国外医学呼吸系统分册[J].2002;22(1):75-77
85 Silva JM,Gonzacez R,Doninguez G,et al. P53 gene mutations in plasma DNA of cancer patients. Genes chromosomes [J]. Cancer,1999,21(2):160-161
86 Sozzi G,Veronese ML,et al. The FHIT gene at 3p14.2 is abnormal in lung cancer [J]. Cell,1996,85(1):17-26
87 Sozzi G,Pastorino U,Moiraghi L, et al.loss of FHIT functionin lung cancer and preinvasive bronchial lesions[J].Cancer Res,1998,58:5 032-5 037
88 Goodwin LO,Mason JM,Hajdu SI. Gene expression patterns of paired bronchioloalveolar carcinoma and benign lung tissue.Ann Clin lab Sci,2001.31:369-375
89 Wang T,Hopkins D,Schmidt C,et al.Identification of genes diferentialy over-expressed in lung squamous cell carcinoma using combination of cDNA subtraction and microarry analysis[J].Oncogene,2000,19: 1519-1528
90 Bangur CS, Switzer A, Fan L, et al. Identification of genes over-expressed in small cell lung carcinoma using suppression subtractive hybridization and cDNA microarray expression analysis[J].Oncegene,2002,21(23):3814-3825
91 Martin VM,Siewert C,Scharl A et al,lmmunomagnetic enrichment of disseminated epithelial tumor cells from peripheral blood by MACS[J]. Exp Hematol,1998,26;252 -264
92王晓光,胡红,刘又宁. 应用纳米免疫磁珠检测早期肺癌循环血中肿瘤细胞[][J]. 中华医学杂志, 2004;84(16):1393 -1395
93 Phillips M ,Cataneo RN,Cummin ARC,et al.Detection of lung cancer with volatile markers in the breath[J]. Chest, 2003,123(6):2115-2123
94 Preti G,Labows JN,Kostelc JG,et al.Analysis of lung air from patients with bronchogenic carcinoma and controlsusing gas chromatography-mass spectrometry [J]. Chromatogr,1988,432(11):1-11
95 Phillips M,Gleeson K,Hughes JM,et al.Volatile organic compounds in breath as markers of lung cancer:a cross sectional study[J]. Lancet,1999,353(9168):1930-1933
96 似学红,郭书云.唾液酸测定对肺癌早期诊断及其观察预后的意义[J].临床医药实践,2005;14(1):42-42
2 Wardwell NR,Massion PP. Novel strategies for the early detection and prevention of lung cancer[J]. Semin Oncol, 2005,32(3):259-268
3 Mountain CF. Revisions in the international system for staging lung cancer [J].Chest,1997,111(6):1710-1711
4 Minna JD.Neoplasms of the lung.In: Fauci AS, Braunward E, Isselbacher KJ, et al.Haxrison's principles of internal medicine, New York:McGraw Hill,1 997:1 221
5 邢学忠.肺癌的早期诊断[J].癌症, 2003;22(2):221-223
6 Kaneko M,et al.Radiology,[J].1996;201:798-802
7 Henschke CI, McCauley DI, Yankelevitz DF,et al. Ealy lung Cancer Action Projict: overall design and findings from baseline screening [J]. lancet,1999,354 (9173):99-105
8 Diederich S, Semik M, lentschig MG, et al. Helical CT of pulmonary nodules in patients with extrathoracic malig- nancy: CT-surgical correlation [J].Am J Roentgenol,1999, 172(2):353-360
9 Swensen SJ, Jett JR, Sloan JA, et al. Screening for lung cancer with low-dose spiral computed Tomography[J].Am JRespir Crit Care Med,2002;165(4):508-513
10 Abe Y, Hanai K, Nakano M, et al. A computer-aided diagnosis (CAD)system in lung cancer screening with computed tomography [J]. Anti cancer Res,2005,25 (1B): 483-488
11 Sone S, Takashima S, Li F, et al. Masss creening for lung cancer with mobile spiral computed to mography scanner[J]. lancet, 19 98;351(9111):1242-1245
12 Chong S, Lee KS, Chung MJ, et al. lung cancer screening with low-dose helical CT in Korea: experiences at the Samsung Medical Center[J]. J Korean Med Sci,2005,20(3): 402-408
13 Diederich S,Wormanns D,Semik M,et al. Screening for early lung cancer with low-dose spiral CT: Prevalence in 817 asymptomatic smokers[J].Radiology,2002;222(3):773-781
14 杨栓盈,王双妮.肺癌早期诊断研究进展[J].国外医学呼吸系统分册,2002;22(1):75-77
15 Fischer BM, Mortensen J, Dirksen A,et al. Positronemission tomography of incidentally detected small pulmonary nodules [J]. Nucl Med Commun,2004,25(1):3-9
16 Pieterman R,Vanputten JWG,Meuzelaar JJ,etal.Preoperative staging of non-small-cell lung cancer with l8-fluorodeoxy- glucose positron-emission tomography [J]. Thorax, 2001, 56 (suppl 1):38-44
17 Aquino Sl,Asmuth JC,Alpert NM,et al. Improved radiologicstaging of lung cancer with 2- [18F]-fluoro-2-deoxy-D- glucose-positron emission tomography and computed tomography registration [J]. J Comput AssistTomogr,2003, 27:479-484
18 张红雨,黄岩.CT 扫描融合显像联合肿瘤标志物检测在肺癌早期诊断中的意义[J].临床内科杂志,2006;23(9):625 - 626
19 Woolner LB, Fontana RS, Cortese DA,et al. Roentgeno- graphically occult lung cancer: pathologic findings and frequency of multicentricity during a l0-year period. Mayo Clin Proc,1984, 59(7):453-466
20 Hirsch FR,Prindiville SA,Miller Y,et al. A randomized study of fluorescence bronchoscopy versus white-light broncho- scopy for early detection of lung cancer in high risk patients[J]. lung Cancer,2000;29(suppl 2):244
21 Lam S, MacAulay C, Hung J, et al. Detection of dysplasia and carcinoma in situ with a lung imaging fluorescence endoscope device. [J]. Thorac Cardiovasc Surg,1993,105(6) 1035-1040
22 Kusunoki Y,Imamura F,Uda H ,et al. Early detection of lung cancer with laser-induced fluorescence endoscopy and speetro-fluorometry[J]. Chest,2000;118(6):1776-1782
23 Hirsch FR,Priudiville SA,Miller YE,et al. Fluorescence versus white-light bronchoscopy for detection of preneoplastic lessiions: arandomized study [J]. CancerIst,2001,93(18):1385-1391
24 Saito Y,Nagamoto N,Ota S ,et al. Results of surgical treatment for roentgeno graphically occult brochogenic squamous cell carcinoma. [J].Thorac Cardiovasc Surg, 1992, 104(2);401-407
25 王孟昭,张力.荧光纤维支气管镜在肺癌早期诊断中的应用[J].中国肺癌杂志,2000;3(6):478-480
26 Gary M,Strauss.Randomized population trials and screening of lung cancer [J]. Cancer,2000,89(11):2399-2412
27 Thomas L. Petty MD. The early indertification of lung carcinoma by sputum Cytology[J].Cancer,2000,89(11): 2461 -2463
28 Qiao YL,Tockman M S,Li L,et al. A case-cohort study of early biomarker of lung cancer in a screening cohort of Yunnan tin miners in China[J].Cancer Epidemiol Biomarkers Prey,1997(6);893-900
29 Sueoka E,Goto Y,Sueoka N,et al. Heterogeneous nuclear ribonucleoprotein Bl as a new marker of early detection for human lung cancers [J]. Cancer Res,1999,59(7): 1404-1407
30 Fielding P,Turnbull L,Prime W,et al. Heterogeneous nuclear ribonucleoprotein A2/Bl up regulation in bronchial lavage specimens: A Clinical marker of early lung cancer detection[J].Clin Cancer Res,1999;5(12):4048-4052
31 Belinsky SA,Palmisano WA,Gilliland FD,et al. Aberrant promoter methylation in bronchial epithelium and sputumfrom current and former smokers[J]. Cancer Res,2002,62 (8):2370-2377
32 Mehsch LS,Weller L,Simmons AL,et al. GLUTl antibody staining in thin-layer specimens of benign and malignant body cavity effusions[J]. Aeta Cytol,2002,46 (5):813
33 吴广平,王恩华,李建华等.液基细胞学检查系统在肺癌患者 痰 液 检 查 中 的 临 床 应 用 价 值 [J]. 中 国 肺 癌 杂志,2006,9(2):192-195
34 Payne PW,Sebo TJ,Doudkine A,et al.Sputum screening by quantitative microscopy: A reexamination of a portion of the National Cancer Institute Cooperative Early lung Cancer Study [J]. Mayo Clin Proe,1997;72(8):697-704
35 Lam S,Paleie B,Garner D,et al.lung cancer control strategy in the new millennium[J].lung Cancer,2000;29(suppl 2):145
36 Jahr S,Hentze H,Englisch S et al. DNA fragments in the blood plasma of cancer patients: Quantitation and evidence for their origin from apoptotic and necrotic cell. Cancer Res,2001,61: 1659-1665
37 Coulet F,Blons H,Cabelguenne A et al. Detection of plasma tumor DNA in head and neck squamous cell carcinoma by microsatellite typing and p53 mutation analysis[J]. Cancer Res,2000,60(3):707-711
38 Mayall F, Fairweather S, Wilkins R,et al. Microsatellite abnormalities in plasma of patients with breast carcinoma: concordance with the primary tumour [J]. J Clin Pathol,1999,52(5):363-366
39 易斌杨,杨和平.微卫星 DNA 与肺癌的研究进展.国外医学肿瘤学分册[J].2000;27(5):306-308
40 郭雪君,倪培华,李莉,等.17 号染色体微卫星不稳定性和杂合性丢失与非小细胞肺癌的关系.[J].中华结核于呼吸杂志,1999.22(12):743-745
41 Sozzi G,Musso K,Ratcliffe C,et al. Detection of micro- satellite alterations in plasma DNA of non-small cell lung cancer patients: a prospect for early diagnosis [J].Clin Cancer Res,1999,5(10):2689-2692
42 Zhang JX.Shen H. Mierosatdlite instability and loss of hetemzygosity of fragile histidine triad gene in lung hyperplastie lesions.Di Yi Jun Yi Da Xue Xue Bao,[J]. 2003, 23(4):313-317
43 易斌,杨和平,阮志华.肺癌患者血浆游离性肿瘤 DNA 的研究[J].肿瘤防治研究,2003;30(2):106-108
44 Powell CA,Klares S,Connor G,et al .loss of heterozygosity in epithelial cell obtained by bronchial brushing:Clinical utility in lung cancer. [J].Clin Cancer Res,1999,5:2 025-2 034
45 汪雨来,罗效梅,涂植光.血浆循环 DNA 在肺癌诊断上的应用[J].武警医学,2005;16(8):570-572
46 舒莉,何亚军,田应选等.肺癌早期诊断研究进展[J].中国医学理论与实践,2005;15(7):1023-1024
47 Stieber P,Dienemann H,Schalhorn A,et al. Pro-gastrin-releasing peptide (ProGRP) a useful marker in small cell lung carcinomas[J].Anti cancer Res,1999,9(4A):2673-2678
48 余秉翔,刘庆锋,陈良安.胃泌素释放肽前体作为小细胞肺癌标志物的临床研究[J].中国肺癌杂志,2003,6(3):209-210
49 Molina R. Tumor marker guidelines of the EYGM:how to sensibly use TM in Clinical practice [J]. Tumor Marker Oncol, 2004,19(4):79-80
50 Lamy P,Grenier J,Kramar A,et al. Pro-gastrin-releasing peptide,neuron specific enolase and chromogranin A as serum markers of small cell lung cancer [J]. lung Cancer, 2000,29(3): 197-203
51 吴京,于治方.胃泌素释放肽前体对小细胞肺癌诊断作用的初探[J].中华结核和呼吸杂志,2000,23(3):570-571
52 杨拴盈,张王刚,孙秀珍,等.血清胃泌素释放肽前体和神经元烯醇化酶在小细胞肺癌早期诊断中的价值及其相关性[J].西安交通大学学报(医学版),2005;26(03):247-249
53 Shibayama T,Ueoka H,Nishii K,et al. Complementary roles of pro-gastrin -releasing peptide (ProGRP) and neuron specific enolase(NSE) in diagnosis and prognosis of small cell lung cancer (SCLC)[J]. lung Cancer,2001,32(1):61-69
54 Alatas F,Alatas O,Metintas M. Diagnostic value of CEA, CA15-3,CA19-9,CYFRA21-1,NSE,and TSA assay in pleural effusions[J]. Lung cancer,2001,31(1):9
55 姚群峰,宁勇,张利平. 血清 p16 基因甲基化联合 Cyfra21-1检测在肺癌诊断中的应用[J].微循环学,2006; 16(1):29-34.
56 Ando S,Kimura H,Iwai N,et al. Positive reaction for both Cyfra21-1 and CA125 indicate worst prognosis in non-small cell lung cancer[J].Antican-cer Res,2003,23(3c):2869-2874
57 Reinmuth N,Brandt B,Semik M,et al. Prognostic impact of CyFra21-1 and other serum markers in completely resected non-small cell cancer(1) [J].lung Cancer,2002,36(3):265-270
58 Nakayama M,Satsh H,Ishikawa H,et al. Cytokeratin 19 fragment in patients with nonmalignant respiratory diseases [J]. Chest, 2003,123:2001-2006
59 Belinsky SA,Nikula KJ,Palmisano WA,et al. Aberrant methylation of p16 (INK4a) is an early event in lung cancer and apotential biomarker for early diagnosis [J].Proc Natl Acad Sci USA,1998,95(20):11891-11896
60 Zemaitis M,Pdeger N,Fischer JR,et al.Aberrant promoter methylation of tumor suppressor genes in sernm from lung cancer patients:frequency and correlation with Clinieo Pathological Characteristics[J].Medieina (Kaunas),2005. 41(2):123-131
61 Palmisano WA,Divine KK,Saccomanno G,et al. Predicting lung cancer by detecting aberrant promoter methylation in sputum[J].CancerRes,2000;60(21):5954-5958
62 姚群峰 , 宁勇 , 张利平 . 血清 p16 基因甲基化联合CYFRA21_1 检测在肺癌诊断中的应用[J].微循环学, 2006;16(1):29-34
63 汪洋,邹丽娟,许冠东,等.微流控芯片检测肺癌患者血浆中p16 基因异常甲基化在临床应用的评价[J].生物化学与生物物理进展,2004;31(12):1085-1090
64 Rosenfeld MR,Malat N,Sehramm L,et al.Serum anti p53 antibodies and prognosis of patients with small-cell lung cancer [J].Natl Cancer Inst,1997.89(5):381-385
65 赵峰.肺癌患者血清 p53 抗体的检测及其临床意义[J].华西医学,2002,17(1)23-24
66 薛建平,王先广,朱虎,等.检测血清恶性肿瘤特异性标志物在肺癌早期诊断中的实验研究[J].肿瘤防治研究,2001,28:467-468
67 Schenk T, Ackermann J, Brummer C,et a1.Detection of chromodomal aneuploidy by interphase fluorescence in situ hybridiztion in bronchoscopicaI1y gained cells from lung cancer patients[J].Chest,l997,111:l69l-l696
68 杨国仪,虞敏红,华惠琦,等.DNA 图像分析技术在肺癌良恶性病变诊断中的价值[J].肿瘤研究与临床,2001,13 (1):31-33
69 Gonzalez R, Silva JM, Sanchez A,et al. Microsatellite alterations and TP53 mutations in plasma DNA of small cell lung cancer patients: follow-up study and prognostic significance[J].Ann Oncol,2000.11(9):1097-1104
70 Mao L,Hruban RH,Boyle JO,et al.Detection of oncogene mutation in sputum precedes diagnosis of lung cancer[J]. Cancer Res,1994,54:1634-1637
71 Yoko Kusssonoki M D,Fumio Imamura.Hiroshi Vda,etal.Early detection of lung cancer with laser-induced fluorescence endoscopy and spectrofluorometry [J].Chest, 2000.118(6):1777- 1779
72 Masahiro K, Masahiko K, Toshiaki K,et al.Computed tomography screening for lung carcinomo in Japan[J], Cancer, 2000,89(11):2485-2487
73 Westra WH,Bass IO,Hruban RH,et al.K-ras oncogene activation in a typical alveolar huperplasias of the human lung [J].Cancer Res,1996,56:2224-2228
74 Marx J.New tumor suppressor may rival p53 [J]. Seience, 1994,264(5157):344-345
75 王洁,王曾礼,高沽.癌基因蛋白在肺癌中的表达及其临床意义[J].中华结核和呼吸杂志,1997,20(5):317-321
76 Moriyama S,Nakashima Y,Yano M,et al.Rattio of expression of p16INK4a to p14ARF correlates with the progression of non-small cell lung cancer.Jpn J Cancer Res,2002,93(7):783-788
77 崔旭,张京岚,周奕等.人肺癌端粒酶活性的研究[J].中国肺癌杂志,2000;3:104-106
78 Yashima K,Litzky LA,Kaiser L,et al.Telomerase expression in respiratory epithelium during the multistage pathogenesis of lung carcinomas[J]. Cancer Res,1997,57(12):2373-2377
79 Ahrendt SA, Chow JT, Xu LH, et al. Molecular detection of tumor cells in bronchoalveolar lavage fluid from patients with early stage lung cancer[J]. J Natl Cancer Inst,1999,91(4):332-339
80 Yashima K, Litzky LA, Kaiser L, etal. Telomerase expre- ssionin respiratory epithelium during the multistage patho- genesis of lung carcinomas[J].Cancer Res,1997;57(12): 2373-2377
81 Zhou,Nong L,Wloch M,et al. Expression of early lung cancer detection marker: hnRNP-A2B1 and its relation to microsatellite alteration in non-small cell lung cancer[J].lung Cancer,2001;34(3):341-350
82 Sueoka E,Sueoka N,Goto Y,et al. Heterogeneous nuclear ribonucleoprotein Bl as early cancer biomarker for occult cancer of human lungs and bronchial dysplasia[J].Cancer Res,2001;61 (5):1896-1902
83 Fielding P,Turnbull L,Prime W,et al. Heterogeneous nuclear ribonucleoprotein A2/B1 up regulation in bronchial lavage specimens: A Clinical marker of early lung cancer detection [J].Clin Cancer Res,1999;5(12):4048-4052
84 杨栓盈 王双妮. 肺癌早期诊断研究进展. 国外医学呼吸系统分册[J].2002;22(1):75-77
85 Silva JM,Gonzacez R,Doninguez G,et al. P53 gene mutations in plasma DNA of cancer patients. Genes chromosomes [J]. Cancer,1999,21(2):160-161
86 Sozzi G,Veronese ML,et al. The FHIT gene at 3p14.2 is abnormal in lung cancer [J]. Cell,1996,85(1):17-26
87 Sozzi G,Pastorino U,Moiraghi L, et al.loss of FHIT functionin lung cancer and preinvasive bronchial lesions[J].Cancer Res,1998,58:5 032-5 037
88 Goodwin LO,Mason JM,Hajdu SI. Gene expression patterns of paired bronchioloalveolar carcinoma and benign lung tissue.Ann Clin lab Sci,2001.31:369-375
89 Wang T,Hopkins D,Schmidt C,et al.Identification of genes diferentialy over-expressed in lung squamous cell carcinoma using combination of cDNA subtraction and microarry analysis[J].Oncogene,2000,19: 1519-1528
90 Bangur CS, Switzer A, Fan L, et al. Identification of genes over-expressed in small cell lung carcinoma using suppression subtractive hybridization and cDNA microarray expression analysis[J].Oncegene,2002,21(23):3814-3825
91 Martin VM,Siewert C,Scharl A et al,lmmunomagnetic enrichment of disseminated epithelial tumor cells from peripheral blood by MACS[J]. Exp Hematol,1998,26;252 -264
92王晓光,胡红,刘又宁. 应用纳米免疫磁珠检测早期肺癌循环血中肿瘤细胞[][J]. 中华医学杂志, 2004;84(16):1393 -1395
93 Phillips M ,Cataneo RN,Cummin ARC,et al.Detection of lung cancer with volatile markers in the breath[J]. Chest, 2003,123(6):2115-2123
94 Preti G,Labows JN,Kostelc JG,et al.Analysis of lung air from patients with bronchogenic carcinoma and controlsusing gas chromatography-mass spectrometry [J]. Chromatogr,1988,432(11):1-11
95 Phillips M,Gleeson K,Hughes JM,et al.Volatile organic compounds in breath as markers of lung cancer:a cross sectional study[J]. Lancet,1999,353(9168):1930-1933
96 似学红,郭书云.唾液酸测定对肺癌早期诊断及其观察预后的意义[J].临床医药实践,2005;14(1):42-42