Pulmonary Malignancies: Pathophysiology and Treatment

  • David S. Schrump

Abstract

Lung cancer is a highly lethal neoplasm, with the worldwide incidence expected to have exceeded one million cases annually by the start of this millennium. Presently, it is the most frequent cause of cancer-related death in both men and women in the United States. Approximately 178,100 new lung cancer cases were diagnosed in 1997, and 160,400 deaths will be attributed to this disease.1 Metastatic disease involving the lungs is observed in a vast number of additional malignancies, including those of gastrointestinal, genitourinary, breast, and mesenchymal origin; in some cases (particularly soft tissue sarcomas), pulmonary disease represents the sole site of distant metastases. This chapter focuses on current aspects of the pathophysiology and treatment of primary and metastatic tumors involving the lungs.

Keywords

Lung Cancer Pulmonary Metastasis Lung Cancer Risk Primary Lung Cancer Pulmonary Resection 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Parker SL, Tong T, Bolden S, Wingo PA. Cancer statistics, 1996. CA Cancer J Clin 1996;46:5–27.PubMedCrossRefGoogle Scholar
  2. 2.
    Roggli VL, Vollmer RT, Greenberg SD, McGavrin MH, Spjut HJ, Yesner R. Lung cancer heterogeneity: a blinded and randomized study of 100 consecutive cases. Hum Pathol 1985;16:569–579.PubMedCrossRefGoogle Scholar
  3. 3.
    Travis WD, T.L.D.S. Lung cancer. Cancer 1995:191–192.Google Scholar
  4. 4.
    Carter D. Squamous cell carcinoma of the lung: an update. Semin Diagn Pathol 1985;2:226–234.PubMedGoogle Scholar
  5. 5.
    Melamed MR, Zaman MB, Flahinger BJ, Martini N. Radio-logically occult in situ and incipient invasive epidermoid lung cancer: detection by sputum cytology in a survey of asymptomatic cigarette smokers. Am J Surg Pathol 1977;1:5–16.PubMedCrossRefGoogle Scholar
  6. 6.
    Kung IT, Lui IO, Loke SL. Pulmonary scar cancer: a pathologic reappraisal. Am J Surg Pathol 1985;9:391–400.PubMedCrossRefGoogle Scholar
  7. 7.
    World Health Organization. Histological typing of lung tumors. In: International Histologic Classification of Tumors. World Health Organization: Geneva, 1981:1–1.Google Scholar
  8. 8.
    Daly RC, Trastek VF, Pairolero PC. Bronchoalveolar carcinoma: factors affecting survival. Ann Thorac Surg 1991:51:368–377.PubMedCrossRefGoogle Scholar
  9. 9.
    Manning JT Jr, Spjut HJ, Tschen JA. Broncholoalveolar carcinoma: the significance of two histopathologic types. Cancer 1984;54:525–534.PubMedCrossRefGoogle Scholar
  10. 10.
    Colby TV, Koss MN, Travis WD. Tumors of the lower respiratory tract. 3. Armed Forces Institute of Pathology: Washington, DC, 1995.Google Scholar
  11. 11.
    Travis WD, Linnoila RI, Tsokos MG. Neuroendocrine tumors of the lung with proposed criteria for large-cell neuroendocrine carcinoma: an ultrastructural, immuno-histochemical, and flow cytometric study of 35 cases. Am J Surg Pathol 1991;15:529.PubMedCrossRefGoogle Scholar
  12. 12.
    Rush W, Zeren H, Griffin JL, et al. Histologic subtypes of pulmonary neuroendocrine carcinomas: prognostic correlations [abstract]. Mod Pathol 1995;8:10.Google Scholar
  13. 13.
    Ihde DC, Pass HI, Glatstein E. Small cell lung cancer. In: DeVita VT Jr, Hellman S, Rosenberg SA (eds) Cancer: Principles and Practice of Oncology. Lippincott-Raven: Philadelphia, 1997:911–949.Google Scholar
  14. 14.
    Hirsch FR, Matthews JM, Aisner S. Histopathologic classification of small cell lung cancer: changing concepts and terminology. Cancer 1988;62:973–977.PubMedCrossRefGoogle Scholar
  15. 15.
    Arrigoni MG, Woolner LB, Bernatz PE. Atypical carcinoid tumors of the lung. J Thorac Cardiovasc Surg 1972;64: 413–421.PubMedGoogle Scholar
  16. 16.
    McCaughan BC, Martini N, Bains MS. Bronchial carcinoids: review of 124 cases. J Thorac Cardiovasc Surg 1985; 89:8–17.PubMedGoogle Scholar
  17. 17.
    Paladugu RR, Benfield JR, Pak HY, Ross RK, Teplitz RL. Bronchopulmonary Kulchitzky cell carcinomas: a new classification scheme for typical and atypical carcinoids. Cancer 1985;55:1303–1311.PubMedCrossRefGoogle Scholar
  18. 18.
    Bonato M, Cerati M, Pagani A. Differential diagnostic patterns of lung neuroendocrine tumours: a clinico-pathological and immunohistochemical study of 122 cases. Virchows Arch 1992;420:201–211.CrossRefGoogle Scholar
  19. 19.
    Advisory Committee to the Surgeon General of the US Public Health Service. Smoking and health. Government Printing Office: Washington, DC, 1964:1103.Google Scholar
  20. 20.
    Osann KE, Anton-Culver LT, Korosak T, Taylor T. Sex differences in lung cancer risk associated with cigarette smoking. Int J Cancer 1993;54:44–48.PubMedCrossRefGoogle Scholar
  21. 21.
    Doll R, Peto R. Cigarette smoking and bronchial carcinoma: dose and time relationships among regular smokers and life-long nonsmokers. J Epidemiol Community Health 1978;32:303–313.PubMedCrossRefGoogle Scholar
  22. 22.
    Freedman DA, Navidi WC. Ex-smokers and the multistage model for lung cancer. Epidemiology 1990;1:21–29.PubMedCrossRefGoogle Scholar
  23. 23.
    Halpern MT, Gillespie BW, Warner KE. Patterns of absolute risk of lung cancer mortality in former smokers. J Natl Cancer Inst 1993;85:457–464.PubMedCrossRefGoogle Scholar
  24. 24.
    Tong L, Spitz MR, Fueger JJ, Amos CA. Lung carcinoma in former smokers. Cancer 1996;78:1004–1010.PubMedCrossRefGoogle Scholar
  25. 25.
    Wistuba II, Lam S, Behrens C, et al. Molecular damage in the bronchial epithelium of current and former smokers. J Natl Cancer Inst 1997;89:1366–1373.PubMedCrossRefGoogle Scholar
  26. 26.
    International Agency for Research on Cancer (IARC). Tobacco smoking: IARC monographs on the evaluation of carcinogenic risk of chemicals to humans. IARC 1986:38.Google Scholar
  27. 27.
    Wynder EL, Muscat JE. The changing epidemiology of smoking and lung cancer histology. Environ Health Per-spect 1995;103:143–148.Google Scholar
  28. 28.
    Lubin JH, Blot WJ, Berrino F. Patterns of lung cancer risk according to type of cigarette smoked. Int J Cancer 1984;33:569–576.PubMedCrossRefGoogle Scholar
  29. 29.
    Wilcox H, Schoenberg J, Mason T. Smoking and lung cancer: risk as a function of cigarette tar content. Prev Med 1988;17:263–272.PubMedCrossRefGoogle Scholar
  30. 30.
    Malkinson AM. Primary lung tumors in mice: an experimentally manipulable model of human adenocarcinoma. Cancer Res 1992;52:2670s-2676s.Google Scholar
  31. 31.
    Thun MJ, Lally CA, Flannery JT, Calle EE, Flanders WD, Heath CW Jr. Cigarette smoking and chages in the his-topathology of lung cancer. J Natl Cancer Inst 1997;89: 1580–1586.PubMedCrossRefGoogle Scholar
  32. 32.
    US Surgeon General. The Health Consequences of Involuntary Smoking. US Department of Health and Human Services, Centers for Disease Control: Washington, DC, 1986.Google Scholar
  33. 33.
    Schottenfeld D. Epidemiology of lung cancer. In: Pass HI, Mitchell JB, Johnson DH, Turrisi AT (eds) Lung Cancer: Principles and Practice. Lippincott-Raven: Philadelphia, 1996:305–321.Google Scholar
  34. 34.
    Ooi WL, Elston RC, Chen VW, Bailey-Wilson JE, Rothschild H. Increased familial risk for lung cancer. J Natl Cancer Inst 1986;76:217–222.PubMedGoogle Scholar
  35. 35.
    Malkinson AM. The genetic basis of susceptibility to lung tumors in mice. Toxicology 1989;54:241–271.PubMedCrossRefGoogle Scholar
  36. 36.
    Chen B, Johanson L, Wiest JS, et al. The second intron of the K-ras gene contains regulatory elements associated with mouse lung tumor susceptibility. Proc Natl Acad Sci USA 1994;91:1589–1593.PubMedCrossRefGoogle Scholar
  37. 37.
    Sithanandam G, Ramakrishna G, Diwan BA, Anderson LM. Selective mutation of K-ras by N-ethylnitrosourea shifts from codon 12 to codon 61 during fetal mouse lung maturation. Oncogene 1998;17:493–502.PubMedCrossRefGoogle Scholar
  38. 38.
    Zang EA, Wynder EL. Differences in lung cancer risk between men and women: examination of the evidence. J Natl Cancer Inst 1996;88:183–192.PubMedGoogle Scholar
  39. 39.
    McDuffie HH, Klassen DJ, Dosman JA. Men, women and primary lung cancer—a Saskatchewan personal interview study. J Clin Epidemiol 1991;44:537–544.PubMedCrossRefGoogle Scholar
  40. 40.
    Begg CB, Zhang ZF, Sun M, Herr HW, Schantz SP. Methodology for evaluating incidence of second primary cancers with application to smoking-related cancers from S.E.E.R. Am J Epidemiol 1995;142:653–665.PubMedGoogle Scholar
  41. 41.
    Slaughter DP, Southwick HW, Smejkal W. “Field cancer-ization” in oral stratified squamous epithelium. Cancer 1953;6:963–968.PubMedCrossRefGoogle Scholar
  42. 42.
    Auerbach O, Stout AP, Hammond EC, Garfinkel L. Changes in bronchial epithelium in relation to cigarette smoking and in relation to lung cancer. N Engl J Med 1961;265:253–267.PubMedCrossRefGoogle Scholar
  43. 43.
    Smith AL, Hung J, Walker L, et al. Extensive areas of aneu-ploidy are present in the respiratory epithelium of lung cancer patients. Br J Cancer 1996;73:203–209.PubMedCrossRefGoogle Scholar
  44. 44.
    Thiberville L, Payne P, Vielkinds J, et al. Evidence of cumulative gene losses with progression of premalignant epithelial lesions to carcinoma of the bronchus. Cancer Res 1995;55:5133–5139.PubMedGoogle Scholar
  45. 45.
    Mao L, Lee JS, Kurie JM, et al. Clonal genetic alterations in the lungs of current and former smokers. J Natl Cancer Inst 1997;89:857–862.PubMedCrossRefGoogle Scholar
  46. 46.
    Wistuba II, Lam S, Behrens C, et al. Molecular damage in the bronchial epithelium of current and former smokers. J Natl Cancer Inst 1997;89:1366–1373.PubMedCrossRefGoogle Scholar
  47. 47.
    Hunter T, Pines J. Cyclins and cancer. II. Cyclin D and CDK inhibitors come of age. Cell 1994;79:573–582.PubMedCrossRefGoogle Scholar
  48. 48.
    Sherr CJ. Cancer cell cycles. Science 1996;274:1672–1677.PubMedCrossRefGoogle Scholar
  49. 49.
    Martin-Castellanos C, Moreno S. Recent advances on cyclins, CDKs and CDK inhibitors. Trends Cell Biol 1997;7:95–98.PubMedCrossRefGoogle Scholar
  50. 50.
    Grana X, Reddy EP. Cell cycle control in mammalian cells: role of cyclins, cyclin dependent kinases (CDKs), growth suppressor genes and cyclin-dependent kinase inhibitors (CKIs). Oncogene 1995;11:211–219.PubMedGoogle Scholar
  51. 51.
    Filmus J, Robles AI, Shi W, Wong MJ, Colombo LL, Conti CJ. Induction of cyclin D1 overexpression by activated ras. Oncogene 1994;9:3627–3633.PubMedGoogle Scholar
  52. 52.
    Lukas J, Bartkova J, Bartek J. Convergence of mitogenic signalling cascades from diverse classes of receptors at the cyclin D-cyclin-dependent kinase-pRb-controlled G1 checkpoint. Mol Cell Biol 1996;16:17–25.Google Scholar
  53. 53.
    El-Deiry WS, Tokino T, Velculescu VE, et al. WAF1, a potential mediator of p53 tumor suppression. Cell 1993; 75:817–825.PubMedCrossRefGoogle Scholar
  54. 54.
    Schauer IE, Siriwardana S, Langan TA, Sclafani RA. Cyclin D1 overexpression vs retinoblastoma inactivation: implications for growth control evasion in non-small cell and small cell lung cancer. Proc Natl Acad Sci USA 1994;91:7827–7831.PubMedCrossRefGoogle Scholar
  55. 55.
    Sreekantaiah C, Ladanyi M, Rodriguez E, Chaganti R. Chromosomal aberrations in soft tissue tumors. Am J Clin Pathol 1994;111:121–134.Google Scholar
  56. 56.
    Lukas J, Aagaard L, Strauss M, Bartek J. Oncogenic aberrations of p16INK4/CDKN2 and cyclin Dl cooperate to deregulate G1 control. Cancer Res 1995;55:4818–1823.PubMedGoogle Scholar
  57. 57.
    Wharton J, Polak JM, Bloom SR, et al. Bombesin-like immunoreactivity in the lung. Nature 1978;273:769–770.PubMedCrossRefGoogle Scholar
  58. 58.
    Moody TW, Carney DN, Cuttitta F, Quattrocchi K, Minna JD. High affinity receptors for bombesin/GRP-like peptides on human small-cell lung cancer. Life Sci 1985;37:105–113.PubMedCrossRefGoogle Scholar
  59. 59.
    Carney DN, Cuttitta F, Moody TW, Minna JD. Selective stimulation of small-cell lung cancer clonal growth by bombesin and gastrin-releasing peptide. Cancer Res 1987; 47:821–825.PubMedGoogle Scholar
  60. 60.
    Layton JE, Scanlon DB, Soveny C, Morstyn G. Effects of bombesin antagonists on the growth of small cell lung cancer cells in vitro. Cancer Res 1988;48:4783–1789.PubMedGoogle Scholar
  61. 61.
    Hunter T. The epidermal growth factor gene and its product. Nature 1984;311:414–416.PubMedCrossRefGoogle Scholar
  62. 62.
    Veale D, Kerr N, Gibson GJ, Harris AL. Characterization of epidermal growth factor receptor in primary human non-small cell lung cancer. Cancer Res 1989;49:1313–1317.PubMedGoogle Scholar
  63. 63.
    Rusch V, Baselga J, Cordon-Cardo C, et al. Differential expression of the epidermal growth factor receptor and its ligands in primary non-small cell lung cancers and adjacent benign lung tissue. Cancer Res 1993;53:2379–2385.PubMedGoogle Scholar
  64. 64.
    Wong ST, Winchell LF, McCune BK, et al. The TGF-a precursor expressed on the cell surface binds to the EGF receptor on adjacent cells leading to signal transduction. Cell 1989;56:495–506.PubMedCrossRefGoogle Scholar
  65. 65.
    Veale D, Kerr N, Gibson GJ, Kelly PJ, Harris AJ. The relationship of quantitative epidermal growth factor receptor expression in non-small cell lung cancer to long term survival. Br J Cancer 1993;68:162–165.PubMedCrossRefGoogle Scholar
  66. 66.
    Bargmann CI, Hung M-C, Weinberg RA. The neu oncogene encodes on epidermal frowth factor receptor-related protein. Nature 1986;319:226–230.PubMedCrossRefGoogle Scholar
  67. 67.
    Shi D, He G, Cao S, et al. Overexpression of the c-erbB-2/neu-encoded p185 protein in primary lung cancer. Carcinogenesis 1992;5:213–218.CrossRefGoogle Scholar
  68. 68.
    Kern JA, Schwartz DA, Nordberg JE, et al. p185neu expression in human lung adenocarcinomas predicts shortened survival. Cancer Res 1990;50:5184–5191.PubMedGoogle Scholar
  69. 69.
    Tsai C-M, Chang K-T, Perng R-P, et al. Correlation of intrinsic chemoresistance of non-small cell lung cancer cell lines with HER-2/neu gene expression but not with ras gene mutations. J Natl Cancer Inst 1993;85:897–901.PubMedCrossRefGoogle Scholar
  70. 70.
    Heldin C-H, Westermark B. Platelet-derived growth factor: mechanism of action and possible in vivo function. Cell Regul 1990;1:555–556.PubMedGoogle Scholar
  71. 71.
    Safi A, Sadmi M, Martinet N, et al. Presence of elevated levels of platelet-derived growth factor (PDGF) in lung adenocarcinoma pleural effusions. Chest 1992;102: 204–207.PubMedCrossRefGoogle Scholar
  72. 72.
    Antoniades HN, Galanopoulos T, Neville-Golden J, O’Hara CJ. Malignant epithelial cells in primary human lung carcinomas coexpress in vivo platelet-derived growth factor (PDGF) and PDGF receptor mRNAs and their protein products. Proc Natl Acad Sci USA 1992;89: 3942–3946.PubMedCrossRefGoogle Scholar
  73. 73.
    Antoniades HR, Galanopoulos T, Neville-Golden J, Kiristy CP, Lynch SE. Injury induces in vivo expression of platelet derived growth factor (PDGF) and PDGF receptor mRNAs in skin epithelial cells and PDGF mRNA in connective tissue fibroblasts. Proc Natl Acad Sci USA 1991;84:565–569.CrossRefGoogle Scholar
  74. 74.
    Rechler MM, Nissley SP. The nature and regulation of the receptors for insulin-like growth factors. Annu Rev Physiol 1985;47:425–142.PubMedCrossRefGoogle Scholar
  75. 75.
    Pietrzkowski Z, Lammers R, Carpenter G, et al. Constitutive expression of insulin-like growth factor 1 and insulin-like growth factor 1 receptor abrogates all requirements for exogenous growth factors. Cell Growth Differ 1992;3:199.PubMedGoogle Scholar
  76. 76.
    Macaulay VM, Everard MJ, Teale JD, et al. Autocrine function for insulin-like growth factor I in human small cell lung cancer cell lines and fresh tumor cells. Cancer Res 1990;50:2511–2517.PubMedGoogle Scholar
  77. 77.
    Kaiser U, Schardt C, Brandscheidt D, Wollmer E, Havemann K. Expression of insulin-like growth factor receptors I and II in normal human lung and in lung cancer. J Cancer Res Clin Oncol 1993;119:665–668.PubMedCrossRefGoogle Scholar
  78. 78.
    Caputi M, DeLuca L, Papaccio G, et al. Prognostic role of cyclin D1 in non-small cell lung cancer: an immunohisto-chemical analysis. Eur J Histochem 1997;41:133–138.PubMedGoogle Scholar
  79. 79.
    Mate JL, Ariza A, Aracil C, et al. Cyclin D1 overexpression in non-small cell lung carcinoma: correlation with Ki67 labelling index and poor cytoplasmic differentiation. J Pathol 1996;180:395–399.PubMedCrossRefGoogle Scholar
  80. 80.
    Feig LA. The many roads that lead to ras. Science 1993; 260:767–768.PubMedCrossRefGoogle Scholar
  81. 81.
    Rodenhuis S, Slebos RJC. Clinical significance of ras oncogene activation in human lung cancer. Cancer Res 1992;52:2665s-2669s.Google Scholar
  82. 82.
    Horio Y, Chen A, Rice P, Roth JA, Malkinson AM, Schrump DS. Ki-ras and p53 mutations are early and late events, respectively, in urethane-induced pulmonary carcinogenesis in A/J mice. Mol Carcinog 1996;17:217–223.PubMedCrossRefGoogle Scholar
  83. 83.
    Westra WH, Baas IO, Hruban RH, et al. K-ras oncogene activation in atypical alveolar hyperplasias of the human lung. Cancer Res 1996;56:2224–2228.PubMedGoogle Scholar
  84. 84.
    Harada M, Dosaka-Akita H, Miyamoto H, Kuzumaki N, Kawakami Y. Prognostic significance of the expression of ras oncogene product in non-small cell lung cancer. Cancer 1992;69:72–77.PubMedCrossRefGoogle Scholar
  85. 85.
    Koskinen PJ, Alitalo K. Role of myc amplification and over-expression in cell growth, differentiation and death. Cancer Biol 1993;4:3–12.Google Scholar
  86. 86.
    Amati B, Brooks MW, Levy N, Littlewood TD, Evan GI, Land H. Oncogene activity of the C-myc protein requires dimerization with max. Cell 1993;72:233–245.PubMedCrossRefGoogle Scholar
  87. 87.
    Brennan J, O’Connor T, Makuch RW, et al. Myc family DNA amplification in 107 tumors and tumor cell lines from patients with small cell lung cancer treated with different combination chemotherapy regimens. Cancer Res 1998; 51:1708–1712.Google Scholar
  88. 88.
    Testa EH, Siegfried JM. Chromosome abnormalities in human non-small cell lung cancer. Cancer Res 1992;52: 2702–2706.Google Scholar
  89. 89.
    Whang-Peng J, Knutsen T, Gazdar A, et al. Nonrandom structural and numerical chromosome changes in non-small-cell lung cancer. Genes Chromosomes Cancer 1991;3:168–188.PubMedCrossRefGoogle Scholar
  90. 90.
    Field JK, Neville EM, Stewart MP, et al. Fractional allele loss data indicate distinct genetic populations in the development of non-small-cell lung cancer. Br J Cancer 1996;74:1968–1974.PubMedCrossRefGoogle Scholar
  91. 91.
    Hung J, Kishimoto Y, Sugio K, et al. Allele-specific chromosome 3p deletions occur at an early stage in the pathogenesis of lung carcinoma. JAMA 1995;273:558–563.PubMedCrossRefGoogle Scholar
  92. 91a.
    Hung J, Kishimoto Y, Sugio K, et al. Erratum. JAMA 1995;273:1908.PubMedCrossRefGoogle Scholar
  93. 92.
    Hibi K, Takahashi T, Yamakawa K, et al. Three distinct regions involved in 3p deletion in human lung cancer. Oncogene 1992;7:445–449.PubMedGoogle Scholar
  94. 93.
    Whang-Peng J, Knutsen T, Gazdar A, et al. Nonrandom structural and numerical chromosome changes in non-small-cell lung cancer. Genes Chromosom Cancer 1991; 3:168–188.PubMedCrossRefGoogle Scholar
  95. 94.
    Lu R, Nash HM, Verdine GL. A mammalian DNA repair enzyme that excises oxidatively damaged guanines maps to a locus frequently lost in lung cancer. Curr Biol 1997; 7:397–407.PubMedCrossRefGoogle Scholar
  96. 95.
    Fong KM, Biesterveld EJ, Virmani A, et al. FHIT and FRA3B 3p14.2 allele loss are common in lung cancer and preneoplastic bronchial lesions and are associated with cancer related FHIT cDNA splicing aberrations. Cancer Res 1997;57:2256–2267.PubMedGoogle Scholar
  97. 96.
    Nelson HH, Wiencke JK, Gunn L, Wain JC, Christiani DC, Kelsey KT. Chromosome 3pl4 alterations in lung cancer: evidence that FHIT exon deletion is a target of tobacco carcinogens and asbestos. Cancer Res 1998;58:1804–1807.PubMedGoogle Scholar
  98. 97.
    Burke L, Khan MA, Freedman AN, et al. Allelic deletion analysis of the FHIT gene predicts poor survival in non-small cell lung cancer. Cancer Res 1998;58:2533–2536.PubMedGoogle Scholar
  99. 98.
    Siprashvili Z, Sozzi G, Barnes LD, et al. Replacement of FHIT in cancer cells suppresses tumorigenicity. Proc Natl Acad Sci USA 1997;94:13771–13776.PubMedCrossRefGoogle Scholar
  100. 99.
    Chen PL, Riley DJ, Lee WH. The retinoblastoma protein as a fundamental mediator of growth and differentiation signals. Crit Rev Eukaryot Gene Expr 1995;1:79–95.Google Scholar
  101. 100.
    Ewen ME. The cell cycle and the retinoblastoma protein family. Cancer Metastasis Rev 1994;13:45–66.PubMedCrossRefGoogle Scholar
  102. 101.
    Harbour JW, Lai S-L, Whang-Peng J, Gazdar AF, Minna JD, Kaye FJ. Abnormalities in structure and expression of the human retinoblastoma gene in SCLC. Science 1988; 241:353–357.PubMedCrossRefGoogle Scholar
  103. 102.
    Reissman PT, Koga H, Takahashi R, et al. Inactivation of the retinoblastoma susceptibility gene in non-small-cell lung cancer. Oncogene 1993;8:1913–1919.Google Scholar
  104. 103.
    Horowitz JM, Park SH, Bogenmann E, et al. Frequent inactivation of the retinoblastoma anti-oncogene is restricted to a subset of human tumor cells. Proc Natl Acad Sci USA 1990;87:2775–2779.PubMedCrossRefGoogle Scholar
  105. 104.
    Okamoto A, Hussain SP, Hagiwara K, et al. Mutations in the p16INK4/MTSl/CDKN2,P15INK4B/MTS2, and pl8 genes in primary and metastatic lung cancer. Cancer Res 1995; 55:1448–1451.PubMedGoogle Scholar
  106. 105.
    Merlo A, Herman JG, Mao L, et al. 5’CpG island methyla-tion is associated with transcriptional silencing of the tumour suppressor pl6/CDKN2/MTSl in human cancers. Nat Med 1995;1:686–692.PubMedCrossRefGoogle Scholar
  107. 106.
    Otterson GA, Khleif SN, Chen W, Coxon AB, Kaye FJ. CDKN2 gene silencing in lung cancer by DNA hyperme-thylation and kinetics of p16INK4 protein induction by 5-aza 2’deoxycytidine. Oncogene 1995;11:1211–1216.PubMedGoogle Scholar
  108. 107.
    Kastan MB, Canman CE, Leonard CJ. p53, cell cycle control and apoptosis: implications for cancer. Cancer Metastasis Rev 1995;14:3–15.PubMedCrossRefGoogle Scholar
  109. 108.
    Kastan MB, Onyekwere O, Sidransky D, Vogelstein B, Craig R. Participation of p53 protein in the cellular response to DNA damage. Cancer Res 1991;51:6304–6311.PubMedGoogle Scholar
  110. 109.
    El-Deiry WS, Harper JW, O’Connor PM, et al. WAF1/CIP1 is induced in p53-mediated G1 arrest and apoptosis. Cancer Res 1994;54:1169–1174.PubMedGoogle Scholar
  111. 110.
    Hollstein M, Sidransky D, Vogelstein B, Harris CC. p53 mutations in human cancers. Science 1991;253:49–53.PubMedCrossRefGoogle Scholar
  112. 111.
    Denissenko MF, Pao A, Tang M, Pfeifer GP. Preferential formation of benzo[a]pyrene adducts at lung cancer mutational hotspots in p53. Science 1996;274:430–432.PubMedCrossRefGoogle Scholar
  113. 112.
    Marchetti A, Buttitta F, Merlo G, et al. p53 Alterations in non-small cell lung cancers correlate with metastatic involvement of hilar and mediastinal lymph nodes. Cancer Res 1993;53:2846–2851.PubMedGoogle Scholar
  114. 113.
    Horio Y, Takahashi T, Kuroishi T, et al. Prognostic significance of p53 mutations and 3p deletions in primary resected non-small cell lung cancer. Cancer Res 1993; 53:1–4.PubMedGoogle Scholar
  115. 114.
    Zhang WW, Fang X, Mazur W, French BA, Georges RN, Roth JA. High-efficiency gene transfer and high-level expression of wild-type p53 in human lung cancer cells mediated by recombinant adenovirus. Cancer Gene Ther 1994;1:5–13.PubMedGoogle Scholar
  116. 115.
    Roth JA, Nguyen D, Lawrence DD, et al. Retrovirus-mediated wild-type p53 gene transfer to tumors of patients with lung cancer. Nat Med 1996;2:985–991.PubMedCrossRefGoogle Scholar
  117. 116.
    Mountain CF. A new international staging system for lung cancer. Chest 1986;89:225S-233S.Google Scholar
  118. 117.
    Dewan NA, Shehan CJ, Reeb SD, Gobar LS, Scott WJ, Ryschon K. Likelihood of malignancy in a solitary pulmonary nodule: comparison of bayesian analysis and results of FDG-PET scan. Chest 1997;112:416–422.PubMedCrossRefGoogle Scholar
  119. 118.
    Guhlmann A, Storck M, Kotzerke J, Moog F, Sunder-Plassmann L, Reske SN. Lymph node staging in non-small cell lung cancer: evaluation by [18F]FDG positron emission tomography (PET). Thorax 1997;52:438–441.PubMedCrossRefGoogle Scholar
  120. 119.
    Scott WJ, Gobar LS, Terry JD, Dewan NA, Sunderland JJ. Mediastinal lymph node staging of non-small-cell lung cancer: a prospective comparison of computed tomography and positron emission tomography. J Thorac Cardiovasc Surg 1996;111:642–648.PubMedCrossRefGoogle Scholar
  121. 120.
    Steinert HC, Hauser M, Allemann F, et al. Non-small cell lung cancer: nodal staging with FDG PET versus CT with correlative lymph node mapping and sampling. Radiology 1997;202:441–446.PubMedGoogle Scholar
  122. 121.
    Santambrogio L, Nosotti M, Bellaviti N, Pavoni G, Radice F, Caputo V. CT-guided needle aspiration cytology of solitary pulmonary nodules: a prospective, randomized study of immediate cytologic evaluation. Chest 1997;112: 423–425.PubMedCrossRefGoogle Scholar
  123. 122.
    Stewart CJ, Stewart IS. Immediate assessment of fine needle aspiration cytology of lung. J Clin Pathol 1996;49: 839–843.PubMedCrossRefGoogle Scholar
  124. 123.
    Takizawa T, Masanori T, Koike T, Akamatsu H, Kurita Y, Yokoyama A. Mediastinal lymph node metastasis in patients with clinical stage I peripheral non-small-cell lung cancer. J Thorac Cardiovasc Surg 1997;113:248–252.PubMedCrossRefGoogle Scholar
  125. 124.
    Carlens E. Mediastinoscopy: a method for inspection and tissue biopsy in the superior mediastinum. Chest 1959; 36:343–348.CrossRefGoogle Scholar
  126. 125.
    Lee JD, Ginsberg RJ. The multimodality treatment of stage III A/B non-small cell lung cancer: the role of surgery, radiation, and chemotherapy. Hematol Oncol Clin North Am 1997;11:279–301.PubMedCrossRefGoogle Scholar
  127. 126.
    Pearson FG, Delarue NC, Iives R, Tood TRJ, Cooper JD. Significance of positive superior mediastinal nodes identified at mediastinoscopy in patients with resectable cancer of the lung. J Thorac Cardiovasc Surg 1982;83:1–11.PubMedGoogle Scholar
  128. 127.
    Ginsberg RJ. Extended cervical mediastinoscopy. Chest Surg Clin North Am 1996;6:21–30.Google Scholar
  129. 128.
    McNeill TM, Chamberlain JM. Diagnostic anterior medi-astinotomy. Ann Thorac Surg 1996;2:532–535.CrossRefGoogle Scholar
  130. 129.
    Lee JD, Ginsberg RJ. Lung cancer staging: the value of ipsi-lateral scalene lymph node biopsy performed at mediastinoscopy. Ann Thorac Surg 1996;62:338–341.PubMedCrossRefGoogle Scholar
  131. 130.
    Mack MJ, Aronoff RJ, Acuff TE, et al. Present role of thoracoscopy in the diagnosis and treatment of diseases of the chest. Ann Thorac Surg 1992;54:403–409.PubMedCrossRefGoogle Scholar
  132. 131.
    Rusch VW, Bains MS, Burt ME, McCormack PM, Ginsberg RJ. Contribution of videothoracoscopy to the management of the cancer patient. Ann Surg Oncol 1994;1:94–98.PubMedCrossRefGoogle Scholar
  133. 132.
    Landreneau RJ, Hazelrigg SR, Mack MJ, et al. Thoracoscopic mediastinal lymph node sampling: useful for mediastinal lymph node stations inaccessible by cervical mediastinoscopy. J Thorac Cardiovasc Surg 1993;106: 554–558.PubMedGoogle Scholar
  134. 133.
    Roseli R, Gómez-Condina J, Camps C, et al. A randomized trial comparing preoperative chemotherapy plus surgery with surgery alone in patients with non-small-cell lung cancer. N Engl J Med 1994;330:153–158.CrossRefGoogle Scholar
  135. 134.
    Dartevelle PG. Extended operations for the treatment of lung cancer. Ann Thorac Surg 1997;63:12–19.PubMedCrossRefGoogle Scholar
  136. 135.
    Mathisen DJaGHC. Carinal resection for bronchogenic carcinoma. J Thorac Cardiovasc Surg 1991;102:16–23.Google Scholar
  137. 136.
    Nesbitt JC, Moores DWO. Staging of lung cancer. In: Roth JA, Ruckdeschel JC, Weisenburger TH (eds) Thoracic Oncology. Saunders: Philadelphia, 1995:84–103.Google Scholar
  138. 137.
    Burt M, Wronski M, Arbit E, Galicich JH, Martini N, Ginsberg RJ. Resection of brain metastases from non-small-cell lung carcinoma: results of therapy. J Thorac Cardiovasc Surg 1992;103:399–411.PubMedGoogle Scholar
  139. 138.
    Luketich JD, Burt ME. Does resection of adrenal metastases from non-small cell lung cancer improve survival? Ann Thorac Surg 1996;62:1614–1616.PubMedCrossRefGoogle Scholar
  140. 139.
    Ferguson MK, Little L, Rizzo L, et al. Diffusing capacity predicts morbidity and mortality after pulmonary resection. J Thorac Cardiovasc Surg 1988;96:894–900.PubMedGoogle Scholar
  141. 140.
    Morice RC, Peters EJ, Ryan MB, Putnam JB Jr, Ali MK, Roth JA. Exercise testing in the evaluation of patients at high risk for complications from lung resection. Chest 1992; 101:356–361.PubMedCrossRefGoogle Scholar
  142. 141.
    Morice RC. Preoperative evaluation of the patient with lung cancer. In: Roth JA, Cox JD, Hong WK (eds) Lung Cancer. Blackwell Science: Maiden, MA, 1998:73–86.Google Scholar
  143. 142.
    Walsh GL, Morice RC, Putnam JB, et al. Resection of lung cancer is justified in high-risk patients selected by exercise oxygen consumption. Ann Thorac Surg 1994; 58:704–711.PubMedCrossRefGoogle Scholar
  144. 143.
    Smart J, Hilton G. Radiotherapy of cancer of the lung: results in a selective group of cases. Lancet 1956;1:880.CrossRefGoogle Scholar
  145. 144.
    Morrison R, Deeley TJ, Cleland W. The treatment of carcinoma of the bronchus: a clinical trial to compare surgery and super-voltage radiotherapy. Lancet 1963;1:683.CrossRefGoogle Scholar
  146. 145.
    Dombernowsky P, Hansen HH. Small cell lung cancer: clinical presentation and natural history of small cell lung cancer. In: Roth JA, Ruckdeschel JC, Weisenburger TH (eds) Thoracic Oncology. Saunders: Philadelphia, 1995: 188–200.Google Scholar
  147. 146.
    Nesbitt JC, Putnam JB, Walsh GL, Roth JA, Mountain CF. Survival in early-stage non-small cell lung cancer. Ann Thorac Surg 1995;60:466–472.PubMedCrossRefGoogle Scholar
  148. 147.
    Martini N, Burt ME, Bains MS, et al. Survival after resection of stage II non-small cell lung cancer. Ann Thorac Surg 1992;54:460–466.PubMedCrossRefGoogle Scholar
  149. 148.
    Ginsberg RJ, Rubenstein LA. A randomized comparative trial of lobectomy versus limited resection for patients with TINO non-small cell lung cancer. Lung Cancer 1991;7: 83–88.CrossRefGoogle Scholar
  150. 149.
    Warren WH, Faber LP. Segmentectomy versus lobectomy in patients with stage I pulmonary carcinoma. J Thorac Cardiovasc Surg 1994;107:1087–1094.PubMedGoogle Scholar
  151. 150.
    Landreneau RJ, Sugarbaker DJ, Mack MJ, et al. Wedge resection versus lobectomy for stage I (TI NO M0) non-small cell lung cancer. J Thorac Cardiovasc Surg 1997; 113:691–700.PubMedCrossRefGoogle Scholar
  152. 151.
    Landreneau RJ, Mack MJ, Dowling RD, et al. The role of thoracoscopy in lung cancer management. Chest 1998;113: 6S-12S.CrossRefGoogle Scholar
  153. 152.
    Yim AP, Liu HP. Thoracoscopic major lung resection—indications, technique, and early results: experience from two centers in Asia. Surg Laparosc Endosc 1997;7:241–244.PubMedCrossRefGoogle Scholar
  154. 153.
    Kawahara K, Iwasaki A, Shiraishi T, Okabayashi K, Shirakusa T. Video-assisted thoracoscopic lobectomy for treating lung cancer. Surg Laparosc Endosc 1997;7:219–222.PubMedCrossRefGoogle Scholar
  155. 154.
    Kaseda S, Hangai N, Yamamoto S, Kitano M. Lobectomy with extended lymph node dissection by video-assisted thoracic surgery for lung cancer. Surg Endosc 1997;11: 703–706.PubMedCrossRefGoogle Scholar
  156. 155.
    Iwasaki A, Shirakusa T, Kawahara K, Yoshinaga Y, Okabayashi K, Shiraishi T. Is video-assisted thoracoscopic surgery suitable for resection of primary lung cancer? Thorac Cardiovasc Surg 1997;45:13–15.PubMedCrossRefGoogle Scholar
  157. 156.
    Roth JA, Fossella F, Komaki R, et al. A randomized trial comparing perioperative chemotherapy and surgery with surgery alone in resectable stage III non-small cell lung cancer. J Natl Cancer Inst 1994;86:673–680.PubMedCrossRefGoogle Scholar
  158. 157.
    Goldie JH, Coldman AJ. The genetic origin of drug resistance in neoplasms: implications for systemic therapy. Cancer Res 1984;44:3643–3653.PubMedGoogle Scholar
  159. 158.
    Strauss GM, Herndon JE, Sherman DD, et al. Neoadjuvant chemotherapy and radiotherapy followed by surgery in stage IIIA non-small-cell carcinoma of the lung: report of a cancer and leukemia group B phase II study. J Clin Oncol 1992;10:1237–1244.PubMedGoogle Scholar
  160. 159.
    Martini N, Kris MG, Flehinger BJ, et al. Preoperative chemotherapy for stage IIIa (N2) lung cancer: the Sloan-Kettering experience with 136 patients. Ann Thorac Surg 1993;55:1365–1374.PubMedCrossRefGoogle Scholar
  161. 160.
    Weiden PL, Piantadosi S. Preoperative chemotherapy (cis-platin and fluorouracil) and radiation therapy in stage III non-small-cell lung cancer: a phase II study of the lung cancer study group. J Natl Cancer Inst 1991;83:266–273.PubMedCrossRefGoogle Scholar
  162. 161.
    Silini EM, Bosi F, Pellegata NS, et al. K-ras gene mutations: an unfavorable prognostic marker in stage I lung adenocarcinoma. Virchows Arch 1994;424:367–373.PubMedCrossRefGoogle Scholar
  163. 162.
    Favaretto A, Paccagnella A, Tornio L, et al. Pre-operative chemoradiotherapy in non-small cell lung cancer stage III patients: feasibility, toxicity and long-term results of a phase II study. Eur J Cancer 1996;31A:2064–2069.CrossRefGoogle Scholar
  164. 163.
    Choi N, Mathisen D, Carey R, et al. Assessment of preoperative accelerated radiotherapy (RT) and chemotherapy (CT) in stage IIIA non-small cell lung cancer (NSCLC) [abstract]. Proc Am Soc Clin Oncol 1994;13:a1097-a1097.Google Scholar
  165. 164.
    Lee JD, Ginsberg RJ. The multimodality treatment of stage III A/B non-small lung cancer: the role of surgery, radiation, and chemotherapy. Hematol Oncol Clin North Am 1997;11:279–301.PubMedCrossRefGoogle Scholar
  166. 165.
    Martini N, Kris MG, Ginsberg RJ. The role of multimodality therapy in locoregional non-small cell lung cancer. Surg Oncol Clin North Am 1997;6:769–791.Google Scholar
  167. 166.
    Cote RJ, Beattie EJ, Benjaporn C, et al. Detection of occult bone marrow micrometastases in patients with operable lung carcinoma. Ann Surg 1995;222:415–425.PubMedGoogle Scholar
  168. 167.
    Roth JA. A clinical trial of retroviral gene transfer of wild-type p53 in lung cancer patients with mutant p53 tumor. Nat Med 1996;2:985–991.PubMedCrossRefGoogle Scholar
  169. 168.
    Swisher SG, Roth JA, Lawrence DD, et al. Adenoviral mediated p53 gene transfer in patients with advanced non-small cell lung cancer (NSCLC) [abstract]. Proc Am Soc Clin Oncol 1997;16:437a.Google Scholar
  170. 169.
    Carbone DP. Immunologic and biologic approaches to lung cancer therapy In: Roth JA, Cox JD, Hong WK (eds) Lung Cancer. Blackwell Science: Maiden, MA, 1998: 343–368.Google Scholar
  171. 170.
    Abrams HL, Spiro R, Goldstein N. Metastases in carcinoma: analysis of 1000 autopsied cases. Cancer 1950;3:74.PubMedCrossRefGoogle Scholar
  172. 171.
    Farrell JT Jr. Pulmonary metastasis: a pathologic, clinical, roentgenologic study based on 78 cases seen at necropsy. Radiology 1935;24:444.Google Scholar
  173. 172.
    Fidler IJ. Special lecture: critical factors in the biology of human cancer metastasis: twenty-eight GHA; Clowes memorial award lecture. Cancer Res 1990;50:6130–6138.PubMedGoogle Scholar
  174. 173.
    Fidler IJ, Balch CM. The biology of cancer metastasis and implications for therapy. Curr Probi Surg 1987;24:137–209.CrossRefGoogle Scholar
  175. 174.
    Miller BJ, Rosenbaum AS. The vascular supply to metastatic tumors of the lung. Surg Gynecol Obstet 1967;125: 1009–1012.PubMedGoogle Scholar
  176. 175.
    Neyazaki T, Ikeda M, Mitusi K, Kimura S, Suzuki M, Suzuki C. Angioarchitecture of pulmonary malignancies in humans. Cancer 1970;26:1246–1255.PubMedCrossRefGoogle Scholar
  177. 176.
    Torek F. Removal of metastatic carcinoma of the lung and mediastinum: suggestions as to technic. Arch Surg 1930; 21:1416–1421.CrossRefGoogle Scholar
  178. 177.
    Alexander J, Haight C. Pulmonary resection for solitary metastatic sarcoma and carcinoma. Surg Gynecol Obstet 1947;85:129–146.PubMedGoogle Scholar
  179. 178.
    Mannix EP Jr. Resection of multiple pulmonary metastases fourteen years after amputation for osteochondrogenic sarcoma of tibia: apparent freedom from recurrence two years later. J Thorac Surg 1953;26:544–549.PubMedGoogle Scholar
  180. 179.
    Gliedman ML, Horowitz S, Lewis FJ. Lung resection for metastatic cancer: 29 cases from the University of Minnesota and a collected review of 264 cases. Surgery 1957;42:521–532.PubMedGoogle Scholar
  181. 180.
    Thomford NR, Woolner LB, Clagett OT. The surgical treatment of metastatic tumors in the lungs. J Thorac Cardiovasc Surg 1965;49:357–363.PubMedGoogle Scholar
  182. 181.
    Lanza LA, Putnam JB. Resection of pulmonary metastases, In: Roth JA, Ruckdeschel JR, Weisenburger TH (eds) Thoracic Oncology. Saunders: Philadelphia, 1996:569–589.Google Scholar
  183. 182.
    McCormack PM, Bains MS, Begg DB, et al. Role of video-assisted thoracic surgery in the treatment of pulmonary metastases: results of a prospective trial. Ann Thorac Surg 1996;62:213–216.PubMedCrossRefGoogle Scholar
  184. 183.
    Gundry SR, Coran AG, Lemmer J. The influence of tumor microfoci on recurrence and survival following pulmonary resection of metastatic osteogenic sarcoma. Ann Thorac Surg 1984;38:473–478.PubMedCrossRefGoogle Scholar
  185. 184.
    Buhr J, Hurtgen M, Heinrichs CM, Weimar B, Morr H, Schwemmle K. Tumor dissemination after thoracoscopic resection of malignant pulmonary coin lesions. Chirurg 1996;67:81–85.PubMedGoogle Scholar
  186. 185.
    Johnstone PA, Rohde DC, Swartz SE, Fetter JE, Wexner SD. Port site recurrences after laparoscopic and thoracoscopic procedures in malignancy. J Clin Oncol 1996;14:1950–1956.PubMedGoogle Scholar
  187. 186.
    Martini N, Huvos AG, Mike V, Marcove RC, Beattie EJ. Multiple pulmonary resections in the treatment of osteogenic sarcoma. Ann Thorac Surg 1971;12:271–280.PubMedCrossRefGoogle Scholar
  188. 187.
    Putnam J, Roth JA, Wesley MN, Johnston MR, Rosenberg SA. Survival following aggressive resection of pulmonary metastases from osteogenic sarcoma: analysis of prognostic factors. Ann Thorac Surg 1983;38:516–523.CrossRefGoogle Scholar
  189. 188.
    Goorin AM, Delorey MJ, Lack EE. Prognostic significance of complete surgical resection of pulmonary metastases in patients with osteogenic sarcoma: analysis of 32 patients. J Clin Oncol 1984;2:425–431.PubMedGoogle Scholar
  190. 189.
    Lanza LA, Putnam JB, Benjamin RS, Roth JA. Response to chemotherapy does not predict survival after resection of sarcomatous pulmonary metastases. Soc Thorac Surg 1991;51:219–224.CrossRefGoogle Scholar
  191. 190.
    Pogrebniak HW, Roth JA, Steinberg SM, Rosenberg SA, Pass HI. Reoperative pulmonary resection in patients with metastatic soft tissue sarcoma. Ann Thorac Surg 1991;52: 197–203.PubMedCrossRefGoogle Scholar
  192. 191.
    McCormack PM, Burt ME, Bains MS, Martini N, Rusch VW, Ginsberg RJ. Lung resection for colorectal metastases: 10-year results. Arch Surg 1992;127:1403–1406.PubMedCrossRefGoogle Scholar
  193. 192.
    Okimura S, Kondo H, Tsubai M. Pulmonary resection for metastatic colorectal cancer: experience with 159 patients. J Thorac Cardiovasc Surg 1996;112:867–874.CrossRefGoogle Scholar
  194. 193.
    Girard P, Ducreux M, Baldeyrou P. Surgery for lung metastases from colorectal cancer: analysis of prognostic factors. J Clin Oncol 1996;14:2047.Google Scholar
  195. 194.
    McAfee MK, Allen MS, Trastek VF, Ilstrup DM, Deschamps C, Pairolero PC. Colorectal lung metastases: results of surgical excision. Ann Thorac Surg 1992;53: 780–786.PubMedCrossRefGoogle Scholar
  196. 195.
    Pogrebniak HW, Haas G, Linehan WM, Rosenberg SA, Pass HI. Renal cell carcinoma: resection of solitary and multiple metastases. Ann Thorac Surg 1992;54:33–38.PubMedCrossRefGoogle Scholar
  197. 196.
    Kavolius JP, Mastorakos DP, Pavlovich C, Russo P, Burt ME, Brady MS. Resection of metastatic renal cell carcinoma. J Clin Oncol 1998;16:2261–2266.PubMedGoogle Scholar
  198. 197.
    Jett JR, Hollinger CG, Zinsmeister AR, Pairolero PC. Pulmonary resection of metastatic renal cell carcinoma. Chest 1983;84:442–445.PubMedCrossRefGoogle Scholar
  199. 198.
    Cerfolio RJ, Allen MS, Deschamps C, et al. Pulmonary resection of metastatic renal cell carcinoma. Ann Thorac Surg 1994;57:339–344.PubMedCrossRefGoogle Scholar
  200. 199.
    Lanza LA, Natarajan G, Roth JA, Putnam JB Jr. Long-term survival after resection of pulmonary metastases from carcinoma of the breast. Ann Thorac Surg 1992;54: 244–248.PubMedCrossRefGoogle Scholar
  201. 200.
    Staren ED, Salerno C, Rongione A, Witt TR, Faber LP. Pulmonary resection for metastatic breast cancer. Arch Surg 1992;127:1282–1284.PubMedCrossRefGoogle Scholar
  202. 201.
    Friedel G, Linder A, Toomes H. The significance of prognostic factors for the resection of pulmonary metastases of breast cancer. Thorac Cardiovasc Surg 1994;42:71–75.PubMedCrossRefGoogle Scholar
  203. 202.
    Vogt-Moykopf I, Krysa S, Bulzebruck H. Surgery for pulmonary metastases: the Heidelberg experience. Chest Surg Clin North Am 1994;4:85–112.Google Scholar
  204. 203.
    Gorenstein LA, Putnam JB Jr, Natarajan G, Balch CA, Roth JA. Improved survival after resection of pulmonary metastases from malignant melanoma. Ann Thorac Surg 1991;52:204–210.PubMedCrossRefGoogle Scholar
  205. 204.
    Harpole DH Jr, Johnson CM, Wolfe WG, George SL, Seigier HF. Analysis of 945 cases of pulmonary metastatic melanoma. J Thorac Cardiovasc Surg 1992;103:743–750.PubMedGoogle Scholar
  206. 205.
    Tafra L, Dale PS, Wanek LA, Ramming KP, Morton DL. Resection and adjuvant immunotherapy for melanoma metastatic to the lung and thorax. J Thorac Cardiovasc Surg 1995;110:119–129.PubMedCrossRefGoogle Scholar
  207. 206.
    Putnam JB Jr, Suell DM, Natarajan G, Roth JA. Extended resection of pulmonary metastases: is the risk justified. Ann Thorac Surg 1993;55:1440–1446.PubMedCrossRefGoogle Scholar
  208. 207.
    Schrump DS. Cardiopulmonary Bypass for Extended Resection of Thoracic Malignancies. In: Franco KL, Putnam JB (eds) Advanced Therapy in Thoracic Surgery. B.C. Decker, Inc.: London, 1998:238–243.Google Scholar
  209. 208.
    Pastorino U, Buyse M, Friedel G, et al. Long-term results of lung metastasectomy: prognostic analyses based on 5206 cases. J Thorac Cardiovasc Surg 1997;113:49.CrossRefGoogle Scholar
  210. 209.
    Roth J. Treatment of the patient with lung metastases. Curr Probi Surg 1996;33:892–952.Google Scholar
  211. 210.
    Jacobs JK, Flexner JM, Scott HW Jr. Selective isolated perfusion of the right lung. J Thorac Cardiovasc Surg 1961;42:546–552.PubMedGoogle Scholar
  212. 211.
    Pierpont H, Blades B. Lung perfusion with chemothera-peutic agents. Cardiovasc Surg 1960;39:159–165.Google Scholar
  213. 212.
    Johnson MR, Minchen RF, Dawson CA. Lung perfusion with chemotherapy in patients with unresectable metastatic sarcoma to the lung or diffuse branchi-oloalveolar carcinoma. J Thorac Cardiovasc Surg 1995; 110:368–373.CrossRefGoogle Scholar
  214. 213.
    Weksler B, Burt M. Isolated lung perfusion with antineoplastic agents for pulmonary metastases. Chest Surg Clin N Am 1998;8:157–182.PubMedGoogle Scholar
  215. 214.
    Putnam JB, Madden T, Tran HT, Benjamin RS. Isolated single lung perfusion (ISLP) with Adriamycin® for unresectable sarcomatous metastases [abstract]. Proc ASCO 1997;16:500a.Google Scholar
  216. 215.
    Mürdter TE, Sperker B, Kivistö KT, et al. Enhanced uptake of doxorubicin into bronchial carcinoma: ß-glucuronidase mediates release of doxorubicin from a glucuronide prodrug (HMR 1826) at the tumor site. Cancer Res 1997;57:2440–2445.PubMedGoogle Scholar
  217. 216.
    Pass HI, Mew DJY, Kranda KC, Temeck BK, Donington JS, Rosenberg SA. Isolated lung perfusion with tumor necrosis factor for pulmonary metastases. Ann Thorac Surg 1996;61:1609–1617.PubMedCrossRefGoogle Scholar
  218. 217.
    Ratto GB, Toma S, Civalleri D, et al. Isolated lung perfusion with platinum in the treatment of pulmonary metastases from soft tissue sarcomas. J Thorac Cardiovasc Surg 1996;112:614–622.PubMedCrossRefGoogle Scholar
  219. 218.
    Benjamin RS, Putnam JB, Tran HT, Hager HK, Madden T. High levels of doxorubicin in human lung and pulmonary metastases following single-pass isolated-single-lung perfusion [abstract]. 88th Annual Meeting. Am Assoc Cancer Res 1997;38:609.Google Scholar
  220. 219.
    Taylor CW, Wang LM, List AF, et al. Amifostine protects normal tissues from paclitaxel toxicity while cytotoxicity against tumour cells is maintained. Eur J Cancer 1997;33:1693–1698.PubMedCrossRefGoogle Scholar
  221. 220.
    Neyazaki T, Ikeda M, Seki Y, Egawa N, Suzuki C. Bronchial artery infusion therapy for lung cancer. Cancer 1969;24: 912–922.PubMedCrossRefGoogle Scholar
  222. 221.
    Nicholson KM, Bibby MC, Phillips RM. Influence of drug exposure parameters on the activity of paclitaxel in multicellular spheroids. Eur J Cancer 1997;33:1291–1298.PubMedCrossRefGoogle Scholar
  223. 222.
    Schrump DS, Zhai S, Nguyen DM, Weiser TS, et al. Pharmacokinetics and Acute Toxicity of Paclitaxel Administered via Hyperthermic Retrograde Isolated Lung Perfusion. 2000, Submitted for publication.Google Scholar
  224. 223.
    Matsuoka H, Furusawa M, Tomoda H, Seo Y. Difference in cytotoxicity of paclitaxel against neoplastic and normal cells. Anticancer Res 1994;14:163–168.PubMedGoogle Scholar
  225. 224.
    Donaldson KL, Goolsby GL, Wahl AF. Cytotoxicity of the anticancer agents cisplatin and taxol during cell proliferation and the cell cycle. Int J Cancer 1994;57:847–855.PubMedCrossRefGoogle Scholar
  226. 225.
    Crossin KL, Carney DH. Microtubule stabilization by taxol inhibits initiation of DNA synthesis by thrombin and epidermal growth factor. Cell 1981;27:341–350.PubMedCrossRefGoogle Scholar
  227. 226.
    Schiff PB, Horowitz SB. Taxol stabilizes microtubules in mouse fibroblast cells. Proc Natl Acad Sci USA 1980;77:1561–1565.PubMedCrossRefGoogle Scholar
  228. 227.
    Hennequin C, Giocanti N, Favaudon V. S-phase specificity of cell killing by docetaxel (Taxotere) in synchronized HeLa cells. Br J Cancer 1995;71:1194–1198.PubMedCrossRefGoogle Scholar
  229. 228.
    Rowinsky EK, Donehower RC, Jones RJ, Tucker RW. Microtubule changes and cytotoxicity in leukemic cell lines treated with taxol. Cancer Res 1988;48:4093–4100.PubMedGoogle Scholar
  230. 229.
    Blagasklonny MV, Schulte T, Nguyen P, Trepel J, Kneckers LM. Taxol-induced apoptosis and phosphorylation of Bcl-2 protein involves c-Raf-1 and represents a novel c-Raf-1 signal transduction pathway. Cancer Res 1996;56: 1851–1854.Google Scholar
  231. 230.
    Milross CG, Mason KA, Hunter NR, Chung WK, Peters LJ, Milas L. Relationship of mitotic arrest and apoptosis to antitumor effect of paclitaxel. J Natl Cancer Inst 1996; 88:1308–1314.PubMedCrossRefGoogle Scholar
  232. 231.
    Wahl AF, Donaldson KL, Fairchild C, et al. Loss of normal p53 function confers sensitization to taxol by increasing G2/M arrest and apoptosis. Nat Med 1996; 2:72–79.PubMedCrossRefGoogle Scholar
  233. 232.
    Safran H, King T, Choy H, et al. p53 mutations do not predict response to paclitaxel/radiation for nonsmall cell lung carcinoma. Cancer 1996;78:1203–1210.PubMedCrossRefGoogle Scholar
  234. 233.
    Maier-Lenz H, Hauns B, Haering B, et al. Phase I study of paclitaxel administered as a 1-hour infusion: toxicity and pharmacokinetics. Semin Oncol 1997;24:S19–16–S19–19.Google Scholar
  235. 234.
    Hainsworth JD, Raefsky EL, Greco FA. Paclitaxel administered by a 1-hour infusion: a phase I-II trial comparing two schedules. Cancer J Sci Am 1995;1:281–287.PubMedGoogle Scholar
  236. 235.
    Hainsworth JD, Thompson DS, Greco FA. Paclitaxel by 1-hour infusion: an active drug in metastatic non-small-cell lung cancer. J Clin Oncol 1995;13:1609–1614.PubMedGoogle Scholar
  237. 236.
    Greenberger LM, Williams SS, Horowitz SB. Biosynthesis of heterogeneous forms of multidrug resistance-associated glycoproteins. J Biol Chem 1987;262:13685–13689.PubMedGoogle Scholar
  238. 237.
    Rischin D, Webster LK, Millward MJ, et al. Cremophor pharmacokinetics in patients receiving 3-, 6-, and 24-hour infusions of paclitaxel. J Natl Cancer Inst 1996;88: 1297–1301.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2001

Authors and Affiliations

  • David S. Schrump

There are no affiliations available

Personalised recommendations