Early Lung Cancer: Methods for Detection



Recent advances in technology over the past two decades have transformed the flexible bronchoscopy into an advanced diagnostic modality through the introduction of endobronchial ultrasound, allowing advanced assessment of the airway as well as the mediastinum and peripheral lung nodules. Advanced airway assessment techniques have opened an avenue for early endobronchial malignancy detection and surveillance. Autofluorescence bronchoscopy (AFB), narrow band imaging (NBI), and high-magnification bronchovideoscope are some of the advanced bronchoscopic imaging techniques capable of detecting preinvasive lesions currently available in clinical practice. The radial probe endobronchial ultrasound (EBUS) allows a more precise evaluation of newly detected preinvasive lesions within the airway. These advancements allow visualization of the endobronchial structures within the superficial mucosal layer with ability to differentiate between premalignant and malignant lesions, utilizing differential patterns of normal and pathological tissue autofluorescence or vasculature. This chapter will review the advanced bronchoscopic mucosal imaging technologies for detection of early lung cancer.


Narrow Band Imaging Lung Cancer Mortality Central Airway Bronchial Mucosa Early Lung Cancer 
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.



Autofluorescence bronchoscopy


Autofluorescence imaging


Angiogenic squamous dysplasia


Carcinoma in situ


Endobronchial ultrasound


High-magnification bronchovideoscope


Narrow band imaging


Nicotinamide adenine dinucleotide hydrogen


Optical coherence tomography


Photodynamic therapy


Squamous cell carcinoma


White light bronchoscopy


  1. 1.
    Horner MJ, Ries LAG, Krapcho M, et al., editors. SEER cancer statistics review, 1975–2006. Bethesda, MD: National Cancer Institute. Available from Based on November 2008 SEER data submission, posted on the SEER website, 2009. Accessed 23 Aug 2011.
  2. 2.
    Ries L, Eisner M, Kosary C, editors. Cancer statistics review, 1975–2002. Bethesda, MD: National Cancer Institute; 2005.Google Scholar
  3. 3.
    The National Lung Screening Trial Research Team. Reduced lung cancer mortality with low-dose computed tomographic screening. N Engl J Med. 2011;365:395–409.CrossRefGoogle Scholar
  4. 4.
    Yasufuku K. Early diagnosis of lung cancer. In: Mehta A, editor. Clin Chest Med (Interventional pulmonology). 2010; 31(1): 40–7.Google Scholar
  5. 5.
    Niklinski J, Niklinski W, Chyczewskis L, et al. Molecular genetic abnormalities in premalignant lung lesions: biological and clinical implications. Eur J Cancer Prev. 2001;10:213–26.PubMedCrossRefGoogle Scholar
  6. 6.
    Thiberville L, Payne P, Vielkinds J, et al. Evidence of cumulative gene losses with progression of the premalignant epithelial lesions to carcinoma of the bronchus. Cancer Res. 1995;155:5133–9.Google Scholar
  7. 7.
    Band PR, Feldstein M, Saccomanno G. Reversibility of bronchial marked atypia: implication for chemoprevention. Cancer Detect Prev. 1986;9:157–60.PubMedGoogle Scholar
  8. 8.
    Venmans BJ, van Boxem TJ, Smith EF, et al. Outcome of bronchial carcinoma in situ. Chest. 2000;117:1572–6.PubMedCrossRefGoogle Scholar
  9. 9.
    Ikeda N, Hayashi A, Iwasaki K, et al. Comprehensive diagnostic bronchoscopy of central type early stage lung cancer. Lung Cancer. 2007;56:295–302.PubMedCrossRefGoogle Scholar
  10. 10.
    Lam S, Kennedy T, Unger M, et al. Localization of bronchial intraepithelial neoplastic lesions by fluorescence bronchoscopy. Chest. 1998;113:696–702.PubMedCrossRefGoogle Scholar
  11. 11.
    Shibuya K, Fujiwara T, Yasufuku K, et al. In vivo microscopic imaging of the bronchial mucosa using an endo-cytoscopy system. Lung Cancer. 2011;72:184–90.PubMedCrossRefGoogle Scholar
  12. 12.
    Keith RL, Miller YE, Gemmill RM, et al. Angiogrnic squamous dysplasia in bronchi of individuals at high risk for lung cancer. Clin Cancer Res. 2000;6:1616–25.PubMedGoogle Scholar
  13. 13.
    Interventional bronchoscopy. Progress in respiratory research, vol. 30. Switzerland: Springer Kaarger; 2000. p. 243.Google Scholar
  14. 14.
    Colt H, Murgu S. Interventional bronchoscopy form bench to bedside: new techniques for early lung cancer detection. In: Mehta A, editor. Clin Chest Med (Interventional pulmonology). 2010; 31(1): 29–37.Google Scholar
  15. 15.
    Chiyo M, Shibuya K, Hoshino H, et al. Effective detection of bronchial preinvasive lesions by a new autofluorescence imaging bronchovideoscope system. Lung Cancer. 2005;48:307–13.PubMedCrossRefGoogle Scholar
  16. 16.
    Sun J, Garfield D, Lam B. The role of autofluorescence bronchoscopy combined with white light bronchoscopy compared with white light alone in diagnosis of intraepithelial neoplasia and invasive lung cancer. J Thorac Oncol. 2011;6:1336–44.PubMedCrossRefGoogle Scholar
  17. 17.
    Van Rens M, Schramel F, Elbers J, et al. The clinical value of lung imaging autofluorescence endoscope for detecting synchronous lung cancer. Lung Cancer. 2001;32:13–8.PubMedCrossRefGoogle Scholar
  18. 18.
    Kusunoki Y, Imamura F, Uda H, et al. Early detection of lung cancer with laser-induced fluorescence endoscopy and spectrofluorometry. Chest. 2000;118:1776–82.PubMedCrossRefGoogle Scholar
  19. 19.
    Sato M, Sakurada A, Sagawa M, et al. Diagnostic results before and after induction of autofluorescence bronchoscopy in patients suspected of having lung cancer detected by sputum cytology in lung cancer mass screening. Lung Cancer. 2001;32:247–53.PubMedCrossRefGoogle Scholar
  20. 20.
    Pierard P, Martin B, Verdebout J, et al. Fluorescence bronchoscopy in high-risk patients – a comparison of LIFE and pentax systems. J Bronchol. 2001;8:254–9.CrossRefGoogle Scholar
  21. 21.
    Chhajed PN, Shibuya K, Hoshino H, et al. A comparison of video and autofluorescence bronchoscopy in patients at high risk of lung cancer. Eur Respir J. 2005;25:951–5.PubMedCrossRefGoogle Scholar
  22. 22.
    Weigel TL, Kosco PJ, Dacic S, et al. Postoperative fluorescence bronchoscopic surveillance in non- small cell lung cancer patients. Ann Thorac Surg. 2001;71:967–70.PubMedCrossRefGoogle Scholar
  23. 23.
    Shibuya K, Fujisawa T, Hoshino H, et al. Fluorescence bronchoscopy in detection of preinvasive bronchial lesions in patients with sputum cytology suspicious or positive for malignancy. Lung Cancer. 2001;32:19–25.PubMedCrossRefGoogle Scholar
  24. 24.
    Haussinger K, Becker H, Stanzel F, et al. Autofluorescence bronchoscopy compared with white light bronchoscopy alone for the detection of precancerous lesions: a European randomised controlled multicentre trial. Thorax. 2005;60:496–503.PubMedCrossRefGoogle Scholar
  25. 25.
    Hirsch FR, Prindiville SA, Miller YE, et al. Fluorescence versus white light bronchoscopy for detection of preneoplastic lesions: a randomised study. J Natl Cancer Inst. 2001;93:1385–91.PubMedCrossRefGoogle Scholar
  26. 26.
    Ernst A, Simoff MJ, Mathur PN, et al. D-light autofluorescence in the detection of premalignant airway changes: a multicenter trial. J Bronchol. 2005;12:133–8.CrossRefGoogle Scholar
  27. 27.
    Edell E, Lam S, Pass H, et al. Detection and localization of intraepithelial neoplasia and invasive carcinoma using fluorescence-reflectance bronchoscopy – an international multicenter clinical trial. J Thorac Oncol. 2009;4:49–54.PubMedGoogle Scholar
  28. 28.
    Short MA, Lam S, McWilliams AM, et al. Using laser Raman spectroscopy to reduce false positive of autofluorescence bronchoscopy. A pilot study. J Thorac Oncol. 2011;6:1206–14.PubMedCrossRefGoogle Scholar
  29. 29.
    Tu AT. Raman spectroscopy in biology: principles and applications. New York, NY: Wiley; 1982.Google Scholar
  30. 30.
    Weigel TL, Yousem S, Dacic S, et al. Fluorescence bornchoscopic surveillance after curative surgical resection for non-small-cell lung cancer. Ann Surg Oncol. 2000;7:176–80.PubMedCrossRefGoogle Scholar
  31. 31.
    Sutedja TG, Codrington H, Risse EK, et al. Autofluorescence bronchoscopy improves staging of radiographically occult lung cancer and has an impact on therapeutic strategy. Chest. 2001;120:1327–32.PubMedCrossRefGoogle Scholar
  32. 32.
    Zaric B, Becker HD, Perin B, et al. Autofluorescence imaging videobronchoscopy improves assessment of tumor margins and affects therapeutic strategy in central lung cancer. Jpn J Clin Oncol. 2010;40:139–45.PubMedCrossRefGoogle Scholar
  33. 33.
    Furukawa K, Ikeda N, Miura T, et al. Is autofluorescence bronchoscopy needed to diagnose early bronchogenic carcinoma? Pro: autofluorescence bronchoscopy. J Bronchol. 2003;10:64–9.CrossRefGoogle Scholar
  34. 34.
    Pierard P, Vermylen P, Bosschaerts T, et al. Synchronous roentgenographically occult lung carcinoma in patients with resectable primary lung cancer. Chest. 2000;7:176–80.Google Scholar
  35. 35.
    Gono K, Obi T, Yamaguchi M, Ohyama N, Machida H, Sano Y, et al. Appearance of enhanced tissue features in narrow-band endoscopic imaging. J Biomed Opt. 2004;9:568–77.PubMedCrossRefGoogle Scholar
  36. 36.
    Gono K, Igarashi M, Obi T, Yamaguchi M, Ohyama N. Multiple-discriminanat analysis for white light-scattering spectroscopy and imaging of two layered tissue phantoms. Opt Lett. 2004;29:971–3.PubMedCrossRefGoogle Scholar
  37. 37.
    Tajiri H, Niwa H. Proposal for a consensus terminology in endoscopy: how should different endoscopic imaging techniques be grouped and defined? Endoscopy. 2008;40:775–8.PubMedCrossRefGoogle Scholar
  38. 38.
    Kaltenbach T, Sano Y, Friedland S, Soetikno R. American Gastroenterological Association (AGA) Institute technology assessment on image-enhanced endoscopy. Gastroenterology. 2008;134:327–40.PubMedCrossRefGoogle Scholar
  39. 39.
    Hirsch FR, Franklin WA, Gazdar AF, Bunn Jr PA. Early detection of lung cancer: clinical perspectives of recent advances in biology and radiology. Clin Cancer Res. 2001;7:5–22.PubMedGoogle Scholar
  40. 40.
    Shibuya K, Nakajima T, Fujiwara T, et al. Narrow band imaging with high-resolution bronchovideoscopy: a new approach for visualizing angiogenesis in squamous cell carcinoma of the lung. Lung Cancer. 2010;69:194–202.PubMedCrossRefGoogle Scholar
  41. 41.
    Hanahan D, Folkman J. Patterns and emerging mechanisms of the angiogenic switch during tomorigenesis. Cell. 1996;86:353–64.PubMedCrossRefGoogle Scholar
  42. 42.
    Hanahan D, Inoue H, Nagai K, Kawano T, et al. The hallmarks of cancer. Cell. 2000;100:57–70.PubMedCrossRefGoogle Scholar
  43. 43.
    Herth FJ, Eberhardt R, Anantham D, et al. Narrow-band imaging bronchoscopy increases the specificity of bronchoscopic early lung cancer detection. J Thorac Oncol. 2009;4:1060–5.PubMedCrossRefGoogle Scholar
  44. 44.
    Zaric B, Perlin B, Becker H, et al. Combination of narrow band imaging (NBI) and autofluorescnece imaging (AFI) videobronchoscopy in endoscopic assessment of lung cancer extention. Med Oncol. 2012;29(3):1638–42 (Published online 09 August 2011).PubMedCrossRefGoogle Scholar
  45. 45.
    Risse EK, Voojis GP, van’t Hoff MA. Diagnostic significance of ‘severe dysplasia’ in sputum cytology. Acta Cytol. 1988;32:629–34.PubMedGoogle Scholar
  46. 46.
    Sawyer RW, Hammond WG, Teplitz RL, et al. Regression of bronchial epithelial cancer in hamsters. Ann Thorac Surg. 1993;56:74–8.PubMedCrossRefGoogle Scholar
  47. 47.
    Breuer RH, Pasic A, Smith EF, et al. The natural course of preneoplastic lesions in bronchial epithelium. Clin Cancer Res. 2005;11:537–43.PubMedGoogle Scholar
  48. 48.
    Vincent B, Fraig M, Silvestri G. A pilot study of narrow-band imaging compared to white light bronchoscopy for evaluation of normal airways and premalignant and malignant airways disease. Chest. 2007;131:1794–9.PubMedCrossRefGoogle Scholar
  49. 49.
    Shibuya K, Hoshino H, Chiyo M, et al. Subepithelial vascular patterns in bronchial dysplasias using a high magnification bronchovideoscope. Thorax. 2002;57:902–7.PubMedCrossRefGoogle Scholar
  50. 50.
    Tanaka H, Yamada G, Sakai T, et al. Increased airway vascularity in newly diagnosed asthma using a high-magnification bronchovideoscope. Am J Respir Crit Care Med. 2003;168:1495–9.PubMedCrossRefGoogle Scholar
  51. 51.
    Kumaji Y, Inoue H, Nagai H, et al. Magnifying endoscopy, stereoscopic microscopy, and the microvascular architecture of superficial esophageal carcinoma. Endoscopy. 2002;34:369–75.CrossRefGoogle Scholar
  52. 52.
    Shibuya K, Nakajima T, Yasufuku K, et al. Narrow band imaging with high resolution bronchovideoscopy: a new approach to visualize angiogenesis in squamous cell carcinoma of the lung. Eur Respir J. 2006;28 Suppl 50:601s.Google Scholar
  53. 53.
    Yasufuku K. Current clinical applications of endobronchial ultrasound. Expert Rev Respir Med. 2010;4:491–8.PubMedCrossRefGoogle Scholar
  54. 54.
    Kurimoto N, Murayama M, Yoshioka S, Nishisaka T. Assessment of usefulness of endobronchial ultrasonography in determination of depth of tracheobronchial tumor invasion. Chest. 1999;115:1500–6.PubMedCrossRefGoogle Scholar
  55. 55.
    Tanaka F, Muro K, Yamasaki S, et al. Evaluation of tracheo-bronchial wall invasion using transbronchial ultrasonography (TBUS). Eur J Cardiothorac Surg. 2000;17:570–4.PubMedCrossRefGoogle Scholar
  56. 56.
    Herth FJ, Becker HD. EBUS for early lung cancer detection. J Bronchol. 2003;10:249.CrossRefGoogle Scholar
  57. 57.
    Miyazu Y, Miyazawa T, Kurimoto N, et al. Endobronchial ultrasonography in the assessment of centrally located early-stage lung cancer before photodynamic therapy. Am J Respir Crit Care Med. 2002;165:832–7.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Division of Thoracic Surgery, Toronto General HospitalUniversity Health Network, University of TorontoTorontoCanada

Personalised recommendations