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Fluorescence versus white-light bronchoscopy for detection of preneoplastic lesions: a randomized study.

Prakash, Udaya B. S. M.D.


Mayo Medical Center and Mayo Medical School, Rochester, Minnesota, U.S.A.

Fluorescence versus white-light bronchoscopy for detection of preneoplastic lesions: a randomized study.

J Natl Cancer Inst 2001;93:1385–91. Hirsch FR, Prindiville SA, Miller YE, Franklin WA, Dempsey EC, Murphy JR, Bunn PA Jr, Kennedy TC. Department of Pathology, Department of Medical Oncology, Department of Preventive Medicine, University of Colorado Health Sciences Center and Cancer Center, Denver, Colorado, U.S.A.

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This study compared the ability of conventional white-light bronchoscopy (WLB) and laser-induced fluorescence endoscopy (LIFE) to detect preneoplastic lung lesions (PNL) in a randomized trial in which both the order of the procedures and the bronchoscopists were assigned randomly. The study included high-risk subjects with a cigarette smoking history (>30 pack-years), air-flow obstruction (FEV1 ≤ 0.75 or < 70% predicted), and either abnormal sputum cytology (n = 48) or previous or suspected lung cancer (n = 7). LIFE and WLB were performed on all patients. Biopsy specimens were assessed for histologic abnormalities, including the presence of angiogenic squamous dysplasia. A total of 55 patients provided 391 biopsy specimens, and 32 patients (58%) had at least one biopsy with moderate or severe dysplasia. In 19 of the 32 patients (59%), moderate or severe dysplasia was diagnosed solely by LIFE. The LIFE system was significantly more sensitive than WLB in detecting moderate dysplasia or worse (68.8% vs. 21.9% respectively; p < 0.001). LIFE was more sensitive for detecting all grades of bronchial atypia, including metaplasia, but not for detecting severe dysplasia or worse. The authors believe that the reason for the lack of significance for detecting severe dysplasia or worse was probably the result of the small number of patients in this category. The relative sensitivities (WLB = 1.0) were 3.1 for LIFE and 3.7 for LIFE and WLB combined. LIFE was better at identifying angiogenic squamous dysplasia lesions than WLB. The authors conclude that LIFE was more sensitive than WLB in detecting bronchial PNLs in high-risk subjects and that the prognostic implication of this finding is not yet clear. The 5-year survival rates for patients with stage IA disease are approximately 70%; however, for those with disease at stages II to IV, the rates range from 40% to less than 5%. Therefore, early diagnosis of lung cancer remains at the forefront of research to minimize deaths from lung cancer. Sputum cytology and chest roentgenography have not succeeded in reducing lung cancer mortality. Other techniques to detect lung cancer at its earliest stages have included molecular biology, gene technology, and spiral CT. Because WLB is not sensitive enough to detect early mucosal changes suggestive of PNLs, autofluorescence bronchoscopy (AFB) using the LIFE technique has been used to detect PNLs in bronchial mucosa (Chest 1998;113:696–702, J Bronchol 1998;5:280–3, J Natl Cancer Inst 1998;90:991–5 ). Conceptually it makes clinical sense to detect PNLs and carcinoma in situ because approximately 10% of patients with moderate cellular atypia in sputum samples and 40 to 80% of patients with severe cellular atypia may develop invasive cancer. In a multicenter study of 700 biopsy specimens from 173 high-risk subjects, the relative sensitivity of WLB and LIFE combined was 6.3 times that of WLB alone for detecting dysplasia and carcinoma in situ, and 2.7 times that of WLB alone for detecting moderate or severe (i.e., high-grade) dysplasia, carcinoma in situ, and invasive carcinoma (Chest 1998;113:696–702 ). However, another study found no difference in the diagnostic efficacy of WLB and LIFE in smokers (J Natl Cancer Inst 1998;90:991–5 ). What is clear from various publications on this subject is that standard bronchoscopy (i.e., WLB) is ineffective in detecting premalignant changes in the bronchial epithelium and in detecting early lung cancers. Another interesting finding of the study was the ability to detect angiogenic squamous dysplasia. Angiogenic squamous dysplasia is a newly recognized morphologic entity found commonly in preneoplastic tissue. LIFE detected 75% of the lesions with angiogenic squamous dysplasia. In contrast, WLB detected only 15%. This substantial difference may be explained by the fact that the angiogenic lesions contain hemoglobin, which affects autofluorescence. Even though the study by Hirsch et al. has demonstrated that LIFE increased the ability to detect premalignant changes in the bronchial epithelium of high-risk patients when compared with WLB, further refinements are needed to establish this particular method over others. Currently, there are no established techniques for the screening for or the early detection of lung cancer.

© 2002 Lippincott Williams & Wilkins, Inc.