Dual digital video-autofluorescence imaging for detection of pre-neoplastic lesions
Introduction
Lung cancer at the beginning of the twentieth century was rare. Since then the rates of lung cancer in men and women have increased 10-fold, making it the second most common cancer and the leading cause of cancer deaths in the United States. Today, lung cancer accounts for more deaths than breast, prostate and colon cancers combined [1]. Prognosis and survival depend on the stage of disease, and since more than two thirds of patients with lung cancer have mediastinal lymph node or distant metastases at presentation, it is not surprising that cure rate remains dismal at 15% [2]. Experience with cervical, oesophageal and colon cancers has demonstrated that if neoplastic lesions can be detected and treated in the intra-epithelial stage, significant improvement in cure rates translating to survival benefit can be achieved [3], [4], [5].
White light bronchoscopy (WLB) is reflectance imaging that exploits three optical properties of reflection, scattering and absorption when bronchial tissue is illuminated by light. This technology has led to the detection of early hilar lung cancer [6], and endoscopic features of dysplasia and carcinoma in situ (CIS) with WLB have been described [7]. However, Woolner have shown that only a third of patients with CIS could be identified with this modality [8].
Laser induced fluorescence endoscopy (LIFE; Xilix Technologies Corp., Richmond, Canada) is a device that has facilitated the detection of pre-neoplastic lesions by capturing the differences in fluorescence emitted by normal, pre-neoplastic or early malignant tissue when excited by monochromatic blue light (442 nm) delivered by a helium cadium laser. Subsequent clinical studies with LIFE have shown marked increase in sensitivity for the localization of lesions with moderate dysplasia and worse [9], [10], [11], [12], [13], [14].
Although LIFE is highly sensitive, difficulties in distinguishing benign epithelial changes such as bronchitis from pre-invasive lesions as well as in the accurate prediction of pathological diagnosis based on the grade of tissue fluorescence have necessitated extensive biopsy with consequent greater health costs, longer procedural time and higher incidence of procedure related bronchitis which may require hospitalization for treatment. In fact, studies have demonstrated that as high as one third of these areas detected with abnormal fluorescence by LIFE represented false positives when correlated with pathology [10], [15], [16]. Of particular clinical relevance would be in chemoprevention trials and surveillance following endobronchial treatment of CIS where previous biopsy sites and consequent airway fibrosis may result in abnormal fluorescence that could persist for months to years, making interpretation a challenge.
This study was therefore undertaken to determine if real-time dual video and autofluorescence (AF) bronchoscopic images could improve specificity without compromising sensitivity for the detection of pre-neoplastic lesions to allow targeted biopsy, shorten procedural time and good pathological correlation.
Section snippets
Material and methods
The protocol was approved by the institutional review board of Vrije University (Amsterdam), and written informed consent was obtained from all patients.
Results
Forty-eight patients (43 males, 5 females) with median age 66 years (range, 62–72) underwent dual imaging bronchoscopy from March to August 2006 for indications as shown in Table 2. All were current and former smokers of 40 pack years (range, 36–48).
A total of 126 biopsy specimens were taken with median 3 (range, 2–4) biopsies per patient. All specimens showed adequate bronchial epithelium for evaluation by the pathologist, and 22 (17.5%) were classified as moderate dysplasia and worse (high
Discussion
Clinical studies have shown that AF improves the detection of high grade dysplasia of the bronchial epithelium (moderate dysplasia and worse) by 1.3 to 6.4 times over WLB [9], [10], [11], [13], [14]. However, these earlier studies were carried out the fiberoptic bronchoscopes. With the advent of the videobronchoscope that has a miniature charge couple device built in its tip which delivers clearer images, sensitivity for the detection of premalignant lesions has correspondingly improved Table 4
Conclusion
Indeed our study with real-time dual display of video and AF images not only achieves good sensitivity and specificity for the detection of high grade dysplasia, it also facilitates targeted biopsy with good pathological correlation thereby translating to shorter procedural time, better patient comfort and safety. More research is required to validate its discriminatory value in distinguishing benign epithelial changes such as bronchitis, previous biopsy site and airway fibrosis from
Acknowledgements
Bronchoscopy system (SAFE 3000) was supported by Pentax (Tokyo, Japan). There was no other financial support for the authors nor does any author have a financial relationship with a commercial entity that has an interest in the subject of this manuscript.
References (20)
- et al.
Localization of bronchial intraepithelial neoplastic lesions by fluorescence bronchoscopy
Chest
(1998) - et al.
Fluorescence bronchoscopy in the detection of preinvasive bronchial lesions in patients with sputum cytology suspicious or positive for malignancy
Lung Cancer
(2001) - et al.
Detection of bronchial preneoplastic lesions and early lung cancer with fluorescence bronchoscopy: a study about its ambulatory feasibility under local anaesthesis
Lung Cancer
(1999) - et al.
Effective detection of bronchial preinvasive lesions by a new autofluorescence imaging bronchovideoscope system
Lung Cancer
(2005) - et al.
Early detection of bronchial lesions using newly developed videoendoscopy-based autofluorescence bronchoscopy
Lung Cancer
(2006) - et al.
Cancer statistics, 2005
CA Cancer J Clin
(2005) Chemotherapy of lung cancer
N Engl J Med
(1992)- et al.
Organisation and results of the cervical cytology screening programme in British Columbia, 1955–85
Br Med J (Clin Res Ed)
(1988) - et al.
Preventing effect of “liuwei dihuang decoction” on esophageal carcinoma
Gan To Kagaku Ryoho
(1989) - et al.
Prevention of colorectal cancer by colonoscopic polypectomy. The National Polyp Study Workgroup
N Engl J Med
(1993)
Cited by (42)
The role of bronchoscopy in the screening and the early diagnosis of lung cancer
2013, Revue des Maladies Respiratoires ActualitesFluorescence and navigational bronchoscopy
2013, Thoracic Surgery ClinicsCitation Excerpt :Depending on the type of reflected light used to combine with the fluorescence image for display, abnormal areas appear brownish red, red, purple, or magenta, while normal areas appear green or light blue.6,8–11 Some devices allow simultaneous display of the white light and fluorescence images.7,12 An example of a carcinoma in situ detected by autofluorescence bronchoscopy is shown in Fig. 1.
Autofluorescence bronchoscopy and new endoscopic methods
2012, Revue des Maladies Respiratoires ActualitesInterventional pulmonology
2011, Medical Clinics of North AmericaA comparison of autofluorescence bronchoscopy and white light bronchoscopy in detection of lung cancer and preneoplastic lesions: A meta-analysis
2011, Lung CancerCitation Excerpt :Hirsch et al. reached a similar conclusion using patient as unit of analysis [28]. Lee et al. examined patients with SAFE3000 bronchoscopy system, in which both white light and autofluorescence bronchoscopic images were displayed simultaneously, and a high sensitivity and specificity were achieved by providing functional and anatomic information at the same time analogous to PET/CT [34]. In a prospective randomized multicentre trial, Haussinger et al. demonstrated that combination of WLB and AFB was significantly superior to WLB alone in detecting preneoplastic lesions [35].
The value of autofluorescence bronchoscopy combined with white light bronchoscopy compared with white light alone in the diagnosis of intraepithelial neoplasia and invasive lung cancer: A meta-analysis
2011, Journal of Thoracic OncologyCitation Excerpt :Two hundred seventy-three reports were originally retrieved after electronic searching, and 41 studies were identified after scanning the titles and abstracts. Twenty studies were excluded for the following reasons: (a) only AFB was performed6–8; (b) sufficient data not presented to calculate sensitivity and specificity9–18; (c) positive result not moderate/severe dysplasia, CIS, or invasive cancer19–21; (d) where data presented in more than one article, article with fewest details was excluded22; and (e) studies were not per-lesion based23–25 (Figure 1). Twenty-one studies meeting the inclusion criteria were identified.26–46