Elsevier

Lung Cancer

Volume 58, Issue 1, October 2007, Pages 44-49
Lung Cancer

Dual digital video-autofluorescence imaging for detection of pre-neoplastic lesions

https://doi.org/10.1016/j.lungcan.2007.04.009Get rights and content

Summary

Aim

The incorporation of autofluorescence (AF) to white light bronchoscopy has led to improved sensitivity for the detection of pre-neoplastic lesions in the airways. However, AF has difficulty distinguishing benign epithelial changes such as bronchitis, previous biopsy, and airway fibrosis from pre-invasive lesions, which necessitates extensive biopsy. This frequently results in longer procedural time and need for additional sedation that may compromise patient safety, increase the risk of bronchospasm, and bleeding from multiple endobronchial biopsies. We postulate that dual imaging with simultaneous video and AF bronchoscopy of the tracheobronchial tree could improve the low specificity observed with AF in the detection of pre-invasive lesions, leading to targeted biopsy, good correlation with pathological diagnosis and shorter procedural time.

Methods

Forty-eight patients with known or suspected of lung cancer underwent video and AF bronchoscopy, which were provided as real-time dual images with SAFE 3000 (Pentax, Tokyo) between March and August 2006. Biopsy specimens were taken from all suspicious areas with two random specimens from normal areas. Values were expressed as median and range, and p < 0.05 was considered statistically significant.

Results

Twenty-five suspicious sites were detected by dual imaging bronchoscopy, and 126 endobronchial biopsies were evaluated, of which 22 (17.5%) were graded as moderate dysplasia and worse. Sensitivity and specificity of dual imaging for the detection of high-grade dysplasia were 86% and 94%, respectively, with good correlation between bronchoscopic assessment and pathology (r = 0.77, p < 0.0001). However, there were three random biopsy specimens obtained from normal or abnormal sites that showed severe dysplasia in two and moderate dysplasia in one. Median time taken for airway examination was 4 min (range, 4–4.8), and 5 min (range, 4–5) for biopsy, giving a total procedural time of 9 min (range, 8–10). There were no procedure-related complications noted.

Conclusion

Dual imaging that allows simultaneous real-time assessment of the lesion with video and AF bronchoscopy not only achieves satisfactory sensitivity for the detection of pre-neoplastic lesions, importantly it improves specificity by allowing targeted biopsy, which has led to a marked decrease in procedural time and better patient safety.

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)

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