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      Detection of premalignant bronchial lesions can be significantly improved by combination of advanced bronchoscopic imaging techniques

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          Abstract

          BACKGROUND:

          The search for the most efficient bronchoscopic imaging tool in detection of early lung cancer is still active. The major aim of this study was to determine sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of each bronchoscopic technique and their combination in detection of premalignant bronchial lesions.

          METHODS:

          This was a prospective trial that enrolled 96 patients with indication for bronchoscopy. Lesions were classified as visually positive if pathological fluorescence was observed under autofluorescence imaging (AFI) videobronchoscopy or dotted, tortuous, and abrupt-ending blood vessels were identified under narrow band imaging (NBI) videobronchoscopy. Squamous metaplasia, mild, moderate, or severe dysplasia, and carcinoma in situ (CIS) were regarded as histologically positive lesions.

          RESULTS:

          Sensitivity, specificity, PPV, and NPV of white light videobronchoscopy (WLB) in detection of premalignant lesions were 26.5%, 63.9%, 34.4%, and 54.9%, respectively; the corresponding values for AFI were 52%, 79.6%, 64.6%, and 69.9% respectively, for NBI were 66%, 84.6%, 75.4%, 77.7%, respectively, while the values for combination of NBI and AFI were 86.1%, 86.6%, 84.6%, and 88%, respectively. Combination of NBI and AFI significantly improves sensitivity when compared to each individual technique ( P < 0.001). When specificity is of concern, combination of techniques improves specificity of WLB ( P < 0.001) and specificity of AFI ( P = 0.03), but it does not have significant influence on specificity of NBI ( P = 0.53).

          CONCLUSION:

          Combination of NBI and AFI in detection of premalignant bronchial lesions increases both sensitivity and specificity of each technique. However, it seems that NBI is most sufficient and effective in detection of these lesions.

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          Most cited references38

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          Progressive 3q amplification consistently targets SOX2 in preinvasive squamous lung cancer.

          Amplification of distal 3q is the most common genomic aberration in squamous lung cancer (SQC). SQC develops in a multistage progression from normal bronchial epithelium through dysplasia to invasive disease. Identifying the key driver events in the early pathogenesis of SQC will facilitate the search for predictive molecular biomarkers and the identification of novel molecular targets for chemoprevention and therapeutic strategies. For technical reasons, previous attempts to analyze 3q amplification in preinvasive lesions have focused on small numbers of predetermined candidate loci rather than an unbiased survey of copy-number variation. To perform a detailed analysis of the 3q amplicon in bronchial dysplasia of different histological grades. We use molecular copy-number counting (MCC) to analyze the structure of chromosome 3 in 19 preinvasive bronchial biopsy specimens from 15 patients and sequential biopsy specimens from 3 individuals. We demonstrate that no low-grade lesions, but all high-grade lesions, have 3q amplification. None of seven low-grade lesions progressed clinically, whereas 8 of 10 patients with high-grade disease progressed to cancer. We identify a minimum commonly amplified region on chromosome 3 consisting of 17 genes, including 2 known oncogenes, SOX2 and PIK3CA. We confirm that both genes are amplified in all high-grade dysplastic lesions tested. We further demonstrate, in three individuals, that the clinical progression of high-grade preinvasive disease is associated with incremental amplification of SOX2, suggesting this promotes malignant progression. These findings demonstrate progressive 3q amplification in the evolution of preinvasive SQC and implicate SOX2 as a key target of this dynamic process.
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            Autofluorescence bronchoscopy with white light bronchoscopy compared with white light bronchoscopy alone for the detection of precancerous lesions: a European randomised controlled multicentre trial.

            The potential of autofluorescence bronchoscopy (AFB) to detect precancerous lesions in the central airways and its role in lung cancer screening is uncertain. A study was undertaken to evaluate the prevalence of moderate/severe dysplasia (dysplasia II-III) and carcinoma in situ (CIS) using a newly developed AFB system in comparison with conventional white light bronchoscopy (WLB) alone. In a prospective randomised multicentre trial, smokers > or = 40 years of age (> or = 20 pack-years) were stratified into four different risk groups and investigated with either WLB+AFB (arm A) or WLB alone (arm B). 1173 patients (916 men) of mean age 58.7 years were included. Overall (arms A and B), preinvasive lesions (dysplasia II-III and CIS) were detected in 3.9% of the patients. The prevalence of patients with preinvasive lesions in the WLB arm was 2.7% compared with 5.1% in the WLB+AFB arm (p = 0.037). For patients with dysplasia II-III, WLB+AFB increased the detection rate by a factor of 2.1 (p = 0.03), while for CIS the factor was only 1.24 (p = 0.75). The biopsy based sensitivity of WLB alone and WLB+AFB for detecting dysplasia II-III and CIS was 57.9% compared with 82.3% (1.42-fold increase). The corresponding specificity was 62.1% compared with 58.4% (0.94-fold decrease). This first randomised study of AFB showed that the combination of WLB+AFB was significantly superior to WLB alone in detecting preneoplastic lesions. Our findings do not support the general use of AFB as a screening tool for lung cancer, but suggest that it may be of use in certain groups. The precise indications await further study.
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              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.

              To compare the accuracy of autofluorescence bronchoscopy (AFB) combined with white light bronchoscopy (WLB) versus WLB alone in the diagnosis of lung cancer. The Ovid, PubMed, and Google Scholar databases from January 1990 to October 2010 were searched. Two reviewers independently assessed the quality of the trials and extracted data. The relative risk for sensitivity and specificity on a per-lesion basis of AFB + WLB versus WLB alone to detect intraepithelial neoplasia and invasive cancer were pooled by Review Manager. Twenty-one studies involving 3266 patients were ultimately analyzed. The pool relative sensitivity on a per-lesion basis of AFB + WLB versus WLB alone to detect intraepithelial neoplasia and invasive cancer was 2.04 (95% confidence interval [CI] 1.72-2.42) and 1.15 (95% CI 1.05-1.26), respectively. The pool relative specificity on a per-lesion basis of AFB + WLB versus WLB alone was 0.65 (95% CI 0.59-0.73). Although the specificity of AFB + WLB is lower than WLB alone, AFB + WLB seems to significantly improve the sensitivity to detect intraepithelial neoplasia. However, this advantage over WLB alone seems much less in detecting invasive lung cancer.
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                Author and article information

                Journal
                Ann Thorac Med
                Ann Thorac Med
                ATM
                Annals of Thoracic Medicine
                Medknow Publications & Media Pvt Ltd (India )
                1817-1737
                1998-3557
                Apr-Jun 2013
                : 8
                : 2
                : 93-98
                Affiliations
                [1] Department of Interventional Pulmonology, Institute for Pulmonary Diseases of Vojvodina, Clinic for Pulmonary Oncology, Sremska Kamenica, Serbia
                [1 ] Intensive Care Unit, Institute for Pulmonary Diseases of Vojvodina, Clinic for Urgent Pulmonology, Faculty of Medicine, University of Novi Sad, Sremska Kamenica, Serbia
                Author notes
                Address for correspondence: Dr. Bojan Zaric, Department of Interventional Pulmonology, Institute for Pulmonary Diseases of Vojvodina, Clinic for Pulmonary Oncology, Faculty of Medicine, University of Novi Sad, Put Doktora Goldmana 4, Sremska Kamenica, Serbia. E-mail: bojanzaric@ 123456neobee.net
                Article
                ATM-8-93
                10.4103/1817-1737.109820
                3667452
                23741271
                1130833b-b314-4967-a129-07d1865d4e1a
                Copyright: © Annals of Thoracic Medicine

                This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 17 September 2012
                : 12 December 2012
                Categories
                Original Article

                Respiratory medicine
                autofluorescence bronchoscopy,bronchoscopy,interventional pulmonology,lung cancer,narrow band imaging,premalignant lesions

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