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      Objective tumor distinction in 5-aminolevulinic acid-based endoscopic photodynamic diagnosis, using a spectrometer with a liquid crystal tunable filter

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          Abstract

          Background

          Recent improvement of the endoscopic system such as image enhancement has led to the better accuracy of the diagnosis of the gastric cancer. However, the objective and efficient detection method of the gastric cancer is still needed because the detection efficiency could sometimes be low due to the fact that the image enhancement diagnosis needs magnification for its full utilization. The photodynamic diagnosis (PDD) with oral intake of 5-aminolevulinic acid (5-ALA) has been widely used for the detection of the cancerous region for bladder cancer and glioblastoma. The application of the 5-ALA based PDD (5-ALA PDD) to the diagnosis of gastric cancer is recently reported. The efficiency of the detection is reported to be good, however, the objectivity of the method can be impaired by the photobleaching effect with fast decreasing of the intensity of the fluorescence under light exposure. In this article, we investigated the fluorescence spectrum of the gastric tumor and non-tumor mucosa of 5-ALA PDD and revealed the property of the photobleaching effect.

          Methods

          Example cases of PDD endoscopy of gastric tumor were investigated for cases of endoscopic submucosal dissection (ESD). Newly developed spectrometer using a spectrometer with a liquid crystal tunable filter was used for investigating the fluorescence spectrum of 5-ALA PDD. The assumed tumor region and non-tumor region in gastric mucosa were biopsied and the fluorescence spectrum was measured using the spectrometer consecutively several times, to estimate the photobleaching effect.

          Results

          The fluorescence spectrum has a primary peak at 630 nm, with a broad peak ranging from 660 to 700 nm. The 630 nm peak diminished quickly upon ultraviolet light exposure, whereas the broad peak from 660 to 700 nm diminished slowly. The sum of the altitudes at 660–700 nm, normalized to the altitude at 600 nm, was not as affected by the photobleaching effect as the 630 nm peak was, and can thus be used for 5-ALA-based PDD.

          Conclusions

          The 5-ALA PDD using the average fluorescence altitude of 660–700 nm instead of the peak altitude at 630 nm, is shown to be more effective in distinguishing between tumorous and non-tumorous tissues, because of the lower photobleaching effect at this specific spectral range. The finding is expected to greatly improve the objective diagnosis of gastrointestinal cancers by 5-ALA-based photodynamic diagnostic endoscopy.

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          Most cited references12

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          Japanese classification of gastric carcinoma: 3rd English edition.

          (2011)
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            Magnifying endoscopy combined with narrow band imaging system for early gastric cancer: correlation of vascular pattern with histopathology (including video).

            The narrow band imaging (NBI) system consists of a sequential electronic endoscope system and a source of light equipped with new narrow band filters, yielding very clear images of microvessels on mucosal surfaces. The aim of this prospective study was to measure the correlation between the magnified images obtained with the NBI system and the histological findings, especially with regard to the vascular pattern. In addition, three-dimensional images of microvessels were reconstructed using a laser scanning microscope. Between July 2001 and August 2003, 165 patients with depressed-type early gastric cancer lesions were enrolled in the study. The lesions were carefully observed with magnification using the NBI system. The images, the pathological characteristics of the lesions, and three-dimensionally reconstructed images of the microvascular networks in biopsied specimens were carefully analyzed. The microvascular patterns were classified into three groups: A, fine network; B, corkscrew; and C, unclassified pattern. The endoscopic images were compared with the histological findings. Of the three types of filter available for use with the NBI system, microvascular formation was best enhanced in B mode images produced using short wavelengths, which focus on the superficial mucosal layer. Among 109 cases of differentiated adenocarcinoma, the group A microvascular pattern was observed in 72 cases (66.1 %). Among 56 cases of undifferentiated adenocarcinoma, the group B pattern was observed in 48 cases (85.7 %; P = 0.0011) The microvascular structure observed using the NBI system corresponded with the superficial mucosal layer in the three-dimensional images obtained using laser scanning microscopy and the resected specimens. Magnifying endoscopy performed in combination with the NBI system is not sufficient to replace conventional histology, but is capable of predicting the histological characteristics of gastric cancer lesions.
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              Magnifying endoscopy combined with narrow-band imaging for differential diagnosis of superficial depressed gastric lesions.

              Magnifying endoscopy combined with narrow-band imaging (ME-NBI) has been used for differential diagnosis of various focal lesions. The aim of our study was to evaluate ME-NBI criteria for cancer diagnosis in superficial depressed gastric lesions in comparison to conventional white light endoscopy (WLE). ME-NBI and WLE images of 100 superficial gastric depressions (55 depressed cancers, 45 benign depressions) were independently evaluated by 11 endoscopists blinded to the diagnosis in each case. The presence or absence of predefined ME-NBI findings relating to microvasculature and fine mucosal structure (FMS) was recorded. A general diagnosis of benign or malignant also had to be given on the basis of a general assessment of features of color and shape as shown in the ME-NBI and WLE images, respectively, without regard to any prespecified criteria. Multivariate and ROC analysis demonstrated that the triad of FMS disappearance, microvascular dilation, and heterogeneity appeared to be the best combination for diagnosis of gastric cancer. ME-NBI diagnosis with the triad attained a good specificity (85 %, theoretically calculated if all of the triad were positive), which was significantly ( P < 0.001) superior to WLE general diagnosis (65 %), and comparable with ME-NBI general diagnosis (80 %). The sensitivities of the three diagnoses (ME-NBI with the triad 69 %, WLE general diagnosis 71 %, ME-NBI general diagnosis 72 %) were comparably moderate. The kappa values (interobserver concordance) for ME-NBI diagnosis with the triad (0.47) and ME-NBI general diagnosis (0.48) were superior to the kappa value for WLE diagnosis (0.34). The triad of FMS disappearance, microvascular dilation, and heterogeneity has good specificity for the diagnosis of superficial depressed gastric carcinoma, but the sensitivity needs to be improved.
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                Author and article information

                Journal
                Ann Transl Med
                Ann Transl Med
                ATM
                Annals of Translational Medicine
                AME Publishing Company
                2305-5839
                2305-5847
                March 2020
                March 2020
                : 8
                : 5
                : 178
                Affiliations
                [1]Faculty of Medicine, Division of Medicine and Clinical Science, Department of Multidisciplinary Internal Medicine, Tottori University , Tottori, Japan
                Author notes

                Contributions: (I) Conception and design: T Yamashita; (II) Administrative support: T Yamashita; (III) Provision of study materials or patients: H Kinoshita, T Sakaguchi; (IV) Collection and assembly of data: H Kinoshita, T Sakaguchi; (V) Data analysis and interpretation: T Yamashita, H Isomoto; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.

                Correspondence to: Hajime Isomoto. Faculty of Medicine, Division of Medicine and Clinical Science, Department of Multidisciplinary Internal Medicine, Tottori University, Nishicho 36-1, Yonago City, Tottori Prefecture, Japan. Email: isomoto@ 123456med.tottori-u.ac.jp .
                Article
                atm-08-05-178
                10.21037/atm.2020.01.108
                7154455
                32309325
                fe52ea54-51a6-4798-a426-02165e861013
                2020 Annals of Translational Medicine. All rights reserved.

                Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0.

                History
                : 09 November 2019
                : 10 January 2020
                Categories
                Original Article

                photodynamic diagnosis (pdd),5-aminolevulinic acid (5-ala),photobleaching effect

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