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      Volatile organic compounds in breath can serve as a non‐invasive diagnostic biomarker for the detection of advanced adenomas and colorectal cancer

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          Summary

          Background

          Colorectal cancer (CRC) is the third most common cancer diagnosis in the Western world.

          Aim

          To evaluate exhaled volatile organic compounds (VOCs) as a non‐invasive biomarker for the detection of CRC and precursor lesions using an electronic nose.

          Methods

          In this multicentre study adult colonoscopy patients, without inflammatory bowel disease or (previous) malignancy, were invited for breath analysis. Two‐thirds of the breath tests were randomly assigned to develop training models which were used to predict the diagnosis of the remaining patients (external validation). In the end, all data were used to develop final‐disease models to further improve the discriminatory power of the algorithms.

          Results

          Five hundred and eleven breath samples were collected. Sixty‐four patients were excluded due to an inadequate breath test (n = 51), incomplete colonoscopy (n = 8) or colitis (n = 5). Classification was based on the most advanced lesion found; CRC (n = 70), advanced adenomas (AAs) (n = 117), non‐advanced adenoma (n = 117), hyperplastic polyp (n = 15), normal colonoscopy (n = 125). Training models for CRC and AAs had an area under the curve (AUC) of 0.76 and 0.71 and blind validation resulted in an AUC of 0.74 and 0.61 respectively. Final models for CRC and AAs yielded an AUC of 0.84 (sensitivity 95% and specificity 64%) and 0.73 (sensitivity and specificity 79% and 59%) respectively.

          Conclusions

          This study suggests that exhaled VOCs could potentially serve as a non‐invasive biomarker for the detection of CRC and AAs. Future studies including more patients could further improve the discriminatory potential of VOC analysis for the detection of (pre‐)malignant colorectal lesions. ( https://clinicaltrials.gov Identifier NCT03488537)

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          Most cited references51

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          Colorectal cancer development and advances in screening

          Most colon tumors develop via a multistep process involving a series of histological, morphological, and genetic changes that accumulate over time. This has allowed for screening and detection of early-stage precancerous polyps before they become cancerous in individuals at average risk for colorectal cancer (CRC), which may lead to substantial decreases in the incidence of CRC. Despite the known benefits of early screening, CRC remains the second leading cause of cancer-related deaths in the United States. Hence, it is important for health care providers to have an understanding of the risk factors for CRC and various stages of disease development in order to recommend appropriate screening strategies. This article provides an overview of the histological/molecular changes that characterize the development of CRC. It describes the available CRC screening methods and their advantages and limitations and highlights the stages of CRC development in which each screening method is most effective.
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            The scent of disease: volatile organic compounds of the human body related to disease and disorder.

            Hundreds of volatile organic compounds (VOCs) are emitted from the human body, and the components of VOCs usually reflect the metabolic condition of an individual. Therefore, contracting an infectious or metabolic disease often results in a change in body odour. Recent progresses in analytical techniques allow rapid analyses of VOCs derived from breath, blood, skin and urine. Disease-specific VOCs can be used as diagnostic olfactory biomarkers of infectious diseases, metabolic diseases, genetic disorders and other kinds of diseases. Elucidation of pathophysiological mechanisms underlying production of disease-specific VOCs may provide novel insights into therapeutic approaches for treatments for various diseases. This review summarizes the current knowledge on chemical and clinical aspects of body-derived VOCs, and provides a brief outlook at the future of olfactory diagnosis.
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              Detection of lung, breast, colorectal, and prostate cancers from exhaled breath using a single array of nanosensors

              Background: Tumour growth is accompanied by gene and/or protein changes that may lead to peroxidation of the cell membrane species and, hence, to the emission of volatile organic compounds (VOCs). In this study, we investigated the ability of a nanosensor array to discriminate between breath VOCs that characterise healthy states and the most widespread cancer states in the developed world: lung, breast, colorectal, and prostate cancers. Methods: Exhaled alveolar breath was collected from 177 volunteers aged 20–75 years (patients with lung, colon, breast, and prostate cancers and healthy controls). Breath from cancerous subjects was collected before any treatment. The healthy population was healthy according to subjective patient's data. The breath of volunteers was examined by a tailor-made array of cross-reactive nanosensors based on organically functionalised gold nanoparticles and gas chromatography linked to the mass spectrometry technique (GC-MS). Results: The results showed that the nanosensor array could differentiate between ‘healthy' and ‘cancerous' breath, and, furthermore, between the breath of patients having different cancer types. Moreover, the nanosensor array could distinguish between the breath patterns of different cancers in the same statistical analysis, irrespective of age, gender, lifestyle, and other confounding factors. The GC-MS results showed that each cancer could have a unique pattern of VOCs, when compared with healthy states, but not when compared with other cancer types. Conclusions: The reported results could lead to the development of an inexpensive, easy-to-use, portable, non-invasive tool that overcomes many of the deficiencies associated with the currently available diagnostic methods for cancer.
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                Author and article information

                Contributors
                kelly.vankeulen@radboudumc.nl
                Journal
                Aliment Pharmacol Ther
                Aliment. Pharmacol. Ther
                10.1111/(ISSN)1365-2036
                APT
                Alimentary Pharmacology & Therapeutics
                John Wiley and Sons Inc. (Hoboken )
                0269-2813
                1365-2036
                20 December 2019
                February 2020
                : 51
                : 3 ( doiID: 10.1111/apt.v51.3 )
                : 334-346
                Affiliations
                [ 1 ] Department of Gastroenterology and Hepatology Radboud University Medical Center Nijmegen The Netherlands
                [ 2 ] Department of Gastroenterology and Hepatology Medisch Spectrum Twente Enschede The Netherlands
                [ 3 ] University Medical Center Groningen Groningen The Netherlands
                [ 4 ] Department of Gastroenterology and Hepatology Bernhoven Uden The Netherlands
                Author notes
                [*] [* ] Correspondence

                Kelly E. van Keulen, Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands.

                Email: kelly.vankeulen@ 123456radboudumc.nl

                Author information
                https://orcid.org/0000-0001-7219-2775
                https://orcid.org/0000-0002-0442-827X
                https://orcid.org/0000-0002-6940-8499
                Article
                APT15622
                10.1111/apt.15622
                7003780
                31858615
                cadf0d0b-fbb0-4f5f-9cd6-28f34b77952e
                © 2019 The Authors. Alimentary Pharmacology & Therapeutics published by John Wiley & Sons Ltd

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                : 11 June 2019
                : 03 July 2019
                : 04 December 2019
                Page count
                Figures: 3, Tables: 4, Pages: 13, Words: 9250
                Categories
                Original Article
                Breath Analysis for Diagnosis of Colorectal Adenomas and Cancer
                Custom metadata
                2.0
                February 2020
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.7.5 mode:remove_FC converted:06.02.2020

                Pharmacology & Pharmaceutical medicine
                Pharmacology & Pharmaceutical medicine

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