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released directly from cancers, but also that metab-olites are conveyed from the blood stream by alveoli and enter the exhaled breath19-21). As a result, it is thought that it is possible to measure the changes in metabolism that are caused by cancer growth in exhaled breath22). In esophageal carcinoma patients, the exhaled breath is thought to include not only metabolites originating from the alveoli, but also many fragrant substances arising from the esophageal carcinoma itself. Thus, it is thought that breath analysis of VOCs would make it possible to identify substances specific to ESCC more accurately compared with other cancers. Altomare et al. found that 15 VOCs, including alkyl aldehydes, ketones, alkanes, and aromatic hydrocarbons, differed between healthy subjects and patients with colorectal cancer23). Huang et al. measured VOCs in urine samples and found differences in acetone, acetic acid, hexane, hydrogen sulfide, methanol, and phenol between patients with gastro esophageal cancer and healthy subjects24). Kumar et al. demonstrated that 12 VOCs in exhaled breath were present at signifi-cantly higher concentrations in the esophageal and gastric adenocarcinoma cancer groups than in the noncancer controls13). They reported that VOCs profiling was useful for early detection of cancers.The present study has several limitations. First, this was a single center study with a small sample Figure 3　Receiver operating characteristic (ROC) curve for the detection of ESCC patients using the combination of acetonitrile, acetic acid, acetone, and 2-butanone concentration in exhalation The area-under-the-curve (AUC) was 0.93.size, and it will be necessary to study a larger number of samples to confirm these findings. Second, the patients in this study had compara-tively advanced cancers. There have been reports that lung, colorectal, and breast cancers could be distinguished from healthy individuals at a rela-tively early stage using this method25-27). Therefore, this method of cancer detection must be tested in patients with early-stage ESCC. Third, there are no established methods for breath analysis of VOCs, and there is a need to evaluate whether food, tobacco use, ingested drugs, concurrent diseases, genetic factors, etc., affect the results of this analysis method. Moreover, the composition of gastrointestinal microbiota could have a major impact on the exhaled breath of suspected diges-tive cancer patients; this factor has not yet been studied sufficiently in the context of diagnostic breath testing28). In conclusion, this study found that the levels of 4 VOCs, i.e., acetonitrile, acetic acid, acetone, and 2-butanone, were significantly higher in the exhaled breath of ESCC patients than in control subjects. Those findings indicate that measurement of VOCs in the exhaled breath has potential as a useful, non invasive method for diagnosis of ESCC.Not applicable.503Acknowledgments