Skip to main content

Advertisement

SpringerLink
Log in

Usefulness of the aldehyde breath test for predicting metachronous recurrence in patients with esophageal squamous cell carcinoma and hypopharyngeal squamous cell carcinoma

  • Original Article
  • Published:
Esophagus Aims and scope Submit manuscript

Abstract

Background

The rate of metachronous recurrence after endoscopic submucosal dissection for early-stage esophageal squamous cell carcinoma and hypopharynx squamous cell carcinoma is as high (10–15%). The acetaldehyde breath test may detect acetaldehyde dehydrogenase 2 gene polymorphisms. Therefore, we evaluated its usefulness in assessing metachronous recurrence in patients with esophageal squamous cell carcinoma and hypopharynx squamous cell carcinoma.

Methods

A total of 76 patients underwent endoscopic submucosal dissection for esophageal squamous cell carcinoma and hypopharynx squamous cell carcinoma and were followed up for at least 3 years (non-recurrence group: 52 patients; recurrence group: 24 patients). The risk factors for carcinogenesis were compared between the recurrence and non-recurrence groups, and the acetaldehyde-to-ethanol ratio was assessed. The cutoff acetaldehyde-to-ethanol ratio that correlated with recurrence was established, and the cumulative recurrence rate was evaluated.

Results

The recurrence group had a higher acetaldehyde-to-ethanol ratio, daily alcohol consumption, and Lugol-voiding lesion grade than the non-recurrence group in the univariate analysis. The cutoff acetaldehyde-to-ethanol ratio for recurrence was 28.1 based on the receiver operating characteristic curve. The multivariate analysis revealed an acetaldehyde-to-ethanol ratio of > 28.1 and a Lugol-voiding lesion grade associated with carcinogenesis. Patients with an acetaldehyde-to-ethanol ratio of ≥ 28.1 had a significantly high recurrence rate using the Kaplan–Meier method.

Conclusions

The acetaldehyde-to-ethanol ratio detected using the acetaldehyde breath test could be a novel biomarker of metachronous recurrence after endoscopic submucosal dissection in patients with esophageal squamous cell carcinoma and hypopharynx squamous cell carcinoma.

Trial registration number

UMIN000040615.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

Data availability

The data that support the findings of this study are available from the corresponding author, [FS], upon reasonable request.

References

  1. Baan R, Straif K, Grosse Y, et al. Carcinogenicity of alcoholic beverages. Lancet Oncol. 2007;8:292–3.

    Article  PubMed  Google Scholar 

  2. Ohashi S, Miyamoto S, Kikuchi O, et al. Recent advances from basic and clinical studies of esophageal squamous cell carcinoma. Gastroenterology. 2015;149:1700–15.

    Article  PubMed  Google Scholar 

  3. Katada C, Muto M, Nakayama M, et al. Risk of superficial squamous cell carcinoma developing in the head and neck region in patients with esophageal squamous cell carcinoma. Laryngoscope. 2012;122:1291–6.

    Article  PubMed  Google Scholar 

  4. Muto M, Minashi K, Yano T, et al. Early detection of superficial squamous cell carcinoma in the head and neck region and esophagus by narrow band imaging: a multicenter randomized controlled trial. J Clin Oncol. 2010;28:1566–72.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Abe S, Hirai Y, Uozumi T, et al. Endoscopic resection of esophageal squamous cell carcinoma: current indications and treatment outcomes. DEN Open. 2022;2: e45.

    Article  PubMed  Google Scholar 

  6. Kawashima K, Abe S, Koga M, et al. Optimal selection of endoscopic resection in patients with esophageal squamous cell carcinoma: endoscopic mucosal resection versus endoscopic submucosal dissection according to lesion size. Dis Esophagus. 2021. https://doi.org/10.1093/dote/doaa096.

    Article  PubMed  Google Scholar 

  7. Urabe Y, Hiyama T, Tanaka S, et al. Metachronous multiple esophageal squamous cell carcinomas and Lugol-voiding lesions after endoscopic mucosal resection. Endoscopy. 2009;41:304–9.

    Article  CAS  PubMed  Google Scholar 

  8. Shimizu Y, Tukagoshi H, Fujita M, et al. Metachronous squamous cell carcinoma of the esophagus arising after endoscopic mucosal resection. Gastrointest Endosc. 2001;54:190–4.

    Article  CAS  PubMed  Google Scholar 

  9. Hori K, Okada H, Kawahara Y, et al. Lugol-voiding lesions are an important risk factor for a second primary squamous cell carcinoma in patients with esosphageal cancer or head and neck cancer. Am J Gastroenterol. 2011;106:858–66.

    Article  PubMed  Google Scholar 

  10. Katada C, Yokoyama T, Yano T, et al. Alcohol consumption and multiple dysplastic lesions increase risk of squamous cell carcinoma in the esophagus, head, and neck. Gastroenterology. 2016;151:860-869.e7.

    Article  CAS  PubMed  Google Scholar 

  11. Secretan B, Straif K, Baan R, et al. A review of human carcinogens–part E: tobacco, areca nut, alcohol, coal smoke, and salted fish. Lancet Oncol. 2009;10:1033–4.

    Article  PubMed  Google Scholar 

  12. Yokoyama A, Muramatsu T, Ohmori T, et al. Esophageal cancer and aldehyde dehydrogenase-2 genotypes in Japanese males. Cancer Epidemiol Biomarkers Prev. 1996;5:99–102.

    CAS  PubMed  Google Scholar 

  13. Yokoyama A, Mizukami T, Yokoyama T. Genetic polymorphisms of alcohol dehydrogense-1B and aldehyde dehydrogenase-2, alcohol flushing, mean corpuscular volume, and aerodigestive tract neoplasia in Japanese drinkers. Adv Exp Med Biol. 2015;815:265–79.

    Article  CAS  PubMed  Google Scholar 

  14. Yokoyama A, Omori T, Yokoyama T. Alcohol and aldehyde dehydrogenase polymorphisms and a new strategy for prevention and screening for cancer in the upper aerodigestive tract in East Asians. Keio J Med. 2010;59:115–30.

    Article  PubMed  Google Scholar 

  15. Bosron WF, Li TK. Genetic polymorphism of human liver alcohol and aldehyde dehydrogenases, and their relationship to alcohol metabolism and alcoholism. Hepatology. 1986;6:502–10.

    Article  CAS  PubMed  Google Scholar 

  16. Crabb DW, Edenberg HJ, Bosron WF, Li TK. Genotypes for aldehyde dehydrogenase deficiency and alcohol sensitivity. The inactive ALDH2(2) allele is dominant. J Clin Invest. 1989;83:314–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Lai CL, Yao CT, Chau GY, et al. Dominance of the inactive Asian variant over activity and protein contents of mitochondrial aldehyde dehydrogenase 2 in human liver. Alcohol Clin Exp Res. 2014;38:44–50.

    Article  CAS  PubMed  Google Scholar 

  18. Gross ER, Zambelli VO, Small BA, et al. A personalized medicine approach for Asian Americans with the aldehyde dehydrogenase 2*2 variant. Annu Rev Pharmacol Toxicol. 2015;55:107–27.

    Article  CAS  PubMed  Google Scholar 

  19. Boyle P, Autier P, Bartelink H, et al. European code against cancer and scientific justification: third version (2003). Ann Oncol Third Vers. 2003;14:973–1005.

    Article  CAS  Google Scholar 

  20. Aoyama I, Ohashi S, Amanuma Y, et al. Establishment of a quick and highly accurate breath test for ALDH2 genotyping. Clin Transl Gastroenterol. 2017;8: e96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Sasaki F, Kanmura S, Oda K, et al. Acetaldehyde breath test as a cancer risk marker in patients with esophageal and hypopharyngeal squamous cell carcinoma. PLoS ONE. 2021;16: e0251457.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Yokoyama T, Yokoyama A, Kumagai Y, et al. Health risk appraisal models for mass screening of esophageal cancer in Japanese men. Cancer Epidemiol Biomarkers Prev. 2008;17:2846–54.

    Article  CAS  PubMed  Google Scholar 

  23. Lachenmeier DW, Sohnius EM. The role of acetaldehyde outside ethanol metabolism in the carcinogenicity of alcoholic beverages: evidence from a large chemical survey. Food Chem Toxicol. 2008;46:2903–11.

    Article  CAS  PubMed  Google Scholar 

  24. Hanada M, Koda H, Onaga K, et al. Portable oral malodor analyzer using highly sensitive In2O3 gas sensor combined with a simple gas chromatography system. Anal Chim Acta. 2003;475:27–35.

    Article  CAS  Google Scholar 

  25. Ishihara R, Iishi H, Uedo N, et al. Comparison of EMR and endoscopic submucosal dissection for en bloc resection of early esophageal cancers in Japan. Gastrointest Endosc. 2008;68:1066–72.

    Article  PubMed  Google Scholar 

  26. Muto M, Katada C, Yokoyama T, et al. Field effect of alcohol, cigarette smoking, and their cessation on the development of multiple dysplastic lesions and squamous cell carcinoma: a long-term multicenter cohort study. Gastro Hep Adv. 2022;1:265–76.

    Article  Google Scholar 

  27. Matsuno K, Ishihara R, Nakagawa K, et al. Endoscopic findings corresponding to multiple Lugol-voiding lesions in the esophageal background mucosa. J Gastroenterol Hepatol. 2019;34:390–6.

    Article  PubMed  Google Scholar 

  28. Ono S, Kawada K, Dohi O, et al. Linked color imaging focused on neoplasm detection in the upper gastrointestinal tract: a randomized trial. Ann Intern Med. 2021;174:18–24.

    Article  PubMed  Google Scholar 

  29. Maeda H, Sasaki F, Kabayama M, et al. Efficacy of endoscopic ultrasonography in evaluating tumor thickness in patients with superficial pharyngeal carcinoma: a pilot study. Auris Nasus Larynx. 2022;49:495–503.

    Article  PubMed  Google Scholar 

  30. Väkeväinen S, Tillonen J, Agarwal DP, Srivastava N, Salaspuro M. High salivary acetaldehyde after a moderate dose of alcohol in ALDH2-deficient subjects: strong evidence for the local carcinogenic action of acetaldehyde. Alcohol Clin Exp Res. 2000;24:873–7.

    Article  PubMed  Google Scholar 

  31. Yokoi A, Maruyama T, Yamanaka R, et al. Relationship between acetaldehyde concentration in mouth air and tongue coating volume. J Appl Oral Sci. 2015;23:64–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors would like to thank Ms. Yuko Morinaga-Nakamura for her technical assistance.

Author information

Authors and Affiliations

  1. Digestive and Lifestyle Diseases, Department of Human and Environmental Sciences, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan

    Fumisato Sasaki, Seiichi Mawatari, Kohei Oda, Hiroki Yano, Hidehito Maeda, Akihito Tanaka, Shiho Arima, Kotaro Kumagai, Shinichi Hashimoto, Shuji Kanmura & Akio Ido

  2. Department of Epidemiology and Preventive Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan

    Shiroh Tanoue

Authors
  1. Fumisato Sasaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Seiichi Mawatari
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kohei Oda
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hiroki Yano
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hidehito Maeda
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Akihito Tanaka
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Shiho Arima
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Kotaro Kumagai
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Shiroh Tanoue
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Shinichi Hashimoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Shuji Kanmura
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Akio Ido
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Conceptualization – FS. Data curation—SM, FS. Formal analysis – KO. Funding acquisition – AI. Investigation—KO, HY, HM. Methodology – SK. Project administration—KO, AI. Resources – SA. Software – SM. Supervision – SH. Validation—ST, AT. Visualization – KK. Writing—original draft – FS. Writing—review & editing—FS, SM, KO, HY, HM, AT, SA, KK, ST, SH, SK, AI.

Corresponding author

Correspondence to Fumisato Sasaki.

Ethics declarations

Conflict of interest

Fumisato Sasaki, Seiichi Mawatari, Kohei Oda, Hiroki Yano, Hidehito Maeda, Akihito Tanaka, Shiho Arima, Kotaro Kumagai, Shiroh Tanoue, Shinichi Hashimoto, Shuji Kanmura, and Akio Ido declare that they have no conflict of interest.

Ethical Statement

This study was approved by the Research Ethics Committee of Kagoshima University (no. 28–137). A written informed consent was obtained from all participants. The procedures were performed in accordance with the 1964 Declaration of Helsinki and its later amendments.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Sasaki, F., Mawatari, S., Oda, K. et al. Usefulness of the aldehyde breath test for predicting metachronous recurrence in patients with esophageal squamous cell carcinoma and hypopharyngeal squamous cell carcinoma. Esophagus 20, 749–756 (2023). https://doi.org/10.1007/s10388-023-01024-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10388-023-01024-w

Keywords

Search

Navigation