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. 2025 Jan 2;8(1):e2454685.
doi: 10.1001/jamanetworkopen.2024.54685.

Esophageal Candida Infection and Esophageal Cancer Risk in Patients With Achalasia

Xiaopei Guo  1 , Suk Yee Lam  1 , Vincent T Janmaat  1 , Pieter Jan F de Jonge  1 , Bettina E Hansen  2 , Ivonne Leeuwenburgh  3 , Maikel P Peppelenbosch  1 , Manon C W Spaander  1 , Gwenny M Fuhler  1
Affiliations

Esophageal Candida Infection and Esophageal Cancer Risk in Patients With Achalasia

Xiaopei Guo et al. JAMA Netw Open. .

Abstract

Importance: Patients with achalasia face a higher risk of developing esophageal cancer (EC), but the surveillance strategies for these patients remain controversial due to the long disease duration and the lack of identified risk factors.

Objective: To investigate the prevalence of esophageal Candida infection among patients with achalasia and to assess the association of Candida infection with EC risk within this population.

Design, setting, and participants: This retrospective cohort study included patients with achalasia diagnosed at or referred for treatment and monitoring to the Erasmus University Medical Center in Rotterdam, the Netherlands, between January 1, 1980, and May 31, 2024. Data analysis was conducted from August 1 to October 31, 2024.

Exposure: Esophageal Candida infection.

Main outcomes and measures: The primary outcomes were the prevalence of esophageal Candida infection and its association with EC development among patients with achalasia. Associations were estimated using time-dependent Cox proportional hazards regression models with esophageal Candida infection as a time-varying covariate, adjusting for age at diagnosis and sex.

Results: This study included 234 patients with achalasia (median [IQR] age at diagnosis, 45 [32-63] years; 117 [50%] male), with a median follow-up time of 13 (4-22) years. Esophageal Candida infection was identified in 29 patients (12%), while EC was observed in 24 patients (10%). Esophageal cancer risk analysis was performed for 207 patients with 2 or more consecutive endoscopy follow-up visits (median [IQR] age at diagnosis, 43 [32-60] years; 104 [50%] male). The median (IQR) follow-up time for this subgroup was 16 (9-26) years. Among these patients, esophageal Candida infection was independently associated with an increased risk of EC (adjusted hazard ratio [AHR], 8.24 [95% CI, 2.97-22.89]). Additionally, age at diagnosis (AHR, 1.06 [95% CI, 1.03-1.10]) and male sex (AHR, 3.34 [95% CI, 1.08-10.36]) were independently associated with EC risk.

Conclusions and relevance: This retrospective cohort study found that prior esophageal Candida infection, older age at diagnosis, and male sex were associated with increased risk of EC among patients with achalasia. These findings provide an important rationale for optimizing the monitoring of patients with achalasia.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Peppelenbosch reported being the director of the Batavian Society for Experimental Philosophy, president of the Life Science Board for NOW Lorentz Center, president of the Microplastics Board for ZonMw, a panel member panel of Fonds Wetenschappelijk Onderzoek (Belgium), a council member for the National Science Center (Poland), a foreign rapporteur for the Czech Science Foundation, an evaluator for H2020-FETOPEN-2018-2019-2020, on the scientific review board for KWF Dutch Cancer Society; on the editorial board for the Journal of Crohn’s and Colitis, Cell, Canadian Journal of Gastroenterology & Hepatology, Biology, and Molecule; receiving royalties for the textbook Medische Celbiologie; having an appointment at Technische Universiteit Delft; being a consultant for Walvax; being a distinguished professor at Minzu North West University; and receiving fees from Pfizer. Dr Fuhler reports having served as speaker for Janssen Cilag and Galapagor Biopharma, and serving as council member for the National Science Center (Poland). No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Kaplan-Meier Curves Illustrating Cumulative Probability of Esophageal Candida Infection and Esophageal Cancer Among All Patients With Achalasia Since Achalasia Diagnosis
Figure 2.
Figure 2.. Extended Standard Kaplan-Meier Curves Illustrating Cumulative Incidence of Esophageal Cancer Among Patients With Achalasia, Stratified by Time-Varying Esophageal Candida Infection Status
See this image and copyright information in PMC

References

    1. Kim GH, Park H, Jung KW, et al. ; Big Data Study Group Under the Korean Society of Neurogastroenterology and Motility . Incidence, morbidity, and mortality of achalasia: a nationwide, population-based cohort study in South Korea. Gut Liver. 2023;17(6):894-904. doi:10.5009/gnl220334 - DOI - PMC - PubMed
    1. Oude Nijhuis RAB, Zaninotto G, Roman S, et al. . European guidelines on achalasia: United European Gastroenterology and European Society of Neurogastroenterology and Motility recommendations. United European Gastroenterol J. 2020;8(1):13-33. doi:10.1177/2050640620903213 - DOI - PMC - PubMed
    1. Leeuwenburgh I, Scholten P, Alderliesten J, et al. . Long-term esophageal cancer risk in patients with primary achalasia: a prospective study. Am J Gastroenterol. 2010;105(10):2144-2149. doi:10.1038/ajg.2010.263 - DOI - PubMed
    1. Meijssen MA, Tilanus HW, van Blankenstein M, Hop WC, Ong GL. Achalasia complicated by oesophageal squamous cell carcinoma: a prospective study in 195 patients. Gut. 1992;33(2):155-158. doi:10.1136/gut.33.2.155 - DOI - PMC - PubMed
    1. Sato H, Terai S, Shimamura Y, et al. . Achalasia and esophageal cancer: a large database analysis in Japan. J Gastroenterol. 2021;56(4):360-370. doi:10.1007/s00535-021-01763-6 - DOI - PubMed

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