{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T19:12:01Z","timestamp":1792523521943,"version":"4.5.0"},"reference-count":41,"publisher":"American Medical Association (AMA)","issue":"1","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"\n Importance<\/jats:title>\n 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.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n \n To investigate the prevalence of esophageal\n Candida<\/jats:italic>\n infection among patients with achalasia and to assess the association of\n Candida<\/jats:italic>\n infection with EC risk within this population.\n <\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n 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.<\/jats:p>\n <\/jats:sec>\n \n Exposure<\/jats:title>\n \n Esophageal\n Candida<\/jats:italic>\n infection.\n <\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n \n The primary outcomes were the prevalence of esophageal\n Candida<\/jats:italic>\n infection and its association with EC development among patients with achalasia. Associations were estimated using time-dependent Cox proportional hazards regression models with esophageal\n Candida<\/jats:italic>\n infection as a time-varying covariate, adjusting for age at diagnosis and sex.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n 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\n Candida<\/jats:italic>\n 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\n Candida<\/jats:italic>\n 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.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions and Relevance<\/jats:title>\n \n This retrospective cohort study found that prior esophageal\n Candida<\/jats:italic>\n 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.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2024.54685","type":"journal-article","created":{"date-parts":[[2025,1,14]],"date-time":"2025-01-14T11:01:46Z","timestamp":1736852506000},"page":"e2454685","source":"Crossref","is-referenced-by-count":9,"title":["Esophageal\n Candida<\/i>\n Infection and Esophageal Cancer Risk in Patients With Achalasia"],"prefix":"10.1001","volume":"8","author":[{"given":"Xiaopei","family":"Guo","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suk Yee","family":"Lam","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent T.","family":"Janmaat","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pieter Jan F.","family":"de Jonge","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bettina E.","family":"Hansen","sequence":"additional","affiliation":[{"name":"Department of Epidemiology & Biostatistics, Erasmus University Medical Center, Rotterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivonne","family":"Leeuwenburgh","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Franciscus, Gasthuis en Vlietland, Rotterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maikel P.","family":"Peppelenbosch","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manon C. W.","family":"Spaander","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gwenny M.","family":"Fuhler","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, Erasmus University Medical Center, Rotterdam, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","published-online":{"date-parts":[[2025,1,14]]},"reference":[{"issue":"6","key":"zoi241533r1","doi-asserted-by":"publisher","first-page":"894","DOI":"10.5009\/gnl220334","article-title":"Incidence, morbidity, and mortality of achalasia: a nationwide, population-based cohort study in South Korea.","volume":"17","author":"Kim","year":"2023","journal-title":"Gut Liver"},{"issue":"1","key":"zoi241533r2","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1177\/2050640620903213","article-title":"European guidelines on achalasia: United European Gastroenterology and European Society of Neurogastroenterology and Motility recommendations.","volume":"8","author":"Oude Nijhuis","year":"2020","journal-title":"United European Gastroenterol J"},{"issue":"10","key":"zoi241533r3","doi-asserted-by":"publisher","first-page":"2144","DOI":"10.1038\/ajg.2010.263","article-title":"Long-term esophageal cancer risk in patients with primary achalasia: a prospective study.","volume":"105","author":"Leeuwenburgh","year":"2010","journal-title":"Am J Gastroenterol"},{"issue":"2","key":"zoi241533r4","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1136\/gut.33.2.155","article-title":"Achalasia complicated by oesophageal squamous cell carcinoma: a prospective study in 195 patients.","volume":"33","author":"Meijssen","year":"1992","journal-title":"Gut"},{"issue":"4","key":"zoi241533r5","doi-asserted-by":"publisher","first-page":"360","DOI":"10.1007\/s00535-021-01763-6","article-title":"Achalasia and esophageal cancer: a large database analysis in Japan.","volume":"56","author":"Sato","year":"2021","journal-title":"J Gastroenterol"},{"issue":"2","key":"zoi241533r6","doi-asserted-by":"publisher","first-page":"289","DOI":"10.14309\/ajg.0000000000000955","article-title":"Risk of squamous cell carcinoma and adenocarcinoma of the esophagus in patients with achalasia: a long-term prospective cohort study in Italy.","volume":"116","author":"Zagari","year":"2021","journal-title":"Am J Gastroenterol"},{"issue":"3","key":"zoi241533r7","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1002\/jgh3.12132","article-title":"Risk of esophageal cancer in achalasia cardia: a meta-analysis.","volume":"3","author":"Gillies","year":"2019","journal-title":"JGH Open"},{"issue":"10","key":"zoi241533r8","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1093\/dote\/dox072","article-title":"Esophageal achalasia: a risk factor for carcinoma: a systematic review and meta-analysis.","volume":"30","author":"Tustumi","year":"2017","journal-title":"Dis Esophagus"},{"issue":"5","key":"zoi241533r9","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1093\/dote\/doy106","article-title":"Incidence and risk factors for esophageal cancer following achalasia treatment: national population-based case-control study.","volume":"32","author":"Markar","year":"2019","journal-title":"Dis Esophagus"},{"issue":"5","key":"zoi241533r10","doi-asserted-by":"publisher","first-page":"13","DOI":"10.3390\/cancers13051009","article-title":"Risk factors of esophageal squamous cell carcinoma beyond alcohol and smoking.","volume":"13","author":"Tarazi","year":"2021","journal-title":"Cancers (Basel)"},{"issue":"5C","key":"zoi241533r11","first-page":"3717","article-title":"Clinicopathological studies of esophageal carcinoma in achalasia: analyses of carcinogenesis using histological and immunohistochemical procedures.","volume":"20","author":"Chino","year":"2000","journal-title":"Anticancer Res"},{"issue":"8","key":"zoi241533r12","doi-asserted-by":"publisher","first-page":"14","DOI":"10.3390\/genes14081521","article-title":"Esophageal dysbiosis in achalasia and cancer development: a critical review.","volume":"14","author":"Tustumi","year":"2023","journal-title":"Genes (Basel)"},{"issue":"6536","key":"zoi241533r13","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1126\/science.abc4552","article-title":"The microbiome and human cancer.","volume":"371","author":"Sepich-Poore","year":"2021","journal-title":"Science"},{"issue":"6","key":"zoi241533r14","doi-asserted-by":"publisher","first-page":"607","DOI":"10.1016\/j.bpg.2017.09.010","article-title":"The gastrointestinal microbiota and its role in oncogenesis.","volume":"31","author":"Lam","year":"2017","journal-title":"Best Pract Res Clin Gastroenterol"},{"issue":"20","key":"zoi241533r15","doi-asserted-by":"publisher","first-page":"3807","DOI":"10.1016\/j.cell.2022.09.015","article-title":"A pan-cancer mycobiome analysis reveals fungal involvement in gastrointestinal and lung tumors.","volume":"185","author":"Dohlman","year":"2022","journal-title":"Cell"},{"issue":"1","key":"zoi241533r16","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1038\/s41392-023-01334-6","article-title":"The fungal mycobiome: a new hallmark of cancer revealed by pan-cancer analyses.","volume":"8","author":"Zong","year":"2023","journal-title":"Signal Transduct Target Ther"},{"issue":"2","key":"zoi241533r17","doi-asserted-by":"publisher","first-page":"302","DOI":"10.4103\/jomfp.JOMFP_111_18","article-title":"Evaluation of candidal species among individuals with oral potentially malignant disorders and oral squamous cell carcinoma.","volume":"23","author":"Roy","year":"2019","journal-title":"J Oral Maxillofac Pathol"},{"issue":"10","key":"zoi241533r18","doi-asserted-by":"publisher","first-page":"4945","DOI":"10.7150\/thno.55209","article-title":"Candida albicans disorder is associated with gastric carcinogenesis.","volume":"11","author":"Zhong","year":"2021","journal-title":"Theranostics"},{"issue":"11","key":"zoi241533r19","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2020105320","article-title":"Fungal-induced glycolysis in macrophages promotes colon cancer by enhancing innate lymphoid cell secretion of IL-22.","volume":"40","author":"Zhu","year":"2021","journal-title":"EMBO J"},{"issue":"6","key":"zoi241533r20","doi-asserted-by":"publisher","first-page":"e2207","DOI":"10.1210\/clinem\/dgaa140","article-title":"Patients with APECED have increased early mortality due to endocrine causes, malignancies and infections.","volume":"105","author":"Borchers","year":"2020","journal-title":"J Clin Endocrinol Metab"},{"issue":"2","key":"zoi241533r21","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1080\/13693780802342545","article-title":"Esophageal cancer associated with chronic mucocutaneous candidiasis. could chronic candidiasis lead to esophageal cancer?","volume":"47","author":"Domingues-Ferreira","year":"2009","journal-title":"Med Mycol"},{"issue":"1","key":"zoi241533r22","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1016\/j.mmcr.2012.02.003","article-title":"Association of esophageal candidiasis and squamous cell carcinoma.","volume":"1","author":"Delsing","year":"2012","journal-title":"Med Mycol Case Rep"},{"issue":"1","key":"zoi241533r23","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1148\/radiology.138.1.7470215","article-title":"Candidiasis in the obstructed esophagus.","volume":"138","author":"Gefter","year":"1981","journal-title":"Radiology"},{"issue":"5","key":"zoi241533r24","doi-asserted-by":"publisher","first-page":"1064","DOI":"10.1007\/s00464-014-3782-5","article-title":"Peroral endoscopic myotomy (POEM) leads to similar results in patients with and without prior endoscopic or surgical therapy.","volume":"29","author":"Orenstein","year":"2015","journal-title":"Surg Endosc"},{"issue":"1","key":"zoi241533r25","doi-asserted-by":"publisher","first-page":"160","DOI":"10.3349\/ymj.2013.54.1.160","article-title":"Prevalence and risk factors of esophageal candidiasis in healthy individuals: a single center experience in Korea.","volume":"54","author":"Choi","year":"2013","journal-title":"Yonsei Med J"},{"issue":"1","key":"zoi241533r26","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1093\/ajcp\/aqw210","article-title":"Challenges to \u201cclassic\u201d esophageal candidiasis: looks are usually deceiving.","volume":"147","author":"Alsomali","year":"2017","journal-title":"Am J Clin Pathol"},{"issue":"2","key":"zoi241533r27","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1001\/jama.2019.8859","article-title":"Effect of peroral endoscopic myotomy vs pneumatic dilation on symptom severity and treatment outcomes among treatment-naive patients with achalasia: a randomized clinical trial.","volume":"322","author":"Ponds","year":"2019","journal-title":"JAMA"},{"issue":"3","key":"zoi241533r28","doi-asserted-by":"publisher","first-page":"464","DOI":"10.1097\/SLA.0b013e318297ae28","article-title":"Surveillance endoscopy at five or more years after cardiomyotomy for achalasia.","volume":"259","author":"Gossage","year":"2014","journal-title":"Ann Surg"},{"issue":"3","key":"zoi241533r29","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1016\/j.ejcts.2004.12.026","article-title":"The incidence of gastroesophageal reflux after transthoracic esophagocardio-myotomy without fundoplication: a long term follow-up.","volume":"27","author":"Lindenmann","year":"2005","journal-title":"Eur J Cardiothorac Surg"},{"issue":"10","key":"zoi241533r30","doi-asserted-by":"publisher","first-page":"956","DOI":"10.1097\/MEG.0b013e3282fbf5e5","article-title":"Life expectancy, complications, and causes of death in patients with achalasia: results of a 33-year follow-up investigation.","volume":"20","author":"Eckardt","year":"2008","journal-title":"Eur J Gastroenterol Hepatol"},{"issue":"2","key":"zoi241533r31","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1136\/gut.23.2.137","article-title":"Gastro-oesophageal candidiasis.","volume":"23","author":"Scott","year":"1982","journal-title":"Gut"},{"key":"zoi241533r32","doi-asserted-by":"publisher","first-page":"S209","DOI":"10.4103\/jcrt.JCRT_581_18","article-title":"Fungal profile and antifungal susceptibility pattern of candidiasis in esophageal cancer patients.","volume":"16","author":"Talukdar","year":"2020","journal-title":"J Cancer Res Ther"},{"issue":"2","key":"zoi241533r33","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1111\/j.1365-2133.1969.tb15992.x","article-title":"Chronic hyperplastic candidiasis and squamous carcinoma.","volume":"81","author":"Williamson","year":"1969","journal-title":"Br J Dermatol"},{"issue":"6","key":"zoi241533r34","first-page":"610","article-title":"Leukoplakia and oral cancer.","volume":"62","author":"Cawson","year":"1969","journal-title":"Proc R Soc Med"},{"issue":"3","key":"zoi241533r35","doi-asserted-by":"publisher","DOI":"10.1128\/mbio.00447-23","article-title":"Candida albicans promotes oral cancer via IL-17A\/IL-17RA-macrophage axis.","volume":"14","author":"Wang","year":"2023","journal-title":"mBio"},{"issue":"7","key":"zoi241533r36","doi-asserted-by":"publisher","first-page":"990","DOI":"10.1111\/j.1567-1364.2009.00573.x","article-title":"Quorum sensing and fungal-bacterial interactions in Candida albicans: a communicative network regulating microbial coexistence and virulence.","volume":"9","author":"De Sordi","year":"2009","journal-title":"FEMS Yeast Res"},{"key":"zoi241533r37","doi-asserted-by":"publisher","first-page":"309","DOI":"10.2147\/CEG.S141642","article-title":"Achalasia and esophageal cancer: risks and links.","volume":"11","author":"Torres-Aguilera","year":"2018","journal-title":"Clin Exp Gastroenterol"},{"issue":"17","key":"zoi241533r38","doi-asserted-by":"publisher","first-page":"1951","DOI":"10.1200\/JCO.2014.58.0423","article-title":"Long-term follow-up of a community assignment, one-time endoscopic screening study of esophageal cancer in China.","volume":"33","author":"Wei","year":"2015","journal-title":"J Clin Oncol"},{"issue":"3","key":"zoi241533r39","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1111\/j.1600-0714.2012.01203.x","article-title":"Production of carcinogenic acetaldehyde by Candida albicans from patients with potentially malignant oral mucosal disorders.","volume":"42","author":"Gainza-Cirauqui","year":"2013","journal-title":"J Oral Pathol Med"},{"issue":"8","key":"zoi241533r40","doi-asserted-by":"publisher","first-page":"805","DOI":"10.1111\/odi.12565","article-title":"Candida virulence and ethanol-derived acetaldehyde production in oral cancer and non-cancer subjects.","volume":"22","author":"Alnuaimi","year":"2016","journal-title":"Oral Dis"},{"issue":"10","key":"zoi241533r41","doi-asserted-by":"publisher","first-page":"1543","DOI":"10.1093\/carcin\/8.10.1543","article-title":"Possible mycological etiology of oral mucosal cancer: catalytic potential of infecting Candida albicans and other yeasts in production of N-nitrosobenzylmethylamine.","volume":"8","author":"Krogh","year":"1987","journal-title":"Carcinogenesis"}],"container-title":["JAMA Network Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamanetworkopen\/articlepdf\/2829184\/guo_2025_oi_241533_1736185778.92682.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,14]],"date-time":"2025-01-14T11:01:50Z","timestamp":1736852510000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamanetworkopen\/fullarticle\/2829184"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,14]]},"references-count":41,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,1,2]]}},"URL":"https:\/\/doi.org\/10.1001\/jamanetworkopen.2024.54685","relation":{},"ISSN":["2574-3805"],"issn-type":[{"value":"2574-3805","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,14]]}}}