Esophageal Achalasia has been investigated as a potential risk factor for esophageal cancer (EC). Longstanding disease, repeated treatment, age and male sex seem the most relevant risk factors, but no clear effect size estimation from large sample cohorts has been provided so far. The aim of the investigators is to estimate EC risk in large sample-size population, and to provide sub-analyses per cancer type and treatment impact on EC risk.
Achalasia is a chronic idiopathic condition characterized by the absence of esophageal peristalsis and reduced relaxation of the lower esophageal sphincter, causing progressive dysphagia and weight loss. Achalasia has been investigated as a potential risk factor for esophageal cancer (EC); squamous cancer due to chronic inflammation related to stasis due to poor esophageal emptying and adenocarcinoma due to uncontrolled gastroesophageal reflux after treatment. Longstanding disease, repeated treatment, age and male sex have been addressed as the most relevant risk factors, but no clear effect size estimation from large sample cohorts has been provided so far. The authors conducted a retrospective cohort study, accessing the global federated health research network "TriNetX", that provides access to electronic medical records from approximately a hundred million patients across large healthcare organizations (HCOs). The analysis will be performed on achalasia patients, based on the ICD-10 code (K22.0), from January 1st 2000 until May 31st 2025. The incidence rate (cases/1000 persons-year) and cumulative prevalence of EC in an achalasia cohort in a span of 25 years will be firstly assessed. Then the absolute and time-to-event risk of EC, by comparing the achalasia cohort with control cohort, after propensity score nearest neighbor greedy matching, for relevant covariates. Kaplan-Meyer (KM) analysis with censoring, Hazard Ratios (HRs) and Risk Ratio (RR) and Risk Difference (RD) estimation for EC risk will be calculated. Log Rank test will be used to compare KM curves. Further sub-group analysis will be implemented between two population of achalasia patients, treated (with endoscopic/surgical myotomy or pneumatic dilation) and treatment-naïve. Further in-depth analyses between histologic type of EC, esophageal localization and comparing different achalasia treatment (myotomy vs pneumatic dilation) will be performed, in order to categorize the risk of EC, if more linked to treatment and therefore to the development of reflux, Barrett esophagus eventually leading to adenocarcinoma, or towards squamous cell cancer driven by chronic stasis and degeneration of the squamous esophageal epithelium
Study Type
OBSERVATIONAL
Enrollment
47,000
esophageal achalasia treatments
IRCCS San Raffaele Hospital
Milan, Lombardy, Italy
Hazard Ratio
Hazard Ratio (HR) with Kaplan Meyer (KM) analysis of EC occurrence in achalasia vs control subjects
Time frame: from Jan 1st 2000 to June 3rd 2025
Incidence proportion, prevalence and incidence rate
Incidence proportion (%), prevalence (%) and incidence rate (100,000 persons-year) of EC (and different histological subtypes)
Time frame: Jan 1st 2000- June 3rd 2025
Risk Ratio
Risk Ratio of EC (and different histologic subtypes) occurrence in achalasia cohort compared to controls, in treated vs untreated achalasia, LHM vs POEM group
Time frame: Jan 1st 2000-Jun 3rd 2025
Risk Difference
Risk Difference of EC (and different histological subtypes) occurrence in achalasia cohort compared to controls, in treated vs untreated achalasia, LHM vs POEM group
Time frame: Jan 1st 2000-June 3rd 2025
Hazard Ratio (HR) with Kaplan Meyer (KM) analysis of EC occurrence
Hazard Ratio (HR) with Kaplan Meyer (KM) analysis of EC occurrence (according to different subtypes) in achalasia vs control subjects and in treated vs untreated achalasia, and in LHM vs POEM
Time frame: Jan 1st 2000- June 3rd 2025
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