INCIDENCE, PREVALENCE AND OVERALL RISK OF ESOPHAGEAL CANCER IN ACHALASIA: A PROPENSITY-MATCHED POPULATION-BASED STUDY FROM A LARGE MULTICENTER DATABASE

NCT ID: NCT07022886

Last Updated: 2025-07-30

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Total Enrollment: 47000 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2025-06-03
• Study Completion Date: 2025-09-07

Brief Summary

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.

Detailed Description

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

Conditions

Achalasia Cardia; Esophageal Cancer (EsC)

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: RETROSPECTIVE

Study Groups

Achalasia primary cohort

Achalasia cohort (both naive or treated)

No interventions assigned to this group

Control subjects

Healthy controls, with the exclusion of achalasia

No interventions assigned to this group

Achalasia without Barrett Esophagus

Sensitivity analysis of achalasia both treated or untreated without Barrett esophagus

No interventions assigned to this group

Treated achalasia

achalasia undergone to various treatments

achalasia treatments

Intervention Type: PROCEDURE

esophageal achalasia treatments

Untreated achalasia

Achalasia without previous treatment

No interventions assigned to this group

LHM

Heller-Dor myotomy

achalasia treatments

Intervention Type: PROCEDURE

esophageal achalasia treatments

POEM

Peroral endoscopic myotomy

achalasia treatments

Intervention Type: PROCEDURE

esophageal achalasia treatments

Interventions

achalasia treatments

esophageal achalasia treatments

Intervention Type: PROCEDURE

Other Intervention Names

POEM; LHM

Eligibility Criteria

Inclusion Criteria

• Esophageal achalasia diagnosed according to guidelines (ICD-10-K22.0)

Exclusion Criteria

• Primary esophaeal and pharyngeal motility disorders (ICD-10-J39.2)

• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

TriNetX, LLC

UNKNOWN

Sponsor Role: collaborator

Vita-Salute San Raffaele University

UNKNOWN

Sponsor Role: collaborator

IRCCS San Raffaele

OTHER

Sponsor Role: lead

Responsible Party

Alberto Barchi

Medical Doctor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Albert Jan Bredenoord, MD, PhD, Prof

Role: STUDY_DIRECTOR

Department of Gastroenterology, Amsterdam UMC Location AMC, Amsterdam, The Netherlands

Locations

IRCCS San Raffaele Hospital

Milan, Lombardy, Italy

Countries

Italy

References

Ponds FA, Moonen A, Smout AJPM, Rohof WOA, Tack J, van Gool S, Bisschops R, Bredenoord AJ, Boeckxstaens GE. Screening for dysplasia with Lugol chromoendoscopy in longstanding idiopathic achalasia. Am J Gastroenterol. 2018 Jun;113(6):855-862. doi: 10.1038/s41395-018-0064-1.

Reference Type: BACKGROUND

PMID: 29748564 (View on PubMed)

Tustumi F, Bernardo WM, da Rocha JRM, Szachnowicz S, Seguro FC, Bianchi ET, Sallum RAA, Cecconello I. Esophageal achalasia: a risk factor for carcinoma. A systematic review and meta-analysis. Dis Esophagus. 2017 Oct 1;30(10):1-8. doi: 10.1093/dote/dox072.

Reference Type: BACKGROUND

PMID: 28859394 (View on PubMed)

Gillies CL, Farrukh A, Abrams KR, Mayberry JF. Risk of esophageal cancer in achalasia cardia: A meta-analysis. JGH Open. 2019 Feb 8;3(3):196-200. doi: 10.1002/jgh3.12132. eCollection 2019 Jun.

Reference Type: BACKGROUND

PMID: 31276035 (View on PubMed)

Related Links

https://live.trinetx.com/

TriNetX platform link

Other Identifiers

RECAP

Identifier Type: -

Identifier Source: org_study_id