Introduction

Eosinophilic esophagitis (EoE) is a chronic inflammatory disease of the esophagus. Inflammation in EoE has been associated with potential risk of esophageal cancer (EC), with controversial results by the most recent studies [1] [2] [3].

Aims & Methods

The aim of this study was to estimate the true risk burden of EC in EoE, further investigating the confounding role of overlapping gastroesophageal reflux disease (GERD) or Barrett Esophagus (BE) on EC occurrence. We conducted a retrospective multicenter cohort study on aggregated data of EoE patients accessing the global federated health research network “TriNetX”, with access to electronic medical records from approximately a hundred million patients across large healthcare organizations (HCOs), based on the ICD-10 code (K20.0), from January 1^st 2000 until March 31^st 2025. We inferred the risk of EC, by comparing two different EoE cohorts: cohort A including EoE diagnosis (excluding eosinophilic gastrointestinal disorders [EGIDS]), not applying any other restrictive criteria; cohort B with only pure EoE diagnosis excluding any instance of GERD (K21.0) and Barrett esophagus (BE) (K22.7) or other EGIDS. The control cohort comprised patients encountered in outpatient clinic for undefined issues (Z00), without diagnosis of EoE/BE or pre-cancerous lesions. We used propensity score nearest neighbor greedy matching, adjusting for PPI use, family history of GI cancer, age, sex, other esophageal diseases (K22.0) and GERD status. Kaplan-Meyer (KM) curves with censoring were built for time-to-event analysis. Log Rank test was used to compare KM curves. Hazard Ratios (HRs) and Risk Ratio (RR) estimation for EC risk were calculated and compared. Sub-analyses for squamous-cell cancer (SCC) vs adenocarcinoma, and for EC location in the esophagus (distal, medium and proximal) were implemented.

Results

After 1:1 propensity score matching, 92,447 patients with EoE (with or without GERD) (cohort A) (mean age 38.9±20.7 years, M 59.7%, previous history of malignant GI neoplasm 2.7%, GERD 40.4%, other esophageal diseases 14.9%, PPI use 40.4%; all p>0.05 with control group) and 32,270 patients pure EoE (without GERD/BE) (cohort B) (mean age 33.9±19.3 years, M 64.7%, previous history of malignant GI neoplasm 1.2%, GERD 0%, other esophageal diseases 8.3%, PPI use 23.2%; all p>0.05 with control group), were compared with controls subjects. Mean follow-up of cohort A was 1298.6 days compared to 1046.5 days in cohort B. The total number of EC occurrences in cohort A were 44 in EA group compared to 31 in the control group, resulting in a HR of 1.676 (1.058-2.657, 95%CI), while a non-significant RR of 1.419 (0.896, 2.247, 95%CI). The KM survival analysis resulted significant (log-rank test p=0.026). Interestingly, when comparing cohort B (pure EoE without GERD or BE) with the control group, only 10 instances of EC in both groups where encountered during the follow-up, with a non-significant HR of 0.893 (0.290-2.754 95%CI) with no difference in the KM survival analysis (p= 0.844). No differences in sub-analysis for squamous cell or adenocarcinoma cancer, neither for EC occurrence in different esophageal localizations were detected.

Conclusion

The results from this global retrospective study on more than 90,000 EoE patients, confirmed the irrelevant risk of EC in pure EoE. The mild association reported in other studies may be likely due to EoE overlap with GERD/BE. No specific surveillance for EC seems needed in EoE when GERD and BE are not present.

References

1. Albaneze N, Cotton CC, Anderson C, Katzka DA, Dellon ES. No Association Between Eosinophilic Oesophagitis and Oesophageal Cancer in US Adults: A Case-Control Study. Aliment Pharmacol Ther. 2025 Jan;61(2):363-368. doi: 10.1111/apt.18431. Epub 2024 Dec 4. PMID: 39629856; PMCID: PMC11680457.
2. Zhou MJ, Hsing AW, Clarke JO. Prevalence and predictors of Barrett's esophagus and esophageal cancer in patients with eosinophilic esophagitis. Dis Esophagus. 2025 Jan 7;38(1):doae120. doi: 10.1093/dote/doae120. PMID: 39775829.
3. Uchida AM, Schuman SS, Pyne A, Peterson K, Carlson M, Garber JJ, Roelstraete B, Ludvigsson JF. Risk of Cancer Diagnosis in Patients With Eosinophilic Esophagitis Using a Nationwide Swedish Population Cohort. United European Gastroenterol J. 2024 Dec;12(10):1378-1387. doi: 10.1002/ueg2.12713. Epub 2024 Nov 20. PMID: 39565026; PMCID: PMC11652337.

Disclosure

E.V. received speaker and/or consulting fees from Sanofi/Regeneron, Falk Pharma, Apollo Therapeutics, and Aurora Biofarma. EVS received consulting fees from Dr Falk Pharma and Reckitt Benckiser; research support from Medtronic and Diversatek Healthcare. DAC.: Medtronic(Speaking, Consulting, License); Diversatek (Consulting); Braintree(Consulting); Medpace (Consulting); Phathom Pharmaceuticals(Speaking); Regeneron/Sanofi(Speaking). AJB received research funding from BMS, Sanofi/Regeneron, SST, and Dr. Falk Pharma and received speaker and/or consulting fees from Uniquity, Laborie, Medtronic, BMS, Dr. Falk Pharma, Calypso Biotech, Eupraxia, Aqilion, Alimentiv, Sanofi/Regeneron, Uniquity, Reckitt, AlfaSigma and AstraZeneca. All other authors did not have any disclosures.

Introduction

In patients with disorders of the gut-brain interaction abdominal bloating is a visceral sensation (sensation of pressure/fullness), whereas visible abdominal distension is a somatic manifestation with abnormal postural tone (abdominophrenic dyssynergia, i.e., diaphragmatic push and abdominal wall relaxation). Abdominophrenic dyssynergia can be corrected by a simple non-instrumental technique, and our aim was to determine the relation of distension and bloating responses over time.

Aims & Methods

In a randomized, placebo-controlled, parallel trial (ClincalTrials.gov number NCT06150638) 40 consecutive patients (34 women, 6 men; age range 18–58 years) with disorders of gut-brain interaction complaining of visible abdominal distension were randomized to receive biofeedback or placebo. Patients in the biofeedback group were explained the mechanism of distension, and were taught to relax the diaphragm and contract the abdominal wall, using an original audiovisual support and hands-on guidance by a trained operator. In the placebo group, sham measurements of abdominal and thoracic motion were performed, and a pill of placebo was administered. Three 30-min sessions were performed over a 4-week intervention period, with instructions to perform daily exercises (biofeedback group) or to take placebo three times a day (control group) at home. After the intervention, patients allocated to the placebo group were offered biofeedback treatment. After receiving biofeedback treatment, patients in both groups were instructed to continue practicing these same exercises over time, and were followed up: visible abdominal distension and sensation of abdominal pressure/fullness (bloating) were measured at 1 and 3 months using 10-cm scales for 7 consecutive days, and the mean values (±SE) were calculated.

Results

After undergoing the three treatment sessions, abdominal distension improved in the biofeedback group (n=19; by 24±7 %), but not in the placebo group (n=20; 8±3 % change; p=0.025 vs feedback group). In the 20 patients randomized to placebo, subsequent biofeedback treatment improved abdominal distension (by 35±7 %). Follow-up in all patients after biofeedback (n=36) showed a sustained improvement in abdominal distension and bloating sensation at 1 month (by 39±5 % and 36±7 %, respectively; p<0.001 vs before treatment for both), and at 3 months (by 37±5 % and 34±8 %, respectively; p<0.003 vs before treatment for both).

Conclusion

In patients with disorders of gut-brain interaction, correction of abdominophrenic dyssynergia by a simple, non-instrumental technique, produces a sustained improvement of visible abdominal distension, associated with a concomitant improvement of bloating sensation.

Disclosure

I have the following Conflict of Interest to declare: Coloplast, Schwabe

Introduction

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. EA 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 [1]. Longstanding disease, repeated treatment, age and male sex have been addressed as the most relevant risk factors [2], but no clear effect size estimation from large sample cohorts has been provided so far [3].

Aims & Methods

We 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 was performed on March 25^th 2025 on the Global collaborative network on achalasia patients, based on the ICD-10 code (K22.0), from January 1^st 2000 until January 31^st 2024. We first investigated the incidence rate (cases/1000 persons-year) and cumulative prevalence of EC in an achalasia cohort in a span of 25 years. Then we inferred the risk of EC, by comparing the achalasia cohort with control population, using propensity score nearest neighbor greedy matching, for relevant covariates. Kaplan-Meyer (KM) analysis with censoring, Hazard Ratios (HRs) and Risk Difference (RD) estimation for EC risk were calculated. Log Rank test was used to compare Kaplan-Meyer curves. Further sub-group analysis was implemented between two population of achalasia patients, treated (with endoscopic/surgical myotomy or pneumatic dilation) and treatment-naïve.

Results

Among a cohort of 68,115 achalasia patients in a span of 25 years of follow-up, the cumulative prevalence of EC was 0.83% (increasing from 0.23% to 0.72% between 2000-2005 and 2020-2025) with an overall incidence rate of 0.87 cases/1000persons-year (increasing from 0.52 to 1.43 between 2000-2005 and 2020-2025). After 1:1 propensity score matching, 63,686 EA patients were compared with 63,686 control subjects (mean age 58.3±19.2 years, M 45%, previous history of malignant GI neoplasm 5.8%, alcohol users 2.1%; PPI use 35%; all p>0.05). The total number of EC occurrences were 517 (risk 0.008) in EA group compared to 86 (risk 0.001) in the control group, resulting in a RD of 0.007 (0.006-0.008, 95%CI, p<0.0001) and an HR of 6.7 (5.3-8.4, 95%CI, p<0.00001). At KM analysis, survival probability was 97.5% in achalasia group compared to 99.6% in controls in more than 20 years of follow-up (log rank test p<0.00001). In subgroup analysis of 4,166 treated vs untreated achalasia patients, the risk of EC after treatment (26 total cases) was considerably higher in the first group with a RD of 0.003 (0.001-0.006 95%CI, p=0.037) and a HR 2.46 (1.26-4.80, 95%CI, p<0.009) in a mean follow-up of 1,031.8 days.

Conclusion

The results from this large population analysis from multicenter global database with 20 years of follow-up of achalasia confirm the higher risk of EC in long-standing achalasia compared with healthy subjects. Furthermore, an in-depth analysis apparently indicated that the risk of EC is higher after treatment of achalasia, suggesting the need of prolonging the endoscopic surveillance, particularly in patients after treatment.

References

1. Zaninotto G, Rizzetto C, Zambon P, Guzzinati S, Finotti E, Costantini M. Long-term outcome and risk of oesophageal cancer after surgery for achalasia. Br J Surg. 2008 Dec;95(12):1488-94. doi: 10.1002/bjs.6413. PMID: 18991316.
2. Oude Nijhuis RAB, Zaninotto G, Roman S, Boeckxstaens GE, Fockens P, Langendam MW, Plumb AA, Smout A, Targarona EM, Trukhmanov AS, Weusten B, Bredenoord AJ. European guidelines on achalasia: United European Gastroenterology and European Society of Neurogastroenterology and Motility recommendations. United European Gastroenterol J. 2020 Feb;8(1):13-33. doi: 10.1177/2050640620903213. PMID: 32213062; PMCID: PMC7005998.
3. 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. PMID: 29748564.

Disclosure

E.V. received speaker and/or consulting fees from Sanofi/Regeneron, Falk Pharma, Apollo Therapeutics, and Aurora Biofarma. EVS received consulting fees from Dr Falk Pharma and Reckitt Benckiser; research support from Medtronic and Diversatek Healthcare. AJB received research funding from BMS, Sanofi/Regeneron, SST, and Dr. Falk Pharma and received speaker and/or consulting fees from Uniquity, Laborie, Medtronic, BMS, Dr. Falk Pharma, Calypso Biotech, Eupraxia, Aqilion, Alimentiv, Sanofi/Regeneron, Uniquity, Reckitt, AlfaSigma and AstraZeneca. All other authors did not have any disclosures.