Introduction

Eosinophilic Esophagitis (EoE) is a chronic, immune-mediated esophageal disease characterized by esophageal dysfunction symptoms and histological eosinophilic infiltration. Diagnosis requires ≥15 eosinophils per high-power field and exclusion of other causes. Though its pathophysiology is not fully understood, food antigens—such as milk and wheat—are considered primary triggers, leading to chronic inflammation, mucosal damage, and fibrosis. EoE predominantly affects white males and is managed through dietary therapy, PPIs, and topical corticosteroids. Since its identification in the 1990s, prevalence has increased, especially in Western populations, with notable regional and ethnic variability. In Latin America, prevalence also varies between countries. Esophageal biopsies are essential in patients with esophageal dysfunction, even in the absence of visible endoscopic changes. However, the frequency of esophageal eosinophilia in this population remains unknown in our region and institution.

Aims & Methods

A cross-sectional, descriptive, and retrospective study was conducted on patients over 18 years of age with symptoms of esophageal dysfunction who underwent upper endoscopy with esophageal biopsies between January 2020 and October 2023. A convenience sample of 164 patients was determined based on a 4% expected prevalence of EoE. Clinical records, endoscopy reports, and pathology files were reviewed to identify cases meeting diagnostic criteria. Data were analyzed using descriptive and inferential statistics, with a significance level set at p < 0.05.

Results

Demographics and Medical Background:The study included 152 patients (72.36% women; mean age 55.28 ± 14.07). Chronic conditions were present in 60.52% of the participants, the most frequent being hypertension (16.44%), asthma (11.18%), and diabetes mellitus (9.21%).Clinical Presentation:Gastroesophageal reflux symptoms (GERD) were reported in 51.31% of patients, with 28.28% presenting alarm symptoms (mainly dysphagia). Dysphagia alone was the second most common symptom (34.86%). Food impaction occurred in 6.57%, and esophageal strictures in 4.60%. Symptoms of Esophageal Dysfunction:Dysphagia was the most common symptom (67.76%), followed by heartburn (47.36%) and regurgitation (44.73%). Less common symptoms included food impaction, globus sensation, and non-cardiac chest pain. Endoscopic Findings:Findings suggestive of eosinophilic esophagitis (EoE) were relatively uncommon: esophageal rings (26.97%), strictures (11.18%), exudates (13.81%), longitudinal furrows (9.21%), and edema (0.65%). Hiatal hernia was observed in 28.94% of patients, and a wide hiatus in 41.44%. Prevalence of EoE:EoE (≥15 eosinophils/HPF) was diagnosed in 11 patients (7.2%). The average age was 48.63 ± 16.5 years, with dysphagia (72.7%), heartburn (63.6%), and regurgitation (54.5%) as the most frequent symptoms. Endoscopic signs suggestive of EoE were present in only 36.36% of these patients.​

Conclusion

This study investigates the clinical and diagnostic characteristics of Eosinophilic Esophagitis (EoE) in a specific population. A high prevalence of chronic comorbidities (60.52%) and a predominance of female patients (72.36%) were found. GERD symptoms were common (51.31%) and overlapped with EoE, especially in dysphagia and heartburn. EoE prevalence was 7.2%, with hiatal hernia linked to symptoms and food impaction. Diagnostic indicators showed good specificity but limited sensitivity. These findings emphasize the need for a comprehensive approach, combining clinical and endoscopic data, for accurate diagnosis and effective management of EoE.

References

1. Furuta GT, Katzka DA. Esofagitis eosinofílica. N Inglés J Med. 2015; 373(17):1640-8.
2. Attwood SE, Smyrk TC, DeMeester TR, et al. Eosinofilia esofágica con disfagia. Un síndrome clinicopatológico distintivo. Dig Dis Sci. 1993; 38:109-16.
3. Straumann A, Spichtin HP, Bernoulli R, Loosli J, Vögtlin J. Esofagitis eosinofílica idiopática: una enfermedad frecuentemente pasada por alto con manifestaciones clínicas típicas y hallazgos endoscópicos discretos. Schweiz Med Wochenschr. 1994; 124:1419-29.
4. Kelly KJ, Lazenby AJ, Rowe PC, Yardley JH, Perman JA, Sampson HA. Esofagitis eosinofílica atribuida a reflujo gastroesofágico: mejoría con una fórmula a base de aminoácidos. Gastroenterología 1995; 109: 1503-1
5. Lucendo AJ, Molina-Infante J, Arias Á, von Arnim U, Bredenoord AJ, Bussmann C; et al. Guías sobre esofagitis eosinofílica: recomendaciones y afirmaciones basadas en la evidencia para el diagnóstico y el tratamiento en niños y adultos. Unidos Europeo Gastroenterol J. 2017; 5(3):335-358.
6. Muir A, Falk GW. Esofagitis eosinofílica: una revisión. JAMA. 2021; 326(13):1310-1318
7. García-Compeán D, González-González JA, González-Moreno EI, Maldonado-Garza HJ. La esofagitis eosinofílica. ¿El Norte contra el Sur? Enfoque mecanicista bio-económico-social e implicaciones clínicas. Rev Gastroenterol Mex. 2017; 82(4):328-336.

Disclosure

Not conflict of interest

Introduction

Graves’ disease (GD) and ulcerative colitis (UC) are two distinct autoimmune disorders with increasing evidence of shared pathophysiological mechanisms. While previous epidemiological studies have reported a higher risk of IBD among individuals with GD, the association between GD and UC specifically remains controversial. In particular, the causal direction, genetic liability, and molecular mediators underlying this relationship are not well defined.

Aims & Methods

We conducted a multi-layered investigation to clarify the relationship between GD and UC. First, a large-scale prospective analysis using the UK Biobank cohort was performed to assess the association between GD and subsequent UC risk, with adjustments for demographic, lifestyle, and clinical covariates utilizing COX proportional hazard models. Second, two-sample Mendelian randomization (MR) analyses were conducted using publicly available genome-wide association study (GWAS) datasets to infer potential causal links. Finally, we performed protein mediation analysis integrating plasma proteomic data to identify potential intermediate proteins and pathways mediating the effect of GD on UC.

Results

Observational analysis revealed that patients with GD had a significantly elevated risk of developing UC. Stratified analysis further revealed that this association was more pronounced among male and obese individuals. The association remained significant even after adjusting for key covariates including medication use, psychological disorders, air pollution exposure, and sunlight exposure. Genetic-level analysis using Mendelian randomization confirmed a potential causal relationship between AITD and UC. This association was independently validated in MR sensitivity analyses. Through mediation analysis based on plasma proteomic data, 28 UC-related proteins were identified as potential mediators of the AITD–UC relationship. Among them, proteins such as Arachidonate 15-lipoxygenase B (ALOX15B) were significantly enriched in the high-risk group. Collectively, six pathways likely represent the core signaling axes through which GD promotes UC pathogenesis, highlighting potential targets for mechanistic and therapeutic exploration.

Conclusion

This study provides robust clinical, genetic, and molecular evidence for a link from GD to UC, mediated through specific immunopathogenic proteins and pathways. These findings offer novel insights into shared autoimmunity and may inform biomarker-driven strategies for early identification and targeted prevention of UC in patients with GD.

References

Ferrari SM. The association of other autoimmune diseases in patients with Graves' disease (with or without ophthalmopathy): Review of the literature and report of a large series. Autoimmun Rev. 2019 Mar;18(3):287-292.
Ordás I. Ulcerative colitis. Lancet. 2012 Nov 3;380(9853):1606-19.
Xian W. Graves Disease and Inflammatory Bowel Disease: A Bidirectional Mendelian Randomization. J Clin Endocrinol Metab. 2023 Apr 13;108(5):1075-1083.
Burisch J. Incidence of Immune-Mediated Inflammatory Diseases Among Patients With Inflammatory Bowel Diseases in Denmark. Clin Gastroenterol Hepatol. 2019 Dec;17(13):2704-2712.e3.

Disclosure

The authors declare no conflicts of interest.

Introduction

Colorectal cancer, the third most prevalent malignancy globally[1], exhibits strong associations with aberrant DNA methylation patterning. While DNA methyltransferase inhibitors (DNMTis) demonstrate therapeutic efficacy in hematologic malignancies, their clinical application in solid tumors remains constrained by dose-limiting genomic instability secondary to genome-wide hypomethylation[2]. Recent mechanistic studies have established methyl-CpG-binding domain protein 2 (MBD2) as a pivotal mediator of methylation-dependent transcriptional repression; however, its potential involvement in context-dependent oncogene activation remains unresolved. This study elucidates that pharmacological MBD2 inhibition achieves dual epigenetic rectification – reactivating tumor suppressor genes through promoter demethylation while selectively attenuating WNT16 overexpression via methylation-sensitive suppression, thereby establishing a targeted therapeutic paradigm that circumvents the pleiotropic toxicity associated with conventional DNMTis.

Aims & Methods

A multi-dimensional platform encompassing clinical specimens, cell lines, patient-derived organoids, and PDX models was employed. Integrative whole-genome bisulfite sequencing and RNA-seq analyses delineated methylation-driven transcriptional networks. Chromatin immunoprecipitation sequencing characterized MBD2 binding at differentially methylated regions, with CRISPR interference validating functional regulatory elements.

Results

CRC cells exhibited pronounced hypomethylation at the WNT16 promoter accompanied by diminished MBD2 occupancy. MBD2 inhibitor treatment downregulated WNT16 expression at both RNA and protein levels, concomitant with suppression of Wnt/β-catenin signaling. In PDX models, MBD2 inhibition reduced tumor burden without inducing genomic instability—a hallmark toxicity of conventional DNMTis.

Conclusion

This study unveils a novel epigenetic mechanism wherein MBD2 facilitates oncogenic WNT16 activation via its "methylation reader" function. Compared to broad-spectrum DNMTis, MBD2-targeted therapy achieves precise correction of carcinogenic epigenetic lesions while avoiding genome-wide hypomethylation risks, advancing a paradigm for targeted CRC treatment.

References

[1] Jiexi Li, Xingdi Ma, Deepavali Chakravarti, Shabnam Shalapour, Ronald A DePinho. Genetic and biological hallmarks of colorectal cancer. Genes Dev.
2021;35(11-12):787-820
[2] Marie Lopez, Julie Gilbert, Jean Contreras, Ludovic Halby, Paola B Arimondo. Inhibitors of DNA Methylation. Adv Exp Med Biol. 2022;1389:471-513
[3] Yang Xie, Feng Wang, Jun Yu, Jing Zhang, Yuting Liu, Mengying Li, Jian Qi. Silencing of MBD2 and EZH2 inhibits the proliferation of colorectal carcinoma cells by rescuing the expression of SFRP. Oncol Rep. 2021;46(6):250.

Introduction

A growing proportion of the general population is affected by Metabolic dysfunction-associated steatotic liver disease (MASLD). The relationship between MASLD and breast cancer is not sufficiently understood. The question, whether MASLD is a risk factor for breast cancer has become of great interest. The other way round, the question to what extent breast cancer therapy with tamoxifen leads to MASLD needs to be addressed.

Aims & Methods

In order to investigate the relationship between MASLD and breast cancer, we analyzed data from the liver Magnetic Resonance Imaging (MRI) subset of the United Kingdom Biobank (UK Biobank) (20,601 women, 3,817 MASLD and 1,048 breast cancer cases) and data from the Mayo Clinic Biobank and Tapestry studies (7,943 women, 1,976 MASLD and 634 breast cancer cases). MRI data were used to differentiate between MASLD and controls in the UK Biobank cohort. In the Mayo Clinic cohort, International Classification of Diseases (ICD) 9 and 10 codes, natural language processing and chart review were used. In the UK Biobank cohort we adjusted the analysis for age and Body Mass Index (BMI) by multivariable logistic regression, whereas in the Mayo Clinic cohort the controls were matched by age and BMI.

Results

We found an association between MASLD and breast cancer among lean women in both cohorts independent of age and BMI (both p<0.001). Most women with breast cancer and MASLD were diagnosed with breast cancer before they were diagnosed with MASLD. Significantly more women used tamoxifen in the MASLD group compared to the control group in the UK Biobank cohort (p=0.002) and the Mayo Clinic cohort (p=0.008) independent of age and BMI. In a subgroup analysis of the women, who were diagnosed with breast cancer after the study MRI of the liver in the UK Biobank, there was no significant association of MASLD and breast cancer independent of age and BMI (p=0.219). This was also not the case among lean or overweight women.

Conclusion

In this study we observed an association between MASLD and breast cancer among lean women. The use of tamoxifen in breast cancer therapy offers a possible explanation for the association. This study raises awareness that the development of hepatic steatosis through breast cancer therapy with tamoxifen might also be relevant for lean women.

Disclosure

financial support:
C.V.S. is supported by a grant from the Interdisciplinary Centre for Clinical Research within the faculty of Medicine at the RWTH Aachen University (PTD 1-13/IA 532313), the Junior Principal Investigator Fellowship program of RWTH Aachen Excellence strategy and the NRW Rueckkehr Programme of the Ministry of Culture and Science of the German State of North Rhine-Westphalia. K.M.S. is supported by the Federal Ministry of Education and Research (BMBF) and the Ministry of Culture and Science of the German State of North Rhine-Westphalia under the Excellence strategy of the federal government and the Laender as well as the NRW Rueckkehr Programme of the Ministry of Culture and Science of the German State of North Rhine-Westphalia. C.D., C.V.S. and K.M.S. are supported by the CRC 1382 project A11 and B09 funded by Deutsche Forschungsgesellschaft (DFG, German Research Foundation) – Project-ID 403224013 – SFB 1382. K.J.W. is supported by the U.S. National Cancer Institute through grant R37CA259201 and the Mayo Clinic Hepatobiliary SPORE (P50 CA210964).

Introduction

Endoscopic retrograde cholangiopancreatography (ERCP) is widely used for biliary diseases, yet safety data in transplant recipients remain scarce.

Aims & Methods

This study aimed to evaluate short-term survival and ERCP-related complications in transplant patients. We conducted a retrospective cohort study using the TriNetX database (December 2020–December 2024). Patients diagnosed with acute cholangitis who underwent ERCP were included. Transplant recipients were matched 1:1 with non-transplant controls without active cancer using propensity score matching. Outcomes assessed included survival (Kaplan-Meier analysis) and ERCP-related complications such as post-ERCP pancreatitis (PEP), sepsis, perforation, retroperitoneal abscess, liver abscess, blood transfusion, and emergency department visits.

Results

Before matching, 2,209 transplant recipients and 41,202 non-transplant controls met the inclusion criteria. After propensity score matching, 1,710 matched pairs were analyzed. Survival rates were comparable between transplant and non-transplant groups. Transplant recipients had significantly lower rates of PEP (HR: 0.591, 95% CI: 0.371–0.943, p=0.0254) and emergency department visits (HR: 0.667, 95% CI: 0.498–0.893, p=0.0061). Rates of other complications were not significantly different: sepsis (HR: 1.183, 95% CI: 0.799–1.754, p=0.4005), retroperitoneal abscess (HR: 1.514, 95% CI: 0.587–3.906, p=0.3468), liver abscess (HR: 1.377, 95% CI: 0.826–2.293, p=0.2176), perforation (HR: 2.088, 95% CI: 0.793–5.493, p=0.1272), and blood transfusions (HR: 1.642, 95% CI: 1.255–2.147, p=0.0003). Subgroup analysis of liver transplant patients showed lower PEP rates (HR: 0.592, 95% CI: 0.347–1.009, p=0.0510), but higher risks of retroperitoneal abscess (HR: 3.499, 95% CI: 0.976–12.544, p=0.0402), liver abscess (HR: 2.682, 95% CI: 1.303–5.521, p=0.0053), and blood transfusions (HR: 1.797, 95% CI: 1.282–2.518, p=0.0005).

Conclusion

ERCP appears safe in transplant recipients, demonstrating comparable short-term survival and overall complication rates to non-transplant patients. However, careful monitoring for post-ERCP bleeding and infections is particularly warranted in liver transplant recipients.

References

1. O'Connor HJ, Vickers CR, Buckels JA, McMaster P, Neuberger JM, West RJ, Elias E. Role of endoscopic retrograde cholangiopancreatography after orthotopic liver transplantation. Gut. 1991 Apr;32(4):419-23. doi: 10.1136/gut.32.4.419. PMID: 2026341; PMCID: PMC1379083.
2. Predictors of Early Repeat Endoscopic Retrograde Cholangiopancreatography After Liver Transplantation by Organ Donor TypeSinha, Jasmine et al. Techniques and Innovations in Gastrointestinal Endoscopy, Volume 24, Issue 2, 159 - 166

Introduction

Studies report that almost 50% of Large Non-Pedunculated Colorectal Polyps (LNPCP) have been subjected to heavy manipulation in form of prior attempts at resection or extensive biopsy sampling prior to referral to an expert centre. This significantly impacts several critical outcomes of endoscopic resection (ER). However, understanding of standardised classifications of LNPCP, endoscopic diagnosis and indications for ER has increased in general endoscopy practice which may have improved decision making prior to referral. We aimed to compare trends in patterns of prior injudicious manipulation and the significance of biopsy sampling over sequential time periods in a large cohort of patients referred to a tertiary referral centre for ER.

Aims & Methods

Referral documentation, including clinic and referral letters, endoscopy reports, and histopathology result, were reviewed for evidence of prior resection attempts or biopsy sampling. Data included the number of biopsy samples taken and corresponding histological results. Patients referred between January 2011 and August 2024 were categorised into five time periods. Heavy manipulation was defined as either a prior resection attempt or ≥6 biopsy samples. Analyses included comparisons of resection attempts, heavy manipulation, biopsy sampling, and the detection of high-grade dysplasia on biopsies (as a marker of improved lesion assessment and targeted sampling). Trends in practice changes were assessed using the Chi-square test for trend.

Results

1407 LNPCP were treated by ER. There was a significant trend toward fewer prior failed attempts at resection over sequential time periods with 30% in Period 1 and only 11% in Period 5 (p<0.001); fewer LNPCP subjected to heavy manipulation with 61% in Period 1 and 27% in Period 5 (p<0.001) and fewer LNPCP with prior biopsy sampling with 77% in Period 1 and 47% in Period 5 (p<0.001). However, there was no trend found for an improvement in biopsy sampling yields of HGD with 18% in Period 1 and 25% in Period 5 (p=0.1).

Conclusion

In a large cohort of ER of LNPCP, this study demonstrates a significant reduction over time in failed resection attempts, heavy manipulation, and biopsy sampling of LNPCP before referral to a tertiary centre for endoscopic resection (ER). This suggests an improvement in endoscopic lesion assessment and decision making by general endoscopists. However, heavy manipulation remains a significant problem. Although fewer LNPCP are biopsied prior to referral, the yield of significant findings did not change, suggesting biopsies are not effectively targeted, and highlighting the need for further improvements in lesion assessment.

Introduction

EUS-hepatico-gastrostomy(HGS) has become indispensable procedure in case of inaccessible cases due to malignant invasion to the duodenum etc. , failed ERCP cases, and failed cases after single balloon assisted ERCP(SBE-ERCP) in surgical altered anatomy.

Aims & Methods

From January, 2016 to April, 2024, we have performed EUS-HGS in 131(Male:79, Female 52, averaged age: 72) cases. The indication of EUS-BD was inaccessible to the duodenal papilla due to malignant invasion or failed cases of ERCP in cases of normal anatomy. In cases without duodenal invasion and intrahepatic bile duct dilatation, we perform EUS-CDS and we perform EUS-BD rendezvous in cases of accessible normal anatomy. And we performed EUS-HGS in remained cases. In surgical anatomy cases, we firstly perform SBE-ERCP, EUS-HGS were performed after failed SBE-ERCP. We have investigated the safety and usefulness of HGS.

Results

The subjects were consisted of malignant diseases (pancreatic cancer: 61(46.6%), biliary cancer: 20(15.3%), and others 35(26.7%) and benign disease (stenosis of bilio-jejunum anastomosis 7(5.3%), bile duct stone7(5.3%), primary sclerosing cholangitis 1(0.8%)). The reason for EUS-HGS were consisted of duodenal invasion 84 (64.1%) cases, inaccessible 21(16%), failed deep canulation 20(15.3%), others 6(4.6%). And normal anatomy cases were 90 (68.7%) and surgical anatomy 41(31.3%). Technical and clinical success was 128(97.7%) and 116(88.5%). The median procedure duration was 36 minutes (range 11-109). The used needle was 19 guage: 113(86.3%) and 22 guage: 18(13.7%). The puncturing branch was B3: 95(72.5%), B2: 35(26.7%), and B1: 1(0.8%). The averaged size of punctured branch was 5.0mm (range2.0-13.0). The dilation method was bougie: 97(74%), balloon: 21(16%), electrocautery: 6(4.6%), drill dilator: 5(3.8%), and not dilate: 2(1.5%). The used stent was plastic stent (PS): 105(80.2%) and covered metallic stent (CMS): 24(18.3%). The stent patency was PS: 120 days and CMS: 226 days (p=0.13). The early complication was peritonitis: 10(7.6%), bacteremia: 5(3.8%), cholangitis: 4(3.1%), bleeding: 2(1.5%), and migration: 3(2.3%). The multivariate analysis revealed only longer procedure duration (more than 36 min.) corelated to early complication(p=0.01).

Conclusion

EUS-HGS is safe and effective and essential for inaccessible cases, failed cases after ERCP and SBE-ERCP. And longer procedure duration corelated with early complication.