Introduction

There is minimal data to support a recommendation to perform colonic stenting (SEMs) in the right colon, but particularly in malignancy in the region of the ileocaecal valve, where only small bowel dilatation results from obstruction. This scenario poses technical challenges in endoscopic access in unprepared proximal colon, and relating to the anatomy of the ileocaecal valve. One recent case series included 13 patients with reported success rate and equivalent outcomes to left-sided stents with median survival of 4 months, although a two-step procedure was described¹.

Aims & Methods

In our centre we attempt self-expanding metal stent insertion (SEMs) in cases of malignant ileocaecal obstruction, which constitutes ~9% of our overall SEMs caseload. We report our outcomes and, as an important metric for palliative patients, stoma-free survival in the context of colorectal cancer management. We perform stenting using colonoscopy to access the stricture and fluoroscopy for wire and stent deployment, with both over the wire and through the scope techniques.

Results

25 patients, median age 77 years, underwent intention to stent for colorectal malignancy at the ileocaecal junction, where stent deployment into the ileum would be necessary to overcome the obstruction. Clinical success with life-time avoidance of surgery or stoma was 68% without any adverse events from attempting SEMs. Median survival was 206 days, compared to 167 days in those where stenting was unsuccessful. This was not significantly different to median stoma-free survival of 272 days for all SEMs patients in our database. One patient, after technically successful stent deployment, re-obstructed within 7 days and underwent surgery. There were no other early or late complications in either group. Reasons for technical failure in 6 cases was inability to pass a wire into the ileum, bowel preparation in 1 case, and failure to adequately resolve obstruction in the aforementioned patient.

Conclusion

Stenting malignant colonic obstruction of the ileocaecal region is more technically challenging but does not appear to disadvantage patients after an unsuccessful procedure. Stoma or surgery is avoided in 68% cases in intention to treat analysis of 25 patients and median survival of 206 days is equivalent to other colonic stent locations.

References

1. Fujisawa et al. J. Clin. Med. 2025, 14(3), 826

Introduction

Despite increasing attention to the rising incidence of Barrett’s esophagus (BE) and its progression to esophageal adenocarcinoma (EAC) in Western populations, the interplay between host factors and epigenetic alterations, including DNA methylation, remains poorly characterized (1). DNA methylation changes are among the earliest and most consistent molecular events observed in BE and EAC, but it is not yet well understood whether these changes are systematically correlated with demographic variables such as age and gender (2).

Aims & Methods

In this study, we explore whether methylation-based molecular subtypes exist within BE and EAC and examine how they are distributed across gender and age groups, leveraging integrated analysis of publicly available datasets. This approach may reveal novel insights into inter-individual variability in the epigenetic landscape of esophageal disease.
DNA methylation data from three GEO datasets (GSE104707, GSE81334, GSE89181) comprising 153 BE and 60 EAC samples were used. Samples with complete diagnostic, age, and gender annotations were retained, and the corresponding metadata was harmonized and used to build a cross-cohort to ensure robustness. Our previously defined Barrett’s progression-associated signature (3) was used to construct a unified methylation matrix across datasets. Batch effects were evaluated and corrected using ComBat, adjusting for diagnosis, age, and gender. Consensus clustering was used to identify molecular subtypes, and associations between clusters and clinical covariates were assessed using Wilcoxon rank-sum tests with FDR correction. Methylation patterns and BE status were visualized to explore subtype-specific features.

Results

Cross-cohort individual and integrated analyses identified two distinct molecular clusters, defined by broad differences in mean DNA methylation across regions selected by the progression-associated signature. Statistically significant differences in mean methylation were observed in both female (FDR = 1.92 × 10⁻⁸) and male (FDR = 1.03 × 10⁻⁶) groups, indicating gender-specific methylation variation stratified by cluster. Age-stratified analyses further revealed significant inter-cluster methylation differences within the 50–60 (FDR = 1.9 × 10⁻⁶) and 60–70 (FDR = 5.2 × 10⁻⁴) age groups, with a modest effect also observed in the 70–80 group (FDR = 1.26 × 10⁻²). These findings suggest the presence of age-associated methylation drift and gender-related differences; however, neither appears sufficient alone to fully account for the observed methylation patterns across BE and EAC patients.

Conclusion

Aging and male gender are established risk factors for BE and EAC, yet their impact on the epigenetic landscape remains poorly defined. Our findings reveal consistent methylation-based clustering across gender and age groups, suggesting that DNA methylation profiles capture biologically relevant variation linked to these demographics. This supports the utility of methylation signatures for early detection and risk stratification. However, key limitations such as sample size imbalances and male overrepresentation reflect broader biases in BE/EAC research and underscore the need for more representative study designs. Further confirmation studies using prospectively collected clinical samples are currently ongoing (NCT06523374) to advance the development of robust, demographically inclusive methylation-based biomarkers.

References

1. Kailasam A, Mittal SK, Agrawal DK. Epigenetics in the Pathogenesis of Esophageal Adenocarcinoma. Clin Transl Sci. 2015 Aug;8(4):394–402.
2. Kaz AM, Wong CJ, Varadan V, Willis JE, Chak A, Grady WM. Global DNA methylation patterns in Barrett’s esophagus, dysplastic Barrett’s, and esophageal adenocarcinoma are associated with BMI, gender, and tobacco use. Clin Epigenetics. 2016;8:111.
3. Dehkordi NR, Higareda-Almaraz JC, Mancuso FM, Kruusmaa K, Bertossi A. 365. METHYLATION BIOMARKERS TO STRATIFY BARRETT’S ESOPHAGUS PATIENTS PROGRESSING AND NON-PROGRESSING TO ESOPHAGEAL ADENOCARCINOMA. Diseases of the Esophagus. 2024 Sep; 37(Supplement_1)

Disclosure

N. Riahi Dehkordi and K. Kruusmaa are employees of Universal Diagnostics d.o.o., Ljubljana, Slovenia
J.C. Higareda-Almaraz and F.M. Mancuso are employees of Universal Diagnostics S.A., Seville, Spain