Introduction

Endoscopic intermuscular dissection has been described to successfully treat rectal pathology when deeper dissection levels are needed for en bloc resection and a clear vertical dissection margin, through dissection of the inner circular muscle from the outer longitudinal muscle of the rectum (1-4). The conventional technique is performed with carbon dioxide insufflation. However, since our description of the saline-immersion/irrigation technique (SITE), this has proven to overcome the disadvantages that occur with the use of CO₂ or de-ionised water (5-6). These include improved endoscopic visualization by reduction of any gas/fluid interface or fat micelles, intrinsic magnification, natural-traction through buoyancy, maintenance of a thick, fluid-soaked submucosa, enhanced patient comfort during operator-delivered conscious sedation, through less distension of the bowel and superior electrical conductivity, obviating the need for higher diathermy

Aims & Methods

A 43-year-old female underwent TAMIS for excision of a bulky sessile rectal lesion. The procedure had to be interrupted due to an intra-procedural complication. At follow-up colonoscopy 3 months after, a residual 50mm sessile (Paris 0-Is, LST-G-MN, JNET 2A) rectal lesion was identified in an area of severe fibrosis. Multidisciplinary team discussion favored endoscopic resection with endoscopic submucosal/intermuscular dissection (ESD/EID)

Results

SITE-ESD was selected as the preferred therapeutic approach. In the area of severe scarring, the distinction between planes was extremely challenging and submucosal space was not detectable, therefore, EID was warranted with some parts of the muscle removed full-thickness. Traction with clip-band was applied to gain access underneath the lesion and facilitate dissection. Resection time was 270 minutes. The deepest parts of the resection site was closed with clip-line method and protein-matrix gel was applied on the surface of the defect. The patient was safely discharged home 48 hours after the procedure, without any significant adverse events. Histopathological examination showed a tubulo-villous adenoma with low-grade dysplasia and focal high-grade, confirming R0 resection
6 months follow-up colonoscopy showed granulation tissue in the centre of the scar, with 2 residuals clips attached. This tissue was excised for histopathological analysis, without evidence of lesion recurrence, dysplasia or malignancy. More than 10 sessile serrated lesions were removed through the colon, suggesting an underlying serrated polyposis syndrome

Conclusion

SITE-EID is a feasible technique for rectal pathology when deeper excisions margins are required to achieve R0 resection, in severe fibrosis or deep submucosal invasion, avoiding the need for invasive surgery. SITE facilitates this technically demanding procedure through enhanced visualization, buoyancy and patient comfort. Further study is merited

References

1. Pimentel-Nunes P, Dinis-Ribeiro M, Ponchon T, Repici A, Vieth M, De Ceglie A, et al. Endoscopic submucosal dissection: European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy 2015;47:829–54.
2. Moons LMG, Bastiaansen BAJ, Richir MC et al. Endoscopic intermuscular dissection for deep submucosal invasive cancer in the rectum: A new endoscopic approach. Endoscopy 2022; 54: 993–8.
3. Nabi Z, Samanta J, Dhar J et al. Device-assisted endoscopic full-thickness resection in colorectum: Systematic review and meta-analysis. Dig Endosc 2024; 36: 116–28.
4. Guillaumot MA, Barret M, Jacques J et al. Endoscopic full-thickness resection of early colorectal neoplasms using an endoscopic submucosal dissection knife: A retrospective multicenter study. Endosc Int Open 2020; 8: E611–16.
5. Despott EJ, Murino A. Saline-immersion therapeutic endoscopy (SITE): An evolution of underwater endoscopic lesion resection. Digestive and Liver Disease [Internet]. 1. Dezember 2017 [zitiert 25. August 2023];49(12):1376. Verfügbar unter: http://www.dldjournalonline.com/article/S1590865817310538/fulltext
6. Yamamoto H, Hayashi Y, Despott EJ. The pocket-creation method for endoscopic submucosal dissection combined with saline-immersion: another potential option to overcome challenges in colorectal endoscopic submucosal dissection. Gastrointest Endosc [Internet]. 1. August 2019 [zitiert 6. August 2023];90(2):288–9. Verfügbar unter: https://pubmed.ncbi.nlm.nih.gov/31327340/

Disclosure

The authors declare the following conflict of interest
EMB: No disclosures
GK: No disclosures
AR: No disclosures
AM: Personal payments/honoraria/fees: Olympus Medical, Laborie, Boston Scientific, Fujifilm Healthcare Europe
EJD: Educational grants in support of conference organization, and honoraria, from Fujifilm Healthcare Europe, Pentax, and Olympus Medical, and honoraria from Ambu and Fujifilm Healthcare Europe

Introduction

Epithelial barrier dysfunction is a hallmark of inflammatory bowel diseases (IBD), contributing to increased permeability, microbial translocation, and sustained mucosal inflammation^1,2. Targeting barrier restoration has emerged as a promising therapeutic strategy³. Gallic acid, a dietary polyphenol with known anti-inflammatory and antioxidative properties, has shown potential in modulating mucosal responses⁴. To investigate its impact on epithelial integrity under inflammatory stress, we utilized intestinal organoids as a physiologically relevant ex vivo model system.

Aims & Methods

The aim of this study was to investigate the potential of gallic acid to restore intestinal epithelial barrier function under inflammatory conditions, using colonic epithelial organoids and integrating transcriptomic and permeability analyses.
The study was approved by the Kaunas Regional Biomedical Research Ethics Committee (protocol no. BE-2-31). Inflamed differentiated colonic epithelial organoids were established from a patient with ulcerative colitis (UC) and non-IBD control individual by exogenous stimulation with TNF-α and IFN-γ (10 ng/mL each) for 24 hours. For gallic acid (GA) screening, organoids were pre-treated with metabolite (100 μM) for 1 hour prior to inflammation induction and co-treated during the induction period. Subsequently, organoids were either processed for mRNA sequencing (1×75 bp, NextSeq 550, Illumina) or subjected to a FITC-Dextran (4kDa) assay. RNA-seq data was processed, analyzed, and visualized using nf-core/RNAseq pipeline and RStudio. Images for permeability assay analysis were acquired using an inverted fluorescence microscope (Zeiss Axio Observer 7), processed with ImageJ, and analyzed and visualized in RStudio.

Results

Principal component analysis of transcriptomic profiles from both UC and non-IBD organoids revealed clear sample clustering driven by stimulation. Differential gene expression and Gene set enrichment (GSEA) analyses indicated a more pronounced cell response to both treatments in UC organoids compared to non-IBD organoids. Inflammation activated immune (CXCL9/10/11, CX3CL1), interferon (IFI44, SOCS1, NOS2), and defense genes (GBP4, GBP5, OAS2), while downregulating metabolic genes (FABP6, CFTR, HMGCS2) in both groups. Gene Ontology-based GSEA confirmed immune pathway enrichment and lipid metabolism suppression in inflamed cultures. In total, 3,148 and 1,479 DEGs were identified in inflamed UC and non-IBD organoids, respectively. GA treatment modulated 2,144 and 384 genes (e.g., LYPD8, MKI67, MT-ATP6, CXCL14, CCL22) in these groups, suggesting potential to rebalance inflammation and metabolism. GA co-treatment enhanced epithelial integrity in UC organoids via upregulation of cell junction, peptide hormone processing, and immune-related pathways. In non-IBD organoids, GA promoted cell adhesion pathways, supporting epithelial cohesion. Functional permeability analysis confirmed GA’s protective role, as supported by transcriptomic data. Mean percentages of FITC-Dextran-permeable organoids were 16.02% (untreated), 86.08% (inflamed), and 42.58% (inflamed + GA). A trend toward statistical significance (Wilcoxon p = 0.125) was observed in both untreated vs. inflamed and inflamed vs. inflamed + GA comparisons.

Conclusion

In conclusion, gallic acid modulates inflammatory and metabolic pathways during colonic inflammation and enhances epithelial barrier integrity.
Study was funded by the European Union and the State Secretariat for Education, Research and Innovation (SERI) (project: miGut-Health, grant no. 101095470).

References

¹Jostins, L., et al. (2012). Host–microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature, 491(7422), 119–124. https://doi.org/10.1038/nature11582
²Cleynen, I., et al. (2016). Inherited determinants of Crohn’s disease and ulcerative colitis phenotypes: A genetic association study. The Lancet, 387(10014), 156–167. https://doi.org/10.1016/S0140-6736(15)00465-1
³Vieujean, S., et al. (2025). Understanding the therapeutic toolkit for inflammatory bowel disease. Nature Reviews Gastroenterology & Hepatology. Online ahead of print. https://doi.org/10.1038/s41575-024-01035-7
⁴Tian, B., Ye, P., Zhou, X., Hu, J., Wang, P., Cai, M., Yang, K., Sun, P., & Zou, X. (2025). Gallic acid ameliorated chronic DSS-induced colitis through gut microbiota modulation, intestinal barrier improvement, and inflammation. Molecular Nutrition & Food Research. Online ahead of print. https://doi.org/10.1002/mnfr.70024