Introduction

In recent years, evidence shows that long non-coding RNAs (lncRNAs) are key regulators of gene transcription and play important roles in the pathogenesis of inflammatory bowel diseases. LncRNAs are involved in the regulation of intestinal epithelial cell apoptosis, cell-cell interactions, and enhancing inflammation, among others. Biological therapies, which are considered the most potent for disease control, only benefit one-third of patients. For this reason, a deeper understanding of the mechanisms by which biological drugs elicit their effect on intestinal mucosal is needed. Hence, we aimed to unravel the ex vivo modulator effect of infliximab on the lncRNAs expression in intestinal biopsies from patients with Crohn´s Disease (CD).

Aims & Methods

We performed an unbiased transcriptomic analysis of intestinal biopsies from the ileum and colon from 30 patients [active CD = 10, quiescent CD = 10, healthy controls (HC) = 10] to identify lncRNA differentially expressed in the setting of infliximab modulation. Endoscopic biopsies were cultured with or without infliximab and the transcriptome was determined by Illumina gene expression array. We used different databases (Ensembl Biomart, RNAcentral and ToppGene) to search for non-annotated lncRNA information and data on the location (cellular component), biological process and molecular function of differentially expressed lncRNAs.

Results

Transcriptomic results revealed a widespread dysregulation of lncRNAs in ileum biopsies from patients with active CD, quiescent CD and HC compared to the colon at baseline and after infliximab culture. These differentially expressed lncRNAs were enriched in such pathways as proliferation, apoptosis, migration, inflammatory response of fibroblasts, response to wounding, posttranscriptional regulation of inflammatory genes and activation of the mitogen-activated protein kinase signaling pathways. Regarding the effect of infliximab according to intestinal location, presence of disease and activity, no significant lncRNAs were identified in the different study comparatives.

Conclusion

We have characterized the basal transcriptomic landscape of lncRNAs in patients with CD (active and quiescent) and HC both in ileum and left colon. However, we have not found differential lncRNA expression due to the effect of infliximab, suggesting that the location (ileum or colon) is more relevant when analyzing differences in lncRNA expression in the intestinal tissue.

Introduction

Colonoscopy is the ‘gold standard’ investigation for assessment of the large bowel allowing diagnosis, biopsies, and therapy to be undertaken. Colonoscopy detects and prevents colorectal cancer through detection and removal of polyps, and is important in the diagnosis and treatment of non-neoplastic conditions. Poor quality colonoscopy is associated with increased rates of interval cancers. High quality colonoscopy cannot occur without good quality bowel preparation. Evidence in the UK show that 22% of failed colonoscopies were due to poor bowel preparation. Apart from the bowel cleansing agent, dietary restriction prior to colonoscopy has been shown to enhance quality of bowel preparation at colonoscopy.

Aims & Methods

We aimed to assess the information received and followed by patients in terms of dietary modification prior to colonoscopy.
A single centre prospective analysis of 60 consecutive patients attending colonoscopy at Chase Farm Hospital in London was undertaken in May 2022. Patients were asked to complete a questionnaire with information gathered about: type of bowel prep undertaken, whether written information about how to take bowel prep was received, whether a telephone consultation explaining dietary restriction prior to procedure happened, whether they followed a low fibre diet and the amount of fluid drunk.

Results

57 patients returned the questionnaire.
Of the 57 patients, 39% patients received written information on dietary restriction. A further 35% of patients received telephone information, 26% of patients receiving both written and verbal information. 56.9% of patients followed the 3 day dietary restriction. The quality of bowel preparation was inadequate (fair and poor by Aronchick scale) in 60% of those who did not follow the low fibre diet compared to 24% when followed. Patients who had seen a clinician in clinic and patients undergoing surveillance procedure were more likely to follow dietary restriction compare to direct access patients.

Conclusion

In this prospective study of clinical practice, we conclude that advice regarding dietary fibre restriction prior to colonoscopy is variable. In clinical practice, there is low compliance of dietary restriction prior to colonoscopy. We find that those who followed a low fibre diet are 40 % more likely to have a favourable bowel preparation compared to those following a high fibre diet. Those that had inadequate bowel prep required a repeat colonoscopy adding to the burden of the already stretched service. We recommend improvements in the implementation of the low residue diet in addition to the guidance of cleansing agents prior to colonoscopy.

Introduction

The introduction of lumen-apposing metal stents (LAMSs) has revolutionized the field of therapeutic endoscopic ultrasound (EUS). In the last decade, its utilization for off-label indications has markedly increased, particularly among patients with surgically altered anatomy to establish access in the excluded segment of the gastrointestinal tract. Indications for anastomosis creation include EUS-directed transgastric endoscopic retrograde cholangiopancreatography (EDGE), EUS-directed transgastric intervention (EDGI), or endoscopic reversal of Roux-en-Y gastric bypass (RYGB) for specific indications (see below).

Aims & Methods

This study aims to evaluate the effectiveness and safety of LAMS in patients with surgically altered anatomy for EDGE, EDGI, and reversal of RYGB. We collected data on all LAMS procedures conducted in patients with surgically altered anatomy, between October 2019 and February 2024 at the University Hospital of Ghent.
We used our prospective LAMS database and retrieved missing data from retrospective analysis of the medical patient records. The main outcome data of interest were technical success, clinical success, and adverse events. Technical success was defined as a successful placement of LAMS in the desired position. Clinical success was defined as either successful endoscopic access to the intended excluded gastrointestinal segment or achievement of the intended therapeutic goal when RYGB reversal was necessary. Adverse events were classified according to the AGREE criteria.

Results

A total of 73 LAMS procedures were performed: 70 cases of EUS-guided gastro-gastrostomy in patients with RYGB and 3 cases of EUS-guided gastro-enterostomy in patients with hepaticojejunostomy. Indications for LAMS procedures included 55 (75.3%) cases of EDGE, 13 (17.8%) cases of EDGI (such as gastroduodenoscopy and EUS), and 5 (6.8%) cases of RYGB reversal. Reversal of RYGB was required for one cachectic patient due to metastatic cholangiocarcinoma, three patients with hyperinsulinemic hypoglycemia, and one patient with therapy-resistant small intestinal bacterial overgrowth (SIBO).
The overall technical and clinical success rates were very high at 97.3% and 95.9%, respectively. Adverse events were observed in 11 out of 73 (15.1%) cases, including 7 (9.6%) minor events (AGREE score < 3) and 4 (5.5%) major events (AGREE score ≥ 3). Major events included stent migration (N=1), persistent fistula (N=2), and respiratory desaturation (N=1). All events could be successfully managed, and there were no procedure-related deaths. In 69.9% of cases, our method involved a dual-step approach, strategically implemented to await fistula maturation and reduce the risk of perforation. The median LAMS dwell time was 38 days (range 7, 431). LAMS was removed in 72.6% of the cases. Loss of LAMS patency occurred in 1 out of 73 (1.4%) cases and was endoscopically managed.

Conclusion

In conclusion, our study demonstrates that EUS-GG and EUS-GE offer an effective and safe approach to create anastomoses between gastrointestinal (GI) segments when performed by experts. With high technical (97.3%) and clinical (95.9%) success rates, LAMS proves beneficial for accessing excluded GI segments and reversing RYGB. Adverse events (15.1%) were mostly minor and manageable, with no procedure-related mortality. The extended patency duration and low re-intervention rate highlight LAMS as a minimally invasive and durable option in therapeutic endoscopic ultrasound procedures. Further prospective studies are required.

Introduction

In Crohn’s disease (CD) a symptomatic luminal stricture occurs in up to 20% of patients at the diagnosis and in more than 50% during lifetime (1,2). Endoscopic balloon dilatation (EBD) or surgical procedures are the currently available treatments (3,4). However, a considerable percentage of patients often require further surgery for post-operative CD recurrence (5). A consequent increased burden of short bowel syndrome is warranted. The combination of biological therapy with EBD could potentially reduce this risk.

Aims & Methods

The aim of our study was to evaluate the efficacy of EBD combined with biologic therapy in symptomatic gastrointestinal strictures in CD’s patients. We conducted a retrospective study including consecutive CD patients who underwent EBD for low bowel strictures from December 2015 until November 2022 at our tertiary IBD Center. Clinical strictures recurrence, needs for steroids and for surgery due to CD stenosis relapse were the primary outcomes evaluated during a follow-up period of six and twelve months. Chi-square and univariate statistical analyses were used when appropriate.

Results

A total of 52 patients treated with EBD with an overall number of 55 strictures were included. In the study population, 14 patients (27%) were smoker, the mean age was of 46,8 (18-77) years; the median of disease duration was 9 (0-42) years. Thirty-nine patients (75%) were in active treatment with biologic therapy at the moment of EBD. Twenty-three patients (44%) underwent EBD for anastomotic stricture, 8 (15%) for ileal stricture, 11 (21%) for ileocecal valve stricture, 5 (6%) for anal stricture and 4 (8%) for colic stricture. Three patients (6%) underwent EBD for multifocal bowel stenosis. Twenty-two (42%) patients had increased CRP value, 40 patients (77%) had evidence of moderate or severe endoscopic disease activity and 42 (81%) patients showed ulcerative lesions at stricture site. EBD was performed by 8-10, 12-15 or 15-18 mm dilation balloon. Technical success was reported in 60% of procedures and no adverse events were registered.
After 6 months from EBD, at univariate analysis, active smoke resulted a risk factor for clinical stricture recurrence (OR 10,25; IC 1,350 to 135,4; p value = 0,022) and for subsequent surgery (OR 10,25; IC 1,350 to 135,4; p value = 0,022). Moreover, increased CRP at the time of dilatation resulted a risk factor for need of steroids (OR 14,63; IC 2,69 to 71,50; p value = 0,0006). Concomitant biologic therapy and presence of ulcerative lesions did not show significative correlation with considered outcomes.
After 12 months from EBD, concomitant biologic therapy resulted a protective factor for prevention of surgery (OR 0,061; IC 0,005 to 0,502; p value = 0,0047), while anastomotic strictures were associated with a lower risk of sub-occlusion events than ileal stenosis (OR 0,07; IC 0,005 to 0,651; p value = 0,015). Increased CRP at the time of EBD, ulcerative lesions at the stricture site and active smoke were not significantly correlated with the considered outcome.

Conclusion

Our results suggest that in patients with CD undergoing EBD for bowel CD stricture, concomitant biological therapy reduces the risk of surgery for CD stenosis recurrence. Further prospective and controlled studies are underway to confirm these observations.

References

1. Rieder F Managing Intestinal Fibrosis in Patients With Inflammatory Bowel Disease. Gastroenterology &amp; hepatology. 2018. February; 14(2):120–122
2. Yoo JH, Holubar S, Rieder F. Fibrostenotic strictures in Crohn’s disease. Intest Res. 2020;0.
3. Paine E, Shen B. Endoscopic therapy in inflammatory bowel diseases (with videos). Gastrointest Endosc 2013;78:819–35.
4. Hassan C, Zullo A, De Francesco V, Ierardi E, Giustini M, Pitidis A, Taggi F, Winn S, Morini S. Systematic review:
Endoscopic dilatation in Crohn's disease. Aliment Pharmacol Ther. 2007 Dec;26(11-12):1457-64
5. Olaison G, Smedh K, Sjödahl R. Natural course of Crohn’s disease after ileocolic resection: endoscopically visualised ileal ulcers preceding symptoms. Gut 1992;33:331–5.