Exabis Library

Learning objectives

At the end of this workshop participants should be able to know:

• ·        Key quality indicators for a good report for intestinal ultrasound (IUS)
• ·        How to assess and how to report intestinal inflammation in IUS
• ·        Relevant findings for inflammation/complications in IUS that should be described in a report
• ·        Cine loops with UC and CD IUS-pathologies will be demonstrated together with the corresponding reports

Interactive cases will be presented to illustrate IUS diagnosis of UC complications, such as acute severe colitis, including monitoring of response to treatment, perforation, chronic structural damage in UC, infectious colitis, pseudopolips and lymphoma. 

Crohn’s disease is a chronic progressive inflammatory disease of the gastro-intestinal tract that may lead to bowel damage and disability. Half of patients will require surgery within ten years of diagnosis. Unfortunately, surgery is not curative, endoscopic recurrence is reported in 80% of patients within one year of diagnosis, and predicts clinical and surgical recurrence. The prevention of post-surgical recurrence is a critical target in the care of Crohn’s disease after surgery. Currently, postsurgical management and treatment of Crohn’s disease are based on endoscopic monitoring performed during the first year after surgery. However, colonoscopy is an invasive and expensive procedure, unpleasant to patients. Bowel ultrasound is a cheap, non-invasive, readily-available tool for the assessment and the monitoring of patients with inflammatory bowel disease, especially patients with Crohn’s disease. This presentation aims to review the evidence for the use of bowel ultrasound in the specific setting of postsurgical recurrence in Crohn’s disease; the diagnostic accuracy of bowel ultrasound in the detection of postsurgical recurrence in alternative to colonoscopy; its predictive value for clinical and surgical recurrence.

Crohn’s disease (CD) is predominantly allocated within the small bowel and characterized by persistent chronic inflammation that may cause an extramural complications. Intestinal Ultrasound (IUS) has shown to be highly effective in detecting and determining CD related complications such as Strictures, fistulas, and inflammatory masses. The aim of this interactive presentation is to show the use of IUS in some real clinical cases.

Clinical cases with contrast-enhanced ultrasound and elastography in Crohn's Disease strictures

Inflammatory bowel disease (IBD) is a complex disease characterised by chronic inflammation of the digestive tract. Genome-wide association studies (GWAS) have identified 241 risk loci significantly associated with the two common forms of IBD, Crohn’s disease and ulcerative colitis. The vast majority of these risk loci reside in non-coding regions of the genome, and we only know which gene is dysregulated to increase risk of disease for a minority. This knowledge gap makes it difficult to draw insights into disease pathology and identify new candidate drug targets.

To improve biological insights from IBD GWAS, we generated single cell RNA-sequencing data from ileal biopsies ascertained from 25 CD patients with active ileal inflammation and 26 non-IBD controls. We identified 49 different cell types among the ~140K sequenced cells (Fig.1), including all major immune, enterocyte, secretory and mesenchymal populations. Our optimized single-cell dissociation protocol preserves the top of villus epithelial cells, which are inherently prone to anoikis, enabling generation of high-quality transcriptomes for the first time. 

Fig. 1
Single-cell atlas of terminal ileum biopsies from Crohn’s disease and non-IBD individuals.

We identified 797 unique genes differentially expressed between CD patients and controls, with notable expression differences in stem cell, secretory, and enterocyte populations. Genes involved in antigen presentation and interferon-gamma signaling were enriched among those most frequently dysregulated cell types. In an attempt to identify which of these expression differences are likely causal of disease, rather than simply a consequence of it, we integrated results from the latest IBD GWAS to assess the extent to which genes captured disease heritability, and in which cell-types. Genes specifically expressed in Tregs, monocytes and IL10RA-negative monocyte-derived macrophages captured a significant fraction of disease heritability, strongly implicating these cell types in disease pathogenesis. We investigated which genes were driving these enrichment signals and identified candidate effector genes at many IBD risk loci. Reassuringly, many confirmed IBD effector genes known to have a role in the normal functioning of these cell types were found, including NOD2, IL18RAP, IL23R, NCF4, and IL2RA.

Single-cell analysis combined with IBD genetics has generated strong evidence for a causal role of novel disease mechanisms that have therapeutic potential. Further experiments are underway to validate this finding. At ECCO we will present an updated version of this analysis, including genetic mapping of gene-regulation across cell types to identify IBD effector genes and causal variants.

This course has been developed for physicians and endoscopists interested in Inflammatory Bowel Disease(s) (IBD). One major aim of this e-learning activity is to increase competence and knowledge with regard to endoscopy in IBD in order to improve patient outcomes.

The main learning objective will be to train participants in the evaluation of endoscopic images  of colonic lesions using multiple endoscopic techniques and modalities including the new advanced optical diagnosis technologies: dye chromoendoscopy, dyeless chromoendoscopy, magnification, when and why to do EMR  and ESD. Further this course will detail EMR and ESD techniques and the challenges of ESD and the management of strictures , fistulae and complications in IBD.

The major aim of the endoscopy course is to increase competence, knowledge, and confidence of the participants with regard to interventional therapy and endotherapy  in IBD and to improve patient management and outcomes.

Environmental factors play an important role in the pathogenesis of IBD. Thereby the question: can we modulate these factors and impact the disease course?
A lifestyle change including physical activity and diet can be beneficial for patients with IBD. 

The main objective of this presentation is to review recent data from intervention trials supporting this lifestyle change in patients with IBD.

Compared to the general population, patients with inflammatory bowel disease (IBD) have an increased risk of developing colorectal cancer. Chronic inflammation is believed to promote the development of neoplasia. Adenocarcinoma complicating UC and CD develops from a precursor lesion, dysplasia. Dysplasia complicating IBD is very variable macroscopically and histologically and is often multifocal. Besides conventional dysplasia in patients with IBD, nonconventional dysplasia are described. Three recent publications allow us to better define these new nonconventional types of dysplasia, from a clinical, morphological and molecular point of view, as well as nonconventional mucosal lesions in patients with IBD. Crohn’s disease (CD) is associated with an increased risk of small bowel adenocarcinoma (SBA). Research papers dedicated to small bowel adenocarcinoma (SBA) in patients with Crohn’s disease (CD) are scarce. (Yet, several advances have been accomplished in epidemiology, natural history and characteristics of SBA, in patients with CD). Several recent publications help us to better understand this entity.

T resident memory (Trm) cells in the intestinal mucosa and in particular subpopulations expressing phenotypic markers such as alphaE-beta7 or NKG2D have been associated with chronic inflammatory bowel disease (IBD) activity. We hypothesize that these populations may have a direct deleterious impact on the intestinal epithelium in IBD.

The phenotypic study of mucosal lymphocytes was performed in two prospective cohorts: ELYP including patients with active IBD before initiation of biotherapy and REMIND including patients with ileal Crohn's disease (CD) requiring ileocaecal resection. These analyses were performed before initiation of treatment and one year after continuous therapy in the ELYP cohort and on the resection specimen in the REMIND cohort. An innovative ex vivo autologous organoid-mucosal T cell coculture model was developed using the REMIND cohort specimens for patients and healthy ileum from individuals without IBD for controls (Figure 1). T cell infiltration within the organoid and epithelial cell death were assessed by confocal microscopy. A panel of 30 cytokines was quantified in the supernatants of cocultures.


Figure 1

In the ELYP cohort, before the start of treatment, IBD patients had lower expression of alphaE-beta7 and NKG2D on mucosal CD8 T cells. While alphaE-beta7 and NKG2D expression on mucosal CD8 T cells had returned to normal in endoscopic responders, it remained decreased in non-responders. Similarly, the inflammatory mucosa of the REMIND surgical specimens had lower levels of CD4 and CD8 T cells expressing alphaE-beta7 and NKG2D compared with controls and non-inflamed regions. We developed a coculture model between mucosal lymphocytes and organoids generated under autologous conditions. We showed an increase in apoptotic cell death in epithelial cells from CD patients which was not found in control cocultures. There was a significant correlation between the degree of epithelial cell death and T cell infiltration (Figure 2). Various proinflammatory cytokines such as IFNgamma, TNFalpha, IL-6 and IL- 17a were also increased in the supernatants. The use of antibodies blocking the alphaE-beta7 and NKG2D pathways of interest inhibited this effect by different mechanisms (Figure 3) While anti-beta7 and anti-NKG2D had comparable effects in terms of cell death inhibition, only anti-beta7 reduced T cell infiltration. Anti-NKG2D had no effect on cell infiltration but a reduction of perforin was observed in the supernatants.

Figure 2

Figure 3
CC= Coculture

These data demonstrate for the first time the direct cytotoxic deleterious effect of mucosal T cells on the epithelium of CD patients using a novel coculture model. AlphaE-beta7 and NKG2D pathways appear to be relevant in this process.

Educational Objectives:
1. To review the type of transducers used in intestinal ultrasound (IUS).
2. To review probe orientation and scan planes in IUS.
3. To have an overview of the normal bowel wall in ultrasound and possible mural and extramural findings.
4. To review how to distinguish between small bowel and colon.
5. To emphasise the anatomical landmarks to search for in IUS.
6. To review intestinal ultrasound technique and how to look for each bowel segment.