Exabis Library

Vedolizumab (VDZ), a monoclonal antibody that targets α4β7 integrin, was approved to treat moderate-to-severe ulcerative colitis (UC) based on the presumption that it blocks T cell recruitment to the inflamed intestinal mucosa. The clinical evidence suggests that up to 50% of UC patients do not achieve disease remission under VDZ treatment. This study aims to identify changes in cell abundances and molecular pathways associated with VDZ response in UC. To this end, we included anti-tumor necrosis factor (anti-TNF)-naïve and anti-TNF-exposed patients with active UC, and utilized single-cell RNA sequencing (scRNAseq) and high-dimensional flow cytometry (Cytek) to assess the peripheral blood and the gut mucosal compartments.

Gut mucosal biopsies from inflamed and non-inflamed regions, and peripheral blood mononuclear cells (PBMCs) were obtained from UC patients 2 wks before (t0) and 14 wks after (t4) the start of VDZ administration. Response to treatment was prospectively evaluated based on endoscopic assessment (defined as a decrease in total Mayo score between t0 and t4) and physician global assessment (PGA) that incorporates disease activity score and biochemical measurements.

A total of 25 UC patients (pts) were included: 44% anti-TNF-naïve. Endoscopic response to VDZ was observed in 32% of UC pts, while 56% of pts showed response based on PGA. The VDZ response rate (by PGA) was higher in anti-TNF-naïve pts vs anti-TNF-exposed pts (82% vs 36% responders, respectively). A preliminary analysis was performed on samples from 8 (out of 25) UC pts, profiling >70,000 gut mucosal cells and >25,000 PBMCs. Within the mucosal compartment, at t0 we identified immune cells (50% of all captured cells), stromal cells (10%), and epithelial cells (40%). Upon inflammation, the proportion of immune cells increased to 70%, stromal cells to 20%, while epithelial cells depleted to 10%. Notably, all main identified immune cell lineages – T cells, B cells and myeloid cells – contributed to the expansion of the immune cell compartment in inflamed mucosa. In line with scRNAseq data, we identified all major immune cell populations and detected expression of both the classic gut-directed and the redundant trafficking integrins by Cytek.

The preliminary results substantiate our current understanding of VDZ biology in UC. We confirm that anti-TNF-naïve pts have a higher response rate to VDZ vs anti-TNF-exposed pts. With this unique cohort, our study has the power to further explore molecular mechanisms and pathways that underlie VDZ response at the single-cell level.

Non melanoma skin cancer (NMSC) is amongst the most common cancers worldwide and the incidence of both melanoma and NMSC is still rising. This is not only due to people reaching an older age, but also to the increasing amount of people receiving immunosuppressive medication. While immunosuppression in organ transplant patients serves as the most well-known model for these iatrogenic induced skin cancers, alternative forms of immunomodulating therapies, such as the biologicals, also caught attention because of their potential to disrupt skin cancer immunosurveillance.  Data on biologicals, with anti-TNFα most studied, are more controversial, however, and diverge according to the  inflammatory disease (Inflammatory Bowel Disease (IBD), psoriasis or rheumatoid arthritis) for which they are given.

In this slide seminar a complicated case of IBD in a pediatric patient will be discussed.
Educational objective:
- evaluation of a case in relation of clinical information
- to think on different diagnosis in IBD 

Objectives
1. The role of endoscopy in the surveillance of IBD-patients
2. The diagnosis of dysplasia and its subtypes on biopsies
3. The consequences for the treatment of the patient

Due to the continuous inflamed state of the mucosa, ulcerative colitis and Crohn’s disease patients are at risk of developing colorectal cancer at an earlier age and with a poorer prognosis. Hence continuous endoscopic surveillance with sampling of biopsies is necessary to detect the preneoplastic lesions in an early stage.  The SCENIC classification is a new endoscopic classification, which categorizes the lesions in to invisible and visible dysplasia.. Histologically these lesions consist of different subtypes, of which the adenomatous type is the most common. The presence of an inflamed mucosa complicates its diagnosis, resulting in a high interobserver variability in the categories indefinite for dysplasia and low grade dysplasia. Hence the ECCO-guidelines recommend to confirm the diagnosis of dysplasia by an expert pathologist in gastrointestinal pathology.

Eductional objective: To illustrate a rare mimicker of IBD pathology.

A middle-aged woman of Turkish origin complained of abdominal pain, watery diarrhea and vomiting since 3 weeks.
Lab tests were negative. Colonoscopy showed moderate to severe, patchy pancolitis.
Pathology was unclear.
She was treated with antibiotics and painkillers.
She went first into remission, and then did a relapse after one month.
At this time there was also arhtritis and oral as well as genital sores.
Colonoscopy showed patchy ulceration with dense perivascular inflammatory cell infiltrates, but without granulomas.

Your diagnosis?

Ulcerative Colitis and Crohn's disease have different macroscopic appearances.
Both diseases show unique and peculiar macroscopic features and it is important to recognise them in order to sample IBD specimens correctly.
The macroscopic examination is the first step for a correct pathological analysis and it is essential for the histological examination.
Educational objectives:
-To identify basic macroscopic features of UC and CD.
-To sample the specimens correctly.
-To recognise elementary lesions.
-To do not underestimate IBD samples.

1. To learn about the epidemiology of Small Bowel Adenocarcinoma. 
2. To understand the absolute risk and relative risk linked to it.  
3. To review practical management of Dysplasia/ SBA