PG Course, Morning Session

10:10 CET

Coffee Break

13:45 CET

Achalasia. What is the ideal long-term treatment?

Speakers

Guy Boeckstaens (KUL)

Wednesday March 4, 2020 13:45 - 14:10 CET
Room TEUN + LIJN

PG Course, Afternoon Session

14:00 CET

Genes involved in gut homeostasis: focus on enteroctyes

Integrin expression changes on the T cell subsets influence the response to vedolizumab in inflammatory bowel disease patients

Authors
C. DE GALAN (1), S. VAN WELDEN (1), S. BOS (1), S. TAVERNIER (2), T. LOBATON ORTEGA (3), G. GONZALES (1), W. VAN MOERKERCKE (4), B. STRUBBE (5), H. PEETERS (5), E. MACKEN (6), M. DE VOS (3), D. LAUKENS (1), P. HINDRYCKX (3) / [1] Ghent University, Ghent, Belgium, IBD research unit - Gastroenterology, Internal Medicine and Pediatrics, [2] University Hospital Ghent, Ghent, Belgium, Primary Immune Deficiency Research Lab, Department of Internal Medicine and Pediatrics, Centre for Primary Immunodeficiency Ghent, Jeffrey Model Diagnosis and Research Centre, [3] University Hospital Ghent, Ghent, Belgium, Department of Gastroenterology, [4] AZ Groeninge Hospital, Kortrijk, , Belgium, Department of Gastroenterology, [5] AZ St Lucas, Ghent, , Belgium, Department of Gastroenterology, [6] University Hospital Antwerp, Edegem, Belgium, Department of Gastroenterology

Introduction
Vedolizumab is a gut-selective alpha4beta7 integrin inhibitor approved for the treatment of Ulcerative Colitis (UC) and Crohn’s disease (CD). The exact mechanism of action remains to be unraveled and there is no consensus whether the response to vedolizumab is associated with integrin expression profiles of the innate, adaptive immunity or both. Response prediction to vedolizumab is particularly relevant since it is a rather slow-acting molecule.

Aim
We investigated whether baseline levels and/or early changes in the integrin-expressing T cell subsets during the induction phase can predict the response to vedolizumab in inflammatory bowel disease (IBD) patients.

Methods
In this prospective multi-centric study, 71 patients with CD (n=28) or UC (n=43) with moderate-to-severe disease were included at the start of vedolizumab treatment. The response to vedolizumab was determined on a clinical, biochemical and endoscopic level at the end of the induction phase (week (W)14). The clinical response was defined as a drop in the Harvey Bradshaw index (HBI) of at least 3 points for CD and a reduction in Mayo score of at least 3 points with no rectal bleeding for UC. The biochemical response was defined as a 50% reduction of CRP or when the CRP normalized (<10 mg/l) for CD and a 50% reduction or normalization (<250µg/g) of calprotectin for UC. The endoscopic response was evaluated positive when there was a drop of at least 1 point in the endoscopic Mayo score for UC. For CD, the endoscopic response was not investigated, because an endoscopy at W14 is not part of the standard of care. During the induction phase, peripheral blood mononuclear cells (PBMCs) were collected at W0, W2, W6, W10 (only CD) and W14, before vedolizumab administration. Variation between the different centers was reduced by isolating the cells 6h after blood collection. The PBMCs were analyzed by flow cytometry to evaluate the CD4+/CD8+ Alpha4Beta7+, Alpha4Beta1+ and AlphaEBeta7+ T cell populations. Based on the distribution of the data, statistics were performed by an independent sample t-test or a Mann-Whitney U test.

Results
The flow cytometry analyses revealed that only the CD4+ Alpha4Beta7+ T cell subset at baseline was significantly increased in UC patients with a favorable clinical (P= 0.042), biochemical (P=0.025) and endoscopic response (P= 0.054). This was not the case in CD. In CD, the baseline number of CD4+ Alpha4Beta1+ T cells was lower in clinical (P= 0.094) and biochemical responders (P= 0.004). No other significant baseline or delta change differences were identified between the responders and non-responders in the other investigated T cell subsets in both UC and CD.

Conclusions
This prospective cohort study showed that in UC patients, clinical, biochemical and endoscopic response to vedolizumab treatment is associated with a high number of CD4+ Alpha4Beta7+ T cells in circulation at baseline. In CD patients, the relationship is less clear and the response is rather linked to a low number of Beta1+ T cells. A second cohort is being recruited to confirm our findings. The final aim is to build a predictive model that is feasible for use in clinical practice.

Wednesday March 4, 2020 14:25 - 14:35 CET
Room TIFFANY-SHAH

BIRD, Session 1 IBD Basic

14:35 CET

The interplay of microbiome dysbiosis and immune system deregulation in patients with Crohn’s disease

Authors
N. SEYED TABIB (1), C. CAENEPEEL (1), K. MACHIELS (2), S. VERSTOCKT (1), B. VERSTOCKT (3), N. ARDESHIR DAVANI (1), J. SABINO (3), M. FERRANTE (3), S. VERMEIRE (3) / [1] KU Leuven, , Belgium, Department of chronic diseases, metabolism , ageing, [2] KU Leuven, euven, Belgium, Department of chronic diseases, metabolism , ageing, [3] University Hospitals Leuven, , Belgium, Department of Gastroenterology

Introduction
The perturbation of composition, function, and structure of the gut microbiota known as dysbiosis is a key factor in inflammatory bowel disease (IBD) pathogenesis. There is a crosstalk between the microbiota and the gut immunological niche.

Aim
To better understand this interaction, we characterized the degree of dysbiosis and dysregulation of the immune proteome in Crohn’s disease (CD) patients to see if subtypes of patients could be identified.

Methods
We collected faecal and serum samples of 146 CD patients (60.3% female, median [IQR] age 39 [26-50], median [IQR] FC 678.0 [153.7-1800.0], median [IQR] C-reactive protein(CRP) 5.2 [1.9-14.7]) and 63 healthy controls (HC) (50% female, median [IQR] age 36 [27-55], median [IQR] FC 30.0 [30.0-32.4], median [IQR] CRP 0.5 [0.4-1.2]). Microbiota phylogenetic profiling was conducted using 16S rRNA gene sequencing. Proteomic analysis was performed using a panel of 91 inflammatory proteins (OLINK Proseek). Microbial dysbiotic index (MDI), defined as the logarithm of the sum of [abundance in organisms increased in CD] over the [abundance of organisms decreased in CD] was calculated and patients were ranked from Q1 (the least dysbiotic state) to Q4 (the most dysbiotic state). For the proteomic score, 32 proteins that correlated (adj. p <0.01) with faecal calprotectin (FC) were selected. A penalized logistic regression model was trained on these proteins, to distinguish HC from super active (defined as FC ≥ 1800 µg/g). We next developed an inflammatory proteomic score (IPS) defined as the weighted sum of serum level of inflammatory proteins, using the coefficient value of the regression model as the protein’s weight. Using the IPS score, patients were clustered from Q1 (the least inflammatory state) to Q4 (the most inflammatory state). Statistical analyses were performed in R version 3.5.2.

Results
The MDI did not correlate with standard phenotypic subgroups based on the Montreal classification but did positively correlate CRP (spearman r=0.27, p<0.001) and FC level (spearman r=0.3, p<0.001). The regression model identified 14 proteins [including CCL20, CXCL1, IL-7, IL-17A, FGF-19] distinguishing super active CD patients from HC with accuracy, sensitivity, and specificity of 95.6%, 92.3%, 100%, respectively. IPS positively correlated with CRP (spearman r=0.73, p<0.001) and FC level (spearman r=0.68, p<0.001). Likewise, MDI and IPS-based clusters were significantly different in CRP and FC levels. Different components of the microbiome correlated with the proteome in a subset of samples. For example, fibroblast growth factor 19 (FGF-19) positively correlated with Faecalibacterium and negatively with Fusicatenibacterium. Of note, we observed a significant positive correlation between MDI and IPS (spearman r=0.33, p<0.001).

Conclusions
We were able to define clusters of patients based on molecular characterization of different players in IBD pathogenesis such as microbiota and proteome. This molecular clustering in a given patient could be considered as a novel therapeutic and personalized approach to IBD. Further validation in larger cohorts is required.

Speakers

Nasim Sadat Seyed Tabib

Clara Caenepeel

Kathleen Machiels

Sare Verstockt

Bram Verstockt

Nooshin Ardeshir Davani

João Sabino

Marc Ferrante

Séverine Vermeire

Wednesday March 4, 2020 14:35 - 14:45 CET
Room TIFFANY-SHAH

BIRD, Session 1 IBD Basic

14:35 CET

Helicobacter pylori in 2020… Still an issue?

Speakers

Fazia Mana (St Jean - BRX)

Wednesday March 4, 2020 14:35 - 15:00 CET
Room TEUN + LIJN

PG Course, Afternoon Session

14:45 CET

Exposure to an inflammatory mix re-induces inflammation in organoids of ulcerative colitis patients, independent of the inflammatory state of the tissue of origin

Authors
K. ARNAUTS (1), B. VERSTOCKT (1), J. SABINO (1), S. VERMEIRE (1), C. VERFAILLIE (2), M. FERRANTE (1) / [1] Translational Research Center for Gastrointestinal Disorders (TARGID), KULeuven, Leuven, Belgium, Department of Chronic Diseases, Metabolism and Ageing, KU Leuven, Leuven, [2] Stem Cell Institute Leuven, Leuven, Belgium, Department of Development and Regeneration, KU Leuven, Leuven

Introduction
Patient-derived intestinal organoids provide a powerful tool to unravel mechanisms underlying inflammatory bowel disease (IBD). Recently, we showed that organoids derived from inflamed regions in ulcerative colitis (UC) patients lose their inflammatory phenotype during ex vivo culture and were undistinguishable from organoids of non-inflamed regions in these patients [1].

Aim
To study UC in an ex vivo model, we hypothesized that inflammation should be re-induced towards levels corresponding to the in vivo situation. In addition, we aimed to elucidate if organoids derived from inflamed regions are more sensitive towards inflammatory stimulation, compared to organoids from non-inflamed regions of UC patients and non-IBD controls.

Methods
Biopsies were obtained from 8 patients with active UC (endoscopic Mayo score of ≥2), both in inflamed and non-inflamed regions, and in 8 non-IBD controls. Crypts were isolated and cultured as organoids for at least four weeks. Organoids were subjected to a predefined inflammatory mix (MIX: 100 ng/ml TNF-α, 20 ng/ml IL-1β, 1 µg/ml Flagellin) or medium only (CTRL) for 24 hours. RNA was extracted from organoids for RNA sequencing by Lexogen QuantSeq for Illumina. Differential gene expression and pathways were studied through DESeq2 and Ingenuity Pathway Analysis (False discovery rate <0.05).

Results
Prior to inflammatory stimulation, principal component analysis (PCA) demonstrated separate clustering between organoids derived from non-IBD controls and UC patients. Exposure to the inflammatory mix induced transcriptional activation of inflammatory genes (CXCL1, DUOXA2, IL1β, IL8, IL23α,.. all p<0.001) and pathways in all conditions. However, organoids of non-IBD controls clustered separate from organoids of UC patients. Within organoids of UC patients (inflamed vs non-inflamed origin), we observed no differentially expressed genes after inflammatory stimulation but organoids clustered per patient instead. Inflammatory markers in UC organoids reached transcriptional expression levels (CXCL1, CXCL2, IFNGR1, IL1β, DUOXA2,..) and activated pathways (antigen presentation, interferon signaling, granulocyte adhesion and diapedesis) similar to those observed in crypts derived from inflamed biopsies.

Conclusions
Inflammation can efficiently be (re-)induced in organoids from both UC and non-IBD origin. However, a different response was observed between organoids of non-IBD and UC origin. Of note, in UC organoids the state of inflammation in the source tissue was irrelevant. In conclusion, we showed that it is essential to re-induce inflammation in patient specific organoids, but there is no need to obtain biopsies from inflamed regions. [1] https://doi.org/10.1093/ecco-jcc/jjy222.010

Speakers

Kaline Arnauts

Bram Verstockt

João Sabino

Séverine Vermeire

Catherine Verfaillie

Marc Ferrante

Wednesday March 4, 2020 14:45 - 14:55 CET
Room TIFFANY-SHAH

BIRD, Session 1 IBD Basic

14:45 CET

Different approaches to Hepato-Cellular Carcinoma diagnosis: from the molecular to the radiological perspective. Radiologist Perspective

Speakers

Martina Pezzullo (Erasme Hospital - Brussels)

Wednesday March 4, 2020 14:45 - 15:30 CET
Room SANCY

Young BASL, Session 1

14:55 CET

Serum protein markers for early and differential IBD diagnosis validated by machine learning approaches

Authors
S. VERSTOCKT (1), N. VERPLAETSE (2), D. RAIMONDI (3), B. VERSTOCKT (1), E. GLORIEUS (4), M. DE DECKER (5), L. HANNES (2), V. BALLET (6), E. VANDEPUT (1), Y. MOREAU (3), M. FERRANTE (1), D. LAUKENS (7), F. MANA (5), M. DE VOS (8), S. VERMEIRE (1), I. CLEYNEN (2) / [1] University of Leuven, Leuven, Belgium, CHROMETA, [2] University of Leuven, Leuven, Belgium, Department of Human Genetics, [3] University of Leuven, Leuven, Belgium, ESAT, [4] University Hospital Ghent, Ghent, Belgium, Department of Gastroenterology, [5] University Hospitals Brussels, , Belgium, Department of Gastroenterology, [6] University Hospitals Leuven, Leuven, Belgium, Department of Gastroenterology and Hepatology, [7] University Hospital Gent, , Belgium, Department of Gastroenterology, [8] University Hospital Gent, Gent, Belgium, Department of Gastroenterology

Introduction
The inflammatory bowel diseases (IBD), Crohn’s disease (CD) and ulcerative colitis (UC), are chronic inflammatory conditions with a polygenic and multifactorial pathogenesis. Intensified treatment early in the disease course of IBD results in better outcomes. This is however challenged by the diagnostic delay faced in IBD, and especially in CD. Therefore, markers supporting early and differential diagnosis are needed.

Aim
In this study, we aimed to discriminate IBD patients from non-IBD controls, and CD from UC patients, using serum protein profiles combined with an IBD polygenic risk score.

Methods
Patients naïve for immunosuppressives and biologicals, and without previous IBD-related surgery were prospectively included within 3 months after diagnosis, across three Belgian IBD referral centres (PANTHER study). We collected serum from 127 patients (88 CD, 39 UC) and 66 age- and gender-matched non-IBD controls. Relative serum levels of 576 unique proteins were quantified (OLINK). Proteins were ranked according to: (1) adjusted (adj.) p values obtained from differential expression analysis; (2) importance scores from machine-learning feature-selection algorithms (univariate feature selection, logistic regression with L2 penalty and Random Forest). For all individuals, a weighted IBD polygenic risk score (PRS) was calculated (PRSice 2.0) for the 242 known IBD risk loci. Receiver operating characteristics (ROC) and area under the curve (AUC) analysis were performed to measure the performance of top ranked proteins and the IBD PRS (R\ROCR).

Results
Following statistical analysis, 243 serum proteins were found to be differentially expressed (adj. p < 0.05) between IBD patients and controls. Three top ranked markers were also identified as top 10 ranked proteins by all feature-selection algorithms, and resulted in a significant AUC of 93% (95% CI: 89-97%) to distinguish IBD from controls. While adding the IBD PRS did not further contribute (AUC 93% [95% CI: 89-97%]), the top ranked protein on its own had a strong discriminative power with an AUC of 87% (95% CI: 82-92%). When comparing UC and CD, we found 15 differentially expressed proteins. Two proteins ranked within the top 10 across all feature-selection algorithms. This two-marker panel could discriminate UC from CD with an accuracy of 88% (95% CI: 82-96%). Adding the IBD PRS did not further improve the prediction model (AUC=88% [95% CI: 81-96%]).

Conclusions
Machine learning approaches validated top differentially expressed serological proteins with diagnostic potential in IBD. We identified a three-marker panel classifying IBD patients and non-IBD controls, and a two-marker panel discriminating UC from CD.

Wednesday March 4, 2020 14:55 - 15:05 CET
Room TIFFANY-SHAH

BIRD, Session 1 IBD Basic

15:00 CET

Constipation: a practical approach

Speakers

Bram Verstockt

Sare Verstockt

Dahham Alsoud

João Sabino

Marc Ferrante

Séverine Vermeire

Wednesday March 4, 2020 16:15 - 16:25 CET
Room TIFFANY-SHAH

BIRD, Session 2 IBD Basic

16:20 CET

Combination of Gene Expression Signature and Model for End-Stage Liver Disease Score Predicts Survival of Patients With Severe Alcoholic Hepatitis.

Speakers

Eric Trepo (ULB - Brussels)

Wednesday March 4, 2020 16:20 - 16:40 CET
Room SANCY

Young BASL, Session 2

16:25 CET

SLC12A2 as a potential histological marker of ulcerative colitis associated colorectal dysplasia

Authors
A. MERLI (1), S. VIEUJEAN (2), C. MASSOT (2), N. BLETARD (3), F. QUESADA CALVO (2), D. BAIWIR (4), G. MAZZUCCHELLI (5), L. SERVAIS (1), O. WÉRA (6), C. OURY (1), L. DE LEVAL (7), C. SEMPOUX (8), M. ROBERTO (9), M. SCHARL (10), G. ROGLER (11), E. DE PAUW (5), C. COIMBRA MARQUES (12), A. COLARD (13), A. VIJVERMAN (14), P. DELVENNE (15), M. MEUWIS (2), E. LOUIS (16) / [1] University of Liege, Liège, Belgium, GIGA Institute, [2] CHU of Liège, , Belgium, Gastroentérologie, hépatologie, oncologie digestive, [3] CHU of Liège, , Belgium, Anatomie et cytologie pathologiques, [4] University of Liege, Liège, Belgium, GIGA Plateforms, [5] University of Liege, Liège, Belgium, Chimie, [6] CHU of Liège, , Belgium, Oncologie médicale, [7] Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland, Service de pathologie clinique, [8] Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland, Pathologie Clinique, [9] University Hospital of Liège Liège, Liège, Belgium, Gastroenterology and Hepatology, [10] University Hospital, Zurich, Switzerland, Gastroenterology, [11] University Hospital, Zurich, Switzerland, Gastroenterology and Hepatology, [12] CHU of Liège, , Belgium, Sciences cliniques, [13] CHC, Liège, Belgium, Gastroenterology, [14] CHR La Citadelle, , Belgium, Gastro-entérologie et Oncologie digestive, [15] CHU of Liège, , Belgium, Sciences biomédicales et précliniques, [16] CHU of Liège, , Belgium, Sciences cliniques - Hépato-gastroentérologie

Introduction
Patients suffering from ulcerative colitis (UC) are at increased risk of developing dysplasia (DAI) and colorectal cancer (CAC). Differentiating DAI from inflammation remains difficult for both endoscopists and anatomopathologists due to macro and microscopic features shared by these lesions.

Aim
The aim of our work was to confirm, by histological evaluation, a potential proteomic biomarker discriminating early DAI lesions from chronic inflamed and normal tissues in UC.

Methods
We included 15 paired tissues from UC patients (n=5) presenting low-grade DAI. Epithelial cells were isolated by laser capture microdissection and analyzed by label-free proteomics. We selected one protein differentially distributed between DAI, inflamed (I) and normal (N) tissues for confirmation by immunochemistry (IHC). IHC characterization was performed using both the staining intensity score (0 to 4) and the staining pattern: “gradient” (staining intensity increasing from the epithelium lumen to the bottom of the crypts) or “no gradient” (homogenous staining). UC patients with DAI (n=28), dysplastic lesion in non-inflammatory colon (DSp) (n=9), CAC (n=14) and at high risk of CAC (>10 years of UC duration) but free of dysplasia or cancer (n=23) were included. We further studied this potential marker tissue distribution in the mouse model of CAC (AOM/DSS treated mice) to trace its presentation at different evolution stages and assessed low (n=51), high-grade DAI (n=35) and CAC (n=38), as well as relevant paired control tissues. This potential tissue marker was finally evaluated in sporadic precancerous colorectal lesions of UC-free patients with low (n=19) and high-grade (n=16) adenomas and cancerous lesions (CRC): pT1 to pT4 (n=82) and compared to paired normal tissues when available.

Results
Proteomics identified 1070 proteins among which 19 showed a differential distribution between DAI and I or N. The sodium chloride co-transporter SLC12A2 was only identified in DAI. SLC12A2 IHC “no gradient” staining pattern was associated to DAI and DSp compared to I or N (with p <0.0001 and 0.0002 respectively). The IHC score was also higher for DAI, DSp and CAC compared to paired I and N (p<0.0001 and 0.0084 respectively). These results were confirmed from low-grade dysplasia to more advanced lesions in the AOM/DSS mice model. The “no gradient” pattern was also significantly associated to low and high-grade adenomas, and CRC of UC-free patients compared to normal control tissues. The sensitivity and specificity of SLC12A2 histological pattern reached 89% and 95% for DAI versus I; 90% and 93% for CAC and/or DAI versus I. In addition, the sensitivity and specificity reached 99% and 87% for all precancerous and cancerous lesions (DAI, DSp, CAC and CRC) versus N and I (including also non-progressing UC patients).

Conclusions
A specific histological pattern for SLC12A2 is associated to precancerous and cancerous colorectal lesions, and is able to be discriminate these lesions from inflammation and normal tissue in UC. The continuous upregulation of SLC12A2 in advanced colorectal lesions in the CAC mice model also suggests a role of this protein in the pathophysiology of inflammation-associated colon neoplasia.

Wednesday March 4, 2020 16:25 - 16:35 CET
Room TIFFANY-SHAH

BIRD, Session 2 IBD Basic

16:25 CET

Lower gastro-intestinal bleeding

Speakers

Catherine Van Kemseke (ULg)

Wednesday March 4, 2020 16:25 - 16:50 CET
Room TEUN + LIJN

PG Course, Afternoon Session

16:35 CET

The gut microbiota during biological therapy for inflammatory bowel disease.

Authors
C. CAENEPEEL (1), S. VIEIRA-SILVA (2), B. VERSTOCKT (1), K. MACHIELS (1), N. DAVANI (1), J. SABINO (3), M. FERRANTE (3), J. RAES (2), S. VERMEIRE (3) / [1] Catholic University of Leuven (KU Leuven), , Belgium, Department of Chronic Diseases, Metabolism and Ageing, [2] Rega Institute for Medical Research, Leuven, Belgium, Department of Microbiology and Immunology, Laboratory of Molecular Bacteriology, [3] University Hospitals Leuven, , Belgium, Department of Gastroenterology and Hepatology

Introduction
The expansion of therapeutic options in IBD brought forward a need to personalize treatment maximizing both efficacy and safety. Gut inflammation in inflammatory bowel disease (IBD) patients has been associated with reduced microbial richness, reduced abundance of short-chain fatty acid producers and of gram-positive bacteria.

Aim
We aimed to explore the longitudinal impact of treatment on the inflammatory burden and fecal microbiota in patients with CD and UC, treated with anti-tumor necrosis factor (anti-TNF) therapy, vedolizumab (VDZ) or ustekinumab (UST).

Methods
We collected faecal samples from 349 IBD patients (112 UC, 237 CD) initiating biological therapy (anti-TNF, VDZ or UST), between 2010 and 2019 at a tertiary referral centre. Samples were collected at baseline, week 14 and week 24. Microbiota phylogenetic profiling was conducted by 16S rRNA gene sequencing and faecal microbial loads were determined using flow cytometry. Moisture levels, as marker for transit time, were measured using lyofilisation. Disease activity and response were assessed by faecal calprotectin (FCal). Statistical analyses were performed in R, version 3.5.1. Enterotyping was based on the Dirichlet multinomial mixtures approach [1]

Results
The faecal microbiota profiles of the cohort showed high diversity, with samples being classified into all four enterotypes (Bact1-, Bact2-, Rum- or Prev-enterotype), although Bact2 was 6-10-fold more prevalent in patients compared to controls. The variation in faecal microbiota composition was explained (multivariate dbRDA) by patient diagnosis (R2=1.2%, p= 1.00E-04), timepoint (pre- or post-treatment (R2=0.52, p=0.006), and followed significantly by age, gender and faecal moisture. The full model only explained 2.85% of the microbiota variation. During treatment, a numeric although non-significant decrease in the dysbiotic Bact2 enterotype prevalence was observed in the CD cohort, but not observed in the UC cohort. A significant decrease in FCal concentrations (UC w0 vs 14, p= 5.12E-08, CD w0 vs 14, p= 2.56E-08 and w0 vs 24, p= 4.86E-08) was observed with treatment, and accompanied by a significant increase in microbial loads (UC w0 vs 14, p= 0.023869, CD w0 vs 14, p= 0.002142 and w0 vs 24, p= 0.020071). Only treatment-associated variables - week of treatment (p=2.4E-18), diagnosis (0.00053) and timepoint (p=0.00733) – were significant predictors for response (FCal used as proxy for disease activity), while microbiota-associated variables (enterotype, microbial load and faecal moisture) were not. Pre-treatment samples were associated to higher FCal levels, together with UC diagnosis. This suggest that the response-time of the microbiota to treatment may be higher than host inflammatory response.

Conclusions
The prevalence of the inflammatory Bacteroides 2 enterotype was 5-10 fold higher in CD and UC patients as compared to controls. Although initiation of biological therapies lead to a decrease in inflammation levels as witnessed by faecal calprotectin, and increase in microbial richness, a shift in enterotypes did not occur.

Speakers

Clara Caenepeel

Sara Vieira-Silva

Bram Verstockt

Kathleen Machiels

Nooshin Ardeshir Davani

João Sabino

Marc Ferrante

Jeroen Raes

Séverine Vermeire

Wednesday March 4, 2020 16:35 - 16:45 CET
Room TIFFANY-SHAH

BIRD, Session 2 IBD Basic

16:40 CET

Invited Talk - Starter Investigators: Contribution of gEnome-wide eXPression profiLes tO the Risk of hEpatocellular carcinoma (EXPLORE)

Speakers

Lukas Otero-Sanchez (ULB - Brussels)

Wednesday March 4, 2020 16:40 - 16:55 CET
Room SANCY

Young BASL, Session 2

16:45 CET

Role of exosomal microRNAs in fibrotic disease

Sébastian Njock (University of Liège)

Jeoffrey Schouten

Wednesday March 4, 2020 17:00 - 19:00 CET
TBA

Ultrasound Course

17:10 CET

Intestinal mucosal immunity in the pathogenesis of primary sclerosing cholangitis

Speakers

Lena Smets (KUL - Leuven)

Wednesday March 4, 2020 17:10 - 17:25 CET
Room SANCY

Young BASL, Session 2

17:10 CET

Satellite Symposium PFIZER

Controlling Ulcerative Colitis in 2020: the doctors' and patients' perspectives

Speakers

Edouard Louis

Anneline Cremer

PFIZERSympo pdf

Wednesday March 4, 2020 17:10 - 17:55 CET
Room TIFFANY-SHAH

08:00 CET

Breakfast Symposium EISAI/MSD

REFLECTing on a new treatment in unresectable and/or advanced hepatocellular carcinoma.

Speakers

Jeroen Dekervel

19 EISA MSD 6625 Lenvima HCC Teaser BWGE v5 pdf

Thursday March 5, 2020 08:00 - 08:30 CET
Room TEUN

BASL / BLIC

08:30 CET

Safety and preliminary efficacy of human adult liver progenitor cells (HepaStem™) in patients with acute-on-chronic liver failure (ACLF) or acute decompensation (AD) at risk of developing ACLF

Authors
F. NEVENS (1), T. GUSTOT (2), P. LATERRE (3), L. LASSER (4), L. HARALAMPIEV (5), V. VARGAS (6), D. LYUBOMIROVA (7), A. ALBILLOS (8), V. BARTHEL (9), N. CLERGET-CHOSSAT (9), E. SOKAL (9) / [1] KU Leuven, , Belgium, Hepatology and Liver Transplantation , [2] Erasme Hospital, Brussels, Belgium, Gastroenterology/HepatoPancreatology/Digestive Oncology, [3] Saint-Luc University Hospital, Brussel, Belgium, Intensive Care, [4] CHU Brugmann, Brussels, Belgium, Gastroenterology, [5] Hospital Medica Ruse, Ruse, Bulgaria, Internal Diseases, [6] Hospital Vall d’Hebron, Barcelona, Spain, Hepatology, [7] University Multiprofile Hospital for Active Treatment "Dr. Georgi Stranski", Pleven, Bulgaria, Clinical Gastroenterology with Hepatology, [8] Hospital Universitario Ramón y Cajal Catedrático de Medicina, Universidad de Alcalá, Madrid, Spain, Gastroenterology and Hepatology, [9] Promethera Biosciences, Mont-Saint-Guibert, Belgium, Product Development

Introduction
Acute-on-chronic liver failure (ACLF) is characterized by acute decompensation (AD) of cirrhosis associated with failure of one or more organs. HepaStem™ is a suspension of Human Allogenic Liver Progenitor Cells derived and expanded from the parenchymal fraction of collagenase-digested adult human liver. The immunomodulatory properties of HepaStem™ are expected to restore immune balance and liver function in patients with ACLF or AD.

Aim
The primary objective is the safety of 1 or 2 infusions of various doses of cells up to Day (D)28 post treatment. Secondary objectives include preliminary efficacy up to month (M)3.

Methods
Twenty-four patients were enrolled. The first patient (ACLF) received no cells due to technical issue. The second patient (ACLF) received 2 infusions of 4.2 x 10⁶ cells/kg, the third patient (ACLF) received 1 infusion of 5.3 x 10⁶ cells/kg, 6 patients (2 ACLF and 4 AD) 1 infusion of 0.6-0.8 x 10⁶ cells/kg, 3 patients (2 ACLF and 1 AD) 2 infusions of 0.6 x 10⁶cells/kg, and 12 patients (9 ACLF and 3 AD) 1 or 2 infusion of 1.2 x 10⁶ cells/kg.

Results
The second patient had severe epistaxis and the third one bled at the puncture site of the transjugular biopsy. They recovered; one had liver transplantation and the other one was well at 1 year. After dose adjustment in the subsequent dose-cohorts, no serious events causally related to HepaStem™ were reported. No other bleedings occurred, or any drop of platelets, fibrinogen, or coagulation factors. Adverse events were in line with those expected regarding the underlying diseases and comorbidities. In patients without liver transplantation (N=18), bilirubin and MELD score decreased, and albumin slightly increased as compared to pre-infusion values. Also, elevated baseline levels of C-Reactive Protein and neutrophil counts returned to normal in most patients.

Conclusions
At high cell doses (250 x 10⁶ cells), 2 patients with initial severe coagulation disturbances experienced bleeding possibly related to HepaStem™. This could be linked to tissue factor expressed by HepaStem™, which activate the coagulation cascade and lead to consumption of coagulation factors, as shown in preclinical studies. No bleedings related to HepaStem occurred at 0.6 to 1.2 x 10⁶ cells/kg doses, or changes in coagulation parameters; these dosages were safe in this AD/ACLF patient population. Preliminary data showed improvement of liver function and systemic inflammation post infusion. The clinically significant MELD and bilirubin improvement is considered as an encouraging sign of efficacy.

Thursday March 5, 2020 08:30 - 08:40 CET
Room TEUN

BASL / BLIC, Session 1

08:40 CET

Viral hepatitis in Belgian prisons: a first-time multicenter prevalence study

Authors
D. BUSSCHOTS (1), R. BIELEN (1), Ö. KÖC (1), E. DERCON (2), C. BRIXKO (3), P. LAUKENS (4), P. BILAEY (4), F. DE SMET (4), G. HELLEMANS (4), G. MUYLDERMANS (5), L. VAN BAELEN (5), H. VAN VLIERBERGHE (6), G. ROBAEYS (1) / [1] Hasselt University, Hasselt, Belgium, Health and Life Sciences, [2] zorGGroep Zin, Hasselt, Belgium, Addiction Care, [3] CHR La Citadelle, , Belgium, Department of Gastroenterology and Hepatology, [4] Federale Overheidsdienst Justitie, Brussel, Belgium, Coördinatie Medische Zorg, [5] Sciensano, Brussels, Belgium, Epidemiology and Public Health, [6] UZGent, Gent, Belgium, Department of Gastroenterology and Hepatology

Introduction
Prevalence of hepatitis C virus (HCV) and hepatitis B virus (HBV) infection among prisoners is many times higher than in the general population. The high rates of viral hepatitis infection in prisoners, and the substantial risks associated with an untreated infection underline the need for screening and access to treatment in prisons. To date, there is no targeted screening in Belgian prisons and currently there are no data on the prevalence of HCV or HBV infections in prison.

Aim
Through targeted screening, we want to map the prevalence of HCV and HBV in prisons in Belgium.

Methods
The study started on 1 April 2019 in several prisons for both prisoners in pre-trial detention and long-term convicts throughout Belgium. The eligible candidates (>18y and signed informed consent form) were tested by finger prick for HCV antibodies (Ab) using the Oraquick® test and hepatitis B surface antigen (HBsAg) using the HBsAg Rapid Test Device®. While waiting for the results (20 minutes), an encoded questionnaire was filled out.

Results
From 1 April 2019 till 7 November 2019 a total of 456 prisoners were screened. Of these, 21 (4.6%) tested positive for HCV Ab and 5 (1.1%) tested positive for HBsAg. The prevalence of HCV Ab did not differ in prisoners in pre-trial detention compared to long-convicts, respectively 10/160 (6.3%) and 11/285 (3.9%, p=0.159). All participants who tested positive on one of the tests was referred to the physician in prison for a vene puncture to determine HCV RNA. To date, HCV RNA was determined in 12/21 and was present in 8 (66.7%).

Conclusions
These preliminary results show an increased prevalence for HCV Ab in prisons in Belgium. This is markedly lower than mentioned in previous European studies.

Thursday March 5, 2020 08:40 - 08:50 CET
Room TEUN

BASL / BLIC, Session 1

08:50 CET

Hypoxia-induced angiogenesis protects the liver from small for size syndrome

Authors
A. DILI (1), M. DE RUDDER (2), B. PIRLOT (2), L. DEWACHTER (3), C. BERTRAND (4), C. BOUZIN (5), I. LECLERCQ (2) / [1] CHU UCL Namur, Yvoir, Belgium, Surgery and Laboratory of Hepato- Gastroenterology; UClouvain - IREC - GAEN department, [2] Laboratory of Gastroenterology and Hepatology, Institut de Recherche Expérimentale et Clinique, UCLouvain, Brussels, Belgium, Laboratory of Gastroenterology and Hepatology, IREC, UCL, Brussels, [3] ULB, Brussels, Belgium, Laboratory of Physiology and Pharmacology, [4] CHU-UCL-Namur site Godinne, Yvoir, Belgium, Surgery, [5] Institut de Recherche Expérimentale et Clinique (IREC), Catholic University of Louvain (UCL), , Belgium, IREC Imaging Platform

Introduction
Liver regeneration is a highly regulated process which requires an equilibrium between the hepatocyte proliferation and angiogenesis in order to maintain liver function. After partial hepatectomy, hepatocyte proliferation (organogenesis) proceeds sinusoidal remodeling (angiogenesis) causing a transient perturbation of the lobular architecture, with proliferating hepatocytes forming avascular clusters. As the magnitude of hepatocyte proliferation correlates with the extent of hepatectomy (and portal hyperperfusion), an extended hepatic resection triggers a vast regenerative response of hepatocytes, with formation of large avascular, and thus non-functional, hepatocyte islands. Such lobular temporospatial disorganization, resulting from a tremendous parenchymal cell proliferation and a slow sinusoidal endothelial cell (SEC) proliferation, causes transient hypoxia in the regenerating liver. Small for size syndrome (SFSS), a clinical entity characterized by hyperbilirubinemia, ascites, coagulopathy and hepatocellular failure, develops after major hepatectomy leaving a very small liver remnant or after liver transplantation with a small graft. Portal hyperperfusion is at the origin of a compensatory constriction of the hepatic artery (hepatic arterial buffer response), desarterialisation of future liver remnant (FLR) and hypoxia. Simultaneously, portal hyperperfusion also enhances hepatocyte proliferation in the early phase of liver regeneration, with the formation of avascular hepatocyte clusters. Hypoxia is, thus, considered at the origin of liver dysfunction in SFSS-setting hepatectomy.

Aim
Recently, based on a rat model of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS), with a small, insufficient for survival FLR, we showed that hypoxia activated an early angiogenic response, resulting in a preserved sinusoidal morphology during the first phase of liver regeneration. When we experimentally induced hypoxia in an upfront SFSS-setting hepatectomy, survival rates significantly improved. Hypoxia had no impact on hepatocyte proliferation. Activation of hypoxia sensors surged an early angiogenic switch and preserved the sinusoidal architecture with a favorable impact on survival, suggesting an improved functional organization of the regenerating hepatocytes.This study aims to decipher the role hypoxia-induced angiogenesis in the setting of a SFSS hepatectomy.

Methods
The first part of the study focused on developing a mouse model of extended, SFSS-setting, partial hepatectomy (PHx-80%). We used a 70% PHx (PHx-70%) model as control animals. To test the impact of hypoxia, SFSS‐hepatectomy mice were submitted to normoxia (inspired oxygen fraction-FiO2: 21%), local hypoxia by hepatic artery ligation, and systemic hypoxia by placing the animals in hypoxic chambers (FiO2: 11%) immediately after the operation and for 3 consecutive days. We assessed mortality, FLR hypertrophy, hepatocyte and liver SEC proliferation at different timepoints.

Results
Compared to 70% partial hepatectomy, resection of 80% of the total liver masse (PHx-80%) showed high mortality rates up to 68% at 7 days (p=0,002), confirming that PHx-80% was a SFSS-setting hepatectomy. After PHx-80% most deaths occurred the first 72hours after the operation (56%), suggesting that liver dysfunction occurred during the early phase of liver regeneration (organogenesis). Hepatocyte proliferation 3 days after the operation was significantly enhanced in PHx-80% compared to PHx-70% (p=0,03), while sinusoidal endothelial cell proliferation did not differ, suggesting an amplified disequilibrium of hepatocyte and SEC proliferation in the regenerating lobule in the SFSS-setting PHx-80%. Hepatic artery ligation, combined to PHx-80%, tended to have a favorable, although not significant, impact on survival (75% on postoperative day (POD) 3, 56% on day 7) compared the normoxic SFSS-setting PHx-80% (46% on POD3). When animals subjected to SFSS-setting hepatectomy were placed into hypoxic chambers (FiO2 11%), survival significantly improved (95% at 7 days) compared to PHx-80% (p=0,0007). FLR mass recovery and hepatocyte proliferation was similar between the hypoxic and normoxic SFSS-liver remnants. However, local and systemic hypoxia significantly triggered early angiogenesis as attested by the sinusoidal endothelial cell proliferation on postoperative day 1.

Conclusions
The current study supports our previously published data and confirms that hypoxia rescues survival from SFSS. While the improved survival cannot be attributed to an increased FLR mass recovery (reflection of hepatocyte proliferation), our data support that a surge of hypoxia during the early phase of liver regeneration triggers early sinusoidal endothelial cell proliferation. By balancing angiogenesis with hepatocyte proliferation, hypoxia improves the cellular “crosstalk” and restores the lobular liver architecture allowing an efficient liver regeneration after major hepatectomy.

Speakers

ALEXANDRA DILI

Maxime De Rudder

Boris Pirlot

Laurence Dewachter

Claude Bertrand

Caroline Bouzin

Isabelle Leclercq

Thursday March 5, 2020 08:50 - 09:00 CET
Room TEUN

BASL / BLIC, Session 1

09:00 CET

18F-Fluorocholine and 18F-Fluorodesoxyglucose PET/CT for Clinical Staging of patients with Hepatocellular Carcinoma

Authors
H. COUVERT (1), R. MARECHAL (2), R. MORENO-REYES (3), O. VIERASU (3), M. PEZZULLO (4), A. BUCALAU (5), G. VERSET (5) / [1] ULB Faculty of Medicine, Anderlecht, Belgium, Medical student, [2] CHU Tivoli, La Louvière, Belgium, Gastroenterology, [3] Erasme Hospital, Brussels, Belgium, Nuclear medicine, [4] Erasme Hospital, Brussels, Belgium, Radiology, [5] Erasme Hospital, Brussels, Belgium, Gastroenterology

Introduction
18F-Fluorocholine positron emission tomography/computed tomography (18F-FCH PET/CT) is an emerging metabolic imaging technique for the diagnosis and management of hepatocellular carcinoma (HCC). 18F-Fluorodeoxyglucose PET/CT (18F-FDG PET/CT) is not recommended for routine detection of intrahepatic HCC due to its low sensitivity. Nevertheless recent studies have shown promising results for the detection of extrahepatic spread and predicting prognosis.

Aim
The aim of this study is to assess the percentage of positivity of 18F-FCH PET/CT, 18F-FDG PET/CT and the combination of the two radiotracers in HCC patients.

Methods
Sixty- two HCC patients that underwent 18F-FCH PET/CT for staging were included in this single centre retrospective study and tumor metabolism was assessed qualitatively. For 51 of them 18F-FDG PET/CT was also performed.

Results
A total of 62 patients (median age 63 years, range 34-83) with radiologically or histopathologycally confirmed HCC were included. Patients were mostly men (85.5%) with cirrhosis (88, 7%). The majority presented a well-compensated cirrhosis (Child A 64.2%) related to alcohol consumption (54.9%). Multifocal disease was observed in 69,4% of patients, with intermediate stage in 33.9% and advanced stage in 14.5%. Forty-two patients were treatment-naïve and 20 had received previous treatments (resection or RFA and/or transarterial therapies). In the global population (n=62), 18F-FCH PET/CT was positive for 45 patients (72.6%). Regarding the 51 patients who benefited of both radiotracers (18F-FCH and 18F-FDG), 47.1% had a positive 18F-FDG PET/CT, 98% were positive for at least one radiotracer and 27.5% were positive for the two. 73.8% of the treatment-naïve patients had a positive 18F-FCH PET/CT. Of the 37 patients evaluated with both radiotracers, 48.6% were 18F-FDG positive, 29.7% were 18F-FDG+18F-FCH positive and 97.3% were 18F-FCH or 18F-FDG positive. Furthermore, in 6 patients, lesions not describe by standard radiology (computed tomography scanner and/or magnetic resonance) were detected by PET/CT.

Conclusions
The combination of 18F-FCH and 18F-FDG PET/CT seems to be useful for the HCC staging, with a combined positivity rate reaching 100%. Prospective trials with quantification of radiotracer uptake are mandatory to confirm this observation.

Speakers

Hugo Couvert

Raphael Marechal

Rodrigo Moreno-Reyes

Ortansa-Irina Vierasu

Martina Pezzullo

Ana-Maria Bucalau

Gontran Verset

Thursday March 5, 2020 09:00 - 09:10 CET
Room TEUN

BASL / BLIC, Session 1

09:00 CET

A curious case of collagenous colitis

Are liver inclusive intestinal grafts protected against rejection?

Authors
M. CLARYSSE (1), E. CANOVAI (1), L. CEULEMANS (1), T. VANUYTSEL (2), G. DE HERTOGH (3), D. MONBALIU (1), J. PIRENNE (1) / [1] University Hospitals Leuven, , Belgium, Abdominal Transplant Surgery, [2] University Hospitals Leuven, , Belgium, Gastro-enterology, [3] University Hospitals Leuven, , Belgium, Pathology

Introduction
Experimental/clinical data suggest that inclusion of a liver (Liv-In) protects against humoral/cellular acute and chronic rejection of simultaneously transplanted organs. This is due to liver clearance of preformed (or prevention of formation of de novo) donor-specific antibodies (DSA) and activation of regulatory/deletional tolerogenic mechanisms. However, data on the liver protective effect in Intestinal Transplantation (ITx) are scarce.

Aim
A thorough review of the effect of Liv-In versus no liver-inclusive graft on the outcome of ITx in University Hospitals Leuven.

Methods
Observational retrospective. In 2000-2019, 22 ITx were performed in 21 patients (1 reTx). Rejection, preformed / de novo DSA, graft loss and survival data were extracted from patient files and analysed according to presence (Liv-In) or absence (NoLiv-In) of liver. Induction immunosuppression (IS) was IL-2 receptor AB (20 patients) or anti-thymocyte globulin (2 patients). Maintenance IS are tacrolimus, azathioprine and steroids. Tacrolimus was more rapidly tapered & lower in Liv-In (<5µg/L) vs NoLiv-In (6-8µg/L) at 1 year postTx.

Results
There were 11 Liv-In (6 combined Liver-ITx (cLi-ITx); 5 Multivisceral Tx) and 11 NoLiv-In ITx. Follow-up: 3 months – 17 years. One patient had preTx class 1 DSA which disappeared after cLi-ITx. Three patients developed de novo DSA, of whom 2 were treated conservatively, as they were clinically well (Liv-In) and there was a low MFI (< 4.500). In the latter patient (NoLiv-In), de novo DSA were successfully treated with azathioprine. The incidence of early (< 3 months) and late acute rejection (AR) (> 3 months) was 64% and 55% in NoLiv-In vs Liv-In, respectively (p=0.5). Overall incidence of grade 3 (severe) AR was 55% versus 9% in NoLiv-In vs Liv-In, respectively (p=.0317). Chronic rejection was seen in the NoLiv-In group only (18%). Overall graft loss was 5 in NoLiv-In {3 to rejection (at 2, 7, 176 months), 1 to AR/CMV 11 months; 1 to ischemia after endoscopy 3,5 years} vs 1 (partial) in Liv-In {acute rejection at 2 months} (p=.155 for graft loss due to rejection). Overall patient death was 3 in NoLiv-In {1 Aspergillus after AR treatment 8 months; 1 sepsis 58 months (51 months post-Txectomy); 1 multi-organ failure 86 months} vs 2 in Liv-In {1 death to Aspergillus after AR treatment 4 months; 1 death to NSAID-induced transplant bowel necrosis 12 years} (p=0.5). One-/5-year death-uncensored graft survival was 91%/91% in Liv-In vs 64%/48% in NoLiv-In (p=.09). 1-/5-year patient survival was 90%/90% in Liv-In vs 88%/71% in NoLiv-In (p=.47).

Conclusions
Liver inclusion protects intestinal grafts against severe acute rejection, despite receiving less immunosuppression. More effective immunosuppression is needed for isolated ITx. Liver inclusive ITx shows a trend for better graft and patient survival, despite being medically/surgically more challenging.

Speakers

Mathias Clarysse

Emilio Canovai

Laurens Ceulemans

Tim Vanuytsel

Gert De Hertogh

Diethard Monbaliu

Jacques Pirenne

Thursday March 5, 2020 09:10 - 09:20 CET
Room TEUN

BASL / BLIC, Session 1

09:15 CET

Intestinal spirochetosis : Think about it to diagnose it.

Authors
F. HAMOIR (1), N. DE SURAY (1), J. DARGENT (2), P. WARZEE (1) / [1] GHDC, charleroi, Belgium, Gastroenterology, [2] IPG, Charleroi, Belgium, Pathology
Background : Intestinal spirochetosis (IS) is a condition characterised by the attachment of spirochetal bacteries to the apical cell membrane of colorectal epithelium. The two main spirochetes species responsible of IS are Brachyspira pilosicoli and Brachyspira aalborgi. Even if IS pathologic significance remains uncertain, it's known as a cause of chronic diarrhea, rectal bleeding or abdominal pain. Prevalence of IS is significantly higher in developing countries than in areas with a high standard of living. In developed countries, the highest rates of colonization of stools with IS are found in homosexual males and in human immunodeficiency virus (HIV) infected individuals. Endoscopic biopsies must be performed to confirm the diagnosis of IS. Most of the time endoscopy is described to be macroscopically normal. Diagnosis is therefore based on histology. We report here five cases of IS recently diagnosed in our department. Case Reports : Mean age of patients at diagnosis was 48.6 ± 13.2 years. All were males and it is worth noting that two patients had homosexual intercourse. Medical treatment included only pantoprazole for two patients, the other three were free of treatment. All five patients were symptomatic and had rectal bleeding. Two patients also complained of diarrhea and abdominal pain. Blood tests revealed CRP elevation (75 mg/L) with normal neutrophils in one and isolated hight level of neutrophils in another patient (9480/mm3). Lab results were unremarkable for the other three patients except for positive TPHA test in one. Lower intestinal tract endoscopy was performed in all patients. Macroscopic aspect of the colon mucosa was normal in three of them. Endoscopic examination showed local hyperhemia of the rectal mucosa in one and appearance of colitis and discontinuous low proctitis in last one. Histology revealed signs of IS in all five patients. Specific treatment (metronidazole 500mg three times a day for 10 days) was given to three patients with long-lasting complaints. Clinical remission was observed in two of them. The third received additional mesalazine treatment due to relapsing symptoms. Conclusion : Intestinal spirochetosis is not frequent but certainly underdiagnosed. IS must be included in the differential diagnosis of chronic diarrhea, rectal bleeding and abdominal pain. Lower gastrointestinal endoscopy with biopsies is essential for its diagnosis.

Speakers

Florine HAMOIR

Nicolas DE SURAY

Jean-Louis DARGENT

Philippe WARZEE

Thursday March 5, 2020 09:15 - 09:30 CET
Room SANCY

Case Reports GE, Session 1

09:20 CET

Prevalence and characteristics of cystic fibrosis-associated liver disease in a cohort of adult cystic fibrosis patients

Authors
Z. ISSA (1), S. GOHY (2), B. DELIRE (1), G. DAHLQVIST (1) / [1] Saint-Luc University Hospital, Brussel, Belgium, Hepato-gastroenterology, [2] Saint-Luc University Hospital, Brussel, Belgium, Pulmonology

Introduction
Cystic fibrosis (CF) is the most common autosomal recessive disease in Caucasians and is caused by CF transmembrane conductance regulator (CFTR) gene mutation. CF-associated liver disease (CFLD) is the 3rd leading cause of death in CF patients. Its prevalence is controversial since the term CFLD is used to describe a wide range of manifestations. Therefore, it is important to distinguish CF-associated from CF-related liver disease. CFLD is thought to be a pediatric disorder although adult-onset CFLD (ad-CFLD) is being increasingly reported together with the arrival of new definition criteria using noninvasive liver fibrosis tests.

Aim
We aim to determine the prevalence and characteristics of CFLD in a cohort of adult CF patients.

Methods
We retrospectively studied a cohort of CF patients followed at our CF clinic. Inclusion criteria were age >18 years, a typical form of CF and at least 1 year of follow-up. We excluded pulmonary transplant patients. Data on baseline and CF characteristics were collected. CFLD was defined as having 2 out of 3 criteria: persistent elevation of transaminases and/or gamma-glutamyltransferase, abnormal ultrasound findings and/or abnormal transient elastography (cutoff >6.8 kPa). Noninvasive fibrosis markers were calculated in all CFLD patients. Ad-CFLD was defined as CFLD diagnosed >18 years. Severe CFLD (s-CFLD) was defined as CFLD with cirrhosis and/or portal hypertension.

Results
A total of 113 patients were included, median age was 29 years and 58 (51%) were male. Median age at CF diagnosis was 6 months, 17% had meconial ileus, 54% had deltaF508 homozygous mutation, and 83% had pancreatic exocrine insufficiency. Sixteen patients (14%) had isolated hepatic steatosis. Forty patients (35%) had CFLD including 28 (70%) male patients. Median age at CFLD diagnosis was 10 years. Twenty-one patients (19%) had s-CFLD with a median age of 13 years and median delay to s-CFLD diagnosis was 2 years. Two s-CFLD patients had nodular regenerative hyperplasia, 1 had hepatocellular carcinoma and 4 others underwent liver transplantation. Six patients (5.3%) had ad-CFLD with a median age of 42 years including 1 patient with s-CFLD.

Conclusions
Thirty-five percent of adult CF patients had CFLD in our cohort and 19% had s-CFLD. We used new definition criteria for CFLD and identified ad-CFLD in 6 patients. Better characterization of liver involvement in CF is crucial in order to better target medical care in this population.

Speakers

Zaina ISSA

Sophie GOHY

Bénédicte DELIRE

Géraldine DAHLQVIST

Thursday March 5, 2020 09:20 - 09:30 CET
Room TEUN

BASL / BLIC, Session 1

09:25 CET

Development and validation of dried blood spot sampling as a tool to identify the best time point to measure predictive ustekinumab serum concentrations in patients with Crohn’s disease

Authors
N. VAN DEN BERGHE (1), B. VERSTOCKT (2), E. VANDEPUT (2), V. BALLET (2), A. GILS (1), M. FERRANTE (2), S. VERMEIRE (2), D. THOMAS (1) / [1] University of Leuven, Leuven, Belgium, Department of Pharmaceutical and Pharmacological Sciences, [2] University Hospitals Leuven, , Belgium, Department of Gastroenterology and Hepatology

Introduction
Therapeutic drug monitoring of ustekinumab (UST), a monoclonal antibody directed against the p40 subunit of interleukin 12/23, can serve as a tool to identify underexposed Crohn’s disease (CD) patients, as UST concentrations have been linked to treatment response. Drug concentrations are most often measured when a patient is losing response. To reduce the risk of loss of response, drug concentrations could be measured upfront to predict the chance of achieving response later on and optimizing treatment if necessary. Identification of the optimal time point to measure UST levels that have a predictive value for long-term outcome requires studies with multiple sampling. Dried blood spot (DBS) sampling allows convenient and remote collection of a blood drop through a small finger prick.

Aim
The current study aimed to develop and validate the DBS method in order to identify the best time point to measure UST concentrations to predict long-term outcome in CD patients and explore the pharmacokinetic profile.

Methods
UST concentrations (0.2-80 µg/ml) were spiked in citrated whole blood and 40 µl was spotted onto protein saver cards. After punching a 6 mm disc, DBS were extracted and the UST concentration was measured with an in-house developed MA-UST56A2D11/MA-UST56C1H12 ELISA. The extraction efficiency, accuracy, precision and the effect of anti-UST antibodies on UST detection were evaluated. Additionally, the effect of the spotted blood volume, the stability of the DBS card at room temperature (RT) and DBS extract at -20°C was examined. To evaluate the correlation between UST in DBS extracts and serum, DBS and serum were simultaneously collected from 8 UST-treated CD patients at two different time points.

Results
Spiking UST to citrated whole blood and subsequent spotting and extraction revealed an average extraction efficiency of 65 ± 9% (n = 11). The accuracy and imprecision of all concentrations tested was 92-109% and 11-18%, respectively. Addition of anti-UST antibodies to spiked UST samples caused a similar decrease in UST concentration in DBS extracts as in serum. Spotted blood volumes between 15 and 50 µl demonstrated similar recoveries. Storing the DBS card at RT for up to 2 weeks and DBS extract at -20°C for 2 months did not impair recovery. UST concentrations in DBS extracts (range: 0.55-12.1 µg/ml) from CD patients correlated strongly with those in serum (Pearson r = 0.982, p <0.0001).

Conclusions
DBS is a robust method that facilitates multiple sampling for the determination of UST concentrations in CD patients. To explore the pharmacokinetic profile of UST and identify the best time point during induction to predict long-term outcome, a prospective study in which multiple DBS are collected in active CD patients initiating UST is warranted.

Speakers

Nathalie Van den Berghe

Bram Verstockt

Eline Vandeput

Vera Ballet

Ann Gils

Marc Ferrante

Séverine Vermeire

Debby Thomas

Thursday March 5, 2020 09:25 - 09:35 CET
Room TEUN

BIRD/BeSPGHAN, Session 3 IBD Clinic/BeSPGHAN

09:30 CET

An ileal GIST as a rare cause of overt lower gastro-intestinal bleeding in a 25-year old woman: a case report.

Authors
E. VAN MIEGHEM (1), S. VAN OUTRYVE (2), J. WAUTERS (2), P. STEGER (2) / [1] GZA Sint-Vincentius ziekenhuis, Antwerpen, , Belgium, Internal Medicine, [2] GZA Sint-Vincentius ziekenhuis, Antwerpen, , Belgium, Gastro-Enterology
Gastro-intestinal stromal tumors (GISTs) are rare mesenchymal tumors of the digestive tract with a reported incidence in Europe of 10-15 per million people. Most frequently they occur in persons older than 40 with median age of 60 years. A small percentage of GISTs present themselves with overt gastro-intestinal bleeding. Case presentation A 25-year old woman presented herself at the Emergency department with profuse rectal bleeding and a syncope. On admission she suffered from normocytic anemia with a hemoglobin of 7,4g/dl. Gastroscopy, rectosigmoidoscopy and total colonoscopy were performed with no identification of an active source of bleeding. To exclude to possibility of a bleeding Meckel diverticulum, a radionuclide scan was performed, which was negative. During hospitalization hemoglobin fell to 5,6g/dl for which transfusion of 3 units packed cells was needed. A CT abdomen was performed on which a contrast-enhancing soft tissue mass was visualized in the left flank. For further work-up a MRI was performed which confirmed the presence of a mass localized next to the small intestine. Due to the possibility of a neuro-endocrine tumor (NET) a DOTANOC PET-CT scan was performed, which excluded the presence of a somatostatin-receptor expressing tumor. A laparoscopic resection was planned for further anatomopathological identification. During surgery a 4cm long – 2.6cm wide tumor originating from the proximal ileum was visualized on the anti-mesenterial side of the bowel. Due to the size of the tumor laparoscopy was converted to mini-laparotomy during surgery. A single lymph node was also sampled during resection. Anatomopathological examination confirmed the diagnosis of a GIST with a low-risk profile according to the NIH-criteria due to only 1 mitotic count per 50 high-power fields (HPF) and tumor diameter

Speakers

Eugénie Van Mieghem

Steven Van Outryve

Jozef Wauters

Piet-Hein Steger

Thursday March 5, 2020 09:30 - 09:45 CET
Room SANCY

Case Reports GE, Session 1

09:30 CET

Brohee Lecture - NASH, think outside the liver

Prof Isabelle Leclercq

Speakers

Isabelle Leclercq

Thursday March 5, 2020 09:30 - 10:00 CET
Room TEUN

BROHEE

09:35 CET

Safety of the sequential use of biological therapy in inflammatory bowel disease: results from a tertiary referral centre.

Authors
A. MOENS (1), V. BALLET (1), J. SABINO (1), S. VERMEIRE (1), M. FERRANTE (1) / [1] University Hospitals Leuven, , Belgium, Gastroenterology and Hepatology

Introduction
Switching between biological therapies is frequently observed in routine management of inflammatory bowel disease (IBD). Yet, it is unknown if sequential use of biologicals affects safety such as serious infections and malignancies.

Aim
We aimed to compare the occurrence of serious infections and malignancies in regards to the number and classes of biologicals to which patients were exposed.

Methods
This retrospective cohort study included all IBD patients exposed to commercially available biologicals from 1999 to 2019 in a tertiary referral centre. Follow-up started at initiation of first biological. Exclusion criteria included: patients <18 years, episodic administration of biologicals or administration for another indication than IBD and loss to follow-up <2 years after start of first biological. Via review of full electronic medical records, we studied the development of serious infections (defined as any infection leading to hospitalization or treatment change) and malignancies. Poisson and Cox regression models were used.

Results
In total 1374 patients [54% female, 75% Crohn’s disease, 87% prior exposure to immunodoluators (IM), median age at last follow-up 44 (33-55) years, median time on biological 6.4 (3.6-10) years] were included. The majority of patients (n=878,64%) was exposed to only one class of biological, 28% (n=379) to two classes and 9% (n=117) to three classes. Almost half of the patients (n=575, 42%) was exposed to one biological therapy, whilst 33% (n=453), 17% (n=239) and 8% (n=107) of patients was exposed to two, three or more than three different biological therapies respectively. During a median (IQR) follow-up of 8 (4-13) years, 373 serious infections and 127 malignancies were reported in 245 (19%) and 92 (7%) patients, leading to an incidence rate of 2.2 and 0.8 per 100.000 patients per year, respectively. The number of serious infections was dependent on prior exposure to IM (p=0.001), the number of biologicals (p=0.042) and the number of biological classes to which the patients was exposed (p=0.004, overall test Poisson model p=0.0001). The risk of serious infections increased when a patient was exposed to three or more different biologicals or two or more different classes of biologicals. The number of malignancies was also affected by the number of biologicals (p=0.028) to which the patient was exposed, with a higher risk of developing a malignancy with exposure to an increasing number of biologicals. Cox regression for the time to develop a first or second malignancy was independent of exposure to IM, number of biologicals as well as number of different biological classes to which the patients was exposed. Median (IQR) time to develop a first or second malignancy after start of the first biological was 6 (3-9) and 6 (4-12) years.

Conclusions
In this large single centre cohort study spanning 20 years, the overall risk of serious infections and malignancies in patients exposed to biologicals remains low, yet the risk increased with more and sequential use of biologicals so close vigilance is needed.

Speakers

Annick Moens

Vera Ballet

Séverine Vermeire

Marc Ferrante

Joao Sabino

Thursday March 5, 2020 09:35 - 09:45 CET
Room TEUN

BIRD/BeSPGHAN, Session 3 IBD Clinic/BeSPGHAN

09:45 CET

Neoplastic lesions outside diseased area in IBD patients: A National Cohort Study

Authors
A. CREMER (1), P. DEMETTER (2), M. DE VOS (3), J. RAHIER (4), F. BAERT (5), T. MOREELS (6), E. MACKEN (6), E. LOUIS (7), S. VERMEIRE (8), D. FRANCHIMONT (1) / [1] Erasme Hospital, Brussels, Belgium, Department of Gastroenterology, [2] Institut Jules Bordet, Brussels, Belgium, Department of Pathology, [3] Ghent University Hospital, Ghent, Belgium, Department of Gastroenterology, [4] CHU UCL Namur, Yvoir, Belgium, Department of Gastroenterology, [5] AZ Delta, , Belgium, Department of Gastroenterology, [6] Antwerp University Hospital, Edegem, Belgium, Department of Gastroenterology, [7] CHU Sart Tilman, Liège, Belgium, Department of Gastroenterology, [8] University Hospitals Leuven, , Belgium, Department of Gastroenterology

Introduction
Patients with inflammatory bowel diseases (IBD) are at increased risk of dysplasia and colitis-associated cancer (CAC). The presentation of neoplastic lesions (low-grade dysplasia (LGD), high-grade dysplasia (HGD) or colorectal cancer (CRC)) is reported to vary depending if the lesions are located inside disease area (IDA) or outside diseased area (ODA).

Aim
The primary aim was to analyse the characteristics and prognostic of IDA compared to ODA neoplastic lesions in a large cohort of IBD patients.

Methods
We performed a multicenter retrospective pathological data collection from 7 tertiary referral regional or academic IBD centers in Belgium. Clinical, endoscopic and pathological data were retrieved through retrospective electronic chart review. From the IBD pathology databases, 1183 colorectal lesions were identified in 541 IBD patients: 415 developed dysplasia (77%) and 126 CRC (23%) during their follow-up. Biopsies and surgical specimen were centrally reviewed by an expert IBD pathologist to confirm the diagnosis of dysplasia and/or CRC.

Results
410 patients had IDA lesions, while 131 patients had ODA lesions. There was more ulcerative colitis among patients with IDA lesions in comparison with patients with ODA lesions (60% vs 44%, p<0.01). More patients with IDA lesions had HGD (9%) or CAC (27%) during their follow-up compared to the group of patients with ODA lesions (3% of HGD and 11% of CRC) (p<0.0001). Median follow-up duration after IBD diagnosis was 19 (IQR 10-29) and 14 (IQR 5-24) years in patients with IDA and ODA lesions, respectively (p<0.01). Mortality was higher in patients with IDA than in those with ODA lesions (15% vs 5%, p<0.05). Associated primary sclerosing cholangitis was present in 10% of patients with IDA lesions, while in none with ODA lesions (p<0.01). When comparing IBD patients with IDA lesions and CAC (=111) to those with ODA lesions and sporadic CRC (n=15), median age at IBD diagnosis was lower (29 (IQR:22-49) vs 41(IQR:28-54) years; p=0.0001). IDA lesions were more frequently non-visible (8% vs 0%), non-polypoid (36% vs 15%), diagnosed during surgery (8% vs 2%), and ≥ 1 cm (37% vs 19%) than ODA lesions (p<0.0001). ODA sporadic CRC were more frequently located in the right colon compared to IDA CAC (5/16 (31%) vs 21/133 (16%), p<0.01).

Conclusions
Neoplastic lesions outside diseased area were more likely to be visible, polypoid, < 1cm, in the right colon and diagnosed at endoscopy than inside disease area lesions. A lower prevalence of HGD and cancer were reported with neoplastic lesions outside diseased area.

Speakers

Anneline Cremer

Pieter Demetter

Martine De Vos

Jean-François Rahier

Filip Baert

Tom Moreels

Elisabeth Macken

Edouard Louis

Séverine Vermeire

Denis Franchimont

Thursday March 5, 2020 09:45 - 09:55 CET
Room TEUN

BIRD/BeSPGHAN, Session 3 IBD Clinic/BeSPGHAN

09:45 CET

Pseudo-achalasia secondary to oesophageal deviation resulting from mediastinal shift and right atrial enlargement after left lower lobectomy.

Authors
M. SURMONT (1), M. AERTS (1), R. KUNDA (1), S. KINDT (1) / [1] UZ Brussel, Vrije Universiteit Brussel, Brussels, , Belgium, Gastroenterology
An 80 year old man presented in May 2019 to the outpatient clinic for further investigation of longstanding dysphagia for solids. A left lower pulmonary lobectomy was performed in 1955 because of abcedation. He remains in follow-up for ischemic cardiomyopathy with enlargement of the left atrium. Repeated upper GI endoscopy since May 2017 provided no explanation for the dysphagia. Oesophageal biopsies excluded eosinophilic oesophagitis. Based on the presence of stasis of contrast in the middle third of the oesophagus associated with tertiary contractions during radiologic evaluation, but without evidence of achalasia, pneumatic dilatation up to 20 mm was performed twice. Because of persistent dysphagia, he was referred to our center for further analysis. Upper GI endoscopy showed slight signs of candidosis for which fluconazole was initiated without symptomatic improvement. Oesophageal manometry was compatible with type II achalasia. Additionally, deviation of the distal oesophagus attributed to an enlarged left atrium in the presence of a leftward mediastinal shift was demonstrated by contrast series and confirmed by CAT scan. Contrast retention was observed in the proximal oesophagus, but with normal evacuation at the oesophagogastric junction. No lung cancer was identified. Cardiac ultrasound confirmed the enlargement of the left atrium, with known reduced inferoseptal-inferior contractility. In the absence of strictures, and because of the advanced age and associated comorbidities, a conservative treatment was advocated. Although a manometrical diagnosis of pseudo-achalasia has been described after fundoplication, gastric banding and lung cancer, this is the first time it is observed as a result of mediastinal shift and left atrial enlargement.

Speakers

Magali Surmont

Maridi Aerts

Rastislav Kunda

Sébastien Kindt

Thursday March 5, 2020 09:45 - 10:00 CET
Room SANCY

Case Reports GE, Session 1

09:45 CET

Human and bacterial-derived amyloids trigger a distinct transcriptional response in primary myenteric networks.

Authors
N. DE LOOSE (1), P. VERSTRAELEN (2), G. GARCIA-DIAZ BARRIGA (2), S. VAN REMOORTEL (2), E. BARTHOLOMEUS (3), A. BRAUN (4), M. GRIES (4), K. SCHÄFER (4), W. DE VOS (2), J. TIMMERMANS (2) / [1] University of Antwerp, Antwerp, Belgium, Laboratory of Cell Biology and Histology, [2] University of Antwerp, , Belgium, Laboratory of Cell Biology and Histology, [3] University of Antwerp, , Belgium, Center for Medical Genetics, [4] University of Applied Sciences Kaiserslautern, Zweibrücken, Germany, ENS Group

Introduction
Recent fundamental and clinical research suggests that the gut and its enteric nervous system (ENS) play a long-underestimated role in amyloid-associated neurodegeneration. With pathological hallmarks being phenocopied in the ENS and with the resident microbiome acting as a major source of amyloid-like proteins, the gut may represent a putative entry route to amyloid-driven degeneration. However, the mechanisms underlying amyloid toxicity in the ENS are poorly characterized, nor is it known whether amyloids of host and bacterial origin alter the gene expression profiles of enteric neurons to a different extent.

Aim
To assess the transcriptional response to amyloid exposure in the ENS and to investigate whether host- and bacterial-derived amyloids differentially affect primary myenteric networks.

Methods
Myenteric neuronal networks of the colon of WT Black6 mice were isolated and exposed to bacterial-derived amyloid aggregates (Curli), human amyloid oligomers (Aβ1-42), or peptides with a scrambled sequence (Aβscr). After 24 hours of incubation, RNA sequencing was performed using a QuantSeq 3’ mRNA library prep kit and an Illumina NextSeq 500 sequencer. Differentially expressed genes were identified with an analysis pipeline combining RsubRead and DESeq2. Dysregulated pathways were explored using bioinformatic tools such as GeneOntology, EnrichR, DAVID, GSEA, SPIA and Pathview. Validation of top hits and associated genes was done via qPCR.

Results
We found that exposure of myenteric neurons to Aβ1-42 give rise to specific transcriptomic alterations that were not observed after incubation with Aβscr. These changes mainly pertained to inhibition of the cell cycle (57 genes including mdm2, PCNA, Cdks and Orc6) and dysregulation of genes implicated in DNA repair (31 genes). Interestingly, exposure to Curli (as compared to control medium) induced a transcriptomic signature that points to activation rather than inhibition of the cell cycle (15 genes). Exposure to Curli additionally induced a signature of genes involved in an innate immune response pathway. Among those, five genes (Tirap, Ptges, Sod2, Cxcl2 and Cxcl5) were associated with TLR signaling. Since amyloids were shown to activate TLR1/2 signaling in cultured macrophages (Tükel et al., 2010), we further focused on this pathway with qPCR and found that many TLRs are expressed in colon and ileum (Tlr1-Tlr13) tissue, and in primary myenteric cultures (Tlr2-Tlr7), and that active inflammation (as induced by DSS or TNBS) significantly triggers their expression. A pro-inflammatory cytokine cocktail (TNFα, IL1β and IFNγ) gave rise to a similar upregulation in primary myenteric cultures, and also resulted in upregulation of the Nlrp3 gene, a critical factor in inflammasome formation.

Conclusions
We have shown that enteric neurons respond differently to host-derived and bacterial amyloids, but that both amyloids may induce gene expression changes that adversely affect cell physiology. We are currently investigating whether these pathways also become dysregulated/activated in vivo, and what the long-term consequences are in the context of pathology development.

Speakers

Nouchin De Loose

Gerardo Garcia-Diaz Barriga

Samuel Van Remoortel

Esther Bartholomeus

Anne Braun

Manuela Gries

Karl-Herbert Schäfer

Peter Verstraelen

Jean-Pierre Timmermans

Thursday March 5, 2020 09:45 - 10:00 CET
Room TIFFANY/SHAH

GIREM, Session 1

09:55 CET

PROSPECTIVE STUDY OF PHARMACOKINETICS OF INFLIXIMAB DURING INDUCTION IN PATIENTS WITH CROHN’S DISEASE AND ULCERATIVE COLITIS (PACIFIC)

Authors
C. LIEFFERINCKX (1), P. BOSSUYT (2), D. THOMAS (3), J. RAHIER (4), E. LOUIS (5), F. BAERT (6), P. DEWINT (7), L. POUILLON (2), G. LAMBRECHT (8), S. VERMEIRE (9), D. FRANCHIMONT (1) / [1] Hopital Erasme, ULB, , Belgium, Department of Gastroenterology, [2] Imelda General Hospital, , Belgium, Department of Gastroenterology, [3] KU Leuven, , Belgium, Department of Pharmaceutical and Pharmacological Sciences, [4] CHU-UCL-Namur site Godinne, Yvoir, Belgium, Deparment of Gastroenterology, [5] Centre Hospitalier Universitaire Sart-Tilman, Liège, Belgium, Department of Gastroenterology, [6] AZ Delta, , Belgium, Department of Gastroenterology, [7] AZ Maria Middelares, , Belgium, Department of Gastroenterology, [8] AZ Damian, , Belgium, Department of Gastroenterology, [9] University Hospitals Leuven, , Belgium, Department of Gastroenterology and Hepatology

Introduction
Loss of response (LOR) to infliximab (IFX) remains a challenge in routine management of IBD patients. Previous studies have pinpointed the interest of early therapeutic drug monitoring (TDM) of infliximab at week 6 to predict LOR.

Aim
We evaluated IFX high resolution pharmacokinetics (PK) during induction with intermediate and peak PK levels.

Methods
This is a prospective, multicentre (n=9), interventional study approved by EC (P2017/484) and registered at EMA (Eudra CT 2015-004618-10). Fourteen blood samples were collected per patient from baseline to week 30. All patients were IFX naïve with active disease according to clinical, biological and endoscopy criteria. The primary outcome evaluated the inter-individual variability of IFX PK during induction and correlation with remission at week 30. In addition to trough levels, intermediate and peak levels were also measured and defined as drug level between two infusions and drug level early on after infusion (+2h), respectively. Remission was defined as having a Harvey Bradshaw Index (HBI) ≤4 and C-Reactive Protein (CRP) ≤5 for Crohn’s disease (CD), and as a clinical Mayo score ≤2 and faecal calprotectin <250 µg/g for ulcerative colitis (UC). IFX samples were measured by ELISA (Apdia) while a drug-tolerant affinity capture elution anti-infliximab assay was used to measure anti-infliximab antibodies (ATI) at week 6, 22 and 30

Results
The study population included 55% (n=34) of CD patients and 45% (n=28) of UC patients. Fifty-three percent of CD patients had complicated phenotypes with 23.5% B2 (n=8) and 29.4% B3 (n=10) while 78.6% of UC patients (n=22) had an extensive disease (E3). A concomitant immunosuppressor was used in 59.6% of patients. At baseline, median HBI was 8 (IQR 6-10) for CD patients with median CRP of 14 (IQR 5.9 – 24) and median SES-CD of 11.8 (IQR 7.25-20) while median clinical mayo score was 7 (IQR 6-9) for UC patients with median faecal calprotectin of 1698 (IQR 226 - 1800) and subscore endoscopic Mayo of 3 (IQR 2-3). Among the 62 patients enrolled, 33.9% of patients (n=21/62) were in remission at week 30. Eight patients dropped out due to disease worsening. Median trough levels at week 6 were higher among patients in clinical remission at week 30 (remission: 21.7 µg/ml, IQR (9.5-36) vs no remission 11.3 µg/ml, IQR (5.7-15.3), p=0.02) confirming previous observations. However, intermediate levels at day 3 (remission 82.4 µg/ml, IQR (58.4-99.5) vs no remission 58.8 µg/ml, IQR (46.9-76.9), p=0.02) as well as peak levels after third infusion (remission 141.1 µg/ml, IQR (117-171) vs no remission 122.8 µg/ml, IQR (98-136.5) p=0.04) were also significantly higher in patients in clinical remission at week 30. Of the 9 patients with detectable ATI (9/62, 14.5%), the great majority was treated with monotherapy (7 mono vs 2 combo, p=0.04). ATI were detected as soon as week 6. At week 2, infliximab levels were significantly lower among patients in which ATI developed at a later time point (p= 0.006) and this observation was confirmed when measuring intermediate levels at day 17 (p=0.002), trough levels at week 6 (p=0.002) and intermediate levels at week 10 (p=0.001).

Conclusions
This multicentre prospective study demonstrates that intermediate levels as early as day 3 predict remission at week 30 in IBD patients. Low IFX levels during induction were correlated to future ATI development. PK modelling may allow to better select patients early on for sustained remission with infliximab.

Thursday March 5, 2020 09:55 - 10:05 CET
Room TEUN

BIRD/BeSPGHAN, Session 3 IBD Clinic/BeSPGHAN

10:00 CET

A PET-positive nodule after chemotherapy

Authors
A. VAN OOSTERWYCK (1), M. COOL (1), G. DEBOEVER (1), L. DEPYPERE (2), G. VAN PARYS (3), G. LAMBRECHT (1) / [1] AZ Damiaan, Oostende, Belgium, Gastroenterology and Digestive Oncology, [2] UZ Leuven, Leuven, Belgium, Thoracic Surgery, [3] AZ Damiaan, Oostende, Belgium, Pathology
Case report: This report describes the case of a 76-year-old woman with complex oncological disease, who developed a rare complication. She has a history of non small cell lung carcinoma in the right upper lobe (stadium cT3N2M0), for which she was treated with neo-adjuvant chemotherapy (cisplatin/gemcitabine) and superior bilobectomy, back in 2011. The same year the diagnosis of an intraductal breast carcinoma (stadium ypT2N1a) was made as well, for which she received radiotherapy and tamoxifen. In 2016 a distal subtotal pancreatectomy was performed for a ductal adenocarcinoma of the pancreas (pT3N1M0). First-line adjuvant chemotherapy was started with an oral fluoropyrimidine (S-1). After 18 months, tumor markers started to rise again, and two new lesions in the liver were found. Gemcitabine/paclitaxel was commenced. In the next years two metastasectomies were carried out. In the first metastasectomy, two lesions in the liver were removed, in the second one a muscle metastasis in the abdominal wall was resected - both histologically proven of pancreatic origin. Gemcitabine/paclitaxel was restarted after an initial pause. The next FDG-PET-scan in 2019 showed a FDG-positive lesion in the right lower lobe, concomitant with slight augmentation of CA 19.9. A VATS wedge resection was performed. Histology however showed no tumoral lesion but a granuloma. PCR examination showed no sign of Mycobacterium infection and further evaluation could also exclude sarcoidosis. Histological analysis of a lesion on the tongue two weeks later also revealed an ulcer with an underlying granuloma. After resection we saw no recurrence so far. Discussion: There was no clear cause for these granulomata. Therefore we can probably assume that this was a drug induced reaction. Review of the literature showed some cases where taxanes such as paclitaxel and docetaxel (sometimes in combination with a monoclonal antibody) caused a granulomatous reaction. One article describes four cases of pyogenic granulomata. They were found on the left cheek, the right cheek, the left occipital region and the lower lip (1). Some other locations were intrahepatic (2), and mainly subungual and periungual (3, 4, 5). No reports of lung or tongue granulomas have been made so far. The granulomata in the other articles subsided after cessation of the chemotherapy. The pathogenesis is unclear. Conclusion: In this patient with three different tissue tumours, two granulomas were discovered, in the lung and on the tongue after therapy with paclitaxel. Given that there was no clear cause for the granulomas (no sarcoidosis, no infection, no Mycobacterium), we suspect there is a link with the chemotherapy she received. Paclitaxel is a taxane used in a wide array of neoplasms (such as breast, pancreatic and lung cancers). We found other reports -albeit few- of paclitaxel-induced granulomata.

Speakers

Aude Van Oosterwyck

Mike Cool

Guido Deboever

Lieven Depypere

Geert Van Parys

Guy Lambrecht

Thursday March 5, 2020 10:00 - 10:15 CET
Room SANCY

Case Reports GE, Session 1

10:00 CET

Sex-difference in the gastrointestinal phenotype depends on the susceptibility for co-morbid disorders such as anxiety.

Authors
S. WELLENS (1), A. ACCARIE (2), J. TOTH (1), L. WAUTERS (1), R. FARRÉ (1), J. TACK (1), T. VANUYTSEL (1) / [1] KU Leuven, , Belgium, Translational Research Center for Gastrointestinal Disorders (TARGID), [2] Translational Research Center for Gastrointestinal Disorders (TARGID), KULeuven, Leuven, Belgium, Clinical and Experimental Medicine

Introduction
Functional gastro-intestinal disorders (FGID) are twice as prevalent in women than in men. Susceptibility to anxiety and stress, both more prevalent in women, are reported as predisposing factors to develop FGID. The Wistar Kyoto (WKY) rat is an anxiety-sensitive strain compared to the more resistant Sprague Dawley (SD).

Aim
We aimed to investigate the intestinal phenotype in male and female WKY and SD rats and evaluate the gender difference in both strains to further unravel the complex interplay between sex and anxiety in the onset of visceral hypersensitivity, hyperpermeability and local immune cell infiltration

Methods
Male and female WKY and SD (n=7/group) were tested for anxiety behavior by using the marble burying test and for colonic sensitivity at d90 by measuring the visceromotor response (VMR) to isobaric (from 15 to 60 mmHg) distensions. Intestinal and colonic permeability, mast cell and eosinophil infiltration were measured with Ussing chamber studies, Chromotrope2R staining and Mast Cell Protease type 2 immunostaining respectively.

Results
For both genders, WKY showed an increased visceromotor response to colorectal distension (Fig.1) compared to SD which was associated with an increased anxiety-like behavior in females (8.5±1.3 vs 13.11±0.9 marbles buried, p<0.03) and males (9±1 vs 12.44±0.9, p<0.05). Female WKY displayed an increased paracellular permeability in the jejunum (197.9±55.64 vs 379±48.14 pmol/cm², p<0.05) associated with a trend to increased eosinophil infiltration (577.9±51.54 vs 732.7±57.58/mm², p=0.09) while male WKY tended to have increased transcellular (0.10±0.019 vs 0.18±0.03 µg/ml, p=0.07) and paracellular (170.3±23.34 vs 319±69.35pmol/cm², p=0.09) permeability. In both strains, females displayed an increased visceromotor response to colorectal distension (Fig.1) compared to males while the anxiety behavior was similar. For the WKY, females presented an increased immune cell infiltration characterized by eosinophils in both the colon (132.9±19.34 vs 407±44.10/mm², p<0.05) and jejunum (375.9±30.4 vs 732.7±57.58, p<0.05/mm²) while for the female SD, an increased transcellular permeability to horseradish peroxidase was found (0.1±0.019 vs 0.2±0.04 µg/ml p<0.05).

Conclusions
Our results highlight that the genetic background and the sensibility to disorders such as anxiety, modify the sex-difference in the gastrointestinal phenotype. These observations further confirm the necessity to consider not only gender, but also the genetic background of the animals in the study of FGID pathophysiology.

Speakers

Senne Wellens

Alison Accarie

Joran Toth

Lucas Wauters

Ricard Farré

Jan Tack

Tim Vanuytsel

Thursday March 5, 2020 10:00 - 10:15 CET
Room TIFFANY/SHAH

GIREM, Session 1

10:00 CET

Coffee Break Symposium BAYER

Decision making in the jungle of therapies for advanced HCC : an evidence based approach

Speakers

Chris Verslype

BAYER PH 351 Onco Flyer symposium unbranded A5 HD pdf

Thursday March 5, 2020 10:00 - 10:30 CET
Room TEUN

BASL / BLIC

10:05 CET

How switching to biosimilar infliximab led to stopping treatment in 3 pediatric Crohn patients

Authors
S. VANDE VELDE (1), R. DE BRUYNE (1), M. VAN WINCKEL (1), V. STEPHANIE (1) / [1] Ghent University Hospital, Ghent, Belgium, pediatric gastroenterology
Objective: Great uncertainty remains about risks and benefits of stopping treatment in patients with inflammatory bowel disease (IBD). Confronted with 3 patients with antibodies for infliximab in stable remission, cessation of treatment was discussed with patients and parents. We present the clinical, and biochemical data of 3 paediatric Crohn patients before and after stopping treatment. Methods: In 2017 all paediatric IBD patients treated with originator infliximab at the Department of paediatric Gastroenterology, Ghent University Hospital, were switched to biosimilar Remsima®. Faecal calprotectin, infliximab through levels and antibodies, white cell count (WBC), haemoglobin (Hb) and C-reactive protein (CRP) were measured before and after switching to biosimilar. Results: In total 21 IBD patients (3 UC – 19 CD) between 7 and 15 years old were switched. In 3 (14%) patients on monotherapy antibodies for infliximab were detected, after 22 to 82 months of use. None of the patients had previous surgery. All 3 were in clinical and biochemical remission (see Table 1). Colonoscopy was performed with normal macroscopic view (Crohn’s Disease Endoscopic Index of Severity score of 0) and confirmed histological remission in all. Switching to another treatment or cessation of treatment was discussed with patients and parents, and all 3 decided to stop treatment. Evaluation after 2 years shows that all 3 are still in clinical remission. Six- monthly clinical and biochemical (Hb, WBC, CRP and calprotectin) follow up is foreseen. Conclusions: We present 3 paediatric Crohn patients with a 2 year medication-free survival after stopping infliximab. These cases may lead an open window to further research in treatment discontinuation in paediatric IBD. Factors predicting relapse, optimal monitoring strategy following withdrawal have to be further elucidated, specifically for children and not converted from adult care.

Speakers

Saskia VANDE VELDE

Ruth De Bruyne

Myriam Van Winckel

Van Biervliet stephanie

Thursday March 5, 2020 10:05 - 10:15 CET
Room TEUN

BIRD/BeSPGHAN, Session 3 IBD Clinic/BeSPGHAN

10:15 CET

Impact of genetic burden on familial aggregation of inflammatory bowel disease

Authors
H. LEE (1), L. HANNES (1), M. VANCAMELBEKE (2), V. BALLET (3), M. FERRANTE (4), S. VERMEIRE (4), I. CLEYNEN (1) / [1] KU Leuven, Leuven, Belgium, Laboratory for Complex Genetics, Department of Human Genetics, [2] KU Leuven, euven, Belgium, Department Chronic Diseases, Metabolism & Ageing (CHROMETA), Translational Research Center for Gastrointestinal Disorders (TARGID), [3] UZ Leuven, Leuven, Belgium, Department of Gastroenterology and Hepatology, [4] KU Leuven, Leuven, Belgium, Department Chronic Diseases, Metabolism & Ageing (CHROMETA), Translational Research Center for Gastrointestinal Disorders (TARGID)

Introduction
Family history of inflammatory bowel disease (IBD) is the strongest risk factor for IBD. There currently, however, is limited understanding of the contribution of genetic risk scores to familial aggregation of IBD.

Aim
We aimed to evaluate the association between the IBD polygenic risk score (PRS) and familial IBD, and determine its contribution to familial IBD.

Methods
We included 54 multiple-affected families (≥ 3 first-degree relatives affected) of European ancestry, including 189 affected IBD patients (156 Crohn’s disease; 33 ulcerative colitis), and 133 unaffected relatives. For all individuals, Immunochip genotypes were available. Weighted PRSs with estimates derived from literature were calculated using PRSice-2.0, including clumping and different p-value thresholds (pT) to select which variants to include in the score. Explained variance (Nagelkerke pseudo-R²) was calculated across different pTs. To account for possible intra-familial correlations, the association between PRS and familial IBD was evaluated in age- and sex-adjusted generalized mixed regression models including family as random effects. Sporadic cases (n=1768) and non-IBD controls (n=868) with Immunochip genotypes were used for comparison.

Results
Using pT=0.05 for PRS calculation, we found that affected relatives had a higher PRS than unaffected relatives (P=1.00x10-02), sporadic cases (P=4.58x10-02), and non-IBD controls (P<2.20x10-16). The risk of disease in families increased by 1.23-fold (95% confidence interval (CI) 1.21–1.24) for every incremental standard deviation in PRS. Individuals in the highest quartile had a 3.45-times higher risk of IBD (95% CI 1.77–6.72) than those in the lowest quartile. However, the proportion of the explained variance between affected and unaffected family members was smaller than that of sporadic IBD and non-IBD controls; and the best pT was different for familial or sporadic IBD. In familial IBD, the best-fit PRS was at pT=6.90x10-03 and explained 5.3% (P=3.07x10-04) of variance, whereas in sporadic IBD, the best-fit PRS was at pT=0.08 and explained 16.7% (P=8.48x10-63). For sporadic IBD, a typical increase in the proportion of variance explained was seen with more liberal p-value thresholds, and levelling off at ~pT=0.1. What was striking however, was that in familial IBD this additive genetic variance was only observed until pT=0.01, after which explained variance dropped dramatically.

Conclusions
Higher IBD polygenic risk increases the risk for familial IBD as it does for sporadic IBD. In sporadic IBD, the increased risk is defined by variants of all p-value levels (until ~pT=0.1). In familial IBD, the difference between those affected or not is in the higher-effect variants (p-value<0.01).

Speakers

Ho-Su Lee

Laurens Hannes

Maaike Vancamelbeke

Vera Ballet

Marc Ferrante

Séverine Vermeire

Isabelle Cleynen

Thursday March 5, 2020 10:15 - 10:25 CET
Room TEUN

BIRD/BeSPGHAN, Session 3 IBD Clinic/BeSPGHAN

10:15 CET

Examining the processing of luminal information by the Enteric Nervous System using Ca2+ imaging.

Authors
C. FUNG (1), M. HAO (2), J. TACK (3), W. BOESMANS (4), P. VANDEN BERGHE (3) / [1] KU Leuven, Leuven, Belgium, TARGID, [2] University of Melbourne, Parkville, Australia, Anatomy and Neuroscience, [3] KU Leuven, , Belgium, TARGID, [4] Hasselt University, Hasselt, Belgium, Biomedical Research Institute (BIOMED)

Introduction
Monitoring of ingested nutrients by an organism is essential for balancing energy input. The gastrointestinal tract plays an important role in this homeostasis. Nutrient signals sensed by specialized enteroendocrine cells in the epithelium are conveyed to the enteric nervous system (ENS) to initiate intestinal reflexes facilitating digestion and absorption. However, the extent to which the ENS is ‘aware’ of the luminal composition remains elusive.

Aim
We aimed to address whether there are specific enteric pathways dedicated to detecting different luminal stimuli and to characterise the neuronal pathways subsequently activated following EEC stimulation.

Methods
Calcium imaging was performed on intact jejunal preparations from Wnt1-cre;R26R-GCaMP3 mice, which express the fluorescent calcium indicator GCaMP3 in their ENS. Glucose (300 mM), acetate (100 mM), and L-phenylalanine (100 mM), as a model sugar, short chain fatty acid, and amino acid respectively, were perfused onto the mucosa whilst imaging the underlying enteric neurons. The mucosal perfusion of high-K+ (75 mM) Krebs was used to broadly depolarize electrically excitable EECs. Nutrient transport or diffusion across the mucosa was mimicked by pressure ejecting nutrients from a micropipette impaled through the epithelium of a villus to target the containing nerve endings, or by applying nutrients onto ganglia in peeled preparations. Responders were further classified by their cell size, and neurochemistry using post-hoc immunolabeling of calbindin and neuronal nitric oxide synthase (nNOS) in the myenteric plexus, and choline acetyltransferase (ChAT) and vasoactive intestinal peptide (VIP) in the submucosal plexus.

Results
Mucosal depolarization, glucose, acetate, and L-phenylalanine each evoked Ca2+ transients in distinct subsets of myenteric (22 ± 3%, 17 ± 6%, 12 ± 2%, and 9 ± 2%) and submucosal neurons (24 ± 6%; 21 ± 4%; 24 ± 7%, and 23 ± 3% of total neurons within the field of view, respectively). The cell size (P < 0.0001; One-way ANOVA) and proportions of calbindin and neuronal nitric oxide synthase (nNOS)-immunoreactive myenteric neurons that responded differed significantly between the stimuli (P < 0.0001; χ2 test), while submucosal responders to all stimuli were predominantly cholinergic (ChAT+) and of similar size. Nutrients applied into villi or onto ganglia did not elicit neuronal responses, indicating that nutrients are first sensed at the epithelium. Myenteric responses to mucosal depolarization were abolished after severing the connections between the myenteric plexus and mucosa, demonstrating that the luminal signal is transmitted via nerve projections running between these layers. The 5-HT3 receptor antagonist ondansetron (10 µM) also significantly reduced the proportion of myenteric neurons responding to mucosal depolarization (ondansetron: 8 ± 1% vs. time control: 37 ± 2%; P = 0.0003, Two-way ANOVA, Sidak’s multiple comparisons test). This suggests that the response to mucosal stimulation is partly mediated via 5-HT acting on 5-HT3 receptors.

Conclusions
Different nutrients applied to the epithelium triggered distinct patterns of myenteric neuronal activation, suggesting that the ENS is able to discriminate between different compositions of luminal content such that it can respond accordingly. Further, our data demonstrate that enteric nerves are not directly sensitive to nutrients, but respond to the release of EEC signalling mediators such as 5-HT.

Speakers

Candice Fung

Marlene Hao

Jan Tack

Werend Boesmans

Pieter Vanden Berghe

Thursday March 5, 2020 10:15 - 10:30 CET
Room TIFFANY/SHAH

GIREM, Session 1

10:15 CET

Coffee Break

Thursday March 5, 2020 10:15 - 10:45 CET
Exposition Area

Case Reports GE

10:25 CET

Coffee Break Symposium BIOGEN

BIOSIMILARS: A FUEL TO INNOVATION

Speakers

Pieter Dewint

BIOGEN A5 Invitation satellite symposium BWGE 2020 final version pdf

Thursday March 5, 2020 10:25 - 10:55 CET
Room TEUN

10:30 CET

Coffee Break

Thursday March 5, 2020 10:30 - 10:45 CET
Exposition Area

BASL / BLIC

10:30 CET

Coffee Break

Thursday March 5, 2020 10:30 - 11:00 CET
Exhibition Area

GIREM

10:45 CET

Neoadjuvant immunotherapy for a MSI-H locally advanced rectal cancer patient: should we define new standard of care for these patients?

Authors
L. MANS (1), M. PEZZULLO (2), A. BUCALAU (3), N. D'HAENE (4), J. VAN DE STADT (5), J. VAN LAETHEM (3) / [1] Erasme University Hospital - Université Libre de Bruxelles (ULB), Bruxelles, Belgium, Gastroenterology , [2] Erasme University Hospital - Université Libre de Bruxelles (ULB), Bruxelles, Belgium, Radiology, [3] Erasme University Hospital - Université Libre de Bruxelles (ULB), Bruxelles, Belgium, Gastroenterology, [4] Erasme University Hospital - Université Libre de Bruxelles (ULB), Bruxelles, Belgium, Anatomopathology, [5] Erasme University Hospital - Université Libre de Bruxelles (ULB), Bruxelles, Belgium, Digestive Surgery
A 27-year-old woman with history of rectal bleeding for 6 months was diagnosed with a tumor at the lower third of the rectum. The biopsy revealed a well differentiated adenocarcinoma with loss of MSH2. The microsatellite instability was confirmed as MSI-high by molecular biology. The CEA level was 1.4 microg/L (normal < 5.2 microg/L). There was no distant metastasis at the thoraco-abdominal CT scan. The FDG PETCT showed a lower rectal neoplasia with a right iliac lymphadenopathy. The rectal EUS showed an uT3N+ lesion without internal anal sphincter invasion and two adenopathies in the mesorectal fat. The pelvic MRI confirmed the neoplasia of the lower third of the rectum classified T3N2 MRF+. There was a history of colon cancer in father, paternal grandfather and paternal great-grandfather, confirming Lynch syndrome. An ovarian tissue preservation and an ovarian pexy were performed. Due to the microsatellite instability, we decided in multidisciplinary board, to perform an induction treatment by immunotherapy combining Ipilimumab (1 mg/kg) and Nivolumab (3 mg/kg). After one cycle, we performed a control rectoscopy showing a complete endoscopic response and the biopsies revealed the absence of tumor cells. The FDG PETCT confirmed a major response at the rectal lesion and stability of the iliac lymphadenopathy. A new rectoscopy was performed after 2 cycles confirming the complete endoscopic response. The treatment was continued with Nivolumab in monotherapy for one additional cycle. The pelvic MRI confirmed also the complete clinical response with the absence of thickening of the rectal mucosa. The FDG PETCT showed a complete response both at the rectal and the lymphadenopathy levels after 3 cycles. A total mesorectal excision was performed on June 12th 2019. The pathological analysis revealed the complete absence of residual tumor cells. The resection margins were clear. There was no lympovascular or perineural invasion and no lymph node invasion (0/51 nodes). The lesion was classified ypT0N0. Due to initial clinical stage, we decided, in multidisciplinary board, to perform adjuvant immunotherapy by Nivolumab monotherapy for 4 months. The first evaluation, 6 months after resection, shows no relapse. Conclusions: this therapeutic approach is based on limited data but the phase II NICHE trial presented at ESMO 2018 showed a 100% (7/7 patients) of major pathological response in patients with dMMR colon cancer (MSI-H), including 4 complete responses. Due to the lack of data on the management of these patients with complete clinical response, we decided to perform surgery to confirm pathologically the complete response. This approach ,still experimental,allowed in a young woman with child-bearing potential, to avoid chemoradiotherapy and therefore save her uterus and ovaries.

Speakers

Laura Mans

Martina Pezzullo

Ana-Maria Bucalau

Nicky D'HAENE

Jean VAN DE STADT

Jean-Luc Van Laethem

Thursday March 5, 2020 10:45 - 11:00 CET
Room SANCY

Case Reports GE, Session 2

10:45 CET

Pitfalls of bariatric surgery in NAFLD and liver transplant patients

Prof. Anja Geerts (UZ Gent)

Thursday March 5, 2020 10:45 - 11:15 CET
Room TEUN

BASL / BLIC, Session 2

10:55 CET

Coffee Break

Thursday March 5, 2020 10:55 - 11:10 CET
Exhibition Area

BIRD/BeSPGHAN

11:00 CET

Spontaneous Pneumobilia

Authors
L. JANSSENS (1), D. PENRICE (1), J. BRANT (1), M. HALLAND (2) / [1] Mayo Clinic, Rochester, United States (the), Internal Medicine, [2] Mayo Clinic, Rochester, United States (the), Gastroenterology and Hepatology
A 57-year-old woman presented to the clinic with a longstanding history of intermittent right upper quadrant discomfort. She had moved from Cameroon to the United States 2 years prior to presentation. Her medical history included a distant history of H. Pylori related gastric ulcer disease reportedly treated with proton pump inhibitors (PPI) and antibiotics. The patient endorsed mild right upper quadrant tenderness on physical exam. Laboratory work-up (normal value ranges in parenthesis) showed Alkaline Phosphatase 415 U/L (35 – 104 U/L), Alanine Aminotransferase 234 U/L (7 – 45 U/L), Aspartate Aminotransferase 75 U/L (8 – 43 U/L) and total Bilirubin 1.3 mg/dL (

Speakers

Laurens Janssens

Daniel Penrice

Joseph Brant

Magnus Halland

Thursday March 5, 2020 11:00 - 11:15 CET
Room SANCY

Case Reports GE, Session 2

11:00 CET

The contribution of sodium channels to sensory Perception in the gut.

Speakers

Frank Bosmans (UGent)

Thursday March 5, 2020 11:00 - 11:45 CET
Room TIFFANY/SHAH

GIREM, Session 2

11:10 CET

How can telemedicine and patient empowerment improve IBD care in 2020? (title to confirm)

Marieke Pierik (University of Maastricht, Netherlands)

Speakers

Marieke Pierik

Thursday March 5, 2020 11:10 - 11:35 CET
Room TEUN

BIRD/BeSPGHAN, Session 4 IBD Clinic/BeSPGHAN

11:15 CET

Plasma protein glycomics combined with circulating fragments of cytokeratin-18 are reliable biomarkers to diagnose alcoholic hepatitis

Authors
X. VERHELST (1), A. GEERTS (2), L. MEURIS (3), H. DEGROOTE (2), M. TANGUY (4), H. DAVY (4), T. ISSOUFALY (4), F. DURAND (5), N. CALLEWAERT (3), H. VAN VLIERBERGHE (2), P. RAUTOU (5) / [1] Ghent University Hospital, Ghent, Belgium, Department of Gastroenteroly and Hepatology, [2] Ghent University Hospital, Ghent, Belgium, Gastroenterology and Hepatology, [3] VIB, Gent, Belgium, VIB-UGent Center for Medical Biotechnology, [4] Université de Paris, , France, Centre de recherche sur l'inflammation, Inserm, U1149, CNRS, [5] Hôpital Beaujon – Hôpitaux Universitaires Paris Nord Val de Seine, Clichy, , France, Service d'Hépatologie, DHU Unity, DMU Digest

Introduction
Alcoholic hepatitis (AH) is a severe liver disease with high mortality if left untreated. The hallmark of AH diagnosis remains histologic examination of a liver biopsy specimen. Transjugular liver biopsy being not available in all centers, there is a need for non-invasive biomarkers of AH. We recently showed that circulating fragments of cytokeratin-18, called M65, are higher in patients with HA and identified cut-off values.

Aim
The goal of this study was to assess the plasma N-glycomic profile of patients with HA and determine whether this glycomic profile could allow non-invasive diagnosis of HA in patients with clinical suspicion of this disease.

Methods
Plasma N-glycomic profiles were analysed using DNA sequencer assisted fluorophore assisted carbohydrate electrophoresis (DSA-FACE). This analysis was performed on plasma samples from a prospective cohort of patients with a clinical suspicion of AH (n=87) who underwent a transjugular liver biopsy. An optimal glycomic profile related to the diagnosis of AH was defined using logistic regression analysis.

Results
Out of the 87 patients included (82% male, median age 53), 44 patients had biopsy proven AH. Patients with AH had a different plasma protein glycosylation profile from patients without AH, characterized by increase in branch fucosylated triantennary glycan (NA3Fb), known to be related to acute phase response, and decrease of undergalactosylated glycans (NG1A2FB). A combination of these glycans (log NA3Fb/NG1A2F) was higher in patients with AH than in those without (OR 3.9 (p=0.001; 95% CI 1.8-8.8)). Using -1.0 and - 0.4 as thresholds for this combination of glycans to exclude and diagnose HA respectively, liver biopsy could be avoided in 69% of the patients and 75 % were correctly classified. When restricting the analyses to the 63 patients with a suspicion of severe AH (age, bilirubin, INR, and creatinine (ABIC) score B or C), using the same cut-offs, liver biopsy could be avoided in 65% of patients with a diagnostic accuracy of 81%. Combining the glycomic marker with plasma M65 levels further increased diagnostic accuracy for AH to 97% and could avoid liver biopsy in 55% of patients with ABIC score B or C.

Conclusions
A specific plasma glycomic signature (log NA3Fb/NG1A2F) is strongly associated with the presence of biopsy proven AH in patients with a clinical suspicion of this disease. Combining this glycomic signature with plasma M65 concentration in patients with a suspicion of severe AH can avoid liver biopsy in 55% of the patients, with a high diagnostic accuracy of 97%. These markers can be analysed using routine equipment, facilitating clinical implementation.

Thursday March 5, 2020 11:15 - 11:26 CET
Room TEUN

BASL / BLIC, Session 2

11:15 CET

Not probiotic-related Saccharomyces cerevisiae fungemia in an intensive care patient, a case report

Authors
M. MORETTI (1), E. MAILLART (2), B. MAHADEB (3), P. CLEVENBERGH (2) / [1] UZ Brussel, Jette, Belgium, Department of internal medicine , [2] CHU Brugmann, Brussels, Belgium, Department of internal medicine and infectious disease, [3] CHU Brugmann, Brussels, Belgium, Department of microbiology
Saccharomyces cerevisiae is a yeast commonly use in food industry and probiotics. It represents a rare, but rising cause of non-albicans Candida fungemia, predominantly in immunocompromised patient. The major source of infection is the use of probiotics and central venous catheter contamination. In the current article, a case of disseminate Saccharomyces cerevisiae infection in a not immunocompromised 68 years is presented. The patient was admitted to intensive care for surveillance after transverse colostomy, complicated by right hypochondria collection. The fungemia was not related to the consumption of probiotic, gut translocation was recognized as the definitive infection origin, as cultures of the abdominal collection and blood yielded Saccharomyces cerevisiae. The inflammatory immunosuppression state related to prolonged septicemia and broad spectrum antibiotics promoted the selection of the yeast and the spreading through the gut barriers. The rarity of Saccharomyces cerevisiae infection and antimycotic resistances may delay the correct diagnosis, the appropriate treatment and pejorate the outcome.

Speakers

Marco Moretti

Evelyne Maillart

Bavhna Mahadeb

Philippe Clevenbergh

Thursday March 5, 2020 11:15 - 11:30 CET
Room SANCY

Case Reports GE, Session 2

11:26 CET

Long-term outcome of symptomatic alcoholic hepatitis with a Maddrey discriminant function < 32.

Peter Starkel

Thursday March 5, 2020 11:37 - 11:48 CET
Room TEUN

BASL / BLIC, Session 2

11:45 CET

Safety and efficacy of combining biological therapies together or with small molecules in patients with Inflammatory Bowel Disease: a retrospective multicenter national observational case series study.

Authors
L. GOESSENS (1), J. COLOMBEL (2), A. OUTTIER (3), M. FERRANTE (3), M. TRUYENS (4), T. LOBATON (4), F. BAERT (5), P. BOSSUYT (6), A. CREMER (7), E. MACKEN (8), B. STRUBBE (9), J. RAHIER (1) / [1] CHU UCL Namur, Site de Godinne, Yvoir, Belgium, Gastroenterology, [2] Mount Sinai School of Medicine, New York, United States (the), Gastroenterology, [3] University Hospitals Leuven, , Belgium, Gastroenterology and Hepatology, [4] Universitair ziekenhuis Gent, , Belgium, Gastroenterology, [5] AZ Delta, Roeselare, Belgium, Gastroenterology, [6] Imelda Hospital, Bonheiden, Belgium, Gastroenterology, [7] Erasme University Hospital - Université Libre de Bruxelles (ULB), Bruxelles, Belgium, Gastroenterology, [8] University Hospital Antwerp, Edegem, Belgium, Gastroenterology, [9] AZ Sint-Lucas, Ghent, Belgium, Gastroenterology

Introduction
Few data is available regarding the combination of biological therapies (anti-TNF, anti-integrin, anti-interleukins (IL4, 12/23, 17A, 23)) or with a small molecule in patients with IBD.

Aim
We here report the safety and efficacy of combining these drugs through a national retrospective multicenter case series.

Methods
Cases were extracted from local databases within the last 3 years. Combined therapy was defined as the concomitant use for a minimum of 1 day of 2 biologics or 1 biologic with a small molecule. Patients’ demographics, disease’ characteristics and types of combined therapies were recorded. Safety was defined as the occurrence of any serious adverse event (SAE): serious infection, opportunistic infection, any hospitalization, cancer and death, whereas the efficacy of combination was clinically appreciated by physicians.

Results
From 8 centers, 23 combined therapies were observed in 19 IBD patients (74% Crohn’s disease, 21% ulcerative colitis and 5% IBD type unclassified). Median age at combination was 43.0 years ([IQR]: 31.5-59.0). Seventeen patients presented with a minimum of 1 concomitant IMID (ankylosing spondylitis (n=11), psoriasis or psoriatic arthritis (n=5) and others conditions (n=5)). Reasons for starting a combination were active IBD (57%), another active IMID (30%) or both (13%). Anti-TNF and anti-integrin were combined in 11 cases, anti-TNF and anti-ILs in 5, anti-integrin and anti-ILs in 4 and other combinations in 3 (anti-TNF+rituximab+methotrexate; anti-IL4+anti-IL12/23; anti-IL12/23+methotrexate+leflunomide). Median duration of combined therapies was 5 months ([IQR]: 2-9). During 15.8 patients/years of combined therapy, 11 adverse events (AE) including 9 SAE were recorded in 8 patients. Eight infections were reported with various combinations: anti-TNF and anti-IL in 4 cases, anti-TNF and anti-integrin in 3 and anti-TNF+rituximab+methotrexate in 1. Two infections (both anti-TNF+ anti-integrin) were graded severe leading to hospitalization, 6 were graded mild or moderate. Cancer and death were not observed. After combined therapy, IBD disease activity was clinically improved in 44% and remained stable in 50% of patients, whereas clinical improvement of IMID was observed in 25% of patients. Overall, combination of treatments was withdrawn due to ineffectiveness or serious adverse events in 39% and 4 % respectively.

Conclusions
In our experience, combination of biologics in patients with IBD +/- another IMID was associated with short term increased efficacy in almost half of patients but also with a risk of infections in one third. No new safety signals was observed in this difficult to treat patients but extensive data are urgently needed.

Thursday March 5, 2020 11:45 - 11:55 CET
Room TEUN

BIRD/BeSPGHAN, Session 4 IBD Clinic/BeSPGHAN

11:45 CET

Mantle cell lymphoma simulating inflammatory bowel disease

Authors
F. LIFRANGE (1), R. DE WIND (1), C. SPILLEBOUDT (2), A. VAN GOSSUM (3), P. DEMETTER (4) / [1] Institut Jules Bordet, , Belgium, Pathology, [2] Institut Jules Bordet, , Belgium, Haematology, [3] Institut Jules Bordet, , Belgium, Medical Oncology, [4] Institut Jules Bordet, Brussels, Belgium, Pathology
A 73 years old man, followed since many years for a thrombopenia of unknown origin, consulted a gastroenterologist after a positive faecal occult blood test. Colonoscopy revealed an erythematous, friable, bleeding on contact mucosa in the rectum, the sigmoïd, the caecum, the ileocaecal valve and the terminal ileum. Initial biopsies suggested an indeterminate colitis or an ulcerative colitis. Entocort and Colitofalk treatment was started. At colonoscopy 6 weeks later, mucosa was still friable and bleeding on contact. Another set of biopsies was taken. Histopathological examination revealed a diffuse monotonous lymphocytic infiltrate. Numerous small lymphocytes expressed CD20, Bcl-2 and cyclin D1 whereas immunohistochemical stainings for CD5, CD10, CD23 and Bcl-6 remained negative. Proliferation fraction was estimated 10-15% based on Ki-67 immunohistochemistry. A diagnosis of mantle cell lymphoma, classic variant was proposed. PET/CT 18F-FDG scan demonstrated multiple hypermetabolic supra- and infradiaphragmatic, cervical and mediastinal lymph nodes, splenomegaly, numerous hypermetabolic peritoneal foci and a diffuse radiotracer uptake throughout the colon wall. Mantle cell lymphoma is a mature B-cell lymphoma, usually very aggressive and incurable. It accounts for approximately 3-10% of non-Hodgkin lymphomas. Median age of onset is about 60 years . This tumour usually occurs in lymph nodes but extranodal involvement is frequent. Gastrointestinal tract is involved microscopically and macroscopically in more than 80% of cases. Most frequently colonic involvement is characterised by the presence of numerous polypoid lesions. Other possible features are superficial ulcers, large tumour masses or diffuse thickening of the mucosa. The t(11 ;14)(q13 ;q32) translocation, characteristic of mantle cell lymphoma, juxtaposes the immunoglobulin heavy chain (IgH) gene with the cyclin D1 gene (CCND1), causing cyclin D1 mRNA upregulation, subsequent cyclin D1 protein overexpression and eventual cell cycle dysregulation. This case illustrates the possible atypical presentation of mantle cell lymphoma and the importance of thorough histopathological examination in case of so-called inflammatory bowel disease that does not respond to treatment – be aware of mimickers...

Speakers

Frédéric Lifrange

Roland de Wind

Chloé Spilleboudt

Andre Van Gossum

Pieter Demetter

Thursday March 5, 2020 11:45 - 12:00 CET
Room SANCY

Case Reports GE, Session 2

11:45 CET

Beneficial effects of the locally administered TRPV4-antagonist HC-067047 in a post-inflammatory rat model for visceral hypersensitivity.

Authors
N. HANNING (1), H. CEULEERS (1), S. VAN REMOORTEL (2), H. DE SCHEPPER (3), A. SMET (1), J. TIMMERMANS (2), J. DE MAN (1), B. DE WINTER (1) / [1] University of Antwerp, , Belgium, Laboratory of Experimental Medicine and Pediatrics, [2] University of Antwerp, , Belgium, Laboratory of Cell Biology and Histology, [3] Antwerp University Hospital, , Belgium, Gastroenterology and Hepatology

Introduction
Transient receptor potential (TRP) channels have been implicated in visceral pain signalling. TRPV4 is expressed in the human colon and is involved in the sensation of chemical, thermal and mechanical stimuli. Sensitization of TRPV4 is one of the potential mechanisms contributing to the development of visceral hypersensitivity in irritable bowel syndrome (IBS) (Beckers et al., APT 2017). However, its role in mechanosensation and the therapeutic potential of TRPV4 antagonism in IBS has been mainly studied in vitro.

Aim
The aim of this study was to investigate the effect of the intrarectal administration of HC-067047, a TRPV4 antagonist, on visceral hypersensitivity in a 2,4,6-trinitrobenzenesulfonic acid (TNBS)-colitis post-inflammatory rat model for IBS.

Methods
At day 0, acute colitis was induced in adult male Sprague-Dawley rats with a TNBS enema (4 mg, in 50% ethanol). Control animals received an enema with 0.9% NaCl. Three days later, the presence of colitis was confirmed by colonoscopic scoring. From day 10 onwards, colonoscopy was repeated every 4 days until full endoscopic healing was observed. Then, electromyographic (EMG) electrodes were sutured into the abdominal musculature and exteriorized at the scapular region. Three days later, the TRPV4 antagonist HC-067047 (0.01-1-10 mg/kg) or its vehicle (25% 2-hydroxypropyl-β-cyclodextrin) was administered in the colorectum under isoflurane anaesthesia (5% induction, 2% maintenance). After 30 min, visceral sensitivity was assessed by quantifying the visceromotor response (VMR) to increasing colorectal distension pressures (10–60 mmHg, 20s, 4min interval). The VMR was expressed as an integral of the EMG response (area under the curve (AUC); µV/20s) and corrected by subtracting the baseline activity. Afterwards, we investigated the effect of HC-067047 on the viscoelastic properties of the colonic wall by measuring the colonic compliance. A pressure-controlled ramp distension protocol was initiated directly after the VMR measurements (0-60 mmHg in steps of 5 mmHg, 30s interval). The corresponding volume of air in the balloon was recorded and volume-pressure curves were used to represent the colonic compliance. Finally, the inflammatory parameters (colonoscopy, macroscopy and myeloperoxidase activity) were scored to confirm the post-inflammatory status at the day of the VMR and compliance measurements.

Results
Rats that received a TNBS enema showed signs of a mild colitis at day 3 of the experiment, as demonstrated by the significantly increased colonoscopic scores compared to control animals (7.39 ± 0.32, n=28 vs. 0.00 ± 0.00, n=16, p<0.001). The post-inflammatory status of the animals at the day of the VMR measurements (days 13-17) was confirmed by colonoscopic and macroscopic scoring, as well as by measuring the myeloperoxidase activity. In the sensitivity experiments, both control animals and vehicle-treated post-colitis rats showed gradually increasing VMRs, but VMRs were significantly higher in post-colitis rats, indicating the presence of visceral hypersensitivity in these animals. VMRs were increased in post-colitis vs control animals at both low distension pressures (20 mmHg: AUC 270.00 ± 62.27, n=8 vs. 51.13 ± 16.84, n=8, p=0.01) and high distension pressures (40 mmHg: AUC 544.88 ± 94.61, n = 8 vs. 147.88 ± 49.96, n=8, p=0.04). Intrarectal treatment with HC-06707 (0.01-1-10 mg/kg) resulted in a dose-dependent decrease of the VMRs compared to vehicle-treated post-colitis animals, with the highest dose completely reversing the visceral hypersensitivity. This effect was present in HC-067047-treated (10 mg/kg) vs. vehicle-treated post-colitis rats at both low distension pressures (20 mmHg: 72.39 ± 28.95, n=7 vs. 270.00 ± 62.27, n=8, p=0.04) and high distension pressures (40 mmHg: 175.29 ± 42.57, n=7 vs. 544.88 ± 96.61, n=8, p<0.001). Administration of a high dose HC-067047 (10 mg/kg) had no effect on visceral sensitivity in control animals. Post-colitis animals displayed a colonic compliance similar to control animals and treatment with HC-067047 increased colonic compliance only in the lowest dose (0.01 mg/kg) in post-colitis rats. Treatment with HC-067047 had no effect on the post-mortem inflammatory parameters.

Conclusions
This study shows that local administration of the TRPV4 antagonist HC-067047 decreased visceral hypersensitivity in a post-inflammatory rat model for IBS. The effects of HC-067-47 in a high dose (10 mg/kg) on visceral pain cannot be attributed to changes in the colonic compliance. Our results confirm that TRPV4 is a potential target for the treatment of visceral pain in IBS.

Speakers

Nikita Hanning

Hannah Ceuleers

Samuel Van Remoortel

Heiko DE SCHEPPER

Annemieke Smet

Jean-Pierre Timmermans

Joris De Man

Benedicte De Winter

Thursday March 5, 2020 11:45 - 12:00 CET
Room TIFFANY/SHAH

GIREM, Session 2

11:48 CET

Role of the gut microbiota in the modulation of the gut-liver-brain axis in alcohol use disorders: proof of concept with the fecal microbiota transplantation

Authors
S. LECLERCQ (1), T. LE ROY (2), S. FURGIUELE (3), V. COSTE (2), L. BINDELS (2), A. NEYRINCK (2), C. QUOILIN (4), C. AMADIEU (2), V. TAGLIATTI (3), P. CANI (2), K. VERBEKE (5), J. COLET (3), P. STÄRKEL (6), P. DE TIMARY (4), N. DELZENNE (2) / [1] UCLouvain, , Belgium, LDRI/MNUT and IoNS, [2] UCLouvain, , Belgium, LDRI/MNUT, [3] UMons, Mons, Belgium, Laboratory of Human Biology & Toxicology, [4] UCLouvain, , Belgium, IoNS, [5] KU Leuven, , Belgium, Translational Research Center in Gastrointestinal Disorders, [6] UCLouvain, , Belgium, IREC/GAEN

Introduction
It is well established that alteration of the gut microbiota composition can disturb many aspects of host physiology, including metabolism, immunity and peripheral and central nervous system with consequences for brain functions and behavior. In a previous study, we showed that alterations of the gut microbiota composition of alcohol-dependent (AD) patients were associated with low scores of sociability, high scores of depression, anxiety and alcohol craving, suggesting the existence of a gut-brain axis in AD patients.

Aim
The aim of the study was to demonstrate the causal role of the gut microbiota in the development of liver and brain alterations associated with alcohol dependence, by using fecal microbiota transplantation.

Methods
The fecal microbiota of AD patients and healthy controls (CT) were transferred into two groups of mice which were subsequently tested for liver metabolism, brain functions and behavior. Metabolomics (H1-NMR) was used to pinpoint key metabolites involved in gut-liver-brain interactions.

Results
We found that mice transplanted with the gut microbiota of AD patients exhibited increased depression-like behavior and decreased social behavior compared to CT-recipient mice. Furthermore, AD-recipient mice showed alterations of brain myelination, neurotransmission and neuroinflammation. Metabolomics analysis revealed, in AD-recipient mice, elevated ethanol concentration in the portal vein and decreased plasma levels of a ketone body, the b-hydroxybutyrate (BHB), which was consistent with a reduced expression of the liver enzyme Hmgcs2, the main control point of ketogenesis. Exposition of mice to a ketogenic diet had beneficial effect on social behavior and brain functions, thereby supporting the hypothesis that BHB is a key metabolite in the gut-liver-brain axis. The involvement of these two metabolites, ethanol and BHB, and their links with the psychological symptoms were confirmed in a cohort of AD patients.

Conclusions
The results of this study confirm the production of ethanol by intestinal bacteria that consequently impacts liver and brain metabolism, and reinforce the existence of a gut-liver-brain axis in alcohol use disorders. Modification of the gut microbiota composition, through nutritional approaches, might be helpful in the management of alcohol-dependent patients.

Thursday March 5, 2020 11:48 - 11:59 CET
Room TEUN

BASL / BLIC, Session 2

11:55 CET

Tofacitinib induces clinical and endoscopic remission in biologic refractory Ulcerative Colitis patients: A real-world Belgian cohort study

Authors
A. CREMER (1), T. LOBATON (2), S. VIEUJAN (3), P. BOSSUYT (4), J. RAHIER (5), F. BAERT (6), O. DEWIT (7), E. MACKEN (8), M. SOMERS (8), A. VIJVERMAN (9), P. VAN HOOTEGEM (10), F. MANA (11), B. WILLANDT (12), P. CAENEPEEL (13), E. HUMBLET (13), F. D'HEYGERE (14), A. VERRETH (15), A. EL NAWAR (16), J. COENEGRACHTS (17), S. DEWIT (18), S. DE CONINCK (19), N. SCHOOFS (20), S. DELEN (21), J. DUTRE (22), C. THIENPONT (23), S. VANDEN BRANDEN (24), D. STAESSEN (25), D. FRANCHIMONT (1) / [1] Erasme Hospital, Brussels, Belgium, Department of Gastroenterology, [2] Ghent University Hospital, Ghent, Belgium, Department of Gastroenterology, [3] CHU Sart Tilman, Liège, Belgium, Department of Gastroenterology, [4] Imelda Hospital, Bonheiden, Belgium, Department of Gastroenterology, [5] CHU UCL Namur, Yvoir, Belgium, Department of Gastroenterology, [6] AZ Delta, Roeselare, Belgium, Department of Gastroenterology, [7] Cliniques universitaires Saint-Luc, Brussels, Belgium, Department of Gastroenterology, [8] Antwerp University Hospital, Edegem, Belgium, Department of Gastroenterology, [9] CHR Citadelle, Liège, Belgium, Department of Gastroenterology, [10] Algemeen Ziekenhuis Sint-Lucas, , Belgium, Department of Gastroenterology, [11] Clinique Saint-Jean, Brussels, Belgium, Department of Gastroenterology, [12] AZ Sint-Jan Brugge-Oostende, Brugge, Belgium, Department of Gastroenterology, [13] Ziekenhuis Oost Limbug (ZOL), Genk, Belgium, Department of Gastroenterology, [14] AZ Groeninge, Kortrijk, Belgium, Department of Gastroenterology, [15] AZ Sint-Jozef, , Belgium, Department of Gastroenterology, [16] CENTRE HOSPITALIER MOUSCRON, Mouscron, Belgium, Department of Gastroenterology, [17] Jessa Ziekenhuis, Hasselt, , Belgium, Department of Gastroenterology, [18] Mariaziekenhuis Noord-Limburg, Overpelt, Belgium, Department of Gastroenterology, [19] Sint Andries ziekenhuis Tielt, Tielt, Belgium, Department of Gastroenterology, [20] Sint-Trudo ziekenhuis, Sint-Truiden, Sint-Truiden, Belgium, Department of Gastroenterology, [21] ZH Maas en Kempen, , Belgium, Department of Gastroenterology, [22] ZNA Jan Palfijn, Merksem, Belgium, Department of Gastroenterology, [23] ZNA Antwerpen, Antwerpen, Belgium, Department of Gastroenterology, [24] OnzeLieveVrouwziekenhuis, Aalst, , Belgium, Department of Gastroenterology, [25] GZA Sint-Vincentius ziekenhuis, Antwerpen, , Belgium, Department of Gastroenterology

Introduction
Tofacitinib, an oral small molecule Janus kinase inhibitor, has been approved in 2018 for the treatment of moderate to severe ulcerative colitis (UC) in Europe. We report on real-world short-term efficacy and safety data from a multicenter Belgium refractory cohort of UC patients with prior exposure to both anti-TNF and vedolizumab.

Aim
The aim of the study was to evaluate clinical and endoscopic response and remission rates at weeks 8 and 16.

Methods
This is an observational, national, retrospective multicenter study including all UC active patients started on tofacitinib (10 mg BID) from 25 centers in Belgium between November 2018 to August 2019. Prospectively collected data were retrospectively analyzed according intention-to-treat. Clinical response was defined as a decrease from baseline in Modified Clinical Mayo score (rectal bleeding, stool frequency) by ≥2 points, with an accompanying decrease in the rectal bleeding subscore of at least 1 point or an absolute rectal bleeding subscore of 0 or 1. Clinical remission was defined as a Modified Clinical Mayo score ≤1. Endoscopic response was defined as a decrease from baseline in Endoscopic Mayo score by ≥1. Endoscopic remission was defined as an Endoscopic Mayo score ≤1. Complete endoscopic remission was defined as an Endoscopic Mayo score of 0. Descriptive statistics and Wilcoxon signed rank test were calculated using Medcal 19.1.

Results
Median disease duration at baseline of the 70 included patients was 13 years (IQR 8-16). Nearly all patients were refractory to at least one anti-TNF and vedolizumab. 3 patients did not receive anti-TNF, and 2 did not receive vedolizumab. Modified Clinical Mayo score at baseline was 5 (IQR 3-5), and Endoscopic Mayo score was 3 (IQR 2-3). Fifty-four percent (38/70) of patients required prolonged induction at 10mg BID. Median follow-up was 16 weeks (IQR 13-26). Clinical evaluation was available in all patients at week 8 and 49 patients at week 16, while endoscopic data were available in 52 patients and 42 at weeks 8 and 16, respectively. Clinical response and remission were 63% and 41% at week 8 and 76% and 53% at week 16. Endoscopic response and remission were 44% and 23% at week 8 and 69% and 50% at week 16. Complete endoscopic remission was 13% at week 8 and 19% at week 16. Fifty percent (21/42) of the patients under steroids at baseline could have stopped steroids at week 16. Median baseline Modified Mayo score (rectal bleeding, stool frequency and endoscopy) decreased from 7 (IQR 5- 8) to 4 (IQR 2-7) after 8 weeks (n=49) (p<0.0001), and down to 2 (IQR 1-5) at week 16 (n=40) (p<0.0001). Median CRP significantly decreased from baseline (5.3 mg/l, IQR [1.9–16.8]) to 1 mg/l at week 8 (IQR 0.5-6.2) (n=49) (p=0.003). Tofacitinib was well tolerated with only 1 reported case of single dermatome herpes zoster and no case of venous thromboembolism.

Conclusions
Tofacitinib very effectively induced short-term clinical and endoscopic response and remission even in a refractory cohort of patients with UC in a real-world clinical setting. During this short-term follow-up, tofacitinib was well tolerated with respect to adverse events.

Thursday March 5, 2020 11:55 - 12:05 CET
Room TEUN

BIRD/BeSPGHAN, Session 4 IBD Clinic/BeSPGHAN

11:59 CET

Myosteatosis is associated with early NASH in the context of obesity and metabolic syndrome

Authors
M. NACHIT (1), G. VANDE VELDE (2), W. KWANTEN (3), O. SCHAKMAN (4), J. THISSEN (5), M. DE RUDDER (1), C. BOUZIN (6), B. OP DE BEECK (7), Y. HORSMANS (8), L. VAN GAAL (9), S. FRANCQUE (3), I. LECLERCQ (1) / [1] UCLouvain, , Belgium, Institut De Recherche Expérimentale Et Clinique, Laboratory of Hepato-Gastroenterology, [2] KU Leuven, , Belgium, Department of Imaging and Pathology, [3] Antwerp University Hospital, , Belgium, Department of Gastroenterology and Hepatology, [4] UCLouvain, , Belgium, Institute of Neuroscience, Laboratory of Cell Physiology, [5] UCLouvain, , Belgium, Institut De Recherche Expérimentale Et Clinique, Endocrinology, Diabetology, and Nutrition Department, [6] UCLouvain, , Belgium, IREC Imaging Platform, [7] Antwerp University Hospital, , Belgium, Department of Radiology, [8] Cliniques universitaires Saint-Luc, Brussels, Belgium, Service D'hépato-Gastro-Entérologie, [9] Antwerp University, , Belgium, Laboratory of Experimental Medicine and Pediatrics - Division of Endocrinology

Introduction
A substantial body of literature supports that a low muscle mass, low strength or a higher muscle fatty infiltration are associated with NAFLD presence and severity. However, whether these muscle alterations are mere consequences of NASH, whether changes in the muscle compartment might be a signature of hepatocellular damages and inflammation, and whether these changes might play a pathophysiological role in NAFL to NASH transition remain hypothetical.

Aim
To investigate muscle changes in correlation with liver disease progression in NAFLD rodent models and in a human cohort

Methods
For over 34 weeks, we followed WT mice fed a standard chow as controls (Ctl), WT mice fed a high fat (HF) diet (60% fat) as a model of simple steatosis (WT HF) and foz/foz mice fed a HF diet as a model of progressive NASH (FOZ HF). We developed and validated a novel preclinical micro-Computed Tomography (micro-CT) based methodology to prospectively study skeletal muscle mass and fatty infiltration in muscle and liver in a high-throughput and non-invasive manner. We used grip strength test to evaluate muscle functionality and analyzed liver histology at monthly intervals. We used CT to measure skeletal muscle mass and fatty infiltration retrospectively in a large cohort of 197 morbidly obese patients with biopsy proven NASH (n=117, 62.4%), NAFL (n=35, 18.9%) or normal liver histology (n=33, 17.8%). All data are mean±SEM.

Results
WT ND mice had normal liver histology at all times; WT HF mice developed modest steatosis at late time points; all FOZ HF had NAS >5 as from W12, with minimal fibrosis at W20 and patent pericellular fibrosis at W34. In FOZ HF with NASH, muscle mass dissociated from body weight gain. The relative decrease in muscle mass was associated with severe loss of muscle strength from W12 on (Ctl : 244±4g; WT HF : 251.9±6g vs FOZ HF : 228.6±4g) which further worsened with time (165.2±5.2g at 34W in FOZ HF). This was not seen in the other groups. Myosteatosis was the earliest muscular change as reflected by a significantly lower muscle density in FOZ HF as early as 4 week (0.79±0.02) when compared to Ctl (0.91±0.02) and reached a minimum at 12W (0.37±0.05 in FOZ HF vs 0.85±0.02 and 0.75±0.02 in Ctl and WT HF) then plateaued. Myosteatosis severity in FOZ HF, unexplained by body weight gain, was strongly correlated with NAS score (r=-0.87, n=67, p<0.001), irrespectively of the time point studied. Importantly, myosteatosis powerfully discriminated NASH from isolated steatosis or normal liver (AUROC = 0.96, p<0.001) in this model. In a large population of 185 morbidly obese patients, the CT-based psoas density index (reflecting myosteatosis) was significantly lower (p<0.01) in patients with NASH F-0,1 (1.44±0.03) and NASH F2+ (1.41±0.08) than in those with isolated steatosis (1.69±0.05) or normal liver histology (1.74±0.04). PDI identified patients with biopsy proven NASH amongst those with uncomplicated steatosis and normal liver histology with a good diagnostic performance (AUROC = 0.74, p<0.001), outperforming classical biomarkers such as FIB4, NFS and CK18 (AUROC = 0.57, 0.52 and 0.55 respectively). Furthermore, PDI and ALT levels were the only independent factors predicting NASH in a multivariate statistical model with associated AUROC of 0.81 (p<0.001).

Conclusions
Our data support that in NAFLD, hepatocellular damage and inflammation that characterize progression to NASH associate with myosteatosis. This observation paves the way for the exploitation of myosteatosis as a non-invasive marker of NASH and suggesting a muscle-liver reciprocal cross-talk during liver disease progression.

Thursday March 5, 2020 11:59 - 12:10 CET
Room TEUN

BASL / BLIC, Session 2

12:00 CET

Duodenal bile salts and mucosal changes are linked with gastric emptying and symptoms in functional dyspepsia patients.

Authors
L. WAUTERS (1), M. CEULEMANS (1), M. LAMBAERTS (1), A. ACCARIE (1), J. TOTH (1), R. MOLS (2), R. FARRÉ (1), P. AUGUSTIJNS (2), J. TACK (1), T. VANUYTSEL (1) / [1] KU Leuven, , Belgium, TARGID, [2] KU Leuven, , Belgium, Drug delivery and disposition

Introduction
Despite increasing evidence for duodenal epithelial hyperpermeability and low-grade inflammation in functional dyspepsia (FD) patients (Vanheel et al. Gut 2014), the role of luminal changes has scarcely been studied.

Aim
We aimed to study duodenal bile salt concentrations and pH in relation to duodenal mucosal changes, gastric emptying and symptoms in FD.

Methods
FD patients (Rome IV) were recruited with aspiration of duodenal fluids via a naso-duodenal tube after endoscopic collection of duodenal biopsies. Bile salt concentrations were measured in fasting and every 15min during 1h in fed state (Fortimel®, 300 kCal) using LC-MS/MS after pH-measurement. Paracellular dextran-passage (4 kDa) was studied in Ussing chambers and eosinophils counted on H&E-stained sections per high-power field (HPF; 0.24 mm2). Gastric emptying for solids (14C-octanoic acid breath test T1/2) and PAGI-SYM scores were determined. Multilevel (mixed) models were constructed with pH and bile salt concentrations (total, primary and secondary) as dependent and time as within-subject independent variable of interest. Next, the effect of individual bile salt concentrations on T1/2 and symptoms was assessed before and after adding mucosal dextran-passage and eosinophils in the model to test for potential mediation.

Results
In total, 22 FD patients (19 female, mean ± SEM age 31 ± 2 years) were included. A significant effect of time was found for the increase in pH (F=5.38, p=0.004) and total bile salt concentrations (F=17.93, p<0.0001) with a similar evolution for primary and secondary bile salts. Mean paracellular dextran- passage was 28.8 ± 2.6 pmol with 12.9 ± 5.4 duodenal eosinophils /HPF. T1/2 was 72.4 ± 8.3 min, which correlated with dextran-passage (r=.73, p=0.002). PAGI-SYM score was 2.4 ± 0.1 and correlated with duodenal eosinophils (r=0.54, p=0.026) but not T1/2 (r=-0.18, p=0.48). A significant effect of the secondary bile salt taurodeoxycholic acid was found on paracellular dextran-passage (F=7.19, p=0.016) and T1/2 (F=7.82, p=0.014), but the effect on gastric emptying was not mediated by dextran-passage (F=0.19, p=0.67). A significant effect of the primary bile salt taurocholic acid was found on duodenal eosinophils (F=6.15, p=0.028) and PAGI-SYM (F=6.26, p=0.022), but the effect on symptoms was not mediated by eosinophils (F=0.93, p=0.35).

Conclusions
In FD patients, gastric emptying rate is associated with duodenal mucosal permeability but not symptoms, indicating that gastric dysmotility may be secondary to duodenal pathology. Indeed, symptoms are associated with duodenal eosinophils in FD patients. Although duodenal bile salts have significant associations with both gastric emptying and symptoms, the mechanisms do not seem to involve duodenal barrier or immune function and require further study in FD.

Speakers

Lucas Wauters

Matthias Ceulemans

Maarten Lambaerts

Alison Accarie

Joran Toth

Raf Mols

Ricard Farré

Patrick Augustijns

Jan Tack

Tim Vanuytsel

Thursday March 5, 2020 12:00 - 12:15 CET
Room TIFFANY/SHAH

GIREM, Session 2

12:00 CET

Oral Top Basic e-Posters

The best Basic e-Posters will give a 5 minute presentation in the ePoster area.

- Defective gut adaptive immunity during early alcoholic liver disease.
- Adoptive cell transfer of regulatory T cells causes an exacerbation of hepatic steatosis in high-fat high-fructose diet-fed mice.
- The effects of oral valsartan treatment on the increased intrahepatic vascular resistance and disease severity of early NAFLD in rats.
- Alterations in bile acids and TGR5 activation in nonalcoholic steatohepatitis.
- Longitudinal characterization of muscle alterations in a rodent model of NASH.
- Discovery of the gut microbial signature driving the efficacy of prebiotic intervention on liver steatosis.
- Intestinal fibrosis in Crohn’s disease patients is marked by an upregulation of innate immune cells and mucosal B cells.
- Fibrogenesis in chronic DSS colitis is driven by an innate lymphoid cell-independent innate immune response.
- Increased Endoplasmic Reticulum stress specific chaperones characterise CD fibrosis epithelium tissues and participate to in vitro induction of intestinal fibrobasts differentiation.
- An easy and rapid targeted Next Generation Sequencing-based genotyping assay for the validated IBD risk loci.

Speakers

Luca Maccioni

Mikhail Vanherck

Denise van der Graaff

Justine Gillard

Héloïse Louvegny

Julie Rodriguez

Brecht Creyns

Sophie Vieujean

Bram Verstockt

Thursday March 5, 2020 12:00 - 13:00 CET
ePoster Area

Oral Top Posters - Short talks, Basic

12:05 CET

How to do a tight monitoring in Crohn’s disease: role of small bowel capsule endoscopy, entero-MRI and other morphologic explorations (title to confirm)

Prof Arnaud Bourreille (University of Nantes, France)

Speakers

Arnaud Bourreille

Thursday March 5, 2020 12:05 - 12:30 CET
Room TEUN

BIRD/BeSPGHAN, Session 4 IBD Clinic/BeSPGHAN

12:10 CET

Hepatitis E Virus Genotype 3 subtype dependent clinical outcomes in Belgium 2010 – 2018

Authors
T. DE SOMER (1), M. PEETERS (2), S. KLAMER (3), F. NEVENS (4), J. DELWAIDE (5), P. STÄRKEL (6), P. WILLEMS (7), S. DE MAEGHT (8), C. MORENO (9), M. VAN HOOF (10), I. COLLE (11), F. SERMON (12), C. VAN STEENKISTE (13), F. JANSSENS (14), J. VAN ACKER (15), A. MAROT (16), E. BOTTIEAU (17), M. REYNDERS (18), C. DE GALOCSY (19), L. LASSER (20), M. STEVERLYNCK (21), J. MAUS (22), W. VERLINDEN (23), A. GEERTS (24), M. GALLANT (25), S. VAN OUTRYVE (26), H. REYNAERT (27), J. MULKAY (28), J. DECAESTECKER (29), V. SUIN (2), S. NEGRIN-DASTIS (30), S. VAN GUCHT (2), T. VANWOLLEGHEM (1) / [1] UZA, Universitair Ziekenhuis Antwerpen, Edegem, Belgium, Gastroenterology & Hepatology, [2] Sciensano, Brussels, Belgium, National Reference Centre of Hepatitis Viruses, Viral Diseases, Infectious Diseases in Humans, [3] Sciensano, Brussels, Belgium, Epidemiology of Infectious Diseases, [4] UZ Leuven, Leuven, Belgium, Gastroenterology & Hepatology, [5] CHU of Liège, , Belgium, Gastroenterology & Hepatology, [6] Cliniques universitaires Saint-Luc, Brussels, Belgium, Gastroenterology & Hepatology, [7] Sint Augustinus Ziekenhuis GZA, Antwerp, Belgium, Clinical Biology, [8] Centres Hospitaliers Jolimont, , Belgium, Gastroenterology & Hepatology, [9] Hopital Erasme, ULB, , Belgium, Gastroenterology & Hepatology, [10] Clinique Saint-luc Bouge, Namur, Belgium, Gastroenterology & Hepatology, [11] ASZ, Aalst, Belgium, Gastroenterology & Hepatology, [12] OLV Aalst, Aalst, Belgium, Gastroenterology & Hepatology, [13] AZ Maria Middelares, Ghent, Belgium, Gastroenterology & Hepatology, [14] Jessa Ziekenhuis, Hasselt, , Belgium, Gastroenterology & Hepatology, [15] AZ Sint-Lucas, Ghent, Belgium, Clinical Microbiology, [16] CHU UCL Namur, Yvoir, Belgium, Gastroenterology & Hepatology, [17] Institute of Tropical Medicine Antwerp, Antwerp, Belgium, Internal Medicine Infectious Diseases, [18] AZ Sint-Jan Brugge-Oostende, Brugge, Belgium, Medical Microbiology, [19] Hôpitaux Iris Sud, Brussels, Belgium, Gastroenterology & Hepatology, [20] CHU Brugmann, Brussels, Belgium, Gastroenterology & Hepatology, [21] CENTRE HOSPITALIER MOUSCRON, Mouscron, Belgium, Gastroenterology & Hepatology, [22] ZNA Middelheim, Antwerpen, Belgium, Gastroenterology & Hepatology, [23] AZ Nikolaas, Sint-Niklaas, Belgium, Gastroenterology & Hepatology, [24] UZGent, Gent, Belgium, Gastroenterology & Hepatology, [25] Jan Yperman Hospital, Ieper, Belgium, Gastroenterology & Hepatology, [26] GZA Sint-Vincentius ziekenhuis, Antwerpen, , Belgium, Gastroenterology & Hepatology, [27] UZBrussel, Brussel, Belgium, Gastroenterology & Hepatology, [28] CHU Saint-Pierre, Brussels, Belgium, Gastroenterology & Hepatology, [29] AZ Delta, Roeselare, Belgium, Gastroenterology & Hepatology, [30] Grand Hopital de Charleroi, Charleroi, Belgium, Gastroenterology & Hepatology

Introduction
Hepatis E Virus (HEV) infections are emerging in the Western civilization with a predominance of HEV genotype 3 (gt3). Except for immunosuppression, male gender, age older than 50 years and chronic liver disease, no correlators with clinical outcomes of a HEV gt3 infection have been identified. In Belgium, diagnosis of HEV is centralized at the National Reference Center (NRC) for Viral Hepatitis, Sciensano.

Aim
We analyzed virological factors and clinical outcomes in a nationwide cohort of HEV patients in Belgium with the aim of finding other correlators with clinical outcomes.

Methods
Demographic, clinical and biochemical parameters of HEV infections documented at the NRC Sciensano between 2010 and 2018 were collected. Serum HEV-IgM, -IgG and HEV RNA were determined by ELISA and RT qPCR. HEV was subtyped by Sanger sequencing of an ORF2 fragment. Odds ratios (OR), risk ratios (RR) and 95% confidence intervals (95% CI) were calculated using STATA.

Results
402 cases were identified. Among 300 cases with clinical data, the median age was 57 years and 69% of patients were males. HEV viremia was detected in 211 patients with a genotype identified in 177 patients. HEV gt3 infections largely predominate (93% [165/177]) with subtypes 3c (38% [67/177]) and 3f (44% [78/177]) almost equally represented. The percentage of immunocompromised patients was higher for patients infected with a virus from the clade of gt3c (achi), compared to a virus from the clade of gt3f (efg) (30% vs 16%; OR3c=2.2 [1.0-4.7] p=0.045). A similar, however non-significant trend was observed for patients with pre-existing liver cirrhosis (9.9% vs 3.4%; OR3c=3.1 [0.8-12.5]). Biochemically, patients with a HEV gt3f infection had higher ALT peak values and higher peak bilirubin values compared to patients with a HEV gt3c infection (respectively mean of 2199 vs 1528 U/L; p=0.005 and mean of 8.6 vs 4.1 mg/dl; p=0.001). In addition, patients with a HEV gt3c infection were treated more frequently in ambulatory care settings compared to patients with a HEV gt3f infection. The percentage of patients admitted to the hospital was higher for patients with a HEV gt3f infection compared to patients with a HEV gt3c infection (61% vs 36%; RR3f=1.7 [1.2-2.4] p=0.003). There were no differences between the subtypes in intensive care unit admissions (5.7%), in hospitalization durations (median of 4.0 weeks), in chronicity (18% vs 14%, RR3f=0.8 [0.4-2.0]), nor in deaths (1.4% vs 4.8%; RR3f=3.4 [0.4-30]).

Conclusions
A similar number of HEV gt3c and gt3f infections have been diagnosed in Belgium. Despite more pre-existing comorbidity in patients infected with HEV gt3c, HEV gt3f infections are associated with a more severe disease course according to laboratory values and hospitalization rates. Our nationwide analysis is the first to identify a correlation between HEV gt3 subtype and clinical outcomes.

Thursday March 5, 2020 12:10 - 12:21 CET
Room TEUN

BASL / BLIC, Session 2

12:15 CET

Inhibition of adhesiogenesis with protease inhibitors Nafamostat Mesylate, UAMC-00050, and Enoxaparin in a murine model for sepsis and peritonitis.

Authors
P. PLAEKE (1), J. DE MAN (1), A. SMET (1), I. DE MEESTER (2), K. AUGUSTYNS (3), P. JORENS (4), G. HUBENS (5), B. DE WINTER (1) / [1] University of Antwerp, , Belgium, Laboratory of Experimental Medicine and Pediatrics, [2] University of Antwerp, , Belgium, Department of Medical Biochemistry, [3] University of Antwerp, , Belgium, Department of Medicinal Chemistry, [4] Universiteit Antwerpen / Antwerp University Hospital, WILRIJK (Antwerpen), Belgium, Laboratory of Experimental Medicine and Pediatrics / Department of Intensive Care Medicine, [5] Universiteit Antwerpen / Antwerp University Hospital, WILRIJK (Antwerpen), Belgium, Antwerp Surgical Training, Anatomy and Research Centre (ASTARC) / Department of Abdominal Surgery

Introduction
Intraperitoneal adhesions following surgery or peritonitis are responsible for a wide range of complications, including bowel obstruction, abdominal pain, and even infertility. Additionally, these adhesions tend to make subsequent abdominal procedures more challenging. Proteases, involved in the coagulation and fibrinolysis, are essential in the etiopathogenesis of adhesions as they assist in the development of fibrin scaffolding. This scaffolding is the first stage of adhesions development and is required for the transition to mature, fibrous adhesions.

Aim
To modulate intraperitoneal adhesiogenesis by administering the serine protease inhibitors nafamostat mesylate (NFM), UAMC-00050 and enoxaparin in a murine sepsis and peritonitis model.

Methods
Intraperitoneal adhesions were induced in OF1 mice (Charles River, France) by caecal ligation and puncture (CLP) under ketamine-xylazine anesthesia. For this, the abdomen was opened by midline incision and the caecum was ligated at 50% of its length. Subsequently, the ligated caecum was punctured once with a 21 G needle. Sham mice underwent the same midline laparotomy without ligating or puncturing the caecum. Analgesia (buprenorphine) and fluid resuscitation were provided throughout the experiments. Wellbeing was monitored using a clinical disease score. Mice were euthanized 48 hours later and adhesions were scored based on the number of abdominal tissues involved (extent), the tenacity of the adhesions, and the time required to gain access to the ileum. This acted as an objective marker for the surgical accessibility of the abdomen. Three treatment schedules were used. In the preventive set-up (NFM, UAMC-00050), the drug was administered once during the CLP procedure. In the curative set-up (NFM), the drug was administered 3 times, starting 12 hours after the CLP procedure. Finally, in the combined preventive and curative setup (NFM, UAMC-00050, enoxaparin), the drug was administered during the CLP procedure and repeated 3 times afterwards. Statistical analysis was performed with SPSS v26 (IBM, USA), using one way ANOVA with Dunnett’s post-hoc test.

Results
The CLP procedure resulted in significantly elevated clinical disease scores (0.22 vs. 4.51, p<0.001) and significant weight loss compared to the sham procedure (-2.40% vs. -9.51%, p<0.001). No significant differences in clinical disease scores or weight loss were observed between any of the different groups that received any kind of treatment. Only one adhesion was encountered in the sham group (n=23), while the CLP procedure resulted in intraperitoneal adhesions in all vehicle-treated mice (n=43). Preventive treatment with NFM at a dose of 10 and 20 mg/kg, significantly reduced the extent of the adhesions with 36.1% and 45.8% respectively and reduced tenacity of the adhesions and the surgical access time with up to 33.9% (10 mg/kg, p<0.001) and 26.4% (20 mg/kg, p<0.001). Similar results were seen when NFM was administered in a combined preventive and curative set-up at a dose of 10 mg/kg. In contrast, the curative treatment schedule, in which NFM was administered 12 hours after the onset of CLP-induced sepsis, failed to make any difference. This indicated the first 12 hours to be crucial for the prevention of adhesions and thus a preventive dose is required to notice a beneficial effect. The protease inhibitor UAMC-00050, which has less factor Xa inhibitory activity compared to NFM, failed to reduce adhesions at any dose (1 to 5 mg/kg) and in any treatment set-up. Enoxaparin (10 mg/kg), which specific inhibits factor Xa, significantly and firmly reduced the extent and tenacity of the adhesions with 58.0% (p<0.001) and 42.5% (p<0.001) and completely normalized the time to gain access and ligate the ileum to control values.

Conclusions
Protease inhibitors significantly reduced the extent and severity of intraperitoneal adhesions under the condition that they were administered preventively and specifically targeted coagulation pathways, as demonstrated by our experiments with enoxaparin and NFM. Since these protease inhibitors should target the coagulation system, accurate titration and specification of the proteases involved are required in future studies.

Speakers

Philip Plaeke

Joris De Man

Annemieke Smet

Ingrid De Meester

Koen Augustyns

Philippe Jorens

Guy Hubens

Benedicte De Winter

Thursday March 5, 2020 12:15 - 12:30 CET
Room TIFFANY/SHAH

GIREM, Session 2

12:21 CET

Transcriptome profiling of liver biopsies before antiviral treatment start can predict HCC development 8.3 years before clinical diagnosis in chronic Hepatitis B and C patients

Authors
S. VAN HEES (1), B. CUYPERS (2), S. BOURGEOIS (3), K. KREEFFT (4), D. SPRENGERS (5), G. ROBAEYS (6), P. MEYSMAN (2), L. VONGHIA (1), P. MICHIELSEN (1), S. FRANCQUE (1), R. DE MAN (4), A. DRIESSEN (7), A. BOONSTRA (4), K. LAUKENS (2), T. VANWOLLEGHEM (1) / [1] Antwerp University Hospital, , Belgium, Department of Gastroenterology and Hepatology, [2] Antwerp University, , Belgium, Department of Mathematics and Computer Science, [3] ZNA Stuivenberg, Borgerhout, Belgium, Department of Gastroenterology and Hepatology, [4] Erasmus Medical Center, Rotterdam, Netherlands (the), Department of Gastroenterology and Hepatology, [5] GZA Antwerp, , Belgium, Department of Gastroenterology and Hepatology, [6] Hospital East-Limburg, , Belgium, Department of Gastroenterology and Hepatology, [7] Antwerp University Hospital, , Belgium, Department of Pathology

Introduction
An accurate prediction of Hepatocellular Carcinoma (HCC) development in Chronic Hepatitis B (CHB) and C (CHC) patients is currently impossible.

Aim
In this study we explored pre-antiviral treatment liver transcriptome profiles of CHB and CHC patients with and without HCC development during long-term follow-up and investigated their potential to predict future HCC development.

Methods
HCC developing cases (n = 34) were identified through retrospective chart review of all CHB and CHC patients with an available pre-antiviral treatment liver biopsy from 5 large Hepatology clinics. Cases were split in 4 subgroups based on infecting virus (HBV/HCV) and cirrhosis status (yes/no) at baseline liver biopsy. Each subgroup of cases was matched for different demographic (e.g. gender and age at biopsy) and clinical (e.g. cirrhosis at biopsy and infecting virus) factors to a group of controls without HCC development during an equal or longer follow-up time. RNA derived from baseline biopsies (total n = 72) was sequenced. Differentially Expressed Genes (DEG; FC > 1.5 and q < 0.2) were called in each subgroup and a random forest classifier was trained to predict HCC development.

Results
The total cohort consisted of 72 patients, of whom 34 developed a HCC at a median of 8.3 years after liver biopsy. Despite perfect matching for clinical and demographic characteristics, at least 452 DEG were found between cases and controls in each subgroup. Among the top 20 up- and down-regulated genes in each subgroup, 40-75 % has previously been linked to oncogenesis, underlining the biological relevance. Ingenuity Pathway Analysis showed an enrichment for the “Wnt-bèta catenin signaling” pathway in the cirrhotic CHB group and the “molecular mechanisms of cancer” pathway in the non-cirrhotic CHC group. These results strongly suggest a genetic imprint for HCC development several years before clinical diagnosis. A random forest classifier tested with leave-one-out-cross-validation was able to predict HCC development with an accuracy of 84.7 %, a Negative Predictive Value of 92.1 % and a Positive Predictive Value of 75.8 % based on the subgroup and baseline expression levels of 20 genes, of whom several have previously been linked to hepatocarcinogenesis.

Conclusions
Pre-antiviral treatment liver biopsies of chronic hepatitis B and C patients show a genetic imprint for future HCC development that allows to accurately predict HCC development 8.3 years before clinical diagnosis.

Thursday March 5, 2020 12:21 - 12:32 CET
Room TEUN

BASL / BLIC, Session 2

12:30 CET

Satellite Symposium JANSSEN

Will Treat-to-Target with early endoscopic assessment lead to better outcomes? (Preliminary) answers from the STARDUST trial of ustekinumab in Crohn's disease

Speakers

Mark Löwenberg

Floris de Voogd

JANSympo pdf

Thursday March 5, 2020 12:30 - 13:15 CET
Room TEUN

12:30 CET

Lunch

Thursday March 5, 2020 12:30 - 13:30 CET
Exhibition Area

GIREM

12:35 CET

Lunch

Thursday March 5, 2020 12:35 - 12:35 CET
Exposition Area

BASL / BLIC

13:00 CET

BeSPGHAN General Assembly

Thursday March 5, 2020 13:00 - 14:00 CET
Room SANCY

BeSPGHAN

13:00 CET

BSGIE e-Posters Session

A multinational retrospective, cohort study of patients with Buried Bumper Syndrome treated endoscopically with a novel dedicated device.

Automated polyp size estimation with deep learning reduces interobserver variability

EUS-directed transgastric intervention (EDGI) in patients with surgically altered anatomy: monocentric experience.

The Real Life Diagnostic Accuracy of Regular Arrangement of Collecting Venules in Detecting H.pylori-negative Patients.

What matters for your patient during gastrointestinal endoscopy: an exploratory research on patient experience and satisfaction.

ESD for oesophageal squamous cell carcinoma: a European tertiary centre prospectively collected experience.

A new 12-French plastic stent may be an alternative in unresectable distal malignant biliary obstruction.

Obstructive complications related to the use of self-expandable metallic stent for the treatment of distal biliary stricture.

We cannot teach our endoscopists to accurately size polyps: a follow-up on the Oostende polyp sizing study.

Risk Stratification of patients in ER presenting with acute upper gastrointestinal bleed using extended Glasgow Blatchford score.

Same day propofol sedation does not impair the completion rate of capsule endoscopy.

Partially covered metallic stent for treatment of gastric leak after sleeve gastrectomy: a retrospective monocentric experience of 760 consecutives surgical procedures.

Radiofrequency ablation of Barrett esophagus: post reimbursement experience of a tertiary Belgian hospital.

Thursday March 5, 2020 13:00 - 14:00 CET
e-Posters Area

BSGIE, e-Posters Tour

13:15 CET

Satellite Symposium GILEAD

THE COUNTDOWN TOWARDS HEP C ELIMINATION HAS STARTED! JOIN US FOR A SPICY DEBATE AND VOTE UPFRONT AT THE GILEAD BOOTH.

Speakers

Marc Van Ranst

Stefan Bratovanov

Werner De Keyzer

Astrid Marot

Mike Cool

Marie-Eve Janssen

Tessa Windelinckx

Wim Verlinden

GILEAD A5 Symposium invitation insert (1) pdf

Thursday March 5, 2020 13:15 - 14:00 CET
Room TEUN

BASL / BLIC

13:30 CET

The gut-liver axis in health and disease – prospects of understanding and targeting macrophages.

Post induction infliximab trough levels predict long-term endoscopic remission in paediatric patients with Inflammatory Bowel Disease.

Authors
K. VAN HOEVE (1), E. DREESEN (2), I. HOFFMAN (3), M. FERRANTE (4), S. VERMEIRE (4) / [1] University Hospitals Leuven, Leuven, Belgium, Department of Paediatric gastroenterology & Hepatology & Nutrition, [2] Katholieke Universiteit Leuven, Leuven, Belgium, Laboratory for Therapeutic and Diagnostic Antibodies, Department of Pharmaceutical and Pharmacological Sciences, [3] University Hospitals Leuven, , Belgium, Department of Paediatric gastroenterology & Hepatology & Nutrition, [4] University Hospitals Leuven, , Belgium, Department of Gastroenterology & Hepatology

Introduction
Although higher infliximab (IFX) trough levels (TL) have been associated with better outcomes, the ideal predictive sampling time and cut-points to achieve endoscopic remission remains unclear in children with inflammatory bowel disease (IBD).

Aim
Therefore, we evaluated the pharmacokinetics of IFX during induction to predict long-term outcome of IFX.

Methods
All children age <18 years with Crohn’s disease (CD) or ulcerative colitis (UC) starting IFX therapy for active luminal disease from May 2017 till May 2019 were enrolled. Only IFX naïve patients were consecutive included and followed-up prospectively six months after initiation of IFX therapy. Exclusion criteria were IFX exposed patients, absence of endoscopic activity or a patient’s refusal to participate. Patients were treated with standard intravenous IFX 5 mg/kg (2h infusion) at weeks 0, 2 and 6 followed by a maintenance therapy starting at week 12. IFX serum levels were measured by Ridascreen IFX Monitoring ELISA (TL at week 2-6-12, peak at week 0-2-6 and intermediate at week 1-4). IFX serum levels and cumulative drug exposure (area under the curve (AUC) till week 12) were correlated with outcome at month six. Clinical remission was defined as PUCAI/PCDAI <10, biochemical remission as CRP ≤5 mg/L + ESR ≤20 mm/h, endoscopic remission as SES-CD <3 or Mayo endoscopic sub-score =0 and deep remission if both clinical + endoscopic remission. Results were analysed using Mann-Whitney U-test (presented as median [interquartile range]).

Results
A total of 252 serum induction levels were included from 32 patients (20 CD and 12 UC; 38% male; median age at start of IFX 13.8 years [11.3-14.9]; 84% on concomitant thiopurines). Clinical remission was achieved in 24 (75%) patients and 18 (56%) were in endoscopic remission (all in deep remission) at month six. Endoscopic remission at month six was associated with significantly higher median IFX serum levels at week 4 (38.8 µg/mL [24.3–46.0] vs 23.5 µg/mL [10.5–36.6], p=0.017), at week 6 (19.9 µg/mL [10.1-26.3] vs 11.1 µg/mL [3.7–19.9], p=0.031), at week 12 (9.6 µg/mL [5.5–11.9] vs 3.5 µg/mL [2.7–7.2], p=0.004) and higher cumulative drug exposure during induction (AUC week 0-12: 4574.7 µg*day/mL [3783.0–5160.8] vs 3722.9 µg*day/mL [3102.2–3991.9], p=0.008). Median IFX TL at week 12 were significantly higher in children with clinical remission (8.6 µg/mL [5.1–12.0] vs 4.3 µg/mL [3.1–5.9], p=0.033), but not for biological remission (6.7 µg/mL [4.0-12.0] vs 4.3 µg/mL [1.2–7.2], p=0.250) at month six. Biological remission was only evaluated in patients with elevated biomarkers at baseline (n= 23/32; 71.9%). However, early and persistent normalization of baseline biomarkers (time between IFX initiation and moment of persistent CRP and ESR normalisation) correlated well with the week 12 TL (rs= -0.522; p= 0.011). ROC analysis identified an IFX TL at week 12 ≥ 5.0 µg/mL and an AUC week 0-12 ≥ 4056.0 µg*day/mL as minimal target to achieve endoscopic remission at month six (AUROC: 0.796 [95%CI: 0.62-0.97] and AUROC: 0.778 [95%CI: 0.61-0.94] respectively). Height, haemoglobin and PCDAI score at start of IFX therapy, significantly correlated with week 12 IFX TL.

Conclusions
Adequate IFX exposure during induction in paediatric IBD patients is associated with significantly better clinical, endoscopic and deep remission rates at month six. Model-informed precision dosing can assist physicians to achieve optimal exposure during induction more precisely (and rapidly) what is essential for an optimal outcome.

Speakers

Karen van Hoeve

Erwin Dreesen

Ilse Hoffman

Marc Ferrante

Séverine Vermeire

Thursday March 5, 2020 14:00 - 14:15 CET
Room SANCY

BeSPGHAN

14:10 CET

Do patients with NAFLD have an increased incidence of cardiovascular complications after liver transplantation?

Authors
J. VAN HERCK (1), L. VERBEKE (2), J. VERBEEK (3), C. VERSLYPE (3), W. LALEMAN (3), H. VAN MALENSTEIN (3), D. CASSIMAN (3), S. VAN DER MERWE (3), I. JOCHMANS (4), M. SAINZ BARRIGA (4), D. MONBALIU (4), J. PIRENNE (4), F. NEVENS (3) / [1] KU Leuven, , Belgium, Medicine, [2] AZ Sint-Maarten, Mechelen, Belgium, Gastroenterology, [3] UZ Leuven, Leuven, Belgium, Gastroenterology and Hepatology, [4] UZ Leuven, Leuven, Belgium, Abdominal Transplantation Surgery

Introduction
Patients with non-alcoholic fatty liver disease (NAFLD) have several risk factors for cardiovascular morbidity. Post-LTX immunosuppression increases cardiovascular mortality.

Aim
We investigated the post-LTX morbidity and mortality in pts transplanted for NAFLD.

Methods
The study population consisted of 232 LTX pts: 112 NAFLD pts and a control group of 120 hepatitis C (HCV) pts. Data collection consisted of metabolic risk factors, recurrence of NAFLD, cardiovascular diseases (coronary artery disease, stroke, atrial fibrillation, heart failure) and death.

Results
At the moment of LTX there were no differences in age, gender and pack years of smoking. NAFLD patients were slightly older (63 vs 61 y), had a higher MELD (16 vs 13) and fewer HCC (46% vs 63%). NAFLD became only recently a frequent indication for LTX and the post-LTX follow-up was shorter (median 6 vs 13 y). NAFLD pts had pre-LTX higher BMI (30 vs 26), more diabetes (DM) (64% vs 28 %), arterial hypertension (70% vs 25%) and dyslipidemia (33% vs 6%). They had a higher pre-LTX total cardiovascular morbidity (24% vs 12%). There was no difference in the 6 wks postoperative mortality (1,7% vs 2,5%).Differences during post-LTX follow-up were: BMI (29,5 vs 25,5), DM (73% vs 42%) and dyslipidemia (57% vs 35%). The incidence of post-LTX NAFLD was significantly higher in NAFLD pts (43% vs 8%)(p < 0,0001). The cardiovascular morbidity was slightly higher in the NAFLD group (12.8 vs 9.3 % at 5 y, p=0,03), although there was no difference in the overall survival between the 2 groups, both in the total group nor in pts without HCC at baseline.

Conclusions
Cirrhosis due to NAFLD is a rapidly growing indication for LTX. These pts have a high pre- and postoperative cardiovascular risk profile. However, there is no difference in the immediate postoperative mortality. There is an important recurrence rate of NAFLD after LTX. At 5 y there is a slightly increased cardiovascular morbidity but this did not result in a higher overall mortality.

Thursday March 5, 2020 14:10 - 14:20 CET
Room TEUN

BASL / BLIC, Session 3

14:12 CET

A prospective, multi-center validation study for automated polyp detection as a second observer.

Authors
T. EELBODE (1), C. HASSAN (2), H. NEUMANN (3), I. DEMEDTS (4), P. SINONQUEL (5), P. ROELANDT (4), C. CAMPS (4), E. CORON (6), P. BHANDARI (7), O. PECH (8), H. WILLEKENS (4), F. MAES (9), R. BISSCHOPS (4) / [1] KU Leuven, , Belgium, Medical Imaging Research Center, [2] Nuovo Regina Margherita Hospital, Rome, Italy, Endoscopy, [3] University Medical Center Mainz, Mainz, Germany, First Medical Department, [4] KU Leuven, , Belgium, Gastroenterology and hepatology, [5] KU Leuven, , Belgium, TARGID, [6] CHU Nantes, , France, Hepatogastroenterology, [7] Portsmouth Hospital, Portsmouth, United Kingdom (the), Solent Centre for Digestive Diseases, [8] Krankenhaus Barmherzige Brüder Regensburg, Regensburg, Germany, Gastroenterology and Interventional Endoscopy, [9] KU Leuven, , Belgium, Medical Imaging Research Center, ESAT/PSI

Introduction
Last year, we developed and presented a deep learning framework for automated polyp detection and localization. In contrast to classical CNN systems, our system uses temporal information or ‘memory cells’ enabling more accurate and confident predictions. Very little evidence is currently available on the performance of AI systems for polyp detection in real clinical practice. Additionally, studies have shown that 25% of all polyps are missed during colonoscopy, but it is unknown how many of these misses are due to failure of polyp recognition and how many due to suboptimal mucosal exposure.

Aim
The aim of this study is to prospectively validate our system in a multi-center clinical setting in order to obtain an estimate for power calculation for future non-inferiority or superiority trial design, to assess preliminary performance in comparison to experienced endoscopists and to assess miss rate due to polyp recognition failure.

Methods
Our AI system was trained with 131.619 semi-automatically annotated video frames from 825 unique polyps from 206 patients. This system was implemented in a module that can be placed bedside during the colonoscopy procedure. For this study, an experienced endoscopist (all with ADR>35%) does not see the output of the system while a second human observer looks at the AI-enhanced screen. We define four different situations that can occur during the procedure: (1) Obvious false positive - the system gives an obviously false detection (e.g. stool, forceps, air bubble, …). These are nuisances caused by the system, but would never cause the endoscopist to take action and are not communicated to the endoscopist. (2) Other positives - a positive prediction that could indicate a missed polyp. When this location disappears from the image, the second observer asks the endoscopist to go back and inspect that location. If there is a polyp, this is an additional detection by the AI system. (3) False negative - a polyp was found by the endoscopist, but the AI system never indicated this location. (4) True positive – the system and endoscopist found the same polyp.

Results
Currently, 99/300 patients are included from three European centers (Leuven, Mainz and Rome). In total 199 polyps were found of which 181 were detected by both the endoscopist and the system. There were 13 polyps that were false negatives (all diminutive) and 5 additional detections made by the system. This corresponds to a 3% increase in polyps-per-colonoscopy for the combination of endoscopist with AI support. A very low average of 1 false positive per minute was recorded.

Conclusions
The interim analysis shows promising results for the clinical validation of a newly developed AI system that was developed in a unique way and different from most existing tools. These exploratory studies are of paramount importance to sufficiently power future trials and to estimate the optimal design of a trial (non-inferiority versus superiority). Our preliminary data suggest that the actual miss rate due to failure of polyp recognition is probably lower than expected and this might affect the design of future studies. We plan to have included 300 patients by the time of the BWGE 2020 and present the full results of this trial.

Thursday March 5, 2020 14:12 - 14:24 CET
Room LIJN

BSGIE, Session 1

14:15 CET

Detection of Helicobacter pylori in children and adolescents: diagnosis and treatment in Jessa Hospital between 2016 and 2019.

Authors
P. HILKENS (1), K. MAGERMAN (1), E. JANSSENS (2), L. WAUMANS (1), R. CARTUYVELS (1), P. ALLIET (2) / [1] Jessa Hospital, Hasselt, Belgium, Clinical laboratory, [2] Jessa Hospital, Hasselt, Belgium, Dept of Paediatrics

Introduction
Recent studies regarding the epidemiology of Helicobacter pylori indicate a significant variation in its worldwide prevalence, which is often associated with socioeconomic status and hygiene standards. The increasing resistance of H. pylori against current antimicrobial therapies and the subsequent failure of infection eradication are major challenges in the management of H. pylori infections in children and adolescents. Current ESPGHAN/NASPGHAN guidelines state that invasive diagnostic testing, i.e. bacterial cultures or histopathology combined with additional (molecular) assays on tissue biopsies, is only recommended when effective treatment can be offered. Furthermore, strain-specific antimicrobial sensitivity needs to be determined in order to provide a tailor-made therapy that will increase the likelihood of successful infection eradication.

Aim
The goal of this study was to obtain more insight into patient demographics of children and adolescents diagnosed with H. pylori infection according to the most recent ESPGHAN/NASPGHAN guidelines. Furthermore, the success of antimicrobial therapy will also be evaluated.

Methods
A retrospective analysis of patient data of children and adolescents diagnosed with and treated for H. pylori infection in Jessa Hospital between 2016 and 2019 was performed.

Results
Between 2016 and 2019, 508 gastric biopsies from paediatric patients (ages 1 to 16 years old) were taken in order to determine the presence of H. pylori by means of bacterial culture combined with a rapid urease test. Bacterial cultures were positive for H. pylori in 5% of these patients. Further analysis indicated that 77% of these positively diagnosed patients had a foreign background and 15% of them had a family history of peptic ulcers. All of the patients complained of abdominal pain and nausea. Nodular gastritis was present in 65% of the cases, as shown by endoscopy. Antimicrobial susceptibility testing pointed out resistance against metronidazole in 20% of these patients, while 8% showed resistance against either amoxicillin or levofloxacin. Given the susceptibility of all tested strains for clarithromycin, all of the culture-positive children and adolescents were treated with a clarithromycin-containing regimen, in accordance with the current ESPGHAN/NASPGHAN guidelines. More specifically, these patients were treated with triple therapy, i.e. 4 weeks of omeprazole and 2 weeks of amoxicillin/clarithromycin. Treatment success was evaluated in 82% of the cases, either with an urea breath test or endoscopy when an urea breath test was difficult to perform. In 17% of these patients, the infection was not successfully eradicated and an additional treatment regimen was started. 18% of the culture-positive and treated patients did not respond to any of the recommended follow-up appointments.

Conclusions
Retrospective analysis pointed out a relatively low prevalence of H. pylori infection in Jessa Hospital between 2016 and 2019. Diagnosis was based on a positive bacterial culture combined with a rapid urease test. The determination of antimicrobial susceptibility allowed clinicians to start a tailor-made treatment regimen which led to successful infection eradication in 83% of the evaluated patients. These data underline the importance of patient-specific therapy and follow-up, as recommended by the most recent ESPGHAN/NASPGHAN guidelines.

Speakers

Petra Hilkens

Koen Magerman

Elke Janssens

Luc Waumans

Reinoud Cartuyvels

Philippe Alliet

Thursday March 5, 2020 14:15 - 14:30 CET
Room SANCY

BeSPGHAN

14:15 CET

Crosstalk between monocyte-derived macrophages and enteric glial cell Is essential for tissue repair and recovery of gastrointestinal transit after intestinal inflammation.

Authors
S. IBIZA (1), M. STAKENBORG (2), S. ABDU RAHIMAN (1), V. DE SIMONE (2), B. KE (2), Q. WU (2), D. PIROTTIN (3), T. MARICHAL (4), G. MATTEOLI (2) / [1] KUL, , Belgium, Targid, Department of Chronic Diseases, Metabolism and Ageing, [2] KU Leuven, , Belgium, Targid, Department of Chronic Diseases, Metabolism and Ageing, [3] University of Liege, Liège, Belgium, Department of Functional Sciences(DSF), [4] University of Liege, GIGA-R, Liège, Belgium, GIGA-R,

Introduction
Patients undergoing open abdominal surgery often suffer from a transient episode of intestinal dysmotility referred to as postoperative Ileus (POI). Intestinal manipulation (IM) during the surgery evokes tissue damage and consequently an inflammatory response leading to impaired gastrointestinal motility. Recently our lab revealed a critical role for monocyte-derived macrophages (Mφs) in supporting neuromuscular function and restoring intestinal homeostasis after surgical trauma. Blocking monocytes recruitment to the muscularis externa (ME) after IM increased neutrophil-mediated immunopathology and prolong the clinical outcome of IM. However, it is yet not clear how monocytes sense environmental cues and differentiate into pro-resolving Mφs with neurotrophic functions.

Aim
The main goal of our project is to clarify how muscularis externa specific cues promote differentiation of monocytes sense and respond to the environmental cues during Intestinal Manipulation. To answer these questions, we have employed state of the art single cell RNA sequencing (sc-RNA seq) of different subset of intestinal myeloid cells at the steady state, during the acute and resolution phase of IM. In addition, interaction between enteric glial cells (EGCs) and monocytes was studied both in vitro and in vivo.

Methods
Wild-type female mice (WT; C57BL/6J) were subjected to IM. The severity of IM was evaluated by assessing gastro-intestinal transit and recruited of immune cells in ME by flow cytometry analysis. Immune cells infiltrating in the ME of day 0, 1 and 3 after IM were isolated by cell sorting analyzed and was performed Sc-RNA seq on the Chromium Single Cell Gene Expression Solution (10x Genomics). The 'Seurat' R package was used for graph-based clustering and visualizations.'SingleR' package was used for immune cell type annotations. Trajectory analysis was performed with 'Monocle2'. Gene set enrichment analysis (GSEA) was done on the average expression of the cell clusters using java GSEA Desktop Application. To study the possible anti-inflammatory effect of EGC-released factors, primary murine embryonic EGCs were co-cultured with bone marrow or monocytes.

Results
SSc-RNAseq of immune cells from the naive, inflamed and resolving muscularis revealed a complex immune cell landscape during different phases of POI. In steady state, muscularis resident Mφs were the main important cells present. However, at day 1 post IM we found mainly recruitment of monocytes and neutrophils, and interestingly at day 3 post IM most of the infiltrated myeloid cells were cleared as the inflammation resolves and only resident Mφs-like were present. Trajectory analysis revealed possible differentiation trajectory of classical monocytes to give rise to mature Mφs via multiple intermediate phenotypes. During this differentiation, the monocyte derived Ly6C low and MHCII low Mφs express the major pro-resolving Mφ factor Arginase 1, and are enriched by several potent neurotrophic factors. Interestingly, IM induced the production of the monocyte chemoattractant CCL2 by EGC, suggesting crosstalk between this cells and monocytes. In vivo imaging revealed recruitment of monocytes in close proximity to EGCs. In vitro, EGCs were able to promote differentiation of bone marrow and intestinal monocytes into pro-resolving Mφs as proven by induction of Arginase1, MRC-1, MSR1 and IL10. In parallel, EGC-secreted factors reduced the expression of pro-inflammatory cytokines such as IL-12 and IL-6 in monocytes stimulated with LPS.

Conclusions
Our study reveals a critical role for monocyte-derived Mφs in restoring intestinal homeostasis after surgical trauma. EGC seems to exert a critical function in attracting and modulating monocytes both in vivo and in vitro. In particular, enteric glial secreted factors promote monocyte differentiation into arginase 1-expressing Mφs with essential tissue repair capability essential in restoring intestinal homeostasis and supporting neuromuscular function after surgical trauma.

Speakers

Sales Ibiza

Michelle STAKENBORG

Saeed ABDU RAHIMAN

Veronica DE SIMONE

Bo Jun KE

Qin Wu

D PIROTTIN

Thomas MARICHAL

Gianluca Matteoli

Thursday March 5, 2020 14:15 - 14:30 CET
Room TIFFANY/SHAH

GIREM, Session 3

14:20 CET

Alcoholic liver disease and liver transplantation in patients with prior bariatric surgery

Authors
L. STROOBANT (1), A. VANLANDER (2), F. BERREVOET (2), X. VERHELST (1), Y. VAN NIEUWENHOVE (3), X. ROGIERS (2), H. VAN VLIERBERGHE (1), A. GEERTS (1), S. LEFERE (1) / [1] Ghent University, Ghent, Belgium, Gastroenterology and Hepatology, Hepatology Research Unit, [2] Ghent University, Ghent, Belgium, General and Hepatobiliary Surgery, [3] Ghent University, Ghent, Belgium, Gastrointestinal Surgery

Introduction
Bariatric surgery (BS) is an effective therapeutic option for severe obesity, yet recent studies have indicated that patients with prior BS, mainly Roux-en-Y gastric bypass, are at increased risk for developing alcohol use disorder. However, whether these patients also develop alcoholic liver disease (ALD), with progression to end-stage liver disease and a need for liver transplantation (LT), has not been described.

Aim
Investigate the occurence and severity of ALD following BS in a cohort of patients undergoing LT evaluation.

Methods
We performed a single-center retrospective cohort study on patients listed for LT due to ALD at the Ghent University Hospital between 2008 and 2018. We compared the clinical, demographic and biochemical characteristics as well as survival of patients with and without a history of BS. Patients with concurrent liver diseases, as well as patients who underwent weight loss surgery less than one year before diagnosis of liver disease were excluded.

Results
We included 11 patients with and 177 patients without a history of BS in this analysis. Liver cirrhosis was diagnosed after a median of 7.4 years following weight loss surgery. BS patients were younger (median 45 versus 60 years, P<0.0001) with a female predominance (72.7% versus 22.0%, P<0.001). Notably, the liver function was impaired to a greater degree in those having undergone BS, as evidenced by a higher MELD score (median 26 versus 17, P = 0.0003), INR (2.30 versus 1.51, P = 0.001) and serum bilirubin (4.90 versus 2.48, P = 0.053). The timeframe between diagnosis, listing and LT was significantly shorter in patients with prior BS. Conversely, hepatocellular carcinoma was less prevalent (9.1% versus 51.1%, P=0.007). After transplantation, the incidence of postoperative complications and 3-year survival rate (90% (95%CI 71.4%-100%) in BS patients versus 83.7% (95%CI 77.6%-89.8%) in the concurrent cohort, P=0.274) were similar. A sensitivity analysis showed that neither exclusion of patients with HCC nor matching by age and gender affected the main results. Similarly, the type of BS surgery (6 out of 11 patients had undergone a Roux-en-Y gastric bypass) had no impact on the main study variables.

Conclusions
Alcohol use disorder after BS can progress to end-stage liver disease. These patients were younger and developed more acutely decompensated disease than those without prior BS. Survival after LT is comparable to ALD patients without a history of BS. These results urge further study in this area.

Speakers

Lenka Stroobant

Aude Vanlander

Frederik Berrevoet

Xavier VERHELST

Yves Van Nieuwenhove

Xavier Rogiers

Hans Van Vlierberghe

Anja Geerts

Sander Lefere

Thursday March 5, 2020 14:20 - 14:30 CET
Room TEUN

BASL / BLIC, Session 3

14:24 CET

The incremental benefit of dye-based chromoendoscopy as compared to high-definition white light and virtual chromoendoscopy for lesion assessment and prediction of SMI.

Authors
M. SIDHU (1), D. TATE (2), M. BOURKE (1) / [1] Westmead Hospital, , Australia, Gastroenterology and Hepatology, [2] UZGent, Gent, Belgium, Gastroenterology

Introduction
Analysis of the surface pit pattern (SPP), of large (>/=20mm) laterally spreading colonic lesions (LSL) can help predict the risk of submucosal invasion (SMI) and identify lesions not suitable for piecemeal endoscopic mucosal resection (EMR). Expert opinion mandates the use of dye-based chromoendoscopy for a reliable assessment of SPP. However, in the era of advanced optics the utility of high definition white light (HDWL) combined with virtual chromoendoscopy (VC) for lesion assessment remains unknown.

Aim
We sought to assess the incremental benefit of dye-based chromoendoscopy in addition to HDWL plus VC for the assessment of SPP and prediction of SMI in colonic LSL referred for EMR.

Methods
A prospective observational study of consecutive lesions referred for EMR at a single tertiary referral centre was performed (NCT03506321). Prior to resection all lesions were assessed for the following surface features; SPP as per the Kudo classification and an area of demarcation [where a regular neoplastic pit pattern (Kudo III/IV) became disordered (Kudo V)], initially performed using HDWL + VC [Narrow band imaging (NBI), Olympus, Tokyo, Japan)] by two trained independent blinded observers. The results were recorded by a third independent observer. Thereafter, indigo-carmine (0.2%) was sprayed directly onto the lesion surface and a repeat assessment performed by the same blinded observers. Overall inter-observer agreement was calculated, and significance reported using kappa co-efficient. Specific institutional review board approval was sought for this study.

Results
Over 22 months to September 2019, 205 consecutive LSL in 205 patients (50.7% – male) were enrolled. Median lesion size was 38mm (IQR: 30-50mm), 46.8% were situated in the right colon. The overall rate of SMI was 9.2% (19/205). Presence of a demarcated area on the lesion surface for all lesions had a negative predictive value (NPV) of [95.1%, 95%CI (90.5-97.6)] for predicting SMI at histology. There was no incremental benefit from the addition of dye-based chromoendoscopy [NPV 94.6%, 95%CI (90.0-97.3)]. 23/205 (11.2%) LSL contained a demarcated area with HDWL plus VC and 20/205 with addition of dye-based chromoendoscopy. In addition, there was a high rate of inter-observer agreement as to the presence of a demarcated area between the two blinded observers, independent of whether dye-based chromoendoscopy was used; kappa co-efficient (k) 0.98 (SE – 0.03) with HDWL plus VC and k 0.96 (SE – 0.03) with the addition of dye-based chromoendoscopy.

Conclusions
The absence of a demarcated area (where a regular neoplastic pit- pattern becomes disordered) within LSL is strongly predictive for the absence of submucosal invasion histologically. It can be determined using high definition white light and virtual chromoendoscopy without the need for dye-based chromoendoscopy and has a high rate of interobserver agreement amongst experts.

Speakers

Mayenaaz Sidhu

David Tate

Michael Bourke

Thursday March 5, 2020 14:24 - 14:36 CET
Room LIJN

BSGIE, Session 1

14:30 CET

Efficacy of enteroscopy-assisted ERCP in liver transplant patients with Roux-en-Y reconstruction and suspected bile duct pathology.

Authors
T. MOREELS (1), P. DEPREZ (1), G. DAHLQVIST (1), B. DELIRE (1), L. COUBEAU (2), O. CICCARELLI (2), E. BONACCORSI RIANI (2), P. GOFFETTE (3), E. SOKAL (4), H. PIESSEVAUX (1) / [1] Cliniques universitaires Saint-Luc, Brussels, Belgium, Hépato-Gastroentérologie, [2] Cliniques universitaires Saint-Luc, Brussels, Belgium, Transplantation abdominale, [3] Cliniques universitaires Saint-Luc, Brussels, Belgium, Radiologie, [4] Cliniques universitaires Saint-Luc, Brussels, Belgium, Gastroentérologie & Hépatologie Pédiatrique

Introduction
Biliary complications after liver transplantation are frequently dealt with by means of endoscopic retrograde cholangiopancreatograpy (ERCP) using a duodenoscope. However, when the bile duct is anastomosed on a Roux-en-Y jejunal limb, the biliary system is out of reach for conventional ERCP, and it is accessed usually via percutaneous transhepatic cholangiography (PTC) or surgery.

Aim
We retrospectively studied the feasibility of enteroscopy-assisted ERCP to evaluate and treat biliary complications in liver transplant patients with Roux-en-Y reconstruction.

Methods
Between 2016 and 2019 all enteroscopy-assisted ERCP procedures in liver transplant patients were analysed for indications and ERCP technical success and complication rates. Clinical success was measured by the evolution of liver function tests (without other interventions). Enteroscopy-assisted ERCP was performed using different types of single-balloon enteroscopes (SBE).

Results
A total of 32 patients (25 males) with a mean age of 42±3 years (range 16-81) underwent 51 enteroscopy-assisted ERCP procedures. Indications were suspicion of anastomotic stricture (53%), cholangitis (31%), bile duct stones (10%), biliary leak (3%) and sepsis of unknown origin (3%). Technical ERCP success rate per patient was 81.25% (26/32). Failure was due to inability to reach the hepaticojejunal anastomosis. ERCP was normal in 10/26 (39%), confirmed the anastomotic stricture in 9/26 (35%), bile duct stones in 5/26 (19%) and biliary leak and an indwelling metallic stent both in 1/26 (4%). Biliary endoscopic interventions: balloon dilatation (6-9 mm), plastic stent insertion (4-7 Fr), stone extraction, bile duct biopsy and direct cholangioscopy in 1 to 6 ERCP procedures per patient with a median number of 1 procedure. Only minor adverse events (self-limiting cholangitis) were encountered in 4/32 patients (12,5%). Of all 51 ERCP procedures, 49% were considered easy, 27% were difficult or very difficult (8%) and 17% were impossible. Technical success rate was highest when the prototype XSIF-180JY SBE was used (100% for 14 procedures) and lowest with the commercially available SIF-Q180 SBE (50% for 6 procedures). Clinical success of therapeutic ERCP was measured by the evolution of biliary liver function tests before the start of the ERCP procedure, 1 day after and 30 days after the last ERCP procedure. There was a significant decrease in gamma-GT serum levels (345±90 U/L before, 257±73 U/L after and 146±27 U/L after 30 days, p=0.023) and alkaline phosphatase levels (337±70 U/L before, 343±89 U/L after and 198±53 U/L after 30 days, p=0.044), whereas the decrease in bilirubine serum levels was not significant.

Conclusions
Endoscopic evaluation of the bile duct system is feasible and safe using enteroscopy-assisted ERCP in liver transplant patients with Roux-en-Y reconstruction. It allows close examination of the hepaticojejunostomy and the intrahepatic bile ducts, and endoscopic therapy leads to clinical improvement of liver function tests. Enteroscopy-assisted ERCP may be considered as an alternative to PTC to evaluate and treat the biliary system in these patients.

Thursday March 5, 2020 14:30 - 14:40 CET
Room TEUN

BASL / BLIC, Session 3

14:30 CET

Achalasia or pseudo-achalasia in a 2-year-old boy

Authors
P. DE BRUYNE (1), S. THEUNS-VALKS (2), A. MUBARAK (3), L. DE RIDDER (1), B. DE KONING (1), J. ESCHER (1) / [1] Sophia Children's Hospital - Erasmus MC Rotterdam, Rotterdam, Netherlands (the), Paediatric Gastroenterology, [2] Albert Schweitzer Hospital, Dordrecht, Netherlands (the), Paediatrics, [3] Sophia Children's Hospital - Erasmus MC Rotterdam, Rotterdam, Netherlands (the), Paediatrics
We present the case of a 2,5 year old boy. At the age of 20 months, he presented with feeding problems. Barium swallowing radiographic study showed signs of achalasia, which was confirmed by esophageal manometry. Treatment with endoscopic balloon dilatation of the lower esophageal sphincter was unsuccessful and was followed by a peroral endoscopic myotomy (POEM). After this procedure, feedings problems unfortunately did not approve and while waiting for a Heller myotomy, he continued to be fed through a nasogastric tube. Four months after the POEM, the boy presented with sudden icterus and itch. Further investigations showed cholestasis caused by obstruction of bile ducts by a surrounding tumour. The tumour turned out to be an inflammatory myofibroblastic tumour (IMT) and the patient is currently treated with immunotherapy. In retrospect, the question is raised whether the feeding problems of this boy are caused by achalasia or by a pseudo-achalasia associated to the tumour.

Speakers

Pauline De Bruyne

Sabine Theuns-Valks

Amani Mubarak

Lissy de Ridder

Barbara de Koning

J.C. Escher

Thursday March 5, 2020 14:30 - 14:45 CET
Room SANCY

BeSPGHAN

14:30 CET

Role of bitter taste receptors on innate immunity in jejunal crypts from lean and obese subjects.

Authors
K. LISZT (1), Q. WANG (1), A. SEGERS (1), L. CEULEMANS (2), B. VAN DER SCHUEREN (3), M. LANNOO (4), D. INGE (1) / [1] KU Leuven, , Belgium, Gut Peptide Research Lab, Targid, [2] University Hospitals Leuven, , Belgium, Department of Abdominal Surgery and Transplant Coordination, [3] University Hospitals Leuven, , Belgium, Clinical and Experimental Endocrinology, [4] University Hospitals Leuven, , Belgium, Department of Abdominal Surgery

Introduction
Bitter is an aversive taste perceived on the tongue, which acts as the first defense mechanism to protect our body against the ingestion of potentially poisonous compounds. Bitter taste is detected by around 25 subtypes of the taste receptor type 2 family (TAS2Rs) in humans. These receptors are expressed at several extra-oral sites of the human body including the gastrointestinal tract. Activation of TAS2Rs in human sinonasal cells induces the secretion of antimicrobial peptides. Since, in a knock-in mouse strain the expression of a TAS2R in Paneth cells and goblet cells has been demonstrated, we hypothesized that activation of TAS2Rs in the gut epithelium may trigger similar effects. In addition, since obesity affects Paneth cell function and TAS2R expression we wanted to investigate whether these mechanisms are altered in obesity.

Aim
This study aimed to investigate the effect of bitter compounds on innate immune factors in jejunal crypts from lean and obese subjects and their potency to induce the killing of intestinal bacteria as E. coli.

Methods
Isolated crypts from the jejunum of lean multi-organ donors (BMI: 23.9 ± 1.1 kg/m2, n=9) and obese patients (BMI: 39.8 ± 0.7 kg/m2, n=25) undergoing Roux-en-Y gastric bypass surgery were treated with aloin and denatonium benzoate (DB) and their effect on the mRNA expression of mucins (MUC2, MUC13), α-defensins (DEFA5, DEFA6) and β-defensins (DEFB1, DEFB4A) was measured by RT-qPCR. To quantify the release of anti-microbial peptides, immunofluorescence staining against α-defensin 5 and 6, and lysozyme were performed after DB treatment. The effect of the cell culture supernatants of crypts stimulated with bitter agonists (synthetic, natural, and quorum signaling molecules) on E.coli growth was investigated by counting the number of colony forming units (CFU).

Results
Obesity did not alter basal mRNA expression of the measured innate immune markers. DB treatment for 4h decreased in a concentration-dependent manner DEFA5 (P<0.05) and DEFA6 (P<0.05) mRNA expression in crypts of lean and obese subjects. In addition, DB treatment decreased (P<0.05) MUC13 and DEFB1, but increased (P<0.05) MUC2 mRNA expression in crypts of obese subjects only. One TAS2R that is targeted by DB and aloin, TAS2R43, is not present in 33% of the world population due to a deletion polymorphism. DB (1 mM) and aloin (30 µM) reduced (P<0.05) DEFA6 mRNA expression by 43±18% and 34±15%, respectively, in obese patients with but not in those without TAS2R43. The effect of DB (-36±13%) on DEFA5 expression was independent of TAS2R43. DB caused an acute release of α-defensin 5 (P<0.05) and lysozyme (P<0.05) in obese but not in lean subjects. The supernatant of DB (0.5 mM) stimulated crypts did not affect E. coli growth. However, the bacterial quorum sensing molecule, C12 acyl homoserine lactone (25 µM), induced an inhibition of E.coli growth by 67±26% (P<0.001) in jejunal crypts, while the natural bitter compounds aloin and quinine (0.1 mM) enhanced (P<0.05) E.coli growth.

Conclusions
Bitter agonists regulate the expression of some innate immune factors in the human jejunum with a higher sensitivity in obese than in lean subjects. Bitter agonists have opposite effects on E.coli growth indicating that they do not only induce the release of antimicrobial peptides but also affect the release of molecules (e.g. mucins) that stimulate bacterial growth. Funded by FWO postdoc fellowship

Speakers

Kathrin Liszt

Qiaoling Wang

Anneleen Segers

Laurens J. Ceulemans

Bart Van Der Schueren

Matthias Lannoo

Depoortere Inge

Thursday March 5, 2020 14:30 - 14:45 CET
Room TIFFANY/SHAH

GIREM, Session 3

14:36 CET

Mucosal capillary pattern recognition based on automated image analysis during endoscopy accurately detects histological remission in ulcerative colitis.

Authors
P. BOSSUYT (1), G. DE HERTOGH (2), T. EELBODE (3), S. VERMEIRE (4), R. BISSCHOPS (5) / [1] Imelda Hospital, Bonheiden, Belgium, Department of gastroenterology, [2] University Hospitals Leuven, , Belgium, Department of Pathology, [3] University Hospitals Leuven, , Belgium, Medical Imaging Research Center, [4] University Hospitals Leuven, , Belgium, Department of Gastroenterology and Hepatology, [5] University Hospitals Leuven, Leuven, Belgium, Department of Gastroenterology and Hepatology

Introduction
A treat to target strategy in ulcerative colitis (UC) requires an objective evaluation tool to assess remission. The Mayo endoscopic subscore (MES) and the ulcerative colitis endoscopic index of severity (UCEIS) have important inter-rater variability mainly in evaluating remission. Histological remission is the best predictor for sustained clinical remission in UC. The infiltration of neutrophils is associated with morphological irregularities of the pericryptal capillaries.

Aim
The aim was to develop a new objective automated tool for a prototype colonoscopic system to assess histological remission based on the evaluation of the morphology of the pericryptal capillaries during endoscopy.

Methods
We used a prototype endoscopic system enabling activation of a short wave-length monochromatic light through adaptation of a LED system. This enables to evaluate in real time the mucosal architecture (crypts, pericryptal capillaries, bleeding) up to a depth of around 200µm. In initial observations histological non-remission was associated with bleeding (mucosal/luminal) and capillary congestion. For this, an image analysis algorithm was applied to provide a score that quantifies the specific morphology of the mucosal capillaries. The algorithm included two steps. First, bleeding (mucosal/luminal) was assessed by pattern recognition. Samples with bleedings were automatically classified as non-remission. In case of non-bleeding (mucosal/luminal), the degree of congestion of the capillaries was measured (maximal localized density estimation after morphological hessian based vessel recognition) to assess an ideal cut off value to identify histological remission (Geboes score (GBS) <2B.1; no neutrophils in the lamina propria). Consecutive UC patients at the University of Leuven were evaluated with the MES, UCEIS, visual capillary evaluation based on short wave-length monochromatic light and the automated image analysis algorithm. To test the reliability of the algorithm and scores, the results were correlated with the GBS. Biopsies were taken in the matching area of the endoscopic evaluation.

Results
Fifty eight patients with UC (53% male, median age 41y IQR 38-56, disease duration 7.1y IQR 2.4-16.4) with 113 evaluable segments (89% rectum or sigmoid) were included. The correlation between GBS and MES, UCEIS and visual short wave-length was good (r= 0.76, 0.75, 0.74, respectively). The automated image analysis algorithm detected histological remission with a high performance (sens 0.79, spec 0.90) compared to UCEIS (sens 0.95, spec 0.69) and MES (sens 0.98, spec 0.61), resulting in a positive predictive value of 0.83, 0.65 and 0.59 for the automated image analysis algorithm, UCEIS and MES respectively. The algorithm detects histological remission with high accuracy (86%).

Conclusions
Mucosal capillary pattern recognition based on image analysis with short wave-length monochromatic light detected histological remission with high accuracy in UC. This technique provides an objective and quantitative tool to assess histological remission, and excludes inter-reader variability.

Speakers

Peter Bossuyt

Gert De Hertogh

Tom Eelbode

Séverine Vermeire

Raf BISSCHOPS

Thursday March 5, 2020 14:36 - 14:48 CET
Room LIJN

BSGIE, Session 1

14:40 CET

Prediction of mortality in cirrhotic patients before surgery

Prof. Rosa Martín Mateos (Hospital Ramón y Cajal , Madrid)

Speakers

Rosa Martín Mateos

Thursday March 5, 2020 14:40 - 15:20 CET
Room TEUN

BASL / BLIC, Session 3

14:45 CET

Use of Ustikinumab in an infant with very early onset inflammatory bowel disease: 18 months follow-up

Authors
B. HAUSER (1), K. HUYSENTRUYT (2), E. DE GREEF (2), G. VEEREMAN (2), Y. VANDENPLAS (2) / [1] UZ Brussel, Jette, Belgium, Pediatrics, [2] UZ Brussel, Jette, Belgium, Paediatrics
Treatment in very early onset inflammatory bowel disease (VEOIBD) is challenging when no genetic defect is found. We describe the succesful use of ustekinumab in an infant with VEOIBD. The healthy born infant developed bloody diarrhea at the age of 5 months. Since both parents were allergic, a cow's milk protein allergy was suspected. An extensive protein hydrolysate was started with temporary improvement. At relapse, a left colonoscopy showed follicular hyperplasia with histologic signs of allergic colitis at 8 months of age. A diet without cow's milk, eggs and soy but with an elemental formula resulted in a temporary improvement. At 12 months of age, an upper endoscopy and ileocolonoscopy were performed because of recurrence of symptoms. They showed a mild antritis and duodenitis as well as some colonic aphteous lesions, one ulcer in the caecum and a normal terminal ileum. Histology showed a mild ileitis and local cryptitis not directly suggestive for an IBD. Blood analysis showed mild anemia, inflammation and hypoalbuminemia. Coprocultures were negative. VEOIBD was suspected, even though immunologic and genetic work-up remained negative. She was started on azathioprine, mesalazine and prednisolone with temporary improvement. A stool culture at 14 and 15 months of age was positive for a toxin-producing Clostridium difficile. She received metronidazole and vancomycine consecutively with temporary improvement. An ileocolonoscopy performed at the age of 16 months showed diffuse aphteous lesions, deep and superficial ulcers and a normal terminal ileum. Cryptitis, cryptabcesses and cryptdestruction confirmed the VEOIBD diagnosis. Clostridium difficile was eradicated. Azathioprine, mesalazine and prednisolone were stopped. Infliximab was started at the age of 16 months (10 mg/kg week 0, 10 mg/kg week 2 and 15 mg/kg week 6) but failed to improve symptoms. Levels remained low and anti-TNF antibodies developed. Methotrexate was tried at 18 months without effect. Transfusion dependent anemia and severe failure to thrive remained with unchanged lesions on an ileocolonoscopy performed at the age of 19 months. Ustekinumab in compassionate use was requested to Janssen and this new treatment could be started. An induction dose of 65 mg ustekinumab IV at the age of 19 months was administered followed by a maintenance dose of 45 mg SC/8 weeks up to now. Methotrexate was continued. Stool consistency and blood loss improved progressively after the third maintenance dose. Growth resumed. A colonoscopy after 14 months of treatment with Ustekinumab showed no macroscopic inflammation and inactive chronic colitis on biopsies and no inflammation biochemically. Through levels after the third, fourth, six and seventh maintenance doses were respectively < 0.3, 0.7, 6.5 and 6.1 µg/ml. Infantile onset IBD is a challenging disease within the group of VEO-IBD. While ustekinumab is an effective therapy approved for adult Crohn’s disease, off-label use in the paediatric population is increasing. The first results suggest that ustekinumab is efficacious and safe in paediatric patients with IBD. We report to the best of our knowledge the first patient with a VEO-IBD successfully treated with ustekinumab without side-effects and in complete remission after 18 months of treatment.

Speakers

Bruno HAUSER

Koen Huysentruyt

Elisabeth De Greef

Gigi Veereman

Yvan Vandenplas

Thursday March 5, 2020 14:45 - 15:00 CET
Room SANCY

BeSPGHAN

14:45 CET

Anti-inflammatory effects on duodenal eosinophilia rather than acid-suppressive effects explain therapeutic efficacy of proton pump inhibitors in functional dyspepsia patients.

Authors
M. CEULEMANS (1), L. WAUTERS (1), D. FRINGS (1), A. ACCARIE (1), R. FARRE (1), G. DE HERTOGH (2), J. TACK (1), T. VANUYTSEL (1) / [1] KU Leuven, , Belgium, TARGID, [2] KU Leuven, , Belgium, Pathology

Introduction
Proton pump inhibitors (PPI) are the first line treatment in functional dyspepsia (FD), a common gastrointestinal (GI) disorder characterized by duodenal mucosal hyperpermeability and eosinophilia (Vanheel et al Gut 2014). PPI lower gastric acid secretion and increase gastric pH, but their effect on duodenal pH, mucosal integrity and eosinophilia remains unclear.

Aim
We aimed to confirm duodenal hyperpermeability and eosinophilia in FD patients vs. healthy volunteers (HV) and to investigate the effect of PPI on duodenal pH, permeability, eosinophils and symptoms in FD patients. Next, we assessed the possible role of intraluminal pH on duodenal barrier and immune function as well as symptoms. Finally, we hypothesized that duodenal eosinophils mediate changes in symptoms in FD patients after PPI-therapy.

Methods
FD patients fulfilling Rome IV criteria and matched HV were recruited to undergo upper endoscopy with duodenal biopsies, followed by aspiration of duodenal fluids via a naso-duodenal catheter. Paracellular passage of a fluorescein-labeled dextran (4 kDa) was recorded in Ussing chambers as a measure for mucosal integrity . Eosinophils were counted on H&E-stained sections per high-power field (HPF; 0.24 mm²). Fasted and fed (1 h after Fortimel®, 300 kCal) pH of duodenal fluids was measured and symptoms were scored using the Patient Assessment of GI Disorders Symptom Severity Index (PAGI-SYM). Procedures were repeated in FD patients after pantoprazole 40 mg OD for 4 weeks (on-PPI). Multilevel (mixed) models were constructed in SAS for each dependent variable (pH, passage, eosinophils and symptoms) with treatment (off- or on-PPI) as within-subject independent variable of interest. Next, duodenal pH and eosinophils were separately added as a between-subject independent variable in the model to test potential mediation.

Results
In total, 22 FD patients (19 female, mean ± SEM age 31 ± 2 years) and 25 HV (16 female, age 30 ± 2 years) were included. Duodenal fasted (6.75 ± 0.2 vs. 5.98 ± 0.27; p=0.03) but not fed pH (6.1 ± 0.2 vs. 5.7 ± 0.2, p=0.21) was higher in FD vs. HV off-PPI. Paracellular dextran-passage (28.77 ± 2.63 vs. 17.94 ± 1.78 pmol; p=0.002), eosinophils (12.88 ± 1.32 vs. 3.65 ± 0.55 /HPF; p<0.0001) and symptoms (2.41 ± 0.12 vs. 0.25 ± 0.08; p=<0.0001) were also higher in FD vs. HV off-PPI. Fasted duodenal pH (delta=0.54; p=0.16) was similar while fed duodenal pH (delta=0.51; p=0.01) increased significantly in FD on- vs. off-PPI. During PPI treatment, a significant decrease was found for dextran-passage (delta=-12.22 pmol; p<0.001), eosinophils (delta=-8/HPF; p<0.0001) and PAGI-SYM scores (delta=-0.72; p<0.001) in FD patients. No mediating effect was found for duodenal pH on paracellular dextran-passage, eosinophils or symptoms on vs. off PPI (all p>0.05). When including duodenal eosinophils in the model, a significant mediating effect of duodenal eosinophilia was found for the PPI-induced decrease in PAGI-SYM (F=5.16, p=0.04).

Conclusions
In FD patients, duodenal hyperpermeability, eosinophilia and GI-symptoms improved significantly on-PPI. The PPI-induced increase in duodenal pH did not mediate the reduction in paracellular dextran-passage, eosinophils and symptoms, suggesting alternative, acid-independent effects of PPI-therapy. Indeed, the PPI-induced decrease in symptoms was mediated by a reduction in duodenal eosinophilia, indicating that anti-inflammatory effects of PPI may also play a role in the duodenum of FD patients.

Speakers

Matthias Ceulemans

Lucas Wauters

Dennis Frings

Alison Accarie

Gert De Hertogh

Jan Tack

Tim Vanuytsel

Ricard Farre

Thursday March 5, 2020 14:45 - 15:00 CET
Room TIFFANY/SHAH

GIREM, Session 3

14:48 CET

Continuous ADR50 monitoring with individual feedback in lower gastrointestinal endoscopy, a quality improvement initiative in a Brussels public hospital.

Authors
G. RASSCHAERT (1), L. DUEZ (1), C. SALEM (1), C. MUSALA (1), M. NKUIZE (1), P. EISENDRATH (1) / [1] CHU Saint-Pierre, Brussels, Belgium, Gastroenterology and Hepatology

Introduction
Adenoma detection rate 50 (ADR50) reflects the percentage of colonoscopies in patients aged 50 years or older with at least one adenoma identified. Apart from being an indicator for adequate bowel mucosa inspection, ADR50 is inversely associated with the risk for interval colorectal cancer (CRC) and CRC mortality. ADR50, with a minimum standard of 25%, is considered by the European Society of Gastrointestinal Endoscopy (ESGE) as one of the key performance measures for lower gastrointestinal endoscopy. Technical and human resources constraints limit implementation of recording of quality monitoring in endoscopy and linkage to the histopathology.

Aim
Deploy a ready able infrastructure for endoscopy quality monitoring with an automated linkage with histopathology to achieve a continuous monitoring of endoscopy quality indicators. Screen the global and individualized ADR50 at our centre. Can an augmentation of ADR50 be seen after individual feedback?

Methods
At first we adapted a company reporting system for colonoscopy by adding a dedicated tab for quality monitoring including: preparation, progression, indication and number of polyps resected. Second we automatically linked this endoscopy database with the histopathology database using the systematized nomenclature of medicine clinical terms® (SNOMED CT®). This results in a continuous monitoring of endoscopy quality indicators. It includes inter alia: rate of adequate bowel preparation, cecal intubation rate (CIR), polyp detection rate 50 (PDR50), ADR50 and percentage of adenoma among polyps resected (%ADR p). Participation was mandatory for all 9 endoscopists working at our centre. After the first 4 months of monitoring (January to April 2019) participants were confronted with their personal numbers and an anonymous ranking was communicated. This was done in a neutral way, without any consequences. After another 5 months of monitoring (May to September 2019) we compared the data of these two separate periods.

Results
A total of 1434 colonoscopies were performed during the first 9 months of monitoring, 682 during the first 4 months, 752 during the following 5 months. CIR was not subject to change (92%). An increase in ADR50 is observed in 7 out of 9 participants, resulting in a global increase of 4.6% (22.9% to 27.5%) (P<0.05). An increase in %ADR p is observed in 7 out of 9 participants, resulting in a global increase of 12.1% (53.4 to 65.5) (P<0.05). The reported ADR50 numbers meet the goals required by international guidelines. We assume these results underestimate reality because neither emergency - nor therapeutic colonoscopy procedures were excluded from our database.

Conclusions
An easy to use infrastructure for registration of quality monitoring in daily endoscopy practice in combination with an automated linkage with the histopathology database facilitates continuous monitoring of endoscopy quality indicators. This system allows giving feedback to individual endoscopists for personal performance assessment. An increase in personal ADR50 was observed in the majority of the endoscopists 5 months after personal feedback. This confirms the pedagogic value of feedback. In total an augmentation of the global ADR50 was observed. An increase in total %ADR p also reflects a better ability of the team for adenoma detection and consequently a more appropriate resection policy. This parameter can be helpful in pointing out individual needs. These results can be translated into a net quality improvement in the performance of lower gastrointestinal endoscopy at our centre.

Speakers

Gertjan RASSCHAERT

Charelle Salem

Carmen Musala

Marcel Nkuize

Jessica Biesiekierski

Linde Besard

Jolien Schol

Esther Colomier

Florencia Carbone

Jan Tack

Thursday March 5, 2020 15:15 - 15:30 CET
Room TIFFANY/SHAH

GIREM, Session 3

15:20 CET

Coffee Break

Thursday March 5, 2020 15:20 - 15:40 CET
Exposition Area

BASL / BLIC

15:30 CET

Coffee Break

Thursday March 5, 2020 15:30 - 16:00 CET
Exhibition Area

BSGIE

15:30 CET

Coffee Break

Thursday March 5, 2020 15:30 - 16:00 CET
Exposition Area

GIREM

15:30 CET

On Boarding Improved Care Now for participating centers.

Dr R Colletti and Cincinnati team.

Thursday March 5, 2020 15:30 - 17:30 CET
Room SANCY

BeSPGHAN

15:40 CET

Myeloid IRE1a deletion alters hepatic macrophage phenotype and attenuates experimental non-alcoholic steatohepatitis-related hepatocellular carcinoma

Authors
S. VAN CAMPENHOUT (1), L. TILLEMAN (2), S. LEFERE (1), A. VANDIERENDONCK (1), A. GEERTS (1), X. VERHELST (1), F. VAN NIEUWERBURGH (2), H. VAN VLIERBERGHE (1), L. DEVISSCHER (3) / [1] Ghent University, Ghent, Belgium, Internal Medicine and Pediatrics, [2] Ghent University, Ghent, Belgium, Pharmaceutics, [3] Ghent University, Ghent, Belgium, Basic and Applied Medical Sciences

Introduction
Obesity, diabetes and associated non-alcoholic steatohepatitis (NASH) are characterized by adipose tissue and hepatic fat accumulation and inflammation and are rising causes of hepatocellular carcinoma (HCC). Macrophages are important immune cells involved in inflammation and tumour development. Inositol-requiring enzyme 1 alpha (IRE1a) has shown to be involved in macrophage cytokine production and myeloid-specific IRE1a knock-out (mKO) mice showed reduced weight gain during high fat diet feeding. However, the effect of myeloid-specific IRE1a deletion on NASH and subsequent HCC development has not been examined.

Aim
Here, we investigated the effect of myeloid-specific IRE1a deletion on experimental NASH-HCC development. Furthermore, the liver macrophage population was characterized during disease development.

Methods
Mice with non-functional myeloid IRE1a were created by crossing IRE1a floxed mice with LysM-Cre mice. Two-day old mKO and wild type (WT) mice were subcutaneously injected with streptozotocin (STZ) or PBS as control and male mice were fed a high-fat, -sucrose, -cholesterol diet (Western diet, WD) or control diet from the age of 4 weeks until 21 weeks. Mice were evaluated for obesity, diabetes, NASH and HCC. The macrophage population was evaluated by flow cytometry and RNA sequencing on FACS isolated cells.

Results
STZ+WD feeding resulted in impaired glucose tolerance, advanced NASH with fibrosis and HCC development. mKO STZ mice showed lower fasting glucose levels at the start of WD feeding, and an improved glucose tolerance and attenuated HCC development after 17 weeks of WD feeding despite a similar degree of liver steatosis and inflammation compared to WT mice. Transcriptomic analysis of liver Kupffer cells (KCs), macrophages and monocytes revealed phenotypical changes in NASH-HCC. Myeloid IRE1a deletion in healthy mice resulted in an altered transcriptomic profile with downregulation of pathways involved in immune system activation in KCs and macrophages, downregulation of metabolic pathways in KCs, whereas pathways involved in cell division and metabolism were upregulated in monocytes. Macrophages showed both up- and downregulated metabolic pathways. NASH-HCC attenuated the differential gene expression profile of mKO and WT liver isolated macrophages.

Conclusions
Our results show that myeloid-specific IRE1a deletion results in an altered transcriptional profile of hepatic macrophages and attenuates diabetes induction and NASH-related HCC development.

Speakers

Sanne Van Campenhout

Laurentijn Tilleman

Sander Lefere

Astrid Vandierendonck

Anja Geerts

Xavier VERHELST

Filip Van Nieuwerburgh

Hans Van Vlierberghe

Lindsey Devisscher

Thursday March 5, 2020 15:40 - 15:50 CET
Room TEUN

BASL / BLIC, Session 4

15:50 CET

Active Non-alcoholic steatohepatitis and severe fibrosis are associated with dysfunctional adipose tissue and worsen with more severe adipose tissue insulin resistance independently of Body mass index

Authors
L. VONGHIA (1), M. GAGGINI (2), A. VERRIJKEN (3), J. WEYLER (1), F. CARLI (2), B. PATRICIO (2), W. KWANTEN (1), T. VANWOLLEGHEM (1), E. DIRINCK (3), A. DRIESSEN (4), L. VAN GAAL (3), S. FRANCQUE (1), A. GASTALDELLI (2) / [1] Antwerp University Hospital, , Belgium, Department of Gastroenterology and Hepatology, [2] Institute of Clinical Physiology, CNR, Pisa, Italy, Pisa, Italy, Cardiometabolic Risk Unit, [3] Antwerp University Hospital, , Belgium, Department of Endocrinology, Diabetology and Metabolic Diseases, [4] Antwerp University Hospital, , Belgium, Department of Pathology

Introduction
Adipose tissue act as an endocrine organ that influences the metabolism by releasing adipokines, proinflammatory factors and free fatty acids (FFA), which contribute to insulin resistance (IR). Non-alcoholic fatty liver disease (NAFLD) occurs in the setting of IR due to increased delivery of free fatty acids (FFA) from peripheral lipolysis and de novo lipogenesis while clearance of hepatic FFA is through mitochondrial beta-oxidation, the dominant oxidative pathway, or by triglycerides (TG) secretion in plasma.

Aim
We explored whether adipose tissue insulin resistance (adipo-IR, which measures the impaired suppression of lipolysis in the presence of high insulin levels), plasma FFA, TG and beta-hydroxybutyrate (BOH) (that reflects liver FFA oxidation) concentrations were associated to the severity of Non-alcoholic steatohepatitis (NASH).

Methods
A large cohort of consecutively recruited patients with liver biopsy (n=211) were included in the study and characterised for presence of glucose intolerance (IGT) or diabetes (T2D) by oral glucose tolerance test. We measured plasma FFA, BOH, lipid profile, Adipo-IR (FFAxInsulin) and fat distribution by CT. Data were analysed by logistic multivariable analysis (LMA) adjusted for age, BMI, presence of IGT/T2D and odd ratios (OR) were calculated.

Results
Liver histology was as follows: 55 no NAFLD, 34 non-alcoholic fatty liver (NAFL) and 122 NASH. TG (128±5 vs 141±8 vs 176±7 mg/dL) and Adipo-IR (9.0±0.7 vs 10.6±1,1 vs 13.5 ±0.9 mmol/l*pmol/l) increased (p<0.008) from noNAFL, NAFL to NASH. Visceral fat was increased similarly in NAFL (218±15 cm2) and NASH (196±6 cm2) compared to noNAFL (139±8 cm2, p<0.0001), while Body mass index (BMI) , subcutaneous fat, BOH and FFA were similar in the 3 groups. Presence of NASH was associated with increased Adipo-IR (OR=2.5, CI 1.5-4.5, p=0.0005) after adjusting for age, BMI, IGT/T2D. In case of increased necro-inflammation (ie “active NASH”, the sum of ballooning and lobular inflammation ≥3) the OR was 2.6 (CI 1.4-4.7, p=0.003). There was no independent association of FFA, BOH or TG. Moreover, NASH with severe fibrosis (F2-F4) had a much higher Adipo-IR (18.7±4.1 mmol/l*pmol/l) vs NASH F0-1 (12.2+0.7 mmol/l*pmol/l), NAFL (10.6±1.1 mmol/l*pmol/l) and noNAFL (8.6±0.8 mmol/l*pmol/l, p<0.001). In NASH with severe fibrosis (F2-4) the association with Adipo-IR had an OR=3.3 (CI 1.4-8.0, p=0.003) adjusted for age, BMI, IGT/T2D.

Conclusions
Increased adipo-IR was significantly associated to presence of active NASH and severe fibrosis independently of BMI, showing the importance of dysfunctional adipose tissue as a main target in this disease.

Thursday March 5, 2020 15:50 - 16:00 CET
Room TEUN

BASL / BLIC, Session 4

16:00 CET

Muscle fat infiltration in obese patients is associated with NAFLD related fibrosis severity – results from a prospective body composition and imaging study

Authors
N. LANTHIER (1), S. HIEL (2), M. NACHIT (3), J. RODRIGUEZ (4), J. THISSEN (5), P. TREFOIS (6), N. DELZENNE (4) / [1] Cliniques universitaires Saint-Luc, UCLouvain, Brussels, Belgium, Service d'Hépato-Gastroentérologie, [2] UCLouvain, , Belgium, Metabolism and Nutrition Research Group, Louvain Drug Research Institute,, [3] UCLouvain, , Belgium, Laboratory of Gastroenterology and Hepatology, Institut de Recherche Expérimentale et Clinique, [4] UCLouvain, , Belgium, Metabolism and Nutrition Research Group, Louvain Drug Research Institute, [5] Cliniques universitaires Saint-Luc, UCLouvain, Brussels, Belgium, Service d'Endocrinologie, [6] Cliniques universitaires Saint-Luc, UCLouvain, Brussels, Belgium, Department of Radiology

Introduction
The association between NAFLD and visceral adipose tissue or sarcopenia has been reported, although results are discordant.

Aim
The goal of this study is to analyze the spectrum of NAFLD among obese patients recruited prospectively and to detect clinical, biological and imaging data associated with steatosis or fibrosis.

Methods
Baseline data of obese patients (BMI ≥ 30) randomized in a single center (Food4Gut study) were included. Transient elastography (TE) was done to quantify both liver steatosis by controlled attenuation parameter (CAP) measurement and liver fibrosis by liver stiffness measurement (LSM). Body composition was evaluated using bioelectrical impedance analysis. Subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), muscle areas and muscle fat infiltration were measured on CT-scan images at the third lumbar level.

Results
Fifty-two Caucasian patients (mean age: 50 years, 50 % male, mean BMI 35.8) were included. TE was successful in 49 patients (94%). XL probe was used in 20 patients (38%). Mean LSM was low (6.5 kPa). Mean CAP result was high (324 dB/m) with the majority of the patients (73%) presenting severe steatosis (CAP ≥ 296 dB/m). 12 patients (24%) had advanced fibrosis defined by LSM ≥ 7.8 kPa (M probe) or ≥ 6.4 kPa (XL probe). Compared to patients with discrete or moderate steatosis, patients with severe steatosis had higher ALAT values (45.3 vs 28.1 UI/L, p<0.01) and fasting blood glucose levels (109.2 vs 95.1 mg/dL, p<0.05). Bioimpedance analysis did not evidence any difference between those two groups. However, CT-scan revealed a significant higher VAT area (275.4 vs 197.3 cm², p<0.01), similar SAT area and unexpected higher skeletal muscle index (61.9 vs 52.9 cm²/m², p<0.05) in patients with severe steatosis compared to others. Patients with severe fibrosis compared to patients with normal liver elasticity had a significant higher fat free mass at bioimpedance analysis (76.3 vs 63.9 kg, p<0.01) and higher whole muscle area (200.1 vs 166.4 cm², p<0.01). Interestingly, those patients had a significant lower muscle density index, compatible with muscle fat infiltration (MFI). In a multivariate logistic regression analysis, MFI was the strongest predictor of advanced liver fibrosis.

Conclusions
Among obese subjects, patients with severe steatosis have a high muscle and visceral adipose tissue mass. Muscle fat infiltration provides a robust, skeletal muscle-specific characteristic linked to advanced liver fibrosis, suggesting a muscle-liver axis in the pathogenesis of NAFLD complications.

Speakers

Nicolas Lanthier

Sophie Hiel

Maxime Nachit

Julie Rodriguez

Jean-Paul Thissen

Pierre Trefois

Nathalie Delzenne

Thursday March 5, 2020 16:00 - 16:10 CET
Room TEUN

BASL / BLIC, Session 4

16:00 CET

Thermal ablation of the mucosal defect margin after endoscopic mucosal resection significantly reduces adenoma recurrence – A prospective, international, multi-centre trial.

Authors
M. SIDHU (1), N. SHAHIDI (1), L. HOURIGAN (2), S. RAFTOPOULOS (3), A. MOSS (4), S. HEITMAN (5), E. LEE (1), N. BURGESS (1), S. WILLIAMS (1), D. TATE (6), M. BOURKE (1) / [1] Westmead Hospital, , Australia, Gastroenterology and Hepatology, [2] Greenslopes Private Hospital, , Australia, Gastroenterology and Hepatology, [3] Sir Charles Gairdner, , Australia, Gastroenterology and Hepatology, [4] Western Hospital, , Australia, Gastroenterology and Hepatology, [5] University of Calgary, , Canada, Departments of Medicine and Community Health Sciences, [6] UZGent, Gent, Belgium, Gastroenterology and Hepatology

Introduction
Thermal ablation of the defect margin (TAM) after endoscopic mucosal resection (EMR) in the treatment of large (>/=20mm) laterally spreading lesions (LSL) has been shown to be efficacious in a clinical trial setting, with a fourfold reduction, in residual or recurrent adenoma (RRA) at 6 months first surveillance colonoscopy (SC1). The clinical effectiveness of this treatment is unknown.

Aim
We sought to evaluate the effectiveness of TAM on the rate of RRA post EMR in an international, multi-center prospective trial (NCT02957058).

Methods
We conducted a study of consecutive LSL, across five tertiary centers, referred for EMR. The primary endpoint was the rate of RRA at SC1. TAM was performed using soft coagulation (ERBE - Tübingen, Germany: 80W, Effect 4) via the snare-tip (STSC) to create a minimum 2-3mm rim of completely ablated tissue around the entire circumference of the resection defect. All endoscopists underwent an educational intervention prior, with two videos circulated at each centre and image review performed of treated LSL, critiqued to assess for uniform completeness of TAM. Detailed demographic, procedural and outcome data were recorded. Recurrence was defined endoscopically as the presence of a neoplastic pit pattern within an EMR scar and confirmed histologically. Exclusion criteria included LSL involving the ileo-caecal valve/appendiceal orifice and circumferential LSL.

Results
Over 40 months to September 2019, 866 LSL (54.7% - right colon, median size - 35mm) were enrolled and underwent EMR. TAM with uniform completeness was achieved in 795 LSL. 71 LSL (median size 40mm) had incomplete treatment with TAM (poor access – 26, patient related – 15, deep mural injury (>/=3) – 10, risk of significant stenosis – 8, other – 12). 424/494 (85.4%) of eligible LSL underwent SC1 at median 5.8 months (IQR:4.8-6.9). 9/424 (2.1%) cases had evidence of RRA (endoscopic or histologic). RRA was commonly unifocal (7/9), diminutive (6/9) and occurred at the edge of the scar (6/9). All recurrences were successfully treated endoscopically. For LSL with incomplete TAM, however, the rate of RRA was 28% (14/50), in those eligible for SC1.

Conclusions
In clinical practice routine thermal ablation of the defect margin after EMR is highly effective in reducing recurrence. This simple and inexpensive technique should be universally employed. Incomplete treatment, in difficult lesions, is associated with a higher rate of recurrence. Therefore, endoscopists should attempt complete margin ablation in all LSL undergoing EMR.

Speakers

Mayenaaz Sidhu

Neal Shahidi

Luke Hourigan

Spiro Raftopoulos

Alan Moss

Steve Heitman

Eric Lee

Nicholas Burgess

Stephen Williams

David Tate

Michael Bourke

Thursday March 5, 2020 16:00 - 16:12 CET
Room LIJN

BSGIE, Session 2

16:00 CET

Exploring the molecular signalling pathways of MUC1 and MUC13 in intestinal epithelial cells during inflammation in vitro: important Mediators of intestinal barrier integrity?

Authors
T. BREUGELMANS (1), B. CUYPERS (2), J. DE MAN (1), K. LAUKENS (2), B. DE WINTER (1), A. SMET (1) / [1] Laboratory of Experimental Medicine and Pediatrics, University of Antwerp, Antwerp, Belgium, Faculty of Medicine and Health Sciences , [2] AdReM Data Lab, University of Antwerp, Antwerp, Belgium, Department of Mathematics and Computer Science

Introduction
The intestinal mucosal barrier consists of a thick mucus layer, a single epithelial cell layer and the lamina propria interacting with innate and adaptive immune cells. Secreted and transmembrane mucins are major components of the mucus barrier. Besides providing protection to the underlying epithelium, transmembrane mucins also participate in the cell signal transduction in response to inflammation. Of particular interest are MUC1 and MUC13, which are increasingly expressed in the inflamed colonic mucosa of patients with inflammatory bowel diseases (IBD). Aberrant expression of mucins could disrupt barrier integrity resulting in chronic inflammation and subsequent progressing to cancer. Nevertheless, the molecular signalling pathways related to aberrant MUC1 and MUC13 expression in response to inflammation remain poorly understood.

Aim
This study aimed to explore and identify potential upstream regulators and downstream effectors of epithelial MUC1 and MUC13 expression during inflammation focusing on intestinal barrier-related genes.

Methods
LS513 intestinal epithelial cells were transfected with silencing RNA (siRNA) targeting MUC1 and MUC13, after which they were stimulated with 20 ng/mL TNF-α or IL-22 for 24h. Untreated cells and cells transfected with negative control siRNA were included as controls. siRNA transfection and cytokine stimulation were validated by qPCR. Subsequently, Illumina mRNA sequencing was performed to investigate differentially expressed genes (DEGs) and the corresponding canonical pathways involved. After data processing (using Trimmomatic v0.38, STAR 2.6.1a and DESeq2 tools), pathway analysis was performed using Ingenuity Pathway Analysis software (fold change > [1.5], p < 0.05, q < 0.1). Additionally, DEGs were further explored individually for their potential role in directly modulating intestinal barrier integrity.

Results
Transcriptome analysis of untreated LS513 cells silenced for MUC1 or MUC13 (vs unsilenced controls) revealed respectively 2006 and 3232 candidate downstream effectors. During the stimulation with TNF-α or IL-22, knockdown of MUC1 resulted in 39 and 857 and of MUC13 in 103 and 88 DEGs respectively. In the latter sets of genes, several molecular pathways were significantly enriched, including those involved in inflammation (e.g. IL-6 signalling, IL-17 signalling pathway), cell invasiveness (e.g. regulation of the epithelial-mesenchymal transition pathway) and cell-cell interactions (e.g. epithelial adherens junction signalling, tight junction signalling). A targeted search on intestinal barrier-related genes showed the differential expression of several claudins (CLDN1, 2, 3, 4, 7), cadherins (CDH3, PCDH1) and tubulins (TUBA1A, TUBA1C, TUBA4A, TUBB, TUBB3) due to silencing of MUC1 or MUC13 during cytokine stimulation. Furthermore, the NFkB complex, ERK, EHF and STAT1/3 were identified as potential upstream regulators of MUC1 and MUC13 expression during TNF-α and IL-22 stimulation.

Conclusions
Silencing of MUC1 and MUC13 in intestinal epithelial cells resulted in cytokine-dependent and -independent changes in gene expression, including genes involved in the modulation of intestinal barrier integrity. These results highlight their importance in co-regulating intestinal barrier homeostasis.

Speakers

Tom Breugelmans

Bart Cuypers

Joris De Man

Kris Laukens

Benedicte De Winter

Annemieke Smet

Thursday March 5, 2020 16:00 - 16:15 CET
Room TIFFANY/SHAH

GIREM, Session 4

16:10 CET

The mechanisms of steatosis pathogenesis during NASH development

Authors
A. LAMOTTE (1), I. LECLERCQ (1), N. LANTHIER (2) / [1] UCLouvain, , Belgium, Laboratory of Gastroenterology and Hepatology, Institut de Recherche Expérimentale et Clinique, [2] Cliniques universitaires Saint-Luc, UCLouvain, Brussels, Belgium, Service d'Hépato-Gastroentérologie

Introduction
In non-alcoholic fatty liver disease (NAFLD), imbalance between fatty acid uptake, synthesis and their combustion or secretion can lead to steatosis. In some patients, non-alcoholic fatty liver (NAFL) evolves in a more aggressive disease form called non-alcoholic steatohepatitis (NASH) which promotes the development of fibrosis. An unanswered question is whether mechanisms for steatosis are stable over time or whether a specific steatotic process occurs during NASH development and promotes disease progression.

Aim
Here, we wanted to define the mechanisms of liver fat accumulation at various stages of NAFLD progression in a well-established NASH mouse model.

Methods
Wildtype (WT) and FOZ -/- mice received either a normal diet or a high fat diet (HFD) for 0, 4, 12 or 32 weeks (n=4-8/group). Liver paraffin-embedded sections were used for NAFLD severity assessment, based on the NAFLD activity score (NAS) and the Sirius red staining (fibrosis). Total RNA was extracted from the liver and the visceral adipose tissue of WT and FOZ -/- mice for gene expression analysis of key pathways potentially involved in steatosis pathogenesis.

Results
FOZ -/- mice fed a HFD developed steatosis after 4 weeks, NASH after 12 weeks (NAS=8) and fibrotic NASH after 32 weeks (NAS=7 + presence of fibrosis). In comparison with baseline situation (FOZ -/- 0 week), the transporter for extracellular fatty acid uptake (liver fatty acid transporter cluster of differentiation 36) significantly increased over time (p<0.01). Acetyl CoA oxidase, an enzyme of the peroxysomal β-oxidation was induced at early time point (4 weeks, p<0.01) and decreased thereafter (p<0,05). However, expression of carnitine palmitoyltransferase 1-α, a gene signing activation of mitochondrial β-oxidation was upregulated from week 4 and up to 32 weeks (p<0.05). De novo lipogenesis (DNL) assessed by stearoyl CoA desaturase 1 expression was stable over time. Apolipoprotein B expression, key for fatty acid export was initially upregulated during steatosis and NASH stages (p<0.01 at 4 and 12 weeks) but not at the fibrotic stage of the disease. Lipolytic enzymes adipose triglycerides lipase and hormone sensitive lipase in the epididymal white adipose tissue were upregulated in FOZ -/- HFD fed mice (p<0.01 and p<0.001, respectively) consistent with adipose tissue lipolysis at the NAFL and NASH stages. In contrast, in WT mice fed a HFD and developing only discrete steatosis over time, liver DNL was downregulated and no adipose tissue lipolysis was observed.

Conclusions
FOZ -/- develop fibrosing NASH over time due to an increased fatty acid transport to the liver, enhanced adipose tissue lipolysis, preserved de novo lipogenesis and at later timepoints downregulation of fatty acid export and defect in fatty acid oxidation. Those results open the possibility to evaluate targeted steatosis therapies according to NAFLD stage. Those pathways are currently investigated in HFD FOZ-/- mice supplemented in high fructose corn syrup as well as in human NAFLD with various disease severity.

Luisa Vonghia

Wilhelmus J Kwanten

Thomas Vanwolleghem

Didier Ebo

Peter P Michielsen

Joris De Man

Benedicte Y De Winter

Sven M Francque

Thursday March 5, 2020 16:20 - 16:30 CET
Room TEUN

BASL / BLIC, Session 4

16:24 CET

Electrocautery-enhanced lumen-apposing metal stents for approved and non-approved indications: a 2-year single-centre experience.

Authors
P. HINDRYCKX (1), D. HELENA (2) / [1] Ghent University Hospital, Ghent, Belgium, gastroenterology, [2] Ghent University Hospital, Ghent, Belgium, Gastroenterology

Introduction
Lumen-apposing stents are FDA-approved for the treatment of peripancreatic fluid collections (pancreatic pseudocysts, abscesses, and walled-off necroses). Over the last years, lumen-apposing metal stents (LAMS) have been used for a number of off-label indications: gastrojejunostomy, gastro-gastrostomy in patients with a gastric bypass, gallbladder drainage and bile duct drainage (choledochoduodenostomy).

Aim
To analyze indications and outcomes of electrocautery-enhanced LAMS placement over the last two years in a tertiary referral centre.

Methods
We performed a retrospective analysis of all electrocautery-enhanced LAMS placed over the last 2 years. We collected data on indications, technical and clinical success rates and early (<7d) or late (>7d) complications). Technical success rate was defined as the successful deployment of the LAMS in the desired position. Clinical success rate was defined as follows: for pancreatic collections: complete resolution without the need for additional interventions; for choledochoduodenostomy: drop in baseline serum bilirubin with at least 50% within 2 weeks OR at least 75% within 4 weeks AND patient can receive chemotherapy if indicated; for gastrojejunostomy: complete resolution of gastric outlet symptoms; for gastro-gastrostomy: successful access to the excluded stomach; for gallbladder drainage: resolution of sepsis.

Results
From March 2018 until November 2019, 40 LAMS (Hot Axios, Boston Scientific) were placed in 38 patients, of which 32/40 (80%) in the last year. Indications were drainage of peripancreatic collections in 21 patients (55.2%), bulbocholedochostomy in 7 patients (18.4%), gastrojejunostomy in 4 patients (10.5%), gastro-gastrostomy in 5 patients (10.5%; 3/5 for biliary intervention and 2/5 to resolve gastric outlet obstruction of the excluded stomach), gallbladder drainage in 1 patient (2.7%) and drainage of a postsurgical abcess in 1 patient (2.7%). Overall technical success rate was high (38/40 LAMS; 95%). In the peripancreatic collection group, clinical success rate was 85.7% (18/21). One patient needed an additional LAMS (multigate approach), one patient needed additional double pigtail drainage (due to LAMS dislocation) and one patient needed surgical necrosectomy. Complications were a new infectious episode in 4 patients (19%), 1 massive bleeding needing urgent embolization in 1 patient (4.8%) and 3 minor bleedings upon LAMS removal (14.3%). Clinical success rate was 100% with zero complications in both the gastrojejunostomy and gastro-gastrostomy group, except for two patients (40%) in the gastro-gastrostomy group suffering from severe reflux that resolved upon removal of the LAMS and closure of the gastro-gastrostomy. Clinical success rate in the choledochoduodenostomy group was 71.4% (5/7). One serious complication occurred: malplacement of the stent with biliary leak and duodenal perforation needing interventional radiology and surgery.

Conclusions
LAMS are an important new tool in interventional endoscopy that may dramatically improve outcomes in adequately selected patient groups. Amongst all (approved and off-label) indications, choledochoduodenostomy is technically the most challenging and severe complications may occur. Hence, it should only be performed in centres with sufficient experience in LAMS placement.

Speakers

Pieter Hindryckx

Degroote Helena

Thursday March 5, 2020 16:24 - 16:36 CET
Room LIJN

BSGIE, Session 3

16:30 CET

Case-finding of Non-alcoholic fatty liver disease-induced liver fibrosis: prevalence and use of non-invasive scoring vs. transient elastography in primary care

Authors
J. WELLENS (1), M. DE VOS (2), L. PRESENT (3), E. VANDERSTRAETEN (1), S. FRANCQUE (4), L. HEYENS (5), G. ROBAEYS (5), C. VAN STEENKISTE (1) / [1] Maria Middelares Medical Centre, Ghent, , Belgium, Gastroenterology and Hepatology, [2] General practice Rendekens, Destelbergen, Belgium, General practice medicine, [3] General practice Rendekens, Destelbergen, Belgium, General practice medicine , [4] University of Antwerp, , Belgium, Gastro-enterology, [5] Hasselt University, Hasselt, Belgium, Faculty of health and life sciences

Introduction
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder in Western countries, with increasing prevalence, paralleling the metabolic syndrome and its components. Since abnormal liver function tests (LFTs) in primary care are poorly correlated with the severity of NAFLD, more sensitive and specific methods are needed to identify significant liver fibrosis. Therefore, non-invasive risk scores and liver stiffness measurements (LSM), were developed, but validation in a primary care-based population is still lacking.

Aim
Our objective was to determine the prevalence of significant fibrosis in a primary care-based cohort at risk for NAFLD. Secondly, we aimed to determine the usefulness of non-invasive risk scores for steatosis and fibrosis in this population.

Methods
This cross-sectional study recruited 165 adult patients >=35 years from 1 primary care practice in Heusden (East Flanders). Inclusion criteria consisted of diabetes mellitus type 2, BMI >= 30 kg/m^2, metabolic syndrome or history of cardiovascular disease. Patients with an alcohol consumption >= 30 and >= 20 g/day in males and females, respectively, were excluded from the analysis. Each participant was subject to an interview, anthropometric measurements and LSM using vibration-controlled transient elastometry VCTE with Fibroscan® with continued attenuation parameter (CAP) to evaluate for liver fibrosis and steatosis, respectively. LSM >= 7.9 kPa (M-probe), and >=7.2 (XL-probe), was used as a cutoff for significant fibrosis (i.e. F2). The non-invasive risk tools Fibrosis-4 (FIB-4), NAFLD fibrosis score and Fatty Liver Index (FLI) were calculated for each subject.

Results
40 out of 165 patients had an elevated LSM on VCTE, suggesting significant fibrosis. Using TE as our gold standard, FIB4 showed a specificity of 49.6% and a sensitivity of 72.5% resulting in a PPV of 31.5% and a NPV of 85%. Since albumin was only available in 53% of patients in our study population, the NAFLD fibrosis score was not reliable as a screening tool. Using CAP as the gold standard, the FLI was a sensitive screening tool (sens 92.3%, spec 68.8%, PPV 95.6, NPV 44) for steatosis. There was a trend towards a greater prevalence of fibrosis in subjects with an increased waist circumference, BMI>30kg/m^2 (RR 1.4), decreased platelet count (RR 1.2), elevated AST/ALT ratio (RR 1.2), dyslipidaemia (RR 1.6), diabetes mellitus (RR 1.7), metabolic syndrome (RR 1.3) and a protective effect of statin use (RR 0.7).

Conclusions
Our study showed, based on VCTE, a prevalence of significant fibrosis of 24.2% in a population at risk for NAFLD in a primary care-based cohort. Secondly, the accuracy of non-invasive risk scores is unsatisfactorily low, questioning their usefulness as a screening tool instrument in this setting. Lastly, the best predictive factors for presence of significant fibrosis included an increased waist circumference, diabetes type 2 and lack of statin use.

Speakers

Judith Wellens

Marlies De Vos

Luc Present

Eric Vanderstraeten

Sven Francque

Leen Heyens

Geert Robaeys

Christophe Van Steenkiste

Thursday March 5, 2020 16:30 - 16:40 CET
Room TEUN

BASL / BLIC, Session 4

16:30 CET

Volatile organic compound profiling of breath samples as a biomarker to discriminate between patients with irritable bowel syndrome and healthy controls: a feasibility study.

Authors
K. VAN MALDEREN (1), E. JANSSENS (1), J. DE MAN (1), B. DE WINTER (1), H. DE SCHEPPER (2), K. LAMOTE (1) / [1] Antwerp University, , Belgium, LEMP, [2] UZA, Universitair Ziekenhuis Antwerpen, Edegem, Belgium, Gastroenterology

Introduction
There is a huge unmet need for non-invasive biomarkers for a better diagnosis and a more personalised treatment of irritable bowel syndrome (IBS) patients. An emerging research field to be explored for this purpose is volatomics, enclosing volatile organic compounds (VOCs). VOCs are detected in exhaled breath and faeces, reflect the human metabolism, and are induced by inflammation and gut microbiota, thereby serving as a potential biomarker source.

Aim
To assess whether VOC profiling of breath samples is feasible to distinguish IBS patients from healthy controls.

Methods
Breath and background samples of 9 IBS patients and 9 matched healthy controls were collected and analysed by multicapillary column/ion mobility spectrometry (MCC/IMS). Participants were requested to refrain from eating, drinking or brushing their teeth at least 2 hours prior to analysis. Participants were asked to put on a nose-clip and breathe tidally through a Spiroscout sampler for 3 minutes, after which 10ml alveolar air is collected and immediately analysed. After breath sampling, 10 ml of background air is collected by the internal MCC/IMS pump and analysed. In order to correct for potential background contamination, the alveolar gradient of VOCs was calculated. These VOC gradients were then used as independent variables in a lasso regression analysis followed by leave-one-out cross-validation, to discriminate IBS patients from healthy controls. Furthermore, principal component analysis was used to cluster IBS patients and healthy controls.

Results
IBS patients and controls were matched and had a mean (SD) age of 33.1 (8.2) years for healthy controls and 33.1 (8.5) years for IBS patients. Both groups included 2 males and 7 females. Considering the low sample size, IBS subtypes were pooled (7 IBS-D and 2 IBS-M). IBS patients were differentiated from healthy controls, with a sensitivity of 100% (71.7%-100%), a specificity of 88.9% (56.2%-99.4%), a positive predictive value of 90% (59.7%-99.5%), a negative predictive value of 100% (68.8%-100%), an accuracy of 94.4% (75.6%-99.7%) and an area under the curve of 0.951 (0.815-1.000). Principal component analysis showed separate clusters of patients and controls.

Conclusions
VOC analysis in exhaled breath from IBS patients and healthy controls shows to be feasible and promising as a diagnostic tool (94.4% accuracy). However, in order to confirm its clinical utility in diagnosing IBS, further research in larger populations is needed, taking the IBS subtypes and confounders (such as medication and diet) into account.

Speakers

Kathleen Van Malderen

Eline Janssens

Joris De Man

Benedicte De Winter

Heiko DE SCHEPPER

Kevin Lamote

Thursday March 5, 2020 16:30 - 16:45 CET
Room TIFFANY/SHAH

GIREM, Session 4

16:36 CET

Covert carcinoma among rectal ESD specimen is high: a European tertiary center prospectively collected experience.

Authors
M. FIGUEIREDO FERREIRA (1), A. BUCALAU (1), V. HUBERTY (1), L. VERSET (2), C. MARIS (2), J. VAN LAETHEM (1), I. EL NAKADI (3), A. LEMMERS (1) / [1] Erasme University Hospital - Université Libre de Bruxelles (ULB), Bruxelles, Belgium, Gastroenterology, [2] Erasme University Hospital - Université Libre de Bruxelles (ULB), Bruxelles, Belgium, Pathology, [3] Erasme University Hospital - Université Libre de Bruxelles (ULB), Bruxelles, Belgium, Digestive Surgery

Introduction
Endoscopic resection (ER) represents the treatment of choice for superficial rectal lesions. Careful assessment of the lesions is crucial for decision making in order to optimize outcomes for the patient. Endoscopic submucosal dissection (ESD) is becoming increasingly common in Western countries and is currently proposed by the European Society of Gastrointestinal Endoscopy (ESGE) for the resection of large lesions due to the risk of harbouring a superficial invasive cancer. The rate of covert SMIC (unpredicted submucosal invasive cancer found on the specimen) has been described among endoscopic mucosal resection (EMR) specimen but is poorly known for rectal ESD in Europe.

Aim
In the current study, we aim to evaluate the rate of covert carcinoma among ESD specimen. Furthermore, we assess the efficacy and safety of this treatment approach in one European academic tertiary center.

Methods
Clinical and technical data from Erasme Hospital (Brussels) was systematically and prospectively collected from June 2015 to March 2019. Covert carcinoma is defined as no suspicion of cancer in the rectal lesion based on pit pattern analysis and pre-ESD biopsies if available. Complete resection (R0) is defined as no carcinoma and no adenoma on the margins. Curative resection is defined as en bloc R0 resection of a superficial lesion, well-differentiated adenocarcinoma (G1/G2), sm1 (≤1mm submucosal invasion, with no lymphovascular invasion, as defined by the ESGE). Procedure-associated complications and recurrence rate were also assessed.

Results
Sixty-four patients, mostly men (67.8%) with a mean age of 67 [30-85] years, underwent ESD for a superficial rectal lesion. Most of the lesions were laterally spreading tumors (61%) and were mainly located in the upper rectum (64% > 5 cm from the anal margin), with a mean size of 49 [10-130] mm. 80% of the lesions had a Paris O-Is component at endoscopic characterisation. The median duration of the procedure was 120 [IQR=120] minutes. En-bloc resection was achieved in 96.9% of patients and R0 resection in 59.4%. Histopathological examination displayed 31.3% (20/64) adenocarcinomas comprising 55% superficial tumors, 35% T1sm2/sm3 and 10% T2 lesions. Only 4 lesions were suspected to be carcinoma at the first evaluation, giving a covert carcinoma rate of 25% and a covert SMIC rate of 16.7%. Curative oncological resection was obtained in 40% of patients with carcinoma. Three out of five patients proposed for complementary surgery already underwent a surgical treatment and the histopathological examination showed no residual tumor on the specimen nor on lymphadenopathies. The other patients with a non-curative resection underwent a conservative follow-up strategy with no complementary treatment proposed, mostly due to the presence of significant comorbidities. Endoscopic follow-up was obtained in 32 benign lesion patients and 11 adenocarcinoma cases, disclosing a free-recurrence rate of 98% with only one case of recurrence (a patient with a non-curative resection of a T2 neoplasia). These results are in favour of coagulation artefacts on the specimen seeing the 59.4% R0 rate. Altogether, 94% of the patients had no complication needing an intervention: 3 presented delayed bleeding managed endoscopically and one patient presented stenosis that was calibrated after one balloon dilation.

Conclusions
ESD for superficial rectal lesions is showing favorable results in terms of efficacy and safety. A 25% rate of covert carcinoma and 16.7% rate of covert SMIC among large rectal polyps underlines the added value of using ESD compared to piece-meal resections in selected cases. Careful assessment of the lesions is crucial, but still not optimal, for decision making in order to improve outcomes for the patient.

Speakers

Mariana Figueiredo Ferreira

Ana-Maria Bucalau

Vincent Huberty

Laurine Verset

Calliope Maris

Jean-Luc Van Laethem

Issam El Nakadi

Arnaud Lemmers

Thursday March 5, 2020 16:36 - 16:48 CET
Room LIJN

BSGIE, Session 3

16:36 CET

Superficial adenocarcinoma of the esophagogastric junction (AEGJ) : outcomes of ESD in a Western cohort.

Authors
M. LEFEBVRE (1) / [1] UCLouvain, , Belgium, Gastro-enterology

Introduction
The incidence of cardia carcinoma is increasing in western societies over the past few years and associated with poor prognosis. Although endoscopic resection is recognized as the first-line therapy for superficial cancer of the gastrointestinal tract, data on ESD for superficial AEGJ in western cohorts remain scarce.

Aim
The aim was to analyze the feasibility, outcomes and safety of ESD for the management of superficial AEGJ in a large cohort of patients.

Methods
This is an observational and retrospective study. All consecutive patients presenting with AEGJ tumours who underwent ESD between 2006 and 2019 were included. The following main outcomes were comparatively evaluated: en-bloc, complete (R0), and curative (depth less than sm2, G1-2, LV0) resection rates, and local recurrence. Secondary outcomes were perforation and delayed bleeding.

Results
Eighty-eight tumours in eighty-four patients were included and classified as HGD (7.9%), well or moderately differentiated carcinoma (60,2%), poorly or undifferentiated carcinoma (31.8%). En bloc resection and R0 rates were 96.6% and 68.2% respectively (R0 for vertical margins 77.9%). Curative resection rate was 48,9% due to LV invasion in 13pts and G3 foci in 9 pt. Local recurrence rates after curative resection was 4.5% at a mean follow-up of 23.7 months [IC 9-36]. Adverse events including perforation, delayed bleeding, and esophageal stricture were 1.7%, 0% and 27.9%, respectively. No perforation required surgery.

Conclusions
ESD for superficial AEGJ showed a high en bloc resection with an acceptable safety profile. The curative resection was however much lower due to unforeseen LV invasion and poorly differentiated areas even in mucosal and submucosal cancer. Recurrence rates remains low after curative resection. Safety profile was acceptable with no serious adverse events.

Speakers

Maxence Lefebvre

Thursday March 5, 2020 16:36 - 16:48 CET
Room LIJN

BSGIE, Session 3

16:40 CET

The effects of oral bosentan treatment on the increased intrahepatic vascular resistance and disease severity of early NAFLD in rats

Authors
D. VAN DER GRAAFF (1), W. KWANTEN (2), J. DE MAN (1), B. DE WINTER (1), P. MICHIELSEN (2), S. FRANCQUE (2) / [1] University of Antwerp, , Belgium, Laboratory of Experimental Medicine and Pediatrics (LEMP), [2] UZA, Universitair Ziekenhuis Antwerpen, Edegem, Belgium, Gastroenterology and hepatology

Introduction
The intrahepatic vascular resistance (IHVR) is increased in early non-alcoholic fatty liver disease (NAFLD), impairing hepatic blood flow and potentially causing tissue hypoxia and disease progression. We previously demonstrated that this increase in IHVR is in part mediated by vascular hypersensitivity to endothelin-1 (ET-1), which could be blocked by ET-A receptor inhibition (Van der Graaff, Hepatol 2018;68(Suppl):1011A).

Aim
The aim of this study was to analyse the potential benefit of bosentan (BOS, an ET-A and -B receptor blocker) on liver haemodynamics and concurrent severity of disease in early NAFLD.

Methods
The effects of ET-1 inhibition were studied in male Wistar rats (n=8/group) fed a methionine-choline-deficient (MCD) diet, which induces severe steatosis after 4 weeks, or a control diet. Rats were daily gavaged with 100 mg/kg BOS or placebo during the complete 4 weeks of diet as preventive treatment or during the second 2 weeks of diet as curative treatment. The IHVR was studied by measuring the transhepatic pressure gradient (THPG) in an in situ ex vivo perfusion model at different flows (10-45 mL/min). Blood samples were collected before liver perfusion to determine ALT levels and liver tissue was harvested for histology.

Results
The basal THPG in steatotic livers was significantly increased compared to controls, with respectively 5.4 ± 0.3 mmHg and 4.4 ± 0.2 mmHg at 30 mL/min (p<0.001), as previously described (Van der Graaff et al., Lab Invest 2018). Preventive BOS treatment significantly decreased the THPG in steatotic livers, without affecting the THPG in controls (controls + placebo 9.2 ± 0.6 mmHg vs. controls + BOS 9.5 ± 0.3 mmHg, p = 0.27; steatosis + placebo 11.5 ± 0.4 mmHg vs. steatosis + BOS 10.1 ± 0.2 mmHg at 40 mL/min, p < 0.01). Moreover, despite comparable weight evolution (steatosis + placebo 199.6 ± 3.5 g and steatosis + BOS 200.3 ± 3.3 g at week 4, p = 0.898), liver weight and liver-to-total-body-weight (TBW) ratio were lower in preventive BOS-treated (4.6 ± 0.1% liver/TBW) compared to placebo-treated rats (5.2 ± 0.3% liver/TBW, p < 0.01) with steatosis. The degree of steatosis, expressed as % fat of total liver surface, was significantly lower in preventive BOS-treated rats (from 52.2 ± 0.7% placebo to 47.1 ± 2.0% BOS, p < 0.05). ALT significantly increased in MCD fed rats (94.9 ± 14.0 U/L), whereas preventive BOS-treated rats showed ALT levels comparable to control rats (48.4 ± 3.0 U/L, p < 0.05). In curative BOS-treated rats, we observed a similar significant decrease in THPG, liver and liver/TBW ratio and ALT level. The degree of steatosis showed an insignificantly decreased trend. In controls, none of the parameters were affected by BOS treatment.

Conclusions
BOS treatment significantly decreased the elevated THPG observed in steatosis. This effect goes along with a decrease in steatosis, lower liver weight and liver/TBW-ratio and normalisation of ALT in the absence of any effect on body weight. These findings strongly support the role of ET-1-related vascular alterations in NASH pathogenesis and its potential as a therapeutic target.

Speakers

Denise van der Graaff

Wilhelmus Kwanten

Joris De Man

Benedicte De Winter

Peter Michielsen

Sven Francque

Thursday March 5, 2020 16:40 - 16:50 CET
Room TEUN

BASL / BLIC, Session 4

16:45 CET

Predictors of treatment response to the traditional and the low FODMAP diet for patients with irritable bowel syndrome.

Authors
E. COLOMIER (1), L. VAN OUDENHOVE (2), J. TACK (1), L. BÖHN (3), S. BENNET (3), S. STÖRSRUD (3), L. ÖHMAN (3), H. TÖRNBLOM (3), M. SIMRÉN (3) / [1] KU Leuven, , Belgium, GI Motility and Sensitivity Research Group, Translational Research Center for GI Disorders, [2] KU Leuven, , Belgium, Laboratory for Brain-Gut Axis Studies, Translational Research Center for GI Disorders, [3] University of Gothenburg, Göteborg, Sweden, Institute of Medicine, Department of Internal Medicine & Clinical Nutrition, Sahlgrenska Academy

Introduction
The NICE traditional diet for irritable bowel syndrome (IBS) patients and the low fermentable oligo-, di-, monosaccharides, and polyols (FODMAP) diet have shown efficacy in IBS patients. Predictors of diet response remain to be identified.

Aim
Therefore, we aimed to investigate psychological, nutritional, and microbial factors as diet response predictors for 4 IBS symptoms.

Methods
Seventy-five IBS patients were randomized to the low FODMAP (n=38) or NICE diet (n=37) for 4 weeks. Baseline measures included stool samples evaluated by the GA-map™ Dysbiosis Test, generating a Dysbiosis Index, 4-day food diaries for calculation of average daily energy and FODMAP intake (DIETIST XP V.3.1, Kostdata.se, Sweden), Patient Health Questionnaire, Hospital Anxiety & Depression Scale and Visceral Sensitivity Index to measure somatic symptoms, psychological distress, and gastrointestinal (GI) anxiety, respectively. Outcome measures were 4 subscales (bloating, constipation, diarrhea, and pain) of the GI symptom rating scale treated as continuous variables in linear mixed models. Models included the main effect of baseline predictors on subscale scores, the main effect of time as a linear slope, and the interaction effect testing if baseline variables predict response slope. Lastly, a diet variable (including its main effect and all interactions) was added to test if baseline variables differentially predict response to the low FODMAP and NICE diet.

Results
We included 65 patients; 32 on low FODMAP and 33 on NICE diet. In models without covariates, both diets were shown to be effective and reduced the severity of bloating, diarrhea, pain (all p<0.0001), and constipation (p<0.05). Adding the diet variable to the model without covariates indicated absence of differences in response between the diets for any of the symptoms, thereby confirming an earlier analysis of Böhn et al. For pain, a lower dysbiosis index (p=0.02) and higher energy intake (p=0.003) predicted better response to both diets (table 1). For constipation, lower dysbiosis index predicted better response to both diets (p=0.009). For diarrhea, FODMAP intake tended to be associated with response to both diets (p=0.057), driven by a significant association between higher baseline FODMAP intake and better response to the NICE diet. For bloating, higher levels of psychological distress predicted worse response to both diets (p=0.03). FODMAP intake emerged as a differential predictor for treatment response (interaction effect: p=0.04), with higher baseline intake associated with worse response to the low FODMAP diet, and better response to the NICE diet.

Conclusions
Patterns of psychological, nutritional, and microbial factors predict treatment response to the low FODMAP and NICE diet for specific symptoms. These findings may inform individual tailoring of dietary treatment advice in IBS patients.

Speakers

Esther Colomier

Lukas Van Oudenhove

Jan Tack

Lena Böhn

Sean Bennet

Stine Störsrud

Lena Öhman

Hans Törnblom

Magnus Simrén

Thursday March 5, 2020 16:45 - 17:00 CET
Room TIFFANY/SHAH

GIREM, Session 4

16:50 CET

Impact of amino acid supplementation on sarcopenia in NASH

Authors
C. PICHON (1), M. NACHIT (1), G. VANDE VELDE (2), Y. HORSMANS (3), I. LECLERCQ (4) / [1] Université Catholique de Louvain, Brussels, Belgium, Laboratory of Hepato-Gastroenterology, [2] KU Leuven, , Belgium, Department of Imaging & Pathology, [3] Cliniques universitaires Saint-Luc, UCLouvain, Brussels, Belgium, Gastroenterology Unit, [4] Université Catholique de Louvain, Brussels, Belgium, IREC / Laboratory of Hepato-Gastroenterology

Introduction
NAFLD represents a spectrum of diseases ranging from benign steatosis (NAFL) to non-alcoholic steatohepatitis (NASH). Unlike simple steatosis, hepatocellular injury and inflammation in NASH promote fibrosis and evolution to end-stage liver disease. Cross-sectional studies clearly showed that decreased muscle functionality and myosteatosis, reflecting poor muscle quality, are strongly associated with NAFLD and linked to the severity of NASH. As previously demonstrated in the lab, NASH in high-fat diet fed foz/foz mice is associated with severe myosteatosis and loss of muscle strength. Yet, mechanisms linking the liver compartment to skeletal muscle are poorly known. Systemic hyperammonemia caused by ammonia detoxification impairment in liver could promote muscle alterations. L-Ornithine L-Aspartate (LOLA) is known as an effective ammonia-lowering agent, often used for treating hepatic encephalopathy.

Aim
To evaluate the impact of administration of LOLA, an ammonia lowering treatment, on muscle during NASH development.

Methods
We used foz/foz mice (FZ) fed a high fat diet (HFD, 60% fat) as a model of NASH. After 4 weeks, mice were randomized and continued on a HFD (Ctrl) or received a HFD with 2 g/kg/j L-Ornithine L-Aspartate supplementation in drinking water for 8 weeks (LOLA group). At 4 weeks intervals, we measured body weight, glycemia and systemic blood ammonia concentration, and performed micro-computed tomography (micro-CT) to monitor changes in body composition, dorsal muscle area, and skeletal muscle and liver fatty infiltration (expressed as muscle or liver density to spleen density ratio). Muscle strength was measured by grip strength test. At the end of the experiment (12 weeks HFD or 8 weeks LOLA treatment), mice were sacrificed to analyze white adipose tissue, liver and muscle histology.

Results
At sacrifice, although LOLA mice had larger epididymal adipose mass (1,78±0,10 g versus 1,45±0,03 g in Ctrl ; p=0,0002), we observed no significant difference between Ctrl and LOLA mice in body weight (56,31±5,73 g and 53,97±2,71 g, respectively), liver weight (5,64±0,35 g and 5,84±1,08 g), glycemia (222,3±50.5 mg/dl and 258,2±73,2 mg/dl) and muscle strenght (217,5±19,0 gr and 189,8±18,8 gr). Systemic ammonia concentration stayed stable and low over time in both groups with no difference between Ctrl and LOLA (108,75±20,1 µg/dl and 91,50±15,1 µg/dl, respectively). In Ctrl, muscle density gradually decreased with duration on HFD. LOLA supplementation prevented further changes in muscle density, such as at 12 weeks muscle density was 0,563±0,070 H.U. in Ctrl and 0,813±0,053 H.U. in LOLA (p<0,0001). This supports that LOLA alleviates NASH-associated myosteatosis. Dorsal muscle area was smaller in LOLA mice than in Ctrl (49,17±3,00 mm² versus 55,25±1,26 mm² ; p=0,0457). Liver density rapidly dropped with HF feeding, but was partially rescued by LOLA treatment such as liver density was significantly higher than in controls at the end of the experiment (-0.610±0,240 H.U. in Ctrl versus -0,105±0,112 H.U. in LOLA ; p<0,0001).

Conclusions
Amino acids supplementation prevents myosteatosis development in a context of NASH. Mechanisms and direction of the crosstalk between liver and muscle in NAFLD are being explored.

Speakers

Camille Pichon

Maxime Nachit

Greetje Vande Velde

Yves Horsmans

Isabelle Leclercq

Thursday March 5, 2020 16:50 - 17:00 CET
Room TEUN

BASL / BLIC, Session 4

16:50 CET

Endoscopic management of chronic pancreatitis

Speakers

A. Tringali (Roma - Italy)

Thursday March 5, 2020 16:50 - 17:20 CET
Room LIJN

BSGIE, Session 3

17:00 CET

Assessment of liver fibrosis stage in active NASH by VCT

Authors
J. WEYLER (1), L. VONGHIA (1), W. VERLINDEN (2), A. BAGDADI (1), P. MICHIELSEN (1), T. VANWOLLEGHEM (1), A. DRIESSEN (3), S. FRANCQUE (1) / [1] UZA, Universitair Ziekenhuis Antwerpen, Edegem, Belgium, Gastroenterology and hepatology, [2] AZ Nikolaas, Sint-Niklaas, Belgium, Gastroenterology and hepatology, [3] UZA, Universitair Ziekenhuis Antwerpen, Edegem, Belgium, Pathology

Introduction
Non-Alcoholic Fatty Liver Disease (NAFLD) is a highly prevalent chronic liver disease and represents a spectrum from Non-Alcoholic Fatty Liver (NAFL) to Non-Alcoholic Steatohepatitis (NASH), fibrosis, cirrhosis and hepatocellular carcinoma. Patients with NAFLD and significant fibrosis (≥F2) are at highest risk for development of complications. Several non-invasive methods have been developed to diagnose and stage fibrosis. Vibration Controlled Transient Elastography (VCTE) is currently the most validated non-invasive technique to determine liver fibrosis stage. Besides food intake, alcohol consumption, congestion, and cholestasis, disease activity (inflammation) is correlated with overestimation of liver stiffness.

Aim
We aimed at studying the accuracy to detect liver fibrosis assessed by the VCTE in patients with NASH compared to patients without NASH in a cohort with biopsy-proven NAFLD.

Methods
Patients who underwent both a liver biopsy and VCTE in our centre and diagnosed with NAFLD were prospectively included. The different pathological features of NAFLD were scored using the Fatty Liver Inhibition of Progression (FLIP) algorithm. The diagnosis of NAFL required the presence of steatosis, whereas the diagnosis of NASH required the combined presence of steatosis, ballooning and lobular inflammation. The discriminative power of VCTE for the different fibrosis stages was assessed using ROC analysis. The potential added value of ALT and AST on the previously described indices was analysed using a binary regression model, ROC analysis was performed on the saved predicted values of these regressions.

Results
131 NAFLD patients were included. 31 patients or 23.7% had NAFL, fibrosis classification in this group was as follows: 45.2 % F0, 25.8% F1, 6.4 % F2, 9.7 % F3 and 12.9 % F4. 100 patients (or 76.3%) were included with NASH with fibrosis classification: 21.0 % F0, 29.0% F1, 20.0 % F2, 26 % F3 and 4 % F4. AUROC for predicting ≥F1 by VCTE was 0.729 in NASH compared to 0.903 in NAFL; AUROC for predicting ≥F2 by VCTE was 0.784 in NASH compared to 0.854 in NAFL; AUROC for predicting ≥F3 by VCTE was 0.804 in NASH compared to 0.899 in NAFL and AUROC for predicting F4 by VCTE was 0.889 in NASH compared to 0.972 in NAFL. To improve the accuracy of predicting fibrosis stage a combination of ALT, AST and VCTE was used. This resulted In the following AUROCs when combining VCTE and ALT: 0.772 for predicting ≥F1, 0.773 for predicting ≥F2, 0.800 for predicting ≥F3 and 0.875 for predicting F4. AUROCS for the combination of VCTE and AST were as follows: 0.783 for predicting ≥F1, 0.787 for predicting ≥F2; 0.798 for predicting ≥F3 and 0.884 for predicting F4.

Conclusions
Although VCTE is able to predict liver fibrosis stage with high accuracy, there is an important negative impact of disease activity on the accuracy when assessing liver fibrosis. Furthermore, there is no significant improvement of accuracy when using a combination of liver stiffness and ALT or AST for the prediction of liver fibrosis stage

Speakers

Jonas Weyler

Luisa Vonghia

Wim Verlinden

Ali Bagdadi

Peter Michielsen

Thomas Vanwolleghem

Ann Driessen

Sven Francque

Thursday March 5, 2020 17:00 - 17:10 CET
Room TEUN

BASL / BLIC, Session 4

17:00 CET

Somatization, anxiety, depression and fear of pain levels are not significantly different across the gastroesophageal reflux disease spectrum.

Authors
A. GEERAERTS (1), L. VAN OUDENHOVE (2), H. GEYSEN (1), T. VANUYTSEL (1), J. TACK (1), A. PAUWELS (1) / [1] KU Leuven, , Belgium, TARGID, [2] KULeuven, Leuven, Belgium, TARGID

Introduction
Co-morbid somatization, (symptom-specific) anxiety and depression symptoms are prevalent in functional gastrointestinal disorders, such as functional dyspepsia. Based on previous research, it has been hypothesized that patients with functional heartburn (FH) display higher levels of anxiety and depression compared to the other phenotypes in the gastroesophageal reflux disease (GERD) spectrum. Furthermore, some studies suggest that psychological aspects play an important role in the pathophysiology of reflux hypersensitivity (RHS). However, it has recently been shown that esophageal hypervigilance and symptom-specific anxiety are consistent among the GERD spectrum, regardless of the acid exposure time (AET).

Aim
To investigate levels of somatization, anxiety, depression, and fear of pain among the different GERD phenotypes in a large cohort of patients seen at a tertiary care center.

Methods
Patients with typical GERD symptoms (‘on' or ‘off' proton pump inhibitors (PPIs), undergoing 24 hour impedance-pH monitoring (MII-pH) were asked to fill out several questionnaires. Patients were classified in 4 categories based on the MII-pH recordings (Lyon consensus): true GERD, borderline GERD, RHS and FH. Depression and somatization were measured using the Patient Health Questionnaire (PHQ-9, PHQ-12, PHQ-15), anxiety was measured using the generalized anxiety module of the PHQ(7) and fear of pain was assessed with the Pain Anxiety Symptom Scale (PASS). Data were analyzed using SAS 9.5 (SAS Institute, Cary, NC, USA). General linear models were used to compare the averages between the 4 groups.

Results
Three hundred fifty-four patients were included, which were classified as follows: 115 true GERD, 68 borderline GERD, 57 RHS and 114 FH. Patients with RHS were significantly younger compared to patients with true GERD, borderline GERD and FH. Although the percentage of females was slightly higher in RHS and FH, this did not reach statistical significance. Patients with true GERD had a significantly higher BMI compared to patients with RHS and FH. Most importantly, we could not find any significant differences between groups in PHQ and PASS scores. The prevalence of depression (PHQ9 sum score ≥10) was 41% in our cohort, which is markedly higher compared to only 5.6% in the general population. 26.5% of our patients displayed a high level of somatization (PHQ15 sum score ≥15), compared to 3.1% in the general population.

Conclusions
This study shows that somatization, anxiety, depression and fear of pain was not higher in FH and RHS compared to patients with true and borderline GERD. Overall, our cohort shows a higher prevalence rate for depression and somatization compared to the general population. Therefore, screening for psychological and extraintestinal symptoms should be routinely performed in all different GERD phenotypes.

Speakers

Annelies Geeraerts

Lukas Van Oudenhove

Hannelore Geysen

Tim Vanuytsel

Jan Tack

Ans Pauwels

Thursday March 5, 2020 17:00 - 17:15 CET
Room TIFFANY/SHAH

GIREM, Session 4

17:15 CET

Satellite Symposium ALNYLAM

The right diagnosis is the only way out. Unravel the cause of unexplained, severe abdominal pain.

Speakers

David Cassiman

Frédéric Cotton

Alnylam satellite symposium A5 HR pdf

Thursday March 5, 2020 17:15 - 17:45 CET
Room TEUN

BASL / BLIC

17:20 CET

BSGIE Award Ceremony (Best Presentation / Best Abstract)

Thursday March 5, 2020 17:20 - 17:25 CET
Room LIJN

BSGIE, Session 3

17:45 CET

BASL Prizes & General Assembly

Thursday March 5, 2020 17:45 - 18:00 CET
Room TEUN

BASL / BLIC, Session 4

08:30 CET

Breakfast Symposium ELI LILLY

Lightning talks on aHCC - Addressing the gaps & looking ahead.
A 30-minute update consisting of 4 short and dynamic topics.

Speakers

Ivan BORBATH

Jeroen Dekervel

ELI LILLY pdf

Friday March 6, 2020 08:30 - 09:00 CET
Room TEUN

BGDO, Session 1

09:00 CET

Real world incidence of microsatellite instability or EBV positivity in a Belgian cohort of patients with adenocarcinoma of the esophagus, gastroesophageal junction and stomach

Authors
S. DE MEULDER (1), X. SAGAERT (2), P. NAFTEUX (3), B. TOPAL (4), C. VERSLYPE (5), S. TEJPAR (5), E. VAN CUTSEM (5), J. DEKERVEL (5) / [1] University Hospital, Gasthuisberg, Leuven, Belgium, , Belgium, Gastro-enterology, [2] University Hospital, Gasthuisberg, Leuven, Belgium, , Belgium, Pathology, [3] University Hospital, Gasthuisberg, Leuven, Belgium, , Belgium, Thoracic Surgery, [4] University Hospital, Gasthuisberg, Leuven, Belgium, , Belgium, Abdominal Surgery, [5] University Hospital, Gasthuisberg, Leuven, Belgium, , Belgium, Gastroenterology and Hepatology

Introduction
Patients with adenocarcinomas of the esophagus, gastroesophageal junction (GEJ) or stomach with microsatellite instability (MSI) or Epstein Bar Virus positivity (EBV+) might be good candidates for immunotherapy. Incidences of about 10% have been reported for both features, but are dependent on geographical region and disease stage (1).

Aim
The aim is to study the occurrence of MSI and EBV + in a single center cohort of patients with adenocarcinoma of the esophagus and stomach.

Methods
We retrospectively assessed the files of all patients with a newly diagnosed adenocarcinoma of the esophagus, GEJ or stomach between 1/8/2018 and 31/10/2019. MSI status was determined using immunohistochemistry (IHC) and polymerase chain reaction (PCR). EBV + was assessed using in situ hybridization.

Results
Between 1/8/2018 and 31/10/2019 there were 226 newly diagnosed adenocarcinomas of the esophagus, GEJ and stomach. 55 (66,0% stage IV) of them were tested for EBV, but only 1 turned out to be EBV positive (1,8%). 97 patients (54,3% stage IV) were tested for MSI using IHC, of which 8 were MSI-high (8,2%). All MSI-high cases were confirmed by PCR. The EBV positive patient had stage IV disease at presentation. Of the MSI-high patients, 2 had stage Ib cancer, 1 stage III and 2 stage IV. The disease stage of 3 patients was unknown. Half of the MSI-high tumors identified were located at the GEJ.

Conclusions
The incidence of EBV+ in our cohort is clearly lower than would be expected after reviewing the literature (2,3). Due to the presence of therapeutic implications, testing was mostly performed in stage IV disease which might entail a selection bias. The lower incidence of EBV+ may also be due to geographical and racial factors (4). Finally, we found a remarkably high incidence of MSI-high tumors in the GEJ. The reflex to test for MSI should therefore not be based on the location of the tumor. References: 1. Nishikawa J, Iizasa H, Yoshiyama H, Shimokuri K, Kobayashi Y, Nakamura M, et al. Clinical Importance of Epstein–Barr Virus-Associated Gastric Cancer. :1–13. 2. Kim ST, Cristescu R, Bass AJ, Kim K, Odegaard JI, Kim K, et al. Comprehensive molecular characterization of clinical responses to PD-1 inhibition in metastatic gastric cancer. Nat Med [Internet]. 2018;24(September). Available from: http://dx.doi.org/10.1038/s41591-018-0101-z 3. Gu L, Chen M, Guo D, Zhu H, Zhang W, Pan J, et al. PD-L1 and gastric cancer prognosis : A systematic review and meta-analysis. 2017;1–14. 4. Bass AJ, Thorsson V, Shmulevich I, Reynolds SM, Miller M, Bernard B, et al. Comprehensive molecular characterization of gastric adenocarcinoma. Nature [Internet]. 2014;513(7517):202–9. Available from: http://dx.doi.org/10.1038/nature13480

Speakers

Sofie De Meulder

Xavier Sagaert

Philippe Nafteux

Baki Topal

Chris Verslype

Sabine Tejpar

Eric Van Cutsem

Jeroen Dekervel

Friday March 6, 2020 09:00 - 09:15 CET
Room TEUN

BGDO, Session 1

09:00 CET

Biliary complications in human alveolar echinococcosis: a case report.

Authors
M. ABDESSALAMI (1), G. RASSCHAERT (1), L. DUEZ (1), C. SALEM (1), P. EISENDRATH (1), T. SERSTE (2) / [1] CHU Saint-Pierre, Brussels, Belgium, Hepato Gastroenterology, [2] CHU Saint-Pierre, Brussels, Belgium, Hépato-Gastroenterologie
Introduction Alveolar echinococcosis (AE) is caused by the larval stage of the fox tapeworm Echinococcus multilocularis. This rare parasitic infection can be associated with biliary complications (biliary strictures, dilations and fistulas) and may eventually lead to secondary biliary cirrhosis. Apart from partial hepatectomy, treatment options include long term antiparasitic chemotherapy. Biliary damage occurs in about 30% of cases and is potentially treated with therapeutic endoscopic procedures. Case report A 30-year-old Caucasian male, presented at our institution with ascites. He was treated 3 years ago in Russia for an undisclosed affection of the liver leading to a partial right hepatectomy. Exact information on his medical record was difficult to obtain. Numerous stellate angiomata and tensed ascites were observed during clinical examination. A chest X-ray suggested the presence of an organized pleural effusion. The blood panel demonstrated mild cholestasis (alkaline phosphatase 1.3 times the upper limit of the normal), mild hyperbilirubinemia (3.1mg/dL), thrombocytopenia (65.000 platelets per µL) and a prothrombin time of 66.9%. Viral serology showed the presence of HBs Ag without detectable DNA levels. Magnetic resonance cholangiopancreatography (MRCP) revealed a highly dysmorphic liver. The post-hepatectomy status of liver segments VI and VII was confirmed. Multiple cystic lesions (uncountable, about 5 to 10 mm) with thick walls, without bile duct communication, were found throughout the liver parenchyma. Multiple biliary duct stenosis and dilations, both intrahepatic and extrahepatic were described on MRCP. These abnormalities mimicked sclerosing cholangitis and were mainly located on right liver. A 2 cm long filiform subhilar bile duct stricture required insertion of 3 plastic biliary stents (12 and 15 cm, 8.5 French) via endoscopic retrograde cholangiopancreatography (ERCP). This endoscopic procedure confirmed the sclerosing cholangitis-like shape of the right intrahepatic bile tree and disclosed a biliary fistula communicating with the right pleural cavity. Three different parasite serology tests for AE performed on a blood sample were positive: a haemagglutination essay, a western blot and an ELISA EM18 (Kit Bordier®). Western blotting was used as confirmatory test. Moreover, the ELISA that was highly positive, is known to be the most specific for AE. Liver biopsy was performed and found to be compatible with the diagnosis of secondary biliary cirrhosis and microscopic cholangitis. The final diagnosis of AE and secondary biliary cirrhosis was retained. A long term treatment with albendazole 800mg daily was initiated. Pleural effusion and ascites were controlled after biliary drainage and proper diuretic prescription. Median and long term clinico-biological evolution is currently under investigation and the hypothesis of a future liver transplant as a definitive cure is not ruled out. Discussion Echinococcus multilocularis is distributed throughout the Northern Hemisphere. It remains a rare disease in Western Europe, compared to endemic regions such as Russia where our patient was born. During the course of the disease, AE can mimic a neoplastic lesion with progressive growth and dissemination from the liver towards several organs. Treatment options include surgery, as the preferred first line therapy (including liver transplantation), and long-term chemotherapy with benzimidazoles. Despite treatment, biliary complications still occur in one third of the patients, significantly influencing the outcome. The bile ducts and the intrahepatic biliary tree can be compressed or even destroyed by the growing parasite. The clinical presentation of these biliary complications encompass cholangitis lesions (defined as abnormal ERCP or MRCP findings that could evocate sclerosing cholangitis), common bile duct stenosis, biliary fistulas and secondary biliary cirrhosis. AE is a severe infectious disease with significant morbidity and mortality despite substantial increases in diagnostic and therapeutic improvements. Conclusion This case report of hepatic AE with biliary strictures and fistulas leading to secondary biliary cirrhosis, illustrates the whole spectrum of biliary complications that potentially characterize the natural course of this rare infectious disease. References 1. Torgerson PR, Schweiger A, Deplazes P,et al. Alveolar echinococcosis: from a deadly disease to a well-controlled infection. Relative survival and economic analysis in Switzerland over the last 35 years. J Hepatol 2008; 49: 72-77 2. Kadry Z, Renner EC, Bachmann LM,et al. Evaluation of treatment and long-term follow-up in patients with hepatic alveolar echinococcosis. Br J Surg 2005; 92: 1110-1116

Speakers

Mohamed Abdessalami

Gertjan RASSCHAERT

Leo DUEZ

Charelle Salem

Pierre Eisendrath

Thomas SERSTE

Friday March 6, 2020 09:00 - 09:15 CET
TBA

Case Reports Hepathology, Session 1

09:00 CET

Oesophagitis (non-Barrett).

Speakers

A. Driessen (UZ Antwerpen)

Friday March 6, 2020 09:00 - 09:30 CET
Room LIJN

WGD Pathology, Session 1

Live Demonstrations

Speakers

D. Blero (ULB Erasme)

A. Tringali (Roma - Italy)

P. Eisendrath (ULB Saint-Pierre)

C. Snauwaert (UCL Saint-Luc - Brussels)

Friday March 6, 2020 09:00 - 10:30 CET
Room TIFFANY-SHAH

BSGIE Live, Session 1

09:15 CET

Induction by mFOLFIRINOX followed by stereotaxic body radiotherapy with simultaneous integrated boost (SIB-SBRT) at the tumor-vessel interfaces (TVI) for the neoadjuvant treatment of localized pancreatic cancers.

Authors
C. BOUCHART (1), J. ENGELHOLM (2), M. BALI (2), J. CLOSSET (3), J. NAVEZ (3), P. LOI (3), Y. GÖKBURUN (4), T. DE GREZ (4), A. HENDLISZ (5), L. MANS (6), P. EISENDRATH (7), D. VAN GESTEL (1), L. MORETTI (1), J. VAN LAETHEM (6) / [1] Institut Jules Bordet - Université Libre de Bruxelles (ULB), Brussels, Belgium, Radiotherapy-Oncology, [2] Institut Jules Bordet - Université Libre de Bruxelles (ULB), Brussels, Belgium, Radiology, [3] Erasme University Hospital - Université Libre de Bruxelles (ULB), Bruxelles, Belgium, Gastrointestinal Surgery, [4] CHR, Namur, Belgium, Gastroenterology and digestive oncology, [5] Institut Jules Bordet - Université Libre de Bruxelles (ULB), Brussels, Belgium, Digestive Oncology, [6] Erasme University Hospital - Université Libre de Bruxelles (ULB), Bruxelles, Belgium, Gastroenterology- Hepatology and Digestive Oncology, [7] CHU Saint-Pierre, Brussels, Belgium, Gastroenterology

Introduction
The optimal treatment sequence for localized pancreatic ductal adenocarcinoma (PDAC) remains controversial. The stereotactic body radiotherapy (SBRT) technique has the advantages of limiting interruption of systemic treatments and increasing the biological equivalent dose delivered potentially leading to improved local control, resection rates and overall survival (OS).

Aim
We report here the preliminary results of our neoadjuvant treatment strategy including mFOLFIRINOX followed by SBRT with simultaneous integrated boost (SIB) at the tumor-vessels interfaces (TVI).

Methods
From August 2017, all patients diagnosed with high-risk resectable (HR-R), borderline (BR), or locally advanced (LA) PDAC - according to the criteria defined by the National Comprehensive Cancer Network (NCCN) - were prospectively included. Induction by mFOLFIRINOX alone or followed by gemcitabine/nab-paclitaxel (G/NabP) if no response or intolerance was delivered for an average of 7 cycles. After a radiological assessment showing no progression, SBRT was delivered (35Gy in 5 sessions) with a TVI-SIB up to 50Gy. Patients with partial, complete response (CR) or stable disease were explored for oncologic resection 4 to 6 weeks after SBRT. Acute toxicities (≤ 6 months) were graded according to CTCAE v.4.

Results
Twenty-seven patients with localized PDAC - 1 HR-R, 9 BR, 17 LA - received either mFOLFIRINOX only (85%) or followed by G/NabP (15%). The median age at diagnosis was 60.5 years (P25 52 - P75 70) and the median follow-up is currently 11.5 months (P25 7 - P75 14.5). After radiological assessment, 3 patients developed metastases, 1 presented a CR and surgery was directly performed, 2 were not candidates for SBRT due to the failure of fiducials insertion and 21 received SIB-SBRT (78%). Of these 21 patients, 4 became metastatic at the pre-surgical assessment (19%), 4 were inoperable due to portal cavernoma or initial contraindication to general anesthesia (19%) and 13 patients (62%; 1HR-R, 5 BR, 7 LA) were explored. Resection was not performed in 4 patients due to per-operative discovery of liver metastases (n=2/13) or non-reconstructible vascular invasion (n=2/13). The R0 resection rates >0.1mm and ≥1mm are respectively 78% (n=7/9) and 44% (n= 4/9). The 6 months OS and progression free survival rates are respectively 100% and 70% for the entire cohort. To date, the 1-year OS for patients with sufficient follow-up who received the complete neoadjuvant sequence with SBRT is 91% (n=10/11) versus 81% for the entire cohort (n=13/16). Acute toxicity is minimal, with most patients experiencing fatigue (grade≤2: 90%) and flare-up epigastric pain (grade 1: 52%). No acute grade ≥3 gastrointestinal toxicity has been reported.

Conclusions
These preliminary results indicate that the integration of SIB-SBRT following multi-agent induction chemotherapy is feasible for the neoadjuvant treatment of localized PDAC. Our first analyses show favorable R0 resection rate, acute toxicity profile and 1-year OS in selected patients.

Friday March 6, 2020 09:15 - 09:30 CET
Room TEUN

BGDO, Session 1

09:15 CET

Just another liver cyst (or not!)

Authors
L. ABREU DE CARVALHO (1), O. UYTTEBROEK (1), A. VANLANDER (2), X. ROGIERS (2), F. BERREVOET (2) / [1] Ghent University Hospital, Ghent, Belgium, HPB surgery and liver transplantation, [2] Ghent University Hospital, Ghent, Belgium, HPB surgery and Liver transplantation
We report the case of a 34-year-old male who was referred to the emergency department after the recent onset of jaundice, weight loss and pain in the upper abdominal quadrants. CT-scan showed a cystic structure at the hepatic hilum of 14 cm diameter with intrahepatic bile duct dilation and a thrombus in the inferior vena cava (IVC). Total bilirubin was 12 mg/dl. Careful interpretation of the imaging led to the diagnosis of a type IV4a bile duct cystic dilation (multiple intra- and extrahepatic bile duct cysts - according to the modified Todani classification) with a thrombus in the IVC as a result of compression. Due to the risk of malignant transformation, an oncologic resection of the affected bile duct segments was planned, although no malignancy was suspected. Surgery was performed according to the planning with a combination of left hepatectomy, duodenopancreatectomy and thrombectomy of the IVC. There were no major complications and the patient was discharged after 20 days. Pathology report showed a pT3N2 cholangiocarcinoma with R0 resection. Cystic dilation of the common bile duct causes biliary obstruction resulting in proximal dilation of the intrahepatic bile ducts, but it is important to distinguish this finding from abnormal cystic dilation to be able to plan a correct and realistic surgical approach. Diffuse intrahepatic cystic dilations of the bile ducts (Todani type V – Caroli disease) can only be treated with a liver transplantation. In this case it meant being able to propose a left hepatectomy. Diagnostic work-up and treatment options for this challenging condition in adult patients shall be discussed.

Speakers

Luís Filipe Abreu de Carvalho

Ortwin Uyttebroek

Aude Vanlander

Xavier Rogiers

Frederik Berrevoet

Friday March 6, 2020 09:15 - 09:30 CET
TBA

Case Reports Hepathology, Session 1

09:30 CET

Feasibility and clinical impact of routine molecular testing of gastrointestinal (GI) cancers at a tertiary centre with a multi-gene, next generation sequencing (NGS) panel

Authors
G. BREGNI (1), T. STICCA (2), T. AKIN TELLI (1), S. CAMERA (1), L. CRACIUN (3), L. SHAZA (1), A. DELERUELLE (1), M. ANCIAUX (1), G. MACHIELS (1), A. DELEPORTE (1), C. VANDEPUTTE (1), P. DEMETTER (3), D. LARSIMONT (3), A. HENDLISZ (1), F. SCLAFANI (1) / [1] Institut Jules Bordet - Université Libre de Bruxelles (ULB), Brussels, Belgium, Medical Oncology, [2] Institut Jules Bordet - Université Libre de Bruxelles (ULB), Brussels, Belgium, Molecular Pathology, [3] Institut Jules Bordet - Université Libre de Bruxelles (ULB), Brussels, Belgium, Pathology

Introduction
High-throughput sequencing technologies have been increasingly used in research, but limited data are available on the feasibility and clinical value of these when adopted as part of standard care. Since 2014, a multi-gene NGS panel has been used in routine clinical practice in our Cancer Network, with a central laboratory being accredited to carry out molecular profiling at the request of the treating physician.

Aim
Five years after the implementation of this NGS panel in our Cancer Network, we have analysed feasibility and clinical implications of routine multi-gene NGS testing in gastrointestinal cancer patients.

Methods
All consecutive gastrointestinal cancer patients for whom tumour genomic testing by a multi-gene NGS panel was requested from April 2014 to Jun 2019 as part of routine practice in the IRIS Network were retrospectively identified from a prospectively maintained database. The Truseq Amplicon Cancer Panel (Illumina) was regularly used as NGS assay over the study period. This is a multiplexed targeted resequencing assay that allows the detection of mutations (at a frequency below 5%) in hotspots regions of 48 cancer-related genes including ABL, AKT, ALK, APC, ATM, BRAF, CDH1, CDKN2A, CSF1R1, CTNNB1, EGFR, HER-2, HER-4, FBXW7, FGFR-1, FGFR-2, FGFR-3, FLT-3, GNA11, GNAQ, GNAS, HNF1A, HRAS, IDH-1, JAK-2, JAK-3, KDR, KIT, KRAS, MET, MLH1, MPL, NOTCH-1, NPM1, NRAS, PDGFRA, PIK3CA, PTEN, PTPN11, RB-1, RET, SMAD-4, SMARCB1, SMO, SRC, STK11, TP53, and VHL. The primary objective of the study was feasibility, assessed by analysing the test success rate and the median turnaround time in the IRIS Network population. Secondary objectives included NGS results and the impact that these had on the management decisions for patients treated at the Institut Jules Bordet. Associations were tested with Fisher’s test or Chi-square test, as appropriate. P values <0.05 were considered as statistically significant.

Results
From April 2014 to June 2019, 447 NGS tests were requested for patients with gastrointestinal cancers within the IRIS Network. Sequencing was successful in 421 cases (93.8%), 279 of which were managed at the Institut Jules Bordet (224 colorectal (CRC), 21 oesophago-gastric, 17 bilio-pancreatic, 9 GIST, 4 appendix, 3 small intestine, 2 hepatocellular). In successful and failed cases, respectively, analyses were attempted on core biopsy (37.0% vs 66.7%), surgery (62.6% vs 16.7%), and fine needle aspiration (0.4% vs 12.4%) samples (p<0.001). Median turnaround time was 12.5 days, reducing from 17 days in 2014 to 10 days in 2019 (p<0.0001). The majority of successfully tested patients (85.6%) had metastatic disease. Across all tumour types, TP53 was the most frequently mutated gene (45.9%), followed by APC (42.1%), KRAS (39.7%), PIK3CA (12.1%), SMAD4 (7.6%), BRAF (6.2%), and NRAS (5.5%). All other mutated genes were detected in less than 5% of samples. Excluding RAS/BRAF and KIT/PDGFR mutations, sequencing results impacted on the management of 4 (1.4%) patients. Using the publicly available OncoKB Database and excluding well known actionable or clinically relevant mutations such as KRAS, NRAS, BRAF, KIT and PDGFRA, 57 out of the 279 successfully tested patients (20.4%) had tumours harbouring at least one altered actionable gene. When taking into account the tumour type in which the altered gene is known to be actionable, only 10 (3.6%) of the study patients could be candidate for targeted treatment. To further evaluate the clinical impact of the additional mutations detected by NGS, we searched through the Clinical Trials Transformation Initiative trials registry for available clinical trials for which patients could have been screened if they all had been tested in October 2019. This analysis revealed that a genomically-matched clinical trial could be offered to up to 65 patients (23.3%).

Conclusions
Our findings confirm that multiple NGS testing is feasible in the clinical setting with acceptably low failure rates and rapid turnaround time. Nevertheless, genomic data that were additional to those routinely provided by standard targeted sequencing had virtually no influence on the management of patients during the study period. The clinical impact of the NGS technology could substantially increase with the identification of new biologically relevant genetic alterations, the increased availability of novel therapeutics and genomically-matched clinical trials, and the routine implementation of institutional/network Molecular Tumour Boards.

Friday March 6, 2020 09:30 - 09:45 CET
Room TEUN

BGDO, Session 1

09:30 CET

Pleural effusion and elevated liver tests: think viral!

Authors
J. MEESTERS (1), J. MAUS (2), S. NAEGELS (2) / [1] Universiteit Antwerpen / Antwerp University Hospital, WILRIJK (Antwerpen), Belgium, Gastroenterology, [2] ZNA Middelheim, Antwerpen, Belgium, Gastroenterology and hepatology
We present a case of a 37-year-old man from Tibetan origin who presented at the emergency ward with diffuse abdominal tenderness, bloating and a dark discoloration of the urine. There were no complaints of fever, nausea or vomiting. There was no weight lost and the stools were normal. There was no significant prior history and he did not take any chronic medication. He had lived in Belgium for the past 15 years and had not gone abroad in that time. Clinical examination was normal, except for reduced breathing noises on the right side on lung auscultation. An x-ray of the thorax showed right-sided unilateral pleural effusion. Laboratory test showed a normal peripheral blood count, normal kidney function tests and normal electrolytes. The liver enzymes were elevated with a conjugated hyperbilirubinemia of 3,9 mg/dL and elevated transaminase liver tests with an ALAT of 1388 U/L and an ASAT of 961 U/L. A urgent CT scan confirmed unilateral pleural effusion and mild ascites, without any other structural problems. The liver parenchyma was homogenous and there were no signs of liver ischemia or vascular abnormalities. Further serological testing showed an acute hepatitis B infection with positive HBV surface antigen, positive HBV e-antigen, positive HBV IgM core antibodies and a viral load of 13600000 IU/L. Other causes of hepatitis were excluded (serology for hepatitis A, C, E, auto-immune causes and storage diseases). A diagnostic punction of the unilateral pleural effusion was performed which showed a exsudative fluid (protein count 34,6 g/L and protein to serum ratio of 0.59) and a lymphocytic predominance. Routine culture of the fluid was negative, TBC was excluded and cytology of the fluid came back negative for malignant cells. The diagnosis of acute hepatitis B infection was made with a secondary unilateral viral pleural effusion. No treatment was started, as there were no signs of acute liver failure. In the following weeks after diagnosis, there was a spontaneous normalization of the liver enzymes. After three weeks, the pleural effusion resolved completely. Unilateral pleural effusion complicating an acute hepatitis B infection is a rare. The first case was reported in 1971, with spontaneous resolution of the pleural effusion. (1) We found no more than ten cases described in Anglo-saxon literature, mostly in the pediatric population. (1-4, 5, 8) Unilateral pleural effusion as a result of viral hepatitis has been discussed in the literature, but mostly secondary to an acute hepatitis A infection. (6-8, 9). The underlying mechanism is not fully understood. It is thought to be immune-mediated secondary to immune circulating complexes. These immune complexes also cause polyarteritis nodosa and glomerulonephritis secondary to hepatitis. The underlying mechanism of immune complexes has been proven in glomerulonephritis, but has not yet been proven as a cause of pleural effusion (4). 1. Gross PA. Pleural effusion associated with viral hepatitis. Gastroenterology. 1971;60(5):898-902. 2. Cocchi P,. Letter: Pleural effusion in HBsAG-positive hepatitis. Journal of pediatrics. 1976;89(2):329-30. 3. Flacks LM. A case of hepatitis B with pleural effusion. Australian and New Zealand journal of medicine. 1977;7(6):636-7. 4. Lee HS. Pleural effusion coinciding with acute exacerbations in a patient with chronic hepatitis B. Gastroenterology. 1989;96(6):1604-6. 5. Merrill WD. Hepatitis antigen in pleural fluid. Annals of internal medicine. 1977;87(2):247. 6. Ko YS. [A case of pleural effusion associated with acute hepatitis A]. Korean journal of gastroenterology. 2010;55(3):198-202. 7. Tesovic G. Pleural effusion associated with acute hepatitis A infection. The Pediatric infectious disease journal. 2000;19(6):585-6. 8. Dalai R. A rare case of childhood Hepatitis A infection with pleural effusion, acalculous cholecystitis, and ascites. Journal of family medicine and primary care. 2018;7(6):1581-3. 9. Nail, Abdelsalam. Recurrent Exudative Pleural Effusion with Flare up of Chronic Hepatitis B Virus Infection. Sudan Journal of Medical Sciences. 2011/12/01: 281-284 10. Dhakal AK. An unusual association of pleural effusion with acute viral hepatitis A infection. Pediatric Health, Medicine and Therapeutics: 23 October 2014 Volume 2014:5 Pages 149—153

Speakers

Johanna Meesters

Jeroen Maus

Serge Naegels

Friday March 6, 2020 09:30 - 09:45 CET
TBA

Case Reports Hepathology, Session 1

09:30 CET

Dysplasia and submucosal oesophageal lesions: what gastroenterologists want to know from pathologists?

Speakers

D. Tate (UZ Gent)

Friday March 6, 2020 09:30 - 10:00 CET
Room LIJN

WGD Pathology, Session 1

09:45 CET

DNA Methylation Analysis of the PDX1 Gene can be used for PNET Subtyping and has a Possible Prognostic Value

Authors
G. BOONS (1), T. VANDAMME (2), J. IBRAHIM (3), A. SCHEPERS (3), G. ROEYEN (4), A. DRIESSEN (4), C. BLENKIRON (5), K. PARKER (6), M. PEETERS (4), G. VAN CAMP (3), K. OP DE BEEK (1) / [1] University of Antwerp, , Belgium, CORE / Human Molecular Genetics, [2] Universiteit Antwerpen / Antwerp University Hospital, WILRIJK (Antwerpen), Belgium, NETwerk, [3] University of Antwerp, , Belgium, Human Molecular Genetics, [4] UZA, Universitair Ziekenhuis Antwerpen, Edegem, Belgium, NETwerk, [5] University of Auckland, , New Zealand, Maurice Wilkins Centre & Department of Molecular Medicine and Pathology, School of Medical Sciences, Faculty of Medicine and Health Sciences, [6] University of Auckland, , New Zealand, Discipline of Oncology, Faculty of Medicine and Health Sciences

Introduction
Estimating prognosis of non-functional pancreatic neuroendocrine tumour (PNET) patients remains challenging. Mutation status of DAXX/ATRX/MEN1, histone modification patterns and immunohistochemistry for relevant transcription factors, including PDX1, have recently been used to perform subtyping and distinguished two main subtypes, A and B. These subtypes are linked to cell-of-origin and associated with clinical outcome.

Aim
In this study, we assessed whether DNA methylation of PDX1 can be used to identify the A and B subtypes, linked to cell-of-origin, and tested the prognostic value of these subtypes.

Methods
DNA methylation analysis using Infinium Methylation EPIC and 450K arrays (Illumina) was performed on DNA from fresh-frozen tissue of 41 PNETs. Additional DNA methylation data of 42 PNETs and healthy alpha and beta cells were collected through public databases. Methylation values of CpGs in the PDX1 region were extracted and used to perform clustering to identify subtypes for survival analysis. Available clinicopathological and sequencing data were included in the analyses.

Results
Clustering analysis identified two separate clusters. One cluster contained the alpha cells and 97% of the mutated PNET samples, suggestive of the A subtype. The other cluster consisted of beta cells and mostly wild type PNETs, suggestive of the B subtype. A significant association was found between mutation status and subtype (Chi-square, p<0.001). Furthermore, Kaplan-Meier analysis showed a trend towards longer overall survival (OS) for patients with subtype B (p=0.058). Median OS for type A was 11.9 years (95% CI 9.9 years – not reached) and has not been reached for type B.

Conclusions
DNA methylation analysis can be used to perform subtyping and links subtype with cell-of-origin by including DNA methylation patterns of alpha and beta cells. This subgrouping might have prognostic properties.

Speakers

Gitta Boons

Timon Vandamme

Joe Ibrahim

Ann Schepers

Geert Roeyen

Ann Driessen

Cherie Blenkiron

Kate Parker

Marc Peeters

Guy Van Camp

Ken Op de Beek

Friday March 6, 2020 09:45 - 10:00 CET
Room TEUN

BGDO, Session 1

09:45 CET

Bile duct stone extraction via PTC rendezvous assisted single balloon ERCP.

Authors
M. SOMERS (1), M. NIEKEL (2), S. BOUHADAN (1), A. JAUREGUI (1), H. DE SCHEPPER (1), S. FRANCQUE (1), E. MACKEN (1) / [1] UZA, Universitair Ziekenhuis Antwerpen, Edegem, Belgium, Department of gastroenterology and hepatology, [2] UZA, Universitair Ziekenhuis Antwerpen, Edegem, Belgium, Department of radiology
Bile duct stone extraction via PTC rendezvous assisted single balloon ERCP. Therapeutic ERCP procedures in patients with surgically altered intestinal anatomy remain challenging. During the last years, several endoscopic techniques have been proposed to increase successful cannulation of the biliary tract (single balloon ERCP (SB-ERCP), surgically assisted ERCP, internal EUS-directed transgastric ERCP and transprosthetic endoscopic therapy). With the single balloon ERCP technique, some of the limitations of the duodenoscope in the setting of an altered intestinal anatomy can be overcome. Nonetheless, one of the major obstacles in SB-ERCP is obtaining biliary access in patients with a native papilla. This can be due to the limited length of the enteroscope, postoperative adhesions or sharp bends of the reconstructed intestine and a rather tangential view of the papilla with the forward viewing enteroscope compared with the side-viewing duodenoscope, without the possibilities made possible by the use of the elevator. We present a case of a 89-year-old patient with a history of gastric cancer and partial gastrectomy who presented with symptomatic choledocholithiasis, cholangitis and sepsis. Patient presented with fever and right upper quadrant pain since three days, despite antibiotic therapy (amoxicillin-clavulanic acid) started by the generalist. Lab results showed a high leukocyte count (19,2x10^9), elevated C-reactive protein (229 mg/l), elevated liver tests (GOT 212 U/l, GPT 200 U/l, gamma-GT 70 U/l) and elevated bilirubin (3.8 mg/dl). Abdominal ultrasound showed dilated intrahepatic bile ducts. Additional MRCP confirmed the presence of several large bile duct stones. Patient was referred to our hospital for a SB-ERCP, but, despite careful inspection, the papilla could not be seen. Therefore, a percutaneous transhepatic cholangiography (PTC) was done by the radiologist, leaving a drain into the duodenum. During a second SB-ERCP procedure a designated radio-opaque guidewire (0.035 inch, 550 cm) was advanced trough the biliodouodenal drain, then firmly grasped with a snare forceps and brought out of the patient, allowing the enteroscope to advance to the papilla. Cannulation and contrast injection of the bile duct confirmed the presence of several stones in the common bile duct (CBD). After sphincterotomy and balloon extraction of several concrements, a very large residual stone (+/- 20 mm) could not be removed and was impacted in the distal CBD. A 7 French, plastic stent was placed to maintain biliary drainage. An additional SB-ERCP is scheduled for additional stone removal. During the last decades, more patients with surgically altered bowel anatomy are being referred for ERCP, owing to a rise in prevalence of bariatric surgery, surgical interventions of pancreaticobiliary lesions and liver transplantation (1). One of the possible options to reach the biliary tract in these patients is single balloon assisted ERCP. In a meta-analysis of 15 trials (461 patients) the SB-ERCP procedural success rate, defined as the ability to provide successful intervention, was reported to be 61.7 % (1), meaning that in one third of the patients the procedure is unsuccessful. Although the rendezvous technique is well known in classic ERCP, we present this case to show that a rendezvous procedure combined with a SB-ERCP (using a long guidewire) can be helpful to accomplish biliary tract cannulation in difficult cases. References 1. Inamdar S., Slattery E., Sejpal DV., Miller LS., Pleskow DK., Berzin TM., et al. Systematic review and meta-analysis of single-balloon enteroscopy–assisted ERCP in patients with surgically altered GI anatomy. Gastrointest Endosc 2015;82(1):9–19.

Speakers

Michaël Somers

Maarten Niekel

Souad BOUHADAN

Aranzazu JAUREGUI

Heiko DE SCHEPPER

Sven Francque

Elisabeth Macken

Friday March 6, 2020 09:45 - 10:00 CET
TBA

Case Reports Hepathology, Session 1

10:00 CET

FIGHT-202: A phase 2 study of pemigatinib in patients with previously treated locally advanced or metastatic cholangiocarcinoma

Authors
E. VAN CUTSEM (1), A. VOGEL (2), V. SAHAI (3), A. HOLLEBECQUE (4), G. VACCARO (5), D. MELISI (6), R. AL-RAJABI (7), A. PAULSON (8), M. BORAD (9), D. GALLINSON (10), A. MURPHY (11), D. OH (12), D. EFRAT (13), D. CATENACCI (14), C. LIHOU (15), H. ZHEN (16), L. FÉLIZ (15), G. ABOU-ALFA (17) / [1] University Hospitals Gasthuisberg and KU Leuven, , Belgium, Department of Digestive Oncology, [2] Hannover Medical School, , Germany, Department of Gastroenterology, Hepatology and Endocrinology, [3] University of Michigan, Ann Arbor, United States (the), Rogel Cancer Center, [4] Gustave Roussy, , France, Department of Adult Medicine, [5] Providence Cancer Center Oncology and Hematology Care Clinic, , United States (the), Hematology Oncology, [6] Università degli studi di Verona, , Italy, Digestive Molecular Clinical Oncology Research Unit, Department of Medicine, [7] University of Kansas Cancer Center, , United States (the), Department of Internal Medicine, Division of Hematology/Oncology, [8] Baylor University Medical Center, , United States (the), Baylor Charles A. Sammons Cancer Center, [9] Mayo Clinic Cancer Center, , United States (the), Department of Internal Medicine, [10] Morristown Memorial Hospital, Carol Cancer Center, , United States (the), Department of Hematology/Oncology, [11] Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, , United States (the), Department of Oncology, [12] Seoul National University Hospital, Seoul National University College of Medicine, , Korea (the Republic of), Department of Internal Medicine, [13] Fox Chase Cancer Center, , United States (the), Department of Hematology/Oncology, [14] University of Chicago Medicine, , United States (the), Department of Medicine, [15] Incyte Corporation, , United States (the), Clinical Development, [16] Incyte Corporation, , United States (the), Biostatistics, [17] Memorial Sloan Kettering Cancer Center, , United States (the), Department of Medicine

Introduction
Fibroblast growth factor receptor (FGFR) 2 alterations are implicated in cholangiocarcinoma. Pemigatinib is a selective, potent, oral FGFR1, 2, and 3 inhibitor.

Aim
We present data from a phase 2, open label, single arm study of pemigatinib in patients with previously treated locally advanced or metastatic cholangiocarcinoma (NCT02924376).

Methods
Eligible adults had documented FGF/FGFR gene status and evident disease progression after ≥1 prior treatment. Patients were assigned to cohorts A (FGFR2 gene rearrangements/fusions), B (other FGF/FGFR gene alterations), or C (no FGF/FGFR gene alterations), and received oral pemigatinib 13.5 mg QD (21-day cycle; 2 weeks on, 1 week off) until disease progression/unacceptable toxicity. Primary endpoint was centrally confirmed objective response rate (ORR; cohort A); secondary endpoints were ORR (cohorts B, A+B, and C); duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety.

Results
As of data cutoff (Mar 22, 2019), 146 patients were enrolled (cohort A, n=107; B, n=20; C, n=18; 1 patient undetermined). Median (range) age was 59 (26–78) years; 61% and 39% had 1 and ≥2 prior therapies, respectively. Fewer patients discontinued therapy in cohort A (71%) vs B and C (each 100%), mainly for progressive disease (53%, 75%, and 67%, respectively). ORR in cohort A was 35.5% (95% CI, 26.5%–45.4%), with 3 complete responses; median DOR was 7.5 (95% CI, 5.7–14.5) months; DCR was 82% (95% CI, 74%–89%); median PFS and median OS were 6.9 (95% CI, 6.2–9.6) and 21.1 (14.8–not reached) months (OS not mature at cutoff), respectively. In cohorts B and C, there were no responses. Overall, most common adverse events (AEs) were hyperphosphataemia (60%; grade ≥3, 0%), alopecia (49%; 0%), diarrhoea (47%; 3%), fatigue (42%; 5%), nail toxicities (42%; 2%), and dysgeusia (40%; 0%). Hyperphosphataemia was managed with diet modifications, phosphate binders, if needed; diuretics or dose reductions/interruptions. Discontinuation, dose reduction and interruption due to AEs occurred in 9%, 14% and 42% of patients, respectively.

Conclusions
These data support pemigatinib as a potential treatment option for previously treated patients with cholangiocarcinoma harbouring FGFR2 gene rearrangements/fusions.

Friday March 6, 2020 10:00 - 10:15 CET
Room TEUN

BGDO, Session 1

10:00 CET

Acute grade IV toxic hepatitis due to the e-sigarette.

Authors
G. VAN ROEY (1), C. CLAESSENS (2), L. VAN TIGCHELT (2), J. SCHOUTEN (3), W. VERLINDEN (3), A. HOORENS (4) / [1] AZ TURNHOUT, Turnhout, Belgium, Gastroenterology, [2] AZ TURNHOUT, Turnhout, Belgium, gastroenterology, [3] AZ Nikolaas, Sint-Niklaas, Belgium, gastroenterology, [4] UZGent, Gent, Belgium, Pathology
Introduction: In this abstract we present a case of Drug Induced Liver Injury (DILI) attributed to exposure of the electronic cigarette. The diagnosis is confirmed by complete recovery after cessation and recurrence of hepatitis following re-exposure to the e-cigarette (RUCAM score of 10). Case report: Phase 1: • Female patient,°1972 with a history of a gastric bypass in 2014 presented at the emergency department at April 23th 2018 because of progressive asthenia, diarrhea, epigastric tenderness and jaundice. She was on ethinylestradiol/levonorgestrel and pantoprazole. She did not report weight loss, alcohol consumption or viral symptoms. • Clinical examination revealed a patient with jaundice and hepatosplenomegaly. • Lab resutls: on admission, maximal values of AST and ALT were 917 and 1448 U/l resp, Bilirubin raised till 9,3 mg/dl. Highest ALP was 167 U/l, INR remained normal. Extensive viral, auto-immune and metabolic work-up was completely negative. • abdominal ultrasound: hepatoslenomegaly but no other abnormalities. • liver biopsy: interface hepatitis with periportal hepatitis; bilirubinostasis; eosinophilic infiltration: features of DILI, with a DD of auto-immune hepatitis. • Follow-up: all liver tests normalised completely within a few months without any therapy. Phase 2: • November 13th 2019: she presented at the emergency ward with symptoms of jaundice, dark urine, nausea and itching • exploration: AST and ALT of 846 and 1022 U/l resp., ALP 170 U/l, bilirubin 5,3 mg/dl, bile salts 411 micromol/l. Again, biochemical, serological and radiological work-up showed no causative abnormalities. • On extensive anamnesis, the only evident toxin she was exposed to was the use of the e-cigarette in 2018, which she stopped after hospitalisation in April 2018. She restarted “vaping” from Oktober 2019 onwards till the last admission. After cessation of the e-cigarette, a slow recovery of the liver tests was noticed. • The RUCAM score for this toxin was 10, making the diagnosis of DILI highly probable. • Looking at the chemical composition of the e-cigarette the patient was using, she was exposed to propylene glycol, glycerine, nicotine and 5% of aroma’s. The most hepatotoxic components are propably propylene glycol and the aroma’s. Conclusion: This is the first report of DILI secondary to the use of e-cigarettes, The calculated RUCAM score was 10, making the diagnosis highly probable. In patients presenting with acute hepatitis vaping must be included in the differential diagnosis of DILI.

Speakers

Guy Van Roey

Christophe Claessens

Laurens Van Tigchelt

Jeoffrey Schouten

Wim Verlinden

Anne Hoorens

Friday March 6, 2020 10:00 - 10:15 CET
TBA

Case Reports Hepathology, Session 1

10:00 CET

Coffee Break

Friday March 6, 2020 10:00 - 10:30 CET
Exhibition Area

WGD Pathology

10:15 CET

“NEOPAC”: A multi-centric prospective observational registry on the NEOadjuvant therapeutic approach to the localised PAncreatiC adenocarcimona, a collaborative multicentric project (CHU Liège – FLCD - CUSL – ULB Erasme).

Authors
J. SIPLET (1), L. MANS (2), M. FIGUEIREDO (3), R. MARECHAL (3), A. FRERE (4), C. RINKEN (4), B. DELHOUGNE (4), G. HOUBIERS (5), C. HUBERT (6), J. CLOSSET (7), F. KREUTZ (8), H. KALANTARI (9), J. VAN LAETHEM (3), D. VAN DAELE (5), I. BORBATH (10) / [1] Clin universitaires St-Luc, UCL, Brussels, Belgium, Gastroenterology, [2] Erasme University Hospital - Université Libre de Bruxelles (ULB), Bruxelles, Belgium, Gastroenterology, [3] Erasme Hospital, Brussels, Belgium, Gastroenterology, [4] CHR La Citadelle, , Belgium, Gastroenterology, [5] CHC, Liège, Belgium, Gastroenterology, [6] Saint-Luc University Hospital, Brussel, Belgium, Digestive surgery, [7] Erasme Hospital, Brussels, Belgium, Digestive surgery, [8] CHR Verviers, Verviers, Belgium, Oncology, [9] CHR Verviers, Verviers, Belgium, Gastroenterology, [10] Saint-Luc University Hospital, Brussel, Belgium, Gastroenterology

Introduction
Therapeutic management of localized pancreatic adenocarcimona (L-PDAC) is currently based on the evaluation of the tumor resectability using radiological criteria and review by expert MD board. These criteria lead to the following three situations : 1. Resectable tumors, 2. Unresectable tumors, that will receive induction chemotherapy eventually followed by radiotherapy. 3. Borderline resectable lesions that rely on specific vascular involvement criteria , for which neoadjuvant therapy is advised, although still proven efficient. These recommendations remain however based on observational retrospective studies. It is therefore important that, in our practice, we either conduct these approaches as part of controlled studies, or that we record these data on prospective registries.

Aim
To implement a multicentric registry of patients with L-PDAC, prospectively enrolled in a common database in order to 1/evaluate the clinical practice of academic and large general hospitals regarding the multimodal management of L-PDAC and 2/ assess the relevant prognostic factors allowing a surgical R0 resection and its prediction to patient‘s outcome.

Methods
The NEOPAC project includes patients with L-PDAC and being treated in one of the following centres : Cliniques Saint-Luc (CUSL), ULB Erasme, CHU Liège, CHR Citadelle, CHC Saint Joseph and CHR Verviers. The recorded data were clinical (gender, age, weight, size, ECOG PS,...), biological (CA 19.9 level, bilirubin level,...), radiological (tumor location, size, vascular involvement, cTNM, metabolic activity) and pathological (R status, N stage,..). Patients were characterized by a single investigator, as resectable, borderline resectable or locally advanced, according to vascular involvement description, based on NCCN guidelines. For each patient, administered treatments (neoadjuvant chemotherapy, radiotherapy, adjuvant chemotherapy, type of surgery), tumor response and feasibility/tolerability of the whole therapeutic sequence were recorded. Follow-up at different time points is planned and ongoing.

Results
From March 2017 to November 2019, 84 patients have been enrolled. Baseline characteristics showed a 1:1 gender ratio, a mean age of 65 years (39-91); ECOG at baseline was 0 (43%), 1 (53%) or 2 (4%). Mean tumor size was 36 (+/-18) mm and mean CA 19.9 level was 1445 (+/-7264) UI/mL. Tumor localization was head in 65%, body and tail in 35%. Among currently evaluated patients, 9 had resectable tumors, 34 had borderline tumor and 33 had unresectable locally advanced diseases. Neoadjuvant chemotherapy was administered to 70/76 (93.4%) patients; mainly FOLFIRINOX (78.7%) or gemcitabine/nab-paclitaxel (14,7%). Forty-seven patients currently achieved complete neoadjuvant chemotherapy sequence. At the end of neoadjuvant treatment, we observed 3 complete response (CR), 23 partial response (PR), 12 stable disease (SD) and 4 progressive disease (5 patients were not evaluable). Grade 3 or 4 toxicity was observed in less than 25% of cases and discontinuation of chemotherapy was necessary because of toxicity in 13% of cases. 17 patients received neoadjuvant chemo-radiotherapy after chemotherapy. Concerning patients who completed full neoadjuvant sequence : among readily resectable patients, 4/5 were resected without any neoadjuvant therapy (3 R0: alive without recurrence, 1 Rx: alive with recurrence) and 1 was given chemotherapy (not resected because unfit for surgery). Among borderline patients, 12/22 were operated (9 R0: 1 recurrence, 2 R1: 1 recurrence, 1 undefined: recurrence). Among locally advanced tumors, 4/19 were resected (3 R0: 1 with recurrence, 1 R2). Preferred adjuvant regimen was gemcitabine (N= 8/20, 42%) followed by FOLFIRINOX (N= 7/20, 37%). Amongst all resected patients, 9 are alive without recurrence, 4 had a relapse (all of them metastatic), and 1 was lost to follow-up. No death in resected patients has been reported so far.

Conclusions
Currently available data among NEOPAC show FOLFIRINOX to be the main neo-adjuvant treatment for borderline resectable and locally advanced L-PDAC. Full neoadjuvant sequence is feasible in most of our patients before attempt of surgery. Its efficacy allowed R0 resection for many borderline tumors and for several initially unresectable diseases. Enrolment of patients is ongoing. Data on more patients, with longer follow-up and OS results will be shown at the meeting.

Friday March 6, 2020 10:15 - 10:30 CET
Room TEUN

BGDO, Session 1

Thomas De Somer

Erik Vanderstraeten

Vincent Bouderez

Els Monsaert

Christophe Van Steenkiste

Friday March 6, 2020 10:45 - 11:00 CET
TBA

Case Reports Hepathology, Session 2

11:00 CET

A rare complication of Lemmel Syndrome: Biliary-Diverticular Fistula from a Duodenal Diverticulum

Authors
S. PATEL (1) / [1] Mayo Clinic, Rochester, United States (the), Department of Internal Medicine
A 77 year old female with no significant medical issues presented to primary care clinic with a seven day history of right upper quadrant abdominal pain radiating to the sternum and back. Examination demonstrated tenderness to midepigastric area and right upper quadrant. Laboratory work-up (normal value ranges in parenthesis) showed a leukocytosis to 12.0 (3.4 - 9.6 x10(9)/L), Alkaline Phosphatase 202 U/L (35 – 104 U/L), Alanine Aminotransferase 581 U/L (7 – 45 U/L), Aspartate Aminotransferase 540 U/L (8 – 43 U/L) and total Bilirubin 6.2 mg/dL (

Speakers

Shruti Patel

Friday March 6, 2020 11:00 - 11:15 CET
TBA

Case Reports Hepathology, Session 2

11:00 CET

Upper GI cancers.

Speakers

Live Demonstrations

Speakers

D. Blero (ULB Erasme)

A. Tringali (Roma - Italy)

P. Eisendrath (ULB Saint-Pierre)

C. Snauwaert (UCL Saint-Luc - Brussels)

Friday March 6, 2020 11:00 - 12:00 CET
Room TIFFANY-SHAH

BSGIE Live, Session 2

11:15 CET

Dubai took my breath away

Authors
C. SCHOONJANS (1), A. GEERTS (2), H. DEGROOTE (2), H. VAN VLIERBERGHE (2), E. VAN BRAECKEL (3), X. VERHELST (2) / [1] UZ Gent, Gent, Belgium, gastroenterology, [2] UZGent, Gent, Belgium, gastroenterology, [3] UZGent, Gent, Belgium, Pulmonology
Christophe Schoonjans, Anja Geerts, Helena Degroote, Hans Van Vlierberghe, Eva Van Braeckel, Xavier Verhelst. UZ Gent A 68-year old patient was admitted to the hospital because of shortness of breath and a dry cough, starting right after a trip to Dubai. Six years ago, he underwent an orthotopic liver transplantation because of alcoholic liver cirrhosis with a small HCC (2 cm), taking immunosuppressive medication (everolimus and mycophenolic acid). Three years ago, he had a coronary artery bypass graft. Blood examination showed minimal inflammation, with no signs of cardiac ischemia. Arterial blood gas showed hypoxia. Chest radiograph showed an interstitial lung pattern, with reticulonodular opacities. CT scan confirmed this with the image of a fibrotic end stage of an interstitial pneumonia. Echocardiography showed minimal decrease in systolic function, inferior akinesia and slightly elevated pulmonal pressure (36 mmHg + CVP). Pulmonary function test was restrictive (being normal pre-transplantation), with TLC of 57% and DLCO of 37%. Everolimus drug level was subtherapeutic (1.3 ng/ml). Infectious serology (including chlamydia/mycoplasma pneumoniae), Mantoux test, autoimmune serology and bronchoscopy with bronchoalveolar lavage (with PCR for Pneumocystis Jirovecii Pneumoniae) was negative. No anamnestic arguments for hypersensitivity pneumonitis. Based on exclusion of other causes, an everolimus-induced interstitial lung disease was suspected. For that matter, everolimus was replaced by tacrolimus. Gradually the oxygen dependence of our patient decreased, as did the symptoms. Five months later chest CT showed decrease of the interstitial/fibrotic findings, lung function tests improved (TLC 63% and DLCO 46%) and our patient did not need oxygen therapy anymore. During the course the persisting normal liver enzymes proved no arguments for liver rejection. In the literature case reports of interstitial lung disease (ILD) under treatment with mTOR (mammalian target of rapamycin) inhibitors were published in solid organ transplant patients (mainly renal), breast and neuro-endocrine tumours. Most of the data come from sirolimus, with better toleration for everolimus. Typically, there is no correlation to the everolimus concentration (as in our case with subtherapeutic levels). Immediate withdrawal of the drug is indicated, and there is no clear benefit from the addition of steroids in terms of improvement of symptoms. To our knowledge this is only the second case of everolimus induced ILD reported in a liver transplant patient, and the first one in which the outcome is not fatal. [1,2] Therefore, clinical suspicion needs to be high in every patient treated with a mTOR inhibitor (sirolimus as well as everolimus) presenting with new onset of pulmonary symptoms. Representative lung CT images can be shown during case presentation. References 1. Lopez et al. Interstitial lung disease associated with mTOR inhibitors in solid organ transplant recipients: results from a large phase III clinical trial program of everolimus and review of the literature. J Transplant, 2014 (2014), p. 305931 2. J. Schrader et al. Everolimus-induced pneumonitis: report of the first case in a liver transplant recipient and review of treatment options, Transplant International, vol. 23, no. 1, pp. 110–113, 2010.

Speakers

Christophe Schoonjans

Anja Geerts

Helena Degroote

Hans Van Vlierberghe

Eva Van Braeckel

Xavier VERHELST

Friday March 6, 2020 11:15 - 11:30 CET
TBA

Case Reports Hepathology, Session 2

11:15 CET

Low-grade dysplasia in Barrett’s esophagus is downgraded in half of the cases after systematic expert pathology review before patient referral for endoscopic treatment.

Authors
P. LECLERCQ (1), G. DE HERTOGH (2), R. BISSCHOPS (1) / [1] UZ Leuven, Leuven, Belgium, Gastroenterology, [2] UZ Leuven, Leuven, Belgium, Pathology

Introduction
Background: Barrett’s esophagus (BE) is the only known precursor condition for esophageal adenocarcinoma (EAC). Progression is thought to occur in a stepwise fashion from non-dysplastic BE (NDBE) to low-grade dysplasia (LGD) to high-grade dysplasia (HGD) and finally to EAC. Therefore, regular endoscopic surveillance with biopsies is required for these patients. Dysplasia in BE biopsies is associated with low observer agreement among general pathologists. Expert pathology review of all diagnosis of dysplasia is advised by most BE guidelines. The majority of patients with community LGD will be down-staged after expert review and have a low progression risk. Confirmed LGD has an increased risk of malignant progression, reported up to 9% per patient-year. Since endoscopic management of BE patients depends on the dysplasia grade, expert pathology review leads to a significant impact on the management and outcome of patients.

Aim
The aim of this study was to document the discrepancy between expert and community pathologists in grading BE dysplasia before patient referral for endoscopic treatment.

Methods
Between January 2017 and August 2019, sets of biopsy specimen from 129 dysplastic BE patients were referred from community centers to our tertiary referral center for expert pathology review as a prerequisite for dysplastic BE endoscopic management. These slides and blocks were reassessed by two gastro-intestinal (GI) expert pathologists. Diagnosis were stratified according Vienna Classification supported by p53 immunostaining. In this study, we retrospectively documented the discrepancy between expert and communautary pathologists in grading dysplasia in this selected BE population.

Results
LGD was confirmed by expert pathologist in 33/68 patients (49%), 20 patients (29%) were downgraded to NDBE, 5 patients (7%) indefinite for dysplasia (IFD) and 10 patients (15%) were upgraded to HGD, no cancer was missed. HGD was confirmed by expert pathologist in 52/61 patients (85%), downgraded to NDBE in 1 patient (2%) or to LGD in 4 patients (7%) and upgraded to EAC in 4 patients (7%).

Conclusions
Discrepancy in BE dysplasia grading between community and tertiary referral centers is still high, especially for LGD. Community diagnosis of LGD is down-staged to NDBE in 49% of the cases after expert GI pathologist review. Therefore, skipping the expert pathology review step in LGD BE patients could lead to overtreat almost half of the patients.

Speakers

Philippe Leclercq

Gert De Hertogh

Raf BISSCHOPS

Friday March 6, 2020 11:15 - 11:30 CET
Room LIJN

WGD Pathology, Session 1

11:20 CET

Hepato-Bilio-Pancreatic cancers.

Speakers

Jeroen Dekervel (UZ Leuven)

Friday March 6, 2020 11:20 - 11:40 CET
Room TEUN

BGDO, Session 2

11:30 CET

Reopening of the native portomesenteric axis after cavoportal hemitransposition in a liver transplant patient

Authors
M. CLARYSSE (1), A. WILMER (2), Y. DEBAVEYE (3), W. LALEMAN (2), F. NEVENS (2), S. VAN DER MERWE (2), H. VAN MALENSTEIN (2), M. SAINZ-BARRIGA (1), D. MONBALIU (1), J. PIRENNE (1) / [1] University Hospitals Leuven, , Belgium, Abdominal Transplant Surgery, [2] University Hospitals Leuven, , Belgium, Gastroenterology and Hepatology, [3] University Hospitals Leuven, , Belgium, Intensive Care Medicine
Introduction. A 19 year old woman presented with recent onset Budd-Chiari and extensive/refractory supra-hepatic and portomesenteric thrombosis (PVT) leading to acute liver failure. Urgent liver transplantation (LTx) was performed. Due to recurrent PVT immediately postTx, urgent reTx was performed. Methods. At reTx sufficient flow from the native portomesenteric axis could not be obtained and therefore a partial cavoportal shunt (30% tapering of the inferior vena cava (IVC) just above the shunt) was created allowing acceptable portal inflow. An acute decline in portal inflow, one day later, rendered full ligation of the IVC necessary to again reach acceptable portal inflow, therefore creating a cavoportal hemitransposition (CPHT). However, an anatomical portoportal anastomosis/connection (despite absent/extremely low native portal flow at that time) was maintained. Results. Postoperative period was uncomplicated. Interestingly, the native portomesenteric axis reopened several days later allowing physiological portal inflow - in addition to flow via the CPHT - . The patient was discharged 27 days later with normal liver function and adequate portal inflow. After 16 months, patient is well with normal liver function and adequate portal inflow through both the CPHT and the reopened native portomesenteric axis. Conclusion. CPHT with maintenance of an anatomical portoportal connection should be considered in patients with extensive PVT in whom physiological portal inflow cannot be restored at the time of LTx, but in whom the native portomesenteric axis may reopen later.

Friday March 6, 2020 11:30 - 11:45 CET
TBA

Case Reports Hepathology, Session 2

11:30 CET

Subacute liver failure in a pregnant female.

Authors
L. KEULEN (1), N. GESTELS (2), P. JORENS (2), S. FRANCQUE (3), A. DRIESSEN (1) / [1] Antwerp University Hospital, , Belgium, Dept. of Pathology, [2] Antwerp University Hospital, , Belgium, Dept. of Intensive Care, [3] Antwerp University Hospital, , Belgium, Dept. of Gastroenterology and Hepatology

Introduction
Liver diseases during pregnancy may pose a clinical diagnostic challenge as it may affect mother as child. Pregnancy-related liver diseases occur in approximately 3% of the pregnancy and may be the cause of maternal death in approximately 6%.

Aim
The aim is to discuss the pregnancy-related liver diseases.

Methods
Macroscopic and microscopic examination.

Results
We present a case of a 29yr old pregnant female, who in the 25th week of gestation, was admitted to the hospital with abdominal pain, disturbed liver tests and progressive jaundice. In early pregnancy she underwent laparoscopic gastric bypass surgery. Previous pregnancies were uneventful. At admission no signs of chronic liver disease or hepatic encephalopathy were detected. Patient had significant disturbed liver enzymes with bilirubinemia, elevated INR, hypoalbuminemia. No proteinuria, nor hypertension was found. No bile duct abnormalities, nor ascites was observed during radiological examination, but a florid steatohepatitis was detected. From clinical point of view the cause of the clinical deterioration of the patient was not obvious. Hence a liver biopsy was performed. After the procedure the condition of the patient suddenly worsened with symptoms of hepatic encephalopathy. As the fetus showed signs of distress, an urgent caesarian section was performed. Postoperatively the liver functions of the mother normalized quickly and patient was discharged after a few days.

Conclusions
During pregnancy there occur several physiologic changes in the mother. Although the liver usually continues normal to function, the high metabolic demand may sometimes cause a mild alteration of the liver enzymes. Liver diseases during pregnancy may be related to pre-existing liver diseases, such as viral hepatitis, or may be unique to the pregnant state, e.g. the HELLP-syndrome. In this patient however there is an additional differential diagnostic problem, as the bariatric surgery was associated with a significant weight loss (27 kg) in a few months time. This may cause a severe liver dysfunction, certainly in this condition of high metabolic demand in this pregnant female. Early diagnosis is however necessary as mother’s as well as child's lives are at risk.

Speakers

L KEULEN

N GESTELS

P JORENS

S FRANCQUE

A DRIESSEN

Friday March 6, 2020 11:30 - 11:45 CET
Room LIJN

WGD Pathology, Session 1

11:40 CET

Colo-Rectal cancers.

Speakers

Marc Peeters (UZ Antwerpen)

Friday March 6, 2020 11:40 - 12:00 CET
Room TEUN

BGDO, Session 2

11:45 CET

The use of ribavirin in a severe case of hepatitis E infection necessitating renal replacement therapy.

Authors
M. STAESSENS (1), T. VANWOLLEGHEM (2), L. VONGHIA (2), S. FRANCQUE (2), T. STEINHAUSER (2), B. BRACKE (3), L. ROOSSENS (4), E. PHILIPSE (5), M. COUTTENYE (5), K. DAMS (1) / [1] Antwerp University Hospital, , Belgium, Intensive Care Unit, [2] Antwerp University Hospital, , Belgium, Gastroenterology and Hepatology, [3] Antwerp University Hospital, , Belgium, Hepatobiliary, Transplantation and Endocrine Surgery, [4] Antwerp University Hospital, , Belgium, Clinical Biochemistry, [5] Antwerp University Hospital, , Belgium, Nephrology
A 59-year-old male of Cambodian descent was admitted to a hospital in the Netherlands due to right upper quadrant pain, diarrhea and vomiting. He had recently travelled and had been staying in Cambodia for about three weeks. There was supposedly no contact with open waters. He had not been drinking tap water. There was no use of over-the-counter drugs, medicinal herbs. He had been taking verapamil, pantoprazole and atorvastatin during several years, and there had been no recent change to his drug dosing or scheme. On clinical examination at presentation there was a prominent icterus with dark discoloration of the urine. Cardiac and respiratory examination were unremarkable. The abdomen was non tender with pain on deep palpation in the epigastric and left hemi-abdomen. There was no apparent hepatosplenomegaly. The vital signs were within normal range. Abdominal ultrasound excluded biliary dilatation and acute cholecystitis. Initial lab results revealed significantly elevated liver enzymes, predominantly of the canalicular type, with total bilirubin above 30 mg/dL, conjugated bilirubin above 10 mg/dL, ALT 1792 U/L, AST 584 U/L, GGT 105 U/L and AP 138 U/L. Liver synthetic function tests were abnormal, with an INR of 1.4 and decreased albumin of 27 g/L. Platelet count was normal. Serology for viral hepatitis (including hepatitis A, B, C, E, EBV and CMV) came back positive for an acute hepatitis E infection (HEV IgM+; HEV IgG+). Due to further deterioration of the liver function tests, a significant acute kidney injury with a creatinine of 4,0 mg/dL, oliguria and respiratory deterioration, the patient was referred to the department of gastroenterology of the University Hospital of Antwerp. Consequently, a PCR for hepatitis E performed at the admitting hospital revealed a genotype 4b. Liver biopsy confirmed the diagnosis of a cholestatic hepatitis, compatible with an acute viral hepatitis. Shortly thereafter, increasing respiratory distress necessitated admission to the intensive care unit. Renal replacement therapy was commenced due to fluid overload, presenting as pulmonary edema, and inadequate urinary output. The diagnosis of acute tubular necrosis due to hyperbilirubinemia was made based on aforementioned findings and the presence of bilirubin crystals in the urine. Ribavirin was started 2 days after presentation. Therapeutic drug monitoring was regularly performed, and the dosage was adapted accordingly. About 3 weeks later, the PCR for hepatitis E became negative, but ribavirin was continued until a second HEV RNA PCR was negative in blood and stool. Unfortunately the patient developed acute intestinal ischemia due to low flow phenomena and succumbed one day later as a result of severe therapy unresponsive septic shock. Hepatitis E is an acute viral hepatitis transmitted through the fecal-oral route, and is most common in developing countries. Genotype 4b, as presented in our case, is mostly seen in southern Asian countries such as Cambodia. Classically, acute infection is asymptomatic, requires no pathogen guided treatment and is mostly supportive. Liver failure ultimately leading to liver transplantation or death is very rare. In severe cases however, ribavirin can be associated to the therapy, although there is little experience regarding the dosing, duration and effectiveness of the therapy, with additional difficulty in patients needing renal replacement therapy. In this case, therapeutic drug monitoring aided in preventing drug overdose and side effects. Finally, hepatitis E was cleared. We will discuss differences in clinical presentation of HEV genotypes and the benefit of RBV drug monitoring in severe acute HEV.

Friday March 6, 2020 11:45 - 12:00 CET
TBA

Case Reports Hepathology, Session 2

11:45 CET

Actinomycosis of the pancreas: a case report.

Authors
E. AMELOOT (1), F. BERREVOET (2), P. HINDRYCKX (3), J. BOELENS (4), J. VAN DORPE (1), A. HOORENS (1) / [1] Ghent University Hospital, Ghent, Belgium, Dept. of Pathology, [2] Ghent University Hospital, Ghent, Belgium, Dept. of General, Hepatobiliary and Liver Transplantation Surgery, [3] Ghent University Hospital, Ghent, Belgium, Dept. of Gastroenterology and Hepatology, [4] Ghent University Hospital, Ghent, Belgium, Dept. of Laboratory Medicine and Dept. of Infection Control
A 65-year-old woman presented to the emergency department with a painful, subcutaneous swelling in the right flank. She had a history of liver cirrhosis due to chronic alcoholism, several episodes of acute pancreatitis and recurrent need of stenting of the common bile duct because of direct compression by an inflammatory mass lesion in the head of the pancreas. The subcutaneous abscess was incised and drained and the patient was admitted to the hospital for intravenous antibiotics. CT abdomen showed progression in size of the pancreatic mass lesion in comparison to previous imaging and was suspect of a pancreatic intraductal papillary mucinous neoplasm (IPMN) with malignant degeneration. The mass was considered operable and a Whipple procedure was performed. Upon gross examination of the pancreas, a distinct mass with a diameter of 1 cm was observed, next to the common bile duct. The mass had a yellow-greenish colour and felt soft. The stent in the common bile duct contained a similar solid, soft, yellow-greenish substance. In the duodenum there were defects in the wall, also containing the same substance. Microscopic examination of the duodenum and common bile duct showed several abscesses composed of a mixed inflammatory infiltrate and tangled long narrow filamentous structures forming rounded basophilic masses with eosinophilic borders, reminiscent of sulphur granules. Morphology and characteristics in HE, PAS, Grocott and gram staining confirmed Actinomyces infection. Besides abscess formation in the common bile duct and pancreatic duct, inflammation and necrosis with inoculation of bacteria in the surrounding pancreatic tissue was observed. There were no signs of malignancy. Despite appropriate antibiotic treatment, the patient died shortly afterwards. Pancreatic, with potentially subsequent abdominopelvic actinomycosis, is a rarely occurring condition, however important to be considered in the differential diagnosis, as it can lead to a progressive suppurative fistulising and fibrosing infection with sinus tracts characteristically burrowing across normal tissue boundaries and into adjacent organs. Eventually sinus tracts may reach external surfaces forming a draining sinus or even penetrating bone leading to osteomyelitis. Early diagnosis and treatment are imperative in preventing serious and potentially life-threatening complications.

Speakers

Eline Ameloot

Frederik Berrevoet

Pieter Hindryckx

Jerina Boelens

Jo Van Dorpe

Anne Hoorens

Friday March 6, 2020 11:45 - 12:00 CET
Room LIJN

WGD Pathology, Session 1

12:00 CET

DPD-flash & BGDO Award

Speakers

Karen Geboes (UZ Gent)

Marc Peeters (BGDO Chairman)

Friday March 6, 2020 12:00 - 12:15 CET
Room TEUN

BGDO, Session 2

12:00 CET

An unusual appendiceal mass rises a diagnostic challenge.

Authors
A. VANDENDRIESSCHE (1), S. DEPREZ (2), J. CORNILLE (3), A. DRIESSEN (1) / [1] Antwerp University Hospital, , Belgium, Pathology, [2] AZ Nikolaas, Sint-Niklaas, Belgium, Pathology, [3] AZ Nikolaas, Sint-Niklaas, Belgium, Surgery

Introduction
Acute appendicitis is one of the most common acute conditions of the abdomen, most commonly treated with acute emergency surgery. Although pathological examination of the resection specimen frequently shows an acute inflammation, in a limited number of cases unusual findings are found.

Aim
To discuss the diagnostic problem of appendiceal mucinous neoplasms.

Methods
Macroscopic and microscopic examination.

Results
We discuss a case of a 54 yr-old women, who presented with an acute appendicitis and a pericaecal abscess. This was at first instance conservatively treated with drainage, anti-inflammatory drugs and antibiotics. Although radiological examination showed a decrease of the size of the pericaecal collection, patient’s complaints of pain and discomfort persisted. An explorative laporatomy with resection of the base of the caecum with appendix was performed. Pathological examination of the specimen (length 7,6 cm, size 5.6*3 cm) revealed a diverticulum of the appendix, covered with an intestinal epithelium that turns into a pseudostratified epithelium. In the depth it extends into mucous lakes, surrounded by inflammatory cells, situated up to the serosal surface. Intermingled with this process we observed several irregular glandular structures with a different appearance. These structures were delineated by a cylindric type of epithelium, surrounded by a cellular stroma. At some areas we observed a transition of the two different types of epithelium into each other. This hampered the evaluation of the growth process of the pseudostratified epithelium. Hence immunohistochemistry was performed to the determine the origin of these morphologically different glandular structures and to assess their extent in the wall of the appendix. This showed that the morphologically different glandular structures had a different immunohistochemical pattern. Hence a diagnosis of a low-grade appendiceal mucinous neoplasm, intermingled with endometriosis was made.

Conclusions
For pathologists it is a diagnostic challenge to determine the risk of peritoneal dissemination of low-grade appendiceal mucinous neoplasms (LAMN). LAMN (incidence 1/100 000/yr) are in situ tumours, if they are limited to the muscularis propia. Extension into the serosa, eventually with penetration of serosal surface increases however the risk for peritoneal disease. In this case LAMN was associated with endometriosis, which is present in up to 35% of the intestine, but rare in this location. Endometriosis makes assessing the degree of invasion difficult, as in this case, the epithelium of endometrial glands are colonized by the mucinous epithelium of the LAMN. Moreover endometrial epithelium may develop intestinal metaplasia. Therefore pathological examination of the complete appendix, supplemented with immunohistochemistry, is required in order to assess the extent of LAMN and hence the risk for peritoneal dissemination.

Speakers

A. VANDENDRIESSCHE

S. DEPREZ

J-B CORNILLE

A DRIESSEN

Friday March 6, 2020 12:00 - 12:15 CET
Room LIJN

WGD Pathology, Session 1

12:15 CET

Gastritis: demographic and environmental factors based on a cross-sectional study in Belgium and Bukavu.

Authors
M. SURMONT (1), M. VAN GOSSUM (1), A. PHILIPPE (2), A. NTERANYA (3), V. MULS (1), M. NKUIZE (1), J. MUNGWETE (3), M. ABEDI (3), M. GOMEZ (4), D. LARSIMONT (2), T. SERSTE (1), R. NTOUNDA (1), J. MULKAY (1), H. NJIMI (5), E. MUNGUAKONKWA (3), P. DEMETTER (6), P. EISENDRATH (1), D. MUKWEGE (7) / [1] CHU Saint-Pierre, Brussels, Belgium, Department of Gastroenterology, [2] Institut Jules Bordet - Université Libre de Bruxelles (ULB), Brussels, Belgium, Pathology Department, [3] Panzi Hospital -UEA , Bukavu, Congo (the Democratic Republic of the), Department of Gastroenterology, [4] Institut Jules Bordet - Université Libre de Bruxelles (ULB), Brussels, Belgium, pathology department, [5] ULB, Brussels, Belgium, Institute of Statistics , [6] CHU Saint-Pierre, Brussels, Belgium, Pathology Department, [7] Panzi Hospital -UEA , Bukavu, Congo (the Democratic Republic of the), department of gynaecology

Introduction
Gastric cancer is currently the fifth most common and the third most deadly cancer worldwide. Based on the gastric carcinogenesis and the Correa cascade, patients with chronic atrophic gastritis and intestinal metaplasia are at risk for gastric adenocarcinoma. Histological gastritis staging scores Operative Link for Gastritis Assessment (OLGA) and Operative Link for Gastritis Intestinal Metaplasia Assessment (OLGIM) allow the selection of patients at risk for gastric cancer. Up to 89% of all gastric cancers can be attributable to Helicobacter Pylori (HP) infection, known as a class I carcinogen for gastric neoplasia. More than 50% of the population worldwide is infected, with the highest prevalence in Africa, Latin America, the Caribbean and Asia. The outdated ‘African Enigma’ refers to the contrast between the high prevalence of HP infection and the low incidence of reported peptic ulcers and gastric cancers in Africa.

Aim
This cross-sectional study compares prevalence and histological findings of gastritis, based on OLGA and OLGIM scores in symptomatic patients in 2 different populations living in respectively Belgium and Congo. The study also evaluates environmental and demographic factors in gastritis.

Methods
In this study, 680 patients in an urban Belgian hospital in Brussels (group 1) and 250 patients in an urban hospital in Bukavu, Democratic Republic of Congo (group 2) with epigastric pain underwent upper endoscopy during the period September 2017 - January 2019. Gastric biopsy sampling was performed according to the Sydney protocol. Each biopsy was revised by a Belgian pathologist. Histopathology identified the presence of acute and chronic inflammation, atrophy, intestinal metaplasia with OLGA and OLGIM scores and dysplasia. Immunohistochemical stains were used for the detection of HP.

Results
580 patients in the Belgian centre and 174 patients in the Congolese centre were included of which respectively 38% and 47% men with a mean age of 46 years. Hundred Belgian patients were excluded of the study because of HP eradication in the past and 76 Congolese patients because of poor quality of the paraffin embedded biopsies. The prevalence of HP infection in the Belgian group and the Congolese group was respectively 36% and 52%. There was significant more use of tobacco and proton pump inhibitors in the Belgian group, whereas the Bukavu population used more alcohol and anti-inflammatory drugs. The prevalence of HIV was not different in both groups. Severe acute and chronic gastric inflammation was in both HP positive subgroups more prevalent in the gastric antrum compared to the fundus. There were statistically significant more patients with OLGA stages 1 or 2 and OLGIM 1 or 2 in the African group than the European group, respectively 22% versus 13% and 18% versus 12%. Nevertheless, there was no significant difference for the presence of OLGA and OLGIM stages 3 and 4 between both groups nor was there a statistically significant difference in dysplasia. Focusing on age, the prevalence of OLGIM stages 1 and 2 was significant higher in the African group older than 60; 13.3% for patients younger than 60, 35.3 % for patients older than 60. There were significant endoscopic lesions such as erosions and ulcerations in 27% of the cases in both groups and there was no significant difference in HP infected patients.

Conclusions
This cross-sectional study shows interesting data on the African situation since there is a paucity of data for this area, related to limited access to endoscopy and health care in general and lack of national cancer registration in most of the African countries. In contrast to what the ‘African Enigma’ claimed, the data shows no significant difference in severity of gastritis in the African and European group nor in presence of significant endoscopic lesions. These data confirms the role of age and HP infection but there is no geographical difference.

Friday March 6, 2020 12:15 - 12:30 CET
Room LIJN

WGD Pathology, Session 1

12:30 CET

Lunch

Friday March 6, 2020 12:30 - 13:30 CET
Exhibition Area

WGD Pathology

13:30 CET

Standardized macroscopic examination for cancer of the oesophagus and oesophagogastric junction.

Speakers

L. Verset (ULB Bordet)

Friday March 6, 2020 13:30 - 14:00 CET
Room LIJN

WGD Pathology, Session 2

14:00 CET

Injection of botulinum toxin significantly increases efficiency of fissurectomy in the treatment of chronic anal fissures

Authors
J. WYNDAELE (1), G. COREMANS (1), P. ROELANDT (1) / [1] UZ Leuven, Leuven, Belgium, Gastroenterology & Hepatology

Introduction
While acute anal fissures can be treated with topical therapy to reduce sphincter hypertonia (e.g. isosorbide dinitrate, diltiazem), chronic fissures frequently require more invasive instrumental therapy. Currently the golden standard remains lateral internal sphincterotomy, however this is complicated by a long-term risk of faecal incontinence. Fissurectomy can be a valuable alternative, but is less efficient because of absence of correction of underlying hypertonia.

Aim
In this study we aim to evaluate the additional effect of injection of botulinum toxin during fissurectomy in the treatment of chronic anal fissures.

Methods
A single-centre retrospective analysis of 298 fissurectomies with or without injection of botulinum toxin was performed.

Results
The majority of patients undergoing fissurectomy were women (65%, mean age 45.0 years vs. 35% men, mean age 48.3 years), often because of ventral fissures (30% in women vs. 8% in men). Fissurectomy resulted in resolution of complaints in 81.1%, while additional injection of botulinum toxin resulted in resolution in 90.1% (p<0.05). Complication rate was identical between the two groups, mainly (flatus) incontinence (4.5% vs 4.9% with botulinum toxin) and post-operative bleeding (1.8% vs 2.5% with botulinum toxin).

Conclusions
Injection of botulinum toxin significantly increases the efficiency of fissurectomy in the treatment of chronic anal fissures without additional complications.

Speakers

Jan Wyndaele

Friday March 6, 2020 14:00 - 16:00 CET
Room TIFFANY/SHAH

Proctology

14:10 CET

Anal dysplasia in HIV-seropositive men. Prevalence in the Ghent population.

Authors
E. GÖKCE (1), J. VAN DORPE (2), A. HOORENS (2), J. PELGROM (3), F. VAN WANZEELE (3), L. VANDEKERCKHOVE (3), S. CALLENS (3), D. DE LOOZE (4) / [1] Ghent University, Ghent, Belgium, Faculty of Medicine and Health Sciences, [2] Ghent University Hospital, Ghent, Belgium, Pathology, [3] Ghent University Hospital, Ghent, Belgium, Internal Medicine, [4] Ghent University Hospital, Ghent, Belgium, Gastroenterology

Introduction
Although anal cancer is rare in the overall population, its incidence is increasing in the last decades. Especially HIV-positive men are at increased risk for developing anal squamous cell carcinoma (SCC), mainly because of the high prevalence of high-grade anal intraepithelial neoplasia (HGAIN; AIN2/3) among those patients. No studies have examined the prevalence and the natural history of anal intraepithelial neoplasia (AIN) in HIV-positive men in Belgium.

Aim
Our study aims to identify the prevalence of AIN in HIV-patients, who underwent anal screening in the Ghent University Hospital. Furthermore, we tried to determine the natural history of HGAIN. In addition, we compared the results of the cytology to those obtained from high-resolution anoscopy (HRA).

Methods
Forty-eight HIV-positive men [95,8% men who have sex with men (MSM)], who underwent ≥2 screening procedures for anal dysplasia, were enrolled in this study. All patients received digital rectal examination, anal cytology and HRA at each visit. Biopsies were taken if suspicious lesions were revealed by HRA. All follow-up visits were included, giving a total of 166 cytology samples and HRA procedures performed between 18/08/2010 – 15/10/2019. The swab samples have been grouped in ‘HSIL’ [high-grade squamous intra-epithelial lesions (HSIL) or atypical squamous cells-cannot exclude HSIL (ASC-H)] and ‘non HSIL’ [Negative for Intraepithelial Lesion or Malignancy (NILM), atypical squamous cells of undetermined significance (ASC-US) or low-grade squamous intra-epithelial lesions (LSIL)].

Results
During a median follow-up period of 44 months the median number of screening procedures was 3 per patient (median age 51 years). 160 of 166 cytology samples were suitable for analysis, 47 (29.4%) of which showed ‘HSIL’ while the remaining 113 (70.6%) swabs showed ‘non HSIL’. Among the participants: the prevalence of HSIL was 50% on the first visit, 23.3% on the second and 16.7% on the third. We identified a regression of 30.2% from ‘HSIL’ to ‘non HSIL’ between the first and second visit (p= 0.001); a regression of 36.7% between the first and third visit (p < 0,001); and a regression of 24.0% between the second and third visit (p = 0,388). Only two patients received coagulation therapy for intra-anal warts; the other patients regressed spontaneously. Throughout the entire follow-up duration, we found one patient, who progressed to carcinoma in situ. Furthermore, a statistically significant association is found between detecting clinically suspicious lesions on HRA and having an anal swab that shows ‘HSIL’. Anoscopic findings suggestive of dysplasia were found during 50 of 160 (31.1%) HRA procedures. If a diagnosis of ‘HSIL’ was detected on cytology, the prevalence of visualizing a suspicious lesion on concurrent HRA was 53.2% (24 of 47), while this percentage was 22.1% (25 of 113) when ‘non HSIL’ was found on anal cytology.

Conclusions
We found a high percentage of spontaneous regression from ‘HSIL’ to ‘non HSIL’ among HIV-positive participants. Further studies with a larger study population and longer median follow-up duration are required to determine the sustainability of these regressions and to generalize our findings to the entire HIV-population. Despite the high regression grade, one patient progressed to carcinoma in situ. This shows the importance of regular screening to prevent invasive SCC. Based on the findings of new studies that are trying to determine biomarkers and risk factors that predict whether HSIL will regress or progress, it may be possible in the future to create a screening program wherein patients with an increased risk of progression can be monitored closely, while patients with a high probability of regression can be screened at larger intervals.

Speakers

Emine Gökce

Jo Van Dorpe

Anne Hoorens

Jolanda Pelgrom

Filip Van Wanzeele

Linos Vandekerckhove

Steven Callens

Danny De Looze

Friday March 6, 2020 14:10 - 14:20 CET
Room TIFFANY/SHAH

Proctology, Session 1

14:20 CET

Postgraduate symposium. Hemorrhoidal disease.

Friday March 6, 2020 14:20 - 16:00 CET
Room TIFFANY/SHAH

Proctology

14:30 CET

Feasibility and safety of EUS-guided placement of fiducial markers for stereotactic body radiation therapy in pancreatic cancer: a prospective evaluation.

Authors
M. FIGUEIREDO FERREIRA (1), C. BOUCHART (2), M. LUIGI (2), L. MANS (1), Y. GOKBURUN (3), T. DE GREZ (3), M. BALI (4), J. ENGELHOLM (5), J. VAN LAETHEM (1), P. EISENDRATH (6) / [1] Erasme University Hospital - Université Libre de Bruxelles (ULB), Bruxelles, Belgium, Gastroenterology, Hepatopancreatology and Digestive Oncology, [2] Institut Jules Bordet - Université Libre de Bruxelles (ULB), Brussels, Belgium, Radiotherapy, [3] CHR, Namur, Belgium, Gastroenterology, [4] Institut Jules Bordet, Brussels, Belgium, Radiology, [5] Institut Jules Bordet - Université Libre de Bruxelles (ULB), Brussels, Belgium, Radiology, [6] CHU Saint-Pierre, Brussels, Belgium, Gastroenterology

Introduction
In patients with high-risk/borderline resectable or locally advanced pancreatic ductal adenocarcinoma (PDAC), stereotactic body radiation therapy (SBRT) is a new potential neoadjuvant treatment option, aiming to improve curative resectability rates, local control and overall survival. The SBRT technique allows the delivery of higher equivalent biological dose to the tumor than conventional radiotherapy, particularly at the tumor/vessels interface, while reducing collateral damage to the adjacent organs. The insertion of inert radiopaque markers in or close to the tumor is a prerequisite for pancreatic SBRT, in order to precisely localize the target and track the tumor motion. Endoscopic ultrasound (EUS) placement of fiducial markers in PDAC is currently the preferred route of insertion.

Aim
The aim of this study was to assess the feasibility and safety of EUS-guided fiducial placement in our two academic centers. Moreover, we intended to co-evaluate both the technical and quality success of this technique, from the endoscopist’s and radiotherapist’s points of view, respectively.

Methods
We prospectively collected clinical and technical data concerning all the PDAC patients that were submitted to EUS-guided placement of fiducial markers and treated with SBRT. The procedures were performed by two experienced endoscopists, in two different academic hospitals. Patients were either under deep sedation or under general anesthesia and received antibiotic prophylaxis prior to insertion. Two types of radio-opaque markers were inserted: polymer markers (Polymark 0.8x3mm) back-loaded in a regular 19G FNA needle and gold markers delivered with a pre-loaded 22G dedicated needle (EchoTip® Ultra Fiducial Needle, Cook). Fluoroscopy was often used. “Technical success” was defined as at least one marker presumed to be inside the tumor at the end of the EUS procedure. After simulation computed tomography (CT), the number of visible markers and their location (in regards to the tumor and to each other) were assessed by the radiotherapist, who proposed a quality score including the following criteria: number of markers inside or < 1 cm from the tumor, number of markers located in the extremity of the tumor, their location in different planes, their distance from the biliary stent (if present) and the distance between the fiducials (if more than one visible marker). The score ranged from 0 to 12 points and “high quality success” was defined as a score equal or higher than 6.

Results
From February 2018 to November 2019, a total of 37 patients were enrolled. The majority were male patients (54.1%), with a median age of 60 year old (IQR 18). The mean tumor size was 25.9 mm (SD 7.7) and lesions were mostly located at the pancreatic head (70%). All the lesions were close or invading at least one vessel, except one (60% and 35% had venous and arterial vessels involvement, respectively). A total of 97 fiducials were implanted, with a median number of 3 fiducials placed per patient (range 0-4). The technical success rate was 92%, with failure of fiducials placement in 3 patients, mostly due to interposing vessels or difficulty to define the tumor limits (altered by induction chemotherapy). Adverse events were observed in three patients (8%), with 1 case of post-procedural fever, 1 case of mild acute pancreatitis and 1 case of biliary stent migration. All the patients that had fiducial markers placed could receive SBRT treatment. At pre-SBRT CT evaluation, however, there were 2 patients whose markers had migrated. From the other 32 patients, 76 % had at least 2 markers inside or less than 1 cm from the tumor and in 75% there was at least one marker located in the tumor's extremity. Nevertheless, markers placement in different spatial planes was achieved in only 56% of the cases and there were 72% with at least 2 markers were positioned too close from each other. As predefined, this resulted in a high quality success rate of 62.5%.

Conclusions
Our results contribute to demonstrate the good feasibility and security of EUS-guided fiducial markers placement, with encouraging results in terms of SBRT achievability. The radiotherapy quality score underlines factors that may improve treatment dose distribution through optimal fiducial position, and highlights the way for improvement in marker delivery.

Friday March 6, 2020 14:30 - 14:45 CET
Room TEUN

BPC, Session 1

14:30 CET

Molecular pathology of oesophageal cancer and its clinical implications.

Speakers

P. Pauwels (UZ Antwerpen)

Friday March 6, 2020 14:30 - 15:00 CET
Room LIJN

WGD Pathology, Session 2

14:45 CET

Long-term safety of indwelling double pigtail stents for drainage of pancreatic collections with disconnected pancreatic duct syndrome.

Authors
P. GKOLFAKIS (1), A. BOURGUIGNON (1), M. ARVANITAKIS (1), A. BAUDEWYNS (1), P. EISENDRATH (2), D. BLERO (1), A. LEMMERS (1), M. DELHAYE (1), J. DEVIÈRE (1) / [1] Erasme Hospital, Brussels, Belgium, Gastroenterology, [2] CHU Saint-Pierre, Brussels, Belgium, Gastroenterology

Introduction
Transmural indwelling double-pigtail stents (DPS) are recommended for patients with disconnected pancreatic duct syndrome (DPDS) and peripancreatic fluid collections (PFC).

Aim
To evaluate the long-term safety and efficacy of indwelling DPS.

Methods
Medical files of patients treated with transmural DPS for DPDS-associated PFC (walled-off necrosis or pseudocysts due to acute or chronic pancreatitis) and a minimum follow-up of 48 months were reviewed. Overall, early (<28 days) and late complication rates were calculated. Long-term outcomes (efficacy and collection recurrence) were assessed.

Results
From 2002 to 2014, 116 patients [86 (74.1%) men; age 48.1±15 years; 57 (49.1%) chronic pancreatitis] with complete pancreatic duct rupture confirmed by MRCP or ERCP were identified. They underwent 175 transmural drainages (150 (85.7%) transgastric access; 2 DPD deployed in 71 (40.5%) of the cases). Sixty-nine (59.4%) of the initial drained collections were pseudocysts (94.2±50mm) and the main indication was infection (55/116; 47.4%). Mean follow-up was 80.6±34.4 months. Per intervention complication rates were 20.5% (36/175); 11.4%(20/175) and 9.1% (16/178) for overall, early and late complications, respectively. Among early complications, 15/20 occurred peri-interventionally (bleeding and pneumoperitoneum) and 8 required further intervention or transfusion. Among late complications (stent-induced ulcer, bleeding, organ compression and abscess) only 2/16 required additional intervention other than stent removal. No death related to the procedure occurred. In per patient analysis, the complication rate was 1 per 21.6 patients-years of follow-up and 1 per 48.7 patients-years of follow-up regarding late complications. Migration (spontaneously or intended) of initial DPS occurred in 86/116 (74.1%) patients (42±36.7 months). Early migration (<6, <12 and <24 months) was related to an increased risk of collection recurrence (p≤0.02). At the end of follow-up endoscopic treatment was considered unsuccessful in 6/116 (0.05%) patients.

Conclusions
Indwelling DPS for DPDS are related to a low risk of long-term complications and lower risk of PFC recurrence.

Speakers

Paraskevas Gkolfakis

Arnaud Bourguignon

Marianna Arvanitakis

Arthur Baudewyns

Pierre Eisendrath

Daniel Blero

Arnaud Lemmers

Myriam Delhaye

Jacques Devière

Friday March 6, 2020 14:45 - 15:00 CET
Room TEUN

BPC, Session 1

15:00 CET

Endoscopic ultrasounded-guided radiofrequency ablation for pancreatic lesions: Belgian experience.

Authors
L. MONINO (1), B. IVAN (1), P. HUBERT (2), M. TOM (2), D. PIERRE (2) / [1] Université Catholique de Louvain, Brussels, Belgium, Gastroenterology, [2] Université Catholique de Louvain, Brussels, Belgium, gastroenterology

Introduction
Radiofrequency ablation (RFA) allow to ablate dysplasic or neoplasic tissue thanks to thermal coagulative necrosis and immunomodulation. Recently, new devices have allowed the use of radiofrequencies guided by EUS. EUS-RFA quickly emerged as a simple technique for the treatment of benign pancreatic tumors.

Aim
We evaluated efficacy and safety of RFA to treat neuroendocrine tumor and metastatic renal cell carcinoma .

Methods
Retrospective study of consecutive case of pancreatic lesion with radiofrequency ablation between July 2018 and May 2019. EUS-RFA was performed with a 18G cooling needle.

Results
11 patients (5 women, mean age 58+/-13 years)underwent EUS-RFA for pancreatic lesion. 13 lesions with an average size of 15.2+/-4.4 mm were treated with EUS-RFA. The indications for performing radiofrequency ablation were: nonfunctional neuroendocrine tumor (n=4), Insulinoma (n=3) and metastatic renal cell carcinoma localized to pancreas (n=4). Technical success rate for the procedure was 100%. Three adverse events were encountered (27%): one gastric wall hematoma and two acute pancreatitis one of these complicated with a pancreatic pseudocyst managing endoscopically. At six month, among the patient with NET three had completed disappear and four a partial response (decrease size tumor>50%). At six month, among the patients with metastatic renal cell carcinoma two had completed response, one partial response and one no response.

Conclusions
EUS-RFA appears to be an interesting treatment of neuroendocrine tumor and metastatic renal cell carcinoma localized to pancreas.

Speakers

Laurent MONINO

Borbat Ivan

Piessevaux Hubert

Moreels Tom

Deprez Pierre

Friday March 6, 2020 15:00 - 15:15 CET
Room TEUN

BPC, Session 1

15:00 CET

What is symptomatic hemorrhoidal disease?

Speakers

D. DE LOOZE (UZ Gent)

Friday March 6, 2020 15:00 - 15:15 CET
Room TIFFANY/SHAH

Proctology, Session 2

15:00 CET

Coffee Break

Friday March 6, 2020 15:00 - 15:30 CET
Exposition Area

WGD Pathology

15:15 CET

Treatment of a large WON with a novel instrument: the EndoRotor DEN Microdebrider.

Authors
E. MACKEN (1), M. SOMERS (1), H. DE SCHEPPER (1), A. JAUREGUI (1), S. BOUHADAN (1), S. FRANCQUE (1) / [1] UZA, Universitair Ziekenhuis Antwerpen, Edegem, Belgium, gastroenterology and hepatology
Walled off necrosis (WON) is a complication of an acute pancreatitis. Endoscopic treatment consists of drainage by placement of a stent, either a metal stent (lumen apposing metal stent (LAMS) or a self expanding metal stent (SEMS)), or plastic stents (double pigtail stents). However, in case of the presence of a large amount of necrotic tissue in the cyst, the placement of stents is seldom sufficient and additional necrosectomy is necessary. Removal of the necrotic tissue can be cumbersome and time consuming because of the sticky and thick nature of the debris. Necrotic tissue is easily teared down in pieces using the grasping forceps or loop, and multiple passages with the endoscope are necessary. Moreover, solid debris will often block the stent(s). We tried the new microdebrider catheter (EndoRotor, Interscope Medical, Inc) for necrosectomy. This device can be used in a 3.2 mm endoscopic working channel to resect and remove solid debris. We hereby present the case of a 64-year old man who presented with an acute necrotic pancreatitis with the development of a big necrotic collection with a diameter of 12 cm and compression of the stomach and duodenum. In September 2019, a Hot Axios stent (Boston Scientific, diameter 15 mm) was placed under endoscopic ultrasonography (EUS) guidance. Subsequent necrosectomies were difficult because of the adherence of the thick necrotic tissue to the wall of the cyst. A lot of debris was still present. In October 2019, two procedures with the EndoRotor were able to remove all of the necrotic tissue. Patient is doing well at the moment and CT confirmed the succesfull clearance of the necrosis and complete resolution of the cyst. The EndoRotor (Interscope Medical, Inc) is a dedicated instrument for transluminal endoscopic debridement of infected pancreatic tissue. It delivers cutting with simultaneous suction and irrigation through standard flexible endoscopes, in this way enabling debridement with the scope remaining in the cyst without the need for multiple passages as is the case with the use of a loop or grasping forceps. The debrided material is automatically collected. The cutter window can be rotated 360 ° to optimize access. The EndoRotor is used with a compact EndoRotor Console with a cutter speed between 1000 rpm and 1750 rpm and an irrigation flow rate of 5 ml/min. In 2018, two patients were treated with the EndoRotor in Rotterdam with complete removal of the necrotic tissue (1) and during the United European Gastroenterology (UEG) week Schlag presented a poster with the interim results of 12 patients who underwent microdebrider-assisted necrosectomy (2). No adverse events were reported, one patient died not attributed to microdebrider use. A 96 % reduction in size of the necroma on CT at 21 days post-initial proceure was reported. By our knowledge, this is the first use of the EndoRotor system in Belgium. We think this is a valuable technique in the case of severe WON when placement of a stent is not sufficient and additional necrosectomy is necessary. 1. van der Wiel S et al, The EndoRotor, a novel tool for the endoscopic management of pancreatic necrosis. Endoscopy 2018; 50: E240-E241 2. Schlag C et al, Endoscopic microdebrider-assisted necrosectomy for walled-off pancreatic necrosis – a prospective international multicenter feasibility study. Poster UEG week 2019

Speakers

Elisabeth Macken

Heiko DE SCHEPPER

Aranzazu JAUREGUI

Souad BOUHADAN

Sven Francque

Michael SOMERS

Friday March 6, 2020 15:15 - 15:30 CET
Room TEUN

BPC, Session 1

15:15 CET

Critical appraisal of (new) interventional techniques in hemorrhoidal disease.

Speakers

L. SIPROUDHIS (Rennes - France)

Friday March 6, 2020 15:15 - 15:30 CET
Room TIFFANY/SHAH

Proctology, Session 2

15:30 CET

Diagnosing Strongyloides in biopsy specimens: a case report.

Authors
S. RUSU (1), C. ROYER-CHARDON (1), P. ROSSIGNON (2), G. VERSET (2), V. HUBERTY (2), D. BLERO (2), L. PEREZ-CASANOVA GOMEZ (1), C. MARIS (1), N. D'HAENE (1) / [1] Erasme Hospital, Brussels, Belgium, Pathology, [2] Erasme Hospital, Brussels, Belgium, Gastroenterology
We report a case of a 71-year-old male who presented bilateral lower limb oedema, diffuse pain, difficult prehension for the last 3 weeks, loss of appetite and weight, complicated by nausea and vomiting the last week prior to medical consult. The clinical examination revealed epigastric and umbilical region abdominal pain. The blood tests revealed an inflammatory syndrome, severe anaemia, hypereosinophilia and electrolyte imbalance (hypokalemia, hypoalbuminemia). Thoraco-abdominal ultrasonography and computed tomography showed multiple hilar and mediastinal adenopathy, bilateral pleural effusion, ground-glass opacity in the right anterior lung basal segment, suggesting an infectious etiology. Considering the patient’s history of gastric ulcer and the epigastric pain, an endoscopy was performed. No peptic ulcer was objectived but a post-Bilroth I status. The mucosal aspect was normal and biopsies were performed. Histological examination of the duodenal biopsies showed blunted and atrophic villi, an increased number of plasma cells, lymphocytes and neutrophils in the lamina propria and in the lining epithelium resulting in cryptitis and crypt abscesses’ images. Multiple coiled adult females, rhabditiform larvae and eggs of Strongyloides stercoralis were observed in the crypts. Although strongyloidiasis could not be confirmed based on microscopy alone, an infection with Strongyloides Stercoralis was confirmed in this particular case using ELISA technique and stool examination. Strongyloidiasis is distributed worldwide, but more common in wet and warm regions. It is transmitted through direct penetration of human skin by infective larvae when in contact with soil. Light infections in healthy subjects often are asymptomatic but in immune suppressed patient the outcome can be fatal. Three clinical phases are described in immunocompetent patient: cutaneous, pulmonary (due to migration of the larvae in the lungs and tracheobronchial pathways) and intestinal (usually three weeks after infection). Symptomatic patients present aspecific complaints such as hunger pains, cramping, intermittent diarrhea and constipation, as well as moderate anaemia, weight loss and leukocytosis with eosinophilia. Diagnosing Strongyloidiasis is challenging, especially in countries where its prevalence is low. It can be evocated on tissue biopsies when adult females and/or larvae and/or eggs are identified. However confirmation by stool examination or serologic test is needed before initiating antiparasitic therapy.

Speakers

Stefan Rusu

Claire Royer-Chardon

Pierre Rossignon

Gontran Verset

Vincent Huberty

Daniel Blero

Luis Perez-Casanova Gomez

Calliope Maris

Nicky D'HAENE

Friday March 6, 2020 15:30 - 15:45 CET
Room LIJN

WGD Pathology, Session 2

15:30 CET

Coffee Break

Friday March 6, 2020 15:30 - 16:00 CET
Exhibition Area

BPC

15:30 CET

Summary of the Belgian guidelines in hemorrhoidal disease: conservative treatment.

Speakers

H. DE SCHEPPER (UZ Antwerpen)

Friday March 6, 2020 15:30 - 16:00 CET
Room TIFFANY/SHAH

Proctology, Session 2

15:45 CET

81-year-old man with ulcerated mass in the caecum.

Authors
C. ROYER-CHARDON (1), S. RUSU (1), . BRAHIMI (2), L. MANS (3), N. BACHIR (4), A. DEMOLS (3), . SIMON (2), L. PEREZ-CASANOVA GOMEZ (1), C. MARIS (1), . NORTIER (2), N. D'HAENE (1) / [1] Erasme Hospital, Brussels, Belgium, Pathology, [2] Erasme Hospital, Brussels, Belgium, Nephrology, [3] Erasme Hospital, Brussels, Belgium, Gastroenterology, [4] Erasme Hospital, Brussels, Belgium, Digestive Surgery
A 81-year-old man with chronic renal failure treated with hemodialysis since 6 years presented with right flanc abdominal pain. His medical history consists of arterial hypertension, renal cysts, monoclonal gammopathy of undetermined significance, carbohydrate intolerance and aortic stenosis. The treatment of the patient consisted of sodium bicarbonate, calcium and magnesium acetate, sevelamer carbonate, acetylsalicylic acid, acenocoumarol and calcium polystyrene sulfonate. Abdominal computed tomography (CT) showed circumferential thickening of the caecum and the right colon up to 2.5 cm thick, over a length of 9.4 cm, which was worrisome for a neoplastic etiology. Colonoscopy showed an ulcerated caecal mass, with a large ulcer extending over 7 cm, and colonic diverticulosis. Differential diagnosis between neoplastic etiology or pseudotumoral mass of ischemic colitis origin was made. The biopsy revealed a largely ulcerated colonic mucosa with no sign of malignancy. Serum CA19-9 was slightly elevated, CEA was normal. Thoraco-abdominal CT did not reveal distant metastasis. Despite negative biopsies, given the high clinical suspicion of malignancy and the presence of lower gastrointestinal bleeding, a right colectomy with lymph node dissection was performed. Gross examination showed a serous adhesion between the caecum and the terminal ileum. At the opening, two ulcers in the caecum were observed. Microscopic examination revealed an ulcerated colon mucosa with acute inflammation of the colon wall associated with a subacute peritonitis. Crystal foreign material was observed in the ulcers but also in the colon mucosa at distance. Two types of crystal foreign material were observed : bright purple crystals consistent with calcium polystyrene sulfonate crystals (Kayexalate) and yellow/pink crystals with fish scale appearance consistent wih sevelamer crystals. Beside calcium acetate/ carbonate supplements, sevelamer is a phosphate binder widely prescribed to patients with severe to end-stage chronic kidney disease. Sevelamer crystals deposition is a rare cause of gastrointestinal mucosal injury. The most common clinical manifestation is bleeding. Despite rarely reported, clinicians should be aware of such pseudotumor presentation named.

Friday March 6, 2020 15:45 - 16:00 CET
Room LIJN

WGD Pathology, Session 2

16:00 CET

Incidence of appendiceal NEN and adherence to pathology classification rules in Belgium.

Authors
S. RIBEIRO (1), F. DE MAEYER (2), M. DE MAN (1), S. CARTON (3), P. CUYLE (3), T. VANDAMME (4), C. VERSLYPE (5), I. BORBATH (6), P. DEMETTER (7), N. VAN DAMME (8), L. VAN EYCKEN (8), A. HOORENS (9), K. GEBOES (1) / [1] UZ Gent, Gent, Belgium, Gastroenterology, [2] AZ Sint-Elisabeth, Zottegem, Belgium, Gastroenterology, [3] Imelda Hospital, Bonheiden, Belgium, Gastroenterology, [4] Netwerk, UZA, Edegem, Belgium, Gastroenterology, [5] KU Leuven, , Belgium, Gastroenterology, [6] UCLouvain, , Belgium, Gastroenterology, [7] Institut Jules Bordet, , Belgium, Pathology, [8] Belgian Cancer Registry, Brussel, Belgium, Register, [9] UZ Gent, Gent, Belgium, Pathology

Introduction
Appendiceal neuroendocrine neoplasms (aNEN) are rare tumors. Classification systems have changed significantly and repeatedly over the years, largely because of changes in terminology. There is a definite need for unbiased data on the epidemiology of NEN. Most existing data are incomplete because they are retrieved from registries kept by groups of (expert) centers, such as the DNET registry. In Belgium, data on patient and tumor characteristics of all newly diagnosed cancers is collected in a national and population based registry, the Belgian Cancer Registry (BCR). The BCR also receives the pathology protocols describing results of (pre-)malignant specimens.

Aim
The aim of the present study is to have epidemiological data of aNEN in Belgium and to investigate the evolution of pathological reporting.

Methods
Pathology reports of all aNENs diagnosed between 2010 and 2015 were thoroughly reviewed. A significant part of pathologists in Belgium use the College of American Pathologists (CAP) guidelines, first introduced for NET in June 2012. All reports were checked for clinicopathological data including size of tumor, WHO grade (Ki 67), grade of differentiation, lymphovascular invasion, location, infiltration of the mesoappendix, nodal involvement and margin status, because treatment algorithms are based on these parameters. Right hemicolectomy should be offered to all patients with appendiceal neuroendocrine tumors (aNET) > 2cm. It is also suggested to advise right hemicolectomy in patients with grade (G)2 aNET. In patients with a tumor size between 1 and 2 cm, right hemicolectomy should be discussed based on certain risk factors. Classification was examined and adapted to the WHO 2019 classification, if necessary.

Results
We identified 584 aNENs over a period of 6 years, corresponding to a steady incidence of 0.9/100.000/year. It was impossible to verify classification in 185 cases because of missing pathological data. Fifty-one patients had to be reclassified according to the WHO 2019 guidelines. After reclassification, there were 348 NET G1, 50 NET G2 and 1 neuroendocrine carcinoma (NEC). Fifty-six% of patients were female, mean age 39y. The size of the tumor was mentioned in 94% of 584 cases. WHO grade and grade of differentiation were both retrievable in 44% of cases in 2010 and in 80% and 72% of cases respectively in 2015. Twenty-one NET G1 and 6 NET G2 tumors were larger than 2cm. We found no information on tumor size in 18 G1 and 3 G2 patients. 71 patients had a G1 tumor sized between 1 and 2 cm. At least 1 of the 4 commonly used prognostic factors was missing for all these patients; 2 prognostic factors were missing for 28 (39,4%) patients, and 3 or more were missing for 23 (32,3%) patients. 15 patients had a G2 tumor between 1 and 2 cm. Only 1 of these patients had all the risk factors reported while at least 1 of the 4 prognostic factors was missing for the majority of them (n= 14; 93,3%) and 2 or more prognostic factors were missing for 7 (46,7%) patients. Of note, depth of infiltration of the mesoappendix is not included in the CAP checklist.

Conclusions
Based on the Belgian cancer registry data, we can withhold an incidence for aNEN of 0.9/100.000/year. Tumor size was reported in the majority of cases. Most patients have NEN < 1cm. We have real life data on the evolution of reporting upon introduction of the new WHO grading system, with uptake in 80% of cases by 2015. 32% of cases could not be verified for correct classification because of missing pathological data. 9% of cases had to be reclassified, pointing out that previous reports based on retrospective datasets should be interpreted with caution and original pathological reports (or specimens) should be checked for specific parameters. Missing information in other parameters may be influenced by size, because these parameters only affect decisions in tumors between 1-2cm. However, in all but 1 of these cases at least 1 of the known risk factors were missing

Friday March 6, 2020 16:00 - 16:15 CET
Room LIJN

WGD Pathology, Session 2

16:00 CET

New ESGE update on PEP prevention guidelines.

Speakers

J.-M. Dumonceau (Hôpital Marie Curie Charleroi)

Friday March 6, 2020 16:00 - 16:30 CET
Room TEUN

BPC, Session 2

16:00 CET

Summary of the Belgian guidelines in hemorrhoidal disease: surgical treatment.

Speakers

D. VANDEPUTTE (UZ Gent)

Friday March 6, 2020 16:00 - 16:30 CET
Room TIFFANY/SHAH

Proctology, Session 2

16:15 CET

Incidence of rectal NEN and adherence to pathology classification rules in Belgium.

Authors
F. DE MAEYER (1), M. DE MAN (2), S. RIBEIRO (2), S. CARTON (3), P. CUYLE (3), T. VANDAMME (4), C. VERSLYPE (5), P. DEMETTER (6), I. BORBATH (7), N. VAN DAMME (8), L. VAN EYCKEN (8), A. HOORENS (9), K. GEBOES (2) / [1] AZ Sint-Elisabeth, Zottegem, Belgium, Gastro-enterology, [2] UZGent, Gent, Belgium, Gastro-enterology, [3] Imeldaziekenhuis, Bonheiden, , Belgium, Gastro-enterology, [4] Ziekenhuis Netwerk Antwerpen, , Belgium, Gastro-enterology, [5] UZ Leuven, Leuven, Belgium, Gastro-enterology, [6] Institut Jules Bordet, Brussels, Belgium, Gastro-enterology, [7] UCLouvain, , Belgium, Gastro-enterology, [8] Belgian Cancer Registry, Brussel, Belgium, Belgian Cancer Registry, [9] UZGent, Gent, Belgium, Pathology

Introduction
Rectal neuroendocrine neoplasms (rNEN) and MiNEN (mixed adenocarcinoma and neuroendocrine carcinoma (NEC) or neuroendocrine tumor (NET)) are rare tumors. Their incidence is rising since the introduction of screening programs for colon cancer. Classification changed significantly and repeatedly over the years, because of changes in terminology. There is a need for unbiased data on the epidemiology of NEN. Most existing data are incomplete because they are retrieved from registries kept by groups of (expert) centres. In Belgium, data on patient and tumor characteristics of all new diagnosed cancers is collected in a national and population based registry, the Belgian Cancer Registry (BCR). The BCR also receives the pathology protocols describing results of (pre-) malignant specimens.

Aim
The aim of the present study is to have epidemiological data of rNEN in Belgium and to investigate the evolution of pathological reporting.

Methods
Pathology reports of 686 rNEN diagnosed between 2004 and 2015 were thoroughly reviewed. A significant part of pathologists in Belgium use the College of American Pathologist (CAP) guidelines, first introduced for NET in 2013. All reports were searched for clinicopathological data including size of tumor, WHO grade (Ki 67), grade of differentiation, lymphovascular or perineural invasion, invasion of the muscularis propria and margin status, because treatment algorithms are based on these parameters. Classification was judged on the basis of the WHO 2019 classification and adapted, if necessary.

Results
Sixteen out of 686 cases were not NEN. A total of 670 cases in 667 patients were withheld. A gradual increase in the number of cases was noted, rising to 70+ cases annually from 2011 onwards. The majority (79%) were well-differentiated G1 NET. Well-differentiated G2 NET and poorly differentiated NEC comprise 8 and 10% of the cases, respectively. Well-differentiated G3 NET (2%) and MiNEN (1%) are rare. Size of the tumor reporting rose from 33% of original reports to 68% in 2015. WHO grade and grade of differentiation were mentioned in 33 and 9% of cases in 2004, increasing to 85 and 55% of cases in 2015, respectively. Invasion of muscularis propria and lymphovascular or perineural invasion were less frequently reported. All diagnoses were verified or adapted according to the WHO 2019 classification. 57% of the 670 cases were classified correctly, 27% could not be verified due to missing data and 16% had to be reclassified. 369/531 (69%) cases were true NET G1, 23% were probably G1 and 4 patients had a Ki 67 < 5%. Ki 67 index and size were reported in 62% of these G1 NET. 25 patients were classified as NET G2 with certainty and another 28 were reclassified to this group, leading to 53 NET G2 patients with 100% reporting of Ki67 index. The number of G3 NET is possibly overestimated, due to missing data in the pathology reports: 8/11 cases had insufficient data to be reclassified. Only 2 patients could be regarded as G3 NET with certainty, because both differentiation and Ki67 index were reported. Sixty-six NEC were withheld. The diagnosis of a true NEC could not be verified in 7 cases, due to insufficient data. Twelve cases were coded as large cell carcinomas. Seventeen G3 NET were reclassified to a large cell NEC, resulting in a total of 29 large cell NECs. A total of 30 cases of small cell NEC were reported. Six G3 NET had to be reclassified to a small cell NEC, resulting in 36 small cell NECs in total. Ki67 index was reported in 71% of the cases.

Conclusions
Based on the cancer registry data we can withhold an incidence in rNEN in Belgium of 0.7/100.000/y from 2011 onwards. We see an increase in annual incidence, mainly due to better reporting and because of the introduction of screening programs for colorectal cancer. Despite changes in terminology and classification systems, only 27 % of cases (mainly G1 NET) could not be verified for correct classification because of missing data in the pathology reports. However, 16% of cases had to be reclassified, pointing out that previous reports based on retrospective datasets should be interpreted with caution and original pathology reports (or specimens) should be checked for specific parameters.

Friday March 6, 2020 16:15 - 16:30 CET
Room LIJN

WGD Pathology, Session 2

16:30 CET

Autoimmune pancreatitis: beware of malignancies.

Authors
C. DUMONT (1), I. BORBATH (1), C. DRAGEAN (2), M. KOMUTA (3), P. DEPREZ (1) / [1] Cliniques universitaires Saint-Luc, Brussels, Belgium, Gastroenterology, [2] Cliniques universitaires Saint-Luc, Brussels, Belgium, Radiology, [3] Cliniques universitaires Saint-Luc, Brussels, Belgium, Pathology
Background: Autoimmune pancreatidis (AIP) is a rare chronic inflammatory disease. AIP type 1 belongs to the spectrum of igG4-related diseases. Manifestations and presentation of the AIP type 1 can mimic adenocarcinoma with pancreatic mass and obstructive jaundice. Evolution in clinical, histological and radiological criteria (International Consensus Diagnostic Criteria for Autoimmune Pancreatitis) allows easier diagnostic. Few articles and studies try to show a correlation between AIP or other Ig4-related diseases and extra-pancreatic neoplasia like gastric, lung and prostate cancer. Case-report: In September 2019, a 58-year-old man, from Romania, well-known from surgical department for a recent laparoscopic total gastrectomy because of diffuse high grade carcinoma and adenocarcinoma in situ, was admitted in the Emergency department for asthenia and jaundice. Laboratory tests showed cholestasis and hyperbilirubinemia (6.5 mg/dl). Abdominal CT and RMN confirmed a pancreatic head tumor (24x20x17 mm) with biliary duct dilatation. EUS-guided biopsies were performed with an FNB needle. Histology did not describe malignant patterns but included inflammatory cells with diffuse lymphoplasmocytic infiltration, fibrosis and obliterative venulitis. After exclusion of other diseases, a diagnostic of AIP type 1 was retained based on a positive plasma-IgG4 serology and histology. Tumor markers (CEA and CA19.9) were negatives. 18F-FDG-PET did not reveal other organs involvements. The patient was treated with corticosteroids. Conclusion: We report a rare case of concomitant presentation of gastric neoplasia and AIP. Few single-center studies, case-reports and reviews of literature begin to support a shared pathogenesis between both entities. These articles state that malignancy appears just before or within one year after AIP diagnostic. It could become an interesting concept to start considering AIP as a paraneoplasic syndrome.

Speakers

Colin Dumont

Ivan BORBATH

Cristina Dragean

Mina Komuta

Pierre Deprez

Friday March 6, 2020 16:30 - 16:40 CET
Room TEUN

BPC, Session 2

16:30 CET

The Belgian Week Proctology Quiz.

Speakers

M.A. Denis (UCL Saint-Luc)

P. Roelandt (KULeuven)

Friday March 6, 2020 16:30 - 16:40 CET
Room TIFFANY/SHAH

Proctology, Session 2

16:40 CET

Groove Pancreatitis.

Authors
J. BRANT (1), S. SWEETSER (2) / [1] Mayo Clinic, Rochester, United States (the), Internal medicine, [2] Mayo Clinic, Rochester, United States (the), Gastroenterology
A 65-year-old man presented to the hospital for worsening abdominal pain and postprandial nausea and vomiting. Medical history was notable for chronic alcohol abuse, a solitary kidney after childhood nephrectomy for a Wilm’s tumor, and diabetes. His abdominal pain was described as diffuse occurring intermittently over the previous 2 months with radiation to the back. On physical exam the patient endorsed mild epigastric tenderness that did not significantly worsen with palpation. Laboratory work up demonstrated a mildly elevated lipase of 95 U/L (reference range 12–61 U/L) and otherwise normal liver biochemistries. Right upper quadrant ultrasound demonstrated mildly dilated intrahepatic ducts as well as a mildly dilated common bile duct measuring up to 8mm in diameter. Adjacent to the distal portion of the common bile duct was a heterogeneous mass-like area felt to represent a soft-tissue mass. Computed tomography of the abdomen with intravenous contrast revealed cystic lesions within the uncinate process of the pancreas with multiple peripancreatic fluid collections and an underlying IPMN. Additionally identified was a diffusely fluid-filled dilated stomach with inflammatory changes surrounding the duodenum felt to likely be reactive inflammation from pancreatitis resulting in a functional gastric outlet obstruction (Figure 1). The patient subsequently underwent upper endoscopy for evaluation of gastric outlet obstruction with identification of acquired duodenal stenosis with two areas of intrinsic moderate stenosis observed in the first and second portions of the duodenum and an associated component of extrinsic compression in the first portion of the duodenum. A healed scar was observed in the second portion of the duodenum and edematous and inflamed mucosal changes in the first portion (Figure 2). Biopsy obtained showed histopathologic evidence of reactive inflammatory changes within the duodenal mucosa without evidence of malignancy. A nasojejunal tube and nasogastric tube were placed endoscopically for nutritional support and gastric decompression. To further exclude malignancy, an endoscopic ultrasound with pancreatic biopsy was considered however due to the degree of duodenal stenosis and lack of a discrete focus for biopsy the procedure was deferred. Carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9) were measured within normal limits at 2.6 ng/mL and 17 U/mL, respectively. Overall, the patient's clinical history, imaging and endoscopic findings were felt to be consistent with groove pancreatitis. The patient was discharged from the hospital with a planned trial of 4 weeks of conservative medical management (enteral feeding, analgesics, and proton-pump inhibitor) allowing for improvement of pancreaticoduodenal inflammatory changes. Follow up with gastroenterology and surgery was planned to determine further management with consideration for pancreaticoduodenectomy. Groove pancreatitis is a rare entity of segmental pancreatitis first described in the 1970s characterized by inflammation and fibrosis of the pancreaticoduodenal groove containing the pancreatic head, duodenum and common bile duct. Groove pancreatitis most commonly occurs in males aged 40-60 with a history of chronic alcohol and/or tobacco abuse. Clinical features include an often chronic and relapsing course of symptoms characterized by abdominal pain, nausea and vomiting. In patients with associated duodenal stenosis postprandial vomiting is often a predominant feature. Similarly, patients with common bile duct stenosis may develop obstructive jaundice. Laboratory values are often nonspecific with only slight elevations in liver biochemistries or pancreatic enzymes. The pathophysiology of groove pancreatitis is complex and felt to be complex and related to physiologic and anatomic factors resulting in inflammatory exudate, cyst formation and deposition of fibrotic tissue. Given the overlapping features of pancreatic adenocarcinoma and groove pancreatitis including risk factors and clinical presentation it is imperative that pancreatic adenocarcinoma is excluded before establishing the diagnosis. In contrast to pancreatic adenocarcinoma, patients with groove pancreatitis do not have significant elevations in tumor markers such as CEA or CA 19-9. CT and MRI imaging along with EUS with biopsy can assist with differentiating to two entities, however it should be noted that the possibility of a sampling error may prevent a negative biopsy from excluding malignancy. Groove pancreatitis can be managed with conservative medical therapy; however in patients with severe clinical symptoms or when malignancy cannot be excluded surgery is often required. Surgical treatment typically involves pancreaticoduodenectomy via Whipple procedure or pylorus-preserving pancreaticoduonectomy.

Speakers

Joseph Brant

Seth Sweetser

Friday March 6, 2020 16:40 - 16:50 CET
Room TEUN

BPC, Session 2

16:50 CET

Nivolumab-induced pancreatitis.

Authors
L. JANSSENS (1), S. PATEL (1), N. TAKAHASHI (2), S. MAJUMDER (3) / [1] Mayo Clinic, Rochester, United States (the), Internal Medicine, [2] Mayo Clinic, Rochester, United States (the), Radiology, [3] Mayo Clinic, Rochester, United States (the), Gastroenterology and Hepatology
A 38-year-old woman with a history of metastatic malignant melanoma treated with nivolumab presented with waxing and waning epigastric pain over the past four months. She denied any symptoms of nausea, vomiting, diarrhea, constipation or weight loss. Laboratory studies (normal value ranges in parenthesis) revealed hemoglobin 12.5 g/dL (11.6 – 15), ALT 15 U/L (7 – 45), AST 20 U/L (8 – 43), AP 60 U/L (35 – 104), total bilirubin 0.3 mg/dL (

Speakers

Laurens Janssens

Shruti Patel

Naoki Takahashi

Shounak Majumder

Friday March 6, 2020 16:50 - 17:00 CET
Room TEUN

BPC, Session 2

17:00 CET

Opioid related sphincter of Oddi dysfunction causing double duct sign in a patient with gastric bypass.

Authors
C. SALEM (1), C. MUSALA (2), G. RASSCHAERT (2), L. DUEZ (2), T. SERSTE (2), P. EISENDRATH (2) / [1] CHU Saint-Pierre, Brussels, Belgium, GASTROENTEROLOGY, [2] CHU Saint-Pierre, Brussels, Belgium, Hepato-Gastro-enterologie
Introduction Chronic morphine abuse has been reported as a rare cause of concomitant dilation of both pancreatic (PD) and common bile duct (CBD), known as the double duct sign (1,2,3). Endoscopic ultrasound (EUS) findings of this rare entity have been occasionally reported (4). We report a 59-year-old man recently diagnosed with double duct sign, with a history of chronic opioid abuse evaluated for episodes of abdominal pain and general status alteration. The patient has a history of bypass surgery, that made the diagnosis more challenging. In order to rule out malignancy, EUS-directed trans gastric intervention (EDGI) was performed to enable pancreatic head EUS and potential ERCP. Case report This is a new report of a 59 year old man admitted to the hospital for several episodes of abdominal pain and general status alteration in May 2019. The patient is a chronic morphine consumer with an average of 300mg per day in a context of fibromyalgia. He was operated of a gastric bypass for morbid obesity in 2017. The patient has no history of alcohol and tobacco consumption. An earlier Computed Tomography scan (CT scan) from two month ago, revealed biliary and pancreatic duct dilation (10mm and 9 mm respectively). The patient didn’t come back for planified workup. During current hospitalization, new CT scan and Magnetic resonance cholangiography (MRCP) were performed and revealed worsening duct dilation (17mm and 19mm respectively) without evidence of an obstructive tumor or lithiasis. Lab analysis showed a new cholestasis onset: alkaline phosphatase 155 U/L, GGT 72 U/L, serum bilirubin of 0.2 mg/dL, aspartate aminotransferase of 20 U/L and alanine aminotransferase of 24 U/L. Endoscopic ultrasound (EUS) revealed simultaneous dilatation of the CBD and PD (double duct sign) with anechoic lumens of both the ducts. Pancreatic and periampullary region exploration was limited due to post bypass anatomy. After a multidisciplinary discussion and in the concern of excluding a periampullary tumor, it was decided to perform an EUS trough an artificial gastro-gastric anastomosis, eventually combined with a biliary sphincterotomy and stenting. At the first stage, using a therapeutic echo-endoscope, a lumen apposing metal stent (LAMS) of 20mm diameter with electrocautery delivery system was inserted between the proximal jejunum and the excluded stomach. The trans-anastomotic EUS was perform 28 days after the LAMS implantation. It revealed biliary and pancreatic duct dilation up to the papilla, in a context of pancreas divisum with some stigmas of chronic pancreatitis, absence of tumor or other cause of obstruction. Both procedures were concluded without any complications. ERCP wasn’t finally realized given the favorable evolution of cholestasis. These results and spontaneous evolution led us to a suspicious diagnosis of chronic sphincter dysfunction. Patient was readmitted to our unit 35 days post procedure, for prosthesis removal. He had no symptoms and stable liver function test. He regained 6 kilos of weight since his last admission with an actual BMI of 23.5. The Axios prothesis was removed under general anesthesia and a double pigtail was inserted without particular difficulties. Discussion Several studies showed that chronic opiate use may responsible of common bile duct dilation by increasing sphincter of Oddi tonicity and resulting in secondary SOD (1,2,3,5). EUS is an important part the work-up in case of bile duct dilation to exclude small malignant lesion in the ampullary area (6). Beside the report of new case with suspected morphine abuse related double duct sign, this case illustrates also the problem of access to pancreatic head in a modified anatomy. EDGI is a recent technique to gain access to the excluded stomach in order to facilitate conventional pancreatic head EUS exploration and ERCP (6,7). Previous case series showed that EDGI is associated with high technical and clinical success, and with insignificant risk of short and long term adverse events (6,7). Opiate abuse is an uncommon cause of SOD and a prolonged history of opiate addiction must be sought in patients with unexplained biliary dilatation or dual duct after adequate workup to evaluate potential underlying pathologies (5,6).

Speakers