Freddy Penninckx

Major histocompatibility class II expression on the small intestinal nervous system in Crohn's disease

Widespread alterations of the gut autonomic nervous system have been described in Crohns disease. Immunohistochemistry shows that these alterations are associated with the expression of major histocompatibility (MHC) class II antigens (HLA-DR) on enteroglial cells in the ganglia of the submucous and myenteric plexuses and on the enteroglial sheaths of the nerve extensions. Neuronal cell bodies and extensions do not express MHC class II antigens. The class II expression is associated with the presence of UCHL1-positive T lymphocytes. MHC class II expression can also be found on endothelial cells and vascular smooth muscle cells but not on smooth muscle cells of the muscularis mucosae or propria. The intensity of MHC class II expression on the glial cells of the enteric nervous plexus and on endothelial cells correlates well with the intensity of class II expression on epithelial cells.

Involvement of interleukin 18 in Crohn's disease: evidence from in vitro analysis of human gut inflammatory cells and from experimental colitis models

An imbalance of immunoregulatory factors and/or cells contributes to uncontrolled mucosal T cell activation and inflammation in Crohns disease (CD). Bioactive interleukin (IL)‐18 has been shown to be produced by macrophages in CD lesions. We report here that T cells freshly isolated from inflamed tissue of CD patients (and not T cells from control intestinal tissue) were responsive to IL‐18. In the presence of IL‐18, these T cells produced more interferon (IFN)‐γ and less IL‐10. To analyse further the role of IL‐18 in this disease, an acute and a chronic model of murine colitis were used. IL‐18 mRNA was significantly enhanced in trinitrobenzene sulphonic acid (TNBS) induced colitis, and treatment with IL‐18 binding protein (IL‐18BPa), which neutralizes IL‐18 bioactivity, significantly reduced the severity of colitis. However, IL‐18BPa did not affect the course of chronic colitis in CD45RBhighCD4+ T cell reconstituted SCID mice. Production of IFN‐γ in lamina propria mononuclear cell cultures from IL‐18BPa‐treated SCID mice was decreased, but at the same time fewer lamina propria CD4+ T cells harvested from IL‐18BPa‐treated mice compared to non‐treated mice were in apoptosis. We conclude that IL‐18 clearly has a modulatory role in the inflammatory cascade of CD and experimental colitis by affecting IFN‐γ and IL‐10 production, and apoptosis. In view of the divergent effects of IL‐18 neutralization in the two different murine colitis models, it is unlikely that IL‐18 is at the top of this cascade.

P262 Patients with refractory pouchitis receiving adalimumab may avoid permanent ileostomy

of psoriasis), and 10 (8%), including 7 women, a RPM (all with severe and disabling polyarthralgia). Median ITL were 5.87 (range: 0.52 19.53) mg/mL in patients with CPM and 5.12 (0.00 49.12) mg/mL in those without (P= 0.560), and 1.9 (0.00 13.5) mg/mL in patients with RPM and 5.57 (0.00 49.12) mg/mL in those without (P= 0.058). ATI have been detected in 16 (13%) patients, including 3 with RPM (P= 0.128) and none with CPM (P= 0.605). In multivariate analysis, no predictive factor associated with CPM could be identified and, the sole factor associated with RPM was anti-nuclear antibodies >1/100 at inclusion. Conclusions: ITL and ATI levels were similar in patients developing IFX paradoxical manifestations. As suggested by elevated antinuclear antibodies, RPM could be related to an autoimmune disorder induced by IFX.

The effect of polyethylene glycol and butyrate on anastomotic healing in the rat colon

AbstractBackgroundThe use of mechanical bowel preparation is much debated.MethodsWe evaluated the effects of polyethylene glycol (PEG), with or without a single dose of 3.0 mmol butyrate (BUT), on the bursting pressure (BP) of an intact colon segment and a colon anastomosis in rats. Also, histopathologic damage was studied.ResultsIn rats without colectomy, the mean BP was 159.2 mmHg (SD=18.9) after PEG treatment and 116.7 mmHg (SD=27.5) in controls (p=0.001). In rats with colectomy, the mean BP was 90.4 mmHg (SD=45.9) in the PEG group, 108.0 mmHg (SD=31.9) in the BUT group, and 102.7 mmHg (SD=44.7) in controls (p=0.44). No significant differences in histopathologic scores were observed between rats treated with PEG and controls.ConclusionsPEG does not interfere with anastomotic healing in rats as measured by BP. No benefit of a single dose of butyrate was observed.

OC-0239: Survival of clinical stage I-III rectal cancer patients: a population-based comparison

Purpose or Objective: Glioblastoma multiforme (GBM) is the most common malignant brain tumour in adults. The current standard of care includes surgery followed by radiotherapy (RT) and chemotherapy with temozolomide (TMZ). Treatment often fails due to the radiation and TMZ resistance of a small percentage of cells with stem cell-like behavior (CSC). The Notch signaling pathway is expressed and active in human glioblastoma and Notch inhibitors attenuate tumor growth in vivo in xenograft models. Here, we investigate the efficacy of a clinically (FDA) approved γ-secretase inhibitor (GSI) RO4929097 in tumor control in combination with standard care of treatment (TMZ+RT) in an orthotopic glioma tumour model.

Effet du volume hospitalier sur la qualité des soins et les résultats oncologiques après chirurgie pour cancer du rectum

Introduction Les etudes analysant le rapport entre qualite des soins et volume hospitalier en matiere de cancer du rectum sont peu nombreuses. Pourtant, la centralisation vers des centres experts semble encouragee. But Evaluer l’effet du volume hospitalier sur la qualite des soins multi-disciplinaires du cancer rectal. Methodes De 2006 a 2011, 1 469 patients presentant un cancer du moyen ou bas rectum ont beneficie d’une proctectomie avec exerese totale du mesorectum et ont ete prospectivement inclus dans PROCARE, projet Belge d’ameliorations des soins. Le volume de patients a ete derive d’une base de donnees nationale et analyse comme variable continue. Les soins sont evalues par des indicateurs de qualite soit individuels soit groupes par domaine. Resultats Un effet du volume est observe sur le taux d’administration d’un traitement neoadjuvant pour les stades II-III. revaluation pre-operatoire de la marge de resection circonferentielle, le taux de resection complete, le taux de resection abdomino-perineale et le nombre de ganglions lymphatiques examines apres radiochimiotherapie. La chirurgie est le seul domaine pour lequel la qualite est correlee au volume. Par contre, aucun effet volume n’est observe sur les resultats oncologiques. Conclusion Un effet du volume sur la qualite des soins du cancer rectal est observe mais se limite a un petit nombre d’indicateurs. Il n’y a pas d’effet sur les resultats oncologiques.