André D'Hoore

The second European evidence-based Consensus on the diagnosis and management of Crohn's disease: Current management

This paper is the second in a series of three publications relating to the European evidence-based consensus on the diagnosis and management of Crohns disease and concerns the management of active disease, maintenance of medically induced remission and surgery. The aims and methods of the ECCO Consensus, as well as sections on diagnosis and classification are covered in the first paper [van Assche et al. JCC 2009a]. The final paper covers post-operative recurrence, fistulating disease, the management of paediatric and adolescent IBD, pregnancy, psychosomatics, extraintestinal manifestations and complementary or alternative therapy for Crohns disease [Van Assche et al JCC 2009b]. #### Principal changes with respect to the 2006 ECCO guidelines The early use of azathioprine/mercaptopurine or methotrexate in combination with steroids is an appropriate option in moderately active localised ileocaecal CD. Anti-TNF therapy should be considered as an alternative for patients with objective evidence of active disease who have previously been steroid-refractory, steroid-dependent, or steroid-intolerant (based on Statement 5B). For those patients with severely active localised ileocaecal Crohns disease and objective evidence of active disease who have relapsed, anti-TNF therapy with or without an immunomodulator is an appropriate option [EL1a, RG B for infliximab]. For some patients who have infrequently relapsing disease, restarting steroids with an immunomodulator may be appropriate (based on Statement 5C). All currently available anti-TNF therapies appear to have generally similar efficacy and adverse-event profiles for inflammatory (‘luminal’) Crohns disease, so the choice depends on availability, route of delivery, patient preference, cost and national guidelines \[EL5, RG D\] (Statement 5I). Patients receiving azathioprine or mercaptopurine who relapse should be evaluated for adherence to therapy and have their dose optimised. Changing their maintenance therapy to methotrexate [EL1b RG B] or anti-TNF therapy [EL1a RGB] should be considered. Surgery should always be considered as an option in localised disease [EL4, …

Success and failure after repair of rectovaginal fistula in Crohn's disease: analysis of prognostic factors.

To compare the healing rate after several types of surgical repair of rectovaginal fistula (RVF) in Crohn’s disease, and to identify factors predicting a successful outcome.

Mortality risk analysis following routine vs selective defunctioning stoma formation after total mesorectal excision for rectal cancer

Objective  To answer the question whether a defunctioning stoma (DS) should be constructed routinely after total mesorectal excision or whether it could be used selectively to ensure patient safety.

Combining bevacizumab and chemoradiation in rectal cancer. Translational results of the AXEBeam trial.

Background:This study characterises molecular effect of bevacizumab, and explores the relation of molecular and genetic markers with response to bevacizumab combined with chemoradiotherapy (CRT).Methods:From a subset of 59 patients of 84 rectal cancer patients included in a phase II study combining bevacizumab with CRT, tumour and blood samples were collected before and during treatment, offering the possibility to evaluate changes induced by one dose of bevacizumab. We performed cDNA microarrays, stains for CD31/CD34 combined with α-SMA and CA-IX, as well as enzyme-linked immunosorbent assay (ELISA) for circulating angiogenic proteins. Markers were related with the pathological response of patients.Results:One dose of bevacizumab changed the expression of 14 genes and led to a significant decrease in microvessel density and in the proportion of pericyte-covered blood vessels, and a small but nonsignificant increase in hypoxia. Alterations in angiogenic processes after bevacizumab delivery were only detected in responding tumours. Lower PDGFA expression and PDGF-BB levels, less pericyte-covered blood vessels and higher CA-IX expression were found after bevacizumab treatment only in patients with pathological complete response.Conclusions:We could not support the ‘normalization hypothesis’ and suggest a role for PDGFA, PDGF-BB, CA-IX and α-SMA. Validation in larger patient groups is needed.

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.

OC-0019: The role of functional imaging and molecular markers for organ-preserving strategies after CRT for rectal cancer

Results: The number of responders was 145 (45%) and 28 (49%), for the training and validation cohort, respectively. Feature space reduction resulted in a set of 34 highly robust and non-redundant features and subsequent model development lead to a multivariable model consisting of 8 features (Table 1) with an out-of-sample AUC of 0.63±0.09. Independent validation resulted in an AUC of 0.77. Model derived ROC curves for both the training and validation cohort and overall AUC values are shown in Figure 1b.

Long-term outcome of endoscopic dilatation in patients with Crohn's disease is not affected by disease activity or medical therapy (vol 59, pg 320, 2010)

it is a fact and needs to be pointed out, that only one third of our identified IAR (80 of 205) participated in the recommended screening programme. A pilot study on 32 of these IAR using standard questionnaires and interviews (Beck Depression Inventory (BDI) and Brief Symptom Inventory (BSI)) around counselling (days 7, 0, +30) conducted by a psychiatrist revealed, that these IAR were critically biased by cognitive coping strategies (unpublished data). Pancreatic cancer (PC) screening is clearly different from other cancer screening programmes, given the disastrous prognosis of PC, the unknown true penetrance in the different settings of hereditary PC, the lack of a major gene defect, the lack of reliable imaging or biomarkers, the lack of evidence to improve prognosis or to save lives by any screening, and the high risk of morbidity and mortality of potential preventive surgery. Some authors even advocate that at present ‘doing nothing’ provides the greatest remaining quality of life-adjusted years and the lowest costs. We fully agree that we need to gain much more knowledge about hereditary PC to draw a definite conclusion about the true value of PC screening in IAR. However, based on our data, we strongly believe, in accordance with the recommendations of the Fourth International Symposium of Inherited Diseases of the Pancreas, that all screening procedures should be performed as part of peer-reviewed protocols combined with a scientific appraisal of the screening methods and human subject protection. At present there is no data, that would justify a general PC screening even of high risk individuals outside of such protocols as suggested by Harinck et al. In contrast, it has to be feared that uncritical use and interpretation of screening results obtained with the presently available tools on a healthcare basis may cause unnecessary physical harm and psychological distress. On the other hand over-estimation of the power of our present screening tools may lead to a deceptive, unjustified and potentially dangerous level of safety, if done uncritically and uncontrolled. The message of our paper thus is not ‘to do nothing’, but to carefully evaluate screening methods for IAR from familial pancreatic cancer (FPC) families in the setting of board approved clinical trials, to continuously improve our knowledge and strategies.