Long-term outcome of patients with steroid-refractory acute severe UC treated with ciclosporin or infliximab.

OBJECTIVE: Ciclosporin and infliximab have demonstrated short-term similar efficacy as second-line therapies in patients with acute severe UC (ASUC) refractory to intravenous steroids. The aim of this study was to assess long-term outcome of patients included in a randomised trial comparing ciclosporin and infliximab. DESIGN: Between 2007 and 2010, 115 patients with steroid-refractory ASUC were randomised in 29 European centres to receive ciclosporin or infliximab in association with azathioprine. Patients were followed until death or last news up to January 2015. Colectomy-free survival rates at 1 and 5 years and changes in therapy were estimated through Kaplan-Meier method and compared between initial treatment groups through log-rank test. RESULTS: After a median follow-up of 5.4 years, colectomy-free survival rates (95% CI) at 1 and 5 years were, respectively, 70.9% (59.2% to 82.6%) and 61.5% (48.7% to 74.2%) in patients who received ciclosporin and 69.1% (56.9% to 81.3%) and 65.1% (52.4% to 77.8%) in those who received infliximab (p=0.97). Cumulative incidence of first infliximab use at 1 and 5 years in patients initially treated with ciclosporin was, respectively, 45.7% (32.6% to 57.9%) and 57.1% (43.0% to 69.0%). Only four patients from the infliximab group were subsequently switched to ciclosporin. Three patients died during the follow-up, none directly related to UC or its treatment. CONCLUSIONS: In this cohort of patients with steroid-refractory ASUC initially treated by ciclosporin or infliximab, long-term colectomy-free survival was independent from initial treatment. These long-term results further confirm a similar efficacy and good safety profiles of both drugs and do not favour one drug over the other. TRIAL REGISTRATION NUMBER: EudraCT: 2006-005299-42; ClinicalTrials.gouv number: NCT00542152; post-results.

Structural robustness of the gut mucosal microbiota is associated with Crohn's disease remission after surgery.

OBJECTIVES: Preventing postoperative recurrence after ileocolonic resection (ICR) for Crohn's disease (CD) is challenging. Defining the disturbances of the microbial composition and community structure after ICR and their link with early disease recurrence is crucial. DESIGN: Microbiota composition (fingerprinting and 16S rDNA sequencing) and community structure (correlation networks of bacterial species) were assessed from ileal mucosa sampled in 20 patients undergoing ICR and 6 months later during endoscopy from above (neoterminal ileum) and below (subanastomotic colon) the surgical anastomosis. RESULTS: ICR had a dramatic effect on gut microbial ecosystem. At surgery, CD mucosa harboured a dysbiotic microbiota with high proportions of α/ß Proteobacteria and Bacilli. Six months later, half of the patients had recurrent lesions at ileocolonoscopy and presented higher numbers of Lachnospiraceae. Recurrence of endoscopic lesions was associated with enrichment in Enterococcus durans while patients in remission had increased proportions of Dorea longicatena and Bacteroides plebeius. Structural differences were striking between recurrence and remission microbiota; while the microbiota of patients with CD recurrence exhibited a loose community structure, the microbiota of patients in remission displayed communities that were robustly correlated to each other. Microbiota colonising the neoterminal ileum and subanastomotic colon 6 months after ICR only differed in patients with recurrence. CONCLUSIONS: ICR modifies the gut microbiome. Remission after 6 months was associated with homogenous bacterial distribution around the anastomosis. Community structure and bacterial networks highlight target species, including Faecalibacterium prausnitzii and Ruminococcus gnavus, which may allow precise modulations of the overall microbial ecosystem towards remission pattern.

IOIBD technical review on endoscopic indices for Crohn's disease clinical trials.

BACKGROUND: Crohn's disease (CD) is a chronic disabling and progressive IBD. Only strategies looking beyond symptoms and based on tight monitoring of objective signs of inflammation such as mucosal lesions may have the potential for disease modification. Endoscopic evaluation is currently the gold standard to assess mucosal lesions and has become a major therapeutic endpoint in clinical trials. Several endoscopic indices have been proposed to evaluate disease activity; unvalidated and arbitrary definitions have been used in clinical trials for defining endoscopic response and endoscopic remission in CD. METHODS: In these recommendations from the International Organization for the Study of Inflammatory Bowel Disease, we first reviewed all technical aspects of available endoscopic scoring systems in the literature. Second, in order to achieve consensus on endoscopic definitions of remission and response in trials, a two-round vote based on a Delphi method was performed among 14 specialists in the field of IBDs. RESULTS: At the end of the voting process, the investigators ranked first a >50% decrease in Simple Endoscopic Score for Crohn's Disease (SES-CD) or Crohn's Disease Endoscopic Index of Severity for the definition of endoscopic response, and an SES-CD 0-2 for the definition of endoscopic remission in CD. All experts agreed on a Rutgeerts' score i0-i1 for the definition of endoscopic remission after surgery.

Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE): Determining Therapeutic Goals for Treat-to-Target.

OBJECTIVES: The Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) program was initiated by the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD). It examined potential treatment targets for inflammatory bowel disease (IBD) to be used for a "treat-to-target" clinical management strategy using an evidence-based expert consensus process. METHODS: A Steering Committee of 28 IBD specialists developed recommendations based on a systematic literature review and expert opinion. Consensus was gained if ≥75% of participants scored the recommendation as 7-10 on a 10-point rating scale (where 10=agree completely). RESULTS: The group agreed upon 12 recommendations for ulcerative colitis (UC) and Crohn's disease (CD). The agreed target for UC was clinical/patient-reported outcome (PRO) remission (defined as resolution of rectal bleeding and diarrhea/altered bowel habit) and endoscopic remission (defined as a Mayo endoscopic subscore of 0-1). Histological remission was considered as an adjunctive goal. Clinical/PRO remission was also agreed upon as a target for CD and defined as resolution of abdominal pain and diarrhea/altered bowel habit; and endoscopic remission, defined as resolution of ulceration at ileocolonoscopy, or resolution of findings of inflammation on cross-sectional imaging in patients who cannot be adequately assessed with ileocolonoscopy. Biomarker remission (normal C-reactive protein (CRP) and calprotectin) was considered as an adjunctive target. CONCLUSIONS: Evidence- and consensus-based recommendations for selecting the goals for treat-to-target strategies in patients with IBD are made available. Prospective studies are needed to determine how these targets will change disease course and patients' quality of life.

Validation of a live animal model for training in endoscopic hemostasis of upper gastrointestinal bleeding ulcers.

BACKGROUND AND STUDY AIMS: The management of upper gastrointestinal bleeding requires training of the endoscopist. We aimed to validate a live animal model of bleeding ulcers for training in endoscopic hemostasis. MATERIALS AND METHODS: Bleeding ulcers were created by repeated grasp-and-snare gastric mucosectomies in pigs rendered "bleeders" by preadministration of clopidogrel, aspirin, and unfractionated heparin. The feasibility and reproducibility of the model (proportion of bleeding ulcers, number of ulcers per animal, and time needed to produce a bleeding ulcer) were prospectively evaluated in six animals. Ten endoscopic experts assessed the similarity of this pig model to human bleeding ulcers (four-point Likert scale). The training capabilities of the model for hemostatic techniques (needle injection, bipolar electrocoagulation, and hemoclipping) were evaluated in 46 fellows (four-point Likert scale). RESULTS: A total of 53 gastric ulcers were created in 6 animals (8.8 ± 1.5 ulcers/animal). Successful active ulcer bleeding (Forrest Ib) was achieved in 96.2 % of cases. Bleeding was moderate to abundant in 79 % of cases. Ulcerations consistently reached the submucosal layer. The mean (± SD) time taken to create a bleeding ulcer was 3.8 ± 0.6 minutes. Endoscopic experts assessed the realism of the ulcers and bleeding at 3.2 ± 0.7 and 3.6 ± 0.7 respectively on a four-point Likert scale. The training significantly improved the endoscopic skills of the 46 fellows (P < 0.0001) in all hemostatic techniques. CONCLUSIONS: The live porcine model of bleeding ulcers was demonstrated to be realistic, reproducible, feasible, time efficient, and easy to perform. It was favorably assessed as an excellent model for training in endoscopic treatment of bleeding ulcers.

Accuracy of imaging for predicting operative approach in Crohn's disease.

BACKGROUND: The aim of this study was to assess the accuracy of preoperative imaging in detecting the extent of disease and predicting the operative approach in patients with Crohn's disease. METHODS: Patients with Crohn's disease who were scheduled to undergo operation were evaluated before operation using computed tomography enteroclysis (CTE) and magnetic resonance enterography (MRE). Preoperative imaging findings were correlated with intraoperative and pathological findings to estimate the capabilities of preoperative imaging in detecting lesions due to Crohn's disease. The operative approach determined before surgery was compared with the procedure actually performed, which was based on intraoperative findings. RESULTS: Fifty-two patients with Crohn's disease were studied; 26 were evaluated before surgery with CTE and 26 with MRE. Eighty-nine lesions due to Crohn's disease were confirmed surgically (60 small bowel stenoses, 21 fistulas and 8 abscesses). CTE confirmed the presence of 38 of 41 lesions (sensitivity 93 per cent) and MRE 48 of 48 lesions (sensitivity 100 per cent); a correct estimation of the disease with an exact prediction of the operative approach was obtained in 49 (94 per cent) of 52 patients. Discrepant findings between preoperative imaging and operative findings were observed in three patients (6 per cent), who had CTE. CONCLUSION: Preoperative imaging using CTE or MRE is highly accurate for assessing Crohn's disease lesions before operation, allowing correct prediction of the operative approach.

Flexible versus rigid single-port peritoneoscopy: a randomized controlled trial in a live porcine model followed by initial experience in human cadavers.

INTRODUCTION: We compared single incision laparoscopic surgery with flexible endoscope ("flexible SILS") and with rigid optic ("rigid SILS") for access to 11 elective sites of peritoneal carcinomatosis. MATERIALS AND METHODS: Back-to-back flexible and rigid SILS peritoneoscopy were performed in ten live pigs. SILS peritoneoscopy was performed using a flexible endoscope or a rigid optic, in random order, together with two rigid 5-mm laparoscopic forceps. Primary endpoint was access success rate to 11 elective sites of peritoneal carcinomatosis. Findings for the most favorable option were then assessed in four human cadavers. RESULTS: In the porcine model, the overall rate of access to targets was 98% with flexible SILS and 87% with rigid SILS (p < 0.001). Both flexible and rigid SILS allowed a 100% access rate to diaphragmatic domes, paracolic gutters, splenic and hepatic hilum, pelvic floor, and trigonal bladder. The rates of access to other sites by flexible versus rigid SILS, respectively, were: root of the mesentery (90 vs. 50%), origin of the inferior mesenteric vein (90 vs. 50%), inferior vena cava (100 vs. 90%), and cul-de-sac of Douglas (100 vs. 50%). No complications were observed. Procedures were performed in mean time of 26 and 24 min, respectively. These findings were confirmed for flexible SILS in four human cadavers. CONCLUSIONS: Flexible SILS is superior to rigid SILS to evaluate the peritoneal cavity in a timely manner. This suggests a need for flexible instrumentation or other technical solutions to perform thorough minimally invasive surgical evaluation of peritoneal carcinomatosis.

A guide for assessing the clinical relevance of findings in small bowel capsule endoscopy: analysis of 8064 answers of international experts to an illustrated script questionnaire.

BACKGROUND AND AIM: Although recommended, the P-score used for assessing the pertinence / relevance of findings seen in small bowel (SB) capsule endoscopy (CE) is based on a low level of knowledge. The aim of this study was to evaluate the clinical relevance of the most frequent SBCE findings through an illustrated script questionnaire. MATERIALS AND METHODS: Sixteen types of SBCE findings were illustrated four times each in three different settings (occult and overt obscure gastrointestinal bleeding and suspected Crohn's disease), and with a variable number (n = 1/n = 2-5/n ≥ 6), thus providing a questionnaire with 192 scenarios and 576 illustrated questions. Fifteen international experts were asked to rate the finding's relevance for each question as very unlikely (-2) / unlikely (-1) / doubtful (0) / likely (+1) / very likely (+2). The median score (≤-0.75, between -0.75 and 0.75, or ≥0.75) obtained for each scenario determined a low (P0), intermediate (P1) or high (P2) relevance, respectively. RESULTS: 8064 answers were analyzed. Participation and completion rates were 93% and 100%, respectively. In overt or occult OGIB, resultant P2 findings were 'typical angiectasia', 'deep ulceration', 'stenosis', and'blood', whatever their numbers, and 'superficial ulcerations' when multiple. While in suspected CD, consensus P2 lesions were 'deep ulceration' and 'stenosis' whatever their numbers, and 'aphthoid erosions' and 'superficial ulcerations' when multiple. CONCLUSION: This study establishes a guide for the evaluation of relevance of SBCE findings. It represents a step forward for SB-CE interpretation and is intended to be used as a tool for teaching and academic research.

Defining and Assessing the Reproducibility of Crohn's Disease Endoscopic Lesions: A Delphi-like Method from the GETAID.

BACKGROUND AND AIMS: Defining and assessing the reproducibility of Crohn's disease [CD] endoscopic lesions is essential in assessing endoscopic healing. METHODS: Twelve endoscopic CD experts from the GETAID defined aphthoid erosions [AE], superficial ulcerations [SU], deep ulcerations [DU], stenosis, and fistulas according to a Delphi-like method. Thirty different GETAID physicians declared if they found acceptable each definition. Intra- and inter-observer agreements were investigated using 100 videos with one tagged specific lesion [AE, SU, DU, or sham lesion] read by 15 independent endoscopists at baseline and 1 month later in a randomised order. Video quality was determined by an external reader. According to kappa estimate [κ ±standard error], intra or inter-observer agreement was qualified as 'moderate' [0.4-0.6], 'substantial' [0.6-0.8], or 'almost perfect' [0.8-1.0]. RESULTS: Among 30 different experts, 83% to 97% found acceptable the definitions retrieved from the Delphi-like method. Intra-observer κ was 0.717 [±0.019] for SU, 0.681 [±0.027] for AE, 0.856 [±0.014] for DU, showing 'substantial' agreement. It was 0.801 [±0.016] for any ulceration [DU or SU]. There was a high variability across readers from 'moderate' to 'almost perfect' agreement. Inter-observer κ was 0.548 [±0.042] for SU, 0.554 [±0.028] for AE 0.694 [±0.041] for DU, and 0.705 [±0.042] for any ulceration. Inter-observer agreement increased when reading the 53 high-quality videos: 0.787 [±0.064] [p = 0.001], 0.607 [±0.043] [p = 0.001], and 0.782 [±0.064][p = 0.001] for DU, AE, and any ulceration, respectively. CONCLUSIONS: Despite variable intra-agreement level across readers, the GETAID definitions for CD endoscopic lesions provided 'substantial' inter-observer agreements, especially in case of high-quality videos.

[The clinical importance of intestinal microbiota]. / L'importance clinique du microbiote intestinal.

Clinicians have long learned of the pathogenic microorganisms that cause intestinal infections and that can be identified by culture methods from fecal, mucosa and blood samples. Nevertheless, much progress has been made due, in large part, to molecular biology which has enabled the discovery of pathogens that are not (yet) able to be cultured, but also to the protective role of some microorganisms within the microbiota. Ecological and clinical disturbances related to antibiotic therapy were decisive for demonstrating the beneficial effects of the endogenous microbiota and establishing the beneficial effects of biotherapeutic agents, known as probiotics. Most areas of gastroenterology (cryptogenic inflammatory bowel disease, irritable bowel syndrome, lymphomas, etc.), but also those in medicine overall (obesity for example), are affected by this new approach and are showing very significant progress. This article summarizes the historical steps of these discoveries and reviews what the "modern" clinician should know in this very dynamic area in regard to research and practical consequences.

Plexitis as a predictive factor of early postoperative clinical recurrence in Crohn's disease.

BACKGROUND AND AIMS: A previous study suggested that the presence of myenteric plexitis in the proximal resection margins could be predictive of early endoscopic recurrence after ileocolonic or ileal resection for Crohn's disease (CD). The aim of the present study was to assess the predictive value of plexitis for early clinical CD recurrence. METHODS: All consecutive patients with ileocolonic or ileal resection for active CD in Lariboisière Hospital (Paris) between 1995 and 2006 were included. Clinical, surgical, histological and follow-up data were extracted from medical charts. Early clinical recurrence was defined as the reappearance of CD clinical manifestations requiring a specific treatment within 2 years postsurgery. The proximal resection margin was analysed using haematein eosin saffron (HES) staining and immunochemistry targeting mastocytes (anti-CD117 antibody) and lymphocytes (anti-CD3 antibody). Eosinophils were detected by HES staining. Ten cases of ileocolonic resections for caecal carcinoma served as controls. RESULTS: Data were available from 171 postoperative follow-up periods in 164 patients with CD. Early clinical recurrence of CD occurred in 28.1%. In multivariate analysis, factors associated with postoperative recurrence were active smoking (hazard ratio (HR) = 1.94; 95% CI 1.06 to 3.60; p = 0.033), submucosal plexitis with >or=3 mastocytes (HR = 1.87; 95% CI 1.00 to 3.46; p = 0.048) and a disease-free resection margin <5 cm (HR = 0.52; 95% CI 0.27 to 1.02; p = 0.059). CONCLUSIONS: Submucosal plexitis is associated with early clinical recurrence and could be taken into account in studies searching for new treatment strategies in the immediate postoperative period.

Clinical evidence for immunomodulatory effects of probiotic bacteria.

Close, tightly orchestrated interactions between the intestinal epithelium and the mucosa-associated immune system are critical for normal intestinal absorptive and immunological functions. Recent data indicate that commensal intestinal microbiota represents a major modulator of intestinal homeostasis. This review analyzes the process of intestinal colonization and the interaction of microbiota with the intestinal epithelium and mucosal immune system, with special reference to the first years of extrauterine life. Dysregulation of the symbiotic interaction between intestinal microbiota and the mucosa may result in a pathological condition with potential clinical repercussions. Based on the concept that there is a beneficial and symbiotic relation between the host and endogenous microbiota, strategies aimed at directly modulating intestinal microbiota with regard to disease prevention or treatment have been developed. One strategy involves administering viable probiotic bacteria. Clinical evidence for the beneficial effect of probiotics in the prevention and/or treatment of necrotizing enterocolitis, infectious and antibiotic-associated diarrhea, allergic diseases, and inflammatory bowel disorders is reviewed herein.

Quality of life improvements attributed to combination therapy with oral and topical mesalazine in mild-to-moderately active ulcerative colitis.

BACKGROUND/AIM: To investigate patient-reported health-related quality of life (HRQoL) in data collected from a multinational randomized double-blind controlled trial comparing oral mesalazine (4 g) + topical mesalazine enema (1 g) to oral mesalazine alone (4 g). METHODS: HRQoL was collected using the EQ-5D at baseline and weeks 2, 4 and 8. The EQ-5D assesses mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Scores from each dimension were reported individually, and converted into a weighted health state which reflects an individual's perception of their health condition. RESULTS: At week 4, a significant HRQoL improvement was observed for patients on mesalazine enemas compared to placebo enemas, with EQ-5D scores of 0.906 and 0.838, respectively (p < 0.05). Mesalazine enema was found to reduce the probability of impairment at week 4 for mobility (p = 0.049) and anxiety/depression (p = 0.048), and was of borderline significance for pain/discomfort (p = 0.053); there was also an increased probability of influencing HRQoL changes for mobility (p < 0.005), usual activities (p < 0.005), pain/discomfort (p < 0.005) and anxiety/depression (p < 0.005), based on reported HRQoL problems at baseline. CONCLUSIONS: Including 1 g mesalazine enemas with 4 g oral mesalazine significantly improved HRQoL in patients with active ulcerative colitis. The improvement in QoL of patients with UC preceded clinical remission, and this underlines the importance of including QoL instruments in clinical studies.

[The future of gastrointestinal therapeutic endoscopy: NOTES]. / Nouvelles perspectives en endoscopie thérapeutique: NOTES.

Natural orifice translumenal endoscopic surgery (NOTES) allows access into the peritoneal cavity with a flexible endoscope, through the wall of the digestive or urogenital tracts. NOTES can be combined to laparoscopic surgery in so-called << hybrid >> techniques. In the absence of any incision of the abdominal wall, NOTES procedures provide perfect cosmetic results, with virtually no risk of parietal complications, and with decreased postoperative pain. NOTES could particularly benefit to overweight patients and to patients receiving intensive or palliative care. Most NOTES studies have been performed on animal models, with great interest for both transgastric and transpelvic approaches. Successful NOTES peritoneoscopy, hysterectomy, oophorectomy, tubal ligation, gastrojejunal anastomosis, cholecystectomy, splenectomy, nephrectomy, and abdominal-wall hernia repair have been described. In human studies, the transvaginal route is preferred. NOTES clinical research focuses on low-morbidity procedures, such as cholecystectomy, appendectomy, and peritoneoscopy. Indirect benefits are expected from this research, with possible technological innovations in the field of endoscopic instrumentation (including sutures, anastomosis, traction and triangulation). Overall, NOTES is believed to make evolve both interventional endoscopy and minimally invasive surgery.

Bacteriotherapy for inflammatory bowel disease: therapeutic tool and/or pharmacological vectors?

Inflammatory bowel diseases are the result of an abnormal immune response to environmental factors including the intestinal microbiota. Epithelial and immune cells of the intestinal mucosa recognise specific bacterial molecules via Toll like and NOD like receptors and this interaction modulates the inflammatory response (activation of the NF-kappaB pathway). It is thus rational to try treatments which could modify the intestinal microbiota i.e. antibiotics, new substrates (prebiotics) or new micro-organisms (probiotics). We review the literature on existing evidence for the efficacy of probiotic strains or combinations in patients with pouchitis (good evidence), ulcerative colitis (fair evidence), and Crohn's disease (no evidence at the present time). We also discuss the mechanisms of action, the use of microbial agents as pharmacological vectors, the development of genetically modified probiotics (including a clinical pilot trial in patients with Crohn's disease), and safety issues.

Liver and inflammatory bowel disease.

Liver disease is exceptional in patients with inflammatory bowel disease. The most common manifestation, sclerosing cholangitis, characterized by inflammation and fibrosis of the intra- and\or extrahepatic bile ducts, is unusual in patients with inflammatory bowel disease. Conversely, inflammatory bowel disease (mainly chronic ulcerative colitis) is not infrequent in patients with sclerosing cholangitis. Gallstone disease, portal vein thrombosis, and hepatic abscesses are complications directly related to inflammatory bowel disease. Drugs prescribed for the treatment of inflammatory bowel disease can be the cause of rare but potentially serious hepatic manifestations which must be recognized and detected early. Recent studies have demonstrated the role of purine analogues in the development of nodular regenerative hyperplasia. Because of the poor prognosis, patients taking purine analogues should be monitored regularly to search for inaugural signs such as an elevation of serum alkaline phosphatase or low platelet counts (which may not necessarily reach thrombopenia). The risk of methotrexate-induced fibrosis is exceptional in inflammatory bowel disease. Patients should be monitored with non-invasive tests to recognize the development of fibrosis. Finally, because of the risk of viral reactivation, patients should be screened for hepatitis B virus surface antigen before introducing infliximab; chronic carriers should be given preventive treatment with nucleoside or nucleotide analogues.

[Management of ileal stenosis in patients with Crohn's disease]. / Prise en charge des sténoses iléales de maladie de Crohn.

Stenosis is the most frequent complication during Crohn's disease. The lesion can be inflammatory, or due to a fibrosing or neoplastic process. The medical treatment with anti-inflammatory drugs is usually sufficient as first line treatment; fibrous lesions require endoscopic or surgical procedures while neoplastic lesions require surgery. A multidisciplinary approach (radiologic, medical, surgical and endoscopic) is needed. In a first part, we discuss the definition of stenosis and the modalities of imaging (particularly MRI) and of treatment (particularly with TNFalpha antagonists). Then we expose the strategy for the management of the most frequent clinical situations: occlusion, ileal inflammatory stenosis, stenosis of an ileocolonic anastomosis and chronic fibrous stenosis. The treatment decision takes into account the results of radiological assessment, CRP level and the effects of the previous treatments.

Online training on how to diagnose anoperineal lesions of Crohn's disease: Do pictures matter? A nationwide randomized study.

Any gastroenterologist must be trained to properly diagnose anoperineal lesions in patients with Crohn's disease (APLOC). The aim of this study was to establish whether adding pictures would improve teaching effectiveness of the diagnosis of APLOC to French gastroenterology trainees. METHOD: Trainees were asked to answer a first web-based survey consisting of evaluating 12 pictures of APLOC with a closed answer questionnaire. They were then randomized in 2 groups. Group A received an online teaching with typical pictures and APLOC definitions and group B definitions only. Trainees were asked again seven days later to answer a second survey with 12 other pictures of APLOC and 14 experts also answered this survey. Diagnostic scores were expressed in %. The primary endpoint was the comparison of the score of survey 2 between the two groups of trainees. Secondary endpoints were to compare results of survey 2 between trainees of both groups and experts, and assess diagnosis of each lesion. RESULTS: Two hundred fourty eight trainees among 465 answered survey 1, and 195 survey 2. The diagnostic score was 71.9% for groups A and B and 74.6% for experts (differences NS). After training diagnosis of ulceration was 72% for group A and 72.9% for group B, fistulae 85.2% versus 85.8%, erythema 44.1% vs. 55.6%, anoperineal scars 67.5% vs. 65.6%, and abscess 100% (differences NS). CONCLUSION: There was no difference between the two teaching methods. Further research should be performed aiming at improving teaching material and quotation baremes.

A double blind randomized controlled trial of a probiotic combination in 100 patients with irritable bowel syndrome.

OBJECTIVES: The purpose of this study was to evaluate the effects of a probiotic combination on symptoms in patients with irritable bowel syndrome (IBS). METHODS: We investigated the efficiency of a probiotic dietary supplement, containing four strains of lactic acid bacteria, on symptoms of IBS. One hundred and sixteen patients with IBS fulfilling the Rome II criteria were randomized in a parallel group, double-blind study to receive a placebo or a probiotic combination (1 x 10(10) cfu once daily) for four weeks. The symptoms that were monitored weekly included discomfort, abdominal pain, and stool frequency and quality. Quality of life was assessed before and at the end of the treatment using the SF36 and FDD-quality-of-life questionnaires. RESULTS: One hundred subjects completed the study (48 probiotic combination, 52 placebo). The probiotic combination was not superior to the placebo in relieving symptoms of IBS (42.6 versus 42.3% improvement). However, the decrease of abdominal pain between the first and the fourth week of treatment was significantly higher in probiotic treated patients (-41.9 versus -24.2%, P=0.048). Interesting findings from the IBS sub-groups were also observed such as a lower pain score at end point in patients with alternating bowel habits (P=0.023) and an increase of stool frequency in the constipated sub-group from the first week of probiotic treatment (P=0.043). CONCLUSIONS: The probiotic combination was not significantly superior to the placebo in relieving symptoms of IBS. Despite the apparent high placebo response, interesting findings from IBS sub-groups were observed in the field of abdominal pain and stool frequency.

Impact of vedolizumab therapy on extra-intestinal manifestations in patients with inflammatory bowel disease: a multicentre cohort study nested in the OBSERV-IBD cohort.

BACKGROUND: The effectiveness of vedolizumab as a treatment for extraintestinal manifestations (EIM) is questionable due to its gut-specificity. AIM: To assess effectiveness of vedolizumab for EIM in patients with inflammatory bowel disease (IBD) in a large real-life experience cohort. METHODS: Between June and December 2014, 173 patients with Crohn's disease and 121 with ulcerative colitis were treated with vedolizumab. Patients were followed until week 54. EIM activity was assessed at weeks 0, 6, 14, 22, 30 and 54 by using a 3-step scale: complete remission, partial response and no response. RESULTS: At baseline, 49 (16.7%) patients had EIMs of which 47 had inflammatory arthralgia/arthritis, four had cutaneous lesions and two had both rheumatologic and skin EIM. At week 54, 21 (44.7%) patients had complete remission for inflammatory arthralgia/arthritis and three (75%) for cutaneous EIM. In multivariate analysis, complete remission of inflammatory arthralgia/arthritis was associated with clinical remission of IBD (OR = 1.89, IC95% [1.05-3.41], P = .03) and recent onset of inflammatory arthralgia/arthritis (OR = 1.99, IC95% [1.12-3.52], P = .02). During the follow-up period, 34 (13.8%) patients without any EIM at baseline, developed incident cases of inflammatory arthralgia/arthritis consisting mostly of peripheral arthralgia without evidence of arthritis and 14 (4.8%) incident cases of paradoxical skin manifestation. CONCLUSION: Vedolizumab therapy is commonly associated with improvement in EIM. This was associated with quiescent IBD and recent EIM. However, paradoxical skin manifestation and inflammatory arthralgia/arthritis may occur upon vedolizumab therapy.