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Background The best management after ileocolonic resection is still unknown in Crohn’s disease (CD). We compared step-up and top-down approaches to prevent short and long-term postoperative recurrences in CD patients. Methods From a comprehensive database, consecutive CD patients who underwent intestinal resection (2014-2021) were included. Top-down (biologics started within the first month after surgery) or step-up strategies (no biologic between surgery and colonoscopy at 6 months) were performed with systematic colonoscopy at 6 months and therapeutic escalation if Rutgeerts index was ≥i2a (endoscopic postoperative recurrence). Propensity score analysis was applied for each comparison. Results Among 115 CD patients, top-down was the most effective strategy to prevent endoscopic postoperative recurrence (46.8% vs 65.9%, P = .042) and to achieve complete endoscopic remission (Rutgeerts index = i0; 45.3% vs 19.3%; P = .004) at 6 months. We did not observe any significant difference between the 2 groups regarding clinical postoperative recurrence (hazard ratio [HR], .86 [0.44-1.66], P = .66) and progression of bowel damage (HR, 0.81 [0.63-1.06], P = .12). Endoscopic postoperative recurrence at 6 months was associated with increased risk of clinical postoperative recurrence (HR, 1.97 [1.07-3.64], P 0.029) and progression of bowel damage (HR, 3.33 [1.23-9.02], P = .018). Among the subgroup without endoscopic postoperative recurrence at 6 months, the risks of clinical postoperative recurrence and progression of bowel damage were significantly improved in the top-down group (HR, 0.59 [0.37-0.94], P = .025; and HR, 0.73 [0.63-0.83], P < .001, respectively). Conclusions Top-down strategy should be the preferred management to prevent short and long-term postoperative recurrence in CD.

International audience; Background and aimsIBS patients have an impaired quality of life (QoL) and feel dissatisfaction with medical care. We aim to describe the expectations of members of the French Association of IBS patients (APSSII) concerning health care providers (HCPs) and a patients’ organization.Patients and methodsFrom January to June 2013, APSSII members were asked to answer questionnaires on their expectations and experiences concerning IBS and HCP.Results222/330 (67%) responded (women: 68.5%, 46.5 ± 17.7 years, disease duration: 8.8 ± 0.7 years, IBS-D 33.6%, IBS-C 26.7%, IBS-M 38.2%. IBS-SSS > 300 in 53% and HAD score > 19 in 45%). QoL impairment was correlated with disease severity and HAD score (r = −0.707 and r = −0.484, P < 0.001 respectively), but not with IBS subtype. Expectations for IBS were “improved health”, “better information on causes and treatments” (94%) and “better disease recognition” (86%). A significant gap was observed between expectations and experiences with HCPs. Better information, less isolation, recognition of the disease and a decrease in medical expenses were the main expectations for joining a patients’ organization.ConclusionsFrench IBS patients have a severe disease with a significant psychological impact and impaired QoL in half of the patients, certain unsatisfied expectations concerning HCP and high expectations in joining a patients’ organization.

Background Magnetic resonance imaging [MRI] is a promising tool to evaluate therapeutic efficacy in ileocolonic Crohn’s disease [CD]. Aims We aimed to assess the feasibility of early MRI evaluation (week 12 [W12]) to predict corticosteroid-free remission [CFREM] at W52 and prevent long-term bowel damage. Methods All patients with active CD needing anti-tumour necrosis factor [anti-TNF] therapy were consecutively enrolled in this multicentre prospective study. MRI was performed before starting therapy, at W12 and W52. CFREM was defined as Crohn’s Disease Activity Index Results Among 46 patients, 22 [47.8%] achieved CFREM at W52. Anti-TNF agents were able to heal almost all CD lesions as soon as W12 [p +10% or ΔRCE [relative contrast enhancement] > −30% was associated with a likelihood of CFREM at W52 of 84.6% vs 37.5% in patients without transmural response [p Conclusion Evaluation of early transmural response by MRI is feasible and is a promising end point to monitor therapeutic efficacy in patients with CD.

Blastocystis is the most frequently isolated protozoan from human stool. Its role in human health is still debated, and a high prevalence was reported in irritable bowel syndrome (IBS) subjects, suggesting a potential link with microbiota. In the present study, we aimed to investigate prokaryotic and eukaryotic microbiota in both IBS-C (constipated) and healthy individuals. We recruited 35 IBS-C patients and 23 healthy subjects, from which 12 and 11 carried Blastocystis, respectively. We performed 16S and 18S rRNA high-throughput sequencing on feces. Whereas we did not observe differences between infected and non-infected controls, several phyla were significantly modified in IBS-C patients according to the presence of Blastocystis. Tenericutes phylum and Ruminococcaceae family were especially increased in Blastocystis carriers. Furthermore, colonization with Blastocystis was associated with discrete changes in the microbial eukaryome, particularly among the Fungi taxa. Depending on the group of patients considered, the mycobiota changes do not go in the same direction and seem more deleterious in the IBS-C group. These results encourage further in vivo and in vitro investigations concerning the role of Blastocystis in the gut environment.

International audience; Background The best option between vedolizumab and ustekinumab after anti-tumour necrosis factor (TNF) failure remains unclear in Crohn's disease.Aims To compare the short- and long-term effectiveness of vedolizumab and ustekinumab in Crohn's disease patients with prior anti-TNF exposure.Methods All Crohn's disease patients treated with ustekinumab or vedolizumab after exposure to at least one anti-TNF agent were included from two referral centres. Primary endpoint was corticosteroid-free clinical remission defined as Crohn's disease activity index 35 years old (OR = 0.41 [0.19-0.87]), with noncomplicated phenotype (OR=0.42 [0.18-0.96]), no prior bowel resection (OR = 0.49 [0.24-0.96]), and no steroids at baseline (OR=0.47 [0.23-0.97]).Conclusion Ustekinumab was more effective to achieve early and long-term effectiveness than vedolizumab in Crohn's disease patients who previously failed response to anti-TNF agents.

Medico-economic data of patients suffering from chronic nausea and vomiting are lacking. In these patients, gastric electrical stimulation (GES) is an effective, but costly treatment. The aim of this study was to assess the efficacy, safety and medico-economic impact of Enterra therapy in patients with chronic medically refractory nausea and vomiting.Data were collected prospectively from patients with medically refractory nausea and/or vomiting, implanted with an Enterra device and followed for two years. Gastrointestinal quality of life index (GIQLI) score, vomiting frequency, nutritional status and safety were evaluated. Direct and indirect expenditure data were prospectively collected in diaries.Complete clinical data were available for142 patients (60 diabetic, 82 non-diabetic) and medico-economic data were available for 96 patients (36 diabetic, 60 non-diabetic), 24 months after implantation. GIQLI score increased by 12.1 ± 25.0 points (p.001), with a more significant improvement in non-diabetic than in diabetic patients (+15.8 ± 25.0 points, p.001 versus 7.3 ± 24.5 points, p = .027, respectively). The proportion of patients vomiting less than once per month increased by 25.5% (p.001). Hospitalisations, time off work and transport were the main sources of costs. Enterra therapy decreased mean overall healthcare costs from 8873 US$ to 5525 US$ /patient/year (p = .001), representing a saving of 3348 US$ per patient and per year. Savings were greater for diabetic patients (4096 US$ /patient/year) than for non-diabetic patients (2900 US$ /patient/year).Enterra therapy is an effective, safe and cost-effective option for patients with refractory nausea and vomiting.gov Identifier: NCT00903799.

There have been conflicting results from trials of gastric electrical stimulation (GES) for treatment of refractory vomiting, associated or not with gastroparesis. We performed a large, multicenter, randomized, double-blind trial with crossover to study the efficacy of GES in patients with refractory vomiting, with or without gastroparesis.For 4 months, we assessed symptoms in 172 patients (66% women; mean age ± standard deviation, 45 ± 12 years; 133 with gastroparesis) with chronic (12 months) of refractory vomiting (idiopathic, associated with a type 1 or 2 diabetes, or postsurgical). A GES device was implanted and left unactivated until patients were randomly assigned, in a double-blind manner, to groups that received 4 months of stimulation parameters (14 Hz, 5 mA, pulses of 330 μs) or no stimulation (control); 149 patients then crossed over to the other group for 4 months. Patients were examined at the end of each 4-month period (at 5 and 9 months after implantation). Primary endpoints were vomiting score, ranging from 0 (daily vomiting) to 4 (no vomiting), and the quality of life, assessed by the Gastrointestinal Quality of Life Index scoring system. Secondary endpoints were changes in other digestive symptoms, nutritional status, gastric emptying, and control of diabetes.During both phases of the crossover study, vomiting scores were higher in the group with the device on (median score, 2) than the control group (median score, 1; P.001), in diabetic and nondiabetic patients. Vomiting scores increased significantly when the device was ON in patients with delayed (P.01) or normal gastric emptying (P = .05). Gastric emptying was not accelerated during the ON period compared with the OFF period. Having the GES turned on was not associated with increased quality of life.In a randomized crossover study, we found that GES reduced the frequency of refractory vomiting in patients with and without diabetes, although it did not accelerate gastric emptying or increase of quality of life. Clinicaltrials.gov, Number: NCT00903799.

Background and Aims Recurrence of Crohn’s disease (CD) after surgery is a major concern. Curcumin has anti-inflammatory properties and induces endoscopic remission in patients with ulcerative colitis. We investigated the efficacy of curcumin vs placebo in preventing post-operative recurrence of CD, based on endoscopic and clinical indices, in patients receiving concomitant thiopurine therapy. Methods We conducted a double-blind randomized controlled trial at 8 referral centers in France, from October 2014 through January 2018, of 62 consecutive patients with CD undergoing bowel resection. Patients received azathioprine (2.5 mg/kg) and were randomly assigned to groups given oral curcumin (3 g/day; n = 31) or an identical placebo (n = 31) for 6 months, and were then evaluated by colonoscopy. We also collected data on CD activity index, results from laboratory tests, and answers to quality of life questionnaires during this 6-month period. The primary endpoint was postoperative recurrence of CD in each group (Rutgeerts’ index score ≥i2) at month 6 (determined by central reading). An interim analysis (intent to treat) was scheduled after 50% of the patients were enrolled. Results At month 6, postoperative recurrence (Rutgeerts’ index score ≥i2) occurred in 18 patients (58%) receiving curcumin and 21 patients (68%) receiving placebo (P = .60). A significantly higher proportion of patients receiving curcumin (55%) had a severe recurrence of CD (Rutgeerts’ index score ≥i3) than patients receiving placebo (26%) (P = .034). We observed a clinical recurrence of CD (CD activity index score >150) at month 6 in 45% of patients receiving placebo and 30% of patients receiving curcumin (P = .80). Quality of life scores at month 6 did not differ significantly between groups (P = .80). Severe adverse events developed in 6% of patients receiving placebo and 16% of patients receiving curcumin (P = .42). Conclusions In a randomized controlled trial of patients who underwent surgery for CD and received thiopurine treatment, we found that curcumin was no more effective than placebo in preventing CD recurrence. There were no significant differences between groups in quality of life or severe adverse events. The study was discontinued after interim analysis due to futility. ClinicalTrials.gov no: NCT 02255370.

Intestinal barrier defects lead to “leaky gut syndrome”, defined as an increase in intestinal permeability that allows the passage of luminal content into intestinal tissue and the bloodstream. Such a compromised intestinal barrier is the main factor underlying the pathogenesis of inflammatory bowel disease, but also commonly occurs in various systemic diseases such as viral infections and metabolic syndrome. The non-pathogenic yeast Saccharomyces boulardii CNCM I-745 has demonstrated its effectiveness as a probiotic in the prevention and treatment of antibiotic-associated, infectious and functional diarrhea. Via multiple mechanisms of action implicated in intestinal barrier function, S. boulardii has beneficial effects on altered intestinal microbiota and epithelial barrier defects in different pathologies. The well-studied probiotic yeast S. boulardii plays a crucial role in the preservation and/or restoration of intestinal barrier function in multiple disorders. This could be of major interest in diseases characterized by alterations in intestinal barrier function.

Duodenal stenosis is one of the most common causes of failed ERCP for obstructive jaundice. Alternative approaches include anterograde biliary drainage, with higher morbidity. We report in this study the efficacy and safety of temporary placement of a covered duodenal self-expandable metal stent (cSEMS) in order to access the papilla and achieve secondary retrograde biliary drainage in patients with obstructive jaundice and failed ERCP due to concomitant duodenal stenosis. From June 2006 to March 2014, a total of 26 consecutive patients presenting obstructive jaundice without severe sepsis with failed ERCP due to duodenal invasion were enrolled. A temporary 7-day duodenal cSEMS was placed during the failed ERCP, and a second ERCP was attempted at day 7 after duodenal stent removal. Duodenal cSEMS placement and retrieval were technically successful in all cases. Access to the papilla at day 7 was possible in 25 cases (96 %, 95 % CI 80–99 %). Secondary successful ERCP was achieved in 19 cases (76 %, 95 % CI 55–91 %, i.e., 73 %, 95 % CI 73–86 %, in an intention-to-treat analysis). Mean bilirubin level was 102 ± 90 µmol/L at baseline rising to 164 ± 121 µmol/L at day 7. There were 6 stent migrations and no adverse events recorded between the two ERCPs. When ERCP for obstructive jaundice fails due to duodenal invasion, temporary cSEMS placement offers a safe and effective way to achieve successful secondary ERCP while avoiding riskier endoscopic ultrasound or percutaneous transhepatic anterograde biliary drainage.

Background Among the different mechanisms involved in irritable bowel syndrome (IBS) physiopathology, visceral hypersensitivity seems to play a key role. It involves sensitization of the colonic primary afferent fibers, especially through an overexpression of ion channels. The aims of this translational study were to investigate the colonic expression of Cav3.2 calcium channels and their involvement in an animal model of colonic hypersensitivity, and to assess their expression in the colonic mucosa of symptomatic IBS patients. Methods This bench-to-bed study combined a preclinical experimental study on mice and a case–control clinical study. Preclinical studies were performed on wild-type and Cav3.2-KO mice. Colonic sensitivity and Cav3.2 expression were studied after a low-dose treatment of dextran sodium sulfate (DSS 0.5%). Regarding the clinical study, colonic biopsies were performed in 14 IBS patients and 16 controls during a colonoscopy to analyze the mucosal Cav3.2 expression. Key results Wild-type, but not Cav3.2-KO, mice developed visceral hypersensitivity without colonic inflammation, after 0.5% DSS treatment. A significant increase of Cav3.2 mRNA (p = 0.04) was found in the colon of low-dose DSS-treated wild-type (WT) mice compared to their controls. In human colonic biopsies, the Cav3.2 mRNA level was significantly higher in the IBS group compared to the control group (p = 0.01). The immunofluorescence staining revealed their protein expression in colonic mucosa, particularly in nerve fibers. Conclusions & inferences This translational study supports the involvement of the calcium channels Cav3.2 in abdominal pain, as observed in IBS patients. It opens new therapeutic perspectives based on molecules specifically blocking these channels.

Background and study aim: Endoscopic ultrasound (EUS)-guided biliary access is an alternative to percutaneous access after failed endoscopic retrograde cholangiopancreatography (ERCP). This report presents 7 years’ cumulative experience of EUS-guided biliary drainage for obstructive jaundice in patients with failed ERCP. Patients and methods: Between February 2006 and February 2013, 101 patients (malignant = 98, benign = 3) with previous failed ERCP underwent an EUS intra- or extrahepatic approach with transluminal stenting or an EUS-guided rendezvous procedure with transpapillary stent placement. A single endoscopist performed all procedures. Results: A total of 71 patients underwent the intrahepatic approach (66 hepatogastrostomies and 5 EUS-guided rendezvous), and 30 underwent the extrahepatic approach (26 choledochoduodenostomies, 1 choledochojejunostomy, 1 choledochoantrostomy, and 2 EUS-guided cholangiographies). Technical and clinical success rates were 98.0 % and 92.1 %, respectively. There was no difference in efficacy between hepatogastrostomies and choledochoduodenostomies (94 % vs. 90 %; P = 0.69) or in major complications (10.6 % vs. 6.7 %; P = 1). Adverse events occurred in 12 patients (11.9 %): 10 in the hepatogastrostomy group (2 limited pneumoperitoneum, 1 hepatic hematoma, 5 bile leakage, 2 sepsis), and 2 in the choledochoduodenostomy group (1 arteriobiliary fistula and 1 sepsis). There were six procedure-related deaths, five among the first 50 patients and one among the last 51 patients. Hepatogastrostomy vs. choledochoduodenostomy, plastic vs. metal stenting, stent-in-stent vs. 1 stent, nasobiliary drain, or postoperative octreotide infusion were not prognostic of bile leakage. Conclusion: EUS-guided biliary drainage is an efficient technique, but is associated with significant morbidity that seems to decrease with the learning curve. It should be performed in tertiary care centers in selected patients. Prospective randomized studies are needed to compare EUS-guided biliary drainage with percutaneous transhepatic cholangiography drainage.

Background Inflammatory bowel diseases (IBD) are systemic, chronic inflammatory conditions that predominately affect the gastrointestinal tract and can induce abdominal pain. Besides, many IBD patients complain about headaches in daily practice. The objective was to assess the prevalence of headaches, including migraines and pain with neuropathic characteristics (NC), in IBD patients compared to historical controls from the general population. Methods Overall, 203 consecutive tertiary-care centre patients completed validated self-administered questionnaires and benefitted from a clinical evaluation performed by an IBD physician at the same time. Results In our cohort, 75% of the patients experienced pain in the previous 3 months. Migraine prevalence was two-fold higher in IBD patients compared to the general population (41% vs. 21.3%, p

Introduction Irritable bowel syndrome (IBS) is characterised by the association of abdominal chronic pain with bowel habit disorders in the absence of identifiable organic disease. This is the first reason for consultation in gastroenterology, with an estimated prevalence of 10%–15% in industrialised countries. Although this is a benign gastrointestinal disease, its chronicity profoundly impacts the patient’s quality of life and causes considerable health spending. Actual medical treatments are poorly efficient on IBS-related abdominal pain, making it a major public health concern. The mechanisms causing IBS symptoms are unknown. Recent studies have shown the involvement of T-type channel in abdominal pain. We aim to evaluate the therapeutic potential of ethosuximide, a T-type channel blocker, on the abdominal pain of patients presenting an IBS. Methods and analysis The IBSET trial is a randomised, controlled, parallel, double-blind and multicentre study. It is the first clinical trial evaluating the efficacy and safety of ethosuximide on abdominal pain related to IBS. Adults with IBS that report significant abdominal pain (≥4/10) at least for 3 months will be included. 290 patients will be randomly assigned to receive either ethosuximide or placebo over 12 weeks after 1 week of run-in period. The primary endpoint is the rate of responders (pain reduction ≥30% and Subject Global Assessment of Relief score ≥4). The intensity of abdominal pain will be assessed by an 11-point Numerical Rating Scale before and after 12 weeks of treatment and the score of the Subject Global Assessment of Relief scale at the end of treatment. The secondary endpoints are the safety of ethosuximide, the intensity and features of IBS and quality of life. Ethics and dissemination The study was approved by an independent medical ethics committee (CPP Sud-Est VI, Clermont-Ferrand, France). The results will be published in a peer-review journal and presented at international congresses. Trial registration number NCT02973542; Pre-results.

International audience

Background: Short- chain fructooligosaccharides (scFOS) have beneficial effects in subjects with minor digestive complaints, but the potential mechanisms involved have not been elucidated. The aim of the study was to evaluate changes in rectal sensitivity related to the clinical effects of scFOS in a selected group of patients with irritable bowel syndrome (IBS) and rectal hypersensitivity. Methods: In 79 IBS patients (defined by Rome III criteria) with rectal hypersensitivity (defined as discomfort threshold ≤ 44 g) a parallel, placebo- controlled, randomized, and double- blind study was performed to assess the effects of dietary supplementation (5 g d −1 ) with scFOS vs placebo for 4 weeks on rectal sensitivity (primary outcome: tolerance to increasing wall tension applied by a tensostat), clinical outcomes (IBS, anxiety/depression and quality of life scores) and composition of fecal microbiota. Key Results: Rectal discomfort threshold, and IBS and quality of life scores, signifi- cantly improved during treatment, but in a similar manner in both scFOS and placebo groups; a post- hoc analysis showed that the effect of scFOS on rectal sensitivity was more pronounced in constipation- predominant- IBS patients ( P =.051 vs placebo). Con- trary with placebo, scFOS significantly reduced anxiety scores and increased fecal Bifi- dobacteria ( P < .05 for both) without modifying other bacterial groups. Conclusions & Interfences: The effect of scFOS on anxiety may be related to modula- tion of the gut microbiota; demonstration of effects of scFOS on rectal sensitivity may require higher doses and may depend on the IBS subgroup.

Summary Background In routine practice, irritable bowel syndrome (IBS) symptoms are often difficult to be relieved and impair significantly patients’ quality of life (QoL). A randomised, double-blind, placebo-controlled study has shown the efficacy of alverine citrate/simeticone (ACS) combination for IBS symptom relief. Aim As IBS symptoms are often intermittent, this pragmatic study was designed to compare the efficacy of an on-demand ACS treatment vs. that of usual treatments. Methods Rome III IBS patients were enrolled by 87 general practitioners who were randomly allocated to one of two therapeutic strategies: on-demand ACS or usual treatment chosen by the physician. The primary outcome measure was the improvement of the IBSQoL score between inclusion and month 6. Results A total of 436 patients (mean age: 54.4 years; women: 73.4%) were included, 222 in the ACS arm and 214 patients in the usual treatment arm, which was mainly antispasmodics. At 6 months, improvement of IBSQoL was greater with ACS than with the usual treatment group (13.8 vs. 8.4; p

International audience; BACKGROUND: Medical therapy efficacy remains controversial in stricturing Crohn's disease. Cross-sectional imaging, especially magnetic resonance imaging, has been suggested as very helpful to guide therapeutic decision making. AIM: To assess efficacy and predictors of therapeutic failure in patients receiving medical treatments for stricturing Crohn's disease. METHODS: In this retrospective study, therapeutic failure was defined as symptomatic stricture leading to surgical or endoscopic therapeutics, hospitalization, treatment discontinuation or additional therapy and short-term clinical response as clinical improvement assessed by two physicians. The 55 cross-sectional imaging examinations (33 magnetic resonance imaging and 22 CT scan) before starting medical therapy were analyzed independently by two radiologists. Results were expressed as hazard ratio (HR) or odds ratio (OR) with 95% confidence intervals (95% CI). RESULTS: Among 84 patients, therapeutic failure rate within 60 months was 66.6%. In multivariate analysis, Crohn's disease diagnosis after 40 years old (HR 3.9, 95% CI [1.37-11.2], p = 0.011), small stricture luminal diameter (HR 1.34, 95% CI [1.01-1.80], p = 0.046), increased stricture wall thickness (HR 1.23, 95% CI [1.04-1.46], p = 0.013) and fistula with abscess (HR 5.63, 95% CI [1.64-19.35], p = 0.006) were associated with therapeutic failure, while anti-TNF combotherapy (HR 0.17, 95% CI [0.40-0.71], p = 0.015) prevented it. Considering 108 therapeutic sequences, the short-term clinical response rate was 65.7%. In multivariate analysis, male gender (OR 0.15, 95% CI [0.03-0.64], p = 0.011), fistula with abscess (OR 0.09, 95% CI [0.01-0.77], p = 0.028) and comb sign (OR 0.23, 95% CI [0.005-0.97], p = 0.047) were associated with short-term clinical failure. CONCLUSION: Anti-TNF combotherapy seemed to prevent therapeutic failure, and cross-sectional imaging should be systematically performed to help medical management in stricturing Crohn's disease.

Background EUS-guided fine needle aspiration biopsy (EUS-FNAB) of deep-seated lymphadenopathy is proposed to identify lymphoproliferative disorders when no superficial lesion is accessible. Methods We analyzed prospectively collected data of 115 EUS-FNABs from 73 thoracic or abdomino-pelvic targets in 52 patients with suspected lymphoproliferative disorders (LPDs) between January 2005 and May 2011 from a single institution. Conventional histology and immunohistochemistry procedures were performed on samples. Results No complications were recorded. An LPD was identified in 29 cases and ruled out in 21 cases. In 2 cases the analysis was negative, but an LPD was identified using a secondary procedure. For the identification of LPDs irrespective of subtype, this procedure has positive and negative predictive values of 100% and 91.3% respectively, with 93.6% sensitivity and 100% specificity. In 31 patients finally diagnosed with LPDs, an accurate diagnosis meeting the 2008 World Health Organization classification criteria was established in 21 (68%) cases, success being significantly associated with target size above 30 mm in multivariate analysis (odds ratio 7.47; p = 0.05). Conclusion EUS-FNAB of deep-seated lymphadenopathy with conventional morphological assessment appears to have a high diagnostic value for LPD identification and can obviate invasive surgery. A sub-classification was possible in two thirds of the cases.

Summary Background Irritable bowel syndrome (IBS), one of the most common gastrointestinal disorders, markedly impairing patients' quality of life. Drug development for IBS treatment has been hampered by the lack of understanding of IBS aetiology. In recent years, numerous data have emerged that suggest the involvement of immune activation in IBS, at least in a subset of patients. Aim To determine whether immune activation and intestinal permeabilisation are more frequently observed in IBS patients compared with healthy controls. Methods The scientific bibliography was searched using the following keywords: irritable bowel syndrome, inflammation, immune activation, permeabilisation, intestine, assay, histology and human. The retrieved studies, including blood, faecal and histological studies, were analysed to provide a comprehensive and structured overview of the available data including the type of assay, type of inflammatory marker investigated or intestinal segment studied. Results Immune activation was more frequently observed in IBS patients than in healthy controls. An increase in the number of mast cells and lymphocytes, an alteration in cytokine levels and intestinal permeabilisation were reported in IBS patients. No consistent changes in the numbers of B cells or enterochromaffin cells or in mucosal serotonin production were demonstrated. Conclusions The changes observed were modest and often heterogeneous among the studied population. Only appropriate interventions improving irritable bowel syndrome symptoms could highlight and confirm the role of immune activation in this pathophysiology.

Background Endoscopist-administered propofol sedation for colonoscopy has not been compared to anaesthetist-administered deep sedation in clinical trials. Our aim was to compare patients’ satisfaction and safety during these two sedation modalities. Methods 90 adult patients undergoing colonoscopy were randomized into Group A, Endoscopist-administered propofol sedation and Group B, anaesthetist-administered deep sedation. Group A patients received an initial dose of 30–50 mg of intravenous propofol; additional doses were injected by the endoscopist using a pre-programmed pump. Global satisfaction was measured on a 0–100 mm visual analogue scale. Results The average satisfaction scores after examination completion amongst group were not statistically different (90.8 mm for Group A vs. 89 mm for Group B). Group A patients expressed more frequently a good level of satisfaction (95% vs. 75%; p = 0.03) and willingness to undergo further colonoscopies under the same conditions (95% vs. 79%; p = 0.02). Total duration time and procedural difficulty did not differ between the groups. Group A received a lower total propofol dose than Group B (94 mg vs. 260 mg) and experienced fewer side-effects (16 vs. 3, respectively; p Conclusion Endoscopist-administered propofol sedation for colonoscopy offered a better level of satisfaction and fewer side-effects than anaesthetist-administered deep sedation.

Background & Aims Little is known about the magnitude of the risk of anal and rectal cancer in patients with anal and/or perineal Crohn's disease. We aimed to assess the risk of anal and rectal cancer in patients with Crohn's perianal disease followed up in the Cancers Et Surrisque Associe aux Maladies Inflammatoires Intestinales En France (CESAME) cohort. Methods We collected data from 19,486 patients with inflammatory bowel disease (IBD) enrolled in the observational CESAME study in France, from May 2004 through June 2005; 14.9% of participants had past or current anal and/or perianal Crohn's disease. Subjects were followed up for a median time of 35 months (interquartile range, 29–40 mo). To identify risk factors for anal cancer in the total CESAME population, we performed a case-control study in which participants were matched for age and sex. Results Among the total IBD population, 8 patients developed anal cancer and 14 patients developed rectal cancer. In the subgroup of 2911 patients with past or current anal and/or perianal Crohn's lesions at cohort entry, 2 developed anal squamous-cell carcinoma, 3 developed perianal fistula–related adenocarcinoma, and 6 developed rectal cancer. The corresponding incidence rates were 0.26 per 1000 patient-years for anal squamous-cell carcinoma, 0.38 per 1000 patient-years for perianal fistula–related adenocarcinoma, and 0.77 per 1000 patient-years for rectal cancer. Among the 16,575 patients with ulcerative colitis or Crohn's disease without anal or perianal lesions, the incidence rate of anal cancer was 0.08 per 1000 patient-years and of rectal cancer was 0.21 per 1000 patient-years. Among factors tested by univariate conditional regression (IBD subtype, disease duration, exposure to immune-suppressive therapy, presence of past or current anal and/or perianal lesions), the presence of past or current anal and/or perianal lesions at cohort entry was the only factor significantly associated with development of anal cancer (odds ratio, 11.2; 95% CI, 1.18-551.51; P = .03). Conclusions In an analysis of data from the CESAME cohort in France, patients with anal and/or perianal Crohn's disease have a high risk of anal cancer, including perianal fistula–related cancer, and a high risk of rectal cancer.

AIM: In patients with acute gastroenteritis, general behaviour of patients as well as medical care remain poorly documented. The aim of this work was to determine clinical and demographic characteristics, reason for visiting a doctor, and medical care in adult patients with acute gastroenteritis. METHODS: During the winter epidemic peak of acute diarrhea, 2,217 general practitioners filled in standardized clinical observations of 17,273 patients (mean age 40 yrs) with acute gastroenteritis. RESULTS: There were abdominal pain, nausea, and vomiting in respectively 72%, 53% and 43% of patients. Thirty one percent of patients had fever. Nausea and vomiting were more frequently observed in younger patients (15-25 yrs) than in older ones. More severe diarrhea more frequent nausea, vomiting and abdominal pain (p

The human gut harbours a wide range of bacterial communities that play key roles in supplying nutrients and energy to the host through anaerobic fermentation of dietary components and host secretions. This fermentative process involves different functional groups of microorganisms linked in a trophic chain. Although the diversity of the intestinal microbiota has been studied extensively using molecular techniques, the functional aspects of this biodiversity remain mostly unexplored. The aim of the present work was to enumerate the principal metabolic groups of microorganisms involved in the fermentative process in the gut of healthy humans. These functional groups of microorganisms were quantified by a cultural approach, while the taxonomic composition of the microbiota was assessed by in situ hybridization on the same faecal samples. The functional groups of microorganisms that predominated in the gut were the polysaccharide-degrading populations involved in the breakdown of the most readily available exogenous and endogenous substrates and the predominant butyrate-producing species. Most of the functional groups of microorganisms studied appeared to be present at rather similar levels in all healthy volunteers, suggesting that optimal numbers of these various bacterial groups are crucial for efficient gut fermentation, as well as for host nutrition and health. Significant interindividual differences were, however, confirmed with respect to the numbers of methanogenic archaea, filter paper-degrading and acetogenic bacteria and the products formed by lactate-utilizing bacteria.

International audience; AIM: to investigate whether an endoscopy-based management could prevent the long-term risk of postoperative recurrence. METHODS: From the pathology department database, we retrospectively retrieved the data of all the patients operated on for Crohn's disease (CD) in our center (1986-2015). Endoscopy-based management was defined as systematic postoperative colonoscopy (median time after surgery = 9.5 mo) in patients with no clinical postoperative recurrence at the time of endoscopy. RESULTS: From 205 patients who underwent surgery, 161 patients (follow-up > 6 mo) were included. Endoscopic postoperative recurrence occurred in 67.6%, 79.7%, and 95.5% of the patients, respectively 5, 10 and 20 years after surgery. The rate of clinical postoperative recurrence was 61.4%, 75.9%, and 92.5% at 5, 10 and 20 years, respectively. The rate of surgical postoperative recurrence was 19.0%, 38.9% and 64.7%, respectively, 5, 10 and 20 years after surgery. In multivariate analysis, previous intestinal resection, prior exposure to anti-TNF therapy before surgery, and fistulizing phenotype (B3) were postoperative risk factors. Previous perianal abscess/fistula (other perianal lesions excluded), were predictive of only symptomatic recurrence. In multivariate analysis, an endoscopy-based management (n = 49/161) prevented clinical (HR = 0.4, 95% CI: 0.25-0.66, p < 0.001) and surgical postoperative recurrence (HR = 0.30, 95% CI: 0.13-0.70, p = 0.006). CONCLUSION: Endoscopy-based management should be recommended in all CD patients within the first year after surgery as it highly decreases the long-term risk of clinical recurrence and reoperation.

The intestinal microbiota of patients with constipated-predominant irritable bowel syndrome (C-IBS) displays chronic dysbiosis. Our aim was to determine whether this microbial imbalance instigates perturbation of the host intestinal mucosal immune response, using a model of human microbiota-associated rats (HMAR) and dextran sulfate sodium (DSS)-induced experimental colitis. The analysis of the microbiota composition revealed a decrease of the relative abundance of Bacteroides, Roseburia-Eubacterium rectale and Bifidobacterium and an increase of Enterobacteriaceae, Desulfovibrio sp., and mainly Akkermansia muciniphila in C-IBS patients compared to healthy individuals. The bacterial diversity of the gut microbiota of healthy individuals or C-IBS patients was maintained in corresponding HMAR. Animals harboring a C-IBS microbiota had reduced DSS colitis with a decreased expression of pro-inflammatory cytokines from innate, Th1, and Th17 responses. The pre-treatment of conventional C57BL/6 mice or HMAR with A. muciniphila, but not with Escherichia coli, prior exposure to DSS also resulted in a reduction of colitis severity, highlighting that the anti-inflammatory effect of the gut microbiota of C-IBS patients is mediated, in part, by A. muciniphila. This work highlights a novel aspect of the crosstalk between the gut microbiota of C-IBS patients and host intestinal homeostasis.

Background and goals Using a self-expandable metallic stent (SEMS) in the cervical esophagus is controversial due to an increased risk of complications. Here we assessed a new type of SEMS purpose-designed for the cervical esophagus area. Study Patients with malignant or benign stenosis within 4 cm distance of the upper esophageal sphincter who underwent placement of a SEMS with a shorter proximal head (Niti-S Esophageal Covered Stent-Cervical-type, NSECSC), were included. Main outcome measures were the functional outcome, tolerance, complications, recurrent dysphagia, and survival. Results About 37 patients had an NSECSC placed between April 2008 and June 2013 for esophageal stenosis (malignant=20, benign=17), 5 with associated tracheoesophageal fistula. The mean stenosis-upper esophageal sphincter distance was 1.86±1.27 cm. The median follow-up was 150 days. Dysphagia improved in 27/37 cases (73%). Short-term and long-term tolerance without needing stent removal was 92% and 82%, respectively. The complication rate was 59% (22/37): 32% (n=14) major complications [fistula (3), perforation (3), aspiration pneumonia (5), laryngeal dyspnea (2), and bleeding (1)], and 27% (n=10) minor complications [pain (7) or dysphonia (3)]. A multivariate analysis confirmed a higher risk of major complications in cases of benign stenosis (odds ratio=5.2; 95% confidence interval, 1.05-25.90; P=0.04). Recurrent dysphagia occurred in 15 patients (obstruction=7, migration=8). Conclusions The NSECSC does not appear less morbid than standard SEMS in the cervical esophageal area, but could be useful in malignant indications as it is well-tolerated and offers effective palliation of the dysphagia. However, this device should not be used in benign cervical esophageal strictures or fistulas.

Aim To assess the proportion of physician-diagnosed irritable bowel syndrome (IBS) patients who conform to Rome II criteria, and evaluate the impact of IBS on quality of life (QoL) and costs in France. Methods This cross-sectional study collected information retrospectively from the preceding year. Physicians (randomly selected) enrolled their first four IBS patients during the study period. Patients were classified (secondarily) according to Rome II criteria. IBS-related costs during the previous year were estimated. Results Of the 452 physician-diagnosed IBS patients (mean age 53.9±14.9 years; 75.4% women), 23% did not meet the diagnostic criteria; 36.5% met all diagnostic criteria, and 32% experienced severe or very severe abdominal pain/discomfort (Subjects' Global Assessment of relief). IBS patients had lower QoL (SF-36 scale) than the general French population, and Rome II patients had the lowest QoL. Most prescriptions treated abdominal pain (72%) and bloating (58%). Approximately 8% of patients had been hospitalized due to IBS during the preceding year. The average total annual direct cost/patient was €756. Conclusions These data confirm that IBS involves large direct medical costs in France, and that IBS patients experience lower QoL than the general population. A small and not significant economic difference between the Rome II and non-Rome II IBS patient groups was observed.

(1) Service d’Hepato-Gastroenterologie et Nutrition Clinique, Nice ; (2) Service d’Hepato-Gastroenterologie, Clermont-Ferrand ; (3) Laboratoire de Nutrition Humaine, CRNH Auvergne ; (4) Service de Geriatrie, Rouen ; (5) Service de Gastroenterologie, Hopital Louis Mourier, Paris ; (6) Service de Chirurgie Viscerale, Rennes ; (7) Service de Chirurgie Viscerale, Nice ; (8) Service de Gynecologie Obstetrique, Clermont-Ferrand ; (9) Service de Gastroenterologie, Vichy ; (10) Service de Gynecologie Obstetrique, Tours ; (11) Hepato-Gastroenterologie liberale, Châteauroux ; (12) Service d’explorations fonctionnelles digestive, Lyon ; (13) Service de Gastroenterologie, Mont-de-Marsan ; (14) Medecine Generale, Villeneuve-le-Roi ; (15) Proctologie, Hopital Leopold Bellan, Paris.

Summary Background In France, general anesthesia is given to more than 90% of patients undergoing colonoscopy although in several countries sedation is limited to intolerant patients. This study was carried out to determine whether Patient-Controlled Sedation (PCS) could provide a lighter sedation than general anesthesia adapted to the patient's individual requirement. Methods Patients aged from 18 to 80 scheduled for elective colonoscopy were prospectively randomized to receive either standard sedation (control group) or patient-controlled-sedation (PCS). In the control group, patients received a continuous infusion of propofol. Patients in the PCS group were connected to an infusion pump containing propofol and self-administered 20-mg boluses as often as they required. An anesthetist was present throughout the procedure. Patient satisfaction measured on a visual analog scale four hours after colonoscopy was the main outcome criterion. Results From December 2002 to September 2003, 402 patients underwent elective colonoscopy, 173 of them were eligible and were asked to participate in the study. Seventy-two gave their informed consent and were prospectively randomized. The patients’ mean satisfaction scores were not statistically different between the two groups: 84.7 mm (PCS group) vs . 91.5 mm (control group); P = 0.24. Mean doses of propofol (60 mg vs . 248 mg; P vs . 4.45 hours) were significantly lower for patients in the PCS group; nine of them (25.7%) did not use the pump and had total colonoscopy without sedation. There were no statistically significant differences between the two groups regarding total duration of colonoscopy (19.4 min (PCS) vs . 18 min (control)) difficulty and therapeutic procedures (biopsy or polypectomy). Two weeks after the procedure, 96.5% of patients in the PCS group were willing to repeat the examination under the same conditions vs . 72.5% of patients in the control group (P = 0.03). Conclusions Our results demonstrate that need of sedation is widely overestimated in France. A subset of our patients is willing to consider colonoscopy without general anesthesia. For them, PCS with propofol is an effective and very well accepted form of sedation.

Summary Aims Heath-related quality of life (QoL) is decreased in patients with irritable bowel syndrome (IBS) but the relationship between symptom intensity of IBS and QoL remains largely unknown. The aim of this prospective survey was to investigate the relationship between intensity of IBS and changes in QoL. Methods Eight hundred and fifty-eight patients with IBS, according to Rome II criteria, completed a symptom questionnaire to measure intensity of IBS, and the gastrointestinal quality of life (GIQLI) questionnaire, which is a general QoL measure in patients with gastrointestinal disorders. Results 37.2% of the patients had constipation-predominant type IBS, 37.3% had diarrhea-predominant IBS and 25.4% had alternating diarrhea and constipation type symptoms. IBS was considered to be in remission or mild in 8.3% of patients; 41.3% had moderate IBS and 50.4% had severe IBS. The mean GIQLI score was 88 ± 20. There was a significant correlation between symptom intensity and changes in QoL. Other significantly related factors were the type of bowel abnormality and gender. Conclusion In IBS patients, symptom intensity and type of IBS have a negative impact on health-related QoL.

Endoscopic snare papillectomy (ESP) is a viable alternative to surgical treatment of ampullary adenomas and T1N0 stage ampullary carcinomas. The main drawback of this technique is the high risk of acute pancreatitis post procedure.The aim of this study was to assess the efficacy, safety, and long-term results of this procedure, and to determine whether routine pancreatic intubation facilitated by intraductal methylene blue (MB) injection reduces the risk for pancreatitis.Between 2004 and 2011, 56 consecutive patients underwent ESP. Before resection, the pancreatic duct was cannulated, and MB was injected intraductally to facilitate stent placement after ampullectomy.ESP was performed en bloc in 45 patients with histological findings of low-grade dysplasia (39%), high-grade dysplasia (25%), carcinoma (32.5%), and others (3.5%). The morbidity rate was 19.5%: acute pancreatitis (n=6), bleeding (n=4), perforation (n=1), and sepsis (n=1). Pancreatic intubation was performed in 89% of the patients. Postprocedure pancreatitis occurred significantly less in the patients with a pancreatic stent than in those without: 3/49 versus 3/6, P=0.013. ESP was considered as curative in 39 patients (75%). Of the 12 recurrences (25%), 10 were managed endoscopically, but with higher morbidity (acute pancreatitis=40%).Endoscopic papillectomy is safe and effective in the hands of experts. Pancreatic-duct stent placement in fewer cannulation attempts could be facilitated by injection of MB before papillectomy, and this decreases the risk for postprocedure pancreatitis. Recurrences can be managed endoscopically, but with a higher risk for pancreatitis.

Background Alterations of intestinal microbiota and hypersensitivity to colonic distension are two features of the irritable bowel syndrome (IBS). However, the role of intestinal microbiota in visceral hypersensitivity of IBS patients is far to be established. The aim of our study was to determine whether the intestinal microbiota is involved in the visceral hypersensitivity in IBS. Methods The painful response to colorectal distension and colonic mucosal parameters were assessed in gnotobiotic rats. Germfree (GF) rats were inoculated with the fecal microbiota from IBS patients characterized by hypersensitivity to colorectal distension (IBS HMA rats) or from non-hypersensitive healthy volunteers (Healthy HMA rats). Conventional rats were studied as normosensitivity control. Fecal microbial analyses were carried out in human and HMA rats fecal samples using cultural and molecular approaches. Key Results The microbial dysbiosis of the IBS gut microbiota (more sulfate-reducing bacteria and Enterobacteriaceae and less bifidobacteria) could be maintained in gnotobiotic rats. The number of abdominal contractions in response to colorectal distensions was significantly higher in IBS HMA rats than in healthy HMA rats. No difference was observed between healthy HMA and conventional rats. Colorectal compliance, epithelial paracellular permeability, and density of colonic mucosal mast cells were similar in the three groups of rats. Conclusions & Inferences We herein showed that sensitivity to colonic distension of IBS patients can be transferred to rats by the fecal microbiota. Mucosal alterations associated with microbiota transfer are not involved in this hypersensitivity. The altered IBS microbiota may have important role in the hypersensitivity characterizing IBS patients through specific bacterial metabolites.

Endoscopic sphincterotomy plus large-balloon dilatation (ESLBD) has an efficacy equal to or higher than that of endoscopic sphincterotomy alone for biliary lithiasis extractions. Our purpose was to evaluate the feasibility, efficacy and morbidity of large-balloon dilatation of the sphincter of Oddi after sphincterotomy or infundibulotomy for large or multiple common bile duct stones.Retrospective analysis.A total of 64 ESLBD procedures were performed in 62 patients: 57 after sphincterotomy and 7 after infundibulotomy. The feasibility was 100%, and full clearance of the common bile duct was achieved in a single session without using mechanical lithotripsy in 95.3% of cases. Short-term complications were observed in 9 patients (14%). There were no perforations. The most frequent complication was delayed bleeding (7.8%). There was no significant difference of overall complications after sphincterotomy or after infundibulotomy (12.3% vs. 28.6%, p = 0.25). The incidence of acute pancreatitis was significantly higher after infundibulotomy than after sphincterotomy (28.6% vs. 0%, p = 0.01).ESLBD after endoscopic sphincterotomy or infundibulotomy is a simple, reproducible and effective technique, associated with a low morbidity rate and helps in avoiding mechanical lithotripsy in 95.3% of cases for the endoscopic extraction of large or multiple common bile duct stones.

International audience; AIM: To assess the effects and safety of Lactobacillus casei rhamnosus LCR35 complete freeze-dried culture (LCR35) in patients suffering from irritable bowel syndrome (IBS). METHODS: A randomized, double-blind pilot study was performed in 50 patients complaining of IBS symptoms complying with Rome III criteria. Patients were allocated to receive either LCR35 (n = 25) at a minimum daily dose of 6 × 10(8) colony forming units or placebo (n = 25) for 4 wk. At inclusion, after treatment and 2 wk later, patients completed the IBS severity scale. Change from baseline in the IBS severity score at the end of treatment was the primary efficacy criterion. Changes were compared between groups in the whole population and in IBS subtypes (IBS with predominance of constipation, IBS with predominance of diarrhoea, mixed IBS, unsubtyped IBS). The presence of lactobacillus casei rhamnosus in stools was investigated at inclusion and at the end of treatment. The gastrointestinal quality of life questionnaire and the hospital anxiety and depression (HAD) scale were also completed. RESULTS: Both groups were balanced for baseline characteristics. In 85% of patients, stool analyses showed that lactobacillus casei rhamnosus able to survive in the digestive tract. In the whole population, improvements in the IBS severity score did not differ significantly between treatments with a 25% decrease after 4-wk treatment, and a 15% decrease from baseline 2 wk later in both groups. In IBS subgroups, statistical analysis could not be performed due to small sample size, but a clinical response in favour of LCR35 was observed in IBS patients with predominance of diarrhoea: no change in the symptom severity score was seen with the placebo after 4 wk treatment, whereas a clinically relevant decrease occurred with LCR35 (-37% vs -3%). Furthermore, in spite of an increase in symptom intensity, the IBS severity score was maintained below the baseline value 2 wk later with LCR35 (-19% from baseline), whilst a slight 5% increase from baseline was observed with placebo. In the IBS subgroup with predominance of diarrhoea only, a clinically relevant decrease in abdominal pain severity score (-36%) was observed with LCR35, whereas no change occurred with placebo. In mixed IBS patients, the 20% and 30% decreases in the IBS severity score observed after treatment with LCR35 and placebo, respectively, were maintained 2 wk later in both groups. A clinical response slightly in favour of placebo was observed at the end of the treatment period in IBS patients with predominance of constipation (-41% vs -20%) and unsubtyped IBS patients (-47% vs -17%), with the same value maintained 2 wk later. In both groups, no clinically relevant changes were observed either for the gastrointestinal quality of life index or HAD score. Thus, these results suggest that sub-grouping of IBS patients may be important for optimizing treatment responses by the physician. CONCLUSION: This pilot study suggests that LCR35 could have some efficacy in IBS patients complaining of diarrhoea. These preliminary results need to be confirmed in larger

SummaryBackground The role of the gut microbiota in patho-physiology of irritable bowel syndrome (IBS) is suggested by several studies. However, standard cultural and molecular methods used to date have not revealed specific and consistent IBS-related groups of microbes. Aim To explore the constipated-IBS (C-IBS) gut microbiota using a function-based approach. Methods The faecal microbiota from 14 C-IBS women and 12 sex-match healthy subjects were examined through a combined strictly anaerobic cultural evaluation of functional groups of microbes and fluorescent in situ hybridisation (16S rDNA gene targeting probes) to quantify main groups of bacteria. Starch fermentation by C-IBS and healthy faecal samples was evaluated in vitro. Results In C-IBS, the numbers of lactate-producing and lactate-utilising bacteria and the number of H2-consuming populations, methanogens and reductive acetogens, were at least 10-fold lower (P

There is a new merging of health economics and nutrition disciplines to assess the impact of diet on health and disease prevention and to characterise the health and economic aspects of specific changes in nutritional behaviour and nutrition recommendations. A rationale exists for developing the field of nutrition economics which could offer a better understanding of both nutrition, in the context of having a significant influence on health outcomes, and economics, in order to estimate the absolute and relative monetary impact of health measures. For this purpose, an expert meeting assessed questions aimed at clarifying the scope and identifying the key issues that should be taken into consideration in developing nutrition economics as a discipline that could potentially address important questions. We propose a first multidisciplinary outline for understanding the principles and particular characteristics of this emerging field. We summarise here the concepts and the observations of workshop participants and propose a basic setting for nutrition economics and health outcomes research as a novel discipline to support nutrition, health economics and health policy development in an evidence and health-benefit-based manner. © 2010 The Authors.