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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.

Summary Background Fructose malabsorption may trigger gastrointestinal symptoms in irritable bowel syndrome patients and a low fructose diet seems to improve digestive symptoms. Aim The aim of our study was to determine whether fructose malabsorption detected by a 25g fructose breath test could be a predictor of the efficacy of a low fructose diet. Methods 88 patients (73 women, median age, 45.5 years, range 18–69) with irritable bowel syndrome according to Rome III criteria were included in this prospective, controlled study. All 88 patients had a 25 g fructose breath test; 37 had a positive test result defining fructose malabsorption. All 88 patients followed a low fructose diet for 2 weeks, blinded to their test results. Patients filled self validated-questionnaires before and at the end of the dietary period. The main outcome measurement was the Irritable Bowel Syndrome-Symptom Severity Score. Results Irritable Bowel Syndrome-Symptom Severity Score significantly decreased in fructose absorbers and fructose malabsorbers after a low fructose diet (−68.0 [−137; 0] versus −73.5 [−173; −11.5]) with no difference according to fructose breath test result (adjusted P = 0.984). Conclusion A positive 25 g fructose breath test is not a predictor of the efficacy of a low fructose diet in irritable bowel syndrome. Registered clinical trial www.clinicaltrials.gov ( NCT02188680 ).

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.

Constipation is common during opioid therapy and can compromise analgesia.The aim of this article is to determine the prevalence and clinical characteristics of opioid-induced constipation (OIC) in France.A questionnaire study was conducted in a representative sample of the French general population. Participants completed a 31-item questionnaire covering opioid use during the previous six months, and the occurrence of constipation (defined as3 bowel movements per week, straining during defaecation, or both) during opioid treatment.Data were obtained from 15,213 participants, of whom 4753 (31.2%) reported opioid use. Most analgesics (96.5%) were classified as World Health Organization step II analgesics, and the remainder were step III. The most common indications for opioids were bone or joint pain, and soft tissue pain. Overall, 414/4753 (8.7%) opioid users reported OIC while the prevalence of OIC reached 21% in case of regular or prolonged (1 month) opioid use. Other characteristics associated with OIC included female gender, age ≥50 years and use of step III opioids. Only 177/414 (42.8%) participants with OIC had used medications (most commonly osmotic laxatives) to treat constipation, and satisfaction with constipation medication was moderate (mean (SD) score 7.2 (1.3) on a scale of 0-10).Approximately one-third of a representative French population had used opioids within the previous six months, and 9% of users had experienced OIC, which is more frequent in case of regular use. OIC appears to be under-treated, and participants' satisfaction with their constipation medications was only moderate, suggesting that significant unmet need remains in OIC management.

Obesity and irritable bowel syndrome (IBS) are two major public health issues. Interestingly previous data report a marked increase of IBS prevalence in morbid obese subjects compared with non-obese subjects but underlying mechanisms remain unknown. Obesity and IBS share common intestinal pathophysiological mechanisms such as gut dysbiosis, intestinal hyperpermeability and low-grade inflammatory response. We thus aimed to evaluate the link between obesity and IBS using different animal models. Male C57Bl/6 mice received high fat diet (HFD) for 12 weeks and were then submitted to water avoidance stress (WAS). In response to WAS, HFD mice exhibited higher intestinal permeability and plasma corticosterone concentration than non-obese mice. We were not able to reproduce a similar response both in ob/ob mice and in leptin-treated non-obese mice. In addition, metformin, a hypoglycemic agent, limited fasting glycaemia both in unstressed and WAS diet-induced obese mice but only partially restored colonic permeability in unstressed HFD mice. Metformin failed to improve intestinal permeability in WAS HFD mice. Finally, cecal microbiota transplantation from HFD mice in antibiotics-treated recipient mice did not reproduce the effects observed in stressed HFD mice. In conclusion, stress induced a more marked intestinal barrier dysfunction in diet-induced obese mice compared with non-obese mice that seems to be independent of leptin, glycaemia and gut microbiota. These data should be further confirmed and the role of the dietary composition should be studied.

Management of functional bowel disorders. The better knowledge of irritable bowel syndrome (IBS) and functional bloating pathogenic mechanisms led to an increase of the possible therapeutic options, which are somewhat different, in IBS, between IBS-D and IBS-C Besides routine options (antispasmodics, alverine, laxatives, loperamide), low-dose antidepressants and non-pharmaceutical options are now recognized as validated and effective therapeutic choices. In addition, dietary advices (particularly indication of a low FODMAPs diet) and treatments acting on gut microbiota (probiotics, antibiotics) are more and more discussed and indicated. In functional bloating, treatment remains empirical. Dietary modifications, simeticone, prokinetics, low-dose antidepressants and microbiome modulation can be proposed.Traitement des troubles fonctionnels intestinaux. Les progrès effectués dans la compréhension de la physiopathologie du syndrome de l’intestin irritable (SII) mais aussi du ballonnement fonctionnel ont conduit à une diversification des solutions thérapeutiques potentielles. Dans le SII, celles-ci sont fonction du sous-type de syndrome, diarrhéique et avec constipation. À côté des médicaments classiques (antispasmodiques, alvérine, laxatifs, lopéramide), les antidépresseurs à faibles doses et les alternatives non médicamenteuses trouvent désormais une place. Surtout, l’utilité d’un régime, notamment appauvri en FODMAP, et les solutions visant à agir sur la flore (probiotiques, antibiotiques) sont de plus en plus discutées. Dans le ballonnement fonctionnel, la prise en charge demeure empirique. Conseils diététiques, prokinétiques, antidépresseurs à faibles doses et agents actifs sur la flore peuvent être testés.

Background Gastroparesis is a functional disorder with a variety of symptoms that is characterized by delayed gastric emptying in the absence of mechanical obstruction. A recent series of retrospective studies has demonstrated that peroral endoscopic pyloromyotomy (G-POEM) is a promising endoscopic procedure for treating patients with refractory gastroparesis. The aim of this prospective study was to evaluate the feasibility, safety, and efficacy of G-POEM. Methods 20 patients with refractory gastroparesis (10 diabetic and 10 nondiabetic) were prospectively included in the trial. Patients were treated by G-POEM after evaluation of pyloric function using an endoscopic functional luminal imaging probe. Clinical responses were evaluated using the Gastroparesis Cardinal Symptom Index (GCSI), and quality of life was assessed using the Patient Assessment of Upper Gastrointestinal Disorders – Quality of Life scale and the Gastrointestinal Quality of Life Index scores. Gastric emptying was measured using 4-hour scintigraphy before G-POEM and at 3 months. Results Feasibility of the procedure was 100 %. Compared with baseline values, G-POEM significantly improved symptoms (GCSI: 1.3 vs. 3.5; P Conclusion G-POEM was efficacious and safe for treating refractory gastroparesis, especially in patients with low pyloric distensibility.

A role for immunoproteasome in the regulation of intestinal permeability has been previously suggested both in mice during water avoidance stress (WAS) and in patients with irritable bowel syndrome (IBS). Here, we provide evidence that the ubiquitin-proteasome system (UPS) contributes to the pathophysiology of IBS. Indeed, we report that colonic proteome is altered in WAS mice and that β2i subunit deficiency modifies the proteome response that is associated with a limitation of colonic hyperpermeability. Interestingly, we show specific alterations of proteins involved in UPS, mitochondrial, and energy metabolism. We also report changes in the pattern of colonic ubiquitome in diarrhea-predominant IBS (IBS-D) patients and particularly a reduced expression of ubiquitinated proteins involved in the nuclear factor-kappa B (NF-κB) inflammatory signaling pathway. All these data suggest that immunoproteasome targeting may represent a new therapeutic strategy for the treatment of IBS patients with increased intestinal permeability.

International audience; Digestive disorders, in particular constipation, are symptoms very often reported by cancer patients as having a major impact on their quality of life. An accurate diagnosis of bowel delayed transit and defecation disorders is required to best adapt therapeutic management. Constipation associated with cancer may be related to several causes, which can be placed in three nosological categories that sometimes overlap: chronic constipation prior to cancer and having its own evolution; constipation related to the cancer condition, in particular the occlusive syndrome, and constipation induced by cancer therapies. The stricter application of diet and lifestyle measures is often necessary and sometimes sufficient. Laxative drug treatments come under various galenic forms and administration routes and must be selected according to the clinical features of constipation. Surgical management can be indicated in case of ileus or pelvic static disorders. In the case of refractory constipation induced by opioids and within the framework of palliative care to treat an advanced pathology, a peripheral morphinic antagonist can offer fast symptom relief. A way forward to improve the patients' quality of life could be to identify the contributing factors (in particular, genetic factors) to determine which patients are the more at risk and anticipate their management.; Les troubles digestifs, et notamment la constipation, constituent des symptômes très fréquemment décrits par les patients atteints de cancer, avec un retentissement important sur leur qualité de vie. Le diagnostic précis du ralentissement du transit et des troubles de la défécation est nécessaire afin d’adapter au mieux la prise en charge thérapeutique. Les étiologies de constipation associées au cancer sont nombreuses et peuvent être séparées en trois cadres nosologiques, s’intriquant parfois entre eux : la constipation chronique antérieure au cancer et évoluant pour son propre compte, la constipation liée à la maladie cancéreuse avec notamment le syndrome occlusif et la constipation liée aux traitements du cancer. Le renforcement des mesures hygiéno-diététiques est souvent nécessaire et parfois suffisant. Les traitements médicamenteux laxatifs présentent des formes galéniques et voies d’administration différentes et seront choisis en fonction des caractéristiques de la constipation. Une prise en charge chirurgicale peut être indiquée en cas d’occlusion intestinale ou de troubles de la statique pelvienne. En cas de constipation rebelle liée aux opioïdes et dans le cadre d’une prise en charge palliative d’une pathologie avancée, un antagoniste morphinique périphérique peut permettre de soulager rapidement les symptômes. Afin d’améliorer la qualité de vie des patients, l’identification de facteurs favorisants notamment génétiques permettrait de déterminer les patients les plus à risque et ainsi anticiper leur prise en charge.

Introduction et but de l’etude La prevalence du syndrome de l’intestin irritable (SII) est augmentee chez des patients en obesite massive [1] . Or, ces deux pathologies, qui sont des enjeux majeurs de sante publique, partagent des mecanismes physiopathologiques intestinaux communs telles que : une dysbiose intestinale, une hyperpermeabilite intestinale et une micro-inflammation intestinale. Le but de cette etude etait donc de chercher a comprendre les mecanismes mis en jeu dans les interactions obesite et SII chez la souris. Materiel et methodes Des souris mâles C57Bl/6, âgees de 8 semaines, ont recu une alimentation standard (SD) ou riche en graisses (60 % de kcal sous forme lipidique, HFD) pendant 12 semaines, puis ont ete soumises a un stress du a l’evitement de l’eau (WAS), 1 heure par jour pendant 10 jours. Des souris genetiquement obeses ob/ob ont egalement ete soumises au WAS. Resultats et analyse statistique Les souris HFD et ob/ob presentent une intolerance au glucose (267,7 ± 11,2 et 261,4 ± 12,4 vs 206,1 ± 5,3 AUC ; p Conclusion En conclusion, le stress induit un dysfonctionnement de la barriere intestinale plus marque chez les souris rendues obeses par une alimentation riche en graisse comparativement aux souris non obeses. Cet effet semble etre independant de la voie de la leptine, de l’hyperglycemie et n’implique pas le microbiote intestinal. Le role des composants de l’alimentation riche en lipides reste a evaluer.

International audience; Background: Gastric electrical stimulation (GES) is used in both the US and Europe, but little research has investigated the demographics of gastroparesis patients receiving GES by geographic location.Methods: We compared data from 380 patients, 296 female and 84 males, mean age 42 years, 246 idiopathic (ID), 107 diabetic (DM), and 27 post-surgical (PS). The statistical significance was calculated by Chi-square test and a P-value obtained for ID, DM, and PS. The statistical significance was calculated by Fischer exact test and a P-value obtained comparing male vs. female.Results: European centers had 61 GES patients compared to 319 from the US. In Europe, 100% of patients had gastric emptying test (GET) values available; in the US, it was 75% of patients. European centers had more DM patients (59%) than the US (22%), and a smaller proportion of ID patients (25%) than the US (72%). There was a statistical difference between the causes of gastroparesis in the patients receiving GES (P-value < 0.00001). There was also significant difference in the gender of the patients receiving GES, with a greater proportion of women in the US (P value = 0.0023).Conclusions: Comparing GES in US vs. Europe demonstrated significant differences in gastroparesis demographics and percentage of patients with GET data. After analyzing the previously discussed results and reviewing recent updates in evidence-based medicine guidelines, the discrepancy and variance in patient populations in the US and Europe emphasizes the need for a database that allows better analysis and treatment of gastroparesis patients worldwide including stimulation therapies.

The clinical challenge of recognizing then treating malabsorption is crucial in older patients, in whom the consequences in terms of both morbidity and mortality are more severe. This challenge is reinforced by a frequent atypical clinical presentation delaying the diagnosis in many cases. Indeed, as in many diseases that occur in old patients, symptoms such as weight loss are often considered to be related to altered appetite or increased catabolism rather than to malabsorption. We now have substantial evidence that malabsorption in older people should not be ascribed to the ageing process and should be evaluated in the same way as malabsorption occurring in younger patients. In an older patient, there may be several contributory causes.

Resume Proposer un regime a un malade est une attitude frequente en hepatogastroenterologie mais l’utilite de tous ces regimes est loin d’etre validee. Enrichir l’alimentation avec 15 a 20 g de fibres en cas de constipation, appauvrir le regime en residus avant coloscopie, reduire la fraction lipidique de l’alimentation en cas d’insuffisance pancreatique uniquement si persistance d’une steatorrhee importante apres adaptation du traitement, adopter un regime sans gluten a vie au cours de la maladie cœliaque ou regime appauvri en lactose en cas de malabsorptions symptomatique sont des attitudes utiles, validees. Meme si toutes les recommandations de societes savantes ne reprennent pas cette proposition, des arguments existent aussi pour considerer qu’une alimentation appauvrie en certains sucres fermentables, les « FODMAPs », peut ameliorer les symptomes des patients souffrant d’un syndrome de l’intestin irritable. Inversement, l’exclusion du gluten est beaucoup plus critiquable et demande a etre validee. Des recommandations nutritionnelles peuvent etre envisagees pour les malades atteints de cirrhose. Les modalites de ce regime sont fonction du degre de severite de la maladie et de l’existence ou non de complications de l’hepatopathie. Enfin, proposer un regime pour amender les symptomes de gastroparesie demeure une voie de recherche. Un regime qui impacte la qualite de vie des malades doit demeurer une prescription medicale avec une evaluation precise du rapport benefice–risque en n’oubliant pas les risques potentiels de carences d’un regime d’exclusion trop strict.

Summary Background Pyloric pressure and compliance have never been investigated in health nor gastroparesis. Aim We hypothesised that pyloric pressure and/or compliance may be altered in gastroparesis. Methods Fasting pyloric pressure and compliance were investigated in 21 healthy volunteers (HV), 27 gastroparetic patients (GP) and 5 patients who had undergone oesophagectomy without pyloroplasty as positive controls. Under videofluoroscopic control, pyloric compliance and pressure were measured by the EndoFLIP technique. Gastric emptying half time (T1/2) using 13C–octanoic acid breath test, as well as symptoms and quality of life (GIQLI score) were also monitored. Results Mean fasting pyloric compliance was measured at 25.2 ± 2.4 mm²/mmHg in HV, and was lower both in GP (16.9 ± 2.1 mm²/mmHg; P

To assess the tolerance and potential nutritional consequences of long-term repeated doses of PEG 4000 (10 to 30 g/day) in elderly patients with chronic constipation as compared to lactulose (10-30 g/day).Single blind, randomised, multicentre, parallel group comparative study.Community-dwelling patients and nursing homes residents aged 70 years and older with a history of chronic constipation. Treatment intervention: PEG 4000 (10-30 g/day) or lactulose (10-30 g/day) for six months.Clinical nutritional status (Mini Nutritional Assessment), blood and stool samples were taken at baseline and after three and six months for assay of nutritional and absorption parameters. A patient diary documented digestive symptoms and adverse events were recorded. Information on efficacy (stool frequency and consistency) was collected as a secondary outcome measure.Of the 316 patients screened, 245 eligible patients constituted the ITT population (PEG 4000: N = 118; lactulose group: N = 127). The proportion of patients receiving PEG 4000 with abnormal levels of electrolytes, nutritional markers or vitamins did not significantly change in the six months after initiating laxative treatment and do not differ between the two groups. After a D-xylose challenge test, the proportion of patients with abnormally low xylosaemia (suggesting malabsorption) varied from 24.6% at baseline to 35.8% after six months in the PEG 4000 group and from 29.1% to 42.4% in the lactulose group, with no significant between-group or within-group differences. The proportion of patients with poor nutritional status (MNA score17) varied from 8.5% at baseline to 9.8% after 6 months in the PEG 4000 group and from 3.9% to 5.0% in the lactulose group. No changes in stool fat or total or soluble stool nitrogen were observed in the minority of patients for whom stool analysis was performed. A significantly higher stool frequency (p0.05) and improved stool consistency (p0.05) was observed in the PEG 4000 group compared to the lactulose group at each monthly evaluation period.After six months of treatment with PEG 4000, no clinically relevant changes in biochemical and nutritional parameters and no unanticipated treatment-related adverse events were detected, demonstrating the good clinical tolerance of PEG 4000 in this population of elderly constipated patients. This tolerance was associated with a better clinical efficacy of PEG 4000 compared to lactulose.

OBJECTIVES Gastric electrical stimulation (GES) is an alternative therapy to treat patients with intractable vomiting. A preclinical study has demonstrated the modulation of the gastrointestinal (GI) peptide ghrelin by GES but such mechanism has never been investigated in patients. The aim of this work was to assess the effect of GES on GI peptide levels in patients with intractable vomiting. MATERIALS AND METHODS Twenty-one patients were randomized to receive either ON or OFF GES, 14 completed the study (10 ON, 4 OFF stimulation). Vomiting episodes, gastric emptying, and gastrointestinal quality of life index (GIQLI) were assessed. Gastric and blood samples were collected before and four months after the ON period of gastric stimulation. mRNA and/or peptide levels were assessed in gastric biopsies for ghrelin, leptin, and NUCB2/nesfatin-1 and in duodenal biopsies for glucagon-like peptide 1 (GLP-1) and peptide YY (PYY) using RT-qPCR and multiplex technology. Ghrelin, leptin, GLP-1, PYY, gastric inhibitory peptide (GIP), and NUCB2/nesfatin-1 levels also were quantified in blood samples. RESULTS Among clinical parameters, vomiting episodes were slightly reduced by GES (p = 0.09). In tissue, mRNA or protein levels were not modified following chronic GES. In blood, a significant reduction of postprandial PYY levels (p

Aim Repetitive transcranial magnetic stimulation (rTMS) applied to the motor cortex can induce analgesic effects in patients with chronic pain syndromes through its effect on central pain-modulatory systems. Our aim was to evaluate the effect of rTMS on rectal sensitivity in irritable bowel syndrome (IBS) patients. Method In this randomized, sham-controlled, proof-of concept trial, 21 IBS patients (11 women and 10 men; mean age 44.0 ± 12.6 years) were randomized, using a double-blind crossover protocol, to active or sham rTMS for 5 days of treatment. The primary outcome was the increase in the pressure pain threshold after rTMS. Secondary outcomes were the changes in maximum tolerated rectal volume, rectal compliance and average pain intensity between baseline and the end of the treatments. Results There were no statistically significant differences between active and sham rTMS in terms of an increase in the pressure pain threshold, maximum tolerated volume and rectal compliance at the end of the treatments compared with baseline. However, in the subgroup of patients with the most marked rectal hypersensitivity, the volume threshold was significantly improved by active, but not by sham, rTMS (P = 0.03). Patients experienced a significant improvement in pain regardless of the type of stimulation. Conclusion This pilot study failed to demonstrate any benefit of rTMS on our primary end-point. However, the effect of rTMS on rectal tolerated volume in the most hypersensitive patients was encouraging enough to plan more powered studies.

Esophageal multichannel intraluminal pH-impedance recording (MII) is now a valid technique for determining the acidic, liquid, gas or mixed nature of gastroesophageal reflux episodes. However, some recordings may stop prematurely due to technical reasons or poor patient tolerance of the probe. Therefore, we questioned whether analysis of post-prandial 3-hour recording could predict the results obtained in ambulatory 24-hour recording. Fifty patients with symptoms of gastroesophageal reflux disease were investigated. For each patient, post-prandial 3-hour MII was recorded after a test meal, then followed by ambulatory 21-hour MII. Correlation between the total number of liquid reflux events in the 3-hour and 24-hour recordings was elevated (R=0.71; P 75reflux/24 h) were 49% and 100%, respectively, for 8 or less liquid/mixed reflux events per 3 hours, and 78% and 88%, respectively for 15 or more liquid/mixed reflux events per 3 hours. The sensitivity and specificity of symptom association probability (SAP) calculated over 3 hours were 56% and 91%, respectively. In conclusion, we identified relevant indicators on the 3-hour post-prandial recording likely to give accurate prediction of absence or presence of gastroesophageal reflux disease from 24-hour MII recording.

Introduction et but de l’etude L’obesite, enjeu majeur de sante publique, peut avoir des effets dichotomiques selon son grade. Ainsi, les sujets en obesite de grade I ou II semblent etre proteges du syndrome de l’intestin irritable (SII) alors que la prevalence du SII est augmentee d’un facteur 6 chez les sujets en obesite de grade III par rapport a la population generale. Le but de ce travail a donc ete d’evaluer la reponse de souris obeses a un modele de stress frequemment utilise pour etudier les mecanismes physiopathologiques du SII, le stress d’evitement de l’eau ou WAS. Materiel et methodes Des souris mâles C57Bl/6 ont ete soumises a un regime riche en lipides (60 % kcal sous forme lipidique ; HFD) ou non (SD) pendant 12 semaines (S12). A S12, les souris ont ete soumises ou non au stress d’evitement de l’eau (WAS) pendant 10 jours consecutifs, aboutissant ainsi a la formation de 4 groupes : SD-CT, SD-WAS, HFD-CT, HFD-WAS (n = 10/groupe). Des mesures de composition corporelle par EchoMRI ont ete realisees a S0, S12 et apres WAS. La permeabilite intestinale globale au cours du dernier jour de WAS a ete etudiee in vivo apres gavage des souris au FITC-dextran. Apres le sacrifice des souris, la permeabilite colique a ete evaluee sur des segments places en chambre de Ussing et la corticosterone plasmatique a ete mesuree par ELISA. Resultats et analyse statistique Les souris HFD presentaient un poids significativement plus eleve que les souris SD (a S12 : 39,8 ± 1,2 vs 29,7 ± 0,4 g, p Conclusion Les souris rendues obeses par une alimentation riche en lipides semblent plus sensibles au stress avec une elevation importante de la corticosterone et une augmentation de la permeabilite intestinale. Les mecanismes mis en jeu ainsi que l’impact sur les troubles fonctionnels intestinaux (motricite, sensibilite) restent a determiner.

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

Resume Objectifs Evaluer la prevalence des symptomes extradigestifs (SED) (asthme, douleur pharyngee, enrouement chronique, sensation d’etouffement nocturne, toux chronique, toux nocturne, douleurs thoraciques pseudo-angineuses) suspects dus a un reflux gastro-œsophagien (RGO) dans une population consultant en medecine generale. Comparer la demarche diagnostique et therapeutique adoptee initialement puis lors du suivi a celle recommandee par la conference de consensus franco-belge sur le RGO de l’adulte (1999). Methodes Cette enquete a ete realisee aupres de 578 medecins generalistes (MG). Les differents SED ont ete systematiquement recherches chez tous les patients (≥ 18 ans) consultant sur trois jours. Seuls les patients consideres a priori comme ayant un ou des SED en rapport avec un RGO ont ete inclus dans l’etude. A chaque consultation (C1 a l’inclusion, C2 a 1 mois et C3 a 4 mois), la demarche diagnostique et therapeutique a ete analysee, notee et le degre de certitude du MG sur la responsabilite du RGO dans ces SED quantifie sur une echelle visuelle analogique (EVA). Les criteres ayant conduit les MG a considerer la responsabilite du RGO comme certaine ou douteuse ont ete etudies. Resultats Sur un total de 33 487 consultants, 14 % decrivaient des SED (toux : 6,7 % ; symptome ORL : 7,7 % ; douleur thoracique : 2,3 %). Parmi les patients avec SED, 22 % (1063) ont ete inclus dans l’etude pour suspicion de RGO alors que 45 % (481) ne decrivaient ni antecedents ni symptome digestif typique de RGO. L’attitude diagnostique n’etait pas differente selon que le patient avait des symptomes typiques de RGO associes aux SED (A+) ou non (A−) : 83,7 % des patients (A+) versus 86,5 % (A−) ont recu d’emblee un traitement anti-reflux, 4,9 % (A+) versus 7,9 % (A−) ont eu des examens complementaires et 5,2 % (A+) versus 4,4 % (A−) un avis specialise. Le traitement anti-reflux initial comprenait a 87 % un inhibiteur de la pompe a protons (IPP) [demi-dose : 47 % ; pleine dose : 50 % ; double dose : 2,5 %], un prokinetique dans 3,2 % des cas et un autre medicament dans 13 % des cas. Au terme des quatre mois de suivi, la responsabilite du RGO etait consideree comme certaine chez 74,7 % des patients inclus (794/1063). L’opinion du MG reposait sur la reponse au traitement anti-reflux a 92 %, sur l’endoscopie a 6,7 %, sur la pHmetrie a 0,3 % et sur un avis specialise a 6 % des cas. Conclusions Il existait une difference importante entre les recommandations de la conference franco-belge de consensus sur le RGO de l’adulte et les pratiques observees en medecine generale. La demarche diagnostique et therapeutique etait empirique avec recours aux examens complementaires dans moins de 10 % des cas. Le degre de certitude sur la responsabilite du RGO reposait essentiellement sur la reponse au traitement par les IPP.

Few studies have evaluated the impact of gastroesophageal reflux disease symptoms on work productivity and no French data are available.To compare the impact of typical symptoms of nocturnal vs diurnal gastroesophageal reflux disease on work productivity and daily activities.A French prospective, multicenter, observational study was performed in primary care setting. Patient characteristics, symptomatology and treatment were reported. Work productivity loss was assessed using the work productivity and activity impairment questionnaire, predictors were identified using multivariate regression models, and estimated cost was calculated.716 eligible patients (mean age: 46.3 years) were included by 407 physicians. Nocturnal symptoms were reported in 50.8% of patients and exclusively diurnal symptoms in 49.2%. Mean work productivity and daily activities decreased by 31.4% and 32.6%, respectively (both p0.001). Work productivity was influenced by symptom intensity, diurnal symptoms occurrence, regurgitation and diurnal sleepiness. The mean associated cost per patient/week (€313) was higher in patients with diurnal symptoms (without (€346) or with nocturnal (€312) symptoms) than in patients with exclusive nocturnal symptoms (€253) (p0.001).Gastroesophageal reflux disease incurs high work productivity loss especially in patients with diurnal symptoms. Further medico-economic analyses are needed to estimate the cost effectiveness ratio according to therapeutic strategies.

INTRODUCTION Gastric electrical stimulation (GES) is now considered as a new therapeutic alternative for patients with medically refractory vomiting and/or nausea, although its mechanisms of action remain poorly understood. METHODS AND PATIENTS Gastric discomfort threshold, measured as the gastric maximal tolerable volume (MTV) to distension, was examined before and after GES, in nine patients implanted for chronic and severe nausea and vomiting. RESULTS GES increased gastric MTV from 522 ± 64 ml at baseline to 628 ± 60 ml 6 months after the start of GES (P=0.03), whereas gastric emptying remained unchanged. The increase in MTV was correlated with symptoms and quality of life at 6 months, whereas gastric emptying was not. Finally, MTV varied in a similar manner at 6 months in patients with delayed and normal gastric emptying measured before implantation. CONCLUSION Taken together, these data indicate that modification of gastric sensation to distension, rather than gastric emptying, is associated with symptoms' outcome during GES.

Background & Aims Capsule enteroscopy (CE) is the best noninvasive tool to explore the entire small bowel of patients with obscure gastrointestinal bleeding (OGIB); it has a diagnostic yield of 40%–80%. However, little is known about the factors associated with a diagnosis of OGIB by CE. Methods We analyzed data from 911 consecutive patients who underwent CE for OGIB from January 2004 to January 2010. Results from upper and lower gastrointestinal endoscopy examinations were negative in all patients. CE findings were recorded. Features of patients that were associated with diagnosis of OGIB by CE were identified by using logistic regression. Results Based on CE, 509 patients (56%) had a confirmed lesion responsible for the OGIB: 203 had disease of the small bowel (22%), 88 had ulcerations (10%), 70 had tumors (8%), 24 had varices (2%), 6 had diverticula (0.5%), and 118 had what appeared to be bleeding lesions of the esophagus or stomach (10.6%) or colon (2%). Factors independently associated with a diagnosis of OGIB by CE were age >60 years (odds ratio [OR], 1.2), male sex, history of overt bleeding (OR, 3.8), and current hospitalization (OR, 1.4). Women were less likely to be diagnosed with OGIB by CE (OR, 0.7). Conclusions A history of overt bleeding is the factor most strongly associated with a diagnosis of OGIB by CE. Male sex, age >60 years, and inpatient status were also independent predictors of positive diagnosis by CE.

International audience; Protease activated receptors (PARs) and the ubiquitin-proteasome system (UPS) regulate inflammatory response in intestinal cells. We aimed to elucidate putative connections between PARs and UPS pathways in intestinal epithelial cells. Caco-2 cells were treated by agonist peptides of PARs and/or IL-1β and/or proteasome inhibitors, bortezomib or MG132. Inflammatory response was evaluated by measuring IL-8 production. Proteasome activities were also evaluated. We showed that PAR-1 and -2 activation increased release of IL-8 compared with vehicle and independently of IL-1β. In contrast, PAR-4 agonist peptide had no effect. Caspase-like and chymotrypsin-like proteasomal activities were increased by PAR-2 activation only in the presence of IL-1β. Interestingly, in polarized Caco-2 cells, the release of IL-8 was predominantly upregulated in the side where PAR-2 agonist peptide was added, apical or basalolateral. In contrast, proteasome activities were only affected when PAR-2 agonist peptide was added in the apical side. Proteasome inhibitors, bortezomib and MG132, enhanced IL-8 production in both sides, apical and basolateral. In conclusion, PAR-2 activation alone did not affect proteasome but needed inflammatory stimulus IL-1β to synergistically increase chymotrypsin-like activity in intestinal epithelial cells. However, proteasome inhibition led to exacerbate inflammatory response induced by PAR-2 activation.

International audience; ObjectivesTo date, no studies have yet assessed the characteristics of non-HCV patients with low level of cryoglobulin (≤ 0.05 g/L). The aims of the current study were thus to: 1) determine the prevalence of cryoglobulin ≤ 0.05 g/L in patients with non-HCV cryoglobulin; and 2) compare clinical features and long term outcome, including organ complications and mortality rate, between non-HCV patients with cryoglobulin level ≤ 0.05 g/L and those exhibiting cryoglobulin level > 0.05 g/L.MethodsAmong 6379 cryoglobulin testing, cryoglobulin was detected in 618 patients (9.69% of cases); of these 618 patients, 453 non-HCV patients were included in the study. The medical records of these patients were reviewed.ResultsOf the 453 non-HCV cryoglobulin-positive patients, 265 (58.6%) exhibited cryoglobulin level ≤ 0.05 g/L. We showed that patients with cryoglobulin level ≤ 0.05 g/L had: 1) less commonly: palpable purpura (p < 0.001), digital ulcers (p = 0.006), peripheral neurologic involvement (p = 0.03) and renal impairment (p = 0.03); and 2) lower median values of ESR (p < 0.001) and C-reactive protein (p = 0.001). The patients with cryoglobulin level ≤ 0.05 g/L less often experienced infections (p = 0.04) and hematological malignancies (p = 0.01); both groups did not differ regarding prevalence of connective tissue diseases and solid tumors. Mortality rate was as high as 13.6% in patients with cryoglobulin level ≤ 0.05 g/L; death was mainly due to: solid tumors (16.6%), cardiovascular complications (13.8%), hematological malignancies (11.1%), infections (8.3%), pulmonary/renal complications of cryoglobulin (8.3%) and connective tissue diseases (8.3%).ConclusionOur study shows a high prevalence of cryoglobulin level ≤ 0.05 g/L in clinical practice. Our findings further underscore that non-HCV cryoglobulin level ≤ 0.05 g/L may be responsible for severe renal and neurological complications, leading to high morbidity and mortality in these patients. Thus, our data suggest that both appropriate therapy and close follow-up may be required to improve such patients' outcome.

Background Intestinal hyperpermeability has been reported in several intestinal and non-intestinal disorders. We aimed to investigate the role of the ubiquitin proteasome system in gut barrier regulation in two mice models: the water avoidance stress model (WAS) and a post-inflammatory model (post-TNBS). Methods Both models were applied in C57BL/6 male mice ( n = 7–8/group); Proteasome was targeted by injection of a selective proteasome inhibitor or by using knock-out mice for β2i proteasome subunit. Finally, glutamine supplementation was evaluated. Results In both models (WAS at day 10, post-TNBS at day 28), we observed an increase in proteasome trypsin-like activity and in inducible β2/constitutive β2 subunit protein expression ratio, associated with an increase in intestinal permeability. Moreover, intestinal hyperpermeability was blunted by intraperitoneal injection of selective proteasome inhibitor in WAS and post-TNBS mice. Of note, knock-out mice for the β2i subunit exhibited a significant decrease in intestinal permeability and fecal pellet output during WAS. Glutamine supplementation also improved colonic permeability in both models. Conclusions In conclusion, the proteasome system is altered in the colonic mucosa of WAS and post-TNBS mice with increased trypsin-like activity. Associated intestinal hyperpermeability was blunted by immunoproteasome inhibition.

Irritable bowel syndrome is a multifactorial disease. Although faecal calprotectin has been shown to be a reliable marker of intestinal inflammation, its role in irritable bowel syndrome remains debated.The aims of this prospective study were to select a subgroup of irritable bowel syndrome patients and to characterise those patients with high faecal calprotectin by systematic work-up.Calprotectin levels were determined by enzyme-linked immunosorbent assay test in consecutive irritable bowel syndrome patients fulfilling Rome III criteria in whom normal colonoscopy and appropriate tests had excluded organic disease. Calprotectin levels were compared in irritable bowel syndrome patients, healthy controls and patients with active and quiescent Crohn's disease. When the calprotectin level was higher than 50 µg/g, the absence of ANCA/ASCA antibodies and a normal small bowel examination were required to confirm irritable bowel syndrome diagnosis. Additional explorations included assessment of irritable bowel syndrome severity, anxiety and depression, impact on quality of life, glucose and fructose breath tests, rectal distension test by barostat and quantitative and qualitative assessment of inflammation on colonic biopsies.Among the 93 irritable bowel syndrome patients (73% women; 66.7% with diarrhoea) recruited, 34 (36.6%) had reproducibly elevated calprotectin. Although they tended to be older than those with normal calprotectin (Elevated faecal calprotectin was observed in one third of patients in this series, without any significant association with a specific clinical phenotype (except age) or specific abnormalities.

Digestive disorders, in particular constipation, are symptoms very often reported by cancer patients as having a major impact on their quality of life. An accurate diagnosis of bowel delayed transit and defecation disorders is required to best adapt therapeutic management. Constipation associated with cancer may be related to several causes, which can be placed in three nosological categories that sometimes overlap: chronic constipation prior to cancer and having its own evolution; constipation related to the cancer condition, in particular the occlusive syndrome, and constipation induced by cancer therapies. The stricter application of diet and lifestyle measures is often necessary and sometimes sufficient. Laxative drug treatments come under various galenic forms and administration routes and must be selected according to the clinical features of constipation. Surgical management can be indicated in case of ileus or pelvic static disorders. In the case of refractory constipation induced by opioids and within the framework of palliative care to treat an advanced pathology, a peripheral morphinic antagonist can offer fast symptom relief. A way forward to improve the patients' quality of life could be to identify the contributing factors (in particular, genetic factors) to determine which patients are the more at risk and anticipate their management.

The prevalence of gastroparesis is increasing. Diabetes mellitus and sequelae of œsogastric surgery are the two main causes of gastroparesis. In some patients, gastroparesis seems a postinfectious disease after its sudden onset after a viral infection. In about one third of the patients, gastroparesis is considered as idiopathic. In diabetic patients, gastroparesis impairs glycaemic control. Due to the low positive predictive value of symptoms, a gastric emptying study is often necessary to confirm a suspected diagnosis of gastroparesis. The symptomatic efficacy of erythromycin is higher than that of other prokinetics. This efficacy is higher when erythromycin is given intravenously. Hyperglycaemia impairs this symptomatic effect. Due to a tachyphylaxis phenomenon, the clinical effect of erythromycin decreases with the duration of treatment. In refractory gastroperis, either duodenal or jejunal enteral feeding, or high-frequency gastric electrical stimulation are possible therapeutic options while endoscopic alternatives (intrapyloric botulinum injection or pyloric balloon dilation) give unsatisfactory results.

Objective To determine the prevalence of delayed gastric emptying using the 13C–octanoic acid breath test in unselected patients with systemic sclerosis (SSc), to evaluate whether findings of the 13C–octanoic acid breath test are associated with clinical digestive manifestations, gastric mucosal abnormalities detected by gastroscopy, motor activity dysfunction detected by antroduodenal manometry, and esophageal motor impairment and extradigestive manifestations of SSc, and to develop a risk prediction score of gastric emptying in SSc. Methods Consecutive patients with SSc (n = 57) underwent the 13C–octanoic acid breath test. All of the patients with SSc completed a questionnaire on digestive symptoms, and a global symptom score (GSS) was calculated. Results The prevalence of delayed gastric emptying was 47.4% in patients with SSc. A marked correlation was observed between a GSS of digestive symptoms ≥5 and the presence of delayed gastric emptying (P < 0.00001). The sensitivity of a GSS ≥5 for predicting delayed gastric emptying was as high as 0.93, while the specificity was 0.73. Moreover, a GSS ≥5, mucosal gastric abnormalities, severe esophageal motor impairment, and interstitial lung disease were factors that were independently associated with the presence of delayed gastric emptying, and these variables were used to create a risk prediction score. The area under the receiver operating characteristic curve for the risk prediction score was 0.90; the sensitivity of this score for the prediction of delayed gastric emptying was 0.93, while the specificity was 0.77. Conclusion The results indicate that delayed gastric emptying occurs often in patients with SSc. Interestingly, using risk models with routine clinical characteristics, a simple risk prediction score can be calculated, allowing prediction of the occurrence of delayed gastric emptying in patients with SSc.

The management of opioid-induced constipation (OIC) is often complicated by the fact that clinical measures of constipation do not always correlate with patient perception. As the discomfort associated with OIC can lead to poor compliance with the opioid treatment, a shift in focus towards patient assessment is often advocated.The Bowel Function Index * (BFI) is a new patient-assessment scale that has been developed and validated specifically for OIC. It is a physician-administered, easy-to-use scale made up of three items (ease of defecation, feeling of incomplete bowel evacuation, and personal judgement of constipation). An extensive analysis has been performed in order to validate the BFI as reliable, stable, clinically valid, and responsive to change in patients with OIC, with a 12-point change in score constituting a clinically relevant change in constipation.The results of the validation analysis were based on major clinical trials and have been further supported by data from a large open-label study and a pharmaco-epidemiological study, in which the BFI was used effectively to assess OIC in a large population of patients treated with opioids. Although other patient self-report scales exist, the BFI offers several unique advantages. First, by being physician-administered, the BFI minimizes reading and comprehension difficulties; second, by offering general and open-ended questions which capture patient perspective, the BFI is likely to detect most patients suffering from OIC; third, by being short and easy-to-use, it places little burden on the patient, thereby increasing the likelihood of gathering accurate information.Altogether, the available data suggest that the BFI will be useful in clinical trials and in daily practice.

Introduction et but de l’etude Les symptomes du syndrome de l’intestin irritable ou SII (troubles de la motricite, douleur abdominale, ballonnements) touchent environ 5 % de la population generale mais egalement des patients ayant une maladie inflammatoire chronique de l’intestin (MICI) en phase de remission. Une hyper-permeabilite intestinale semble contribuer a la physiopathologie de ces troubles. Des etudes precedentes suggerent que la glutamine regule l’expression des proteines de jonctions serrees et la permeabilite intestinale dans differentes conditions. Le but de ce travail a ete d’evaluer les effets d’une supplementation en glutamine sur la fonction de barriere intestinale dans deux modeles murins mimant les symptomes du SII. Materiel et methodes Des souris males C57Bl/6 ont ete utilisees (n = 8–10/groupe). Des prelevements coliques etaient realises (i) chez des souris soumises au modele de stress d’evitement de l’eau (WAS), consistant a placer les souris une heure par jour pendant 10 jours sur une petite plateforme au milieu d’une bassine d’eau et (ii) chez des souris au 28e jour apres l’injection de TNBS en intra-colique (post-TNBS). Une supplementation en glutamine (2 g/kg/j) etait realisee de j1 a j10 chez les souris WAS et de j21 a j28 chez les souris post-TNBS. La permeabilite intestinale a ete evaluee en etudiant les flux de FITC-dextran (4kDa) sur des segments coliques places en chambre de Ussing. Resultats et analyse statistique Les souris WAS recevant une supplementation en glutamine ne presentaient pas de modification de la permeabilite intestinale alors qu’une hyper-permeabilite colique etait observee chez les souris WAS non supplementees par rapport au souris controles (49,07 vs. 14,28 μg/mL FITC-dextran, p Conclusion En conclusion, une supplementation en glutamine diminue l’hyper-permeabilite colique dans deux modeles murins mimant le SII, en particulier en augmentant l’expression de la proteine de jonction serree, occludine. Ces resultats devront etre confirmes chez l’homme.

Several types of gastrointestinal complications can occur during treatment with targeted therapies: diarrhoea, nausea and vomiting, abnormalities in hepatic and pancreatic profiles, etc. Gastrointestinal problems in targeted therapy can have a significant impact on the general status of patients, their weight and their adherence to the treatment. The prevention, screening and rapid treatment of these side-effects are essential elements of patient care and can limit the associated dose reductions and loss of therapeutic benefit. In the case of diarrhoea, treatment must be started at the onset of grade 1 or 2 diarrhoea (four to six stools per day), with loperamide or racecadotril. Treatment with targeted therapy must be stopped if there is diarrhoea of grade 3 or 4 (more than six stools per day). In the case of nausea/vomiting or burning pain in the oesophagus, symptomatic treatment without stopping the targeted therapy is recommended. Biological assessment including transaminases, total and conjugated bilirubin should be prescribed before treatment initiation with targeted therapy. An elevation in alkaline phosphatases without elevation of transaminases suggests primarily the existence of hepatic metastases. In the event of worsening of the hepatic profile, if ALT greater than 5N, treatment must be stopped and specialist advice sought.

To date, Lugol chromo-endoscopy is the reference technique to detect an esophageal neoplasia in patients with prior esophageal squamous-cell carcinoma (ESCC), but is not easy to perform without general anesthesia, which can limit its use in routine practice. The objective of this study were to compare the accuracy of white light, narrow band imaging (NBI), and Lugol to detect esophageal neoplasia in patients with a history of cured ESCC, in a prospective study. Thirty patients were prospectively included between June 2006 and June 2009. They all had a history of cured ESCC. Esophageal mucosa was examined first using white light, second NBI, and third after Lugol staining. Histology was obtained in all abnormalities detected by white light, NBI, and/or Lugol. Five neoplastic lesions in five different patients were identified at histology, four cancers, and one high-grade dysplasia. NBI and Lugol both detected all esophageal neoplastic lesions, whereas white light detected the four cancers but missed the high-grade dysplasia. In this feasibility study, NBI and Lugol both detected all identified esophageal neoplasia in very high-risk patients of ESCC. This result suggests that NBI could be used instead of Lugol to detect an esophageal neoplasia in patients with high risk of ESCC, but needs to be confirmed in a larger study.

Gastric electrical stimulation (GES) is a new therapeutic option for functional dyspepsia and gastroparesis. In addition to ameliorating nausea and vomiting, GES results in improved appetite which is not always associated with accelerated gastric emptying. To explore the central and peripheral factors underlying GES-associated improvement of appetite we developed a GES model in anaesthetized Wistar rats. During laparotomy, two electrodes were implanted into the stomach and high-frequency low-energy GES (14 Hz, 5 mA) was applied. The effects of 1 h GES were compared with sham stimulation. After GES, c-Fos expression was increased in the mucosal and submucosal layers of the stimulated area (174%). In the stomach, GES increased ghrelin mRNA (178%) and doubled the number of ghrelin-positive cells, resulting in elevated plasma levels of ghrelin (2.3 ± 0.2 vs. 1.6 ± 0.2 ng ⁄mL). In the arcuate nucleus of the hypothalamus, GES increased c-Fos (277%) and agouti-related protein (AgRP) mRNA expression (135%). GES reduced the number of c-Fos-positive cells throughout the nucleus of the solitary tract (between 93 and 75% from rostral to caudal levels) including catecholaminergic neurons (81% at caudal level). Gastric emptying, plasma glucose and heart rate variability were not affected by GES. This study shows that GES may improve appetite via stimulation of main orexigenic pathways, including ghrelin production in the stomach and AgRP in the hypothalamus, as well as by reducing the activity of catecholaminergic brainstem neurons.

Resume D’un point de vue physiopathologique, le syndrome de l’intestin irritable (SII) est une affection multifactorielle. Cependant, l’accent est mis actuellement sur le role probablement important joue par les anomalies de la flore, en particulier dans la sensibilisation des terminaisons sensitives et l’activation des cellules immunitaires dans la paroi digestive. Epidemiologiquement, un SII, surtout a forme diarrheique, peut apparaitre au decours d’une gastroenterite aigue, essentiellement d’origine bacterienne. L’action metabolique de la flore parait excessive, pouvant contribuer a certain symptomes comme le ballonnement et peut-etre favoriser la survenue d’une hypersensibilite viscerale. Des anomalies qualitatives de la flore a la fois endoluminale et adherente au biofilm present au contact de l’epithelium ont ete decrites. Enfin, une pullulation bacterienne endo-luminale parait etre une realite dans un sous groupe de patients souffrant de SII, sans que l’on sache actuellement si cette anomalie est primitive ou secondaire aux troubles moteurs, notamment greliques, qui s’observent au cours du SII. Ce role deletere de la flore ouvre des perspectives therapeutiques avec un recours possible aux pre- ou probiotiques et peut-etre aux antibiotiques.

Mallory-Weiss syndrome is relatively common and is involved in 3 to 10% of cases of upper gastrointestinal bleeding. Most of the time, the hemorrhage is mild and stops spontaneously. Clinical suspicion requires confirmation by an upper gastrointestinal endoscopy, which must be performed rapidly after the first hematemesis. Mallory-Weiss syndrome is diagnosed when it shows a longitudinal mucosal tear at the esophagogastric junction. Patients with active bleeding or signs of recent bleeding at endoscopy need immediate endoscopic treatment for hemostasis. Band ligation seems to be the most efficient procedure for primary hemostasis and for preventing recurrent bleeding. The use of proton pump inhibitors and antiemetics seems logical in all cases, although nothing in the literature demonstrates their efficacy.

Proteasome-mediated protein degradation may contribute to the regulation of intestinal inflammation. At the same time, low-grade inflammation and increased intestinal permeability seem to be involved in the pathophysiology of irritable bowel syndrome (IBS). Thus, we aimed to evaluate proteasome composition and activities in colonic mucosa of IBS patients and its putative pathogenic role.Proteasome activities and proteasome subunit expression were measured in colonic mucosa of IBS, Crohn's disease (CD), and control patients by fluorometric assays and western blot, respectively. Expression of inhibitor of kappa B factor (IkappaB alpha) and occludin, a tight junction protein, was also evaluated in colonic biopsies. The degradation of recombinant occludin incubated with protein extracts from colonic mucosa was evaluated in the presence or absence of proteasome inhibitor, MG132.Proteasome trypsin-like activity was increased in IBS patients compared with CD and controls, whereas chymotrypsin-like activity was upregulated in CD patients only. Caspase-like activity was reduced both in IBS and CD patients. IkappaB alpha expression was similar between IBS and controls. In contrast, occludin expression was lower in IBS than in controls, but occludin mRNA level was similar. Protein extracts from IBS patients but not from controls degraded recombinant occludin (20% over 160 min), which was blocked by MG132. Although mast cell number was increased in IBS patients, no correlation was found between this number and proteasome alterations.Our study shows that proteasome alterations are present in the colonic mucosa of IBS patients and may contribute to the pathophysiology of IBS by increasing occludin degradation.

BACKGROUND Some consider that patients with visceral hypersensitivity may represent a separate entity within the IBS population not only from a pathophysiological but also from a clinical perspective. The aim of this prospective exploratory study was to assess whether characteristics of abdominal pain in IBS patients could be suggestive of hypersensitivity. METHODS This prospective study included consecutive IBS patients selected by Rome III criteria. Validated scores (IBS-SSS, Bristol stool scale, HADS) were used to phenotype patients who were also asked to describe the main location of their abdominal pain on a simple image (abdomen divided into 6 zones). Progressive isobaric rectal distensions were performed to demonstrate, with the ascending method of limits, allodynia (pain threshold lower than 24 mmHg). KEY RESULTS Fifty patients (women: 72%), 42.6 ± 15.7 years old, were included. Sub-types were IBS-D, IBS-C and IBS-M in 58%, 22% and 20% of cases, respectively. Allodynia was present in 18% of cases. Neither IBS-SSS nor intensity of pain was predictive of hypersensitivity. In hypersensitive patients, pain was more often located in one of the two iliac fossa (P = 0.02) and located outside these areas in only 11% of cases. The sensitivity and the specificity of this pain location to differentiate hyper from normosensitive patients were 0.89 and 0.59, respectively. CONCLUSIONS & INFERENCES The location of pain is different between hyper and normosensitive IBS patients. Pain located outside one of the two iliac fossa suggests that the patient is normosensitive.

Resume La constipation est l’effet secondaire indesirable le plus frequent au cours des traitements par les opioides. Elle altere la qualite de vie des malades et peut compromettre l’obtention d’une analgesie optimale du fait de la limitation des doses d’opioides qu’elle impose. Elle est la consequence de l’action des opioides sur les recepteurs μ du systeme nerveux enterique aboutissant a une diminution de l’excitabilite neuronale et de la liberation de neurotransmetteurs, en particulier l’acetylcholine. La constipation est multifactorielle, motrice et secretoire. Les opioides stimulent les contractions segmentaires, reduisent les mouvements de masse propulsifs et augmentent la capacite de stockage des matieres du colon, notamment gauche. Au niveau anorectal, ils emoussent le besoin exonerateur et augmentent la pression anale. L’absorption accrue d’eau et d’electrolytes dans le grele et le colon favorise la constitution de selles dures, difficiles a evacuer. Sur le plan therapeutique, l’emploi de laxatifs stimulants (sennosides, bisacodyl) est souvent utile. Le recours a un traitement par voie rectale (suppositoires) ne doit pas etre oublie. L’administration de naloxone est egalement envisageable mais la naloxone orale expose au risque de recrudescence des douleurs, meme a des posologies faibles (2 mg). Le developpement de nouveaux antagonistes morphiniques peripheriques (methylnaltrexone, almivopan) apparait un progres therapeutique important pour autoriser une analgesie suffisante sans alterer le confort de vie du malade par des effets secondaires digestifs notables.

Background Gastric electrical stimulation (GES) represents a new therapy in patients with intractable vomiting and nausea. We aimed to determine preoperative factors associated with positive response during GES. Thirty-three consecutive patients received implants for medically refractory nausea or vomiting or both. Study Design Symptoms, Quality of Life (QOL), and gastric emptying (GE) were monitored before and 6 months after implantation. Compared with baseline, dyspeptic symptoms including nausea and vomiting, and QOL all improved at 6 months, yielding a significant weight gain while the GE rate remained unchanged. Twenty-four patients reported improvement; nine remained unimproved at 6 months. Results In multivariate analysis, baseline QOL and appetite alterations were predictive of improvement; previous history of gastric surgery was associated with failure. Surprisingly, patients with initial delayed GE (21 of 33) displayed similar improvement compared with patients with normal GE. Likewise, basal GE was not found to be predictive of positive outcomes, QOL, or symptoms improvement. Conclusions Patients with severe symptoms and altered QOL at inclusion particularly benefit from GES; delay in GE is not predictive of positive outcomes. This suggests that indication for GES should be based on clinical settings rather than initial GE, and then possibly extended to patients with normal GE.

Summary Background Mallory–Weiss syndrome (MWS) with active bleeding at endoscopy may require endoscopic haemostasis the modalities of which are not well-defined. Aim To compare the efficacy of endoscopic band ligation vs. hemoclip plus epinephrine (adrenaline) in bleeding MWS. Methods From 2001 to 2008, 218 consecutive patients with a MWS at endoscopy were hospitalized in our Gastrointestinal Bleeding Unit. In 56 patients (26%), an endoscopic haemostasis was required because of active bleeding. Band ligation was performed in 29 patients (Banding group), while hemoclip application plus epinephrine injection was performed in 27 patients (H&E group). Treatment efficacy and early recurrent bleeding were retrospectively compared between the two groups. Results Primary endoscopic haemostasis was achieved in all patients. Recurrent bleeding occurred in 0% in Banding group vs. 18% in HE 95% CI = 1.15–15.8) and active bleeding at endoscopy (OR = 1.9; 95% CI = 1.04–5.2) were independent predictive factors of early recurrent bleeding. Conclusions Haemostasis by hemoclips plus epinephrine was an independent predictive factor of rebleeding. This result suggests that band ligation could be the first choice endoscopic treatment for bleeding MWS, but requires further prospective assessment.

Although sacral nerve root stimulation (SNS) can result in a symptomatic improvement of faecal incontinence, the mechanism of action remains unknown. The aim of this study was to assess whether short-term magnetic SNS can inhibit pharmacologically induced propulsive colonic contractions. Twelve healthy volunteers (median age: 43.5 years old) were studied on two separate occasions and randomized into either active (15 Hz, 100% output intensity for 5 s min−1 for 30 min) or sham rapid rate lumbosacral magnetic stimulation (rLSMS). Colorectal motility was recorded with a manometric catheter located at the most proximal transducer in the left colon and the most distal, in the rectum. Colonic contractions were provoked by instilling Bisacodyl. The effects of rLSMS on colonic, sigmoid and rectal contractions were monitored and recorded after Bisacodyl instillation. The appearance of high-amplitude contractions propagated or not (HAC/HAPC) provoked by Bisacodyl instillation was significantly delayed during active compared to sham stimulation (P = 0.03). There was no difference in the characteristics of HAC/HAPC (i.e. frequency, amplitude, duration, velocity of propagation) or the motility index with active or sham stimulation. The perception of urgency tended to be decreased with rLSMS following Bisacodyl instillation. The catheter was expulsed within a median of 16.5 min (range 8–39) after Bisacodyl administration during active stimulation compared to 14 min (range 5–40) during sham stimulation (P = 0.03). This study suggests that rLSMS could delay the appearance of the first Bisacodyl-induced colonic contractions.