Florent Gonzalez

Mesenteric fat in Crohn’s disease: a pathogenetic hallmark or an innocent bystander?

In the first half of the 20th century, white adipose tissue (WAT) was mainly viewed as an isolated tissue protecting the organism from heat loss and a passive energy storage compartment. Similarly to other species such as Drososophila melanogaster , it is now well recognised that mammalian fat tissue is not solely a reservoir for excess nutrients but also an active and dynamic organ involved in the development of metabolic syndromes and the regulation of immunity and inflammation. The older anatomical literature repeatedly mentions a close association between adipose tissue and lymphoid organs in various mammals including humans, suggesting a potential role of WAT in the host immune response. Several recent studies indicate that adipocytes could function as macrophage-like cells1 as they express receptors related to the innate immune system and secrete major mediators of inflammation, such as tumour necrosis factor alpha (TNFα). Consistent with this hypothesis,2 the biology of adipocytes is particularly implicated in chronic diseases, such as obesity3 and atherosclerosis.4 This review will focus on the normal and pathophysiological functions of mesenteric WAT (mWAT), which may play an important role in the inflammatory and fibrotic processes in Crohn’s disease, a frequent and complex form of inflammatory bowel disease (IBD). Long considered as the “anatomists’ Cinderella”,5 mWAT is now recognised as a multifunctional organ. Notably located around organs such as the gut or the lungs, adipocytes may have evolved strategies to drive immune responses to microbial invaders by expressing different innate immune sensors. In addition its function as a storage organ, WAT plays a major endocrine and immune role by expressing several hormones and various mediators (fig 1). To clarify the nomenclature, we will refer to the hormones and immunomodulatory molecules derived from adipocytes as adipormones and adipocytokines, respectively. Figure 1  Adipormones, adipocytokines and their receptors. …

Mesenteric fat as a source of C reactive protein and as a target for bacterial translocation in Crohn's disease

Objective Mesenteric fat hyperplasia is a hallmark of Crohns disease (CD), and C reactive protein (CRP) is correlated with disease activity. The authors investigated whether mesenteric adipocytes may be a source of CRP in CD and whether inflammatory and bacterial triggers may stimulate its production by adipocytes. Design CRP expression in the mesenteric and subcutaneous fats of patients with CD and the correlation between CRP plasma concentrations and mesenteric messenger RNA (mRNA) levels were assessed. The impact of inflammatory and bacterial challenges on CRP synthesis was tested using an adipocyte cell line. Bacterial translocation to mesenteric fat was studied in experimental models of colitis and ileitis and in patients with CD. Results CRP expression was increased in the mesenteric fat of patients with CD, with mRNA levels being 80±40 (p<0.05) and 140±65 (p=0.04) times higher than in the mesenteric fat of patients with ulcerative colitis and in the subcutaneous fat of the same CD subjects, respectively, and correlated with plasma levels. Escherichia coli (1230±175-fold, p<0.01), lipopolysaccharide (26±0.5-fold, p<0.01), tumour necrosis factor α (15±0.3-fold, p<0.01) and interleukin-6 (10±0.7-fold, p<0.05) increased CRP mRNA levels in adipocyte 3T3-L1 cells. Bacterial translocation to mesenteric fat occurred in 13% and 27% of healthy and CD subjects, respectively, and was increased in experimental colitis and ileitis. Human mesenteric adipocytes constitutively expressed mRNA for TLR2, TLR4, NOD1 and NOD2. Conclusion Mesenteric fat is an important source of CRP in CD. CRP production by mesenteric adipocytes may be triggered by local inflammation and bacterial translocation to mesenteric fat, providing a mechanism whereby mesenteric fat hyperplasia may contribute to inflammatory response in CD.

Natural history of eosinophilic gastroenteritis.

BACKGROUND & AIMS Eosinophilic gastroenteritis (EGE) is a rare gastrointestinal disorder; little is known about its natural history. We determined the clinical features and long-term outcomes of patients with EGE. METHODS We reviewed files from 43 patients diagnosed with EGE who were followed from January 1988 to April 2009. The diagnosis was made according to standard criteria after other eosinophilic gastrointestinal disorders were excluded. We analyzed data on initial clinical presentation and long-term outcomes. RESULTS EGE was classified as mucosal, subserosal, or muscular in 44%, 39%, and 12% of cases, respectively. Disease location was mostly duodenal (62%), ileal (72%), or colonic (88%); it was less frequently esophageal (30%) or gastric (38%). Blood eosinophilia (numbers >500/mm(3)) was observed in 74% of cases. Spontaneous remission occurred in 40% of patients; the majority of treated patients (74%) received oral corticosteroids, which were effective in most cases. After a median follow-up period of 13 years (0.8-29 years), we identified 3 different courses of disease progression: 18 patients (42%; 9 with subserosal disease) had an initial flare of the disease without relapse, 16 (37%) had multiple flares that were separated by periods of full remission (recurring disease), and 9 (21%) had chronic disease. CONCLUSIONS The clinical presentation of EGE is heterogeneous and varies in histologic pattern; about 40% of patients resolve the disease spontaneously, without relapse. Approximately 50% have a more complex disease, which is characterized by unpredictable relapses and a chronic course.

Acute hepatitis C during the third trimester of pregnancy

A pregnant woman presented at 32 weeks of amenorrhea with jaundice secondary to acute hepatitis C. Spontaneous delivery took place 3 days later. The infants serum tested negative for C viral RNA 6 months after delivery. Treatment with high doses of interferon-alpha for a period of 4 weeks was begun 4 days after delivery. Although a virological response was noted at the end of the treatment, the hepatitis relapsed and progressed toward chronicity. Case reports of acute hepatitis C during pregnancy are very rare, as the methods used for the follow-up of pregnant women render the diagnosis of asymptomatic forms difficult. In one case, the acute hepatitis C was severe. The occurrence of acute hepatitis C during pregnancy seems to increase the risk of premature delivery, but not that of vertical transmission. Given the frequency of side effects, it seems preferable not to begin interferon treatment until after delivery.

Extensive portal vein thrombosis related to abdominal trauma.

Abdominal trauma is a classic but very rare cause of portal vein thrombosis. We report the case of a patient with portal vein thrombosis and cavernoma associated with portal hypertension. Anamnesis identified a serious thoraco-abdominal trauma related to a bicycle accident 6 months before. Biological screening identified an inherited heterozygous G20210A factor II gene mutation which supports a recent notion that portal vein thrombosis most often occurs when both local and systemic aetiological factors are combined.

M1190 Natural History of Eosinophilic Gastroenteritis

Background: Collagenous sprue (CS) is a very rare cause of severe malabsorption with an enteropathy that is characterized by villous atrophy and a distinctive band of subepithelial collagen deposition. A poor outcome has been reported historically. Aim: To describe the clinical characteristics, treatment, and prognosis in a contemporary cohort of patients with CS. Methods: We included cases with biopsy-proven CS evaluated at the Mayo Clinic Results: 15 patients (80% females) with a median age of 67 years (range, 53-83) were included. The clinical manifestations were diarrhea (100%), loss of weight (93%), and abdominal pain (14%). Hospitalizationwas required because severe diarrhea in 9 (64%) patients. Hypoalbuminemia and anemia were evident in 9 (64%) and 7 (50%) patients, respectively. Humanleukocyte antigen genes DQ2 or DQ8 were present in 12 (80%) patients (DQ2+ single dose [n=8], DQ2+ double dose [n=3], and DQ2+/DQ8+ [n=1]). Celiac antibodies were present in only 1 patient. A prior diagnosis of celiac disease was evident in 7 (47%) patients. Histologically, all cases had both the abnormal collagen deposition and some degree of villous atrophy. Aberrant (clonal) intraepithelial lymphocytes were detected in 1 (of 12) patients tested by both immunostaining and T-cell clonality analysis. Associated disorders were collagenous gastritis (n=4), collagenous colitis (n=4), small-intestine bacterial overgrowth (n=4), lymphocytic colitis (n=2), lymphocytic gastritis (n=1), autoimmune hepatitis (n=1), and hyposplenism (n=1). All patients received treatment with a combination of a strict gluten-free diet and steroids such as budesonide 9mg/day (n=12), prednisone 30-40 mg/day (n=2) and dexamethasone 8 mg/day (n=1). Parenteral nutrition was necessary in 11 (79%) patients. One patient developed enteropathy-type T-cell lymphoma during followup and received a combination of nitrogen mustard and methylprednisolone. Clinical followup after treatment was available in 12 (92%) patients (median time = 16 months; range, 172), disappearance of diarrhea was observed in 11 with complete histologic remission documented in one case. Three patients died during follow-up because of emaciation, enteropathy-type T-cell lymphoma, and aspiration pneumonia, respectively. Conclusions: We report the largest case series of CS. Treatment with a combination of gluten-free diet and steroids (especially budesonide) was useful to control symptoms in most patients; however, length of follow-up was limited so far to a few months in the majority of our patients. CS was associated with collagen deposition in other organs, autoimmune conditions, and lymphoma.

CO.43 Histoire naturelle de la gastroentérite à éosinophiles

Introduction La gastroenterite a eosinophiles (GEE) est une maladie rare dont l’histoire naturelle est mal connue [1,2]. Le but du travail a ete de rapporter les caracteristiques cliniques et l’evolution a long terme des malades atteints de GEE suivis dans notre centre de 1992 a 2007. Patients et Methodes Dans une etude retrospective sur dossiers, le diagnostic de GEE etait porte sur les criteres habituels [1] apres exclusion des autres causes d’eosinophilie digestive. Les GEE etaient classes en forme muqueuse, musculeuse ou sereuse selon la classification de Klein [2]. Un questionnaire de suivi standardise etait rempli lors d’une consultation ou apres contact avec le medecin traitant et/ou le malade. Resultats Quarante et un malades atteints de GEE ont ete recenses, 27 H et 14 F, d’un âge median de 38 ans (16 - 70) au diagnostic. Des douleurs abdominales, une diarrhee, des nausees et/ou vomissements, une ascite, etaient les symptomes inauguraux les plus frequents : 70, 48, 45 et 39 % des cas respectivement. Les autres symptomes revelateurs etaient plus rarement une dysphagie, une rectorragie et un ictere. Le delai median entre les premiers symptomes et le diagnostic etait de 1,5 ans (0,16 - 27). La GEE etait muqueuse, sereuse et musculeuse dans, 44, 39 et 12 % des cas respectivement. L’atteinte, evaluee par des biopsies digestives etagees, etait le plus souvent duodenale (63 %), ileale (45 %) et colique (66 %) plus rarement œsophagienne (20 %) et gastrique (32 %). Trois malades presentaient une atteinte duodeno-pancreatique se revelant par un tableau de pancreatopathie chronique. Une hyper-eosinophilie sanguine (> 500/mm 3 ) etait presente chez 31 malades (79 %) et une elevation des IgE chez 22 (66 %). Sur 27 malades traites (66 %), plus de la moitie (17) avait recu une corticotherapie (1 mg/kg/j), 4 du chromoglycate et 6 des antihistaminiques. Apres un suivi median de 15 ans (1 - 27) trois profils evolutifs pouvaient etre individualises : 18 malades (44 %), (dont 9 etaient des formes sereuses) presentaient une poussee unique inaugurale sans recidive, 14 (36 %) presentaient des poussees entrecoupees de periodes de remission (formes recurrentes) et 9 (21 %) une forme chronique continue. Trois malades etaient cortico-dependants a une faible dose. Aucune transformation myeloproliferative n’etait observee. Conclusion La GEE se revele par des symptomes digestifs varies en fonction de la forme histologique de la maladie. Elle se caracterise souvent par une evolution benigne sans recidive. Cependant, plus de la moitie des malades presente un profil evolutif plus complexe marque par des recidives imprevisibles, sensibles aux corticoides, et une evolution chronique chez plus d’un malade sur cinq.

Faut-il abandonner les corticoïdes dans le traitement de la maladie de Crohn au profit d’une stratégie « top down » ?

Les corticoides ont ete historiquement les premiers a faire la preuve de leur efficacite dans le traitement des poussees moderees a severes de la maladie de Crohn (MC). En revanche, il a ete clairement etabli qu’ils etaient inefficaces pour le maintien de la remission. En outre, les effets secondaires frequents et potentiellement graves qu’ils induisent limitent considerablement leur emploi, particulierement chez l’enfant. Depuis une dizaine d’annees, les biotherapies, au 1 er rang desquelles figurent les agents anti-tumor necrosis factor (anti-TNF), ont revolutionne la prise en charge des patients atteints de MC refractaire au traitement standard. Ces avancees therapeutiques sont toutefois contrebalancees par un risque d’infections severes d’environ 4 %, et d’un possible surrisque de lymphomes. Certains auteurs ont suggere que les biotherapies ciblees, qui peuvent induire une cicatrisation complete des lesions intestinales, pourraient modifier l’histoire naturelle de la MC si elles etaient prescrites precocement chez les malades, permettant ainsi d’eviter une evolution defavorable. Face a la place grandissante que prennent les biotherapies dans la prise en charge de la MC, la prescription des corticoides a-t-elle encore un avenir ?

Retentissement hépatique de la chirurgie de l’obésité

L’ABSENCE DE PRISE EN COMPTE DE L’HISTOIRE NATURELLE DE L’HÉPATOPATHIE LIÉE À L’OBÉSITÉ ET PRÉEXISTANTE À LA CHIRURGIE : UNE LIMITE COMMUNE AUX ÉTUDES CHIRURGICALES LA DÉRIVATION JÉJUNO-ILÉALE • Une technique chirurgicale historique • Physiopathologie de l’atteinte hépatique après dérivation jéjuno-iléale Pullulation microbienne et anomalies du métabolisme des acides biliaires Malnutrition protéique • Caractérisation de l’atteinte hépatique après dérivation jéjuno-iléale • Traitement des complications hépatiques liées à la dérivation jéjuno-iléale LES NOUVELLES TECHNIQUES MALABSORPTIVES ET COMBINÉES POURRAIENT, À L’INVERSE DE LA DÉRIVATION JÉJUNO-ILÉALE, AVOIR UN EFFET BÉNÉFIQUE SUR LE FOIE UNE AMÉLIORATION DE L’ATTEINTE HÉPATIQUE SERAIT OBSERVÉE APRÈS CHIRURGIE BARIATRIQUE RESTRICTIVE • Atteinte hépatique après gastroplastie verticale calibrée • Atteinte hépatique après anneau gastrique ajustable CONCLUSION CONTENTS