Maintenance of remission in Crohn's disease.

When remission of Crohn's disease is achieved, the next goal is to maintain long-term remission. Aminosalicylates may be recommended for maintenance remission, even though the results are less consistent than those observed in ulcerative colitis. The benefit is mainly observed in the post-surgical setting and in patients with ileitis, and with a prolonged disease duration. Corticosteroids are not effective in maintaining remission and should not be used for this indication. Azathioprine and 6-mercaptopurine are effective in maintaining remission. Maintenance benefits remain significant for patients who continued with the therapy for up to 5 years. Methotrexate has also been found to be effective in maintaining remission in Crohn's disease in patients who have responded acutely to methotrexate. Cyclosporine has not been found to be an effective maintenance agent. Mycophenolate mofetil could be considered a therapy in patients who are either allergic to azathioprine or in whom azathioprine failed to induce remission. The use of infliximab may change the future approach to maintenance therapy for Crohn's disease. Patients who responded clinically to infliximab have maintained their clinical response when receiving repeat infusions at 8-week intervals. In patients refractory to other therapies, infliximab may be effective in maintaining remission.

Calprotectine fécale: outil diagnostique dans les maladies inflammatoires chroniques de l'intestin [Fecal calprotectin: a diagnostic tool for inflammatory bowel disease].

Fecal calprotectin (FC) is a valid biomarker to discriminate with a good sensitivity and specificity the presence of mucosal lesions of the gastrointestinal tube (e.g. ulcers in the context of inflammatory bowel disease (IBD)) from functional disorders (e.g. irritable bowel syndrome). FC is not specific for IBD and can be elevated also in gastrointestinal infections, ischemic colitis or neoplasia. An elevated FC should stimulate further investigations, notably an endoscopic workup. The level of FC correlates with the endoscopic score in Crohn's disease and ulcerative colitis. The correlation of FC and the endoscopic severity is better than the one of CRP or blood leukocytes. Thus, FC can also be used in the follow-up of IBD patients.

Upper gastrointestinal bleeding in cirrhosis: clinical and endoscopic correlations

The clinical data of 180 episodes of upper gastrointestinal bleeding in 168 patients with cirrhosis of the liver are examined. The source of bleeding had been determined by early endoscopy in all cases. In men under the age of 50 years, and without symptoms of liver failure, bleeding was due to ruptured gastro-oesophageal varices in 84% of cases. Severe liver failure was associated with acute lesions of gastric mucosa in many cases. No presumptive diagnosis of the source of haemorrhage could be based on the examination of other clinical data (presence of ascites, mode of presentation and pattern of bleeding, history of ulcer disease, alcoholism, and previous medication.

Upper gastrointestinal bleeding in cirrhosis: clinical and endoscopic correlations

The clinical data of 180 episodes of upper gastrointestinal bleeding in 168 patients with cirrhosis of the liver are examined. The source of bleeding had been determined by early endoscopy in all cases. In men under the age of 50 years, and without symptoms of liver failure, bleeding was due to ruptured gastro-oesophageal varices in 84% of cases. Severe liver failure was associated with acute lesions of gastric mucosa in many cases. No presumptive diagnosis of the source of haemorrhage could be based on the examination of other clinical data (presence of ascites, mode of presentation and pattern of bleeding, history of ulcer disease, alcoholism, and previous medication.

Nilotinib in the treatment of advanced gastrointestinal stromal tumours resistant to both imatinib and sunitinib.

Patients diagnosed with advanced gastrointestinal stromal tumours (GISTs) who are resistant or intolerant to both imatinib and second-line sunitinib have a poor prognosis and few therapeutic options. We evaluated the efficacy of nilotinib, a novel tyrosine kinase inhibitor (TKI) in patients pretreated with imatinib and sunitinib. Fifty-two consecutive patients treated with oral nilotinib, 400mg twice daily, within the nilotinib compassionate use programme in 12 European cancer centres, were included in this retrospective analysis. Median age was 59 years (range 24-80), and all patients had WHO performance score better than 3. All patients had failed both imatinib and sunitinib pretreatment, either due to progressing GIST (96%) or intolerance (4%). Five patients (10%; 95% confidence interval (CI) 2-18) responded to nilotinib and 19 patients (37%; 95% CI 24-50) achieved a disease stabilisation. Nilotinib was generally well tolerated, but six patients (12%) discontinued treatment due to intolerance. Median progression-free survival of nilotinib treatment was 12 weeks (95% CI 9-15; range 0-104) and median overall survival was 34 weeks (95% CI 3-65; range 2-135). Nilotinib is active in GIST resistant to both imatinib and sunitinib. These results warrant further investigation of nilotinib in GIST.

Sorafenib as third- or fourth-line treatment of advanced gastrointestinal stromal tumour and pretreatment including both imatinib and sunitinib, and nilotinib: A retrospective analysis.

BACKGROUND: Tyrosine kinase inhibitors (TKI) improve the outcome of patients with advanced gastrointestinal stromal tumour (GIST), but treatment failure is frequent, and prognosis then bleak. Smaller trials in this setting suggested activity for sorafenib, a multikinase inhibitor of receptor tyrosine kinases and RAF serine/threonine kinases. PATIENTS AND METHODS: We retrospectively evaluated the efficacy of sorafenib, starting dose 400mg twice daily, in a large community-based cohort of 124 patients treated in 12 European and one United States (U.S.) cancer centre. All but one patient had a WHO performance score 0-2. All had failed both imatinib and sunitinib, 68 patients nilotinib and 26 had failed investigational therapy, too. RESULTS: Twelve (10%) patients responded to sorafenib and 70 (57%) patients achieved disease stabilisation. Sorafenib was moderately tolerated, and toxicity reported in 56% of the patients. Rash, hand-foot-syndrome and diarrhea occurred frequently. Sorafenib dosage was reduced in a third of patients, but this did not have an impact on progression-free survival (PFS) (p=0.15). Median PFS was 6.4months (95% confidence interval [CI], 4.6-8.0months) and median overall survival (OS) 13.5months (95% CI, 10.0-21.0months). Patients with a good performance status and those who responded to sorafenib had a significant better PFS. CONCLUSION: We conclude that sorafenib is active in GIST resistant to imatinib, sunitinib and nilotinib. These results warrant further investigation of sorafenib or similar molecules in GIST.

Place de l'aspirine en prévention primaire des maladies cardiovasculaires [The role of aspirin in the primary prevention of cardiovascular disease]

For persons without cardiovascular disease, the benefit of aspirin in primary prevention has been controversial until the recent publication of several major randomized controlled trials. Since then, several medical societies recommend that clinicians discuss aspirin prevention with adults at high cardiovascular risk. Patients with low cardiovascular risk are unlikely to benefit from aspirin, as potential harms (hemorrhagic strokes, gastrointestinal bleedings) may outweigh benefits. Aspirin should be recommended in primary prevention only in patients with a 10-year cardiovascular risk > or = 10% or in diabetic patients aged > or = 40 years with a concomitant cardiovascular risk factor, after assessing contraindications for aspirin and individual's preferences for the risks and benefits associated with aspirin.

Early prediction of response to sunitinib after imatinib failure by 18F-fluorodeoxyglucose positron emission tomography in patients with gastrointestinal stromal tumor.

PURPOSE: Positron emission tomography with (18)F-fluorodeoxyglucose (FDG-PET) was used to evaluate treatment response in patients with gastrointestinal stromal tumors (GIST) after administration of sunitinib, a multitargeted tyrosine kinase inhibitor, after imatinib failure. PATIENTS AND METHODS: Tumor metabolism was assessed with FDG-PET before and after the first 4 weeks of sunitinib therapy in 23 patients who received one to 12 cycles of sunitinib therapy (4 weeks of 50 mg/d, 2 weeks off). Treatment response was expressed as the percent change in maximal standardized uptake values (SUV). The primary end point of time to tumor progression was compared with early PET results on the basis of traditional Response Evaluation Criteria in Solid Tumors (RECIST) criteria. RESULTS: Progression-free survival (PFS) was correlated with early FDG-PET metabolic response (P < .0001). Using -25% and +25% thresholds for SUV variations from baseline, early FDG-PET response was stratified in metabolic partial response, metabolically stable disease, or metabolically progressive disease; median PFS rates were 29, 16, and 4 weeks, respectively. Similarly, when a single FDG-PET positive/negative was considered after 4 weeks of sunitinib, the median PFS was 29 weeks for SUVs less than 8 g/mL versus 4 weeks for SUVs of 8 g/mL or greater (P < .0001). None of the patients with metabolically progressive disease subsequently responded according to RECIST criteria. Multivariate analysis showed shorter PFS in patients who had higher residual SUVs (P < .0001), primary resistance to imatinib (P = .024), or nongastric GIST (P = .002), regardless of the mutational status of the KIT and PDGFRA genes. CONCLUSION: Week 4 FDG-PET is useful for early assessment of treatment response and for the prediction of clinical outcome. Thus, it offers opportunities to individualize and optimize patient therapy.

Hémorragie par le canal de Wirsung: forme rare d'hémorragie digestive haute. A propos d'une observation [Hemorrhage through Wirsung's duct: rare form of upper gastrointestinal hemorrhage. A case report].

The case of a 41-year-old alcoholic patient who presented with massive upper gastrointestinal bleeding is reported. The diagnosis was established rapidly by endoscopy which revealed bleeding through the papilla of Vater. Selective angiography of the superior mesenteric artery opacified the pancreatic duct as well as the duodenum. CT scan showed signs of chronic pancreatitis. Because of the recurrence of bleeding and shock, an urgent operation was necessary and a Whipple procedure was performed. Recovery was complete. The clinical presentation, the etiology, the diagnostic modalities and the treatment of this particular condition are discussed. Usually, hemorrhage through the pancreatic duct presents as repeated episodes of upper gastrointestinal bleeding with no source found at endoscopy. The presence of chronic pancreatitis or of epigastric pain during bleeding should suggest the diagnosis. Upper gastrointestinal endoscopy and angiography are the principal diagnostic tools. Definitive treatment requires surgery, and resection in most of the cases.

Health management practices and disease prevalence in dairy sheep systems in Argentina

A cross-sectional survey of 19 dairy sheep farms in Argentina was carried out with the purpose to know farm management, health practices, and occurrence and mortality of diseases. The survey comprised 40% of all sheep milking farms in Argentina. A questionnaire was conducted by way of personal interviews with sheep owners during farm visits. The proportions of farms reporting routine vaccination for clostridial diseases, contagious ecthyma, pneumonia and mineral and vitamin parenteral administration were 63%, 47.3%, 16.6% and 42.1% respectively. Regular treatment against lice was used in 37.5% of the farms, and 89.5% o the farmers treated against gastrointestinal nematodes (GIN). The mean number of GIN drenches per farm was 2.26±1.78 annually. In 68.4% of the milking flocks the California Mastitis Test was regularly done and 55.6% of the farmer managers had sampled their flocks once a year for Brucella ovis antibodies. During the pre-mating period respectively 68.4% and 50% of farmers clinically examined their rams and ewe for general health and teeth condition. The udders of ewes were frequently inspected at the start of each milking period. The most important parasite problems noticed were GIN (reported by 57.9% of farmers), lice (57.9%) and scabies (10.5%) and the most frequent infectious diseases were ecthyma (73.7%), pneumonia and other respiratory problems (57.9%), clinical mastitis (55.6%), clostridial diseases (36.9%) and foot lameness (35.2%). Photosensitivity (47.4%) and ruminal acidosis (42.1%) were reported as other frequent toxic or metabolic disorders. Owners mentioned that the mean lifespan or milk productive time per ewe was 4.5±1.4 years. Perinatal lamb mortality was 8.5% and the total flock mortality rates, above the first 24 h of life was 6.9%. The high rates of lamb mortality during the pre-weaning (10.3%) and post-weaning (5.9%) periods indicate that this problem, as well as the most prevalent diseases, should be the subject of further studies.

Prevalence of celiac disease in Brazilian children of short stature

The aim of the present study was to determine the prevalence of celiac disease in children of short stature and to assess whether some of the routine laboratory examinations performed to determine the cause of short stature could suggest the presence of celiac disease. A total of 106 children of short stature and no gastrointestinal symptoms were studied. An extensive endocrine work-up had been negative for all of them and an additional investigation was performed by measuring the concentration of antiendomysial antibody. Patients who were positive for antiendomysial antibody ( > or = 1:10) or who exhibited IgA deficiency (less than 5 mg/dl) were referred for an endoscopic intestinal biopsy. We detected a pathological titer of antiendomysial IgA in six of these patients. Five of them showed histological abnormalities compatible with celiac disease and one had normal histology and was considered to have potential celiac disease. The prevalence of celiac disease in the population studied was 4.7% (with another 0.9% of the subjects being considered to have potential celiac disease). The children with celiac disease did not differ in any of the parameters tested when compared to those without celiac disease, though they showed an improvement in growth velocity after treatment with a gluten-free diet. We conclude that it is important to test all children with short stature for celiac disease by measuring antiendomysial IgA.

Anti-tumor necrosis factor-a for the treatment of steroid-refractory acute graft-versus-host disease

Allogeneic stem cell transplantation has been increasingly performed for a variety of hematologic diseases. Clinically significant acute graft-versus-host disease (GVHD) occurs in 9 to 50% of patients who receive allogeneic grafts, resulting in high morbidity and mortality. There is no standard therapy for patients with acute GVHD who do not respond to steroids. Studies have shown a possible benefit of anti-TNF-a (infliximab)for the treatment of acute GVHD. We report here on the outcomes of 10 recipients of related or unrelated stem cell transplants who received 10 mg/kg infliximab, iv, once weekly for a median of 3.5 doses (range: 1-6) for the treatment of severe acute GVHD and who were not responsive to standard therapy. All patients had acute GVHD grades II to IV (II = 2, III = 3, IV = 5). Overall, 9 patients responded and 1 patient had progressive disease. Among the responders, 3 had complete responses and 6 partial responses. All patients with cutaneous or gastrointestinal involvement responded, while only 2 of 6 patients with liver disease showed any response. None of the 10 patients had any kind of immediate toxicity. Four patients died, all of them with sepsis. Six patients are still alive after a median follow-up time of 544 days (92-600) after transplantation. Considering the severity of the cases and the bad prognosis associated with advanced acute GVHD, we find our results encouraging. Anti-TNF-a seems to be a useful agent for the treatment of acute GVHD.

Gut permeability to lactulose and mannitol differs in treated Crohn's disease and celiac disease patients and healthy subjects

The gut barrier monitors and protects the gastrointestinal tract from challenges such as microorganisms, toxins and proteins that could act as antigens. There is evidence that gut barrier dysfunction may act as a primary disease mechanism in intestinal disorders. The aim of the present study was to evaluate the barrier function towards sugars after the appropriate treatment of celiac disease and Crohn's disease patients and compare the results with those obtained with healthy subjects. Fifteen healthy volunteers, 22 celiac disease patients after 1 year of a gluten-free diet, and 31 Crohn's disease patients in remission were submitted to an intestinal permeability test with 6.0 g lactulose and 3.0 g mannitol. Six-hour urinary lactulose excretion in Crohn's disease patients was significantly higher than in both celiac disease patients (0.42 vs 0.15%) and healthy controls (0.42 vs 0.07%). Urinary lactulose excretion was significantly higher in celiac disease patients than in healthy controls (0.15 vs 0.07%). Urinary mannitol excretion in Crohn's disease patients was the same as healthy controls (21 vs 21%) and these values were significantly higher than in celiac disease patients (10.9%). The lactulose/mannitol ratio was significantly higher in Crohn's disease patients in comparison to celiac disease patients (0.021 vs 0.013) and healthy controls (0.021 vs 0.003) and this ratio was also significantly higher in celiac disease patients compared to healthy controls (0.013 vs 0.003). In spite of treatment, differences in sugar permeability were observed in both disease groups. These differences in the behavior of the sugar probes probably reflect different mechanisms for the alterations of intestinal permeability.

Genes involved in the metabolism of fatty acids and risk for Crohn's disease in children: a candidate gene study

Contexte - La prévalence de la maladie de Crohn (MC), une maladie inflammatoire chronique du tube digestif, chez les enfants canadiens se situe parmi les plus élevées au monde. Les interactions entre les réponses immunes innées et acquises aux microbes de l'hôte pourraient être à la base de la transition de l’inflammation physiologique à une inflammation pathologique. Le leucotriène B4 (LTB4) est un modulateur clé de l'inflammation et a été associé à la MC. Nous avons postulé que les principaux gènes impliqués dans la voie métabolique du LTB4 pourrait conférer une susceptibilité accrue à l'apparition précoce de la MC. Dans cette étude, nous avons exploré les associations potentielles entre les variantes de l'ADN des gènes ALOX5 et CYP4F2 et la survenue précoce de la MC. Nous avons également examiné si les gènes sélectionnés montraient des effets parent-d'origine, influençaient les phénotypes cliniques de la MC et s'il existait des interactions gène-gène qui modifieraient la susceptibilité à développer la MC chez l’enfant. Méthodes – Dans le cadre d’une étude de cas-parents et de cas-témoins, des cas confirmés, leurs parents et des contrôles ont été recrutés à partir de trois cliniques de gastro-entérologie à travers le Canada. Les associations entre les polymorphismes de remplacement d'un nucléotide simple (SNP) dans les gènes CYP4F2 et ALOX5 ont été examinées. Les associations allélique et génotypiques ont été examinées à partir d’une analyse du génotype conditionnel à la parenté (CPG) pour le résultats cas-parents et à l’aide de table de contingence et de régression logistique pour les données de cas-contrôles. Les interactions gène-gène ont été explorées à l'aide de méthodes de réduction multi-factorielles de dimensionnalité (MDR). Résultats – L’étude de cas-parents a été menée sur 160 trios. L’analyse CPG pour 14 tag-SNP (10 dans la CYP4F2 et 4 dans le gène ALOX5) a révélé la présence d’associations alléliques ou génotypique significatives entre 3 tag-SNP dans le gène CYP4F2 (rs1272, p = 0,04, rs3093158, p = 0.00003, et rs3093145, p = 0,02). Aucune association avec les SNPs de ALOX5 n’a pu être démontrée. L’analyse de l’haplotype de CYP4F2 a montré d'importantes associations avec la MC (test omnibus p = 0,035). Deux haplotypes (GAGTTCGTAA, p = 0,05; GGCCTCGTCG, p = 0,001) montraient des signes d'association avec la MC. Aucun effet parent-d'origine n’a été observé. Les tentatives de réplication pour trois SNPs du gene CYP4F2 dans l'étude cas-témoins comportant 225 cas de MC et 330 contrôles suggèrent l’association dans un de ceux-ci (rs3093158, valeur non-corrigée de p du test unilatéral = 0,03 ; valeur corrigée de p = 0.09). La combinaison des ces deux études a révélé des interactions significatives entre les gènes CYP4F2, ALOX et NOD2. Nous n’avons pu mettre en évidence aucune interaction gène-sexe, de même qu’aucun gène associé aux phénotypes cliniques de la MC n’a pu être identifié. Conclusions - Notre étude suggère que la CYP4F2, un membre clé de la voie métabolique LTB4 est un gène candidat potentiel pour MC. Nous avons également pu mettre en évidence que les interactions entre les gènes de l'immunité adaptative (CYP4F2 et ALOX5) et les gènes de l'immunité innée (NOD2) modifient les risques de MC chez les enfants. D'autres études sur des cohortes plus importantes sont nécessaires pour confirmer ces conclusions.