Issue Highlights
2013; Elsevier BV; Volume: 11; Issue: 8 Linguagem: Inglês
10.1016/j.cgh.2013.06.003
ISSN1542-7714
Autores Tópico(s)Clostridium difficile and Clostridium perfringens research
ResumoIn 2013, it seems that the microbiome is involved in everything and that probiotics may cure just about every disease. The intestinal flora has long been suspected to be involved in the pathogenesis of inflammatory bowel disease (IBD). Studies in animal models of IBD have provided robust evidence for the importance of the gut microbial environment in IBD. Serologic markers directed towards several gut microbes have been identified in Crohn's disease. There have been some tantalizing studies that suggest that probiotics may be a therapeutic modality in IBD. Saccharomyces boulardii (S boulardii) has been a focus of considerable interest as a possible therapeutic agent for IBD both in the scientific community and the lay population. It is readily available in several different preparations in most health food stores and over the internet. Two small randomized trials suggested that S boulardii may be beneficial in either treating active Crohn's disease or maintaining remission. However, well designed trials are critically important to help us sort through the hype. S boulardii is a tropical strain of yeast first isolated from lychee and mangosteen fruit in 1923 by French scientist Henri Boulard. Boulard isolated the yeast after he observed natives of Southeast Asia chewing on the skin of these fruits in an attempt to control cholera. It is related to, but distinct from, Saccharomyces cerevisiae in several taxonomic, metabolic, and genetic characteristics. S cervisiae is brewer's yeast and the official state microbe of Oregon. From a medical perspective, however, its importance is linked to IBD, because of the identification of specific antibodies directed against it in Crohn's disease. In this issue of Clinical Gastroenterology and Hepatology, Bourreille et al report the results of a large, 52-week, well-designed randomized, double-blind placebo-controlled trial to evaluate the effect of S boulardii in maintenance of remission in mild-moderate Crohn's disease. The study enlisted 196 patients (32 centers) and took almost 6 years to complete, an indication of the challenges in recruiting an adequate number of patients for the trial. An accompanying editorial by Drs Quezeda and Cross discusses the study. Eligible patients were recruited during an acute phase of Crohn's disease (Harvey–Bradshaw index >4) and treated with corticosteroids, budesonide or aminosalicylates for active disease. Once in remission, they were randomized to treatment with either 1 gm oral S boulardii or placebo and followed for 52 weeks or until relapse. The primary efficacy end point was the number of patients who relapsed. Secondary end points included time to relapse, the percentage of relapses during withdrawal of induction therapy, and the changes in laboratory parameters of inflammation. The S boulardii and placebo groups were similar except there was a statistically greater number of patients in the placebo group who had Crohn's restricted to the small bowel. There was no significant difference in the number of relapsers in the S boulardii group (47.5%) and the placebo group (53.2%). The time to relapse was not statistically different. There were no major differences in adverse events. In subgroup analysis, always a risky exercise, some differences emerged. Smokers in the S boulardii group were less likely to relapse than nonsmokers. The presence of extraintestinal manifestations was also a predictor of relapse. In summary, this well designed study failed to demonstrate a significant benefit of S boulardii in maintenance of remission in mild to moderate Crohn's disease. Similarly, several meta-analyses failed to demonstrate a beneficial effect of probiotics in maintenance of remission in Crohn's disease. Therefore, there is no evidence to justify the use of probiotics in this clinical setting. Whether it is a true failure of probiotics or a matter of finding the right dose, right cocktail, or right subset of patients remains to be determined. See page 982. Pancreatic intraductal papillary mucinous neoplasms (IPMNs) are intraductal mucin producing neoplasms that cause cystic dilation of the pancreatic duct, and are classified into main duct and branch duct subtypes. There appears to be a progressive transformation in IPMN from adenoma to borderline neoplasms to carcinoma. The diagnosis of IPMNs is increasing, most likely related to the frequent use of abdominal imaging. In this issue of Clinical Gastroenterology and Hepatology, Anand et al perform a meta-analysis to determine which factors based on the consensus meeting of the International Association of Pancreatology published guidelines (Sendai 2006 criteria) are associated with a higher risk of malignancy in IPMNs. Search criteria for the meta-analysis included the following: articles in English; full manuscript publications between 1996–2011; a study design that was either prospective or retrospective cohort or a case series; adequate preoperative imaging; histological characterization of the IPMNs or long-term follow up; and, finally sufficient data to determine an odds ratio for malignancy for at least one of the Sendai criteria. A total of 41 articles met these criteria. They included 5788 patients and 3304 branch duct IPMNs. Not all articles could be analyzed for all criteria. Separate meta-analysis was performed for each risk factor of the Sendai criteria: cyst size, mural nodules, main vs branch duct IPMN, and symptoms. Cyst size greater than 3 cm was found to carry the greatest increase in the risk of malignancy (OR, 62.4; 95% CI, 30.8–126.3). Mural nodules within the cyst were also a strong risk factor for malignancy (OR, 9.3; 95% CI 5.3–16.1). Pancreatic duct dilation also had a significant increased risk (OR, 7.27; 95% CI, 3.0–17.4). Main duct IPMN was associated with significantly increased risk of malignancy compared to side branch lesions (OR, 4.7; 95% CI, 3.3–6.9). Not surprisingly, the weakest association was between patient symptoms and malignancy (OR, 1.6; 95% CI, 1.0–2.6). The authors acknowledge several limitations to this study. There may have been some selection bias because the majority of data were from surgical case series. There were limitations in their ability to extract data to determine specific cyst features in some articles. Several studies were excluded based on cyst size thresholds different than the Sendai criteria. The Sendai criteria were recently updated to include worrisome features (cysts greater than 3 cm, thickened enhanced cyst wall, nonenhanced mural nodules, MPD of 5–9 mm, or an abrupt change in MPD caliber with distal pancreatic atrophy) and high-risk stigmata (MPD >10 mm and enhanced solid component). Therefore, it will be important for future studies to prospectively record data according to the above criteria and to examine if these revised criteria allow for a more refined risk assessment. See page 913. Saccharomyces boulardii Does Not Prevent Relapse of Crohn's DiseaseClinical Gastroenterology and HepatologyVol. 11Issue 8PreviewSaccharomyces boulardii is a probiotic yeast that has been shown to have beneficial effects on the intestinal epithelial barrier and digestive immune system. There is preliminary evidence that S boulardii could be used to treat patients with Crohn's disease (CD). We performed a randomized, placebo-controlled trial to evaluate the effects of S boulardii in patients with CD who underwent remission during therapy with steroids or aminosalicylates. Full-Text PDF Cyst Features and Risk of Malignancy in Intraductal Papillary Mucinous Neoplasms of the Pancreas: A Meta-AnalysisClinical Gastroenterology and HepatologyVol. 11Issue 8PreviewInternational guidelines for the management of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas recommend surgical resection of those with specific characteristics. We performed a meta-analysis to evaluate the risk of malignancy associated with each of these features of IPMNs. Full-Text PDF
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