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Small intestinal biopsy interpretation has been the cornerstone for the diagnosis of celiac disease for over 50 years. Despite the existence of sensitive and specific serological tests, duodenal mucosal biopsies continue to be obtained in the vast majority of patients in whom a diagnosis of celiac disease is being considered. The accurate evaluation of these biopsies requires coordination and information sharing between the gastroenterologist, laboratory, and pathologist in order to optimize tissue sampling, preparation and interpretation. This document, a collaboration between the Rodger C. Haggitt Gastrointestinal Pathology Society and the North American Association for the Study of Celiac Disease, is intended to provide clinicians and pathologists with a summary of best practices in the use of endoscopy and biopsy for patients with suspected celiac disease. The authors present a comprehensive and critical appraisal of the literature with respect to the topics of endoscopic findings, best methods for the obtaining biopsies, completing the pathology form and pathologic assessment, including evaluating intraepithelial lymphocytes and villous architecture. A discussion of conditions with overlapping pathologic findings in duodenal mucosal biopsies is presented. In order to provide additional guidance for challenging situations, the authors include an appendix containing practical suggestions. This review may be utilized in interdisciplinary discussions to optimize care for patients with possible celiac disease.

Probiotics are increasingly used for prevention and treatment of diarrhea more in children than in adults. Given the broad spectrum of diarrhea, this review focuses on the main etiologies: acute gastroenteritis, antibiotic-associated diarrhea (AAD), and necrotizing enterocolitis (NEC). For each, we reviewed randomized controlled trials, meta-analyses, and guidelines. For acute gastroenteritis we found 12 guidelines: 5 recommended probiotics and 7 did not. However, the guidelines containing positive recommendations provided proof of evidence from clinical trials and meta-analyses. Lactobacillus rhamnosus GG (LGG) and Saccharomyces boulardii had the most compelling evidence of efficacy as they reduced the duration of the disease by 1 day. For AAD 4 meta-analyses were found, reporting variable efficacy of probiotics in preventing diarrhea, based on the setting, patient's age, and antibiotics. The most effective strains were LGG and S. boulardii. For NEC, we found 3 randomized controlled trials, 5 meta-analyses, and 4 position papers. Probiotics reduced the risk of NEC enterocolitis and mortality in preterm babies. Guidelines did not support a routine use of probiotics and asked for further data for such sensitive implications. In conclusion, there is strong and solid proof of efficacy of probiotics as active treatment of gastroenteritis in addition to rehydration. There is solid evidence that probiotics have some efficacy in prevention of AAD, but the number needed to treat is an issue. For both etiologies LGG and S. boulardii have the strongest evidence. In NEC the indications are more debated, yet on the basis of available data and their implications, probiotics should be carefully considered.

Celiac disease (CD) is regarded as the most common autoimmune enteropathy in western countries. Epidemiological studies indicate that approximately 1:100 individuals may present with histologically proven CD. CD develops in genetically predisposed subjects after gluten ingestion. It usually subsides after gluten is withdrawn from their diet. Gluten is the only known environmental factor that affects the progression/regression of the intestinal villous atrophy, which is the hallmark of this disease. CD generally follows a benign course after gluten elimination. However, it is also associated with the development of other autoimmune disorders or of intestinal malignancies. The issue of whether such complications, sometimes of significant clinical and prognostic impact, are or are not the result of ongoing gluten ingestion, is an important one that has been investigated over the recent years with conflicting results. In terms of practical implications, the presence of a positive correlation between gluten intake and the development of severe complications would lead to the need for early diagnosis and mass screening. The lack of such correlation would instead suggest a less aggressive diagnostic strategy. This review aims at critically summarizing the evidence supporting either hypothesis.

Aim: Our group hypothesized that significant variation exists between suggested clinical guidelines, the clinical practices of practicing gastroenterologists and academic experts in celiac disease (CD)., Method: We designed 4 CD vignettes comparing experts and practicing gastroenterologists. Practicing gastroenterologists (n=169) were surveyed during Digestive Disease Week 2009 and experts (n=22) answered e-mail surveys. Ratings for answers in each vignette was done using a 9-point RAND Appropriateness Scale (RAS) with endorsement defined as RAS score of 7 to 9. We also calculated the RAND "Disagreement Index" (DI) was calculated, with DI>1.0 indicated extreme variation., Results: A total of 169 practicing gastroenterologists and 22 experts were included. Differences in all vignette answers were present. Differences were seen for use of IgA anti-endomysial antibodies (P=0.0241), human leukocyte antigen DQ2/8 testing (P=0.0325), gluten challenge (P<0.0001), and oat consumption (P<0.0001). There were differences in recommendations for biopsy review (P=0.0479) and management of dermatitis herpetiformis (P=0.0025). Experts consistently endorsed CD screening in patients with type 1 diabetes, Down and Turner syndromes, and relatives of CD patients compared with practicing physicians (P=0.0054, 0.0003, <0.0001, 0.0304). Experts endorsed CD screening for atypical presentations (delayed puberty, elevated transaminases, primary biliary cirrhosis, autoimmune hepatitis, and infertility)., Conclusion: There is significant disagreement between nonexperts and experts in diagnosis and management of CD. Promotion of existing guidelines and further research is advised.

This study describes the consensus opinion of the participants of the third Yale Workshop on probiotic use. There were 10 experts participating. The recommendations update those of the first 2 meetings that were published in 2005 and 2008. The workshop presentations and papers in this supplement relate to the involvement of normal microbiota involved in intestinal microecology, how the microbes interact with the intestine to affect our immunologic responses, the stability and natural history of probiotic organisms, and the role of the intestinal microbatome with regard to affecting cardiac risk factors and obesity. Recommendations for the use of probiotics in necrotizing enterocolitis, childhood diarrhea, inflammatory bowel disease, irritable bowel syndrome, and Clostridium difficile diarrhea are reviewed. As in previous publications, the recommendations are given as A, B, or C ratings. The recent positive experiences with bacteriotherapy (fecal microbiome transplant) are also discussed in detail and a positive recommendation is made for use in severe resistant C. difficile diarrhea.

Probiotics have been extensively studied over the past several years in the prevention and, to a larger extent, in the treatment of diarrheal diseases, especially in pediatric populations. Diarrhea is a symptom, and not a disease. This review will not address chronic disorders associated with diarrhea, or Clostridium difficile-induced diarrhea. Rather it will focus on published clinical trials performed on acute-onset, likely infectious diarrhea occurring in the settings of day-care centers, in the community, acquired in the hospital, antibiotic-associated diarrhea, and treatment of acute infectious diarrhea. For prevention of diarrhea acquired in day-care centers, 9 randomized and placebo-controlled trials have been published, conducted in different parts of the world. Probiotics tested were Lactobacillus GG, Bifidobacterium lactis (alone or in combination with Streptococcus thermophilus, and Lactobacillus reuteri, Lactobacillus rhamnosus (not GG), and Lactobacillus acidophilus, in various trials either alone or in comparison with each other. The evidence of their efficacy in these settings is only modest for the prevention of diarrhea, although somewhat better for prevention of upper respiratory infections. In the community, new trails conducted in underprivileged areas of India, again with modest efficacy. Previous trials that examined the potential role of probiotics in preventing the spreading of diarrhea in hospitalized children had yielded conflicting results. More recently, a large trial in Poland showed, however, rather good evidence of efficacy for Lactobacillus GG. The prevention of antibiotic-associated diarrhea has been the subject of many investigations, both in children and in adults. Most commonly used probiotics were Lactobacillus GG, Lactobacillus acidophilus, Lactobacillus casei, Bifidobacterium ssp, Streptococcus ssp, and the yeast Saccharomyces boulardii. In general, most of these trials do show clear evidence of efficacy, with the 2 most effective strains being Lactobacillus GG and S. boulardii. Evidence is also emerging on the importance of the dose in reducing the incidence of this type of diarrhea, and the incidence of Clostridium difficile-associated postantibiotic diarrhea. As for treatment, a large body of data is available, especially in children, on the effect of several strains of probiotics in treating sporadic infectious diarrhea. The vast majority of the published trials show a statistically significant benefit and moderate clinical benefit of a few, well-identified probiotic strains-mostly Lactobacillus GG and S. boulardii-in the treatment of acute watery diarrhea, and particularly those due to rotavirus. Such a beneficial effect results, on average, in a reduction of diarrhea duration of approximately 1 day. The effect is strain-dependent and dose-dependent.

Recommendations for the clinical use of probiotics were published after a Yale University Workshop in 2005. A similar workshop was held in 2007, and the recommendations were updated and extended into other areas. The recommendations are graded into an "A," "B," "C" or no category based on the expert's opinion and review by the workshop participants. An "A" recommendation is made for acute childhood diarrhea, prevention of antibiotic-associated diarrhea, preventing and maintaining remission in pouchitis, and in an immune response for the treatment and prevention of atopic eczema associated with cow's milk allergy. The group maintained several "B" recommendations in other areas of treating inflammatory bowel disease and irritable bowel syndrome. Although there are significant studies in the "B" group, most "B" recommendations did not reach an "A" level because of some negative studies or a limited number of studies. Many reports in the "C" recommendations were significant but fell short of receiving stronger ratings because of the size of reported patient studies, and also the factors that limited categories to the "B" rating.

This review focuses on the efficacy of probiotics for diarrhea in children in different settings: day-care centers, diarrhea acquired in the hospital, antibiotic-associated diarrhea, and treatment of acute infectious diarrhea. For prevention of diarrhea acquired in day-care centers, 5 randomized and placebo-controlled trials have been published. Probiotics tested were Lactobacillus GG, Bifidobacterium lactis (alone or in combination with Streptococcus thermophilus), and Lactobacillus reuteri. The evidence of their efficacy in these settings is only modest: statistically significant for some strains only and in any case of minimal to mild clinical importance. Few trials have examined the potential role of probiotics in preventing the spread of diarrhea in hospitalized children, an event most commonly due to either rotavirus or Clostridium difficile, and they have yielded conflicting results. Overall, these studies provide only weak evidence on the efficacy of probiotics. On the other hand, a large number of trials on the role of probiotics in preventing the onset of antibiotic-associated diarrhea have been published. Most commonly employed probiotics were Lactobacillus GG, Bifidobacterium spp., Streptococcus spp., and the yeast Saccharomyces boulardii. In general, these trials do show clear evidence of efficacy, with the 2 most effective strains being Lactobacillus GG and S. boulardii. Today, we have a large number of published clinical trials on the role of probiotics in treating sporadic infectious diarrhea in children, and many of them are randomized, blinded, and controlled. They consistently show a statistically significant benefit and moderate clinical benefit of a few, well-identified probiotic strains-mostly Lactobacillus GG and S. boulardii, but also L. reuteri-in the treatment of acute watery diarrhea, primarily rotaviral, in infants and young children of developed countries. Such a beneficial effect seems to result in a reduction of diarrhea duration of little more than 1 day, and to be exerted mostly on diarrhea due to rotavirus. The effect is not only strain-dependent, but also dose-dependent, with doses of at least 10 billion/d being necessary.

The use of probiotics in diarrheal diseases of children is increasing. Probiotics, mostly lactic acid bacteria such as Lactobacilli and Bifidobacteria, but also the yeast Saccharomyces boulardii, have been tried in many double-blinded, randomized, placebo-controlled studies, and several well-conducted meta-analyses are now available. There is some evidence of efficacy in the prevention of community-acquired and nosocomial diarrhea. More solid evidence of efficacy is found in the treatment of sporadic, infectious diarrhea, where several probiotics, and especially Lactobacillus GG, have been found capable of reducing by approximately 1 day the duration of diarrhea, shorten the initial phase of watery stools, and reducing hospital stay in developed countries. The effect is best documented in viral diarrheas. Although there are valid conceptual premises for probiotics to be helpful in inflammatory bowel diseases, only 1 trial has been published in children, showing Lactobacillus GG not to be superior to placebo in maintaining remission of Crohn disease. All considered, more research is needed for a better understanding of the role of probiotics in gastrointestinal diseases of children, addressing issues such as pharmacokinetics, mechanism of action, and role of specific probiotics, alone or in combination, in different disorders.

Probiotics are live microbial organisms that are administrated as supplements or in foods to benefit the host. It is the recommendation that they may be helpful in the prevention and treatment of acute diarrhea in adults and children, the prevention of antibiotic-associated diarrhea in adults and children, and the maintenance of remission and prevention of pouchitis. Although early results indicate that probiotics may also be useful in immunologic modulation to prevent atopy, treatment of radiation intestinal disease, vaginosis, ulcerative colitis, and the irritable bowel syndrome, the studies available are not sufficient to say they are definitely helpful. Even fewer data are available to recommend probiotics for the treatment of H pylori and Crohn disease and for the prevention of cardiovascular risk factors or other degenerative diseases. Clearly, larger and better-designed studies of probiotics are necessary, including comparative and dose-ranging trials.