Interobserver reliability of methods to determine complete resection of adenomas in colonoscopy.

BACKGROUND: Forceps margin biopsy and polypectomy specimen margins have both been used to assess for polypectomy resection adequacy. The interobserver reliability of the two methods has not been well described. METHODS: The interpretability of polypectomy specimens for presence of residual neoplasia at the margin was assessed by two blinded pathologists. Next, the concordance of forceps margin biopsy interpretations between three blinded pathologists was evaluated by calculation of interobserver κ. RESULTS: Rates of polypectomy specimen margin interpretability were low: 24/92 (26 %) for pathologist A, 28/92 (30.4 %) for pathologist B. Concordance of forceps margin biopsy interpretations (n = 129) between pathologists was high. Two internal pathologists showed substantial agreement in margin biopsy interpretations (κ 0.779; 95 %CL 0.543, 0.912). The concordance remained strong after biopsies were reviewed by a third, external pathologist (κ 0.829; 95 %CL 0.658, 0.924). There was complete agreement on 123/129 (95.3 %) between all three pathologists for presence of neoplasia. CONCLUSION: The majority of polypectomy specimen margins were uninterpretable by pathologists for presence of residual neoplasia. Forceps margin biopsy shows strong interobserver reliability in adenomatous lesions.

In vitro evaluation of intestinal epithelial TLR activation in preventing food allergic responses.

Alterations in the gut microbiota composition are associated with food allergy. Toll-like receptors (TLRs) respond to microbial stimuli. We studied the effects of the ligation of TLRs on intestinal epithelial cells (IECs) in preventing an allergic effector response. IEC monolayers (T84 cells) were co-cultured with CD3/28-activated PBMCs from healthy controls or atopic patients and simultaneously apically exposed to TLR2, TLR4 or TLR9 ligands. The barrier integrity of T84 cell monolayers was significantly reduced upon co-culture with PBMCs of food allergic subjects compared to healthy subjects. Apical exposure of IECs to a TLR9 ligand prevented PBMC-induced epithelial barrier disruption. Using PBMCs from food allergic subjects, apical TLR9 activation on IECs increased the IFN-γ/IL-13 and IL-10/IL-13 ratio, while suppressing pro-inflammatory IL-6, IL-8 and TNF-α production in an IEC-dependent manner. Hence, the activation of apical TLR9 on IECs, potentially by microbiota-derived signals, may play an important role in the prevention of allergic inflammation.

An Unusual Case of Black Esophagus.

Patients with acute esophageal necrosis often present with hematemesis and upper gastrointestinal bleeding. Our case report describes a patient's incidental discovery of black esophagus without recent hemodynamic instability, symptoms, or evidence of blood loss anemia. As illustrated in this case, it is important to recognize these findings in patients without classic signs and symptoms to act promptly and prevent tissue ischemia or perforation. Early recognition can also help reduce the risk of long-term complications such as stricture formation. Thus, a high index of suspicion is essential for the diagnosis of acute esophageal necrosis.

Multicenter approach to recurrent acute and chronic pancreatitis in the United States: the North American Pancreatitis Study 2 (NAPS2).

BACKGROUND: Recurrent acute pancreatitis (RAP) and chronic pancreatitis (CP) are complex syndromes associated with numerous etiologies, clinical variables and complications. We developed the North American Pancreatitis Study 2 (NAPS2) to be sufficiently powered to understand the complex environmental, metabolic and genetic mechanisms underlying RAP and CP. METHODS: Between August 2000 and September 2006, a consortium of 20 expert academic and private sites prospectively ascertained 1,000 human subjects with RAP or CP, plus 695 controls (spouse, family, friend or unrelated). Standardized questionnaires were completed by both the physicians and study subjects and blood was drawn for genomic DNA and biomarker studies. All data were double-entered into a database and systematically reviewed to minimize errors and include missing data. RESULTS: A total of 1,000 subjects (460 RAP, 540 CP) and 695 controls who completed consent forms and questionnaires and donated blood samples comprised the final dataset. Data were organized according to diagnosis, supporting documentation, etiological classification, clinical signs and symptoms (including pain patterns and duration, and quality of life), past medical history, family history, environmental exposures (including alcohol and tobacco use), medication use and therapeutic interventions. Upon achieving the target enrollment, data were organized and classified to facilitate future analysis. The approaches, rationale and datasets are described, along with final demographic results. CONCLUSION: The NAPS2 consortium has successfully completed a prospective ascertainment of 1,000 subjects with RAP and CP from the USA. These data will be useful in elucidating the environmental, metabolic and genetic conditions, and to investigate the complex interactions that underlie RAP and CP.

Influence of dietary fiber on inflammatory bowel disease and colon cancer: importance of fermentation pattern.

The benefits of dietary fiber on inflammatory bowel disease may be related to the fermentative production of butyrate in the colon, which appears to decrease the inflammatory response. The benefits of dietary fiber against colon cancer may be related to both fermentative and non-fermentative processes, although poorly fermentable fibers appear more influential. Dietary fiber fermentation profiles are important in determining optimal fibers for colonic health, and may be a function of structure, processing conditions, and other food components. A greater understanding of the relationships between fermentation rate and dietary fiber structure would allow for development of dietary fibers for optimum colonic health.

The Effects of Bowel Preparation on Microbiota-Related Metrics Differ in Health and in Inflammatory Bowel Disease and for the Mucosal and Luminal Microbiota Compartments.

OBJECTIVES: Bowel preparations (BPs) taken before colonoscopy may introduce a confounding effect on the results of gastrointestinal microbiota studies. This study aimed to determine the effect of bowel preparation on the mucosa-associated and luminal colonic microbiota in healthy subjects (HC) and inflammatory bowel disease (IBD) patients. METHODS: Biopsy samples (n=36) and fecal samples (n=30) were collected from 10 HC and 8 IBD subjects pre- and post-BP. 16S rRNA gene was pyrosequenced using 454 Titanium protocols. We compared the differences between the pre- and post-BP samples (i.e., comparisons-across-bowel-prep); we examined the effect of BP on the expected separation of the mucosal vs. the luminal compartments (i.e., comparisons-across-compartments). Last, we compared the baseline differences between the HC vs. IBD groups (a secondary analysis), and examined whether the differences between the HC vs. IBD changed after BP. RESULTS: In comparisons-across-bowel-prep, the Shannon's index (SI) decreased only in the biopsy samples of IBD subjects post-BP (P=0.025) and phylogenetic diversity-whole tree (PD-WT) metric decreased in biopsy samples of HC subjects post-BP (P=0.021). In secondary comparisons, the subtle differences between the fecal samples of the HC vs. IBD groups, in terms of evenness and the SI, were not apparent post-BP. In terms of ß-diversity, in comparisons-across-bowel-prep, the proportion of shared operational taxonomic units (OTUs) in pre- and post-BP samples was low (~30%) and unweighted Unifrac distances between pre- and post-BP specimens ranged from 0.52 to 0.66. HC biopsies were affected more than IBD biopsies with BP (P=0.004). In comparisons-across-compartments, the proportion of shared OTUs between biopsy and fecal samples increased and Unifrac distances decreased post-BP in IBD subjects, reducing the differences between the mucosal and luminal compartments of the gut microbiota. Interindividual differences in Unifrac distances were preserved even with BP effects, although the effects were greater on weighted Unifrac distances. Bacteroidetes and its subtypes increased post-BP in both the luminal and mucosal compartments. CONCLUSIONS: Bowel preparations affect the composition and diversity of the fecal and luminal microbiota in the short term, introducing potential bias into experiments examining the gut microbiota. The magnitude of the effect of BP is not greater than that of interindividual variation. Both the luminal and mucosal compartments of the gut microbiota get affected, and samples from controls and IBD subjects may get affected differently. Studies of the colonic microbiota should take into account the direction and the magnitude of the change introduced by BP during the design stage of the experiments, and consider sample sizes so that potential bias is minimized.

Physiology of the aerodigestive system and aberrations in that system resulting in aspiration.

BACKGROUND: Aspiration pneumonia remains a significant and often devastating problem in critically ill patients. It is unclear whether aspiration pneumonia occurs because of problems in the handling of oropharyngeal secretions or if the reflux of gastric contents is the major etiological factor. Additionally, the obvious breakdown of upper aerodigestive protective mechanisms in the critically ill patient population is largely unstudied. Finally, the impact and contribution of tubes, both endotracheal and nasoenteral, on aspiration pneumonia is unclear. METHODS: A Medline literature search on scientific and review articles concerning the normal physiology of the aerodigestive tract and factors that compromised normal physiology was undertaken. Readings were supplemented by expert outside opinion from researchers in these fields and from the combined expertise from a multidisciplinary panel of experts assembled at a recent summit on aspiration pneumonia. RESULTS: Changes in the normal physiology of the aerodigestive tract are vast and varied and dependent on the response to injury, iatrogenic interventions, and the use of nasoenteral and endotracheal tubes. The effects on gastric and esophageal motility are likely dynamic and represent an ongoing but changing risk of reflux for the patient. Nasoenteral and endotracheal tubes likely compromise upper aerodigestive protective mechanisms. CONCLUSIONS: More research is needed on the functioning of the aerodigestive protective mechanisms in critically ill patients. Understanding of the dynamic changes in gastrointestinal motility will also be an important factor to decrease the incidence of aspiration pneumonia in this patient population.

North American Summit on Aspiration in the Critically Ill Patient: consensus statement.

Aspiration is the leading cause of pneumonia in the intensive care unit and the most serious complication of enteral tube feeding (ETF). Although aspiration is common, the clinical consequences are variable because of differences in nature of the aspirated material and individual host responses. A number of defense mechanisms normally present in the upper aerodigestive system that protect against aspiration become compromised by clinical events that occur frequently in the critical care setting, subjecting the patient to increased risk. The true incidence of aspiration has been difficult to determine in the past because of vague definitions, poor assessment monitors, and varying levels of clinical recognition. Standardization of terminology is an important step in helping to define the problem, design appropriate research studies, and develop strategies to reduce risk. Traditional clinical monitors of glucose oxidase strips and blue food coloring (BFC) should no longer be used. A modified approach to use of gastric residual volumes and identification of clinical factors that predispose to aspiration allow for risk stratification and an algorhythm approach to the management of the critically ill patient on ETF. Although the patient with confirmed aspiration should be monitored for clinical consequences and receive supportive pulmonary care, ETF may be continued when accompanied by appropriate steps to reduce risk of further aspiration. Management strategies for treating aspiration pneumonia are based on degree of diagnostic certainty, time of onset, and host factors.

Hepatitis B vaccination in patients with inflammatory bowel disease.

AIM: To determine the prevalence for hepatitis B virus (HBV) and HBV screening and vaccination practices for inflammatory bowel disease (IBD). METHODS: This study is a retrospective, cross-sectional observational study. A retrospective chart review was performed in 500 patients who have been consecutively treated for IBD between September 2008 and January 2013 at the Rush University Medical Center Gastroenterology section. The patients were identified through the electronic medical record with the criteria that they attended the gastroenterology clinic, and that they had a diagnosis of IBD at the time of visit discharge. Once identified, each record was analyzed to determine whether the subject had been infected with HBV in the past, already been vaccinated against HBV, or advised to get vaccinated and followed through with the recommended vaccination. RESULTS: About 254 out of 500 patients (51%) had HBV screening ordered. Among those ordered to have screening tests, 86% followed through with HBV serology. Gastroenterology physicians had significantly different screening ratios from each other (P < 0.001). There were no significant differences in the ratios of HBV screening when IBD specialists were compared to other gastroenterology physicians (0.505 ± 0.023 vs 0.536 ± 0.066, P = 0.66). Of those 220 patients screened, 51% of IBD patients were found not to be immune against HBV. Approximately 50% of gastroenterology physicians recommended HBV vaccinations to their patients in whom serology was negative for antibodies against HBV. IBD specialists recommended vaccinations to a higher percentage of their patients compared to other gastroenterology physicians (0.168 ± 0.019 vs 0.038 ± 0.026, P = 0.015). Present and/or past HBV infection was found in 3.6% of the patients who had serology checked. There was no statistically significant difference in the prevalence of hepatitis B surface antigen (HBsAg) between our study and that reported in previous studies done in Spain (4/220 vs 14/2076 respectively, P = 0.070); and in France (4/220 vs 3/315 respectively, P = 0.159). But, the prevalence of anti-HBcAb in this study was less than that reported in the study in Spain (7/220 vs 155/2076 respectively, P = 0.006); and was not significantly different from that reported in the study in France (7/220 vs 8/315 respectively, P = 0.313). CONCLUSION: The prevalence of HBsAg in our IBD patients was not higher than previously reported European studies. Most IBD patients are not routinely screened or vaccinated against HBV at a tertiary referral center in the United States.

Safety and efficacy of glucomannan for weight loss in overweight and moderately obese adults.

BACKGROUND: Few safe and effective dietary supplements are available to promote weight loss. We evaluated the safety and efficacy of glucomannan, a water-soluble fiber supplement, for achieving weight loss in overweight and moderately obese individuals consuming self-selected diets. METHODS: Participants were randomly assigned to take 1.33 grams of glucomannan or identically looking placebo capsules with 236.6 mL (8 ounces) of water one hour before breakfast, lunch, and dinner for 8 weeks. The primary efficacy outcome was change in body weight after 8 weeks. Other efficacy outcomes were changes in body composition, hunger/fullness, and lipid and glucose concentrations. Safety outcomes included gastrointestinal symptoms/tolerance and serum liver enzymes and creatinine levels. RESULTS: A total of 53 participants (18-65 years of age; BMI 25-35 kg/m²) were enrolled and randomized. The two groups did not differ with respect to baseline characteristics and compliance with the study supplement. At 8 weeks, there was no significant difference between the glucomannan and placebo groups in amount of weight loss (-.40 ± .06 and -.43 ± .07, resp.) or other efficacy outcomes or in any of the safety outcomes. CONCLUSIONS: Glucomannan supplements administered over 8 weeks were well tolerated but did not promote weight loss or significantly alter body composition, hunger/fullness, or lipid and glucose parameters. This trial is registered with NCT00613600.

Atopic irritable bowel syndrome: a novel subgroup of irritable bowel syndrome with allergic manifestations.

BACKGROUND: Mast cells have a primary role in atopy. Mast cells may play a unique role in a subgroup of patients with irritable bowel syndrome (IBS). This observation suggests a link between atopic disorders and IBS. OBJECTIVE: To determine whether there is an association between atopic disorders and IBS. METHODS: We undertook a prospective study using structured questionnaires. We administered questionnaires to 125 consecutive patients seen in the following clinics from July 1 through October 31, 2001: allergy/immunology (AI) (n = 39), gastroenterology (n = 36), and general medicine (n = 50). The survey included questions detailing gastrointestinal and allergic symptoms. Diagnosis of IBS was based on Rome II criteria. Diagnosis of atopy was based on clinical parameters. RESULTS: The AI clinic reported a significantly (P = .015) higher rate of IBS than the general medicine clinic. The IBS incidence reported in the AI clinic was similar to that reported in the gastroenterology clinic. The likelihood of IBS was significantly higher in patients with seasonal allergic rhinitis (2.67 times; 95% confidence interval [CI], 1.10-6.49; P = .03), patients with allergic eczema (3.85 times; 95% CI, 1.72-8.60; P = .001), and patients with depression (2.56 times; 95% CI, 1.05-6.14; P = .04). Patients reporting atopic symptoms (seasonal allergic rhinitis, allergic eczema, and asthma) were 3.20 times (95% CI, 1.20-8.50) (P = .02) more likely to fulfill the criteria for IBS. CONCLUSIONS: Adults with atopic symptoms report a high incidence of IBS, suggesting a link between atopy and IBS. We proposed a subgroup of patients with IBS (atopic IBS) who have typical IBS symptoms in association with atopic manifestations. Identifying atopic vs nonatopic IBS may help in identifyingthe underlying pathophysiologic mechanisms and therapeutic options.

Mastocytic enterocolitis: increased mucosal mast cells in chronic intractable diarrhea.

CONTEXT: In some adult patients with chronic intractable diarrhea, the diagnosis remains elusive even after detailed evaluations, and colonic or duodenal biopsy specimens may appear unremarkable on routine hematoxylin-eosin staining. OBJECTIVES: To assess the concentration of mast cells in colonic or duodenal biopsy specimens by immunohistochemical analysis for mast cell tryptase from patients with chronic intractable diarrhea and to evaluate their response to drugs affecting mast cell function. DESIGN: Mast cells per high-power field were assessed in biopsy specimens from 47 patients with chronic intractable diarrhea, from 50 control subjects, and from 63 patients with other specific diseases that cause chronic diarrhea (inflammatory bowel disease, celiac disease, collagenous colitis, and lymphocytic colitis). Patients with chronic intractable diarrhea who had more than 20 mast cells per high-power field were administered drugs affecting mast cell mediator function and release. RESULTS: The mean +/- SD concentration of mast cells in the 50 control subjects was 13.3 +/- 3.5 cells per high-power field; hence, patients with more than 20 mast cells per high-power field were considered to have increased mast cells. Thirty-three (70%) of 47 patients with chronic intractable diarrhea had increased mast cells, and symptoms were controlled by drug therapy in 22 (67%) of the 33 patients. No patient had systemic or cutaneous mastocytosis. No increase in mast cells was seen in patients with other common causes of chronic diarrhea. CONCLUSIONS: In chronic intractable diarrhea, colonic or duodenal biopsy specimens may appear unremarkable on routine hematoxylin-eosin staining, but increased mast cells may be demonstrated by immunohistochemistry for mast cell tryptase, with the novel term mastocytic enterocolitis describing this condition. Similar increases in mast cells are not apparent in control populations or in patients with other specific diseases that cause chronic diarrhea. The cause of the increased mast cells remains to be elucidated.

Intestinal permeation and gastrointestinal disease.

The gastrointestinal tract constitutes one of the largest sites of exposure to the outside environment. The function of the gastrointestinal tract in monitoring and sealing the host interior from intruders is called the gut barrier. A variety of specific and nonspecific mechanisms are in operation to establish the host barrier; these include luminal mechanisms and digestive enzymes, the epithelial cells together with tight junctions in between them, and the gut immune system. Disruptions in the gut barrier follow injury from various causes including nonsteroidal anti-inflammatory drugs and oxidant stress, and involve mechanisms such as adenosine triphosphate depletion and damage to epithelial cell cytoskeletons that regulate tight junctions. Ample evidence links gut barrier dysfunction to multiorgan system failure in sepsis and immune dysregulation. Additionally, contribution of gut barrier dysfunction to gastrointestinal disease is an evolving concept and is the focus of this review. An overview of the evidence for the role of gut barrier dysfunction in disorders such as Crohn's disease, celiac disease, food allergy, acute pancreatitis, non-alcoholic fatty liver disease, and alcoholic liver disease is provided, together with critical insight into the implications of this evidence as a primary disease mechanism.

Acute pancreatitis in children.

OBJECTIVES: Currently, there is no scoring system for predicting severity in acute pancreatitis in children. Our intent was to evaluate the performance of existing scoring systems in children, to develop a system for children, and to examine the etiology of acute pancreatitis in children. METHODS: A chart review of children with acute pancreatitis was conducted at six centers, three serving as criterion centers and three as validation centers. Ranson and Glasgow scores were calculated for each admission. Additional clinical data were collected, and parameters correlating with severity were incorporated into a new scoring system. Performance characteristics were calculated for each system. RESULTS: A total of 301 admissions were reviewed, 202 in the criterion group and 99 in the validation group. Eight parameters were included in a new scoring system for children. The parameters were as follows: age (<7 yr), weight (<23 kg), admission WBC (>18,500), admission LDH (>2,000), 48-h trough Ca2+ (<8.3 mg/dl), 48-h trough albumin (<2.6 g/dl), 48-h fluid sequestration (>75 ml/ kg/48 h), and 48-h rise in BUN (>5 mg/dl). When the cut-off for predicting a severe outcome was set at 3 criteria, the new system had better sensitivity versus Ranson and Glasgow scores (70% vs 30% and 35%, respectively) and a better negative predictive value (91% vs 85% and 85%). The specificity (79% vs 94% and 94%) and positive predictive value (45% vs 57% and 61%) fell slightly. CONCLUSION: The new scoring system performs better in this group than do existing systems.