Showing papers in "Digestive Diseases and Sciences in 2012"

Butyrate enhances intestinal epithelial barrier function via up-regulation of tight junction protein Claudin-1 transcription.

Abstract: Barrier function is essential for the maintenance of normal intestinal function. Dysregulation of the intestinal barrier underlies a wide range of disorders. Previously, we found that sodium butyrate (NaB) decreased the molecular permeability of intestinal barrier in vivo model, but the mechanism by which NaB facilitated the tightness of tight junctions (TJs) in small intestinal epithelium needed further studies. In vitro culture of the cdx2-IEC monolayer was used to mimic barrier function. The TJs were assessed by transepithelial electrical resistance (TEER) and paracellular flux of fluorescein isothiocyanate-conjugated dextran 40,000 (FD-40), Western blot, Q-RT-PCR, and immunofluorescence. Promoter and chromatin immunoprecipitation (ChIP) assays were also done to analyze the Claudin-1 gene. NaB decreased FD-40 flux, increased TEER and TJ protein Claudin-1 expression, induced ZO-1 and Occludin redistribution in cellular membrane, and reversed the damage effect after calcium (Ca2+) switch assay. Silencing Claudin-1 prevented protective function of NaB from enhancing intestinal barrier integrity. Further studies demonstrated that NaB increased Claudin-1 transcription by facilitating the interaction between transcription factor SP1 and a specific motif within the promoter region of Claudin-1. This SP1 binding motif was located upstream of the coding region (−138 to −76 bp) and indispensable for the transcription of Claudin-1 following NaB treatment. ChIP assay confirmed the association between SP1 and Claudin-1 promoter, and the elimination of the SP1 binding site by point mutation resulted in a significant loss of Claudin-1 transcription after NaB dealing. NaB enhanced intestinal barrier function through increasing Claudin-1 transcription via facilitating the association between SP1 and Claudin-1 promoter.

Bifidobacterium longum with Fructo-Oligosaccharides in Patients with Non Alcoholic Steatohepatitis

Abstract: Background Increased exposure to intestinal bacterial products may contribute to the pathogenesis of non alcoholic steatohepatitis (NASH). Bifidobacteria are predominant bacterial species in the human gut microbiota and have been considered to exert a beneficial effect on human health by maintaining the equilibrium of the resident microbiota.

Elevated Fecal Short Chain Fatty Acid and Ammonia Concentrations in Children with Autism Spectrum Disorder

Abstract: Background and Aim Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder where a high frequency of gastrointestinal disturbance (eg, constipation and diarrhea) is reported As large bowel fermentation products can have beneficial or detrimental effects on health, these were measured in feces of children with and without ASD to examine whether there is an underlying disturbance in fermentation processes in the disorder

Identification of Suitable Reference Genes for qPCR Analysis of Serum microRNA in Gastric Cancer Patients

Abstract: Background Circulating microRNA expression profiles may be promising biomarkers for diagnosis and assessment of the prognosis of cancer patients. Quantitative polymerase chain reaction (qPCR) is a sensitive technique for estimating expression levels of circulating microRNAs. However, there is no current consensus on the reference genes for qPCR analysis of circulating microRNAs.

Nutrition, Intestinal Permeability, and Blood Ethanol Levels Are Altered in Patients with Nonalcoholic Fatty Liver Disease (NAFLD)

Abstract: Background A role of an altered dietary pattern (e.g., a diet rich in sugar) but also alterations at the level of the intestinal barrier have repeatedly been discussed to be involved in the development and progression of nonalcoholic fatty liver disease (NAFLD).

Diabetes Mellitus and the Incidence of Colorectal Cancer: An Updated Systematic Review and Meta-Analysis

Abstract: The purpose of this study was to determine whether diabetes mellitus is associated with an increased risk of colorectal cancer. Relevant studies were identified in MEDLINE and EMBASE (up until November 1st, 2011). Inclusion criteria were original, peer-reviewed publications, with case–control and cohort studies (for studies on diabetes mellitus and colorectal cancer). Summary relative risks with 95% confidence intervals were calculated with a random-effects model. Twenty-four studies including eight case–control and 16 cohort studies, with a total of 3,659,341 participants, were included in this updated systematic review and meta-analysis, and all involved diabetes mellitus and colorectal cancer risk. Meta-analysis of the 24 included studies indicated that diabetes was associated with an increased risk of colorectal cancer, compared with no diabetes (summary RR of colorectal cancer incidence = 1.26, 95% CI = 1.20–1.31), without heterogeneity between studies (P heterogeneity = 0.296). Sub-group analyses found that these results were consistent between case–control and cohort studies and among studies conducted in different areas. The association between diabetes and colorectal cancer incidence did not differ significantly by sex and sub-sites. Insulin therapy was also positively associated with risk of colorectal cancer (summary RR = 1.61, 95% CI 1.18–1.35), with evidence of heterogeneity between studies (P heterogeneity = 0.014). Our findings further support a relationship between diabetes and increased risk of colon and rectal cancer in both women and men, and insulin therapy for diabetes may increase this risk.

The Prevalence of Overgrowth by Aerobic Bacteria in the Small Intestine by Small Bowel Culture: Relationship with Irritable Bowel Syndrome

Abstract: Many studies have linked irritable bowel syndrome (IBS) with small intestinal bacterial overgrowth (SIBO), although they have done so on a qualitative basis using breath tests even though quantitative cultures are the hallmark of diagnosis. The purpose of this study was to underscore the frequency of SIBO in a large number of Greeks necessitating upper gastrointestinal (GI) tract endoscopy by using quantitative microbiological assessment of the duodenal aspirate. Consecutive subjects presenting for upper GI endoscopy were eligible to participate. Quantitative culture of aspirates sampled from the third part of the duodenum during upper GI tract endoscopy was conducted under aerobic conditions. IBS was defined by Rome II criteria. Among 320 subjects enrolled, SIBO was diagnosed in 62 (19.4%); 42 of 62 had IBS (67.7%). SIBO was found in 37.5% of IBS sufferers. SIBO was found in 60% of IBS patients with predominant diarrhea compared with 27.3% without diarrhea (P = 0.004). Escherichia coli, Enterococcus spp and Klebsiella pneumoniae were the most common isolates within patients with SIBO. A step-wise logistic regression analysis revealed that IBS, history of type 2 diabetes mellitus and intake of proton pump inhibitors were independently and positively linked with SIBO; gastritis was protective against SIBO. Using culture of the small bowel, SIBO by aerobe bacteria is independently linked with IBS. These results reinforce results of clinical trials evidencing a therapeutic role of non-absorbable antibiotics for the management of IBS symptoms.

Prevalence of Hypothyroidism in Nonalcoholic Fatty Liver Disease

Abstract: A possible association between nonalcoholic fatty liver disease (NAFLD) and hypothyroidism has been suggested. The recognized link between hypothyroidism and elements of the metabolic syndrome may explain this association. The purpose of this study was to determine the prevalence of hypothyroidism in a cohort of patients with NAFLD and analyze the potential factors associated with hypothyroidism in this patient population. Two hundred forty-six patients with biopsy-proven NAFLD attending hepatology clinics at the Cleveland Clinic between October 2006 and June 2009, and 430 age-, gender-, race- and BMI-matched control subjects seen in the general internal medicine clinic were included. Patients with a clinical diagnosis of hypothyroidism who were on thyroid replacement therapy were considered to be hypothyroid. Hypothyroidism was more frequent among patients with NAFLD (21% vs. 9.5%; P < 0.01) compared to controls, and was higher in NASH patients than NAFLD patients without NASH (25% vs. 12.8%, P = 0.03). Subjects with hypothyroidism were 2.1 (95% CI 1.1–3.9, P = 0.02) and 3.8 (95% CI 2–6.9, P < 0.001) times more likely to have NAFLD and NASH, respectively. By multivariate analysis, female gender (P < 0.001) and increased BMI (P = 0.03) were associated with hypothyroidism. NAFLD subjects who reported mild alcohol consumption were less likely to have hypothyroidism compared to those who reported complete abstinence (OR 0.37, P = 0.008). A higher prevalence of hypothyroidism was demonstrated in patients with NAFLD compared to controls. Among subjects with NALFD, female gender, increased BMI and history of abstinence from alcohol were associated with hypothyroidism. Patients with hypothyroidism were also more likely to have NASH.

Urinary Neutrophil Gelatinase-Associated Lipocalin Predicts Mortality and Identifies Acute Kidney Injury in Cirrhosis

Abstract: Background Kidney failure predicts mortality in patients with cirrhosis. Identification of kidney failure etiology and recognition of those at the highest mortality risk remains a challenge.

Geriatric Inflammatory Bowel Disease: Phenotypic Presentation, Treatment Patterns, Nutritional Status, Outcomes, and Comorbidity

Abstract: The U.S. population is aging and the burden of geriatric inflammatory bowel disease (IBD) patients has increased. Systematic data describing phenotypic presentation, treatment regimens, outcomes and comorbidities in elderly IBD patients is limited. We performed a retrospective observational study of IBD patients age ≥65 followed in a 20-hospital system to determine patterns of phenotypic presentation, treatment, polypharmacy, nutritional status and comorbidity. Data were extracted from electronic medical record based on ICD-9 coding/indexed terms on Crohn’s disease (CD) and ulcerative colitis (UC) patients. A total of 393 geriatric IBD patients were identified (49.1% males; 50.9% females; 61.8% UC; 38.2% CD; 73.4 ± 6.6 years old). Younger age at diagnosis of CD (≤64) was associated with greater prevalence of small bowel surgeries (63.6%) compared with those diagnosed after age ≥65 (20.9%) (p < 0.005). Fistulizing/penetrating disease was frequent in patients diagnosed with CD at a younger age (43.6% compared to 7%) (p < 0.005). IBD maintenance treatment included: 44% 5-ASA agents; 31.6% maintenance prednisone (defined as ≥6 months treatment duration); 4.8% steroid suppositories; 5.6% 6MP/azathioprine; 1.3% methotrexate; 1.3% adalimumab; 1.3% infliximab; 9.4% loperamide/diphenoxylate/atropine; 0.5% had no IBD medications. Longer duration of CD disease correlated with vitamin B12, vitamin D and iron deficiency. Geriatric patients diagnosed with CD earlier in life had greater small bowel involvement compared with new onset geriatric CD. There is low utilization of immunomodulator and biologic agents in geriatric IBD patients. Duration of CD correlates with nutrient deficiency. Prospective studies are warranted in this respect.

The Physiology of Human Defecation

Abstract: Human defecation involves integrated and coordinated sensorimotor functions, orchestrated by central, spinal, peripheral (somatic and visceral), and enteric neural activities, acting on a morphologically intact gastrointestinal tract (including the final common path, the pelvic floor, and anal sphincters). The multiple factors that ultimately result in defecation are best appreciated by describing four temporally and physiologically fairly distinct phases. This article details our current understanding of normal defecation, including recent advances, but importantly identifies those areas where knowledge or consensus is still lacking. Appreciation of normal physiology is central to directed treatment of constipation and also of fecal incontinence, which are prevalent in the general population and cause significant morbidity.

Methanobrevibacter smithii Is the Predominant Methanogen in Patients with Constipation-Predominant IBS and Methane on Breath

Abstract: Purpose Among irritable bowel syndrome (IBS) patients, breath methane producers overwhelmingly have constipation predominance (C-IBS). Although the most common methanogen in humans is Methanobrevibacter smithii, incidence and type of methanogenic bacteria in C-IBS patients are unknown.

Reduced diversity and imbalance of fecal microbiota in patients with ulcerative colitis.

Abstract: Clinical observations and experimental colitis models have indicated the importance of intestinal bacteria in the etiology of ulcerative colitis (UC), but a causative bacterial agent has not been identified. To determine how intestinal bacteria are associated with UC, fecal microbiota and other components were compared for UC patients and healthy adults. Fresh feces were collected from 48 UC patients. Fecal microbiota were analyzed by use of terminal-restriction fragment length polymorphism (T-RFLP), real-time PCR, and culture. The concentrations of organic acids, indole, and ammonia, and pH and moisture, which are indicators of the intestinal environment, were measured and compared with healthy control data. T-RFLP data divided the UC patients into four clusters; one cluster was obtained for healthy subjects. The diversity of fecal microbiota was significantly lower in UC patients. There were significantly fewer Bacteroides and Clostridium subcluster XIVab, and the amount of Enterococcus was higher in UC patients than in healthy subjects. The fecal concentration of organic acids was significantly lower in UC patients who were in remission. UC patients have imbalances in the intestinal environment—less diversity of fecal microbiota, lower levels of major anaerobic bacteria (Bacteroides and Clostridium subcluster XIVab), and a lower concentration of organic acids.

Pathologic changes in ipilimumab-related hepatitis in patients with metastatic melanoma.

Abstract: Ipilimumab is a fully human monoclonal antibody which blocks cytotoxic T-lymphocyte antigen-4, an immune checkpoint molecule that down-regulates pathways of T-cell activation. Ipilimumab has demonstrated a statistically significant improvement in overall survival in two randomized controlled phase III trials of patients with metastatic melanoma. A main complication of ipilimumab therapy is the development of inflammatory events which can occur in various organs, including the liver (i.e., hepatitis). Hepatic injury is a concern because it can develop with little warning and may potentially be severe. We analyzed liver biopsy findings in 4 cases of ipilimumab treatment-related hepatitis and compared them to a fifth, previously reported case. All 5 patients had a histologic pattern of injury that was similar to what is observed with acute viral and autoimmune hepatitis; however, the findings are not specific and require clinicopathologic correlation. Pathologic evidence of hepatitis resolved in all 5 patients with appropriate immunosuppressive therapy. Although a relatively uncommon adverse event with ipilimumab, patients should be monitored at regular intervals for biochemical/pathological evidence of hepatitis.

Association between red cell distribution width and disease activity in patients with inflammatory bowel disease.

Abstract: Recent studies have suggested that a higher red blood cell distribution width (RDW) is associated with disease activity in patients with inflammatory bowel disease (IBD). However, the RDW in IBD patients without anemia has not been investigated. This study aimed to determine whether or not RDW could be used for the assessment of disease activity in IBD patients with and without anemia. The serum C-reactive protein (CRP) level, erythrocyte sedimentation rate (ESR), hemoglobin concentration, platelet and white blood cell counts, and RDW were assessed in 221 IBD patients, comprised of 120 patients with ulcerative colitis (UC) and 101 patients with Crohn’s disease (CD). Disease activity was determined for UC and CD with the Mayo score and the Crohn’s disease activity index, respectively. The CRP level, ESR, hemoglobin concentration, hematocrit, and RDW increased according to disease activity in patients with and without anemia (all P < 0.05). Multivariate analysis demonstrated that RDW was the best independent indicator for predicting disease activity in CD patients without anemia [odd ratios (OR), 1.702; 95% confidence interval (CI), 1.185–2.445; P = 0.004] and UC patients without anemia (OR, 4.921; 95% CI, 2.281–10.615; P < 0.001). Also, ROC curve analysis showed the RDW to be the most significant indicator of non-anemic active IBD [area under curve (AUC) in CD, 0.852, P < 0.001; AUC in UC, 0.827, P < 0.001]. The association between increased RDW and active IBD was evident in IBD patients with and without anemia.

Transient PPI responsive esophageal eosinophilia may be a clinical sub-phenotype of pediatric eosinophilic esophagitis.

Abstract: Eosinophilic esophagitis (EoE) and gastroesophageal reflux (GERD) both cause esophageal eosinophilia Reports show that esophageal eosinophilia meeting criteria for EoE may respond to acid suppression mono-therapy Consensus guidelines have termed this entity “PPI-responsive esophageal eosinophilia” (PPIRee) and recommend a trial with proton-pump inhibitors (PPIs) prior to a definitive EoE diagnosis The mechanisms of PPIRee and whether this represents a sub-phenotype of GERD, a sub-phenotype of EoE, or its own distinct entity remain unclear A database search revealed children who had an initial histologic response to PPI monotherapy but had recurrence of esophageal eosinophilia and symptoms despite continued PPI therapy In order to understand the patterns of esophageal inflammatory cells during PPI therapy we performed quantitative immunohistochemistry for mast cells, CD1a positive antigen presenting cells, and CD45RO memory T cells Four pediatric patients (mean age 95 years) had a mean peak eosinophil count of 52 eos/hpf which initially resolved completely during PPI mono-therapy However, despite continued PPI therapy, endoscopic abnormalities and pan-esophageal eosinophilia recurred (mean peak eosinophil count of 64 eos/hpf) There was no seasonal variation or lack of PPI adherence that explained the return of eosinopihlia Similar to eosinophilia, mastocytosis and CD45RO cells were transiently decreased during PPI therapy PPIs appear to be capable of transiently resolving multiple inflammatory cell subsets including eosinophils, mast cells, and CD45RO cells Our data suggest that patients with PPIRee should have continued monitoring for EoE during PPI monotherapy The numbers of patients in whom PPIRee is a transient phenomenon and whether PPIRee represents a sub-phenotype of EoE in children merits further investigation

Effect of Boswellia serrata on antioxidant status in an experimental model of colitis rats induced by acetic acid.

Abstract: Aim of the Study To evaluate the antioxidant effect of an extract of the plant Boswellia serrata in an experimental model of acute ulcerative colitis induced by administration of acetic acid (AA) in rats.

Tenofovir Disoproxil Fumarate for Prevention of Vertical Transmission of Hepatitis B Virus Infection by Highly Viremic Pregnant Women: A Case Series

Abstract: Despite appropriate immunoprophylaxis, up to 10 % of infants born to highly viremic hepatitis B virus (HBV–DNA ≥ 7 log IU/mL) mothers are infected with HBV. Use of TDF to prevent vertical transmission (VT) by such mothers has not been evaluated. To evaluate the efficacy and safety of TDF in preventing VT from highly viremic HBV-infected mothers. Data were collected retrospectively from HBV mono-infected, hepatitis B e antigen (HBeAg) positive, pregnant women between 6/2008 and 11/2010. Cases enrolled were HBV mono-infected mothers who received TDF (300 mg orally once a day) in the third trimester. Those with pregnancy complications or an abnormal fetus on sonography were excluded from use of TDF. All infants received hepatitis B immunoglobulin and vaccination at birth and subsequently. Eleven Asian mothers received TDF at the median gestational age of 29 (28–32) weeks and the median duration of TDF use before delivery was 10 (7–12) weeks. A significant reduction in serum HBV–DNA was achieved at delivery compared with baseline (mean 5.25 ± 1.79 vs. 8.87 ± 0.45 log10 copies/mL, respectively; p < 0.01). Three had serum ALT levels more than 1.5 times the upper limit of normal and two of these normalized before delivery. The 11 infants were born with no obstetric complication or birth defects. Five infants were breastfed. All infants were hepatitis B surface antigen negative 28–36 weeks after birth. Our preliminary data suggest that TDF use in the third trimester is safe, and effectively prevents VT of HBV from high viremic HBeAg-positive mothers.

Sorafenib for Treatment of Hepatocellular Carcinoma: A Systematic Review

Abstract: Background Sorafenib, a drug that inhibits Raf serine/threonine kinases mediating cell proliferation and receptor tyrosine kinases involved in angiogenesis, is approved for treatment of advanced hepatocellular carcinoma.

Clinicopathologic Features and Treatment Outcomes in Cronkhite–Canada Syndrome: Support for Autoimmunity

Abstract: Cronkhite–Canada syndrome (CCS) is a noninherited condition, associated with high morbidity, and characterized by gastrointestinal hamartomatous polyposis, alopecia, onychodystrophy, hyperpigmentation, and diarrhea. All features may respond to immunosuppressive therapy, but little is known about the etiology. An autoimmune origin has been suggested but not proved. From a retrospectively selected cohort, we evaluated clinicopathologic features, including immunostaining for IgG4 (an antibody associated with autoimmunity), and therapeutic outcomes in a cohort of CCS patients to provide further insights into this disease. Cases included 14 consecutive CCS patients seen at the Mayo Clinic on whom tissue and follow-up were available. All histology was reviewed by an expert gastrointestinal pathologist. Immunostaining for IgG4 was performed on 42 polyps from CCS cases and on control tissues, including 46 histologically similar hamartomas [from juvenile polyposis syndrome (JPS)] and 20 normal mucosae (six stomach, three small bowel, and 11 colon). Clinical features and treatment outcomes were descriptive. All CCS cases had both upper and lower gastrointestinal polyps; most had typical dermatologic features of alopecia, hyperpigmentation, and onychodystrophy; and most had evidence of protein-losing enteropathy. Ten patients (71%) had adenomatous polyps and 2 (14%) had colorectal cancer. IgG4 immunostaining was positive (>5 cells/HPF) in 52% of CCS polyps compared to 12% of JPS polyps (P = 0.001); IgG4 staining was negative in all other control tissues. Of 11 CCS patients treated with oral corticosteroids, 91% achieved remission. Relapse was common with steroid tapering. Five patients who initially responded to corticosteroids were maintained in remission on azathioprine (2 mg/kg/day) with no relapse after a median of 4.5 years. Immunostaining for the autoimmune-related IgG4 antibody is significantly increased in CCS polyps compared to disease and normal control tissues. Furthermore, immunosuppression by corticosteroids or long-term azathioprine may eradicate or lessen manifestations of CCS. These histologic findings and treatment responses are consistent with an autoimmune mechanism underlying CCS.

Epstein-Barr Virus Infection Is Common in Inflamed Gastrointestinal Mucosa

Abstract: Epstein-Barr virus (EBV) is present in the malignant epithelial cells of 10% of all gastric adenocarcinomas; however, localization of the virus in normal gastrointestinal mucosa is largely unexplored. In the present study, we measured EBV DNA and localized viral gene products in gastritis specimens (n = 89), normal gastric and colonic mucosa (n = 14), Crohn’s disease (n = 9), and ulcerative colitis (n = 11) tissues. A battery of sensitive and specific quantitative polymerase chain reactions targeted six disparate regions of the EBV genome: BamH1 W, EBNA1, LMP1, LMP2, BZLF1, and EBER1. EBV infection was localized by EBV-encoded RNA (EBER) in situ hybridization and by immunohistochemical stains for viral latent proteins LMP1 and LMP2 and for viral lytic proteins BMRF1 and BZLF1. B lymphocytes were identified using CD20 immunostains. EBV DNA was essentially undetectable in normal gastric mucosa but was present in 46% of gastritis lesions, 44% of normal colonic mucosa, 55% of Crohn’s disease, and 64% of ulcerative colitis samples. Levels of EBV DNA exceeded what would be expected based on the numbers of B lymphocytes in inflamed tissues, suggesting that EBV is preferentially localized to inflammatory gastrointestinal lesions. Histochemical staining revealed EBER expression in lymphoid cells of some PCR-positive lesions. The viral lytic viral proteins, BMRF1 and BZLF1, were expressed in lymphoid cells of two ulcerative colitis tissues, both of which had relatively high viral loads by quantitative PCR. EBV-infected lymphocytes are frequently present in inflamed gastric and colonic mucosa. Active viral replication in some lesions raises the possibility of virus-related perpetuation of gastrointestinal inflammation.

Upper Gastrointestinal Involvement of Crohn’s Disease: A Prospective Study on the Role of Upper Endoscopy in the Diagnostic Work-Up

Abstract: Prevalence of upper gastrointestinal (GI) tract involvement in adult Crohn’s disease (CD) has been reported to be very low (03–5%) In routine practice, upper endoscopy is recommended only in CD patients with upper GI symptoms Available data concerning the prevalence of asymptomatic upper GI lesions in CD patients are controversial The aim of this study was to prospectively evaluate the prevalence of upper GI CD involvement in CD patients, irrespective of upper GI symptoms A series of 119 consecutive CD patients underwent clinical assessment, including occurrence and score of upper GI symptoms, and upper endoscopy with biopsy samples for histological assessment and Helicobacter pylori (Hp) infection detection In an attempt to further recognize the upper GI tract lesions as CD or other form of inflammation, in a subgroup of CD patients, the histological and endoscopic evaluation was repeated following 12 weeks of anti-TNF-α or other treatments in association with proton-pump inhibitors Upper CD involvement was found in 19/119 (16%) patients Hp infection was detected in 10/119 (84%) CD patients Hp-negative focally active chronic gastritis was found in 34/119 (286%) CD patients At presentation, 12/19 patients (63%) showing upper CD involvement were asymptomatic and 7 (37%) symptomatic A high prevalence of upper GI tract involvement has been observed in CD patients, irrespective of upper symptoms This finding suggests the usefulness of routine upper endoscopy in the diagnostic work-up of CD patients in order to correctly classify the distribution and extent of the disease

Side-by-Side Versus Stent-in-Stent Deployment in Bilateral Endoscopic Metal Stenting for Malignant Hilar Biliary Obstruction

Abstract: The clinical differences between side-by-side and stent-in-stent deployment using a self-expanding metal stent for hilar malignant obstruction have not been evaluated. The purpose of this study was to compare the clinical features between side-by-side and stent-in-stent deployment. We compared side-by-side and stent-in-stent deployment in 52 consecutive patients with malignant hilar biliary obstruction who underwent endoscopic bilateral drainage using self-expanding metal stent. Side-by-side deployment (SBS group) was performed in 28 patients from 2002 to 2005, and stent-in-stent deployment (SIS group) in 24 patients from 2006 to 2010. Technical success, functional success, complications, stent occlusion and cumulative stent patency in the SBS and SIS groups were evaluated and compared retrospectively. There were no significant inter-group differences in technical success (SBS vs. SIS, 89 vs. 100 %, respectively), functional success (96 vs. 100 %), early complications (11 vs. 4 %), late complications (32 vs. 8 %) or stent occlusion (20 vs. 42 %). The incidence of complications was significantly higher for SBS than for SIS (44 vs. 13 %; p = 0.016). Cumulative stent patency was significantly better for SBS than for SIS (log-rank, p = 0.047). SBS was not associated with significantly longer cumulative stent patency in univariate Cox proportional hazard analysis (HR 0.35; 95 % CI 0.12–1.03; p = 0.056) and multivariate analysis (HR 0.39; 95 % CI 0.13–1.16; p = 0.090). The incidence of complications is higher for side-by-side than stent-in stent deployment in bilateral metal stenting. In terms of cumulative stent patency, side-by-side deployment tends to be more effective than stent-in-stent deployment.

Dietary Kaempferol Suppresses Inflammation of Dextran Sulfate Sodium-Induced Colitis in Mice

Abstract: In ulcerative colitis (UC), reduction of inflammation may represent a key mechanism in UC therapy, and anti-inflammatory agents would be good candidates for preventing UC. Kaempferol, a natural flavonoid, is believed to have anti-inflammatory activities and has been shown to be potentially immune-modulatory. The aim of this study was to determine whether kaempferol alleviates the inflammatory responses of dextran sulfate sodium (DSS)-induced colitis in mice. Female C57BL/6J mice were divided into six groups: a negative control group, a DSS control group, and DSS + 0.1% or 0.3% kaempferol pre- or post-fed groups. At the end of the experimental period, clinical and biochemical markers were evaluated. Plasma levels of NO and PGE2 were significantly decreased in both the 0.3% kaempferol pre- and post-fed groups. The plasma LTB4 level was profoundly decreased in all animals fed kaempferol. Colonic mucosa MPO activity was also suppressed in both the 0.3% kaempferol pre- or post-fed groups. TFF3 mRNA, a marker for goblet cell function, was up-regulated in kaempferol pre-fed animals. These results indicate that kaempferol is an effective anti-inflammatory agent that protects colonic mucosa from DSS-induced UC. Dietary kaempferol fed prior to colitis induction was more effective to suppress some of the colitis-associated markers.

Serum miR-18a: A Potential Marker for Hepatitis B Virus-Related Hepatocellular Carcinoma Screening

Abstract: Background Alpha-fetoprotein detection is currently mainly used in clinic for diagnosis of primary hepatocellular carcinoma (HCC). However, its sensitivity and specificity are not satisfying. Approximately 60–80 % of patients with HCC have an established background of chronic infection with hepatitis B virus (HBV).

Liver stiffness measurement using acoustic radiation force impulse (ARFI) elastography and effect of necroinflammation.

Abstract: Acoustic radiation force impulse (ARFI) elastography can be used to assess the degree of liver fibrosis. We evaluated the performance of ARFI elastography in assessment of liver fibrosis and compared it with the performance of aspartate aminotransferase-to-platelet ratio index (APRI) and transient elastography with Fibroscan (FS). We prospectively analyzed 250 consecutive patients who underwent liver biopsy and ARFI from June 2010 to May 2011. Reliable FS values were obtained for 97 (38.8%) patients. The mean age of patients (147 male and 103 female) was 46.6 years. Liver stiffness values obtained by use of ARFI elastography significantly correlated with histological fibrosis stage (R = 0.575, P < 0.001). Area under the receiver operating characteristics curves (AUROCs) of ARFI elastography for predicting significant fibrosis (≥F2) and cirrhosis (F4) was 0.74 (95% confidence interval [CI], 0.64–0.86, P = 0.001) and 0.79 (95% CI, 0.67–0.91, P = 0.001), respectively, and those for APRI were 0.69 (95% CI, 0.58–0.79, P = 0.001) and 0.76 (95% CI, 0.64–0.85, P < 0.001), respectively. The optimum cutoff values for ARFI elastography were 1.13 m/s for ≥F2 and 1.98 m/s for F4; these decreased to 1.09 m/s for ≥F2 and 1.81 m/s for F4 when 131 patients with normal alanine aminotransferase (ALT) were selected. In the sub-group of 97 patients with reliable FS values, the performance in predicting ≥F2 or F4 was equivalent between ARFI elastography and FS. ARFI elastography is a reliable surrogate marker of liver fibrosis, if its relationship with biochemical markers, for example ALT level, is taken into account.

Safety, Tolerability, and Activity of ALV003: Results from Two Phase 1 Single, Escalating-Dose Clinical Trials

Abstract: Celiac disease is the most common hereditary autoimmune disease in humans. The only treatment option for non-refractory celiac disease patients is adherence to a strict life-long gluten-free diet, which often fails to normalize small bowel histology. ALV003 is a mixture of two proteases that degrades gluten and is in clinical development as an oral therapy for patients with celiac disease. The safety, tolerability, and activity of ALV003 were assessed in two phase 1 clinical trials. In study 1 (N = 28) the study drug was administered in the fasted state; in study 2 (N = 53) the study drug was administered together with a gluten-containing meal. Both studies were single-dose, single-blind, placebo-controlled, cross-over trials. ALV003 was dosed at escalating dose levels by cohort (100, 300, 900, and 1,800 mg) and gastric samples were aspirated using a nasogastric tube. Adverse events, serum drug levels, and anti-drug antibody titers were measured. Gastric samples were assessed for ALV003 enzymatic activity over time (gastric pharmacokinetics) and gluten degradation (gastric pharmacodynamics). All doses were well tolerated, and no serious adverse events or allergic reactions were observed. Gastric aspirates collected 30 min following a meal showed that 100 and 300 mg ALV003 degraded 75 ± 10% (N = 8) and 88 ± 5% (N = 8), respectively, of one gram of wheat bread gluten. ALV003 is an orally active protease that appears to be stable in the fed stomach and degrades dietary gluten in this compartment. Single doses of oral ALV003 were not associated with serious adverse reactions.

Lewis Score Correlates More Closely with Fecal Calprotectin Than Capsule Endoscopy Crohn’s Disease Activity Index

Abstract: Small-bowel capsule endoscopy (SBCE) is an invaluable imaging method for the small bowel. The Lewis score (LS) and the Capsule Endoscopy Crohn’s Disease Activity Index (CECDAI) have been developed to standardize the reporting of small-bowel inflammation. Fecal calprotectin (FC) represents a highly reliable biomarker of intestinal inflammation. To assess the performance of the two SBCE inflammation scoring systems by correlating them with FC. Furthermore, to define threshold levels for CECDAI. Retrospective study; patients who underwent SBCE and had FC measurement shortly before or after SBCE. LS and CECDAI were calculated by a single reviewer and correlated [Spearman’s (r s )] with the FC results. Linear regression analysis was used to identify threshold levels for CECDAI. Forty-nine patients; three subgroups A, B and C (based on FC levels <100, 100–200, and ≥200 μg/g, respectively). LS appears to correlate with FC (r s = 0.448, p = 0.0014), unlike CECDAI, which does not demonstrate significant correlation (r s = 0.245, p = 0.089). Strongly positive correlation between FC and LS was observed in subgroup A (r s = 0.68, p = 0.0047), while in subgroups B and C, neither LS nor CECDAI showed correlation with FC. Significant correlation between LS and CECDAI was demonstrated (r s = 0. 6324, p < 0.0001). Linear regression analysis demonstrates that LS thresholds of 135 and 790 correspond with CECDAI levels of 3.8 and 5.8, respectively. LS performs better than CECDAI in describing small-bowel inflammation, especially at FC levels of <100 μg/g. Furthermore, CECDAI levels of 3.8 and 5.8 seem to correspond to LS thresholds of 135 and 790, respectively.

Serum metabolic profiling in inflammatory bowel disease.

Abstract: Background The inflammatory bowel diseases (IBD), Crohn’s disease (CD), and ulcerative colitis (UC), are chronic inflammatory conditions of the gastrointestinal tract whose pathogenesis is not completely understood. 1H nuclear magnetic resonance (NMR) spectroscopy of serum generates comprehensive metabolic profiles, reflecting systemic metabolism, which may be altered in disease states.

Gut Bacterial Translocation Contributes to Microinflammation in Experimental Uremia

Abstract: Background Microinflammation frequently develops in chronic uremia with pathological intestinal changes. However, the relationship between gut bacterial translocation and microinflammation in uremia has not been widely investigated.