Soluble Syndecan-1: A Novel Biomarker of Small Bowel Mucosal Damage in Children with Celiac Disease.

BACKGROUND: Syndecan-1 (SDC1) is essential for maintaining normal epithelial barrier. Shedding of SDC1 ectodomain, reflected by serum soluble syndecan-1 (SSDC1) levels, is regulated by inflammation. Increased intestinal permeability plays a central role in celiac disease (CD). The association between SSDC1 levels and mucosal damage in CD has not been evaluated. AIMS: To evaluate serum SSDC1 levels in children with CD and to determine its relationship with histological grading classified by modified Marsh criteria. METHODS: This is a cross-sectional, pilot study, in which serum SSDC1 was analyzed by ELISA in a cohort of 49 untreated children with CD and 15 children with nonspecific abdominal pain (AP). CD was diagnosed based on positive celiac serology and small intestinal biopsy. SSDC1 levels at the time of biopsy were correlated with Marsh grading. Controls were defined by AP, negative celiac serology, normal upper endoscopy, and small intestinal biopsies. RESULTS: SSDC1 levels were significantly higher in CD patients compared to AP controls (116.2 ± 161 vs. 41.3 ± 17.5 ng/ml, respectively, p < 0.01). SSDC1 levels were significantly higher in patients with Marsh 3c lesion compared to AP controls (170.6 ± 201 vs. 41.3 ± 17.5 ng/ml, respectively, p < 0.05). SSDC1 concentrations displayed a significant correlation with mucosal damage defined by Marsh (r = 0.39, p < 0.05). CONCLUSION: This is the first study demonstrating elevated levels of serum SSDC1 in children with CD. Our results suggest that SSDC1 is a potentially novel marker of intestinal mucosal damage in patients with CD. Its applicability as a surrogate biomarker in CD remains to be determined.

Diffusion-weighted imaging in quiescent Crohn's disease: correlation with inflammatory biomarkers and video capsule endoscopy.

AIM: To investigate the role of restricted diffusion in quiescent Crohn's disease (CD) patients and its association with inflammatory biomarkers and endoscopic disease. MATERIAL AND METHODS: Fifty-two quiescent CD patients prospectively underwent magnetic resonance enterography (MRE) and video capsule endoscopy (VCE) and were tested for the inflammatory biomarkers, faecal calprotectin (FCP) and C-reactive protein (CRP). Restricted diffusion in the distal ileum was qualitatively (absence/presence) and quantitatively (apparent diffusion coefficient [ADC]) assessed by two readers. The VCE-based Lewis score was calculated for the distal ileum. Restricted diffusion sensitivity and specificity for VCE ulcerations were assessed for patients with elevated (>100 µg/g) or normal (<100 µg/g) FCP. Receiver operating characteristic (ROC) curve was used to assess the ability of ADC to identify patients with concurrent VCE ulceration and elevated FCP. RESULTS: The sensitivity and specificity of restricted diffusion for patients with VCE ulceration were higher in patients with elevated FCP (reader 1: 71.4%, 80%, reader 2: 76.2%, 100%, respectively) compared to patients with normal FCP (reader 1: 46.2%, 61.5%; reader 2: 15.4%, 76.9%, respectively). The ADC had a high diagnostic accuracy for identifying patients that had concurrent VCE ulceration and elevated FCP (reader 1: AUC=0.819, reader 2: AUC=0.832). CONCLUSION: In quiescent CD patients, the presence of restricted diffusion is suggestive of an active inflammation, associated with elevated FCP. Thus, DWI may serve as a clinical tool in the follow-up of these patients, implying subclinical inflammatory flares.

Capsule endoscopy in acute upper gastrointestinal hemorrhage: a prospective cohort study.

BACKGROUND AND STUDY AIMS: Capsule endoscopy may play a role in the evaluation of patients presenting with acute upper gastrointestinal hemorrhage in the emergency department. PATIENTS AND METHODS: We evaluated adults with acute upper gastrointestinal hemorrhage presenting to the emergency departments of two academic centers. Patients ingested a wireless video capsule, which was followed immediately by a nasogastric tube aspiration and later by esophagogastroduodenoscopy (EGD). We compared capsule endoscopy with nasogastric tube aspiration for determination of the presence of blood, and with EGD for discrimination of the source of bleeding, identification of peptic/inflammatory lesions, safety, and patient satisfaction. RESULTS: The study enrolled 49 patients (32 men, 17 women; mean age 58.3 ±â€†19 years), but three patients did not complete the capsule endoscopy and five were intolerant of the nasogastric tube. Blood was detected in the upper gastrointestinal tract significantly more often by capsule endoscopy (15 /18 [83.3 %]) than by nasogastric tube aspiration (6 /18 [33.3 %]; P = 0.035). There was no significant difference in the identification of peptic/inflammatory lesions between capsule endoscopy (27 /40 [67.5 %]) and EGD (35 /40 [87.5 %]; P = 0.10, OR 0.39 95 %CI 0.11 - 1.15). Capsule endoscopy reached the duodenum in 45 /46 patients (98 %). One patient (2.2 %) had self-limited shortness of breath and one (2.2 %) had coughing on capsule ingestion. CONCLUSIONS: In an emergency department setting, capsule endoscopy appears feasible and safe in people presenting with acute upper gastrointestinal hemorrhage. Capsule endoscopy identifies gross blood in the upper gastrointestinal tract, including the duodenum, significantly more often than nasogastric tube aspiration and identifies inflammatory lesions, as well as EGD. Capsule endoscopy may facilitate patient triage and earlier endoscopy, but should not be considered a substitute for EGD.

The impact of pseudomembrane formation on the outcome of Clostridium difficile-associated disease.

PURPOSE: Although pseudomembranes are the hallmark manifestation of Clostridium difficile-associated diarrhea (CDAD), there are scant data specifically addressing their impact on the clinical outcome. We investigated whether the formation of pseudomembranes predicts a worse CDAD outcome. METHODS: CDAD patients hospitalized during 2010 underwent sigmoidoscopy and were followed prospectively. In addition, all hospitalized CDAD patients in the period 01/2000-12/2009 who underwent lower endoscopy were retrospectively identified and their charts reviewed. Patients with detectable pseudomembranes on endoscopy were compared to those in whom pseudomembranes were absent. Thirty-day mortality and a composite outcome comprised of mortality within 30 days of diagnosis, admission to the intensive care unit (ICU), colectomy, peritonitis, hemodynamic instability, or respiratory insufficiency were addressed. Additional clinical outcomes used for comparison between the two groups were 60-day mortality, duration of hospitalization, and the failure of metronidazole and vancomycin. RESULTS: A total of 117 CDAD patients (mean age 62.9 ± 19 years) who underwent lower endoscopy were included; 46 with pseudomembranes and 71 without. Seven out of the 46 patients with pseudomembranes died within 30 days compared to 9/71 in the non-pseudomembrane group [odds ratio (OR) 1.2, 95% confidence interval (CI) 0.4-3.6, P = 0.8]. Similarly, there was no correlation between the occurrence of pseudomembranes and the rate of the composite adverse outcome (P = 0.6). In contrast, acute renal insufficiency (OR 15, 95% CI 3.2-72, P < 0.001) and hypoalbuminemia (OR 5.7, 95% CI 1.8-18, P = 0.002) were both independently predictive of a severe clinical outcome. CONCLUSIONS: Our findings suggest that the presence of pseudomembranes is not associated with an adverse outcome in CDAD patients.

Endoscopy in inflammatory bowel disease.

Small bowel imaging and endoscopy in inflammatory bowel disease (IBD) underwent a lot of change and advancement in the recent years. Modalities have shifted from gastroscopy, colonoscopy and small bowel follow through, to ileo-colonoscopy, computed tomography (CT) or magnetic resonance (MR), enteroscopy, wireless video capsule endoscopy and balloon assisted enteroscopy. Nowadays endoscopy has a major role in the diagnosis of IBD, assessing its extent, treating some of its complications (stricture, bleeding), assessing the success of various treatments (mucosal healing), and as a predictor of disease course. Wireless capsule endoscopy (WCE) is a relatively new "toy" allowing direct, patient friendly, visualization of the entire small bowel mucosa. It has gained a substantial role in the evaluation of patients with suspected Chron's Disease (CD) and indeterminate colitis. WCE has a high positive predictive value in patients with suspected CD, when one uses more than two of the International Conference on Capsule Endoscopy (ICCE) criteria, and not less important, a very high negative predictive value in patients with suspected CD. Its role in patients with known CD, assessing their disease activity and extent, its role in assessing postsurgical small bowel recurrence and its role in the evaluation of mucosal healing are still unclear. Balloon assisted enteroscopy has established its role as a complementary tool in cases where there is need of biopsies or treatment (dilatation of strictures). The present review will summarize the role of endoscopy in the diagnosis of IBD, in assessing its activity, its management, interventional endoscopy and cancer surveillance.

A novel device to improve colon cleanliness during colonoscopy.

BACKGROUND AND STUDY AIM: Effective colonoscopy depends on adequate visualization of the intestine, which might be ensured by intraprocedural use of a cleansing device. We investigated the performance of a novel endoscopic device with regard to cleanliness, safety, and tolerability during colonoscopy, compared with standard cleansing. PATIENTS AND METHODS: At a single center, colonoscopy patients in whom the cecum was accessed and at least one bowel segment was inadequately cleansed were assigned to either use of a disposable catheter cleansing device (JetPrep), used through the endoscope working channel, or standard manual cleansing using a 50-ml syringe. The cleansing quality, for each segment and before and after irrigation, was recorded using a 4-point scale ranging from excellent (grade 1, no more than small bits of adherent feces) to poor (grade 4, large amount of fecal residue). RESULTS: 38 patients were included, 19 in each group. Reasons for referral included colorectal cancer screening (52 %), or blood loss (31 %). Each segment showed improvement after cleansing with JetPrep. Overall cleansing grade improved by a mean of 0.74 points (standard deviation [SD] 0.82) in the investigation group compared with 0.19 (0.40) in the control group (P < 0.0001), and right colon cleansing improved by 1.59 points (0.71) versus 0.31 (0.48) in the controls (P < 0.0001). There was no significant difference in procedure time between the groups. No adverse events or side effects were encountered. CONCLUSIONS: The JetPrep disposable catheter device is safe and efficient for intraprocedural cleansing of a suboptimally prepared colon, allowing higher quality colonoscopy.

Validation of the Capsule Endoscopy Crohn's Disease Activity Index (CECDAI or Niv score): a multicenter prospective study.

BACKGROUND AND STUDY AIMS: The Capsule Endoscopy Crohn's Disease Activity Index (CECDAI or Niv score) was devised to measure mucosal disease activity using video capsule endoscopy (VCE). The aim of the current study was to prospectively validate the use of the scoring system in daily practice. METHODS: This was a multicenter, double-blind, prospective, controlled study of VCE videos from 62 consecutive patients with isolated small-bowel Crohn's disease. The CECDAI was designed to evaluate three main parameters of Crohn's disease: inflammation (A), extent of disease (B), and stricture (C), in both the proximal and distal segments of the small bowel. The final score was calculated by adding the two segmental scores: CECDAI = ([A1 × B1] + C1) + ([A2 × B2] + C2). Each examiner in every site interpreted 6 - 10 videos and calculated the CECDAI. The de-identified CD-ROMs were then coded and sent to the principal investigator for CECDAI calculation. RESULTS: The cecum was reached in 72 % and 86 % of examinations, and proximal small-bowel involvement was found in 56 % and 62 % of the patients, according to the site investigators and principal investigator, respectively. Significant correlation was demonstrated between the calculation of the CECDAI by the individual site investigators and that performed by the principal investigator. Overall correlation between endoscopists from the different study centers was good, with r = 0.767 (range 0.717 - 0.985; Kappa 0.66; P < 0.001). There was no correlation between the CECDAI and the Crohn's Disease Activity Index or the Inflammatory Bowel Disease Quality of Life Questionnaire or any of their components. CONCLUSION: A new scoring system of mucosal injury in Crohn's disease of the small intestine, the CECDAI, was validated. Its use in controlled trials and/or regular follow-up of these patients is advocated.

Colon capsule endoscopy: European Society of Gastrointestinal Endoscopy (ESGE) Guideline.

PillCam colon capsule endoscopy (CCE) is an innovative noninvasive, and painless ingestible capsule technique that allows exploration of the colon without the need for sedation and gas insufflation. Although it is already available in European and other countries, the clinical indications for CCE as well as the reporting and work-up of detected findings have not yet been standardized. The aim of this evidence-based and consensus-based guideline, commissioned by the European Society of Gastrointestinal Endoscopy (ESGE) is to furnish healthcare providers with a comprehensive framework for potential implementation of this technique in a clinical setting.

A guide for assessing the clinical relevance of findings in small bowel capsule endoscopy: analysis of 8064 answers of international experts to an illustrated script questionnaire.

BACKGROUND AND AIM: Although recommended, the P-score used for assessing the pertinence / relevance of findings seen in small bowel (SB) capsule endoscopy (CE) is based on a low level of knowledge. The aim of this study was to evaluate the clinical relevance of the most frequent SBCE findings through an illustrated script questionnaire. MATERIALS AND METHODS: Sixteen types of SBCE findings were illustrated four times each in three different settings (occult and overt obscure gastrointestinal bleeding and suspected Crohn's disease), and with a variable number (n = 1/n = 2-5/n ≥ 6), thus providing a questionnaire with 192 scenarios and 576 illustrated questions. Fifteen international experts were asked to rate the finding's relevance for each question as very unlikely (-2) / unlikely (-1) / doubtful (0) / likely (+1) / very likely (+2). The median score (≤-0.75, between -0.75 and 0.75, or ≥0.75) obtained for each scenario determined a low (P0), intermediate (P1) or high (P2) relevance, respectively. RESULTS: 8064 answers were analyzed. Participation and completion rates were 93% and 100%, respectively. In overt or occult OGIB, resultant P2 findings were 'typical angiectasia', 'deep ulceration', 'stenosis', and'blood', whatever their numbers, and 'superficial ulcerations' when multiple. While in suspected CD, consensus P2 lesions were 'deep ulceration' and 'stenosis' whatever their numbers, and 'aphthoid erosions' and 'superficial ulcerations' when multiple. CONCLUSION: This study establishes a guide for the evaluation of relevance of SBCE findings. It represents a step forward for SB-CE interpretation and is intended to be used as a tool for teaching and academic research.

Prospective multicenter performance evaluation of the second-generation colon capsule compared with colonoscopy.

BACKGROUND AND STUDY AIMS: A second-generation capsule endoscopy system, using the PillCam Colon 2, was developed to increase sensitivity for colorectal polyp detection compared with the first-generation system. The performance of this new system is reported. PATIENTS AND METHODS: In a five-center feasibility study, second-generation capsule endoscopy was prospectively compared with conventional colonoscopy as gold standard for the detection of colorectal polyps and other colonic disease, in a cohort of patients scheduled for colonoscopy and having known or suspected colonic disease. Colonoscopy was independently performed within 10 hours after capsule ingestion. Capsule-positive but colonoscopy-negative cases were counted as false-positive. RESULTS: 104 patients (mean age 49.8 years) were enrolled; data from 98 were analyzed. Patient rate for polyps of any size was 44 %, 53 % of these patients having adenomas. No adverse events related to either procedure were reported. The capsule sensitivity for the detection of patients with polyps >or= 6 mm was 89 % (95 % confidence interval [CI] 70 - 97) and for those with polyps >or= 10 mm it was 88 % (95 %CI 56 - 98), with specificities of 76 % (95 %CI 72 - 78) and 89 % (95 %CI 86 - 90), respectively. Both polyps missed by colonoscopy and mismatch in polyp size by study definition lowered specificity. Overall colon cleanliness for capsule endoscopy was adequate in 78 % of patients (95 %CI 68 - 86). CONCLUSIONS: The new second-generation colon capsule endoscopy is a safe and effective method for visualizing the colon and detecting colonic lesions. Sensitivity and specificity for detecting colorectal polyps appear to be very good, suggesting a potential for improved accuracy compared with the first-generation system. Further prospective and comparative studies are needed.

Role of small-bowel endoscopy in the management of patients with inflammatory bowel disease: an international OMED-ECCO consensus.

Crohn's disease and ulcerative colitis are lifelong diseases seen predominantly in the developed countries of the world. Whereas ulcerative colitis is a chronic inflammatory condition causing diffuse and continuous mucosal inflammation of the colon, Crohn's disease is a heterogeneous entity comprised of several different phenotypes, but can affect the entire gastrointestinal tract. A change in diagnosis from Crohn's disease to ulcerative colitis during the first year of illness occurs in about 10 % - 15 % of cases. Inflammatory bowel disease (IBD) restricted to the colon that cannot be characterized as either ulcerative colitis or Crohn's disease is termed IBD-unclassified (IBDU). The advent of capsule and both single- and double-balloon-assisted enteroscopy is revolutionizing small-bowel imaging and has major implications for diagnosis, classification, therapeutic decision making and outcomes in the management of IBD. The role of these investigations in the diagnosis and management of IBD, however, is unclear. This document sets out the current Consensus reached by a group of international experts in the fields of endoscopy and IBD at a meeting held in Brussels, 12-13th December 2008, organised jointly by the European Crohn's and Colitis Organisation (ECCO) and the Organisation Mondiale d'Endoscopie Digestive (OMED). The Consensus is grouped into seven sections: definitions and diagnosis; suspected Crohn's disease; established Crohn's disease; IBDU; ulcerative colitis (including ileal pouch-anal anastomosis [IPAA]); paediatric practice; and complications and unresolved questions. Consensus guideline statements are followed by comments on the evidence and opinion. Statements are intended to be read in context with qualifying comments and not read in isolation.

Detecting esophageal disease with second-generation capsule endoscopy: initial evaluation of the PillCam ESO 2.

BACKGROUND AND STUDY AIM: Esophageal capsule endoscopy (ECE) provides an alternative, minimally invasive modality for evaluating the esophagus. This study evaluates the performance and test characteristics of a second-generation esophageal capsule endoscope, the PillCam ESO 2. METHODS: Adults with known or suspected esophageal disease were included. Using the simplified ingestion procedure, each patient underwent capsule endoscopy with the PillCam ESO 2. Following ECE, esophagogastroduodenoscopy (EGD) was performed on the same day by an investigator who was blinded to the results of the ECE. In random order, capsule endoscopy videos were read and interpreted by the study investigator blinded to EGD results. RESULTS: 28 patients (19 men, 9 women; mean age 53.3 years) were included. In 82 % of the patients, at least 75 % of the Z line was visualized by the PillCam ESO 2. A per-lesion analysis demonstrated that the PillCam ESO 2 had definitive results in 30/43 lesions (69.8 %) and EGD in 29/43 (67.4 %), P value = 0.41. Compared with EGD for detecting suspected Barrett's esophagus and esophagitis, the PillCam ESO 2 had a sensitivity of 100 % and a specificity of 74 %, and a sensitivity of 80 % and a specificity of 87 %, respectively. The PillCam ESO 2 demonstrated 86 % agreement with EGD in describing the Z line (kappa statistic 0.68). The modified ingestion protocol provided excellent cleansing, with bubbles/saliva having no or only a minor effect on Z line images in 86 % of cases. CONCLUSIONS: The PillCam ESO 2 demonstrated excellent visualization of the Z line. Compared with standard EGD, the PillCam ESO 2 had good test characteristics with high rates of detection of suspected Barrett's esophagus and esophagitis. This study provides indirect validation of the simplified ingestion procedure. The PillCam ESO 2 acquires high quality esophageal images, performs safely, and should be able to replace the current PillCam ESO.

Safety, efficacy and pharmacokinetics of vedolizumab in patients with simultaneous exposure to an anti-tumour necrosis factor.

BACKGROUND: Data on combination-biologic treatment in (IBD) are still scant. AIM: To explore outcomes of patients co-exposed to anti-TNF and vedolizumab. METHODS: Patients starting vedolizumab having measurable anti-TNF levels after recently stopping adalimumab/infliximab ('VDZ-aTNF' group), were compared with control vedolizumab patients in a retrospective 1:2 matched case-control study. RESULTS: Seventy-five patients were included (25 VDZ-aTNF, 50 VDZ). Adverse events were experienced by 9/25 VDZ-aTNF compared to 13/50 VDZ patients (P = 0.4, follow-up 14 weeks in all). Week 14 clinical remission was attained in 10/25 (40%) of VDZ-aTNF patients versus 23/50 (46%) of VDZ patients (OR = 0.8, 95% CI 0.3-2.1, P = 0.6) and clinical response in 19/25 (76%) versus 39/50 (78%) respectively (OR = 0.9, 95% CI 0.3-2.7, P = 0.8). Corticosteroid-free remission and corticosteroid-free response were experienced by 30% and 54%, respectively, of the entire cohort, and were similar between the two groups. Vedolizumab drug concentrations at week 2, 6 and 14 were similar among VDZ-aTNF and VDZ patients (P > 0.5). Multi-variable analysis showed independent association of some vedolizumab drug-levels time-points with baseline albumin and weight, but not with anti-TNF co-exposure. In a prospective study of a separate cohort of patients starting infliximab (n = 12), the percentage of α4ß7+ memory T cells, slightly but nonsignificantly increased throughout weeks 0, 2 to 14 (26 ± 2.3%, 27.8 ± 2.9%, 29.5 ± 2.6% respectively, P = 0.06). CONCLUSIONS: Vedolizumab/anti-TNF co-exposure did not generate new safety signals during 14-weeks induction, nor did it reduce efficacy or alter vedolizumab pharmacokinetics. These observations may aid the design of future co-biologics trials and also suggest that a deliberate waiting-interval between anti-TNF cessation and subsequent vedolizumab initiation may not be warranted.

Early drug and anti-infliximab antibody levels for prediction of primary nonresponse to infliximab therapy.

BACKGROUND: Primary nonresponse, defined as lack of clinical benefit during the induction phase, occurs in up to 30% of IBD patients treated with infliximab. The mechanisms underlying primary nonresponse have not yet been clearly defined. AIM: To evaluate the association of early (week 2 and week 6) induction infliximab and anti-infliximab antibody levels with primary nonresponse. METHODS: A retrospective observational case-control study of inflammatory bowel disease patients treated with infliximab and followed at Sheba Medical Center between 2009 and 2016 was performed. Pre-infusion infliximab and antibodies to infliximab (ATI) levels were measured by our previously described drug-tolerant ELISA assay. RESULTS: Thirty-five primary nonresponders have been identified and matched with 105 primary responders (1:3 ratios). Both week 2 and week 6 infliximab levels were significantly lower among primary nonresponders compared to responders (week 2, 6: median level 7.2, 2.2 µg/mL vs 13.5, 9.5 µg/mL, P = .0019, P < .0001 respectively). Antibodies to infliximab appeared more frequently (either week 2 or 6, 68% vs 28% prevalence, P = .0004) and at higher levels in nonresponders compared to responders (week 2, 6: median ATI 7.3, 10.8 µg/mL-eq vs 3.8, 4.4 µg/mL-eq, P = .005, P = .008 respectively). Moreover, week 2 infliximab levels <6.8 µg/mL (AUC = 0.68, P = .002, sensitivity 50%, specificity 86%) and antibodies to infliximab levels >4.3 µg/mL-eq (AUC = 0.78, P = .0004, sensitivity 77%, specificity 71%) were predictive of primary nonresponse. Among the other clinical and demographic variables, higher baseline ulcerative colitis clinical score, infliximab monotherapy, prior adalimumab therapy and previous Crohn's disease-related surgeries were also associated with an increased risk of primary nonresponse. CONCLUSIONS: Infliximab levels below 6.8 µg/mL and antibodies to infliximab levels above 4.3 µg/mL-eq before the second infusion are associated with primary nonresponse, especially among Crohn's disease patients.

Intestinal surfactant-like material. A novel secretory product of the rat enterocyte.

Surface-active phospholipid-containing particles are traditionally considered to be the product of type II pneumocytes. We now demonstrate membrane-bound lamellar cytoplasmic organelles in adult and suckling rat enterocytes that are densely reactive with phospholipid-staining reagents. These structures were seen in the basolateral space, within the intercellular junctions, and unraveling on the lumenal surface, and were more abundant after fat feeding. Light scrapings of intestinal mucosa and lumenal washings that contained these bodies, as evidenced by morphology and biochemical analysis, lowered surface tension in a pulsating bubble assay. Production by normal enterocytes of material with surfactant-like appearance and properties demonstrates that these structures are present in extrapulmonary epithelia, and extends the possible range of their function beyond gaseous exchange, e.g., solute exchange or lubrication on membrane surfaces.

A possible role for rat intestinal surfactant-like particles in transepithelial triacylglycerol transport.

To further examine whether surfactant-like particles (DeSchryver-Kecskemeti, K., R. Eliakim, S. Carroll, W. F. Stenson, M. A. Moxley, and D. H. Alpers. 1989. J. Clin. Invest. 84:1355-1361) were involved in the transepithelial transport of lipid, alkaline phosphatase activity and surfactant-like particle content were measured in apical mucosal scrapings, enterocytes, lamina propria, and serum after inhibition of chylomicron transport. Serum triacylglycerol levels were decreased 60-76% by Pluronic L-81, fenfluramine, and choline deficiency compared with fat-fed controls. 5 h after triacylglycerol feed, alkaline phosphatase activity in all three experimental groups was decreased compared with controls by 52-69% in mucosal scrapings and by 33-72% in serum. A parallel decline (60%) in alkaline phosphatase activity occurred in the lamina propria of Pluronic-treated animals. Total particle content (measured by an ELISA using antiserum against purified particle) after Pluronic treatment was decreased in mucosal scrapings, lamina propria, and serum by 16, 22, and 29% at 3 h and by 33, 40, and 8%, respectively, at 5 h after fat feeding. In contrast, particle content was increased in enterocytes by 29% 3 h and by 8% 5 h after fat feeding. By electron microscopy, enterocytes from Pluronic- and fenfluramine-treated animals exhibited a two- to threefold increase in large intracellular cytoplasmic lipid globules and the appearance of lamellae in apposition, with a marked decrease in the number of surfactant-like particles overlying the brush border. These changes, produced by inhibition of chylomicron transport, in the distribution of surfactant-like particles and particle-bound alkaline phosphatase are consistent with a role for these particles in transepithelial triacylglycerol transport across and out of the enterocyte.

Clinical trial: randomized-controlled clinical study comparing the efficacy and safety of a low-volume vs. a high-volume mesalazine foam in active distal ulcerative colitis.

BACKGROUND: Rectally administered mesalazine (mesalamine; 5-aminosalicylic acid) is the first-line therapy for treatment of distal ulcerative colitis. Recently, a high-volume 5-aminosalicylic acid foam has been shown to be as effective and safe as standard 5-aminosalicylic acid enema. AIM: To study the efficacy and safety of a low-volume vs. a high-volume 5-aminosalicylic acid foam. METHODS: In this investigator-blinded study, patients with active distal ulcerative colitis [Clinical Activity Index (CAI) > 4, Endoscopic Index > or = 4] were randomized to receive 2 x 1 g/30 mL low-volume (n = 163) or 2 x 1 g/60 mL high-volume 5-aminosalicylic acid foam (n = 167) for 42 days. Primary end point was clinical remission (CAI < or = 4) at the final/withdrawal visit (per-protocol). RESULTS: 330 patients were evaluable for efficacy and safety by intention-to-treat, 290 for per-protocol analysis. Clinical remission rates at week 6 (per-protocol) were 77% on low-volume foam vs. 77% on high-volume foam (P = 0.00002 for non-inferiority). The low-volume foam was associated with a lower frequency of severe discomfort, pain and retention problems. CONCLUSIONS: Low-volume 5-aminosalicylic acid foam is as effective and safe as a high-volume 5-aminosalicylic acid foam in the treatment of active distal ulcerative colitis, but offers compliance advantages compared to the high-volume preparation.

Wireless video capsule in pediatric patients with functional abdominal pain.

OBJECTIVES: Upper endoscopy (esophagogastroduodenoscopy [EGD]) has a limited role, if any, in the evaluation of functional abdominal pain (FAP). Nevertheless, children with intractable FAP are occasionally referred to EGD to rule out intestinal pathology. We evaluated the role of wireless video capsule endoscopy (VCE) in children referred for EGD with a diagnosis of FAP. PATIENTS AND METHODS: Ten children older than 10 years of age were prospectively enrolled. Children were first studied with the PillCam SB (VCE; Given Imaging, Yokneam, Israel) followed by standard EGD within 2 weeks. After the completion of the study, a questionnaire of tolerance and content regarding the 2 procedures was completed by the patients. RESULTS: Physical examinations and laboratory tests were within normal limits in all of the patients. Patients swallowed the endoscopic capsules without difficulty. There were no complications. VCE identified gastritis in 4 patients (confirmed by biopsies), whereas EGD detected erosive gastritis in only 1 of the 4 children. EGD detected no duodenal abnormalities. VCE detected Crohn disease in the small intestine and cecum in 1 patient. VCE was ranked by 8 patients as convenient and as a preferable procedure compared with EGD. CONCLUSION: The results of this small cohort suggest that in children with FAP, VCE is more sensitive than EGD for detection of macroscopic gastric and small bowel pathologies.