Small Intestinal Pathology Research Articles

Cross-sectional small intestinal surveillance of maintenance hemodialysis patients using video capsule endoscopy: SCHEMA study.

Background and study aims: Small intestinal pathology in hemodialysis (HD) patients has been studied in only a small number of retrospective case series. One method for noninvasively surveying small intestinal disorders is video capsule endoscopy (VCE). The primary aim of this study was to investigate the prevalence of small intestinal abnormalities among asymptomatic maintenance HD outpatients using VCE. The secondary aim was to assess the clinical impact of these abnormalities. Patients and methods: This study consisted of two phases. In phase I, a cross-sectional study, a cohort of patients who received maintenance HD three times weekly at an outpatient hemodialysis clinic were studied using VCE. Phase II was a prospective cohort study with follow up for 1 year after VCE. Results: Fifty-six patients were enrolled in this study, and two were excluded from analysis due to capsule retention in the stomach. The prevalence of small bowel abnormalities in HD patients was 64.8 % (35/54) (95 % confidential interval 52.1 % – 77.6 %). Of 54 patients, 21 (38.9 %) had mucosal lesions, 10 (18.5 %) had vascular lesions, and 4 (7.4 %) had both lesion types. During the 1-year follow-up period, events occurred in four patients. A small bowel-associated event was observed in one patient, who underwent laparoscopy-assisted small intestinal partial resection 3 months after diagnosis by VCE. All patients in whom events were seen had small bowel abnormalities; no events were observed in the VCE-negative group. Conclusions: Although asymptomatic maintenance HD patients had a high prevalence of small bowel abnormalities (64.8 %), they did not have a high incidence of small bowel-associated events during the 1-year follow-up.

Peculiarities of the small intestine pathology in chronic pancreatitis

Peculiarities of the small intestine pathology in chronic pancreatitis

PWE-439 Delivering training in small intestinal capsule endoscopy: report of the inaugural uk regional deanery training day

Introduction Capsule endoscopy (CE) is widely used to image the small intestine. No formal training programme for CE exists in the UK, commercially run courses are available. The BSG CE group is developing formalised accreditation processes through which trainees will pass as part of their standard specialist training in gastroenterology, the level will depend on whether they wish to offer CE as a sub specialist interest. Regionally delivered training provides an opportunity to introduce CE, a valuable rsesource where training opportunities remain otherwise limited. We delivered the first regional training day in CE in January 2014 and describe its format and subsequent feedback. Method Health Education South West (Peninsula and Severn Deaneries) run combined specialist training days for gastroenterology trainees. In January 2014, we delivered the first regional training day on CE in the UK. Trainees attended as part of their bi-monthly regional training programme. The teaching was provided by a consultant gastroenterologist with a wide experience in capsule endoscopy, supported by two colleagues. Following an introductory lecture, each trainee had access to an individual laptop loaded with interpretation software. 15 cases were studied throughout the day, demonstrating a wide variety of small intestinal pathology commonly seen with CE. The trainees were asked to give feedback at the end of the day and subsequently asked to complete a follow up online survey regarding their CE experiences during the following year. Results 13 trainees attended (52%). Feedback on the day was graded as good/ very good (7/13) to excellent (4/13), 2 non responders. The use of individual laptops was particularly appreciated. 11 subsequently responded to the online survey (92%). All found the day useful. 3/11 (27%) intended to offer CE as a skill for Consultant applications. Prior to the session only 1 attendee had reported any CE, their training was adhoc informal departmental learning. This increased to 3 attendees at 1 year follow up (27%). Of those who had not reported any CE subsequently, 63% cited the reason as lack of the service at their current/ previous placement, whereas 38% had opportunity, but limited training time to do so. Trainee requests for CE after the training day increased by 27%, the majority of requests for iron deficiency anaemia. 56% of trainees felt a regional or national course such as this should be mandatory for all trainees and form part of core competence expected for CCT. Conclusion Regionally delivered CE training as part of specialist training programme offers a unique opportunity for CE training in a group environment, until now only available commercially. UK trainess should have access to such training as part of their structured specialist training programme. Disclosure of interest None Declared.

Incidence of inflammatory bowel disease in Iceland 1995 – 2009. A nationwide population-based study

Objective. We analyzed the incidence of inflammatory bowel disease (IBD) in Iceland for the period 1995–2009. Material and methods. New cases of ulcerative colitis (UC) and Crohn’s disease (CD) were retrieved by thorough review of all small and large intestinal pathology reports with any type of inflammation from all the pathology departments in Iceland for the period 1995–2009. All suspicious new cases of IBD were then scrutinized retrospectively by examination of their clinical records. Results. A total of 1175 cases of IBD were diagnosed, 884 UC, 279 CD and 12 IBD unclassified. The crude annual incidence of UC was 20.5/100,000, increasing from 18.1 the first 5-year period to 22.1 the last 5-year period. The crude annual incidence of CD was 6.5/100,000, 6.7 the first 5-year period and 6.6 the last 5-year period. Conclusions. This study shows statistically significant increase in the incidence of UC during the study period. The incidence of CD has however remained stable.

Suggestions for automatic quantitation of endoscopic image analysis to improve detection of small intestinal pathology in celiac disease patients

Although many groups have attempted to develop an automated computerized method to detect pathology of the small intestinal mucosa caused by celiac disease, the efforts have thus far failed. This is due in part to the occult presence of the disease. When pathological evidence of celiac disease exists in the small bowel it is visually often patchy and subtle. Due to presence of extraneous substances such as air bubbles and opaque fluids, the use of computerized automation methods have only been partially successful in detecting the hallmarks of the disease in the small intestine—villous atrophy, fissuring, and a mottled appearance. By using a variety of computerized techniques and assigning a weight or vote to each technique, it is possible to improve the detection of abnormal regions which are indicative of celiac disease, and of treatment progress in diagnosed patients. Herein a paradigm is suggested for improving the efficacy of automated methods for measuring celiac disease manifestation in the small intestinal mucosa. The suggestions are applicable to both standard and videocapsule endoscopic imaging, since both methods could potentially benefit from computerized quantitation to improve celiac disease diagnosis.

Dengue Virus Infection with Highly Neutralizing Levels of Cross-Reactive Antibodies Causes Acute Lethal Small Intestinal Pathology without a High Level of Viremia in Mice.

Severe dengue virus (DENV)-associated diseases can occur in patients who have preexisting DENV antibodies (Abs) through antibody-dependent enhancement (ADE) of infection. It is well established that during ADE, DENV-antibody immune complexes (ICs) infect Fcγ receptor-bearing cells and increase the systemic viral burden that can be measured in the blood. For protection against infection with DENV serotypes 1 to 4, strongly neutralizing Abs must be elicited to overcome the effect of ADE. Clinical observations in infants who have maternal DENV Abs or recent phase II/III clinical trials with a leading tetravalent dengue vaccine suggested a lack of correlation between Ab neutralization and in vivo disease prevention. In addressing this gap in knowledge, we found that inoculation of ICs formed with serotype cross-reactive Abs that are more than 98% neutralized in vitro promotes high mortality in AG129 mice even though peak viremia was lower than that in direct virus infection. This suggests that the serum viremia level is not always correlated with disease severity. We further demonstrated that infection with the ICs resulted in increased vascular permeability, specifically in the small intestine, accompanied with increased tissue viral load and cytokine production, which can be suppressed by anti-tumor necrosis factor alpha (anti-TNF-α) Abs. Flow cytometric analysis identified increased infection in CD11b(int) CD11c(int/hi) CD103(-) antigen-presenting cells by IC inoculation, suggesting that these infected cells may be responsible for the increase in TNF-α production and vascular permeability in the small intestine that lead to mortality in mice. Our findings may have important implications for the development of dengue therapeutics. We examined the relationship between the neutralizing level of Abs at the time of infection and subsequent disease progression in a mouse model in order to understand why patients who are shown to have a neutralizing quantity of Abs still allow sufficient DENV replication to induce severe dengue manifestations, which sometimes do not correlate with viremia level. Strikingly, we found that high mortality was induced in AG129 mice by the increase in TNF-α-induced vascular permeability accompanied by an increased viral load, specifically in the small intestine, even when the initial infection level is suppressed to less than 5% and the peak viremia level is not enhanced. This suggests that ADE overcomes the protective efficacy of Abs in a tissue-dependent manner that leads to severe small intestinal pathology. Our findings may serve to address the pathogenic role of Abs on severe dengue disease and also help to develop safe Ab-based therapeutic strategies.

Intraluminal administration of poly I:C causes an enteropathy that is exacerbated by administration of oral dietary antigen.

Systemic administration of polyinosinic:polycytidylic acid (poly I:C), mimics virally-induced activation of TLR3 signalling causing acute small intestine damage, but whether and how mucosal administration of poly I:C causes enteropathy is less clear. Our aim was to investigate the inflammatory pathways elicited after intraluminal administration of poly I:C and determine acute and delayed consequences of this locally induced immune activation. Intraluminal poly I:C induced rapid mucosal immune activation in C57BL/6 mice involving IFNβ and the CXCL10/CXCR3 axis, that may drive inflammation towards a Th1 profile. Intraluminal poly I:C also caused enteropathy and gut dysfunction in gliadin-sensitive NOD-DQ8 mice, and this was prolonged by concomitant oral administration of gliadin. Our results indicate that small intestine pathology can be induced in mice by intraluminal administration of poly I:C and that this is exacerbated by subsequent oral delivery of a relevant dietary antigen.

Delayed presentation of an aspirated capsule endoscope

Capsule endoscopy has revolutionized the investigation of small intestinal pathology with an increasing repertoire of indications. We present the first reported case of an aspirated capsule presenting after a long asymptomatic period that was removed with no permanent pulmonary sequelae. This report highlights a cohort of patients who could be susceptible to this rare complication. The report also encourages the development of local/national guidelines to investigate misplaced/lost capsules during the procedure.

Histopathology of Small Intestine Induced by Cisplatin in Male Wistar Rats

Cisplatin, cis -diamminedichloroplatinum (II) is a highly effective drug used to treat several cancers. Unfortunately, it has various clinical side effects affecting many tissues. However, small intestine toxicity induced by cisplatin has been rare reports to date. This study aims to investigate the pathology of small intestine upon cisplatin treatment at various doses using histological techniques. Male Wistar rats were divided into 5 groups: group 1 was intraperitoneally (IP) injected with normal saline; group 2, 3, 4 and 5 were IP injected with cisplatin at doses of 25, 50, 75 and 100 mg/kg body weight (BW), respectively. On day 3, rats were weighed and small intestines were collected. This study found that cisplatin significantly reduces BW at all concentrations compared to saline group. Histological analysis of small intestine induced by cisplatin illustrating various pathologies includes hemodynamic change (hemorrhage), reversible injuries (distortion of mucosal architecture, development of subepithelial space and lifting of epithelial layer from the lamina propria) and irreversible injuries (degenerative changes of villi, sloughing of necrotic villi into intestinal lumina and loss of villi). Additionally, cellular adaptations were also elicited including hyperplasia of lamina propria and columnar epithelium lining villi and atrophy of villi. In conclusion, cisplatin administrations lead to pathologies of small intestine, consequently causing weight loss whose severity depends on its concentrations .

180 : The TNF family member TL1A: A key player in type 2 immunity in both adaptive and innate lymphocytes

The TNF-family cytokine TL1A costimulates T cells through its receptor DR3. TL1A polymorphisms and increased TL1A expression has been linked to Rheumatoid Arthritis and Inflammatory Bowel Disease. TL1A-DR3 interactions are required for diverse mouse models of autoimmune disease. The effects of TL1A on T cell differentiation and its role in innate lymphocyte biology has not been explored. During T cell activation, we have found that TL1A costimulation specifically promotes production of the allergy-promoting cytokine IL-9 through a mechanism dependent on IL-2 and STAT5 signaling, and TL1A promotes pathology in mouse models of asthma and ocular inflammation. Transgenic mice chronically expressing TL1A spontaneously develop small intestinal pathology characterized by high levels of IL-13, muscular and goblet cell hyperplasia, and infiltration with immune cells. These histological changes are dependent on IL-13 but not T cells or commensal flora. We find that the major IL-13 producing cells in TL1A transgenic mice lack T and B cell lineage markers and are phenotypically similar to ‘type 2’ innate lymphocytes (ILC2), which promote allergic and anti-parasitic responses in mice. ILC2 express surface DR3 and produce IL-13 in response to TL1A ex vivo. However, ILC2 can be expanded normally in DR3 deficient mice by IL-25 or IL-33, or Nippostrongylus brasiliensis, and DR3 deficient mice clear Nippostrongylus normally from the intestine. TL1A can thus induce IL-13 production by innate lymphocytes through mechanisms distinct from parasitic infection. Taken together, these data demonstrate that TL1A coordinately enhances type 2 immunity in both innate and adaptive lymphocytes and may be a good target for therapy in allergic diseases.

Safety of capsule endoscopy in the octogenarian as compared with younger patients

There has been an increased use of capsule endoscopy for the evaluation of small-intestine pathology in very elderly patients, yet the safety profile of this procedure has not been well-established. To estimate the adverse event rate of capsule endoscopy in patients aged ≥80 years and to compare this rate with that of capsule endoscopy patients aged <80 years. Retrospective matched cohort study. Single tertiary-care referral center. All 195 patients aged ≥80 years who underwent capsule endoscopy between 2005 and 2011 were included, along with 585 capsule endoscopy patients aged <80 years who were matched by sex in a 1:3 fashion. All patients underwent capsule endoscopy and, in selected cases, double-balloon enteroscopy. Adverse event rate of capsule endoscopy, which was defined as capsule retention or aspiration. Adverse events occurred at a similar frequency in patients aged ≥80 years compared with those aged <80 years (1.03% vs 0.85%; P = 1.00), resulting in a difference of 0.2% (95% confidence interval, -1.8% to 2.1%). All adverse events were related to capsule retention, with no study patients experiencing aspiration. This was a single-center, retrospective study. Adverse events resulting from capsule endoscopy occur at a similar rate in patients aged ≥80 years compared with those aged <80 years. Capsule endoscopy can be performed safely in the very elderly patient population.

The TL1A-IL13 axis: a novel pathway for Type 2 immunity mediated by innate lymphocytes independent of helminth infection (P6264)

Abstract The TNF-family cytokine TL1A costimulates T cells through its receptor DR3 and is required for diverse autoimmune disease models, but its role in innate lymphocyte biology has not been explored. Transgenic mice chronically expressing TL1A have increased activated T cells and develop small intestinal pathology characterized by high levels of IL-13, muscular and goblet cell hyperplasia, and infiltration with immune cells, all of which depend on DR3. Genetically eliminating T cells reduces T cell hyperactivation and gut infiltration with lymphocytes but not IL-13 production or mucosal hyperplasia. These data suggest that TL1A can induce another cell type to produce IL-13 and induce gastrointestinal pathology. Using a DsRED reporter mouse for IL-13, we find that the major IL-13 producing cells in TL1A transgenic mice lack T and B cell lineage markers and are phenotypically similar to ’type 2’ innate lymphocytes (ILC2) which expand and produce IL-13 in response to IL-25, IL-33 or parasitic infection. TL1A directly promotes IL-13 production by ILC2 ex-vivo. However, DR3 deficient mice mount a vigorous response to the intestinal nematode Nippostrongylus brasiliensis, and IL-13 producing innate lymphocytes can be expanded by IL-25 in the absence of DR3. Thus, TL1A can directly induce IL-13 production by innate lymphocytes through mechanisms distinct from parasitic infection. TL1A may be an attractive target for immunotherapy of diverse diseases associated with this cytokine.

Transabdominal Ultrasonography of the Small Bowel

In the era of double balloon enteroscopy, capsule endoscopy, CT, and MRI enterography is transabdominal ultrasonography (TUS) underestimated method for evaluation of small bowel pathology. As often initial imagine method in abdominal complaints, nowadays has TUS much better diagnostic potential than two decades ago. High-resolution ultrasound probes with harmonic imaging significantly improve resolution of bowel wall in real time, with possibility to asses bowel peristalsis. Color flow doppler enables evaluation of intramural bowel vascularisation, pulse wave doppler helps to quantificate flow in coeliac and superior mesenteric arteries. Small intestine contrast ultrasonography with oral contrast fluid, as well as contrast enhanced ultrasonography with intravenous microbubble contrast also improves small bowel imaging. We present a review of small intestine pathology that should be detected during ultrasound examinations, discuss technical requirements, advantages and limitations of TUS, typical ultrasound signs of Crohn's disease, ileus, celiac disease, intussusception, infectious enteritis, tumours, ischemic and haemorrhagic conditions of small bowel. In the hands of experienced investigator, despite some significant limitations(obesity, meteorism), is transabdominal ultrasonography reliable, noninvasive and inexpensive alternative method to computerised tomography (CT) and magnetic resonance imaging (MRI) in small bowel examination.

A Case of Celiac Disease

Celiac disease is a chronic absorptive disorder of the small intestine caused by gluten. The prevalence rate of celiac disease is 1% in Western countries. But, it is rare in Asian countries, and there is no celiac disease reported in Korea. Here, we report a case of celiac disease. An 36-years-old woman complained non-specific abdominal pain and diarrhea. She had anemia and was taking medication for osteoporosis. Colonoscopy showed no abnormality except shallow ulcer at the terminal ileum. Gastroduodenoscopy showed micronodularity at the duodenum 2nd and 3rd portion. Capsule endoscopy and enteroscopy showed villous atrophy and blunting of villi from the duodenum. Small intestinal pathology showed villous atrophy with lymphocyte infiltration. After gluten free diet, diarrhea, abdominal pain, anemia and osteoporosis were improved. And, she felt well-being sensation. This is a first case of celiac disease in Korea.

Treatment with interleukin-18 binding protein amelioratesToxoplasma gondii-induced small intestinal pathology that is induced by bone marrow cell-derived interleukin-18

Peroral infection with Toxoplasma gondii results in a Th1-type immunopathology characterized by small intestinal necrosis and is dependent on IL-18. In the present study, we investigated whether treatment with IL-18 binding protein (IL-18bp) prevents ileal pathology. We observed increased expression of IL-18bp in intestinal biopsies of mice following infection. Whereas small intestines of control mice showed severe necrosis with complete destruction of the small intestinal architecture, mice treated with IL-18bp daily displayed only mild inflammatory changes including flattening of villi and edema in the space between the epithelium and lamina propria. Small intestinal parasite loads and concentrations of pro-inflammatory cytokines did not differ in control and IL-18bp-treated mice. Binding of IL-18 to immobilized IL-18bp revealed a remarkably slow dissociation rate, indicating high affinity. Using chimeric mice we observed that bone marrow-derived rather than stromal cells were the primary source of IL-18 that resulted in small intestinal pathology following peroral infection with T. gondii. In conclusion, the results presented here suggest that IL-18bp may be an effective and safe treatment for small intestinal inflammation. Antigen-presenting rather than epithelial cells appear to be the main source of IL-18 in T. gondii-induced small intestinal inflammation.

Mo2012 Augmentation of Colonic Inflammation by TL1A is Most Severe in the Presence of a Genetic Susceptibility and Bacterial Trigger

TL1A (TNFSF15) is a costimulatory molecule in the TNF superfamily that binds to the receptor DR3 (TNFRSF25). TL1A has been genetically associated with susceptibility to Crohn's disease and ulcerative colitis in humans. Mice overexpressing TL1A develop small intestinal pathology and fibrotic responses somewhat akin to Crohn's disease. In this study, we used Helicobacter bilis infected mdr1a-/mice as a model of colitis to investigate the relevance of TL1A to disease. Blockade of TL1A with a monoclonal antibody delayed disease development, but did not reduce intestinal signs of disease. However, qPCR analysis of mRNA isolated from the colon of diseased control mice demonstrated minimal upregulation of TL1A in this model. In contrast to the blocking study, dosing of H. bilis infected mdr1a-/mice with TL1A-Fc, an agonist reagent, significantly accelerated disease development and mortality. Disease exacerbation was also observed in uninfected mdr1a-/mice, although disease was much milder. No disease was observed in uninfected wild type FVB mice. These data suggest that TL1A signaling can augment intestinal inflammation, but that on its own, it is not enough to induce inflammation. In the presence of a genetic susceptibility and triggering factor, TL1A can significantly accelerate intestinal pathology.

Sa1742 Capsule Endoscopy in Octogenarians: Analysis of a Large Prospectively Collected Database

Capsule endoscopy (CE) is a well accepted and accurate diagnostic tool for evaluation of small intestinal pathology. With the increasing population of geriatric patients, the etiology for iron deficiency anemia (IDA), overt and occult obscure gastrointestinal bleeding (OGIB) can be evaluated with the use of CE. There is limited published data on the outcomes and findings of CE in patients particularly over the age of 80.

Transformation of videocapsule images to detect small bowel mucosal differences in celiac versus control patients

BackgroundVideocapsule endoscopy can be useful to detect small intestinal pathology in celiac disease patients. However, presence of extraneous features including air bubbles and opaque fluids can complicate the analysis. A technique for quantitative analysis of videocapsule images is presented that is robust to presence of extraneous features. MethodVideocapsule clips were acquired from five small intestinal locations in 12 celiacs with villous atrophy and 11 control patients. Clips were 200 frames in length, their resolution was 576×576 pixels and 256 grayscale levels, with 2/s frame rate. The dominant period (DP), defined as the tallest peak in the ensemble average power spectrum, was computed over each clip without removal of extraneous features. Ensemble average basis images were constructed, and measurements were made of their frame-to-frame variation in brightness and texture. ResultsFrom pooled basis images, celiac images had greater texture than controls and exhibited more brightness variation (p<0.05 in mean and p<0.01 in standard deviation). In celiacs, correlation existed between greater textural alterations versus longer DP (r2=0.47), and between greater brightness variation and longer DP (r2=0.33). There was no significant correlation between quantitative features and DP in controls (r2<0.25). ConclusionsUsing this new method, celiac videoclips were quantitatively distinguishable from control videoclips without manual or computer-assisted detection, masking, and removal of extraneous image features. Furthermore, in celiac but not control basis images, larger textural and brightness alterations were correlated to longer DP. Greater textural and brightness alterations, and thus longer periodicities, are likely related to presence of villous atrophy.

Magnesium sulfate as an oral contrast medium in magnetic resonance imaging of the small intestine

To explore the use of magnesium sulfate (MgSO4) as an oral contrast medium (CM) in MRI of the small intestine. By comparing MgSO4 SNRs at different concentrations, we determined that 2.5% MgSO4 is the ideal concentration for small bowel MRI. Twenty volunteers underwent MRI after drinking 2.5% MgSO4. Thirty-one patients with clinical suspicion of small intestinal pathology underwent both MRI and the air-barium contrast examination. The patient's tolerance, side effects and complications were noted. 2.5% MgSO4 can decrease the absorption of water and fully fill the enteric cavity, thereby increasing the contrast between the intestinal wall and lumen and facilitating radiographic examination of the small bowel. The mean diameter of the small intestine was 19.8±1.21 mm in the 20 volunteers consuming 2.5% MgSO4 and 12.7±0.84 mm in the 20 volunteers given water. There was a significant difference (P<0.05) between the diameters of the small intestine of the two groups. But there were no significant differences (P>0.05) in side effects between MgSO4 and water groups. Small intestinal MRI was successfully performed in all 31 patients, who were also examined by the double contrast barium, which gave almost identical diagnoses to MRI in all cases except for 1 patient with small intestinal hemorrhage. MRI with 2.5% MgSO4 can demonstrate intestinal abnormalities. Therefore, 2.5% MgSO4 solution is an ideal oral CM for small bowel MRI.

Morphometric study of the layers of the canine small intestine at five sampling sites

The histology of the canine intestine has not been accurately defined. To establish the precise thickness of its different layers, whole wall samples of the small intestine were removed from 41 cadavers at five standardised sampling sites (duodenum, proximal jejunum, distal jejunum, proximal ileum and distal ileum). The total thickness was estimated by morphometry, as was the thickness of the mucosa, muscularis mucosae, submucosa and muscularis externa. In addition, the size of the lymphoid aggregates in the submucosa and the thickness of the circular and longitudinal layers within both the muscularis mucosae and the muscularis externa were estimated. The total intestinal thickness depended very much upon the thickness of the mucosa and submucosa. The mucosa decreased progressively from proximal to distal parts of the small intestine (47% reduction). The thickness of the submucosa, however, changed little from the duodenum to the distal jejunum, but increased significantly in the ileum; this change was positively correlated with the amount of lymphoid tissue. Sex influenced the thickness of the intestinal wall, with males displaying higher thickness values along the small intestine. Conversely, no correlation between bodyweight and intestinal thickness was found for any of the five sampling sites. This study gives absolute and relative values for the thickness of the layers of the dog intestine which might help in the diagnosis of small intestinal pathology from postmortem samples and/or endoscopic biopsies.