Herbal medicinal products for inflammatory bowel disease: A focus on those assessed in double-blind randomised controlled trials.

Inflammatory bowel disease patients frequently use herbal products as complementary or alternative medicines to current pharmacotherapies and obtain information on them mainly from the internet, social media, or unlicensed practitioners. Clinicians should therefore take a more active role and become knowledgeable of the mechanisms of action and potential drug interactions of herbal medicines for which evidence of efficacy is available. The therapeutic efficacy and safety of several herbal medicines have been studied in double-blind randomised controlled trials (RCTs). Evidence of efficacy is available for Andrographis paniculata extract; curcumin; a combination of myrrh, extract of chamomile flower, and coffee charcoal; and the Chinese herbal medicines Fufangkushen colon-coated capsule and Xilei san in patients with ulcerative colitis; and Artemisia absinthium extract and Boswellia serrata resin extract in patients with Crohn's disease. However, most of this evidence comes from single small RCTs with short follow-up, and the long-term effects and safety of their use have not yet been established. Thus, our findings indicate that further appropriately sized RCTs are necessary prior to the recommended use of these herbal medicines in therapy. In the meantime, increasing awareness of their use, and potential drug interactions among physicians may help to reduce unwanted effects and adverse disease outcomes.

The use of single balloon enteroscopy in Crohn's disease and its impact on clinical outcome.

OBJECTIVES: Single balloon enteroscopy (SBE) is an effective and safe modality for the diagnosis and therapeutic intervention of small bowel disorders. Its use in patients with Crohn's disease (CD) and particularly its effect on management changes in CD have not yet been determined. MATERIALS AND METHODS: We performed a retrospective review of the endoscopic and clinical data available on a cohort of patients with small bowel CD who had undergone SBE to determine the diagnostic and therapeutic yield of the procedure and the initial and longer-term impact it had on clinical management. RESULTS: About 52 patients have undergone SBE in our unit for the investigation of known (n = 39) or suspected (n = 13) small bowel CD with a diagnostic yield of 77% and 39%, respectively. SBE had an immediate clinical impact in 69% (n = 33) of patients, including dilatation of a stricture in 27% (n = 13), initiation or adjustment of dose of medications in 48% (n = 23), referral for surgical resection in 6% (n = 3). Moreover, the procedure permitted determining a new diagnosis of CD in 8% of the patients (n = 4), and excluding it in 8% (n = 4). Longer term follow-up was available in 34 patients (65%) which showed a significant difference in mean HBI score from 6.6 before the procedure to 4.2 after it (p < .0001). CONCLUSIONS: SBE has a high diagnostic and therapeutic yield in CD and significantly impacts disease management. Careful patient selection is a key factor in optimizing its use in CD.

The Innate and Adaptive Immune System as Targets for Biologic Therapies in Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is an immune-mediated inflammatory condition causing inflammation of gastrointestinal and systemic cells, with an increasing prevalence worldwide. Many factors are known to trigger and maintain inflammation in IBD including the innate and adaptive immune systems, genetics, the gastrointestinal microbiome and several environmental factors. Our knowledge of the involvement of the immune system in the pathophysiology of IBD has advanced rapidly over the last two decades, leading to the development of several immune-targeted treatments with a biological source, known as biologic agents. The initial focus of these agents was directed against the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) leading to dramatic changes in the disease course for a proportion of patients with IBD. However, more recently, it has been shown that a significant proportion of patients do not respond to anti-TNF-α directed therapies, leading a shift to other inflammatory pathways and targets, including those of both the innate and adaptive immune systems, and targets linking both systems including anti-leukocyte trafficking agents-integrins and adhesion molecules. This review briefly describes the molecular basis of immune based gastrointestinal inflammation in IBD, and then describes how several current and future biologic agents work to manipulate these pathways, and their clinical success to date.

The natural history of small bowel angiodysplasia.

BACKGROUND: Small bowel angiodysplasias (SBA) account for 50% of obscure gastrointestinal bleeding. Lesions bleed recurrently and current treatments are relatively ineffective at reducing re-bleeding. Little is known about the natural history of SBA which is needed to guide treatment decisions and counsel patients on prognosis. AIM: The aim of this study is to describe the natural history of a cohort of patients with SBA. METHODS: Patients with SBA were identified retrospectively and clinical and outcome information were collected. Logistic regression analysis was performed to identify factors associated with re-bleeding. RESULTS: SBAs were found in 86 patients of which 54% (n = 47) were female, and the average age was 71.6 years. The majority (69%) had multiple lesions, mean of 2.76/patient, and 65% were located in the jejunum. Follow-up was available in 65% (n = 56). There was a significant increase in haemoglobin level from 10.05g/dL to 11.94g/dL, p < 0.001 after mean follow up of 31.9 (6-62) months. Re-bleeding events occurred in 80% (n = 45), with an average of 2.91/person. The mean interval between diagnosis and the first re-bleeding event was 10.7 months. Of the group overall, 70% (n = 40) required transfusions during follow up, and 67% required hospitalisation due to re-bleeding. About 50% received a directed treatment, including argon plasma coagulation, somatostatin analogues, or surgical resection. A total of 3.5% (n = 2) died as a direct consequence of bleeding from SBAs. Multiple lesions (p = 0.048) and valvular heart disease (p = 0.034) were predictive of re-bleeding. CONCLUSION: Our results show the significant impact of SBA on patients' morbidity, with high rates of re-bleeding, persistent anaemia and a mortality rate of 3.5%, despite the use of currently available medical and endoscopic therapies.

Expression of Angiogenic Factors in Patients With Sporadic Small Bowel Angiodysplasia.

GOALS: To identify putative angiogenic factors associated with sporadic small bowel angiodysplasia (SBA). BACKGROUND: SBAs account for 50% of obscure gastrointestinal bleeding and due to delays in diagnosis and ineffective treatments, are associated with high levels of morbidity and mortality. Treatment development is impeded by a limited knowledge of the pathophysiology behind SBA formation. STUDY: We identified patients with definite sporadic SBA, and fecal immunochemical-negative controls were recruited from our institution's colorectal cancer screening program. Serum levels of VEGF, endoglin, Angiopoietin-2 (Ang-2), PDGF, Angiopoietin-1 (Ang-1), and TNF-α were measured using commercially available enzyme-linked immunosorbent assay kits. On the basis of serum results, we measured gene expression of target angiogenic factors in small bowel biopsy samples from angiodysplasias and unaffected tissue by quantitative PCR assessment. RESULTS: Serum samples were analyzed from 40 SBA patients and 40 controls. Median serum levels of Ang-2 were significantly higher in patients than controls with levels of Ang-1 and TNF-α significantly lower. There were no differences in serum levels of VEGF, endoglin, or PDGF. Gene expression levels of Ang-1, Ang-2, and their receptor Tie2 were all significantly higher in biopsies from areas of angiodysplasia compared with normal small bowel. CONCLUSIONS: This study, the first to explore the role of angiogenic factors in SBA, has identified a positive association between SBA and the Angiopoietin pathway, with increased serum and mucosal expression of Ang-2, which could potentially be used as a serum biomarker and future therapeutic target to improve outcome in affected patients.

Small bowel Crohn's disease: an emerging disease phenotype?

An increasing understanding of the pathogenesis of Crohn's disease (CD), coupled with improvements in therapeutic options, has promoted the concept of stratifying patients with CD into distinct disease phenotypes according to risk. Small bowel CD, due to the numerous non-specific potential symptoms and the anatomical location of the disease, is a particularly difficult phenotype to identify. The fact that the majority of de novo strictures occur in the ileum/ileo-colonic region ensures that recognition of small bowel involvement is essential. Certainly, it is becoming increasingly recognised due to improvements in imaging and endoscopic techniques. Both CT and MR enterography appear capable of accurately diagnosing small bowel CD. Furthermore, the development of capsule endoscopy and balloon-assisted enteroscopy allow direct visualisation of the small bowel. Limited data to date would suggest that small bowel CD is a difficult entity to treat even in the current era of the ever-expanding field of biological therapies. Further long-term follow-up studies are necessary using both small bowel capsule endoscopy and cross-sectional imaging to truly assess, firstly, whether small bowel CD is more resistant to treatment and, secondly, whether it has an effect over time in terms of complications. In the future, serological and genetic tests, coupled with the aforementioned investigations, will permit early diagnosis and early treatment of small bowel CD.

Colon capsule endoscopy as possible filter test for colonoscopy selection in a screening population with positive fecal immunology.

BACKGROUND AND STUDY AIMS: Stool tests are highly useful in colorectal cancer (CRC) screening programs; however, they are not as specific as users would like, and place a major burden on resources and subject a number of patients to the risks of invasive optical colonoscopy unnecessarily. Colon capsule endoscopy (CCE) has the potential to reduce the need for optical colonoscopy. To date, the role of CCE in a fecal immunological test (FIT)-based CRC screening program has not been formally evaluated. The aims of this study were to assess the sensitivity, specificity, and negative and positive predictive values of CCE compared with optical colonoscopy in an FIT-positive CRC screening cohort. PATIENTS AND METHODS: A prospective comparison study of CCE compared with optical colonoscopy was undertaken within the second round of a FIT-based bowel screening pilot. Participants with a positive FIT result were invited to undergo both CCE and optical colonoscopy. CCE was performed on Day 1 and optical colonoscopy was performed the following morning. RESULTS: A total of 62 participants were recruited. Optical colonoscopy detected at least one polyp in 36 participants (58 %), significant lesions in 18 (29 %), and cancer in 1 (2 %). There was good correlation between CCE and optical colonoscopy for any lesion and for significant lesions (r = 0.62 and 0.84, respectively). The negative predictive value of CCE was high both for any polyp (90 %) and for significant lesions (96 %). CONCLUSIONS: CCE is a safe and effective means of detecting cancer and polyps in a positive FIT screening cohort. The results suggest that CCE would be a useful "filter test" in this situation, and would reduce the number of colonoscopies performed by 71 %.

Current applications and potential future role of wireless capsule technology in Crohn's disease.

BACKGROUND: The development of capsule technology has modified our approach to the diagnosis of gastrointestinal disease. The relatively rapid uptake of capsule endoscopy as an important clinical tool can be largely ascribed to a number of key factors, including the fact that it is a relatively easy examination to perform in an outpatient setting. It has been established as an integral part of the investigation pathway for obscure gastrointestinal bleeding and suspected small bowel Crohn's disease (CD). CURRENT USE OF CAPSULE ENDOSCOPY: Small bowel CD can be a challenging entity to diagnose. Capsule endoscopy has been shown to be both useful and safe in patients with both suspected and established small bowel CD. In suspected disease, capsule endoscopy has both a high diagnostic yield and negative predictive value. Capsule findings lead to changes in management in up to 73% of patients with established CD. However, while the technology appears capable of detecting subtle mucosal changes not readily apparent on alternate imaging modalities, the question of what actually constitutes small bowel CD as described by capsule is an issue that remains unresolved to date. Thus, capsule endoscopy is best utilised in tandem with advanced imaging and endoscopic techniques such as balloon- assisted enteroscopy. FUTURE DEVELOPMENTS: The development of a capsule capable of viewing the colon coupled with improvements in image quality and battery life are likely to lead to the increasing uptake of this technology. In the future, 'interactive' capsules with the ability to view the entire gastrointestinal tract may be a reality.

Microscopic colitis: clinical characteristics, treatment and outcomes in an Irish population.

BACKGROUND AND AIMS: Many aspects of microscopic colitis remain poorly understood. Our aim was to report a single centre experience with this condition. METHODS: Two hundred and twenty-two patients (52 male, 170 female; median age 64 years; range 32-90) diagnosed between 1993 and 2010 were studied. Medical notes were reviewed, and data on age, gender, clinical features, history of autoimmune diseases, medication use, cigarette smoking, histology and outcome were collected. RESULTS: There were 99 cases of lymphocytic and 123 of collagenous colitis. Diarrhoea was almost invariably present (98 %) while abdominal pain (24 %), weight loss (10 %), faecal incontinence (8 %) and blood PR (5 %) were also described. Twenty-eight percent had concomitant autoimmune diseases, most commonly coeliac disease. Patients were taking a variety of medications at diagnosis thought to be associated with microscopic colitis including NSAIDs (22 %), aspirin (19 %), statins (15 %), proton pump inhibitors (19 %) and SSRIs (10 %) at diagnosis. Prior to the widespread use of budesonide in our institution, 33 % of patients required two or more medications during therapy compared to 15 % following the introduction of budesonide (p = 0.001). Thirty-eight percent of patients achieved spontaneous remission with either no treatment or simple anti-diarrhoeals. Using a multivariate model, the only factor associated with spontaneous remission was male gender (RR 1.9; 95 % CI 1.0-3.6; p = 0.04). Two patients had refractory microscopic colitis; one required a colectomy while a more recent case has responded to anti-TNFα therapy. CONCLUSION: Microscopic colitis is predominantly a benign and self-limiting disorder. The introduction of budesonide has revolutionised treatment of this lesser studied inflammatory bowel disease.

Small bowel angiodysplasia and novel disease associations: a cohort study.

OBJECTIVE: Gastrointestinal angiodysplasias recurrently bleed, accounting for 3-5% of obscure gastrointestinal bleeding. The advent of small bowel capsule endoscopy (SBCE) has led to an increased recognition of small bowel angiodysplasias (SBAs) but little is known about their etiology. Previous small cohorts and case reports suggest an equal gender incidence and associations with cardiovascular disease, renal impairment, and coagulopathies. METHODS: Patients with SBA were identified from our SBCE database. A control group, in whom gastrointestinal bleeding had been excluded, was also identified. Information on patient demographics, past medical/surgical/social history and medications was prospectively obtained. RESULTS: A total of 82 patients and 95 controls were identified. Data was available from 81% (n = 66) of SBA patients. The mean age of patients and controls was 66.9 years (35-90) and 69.2 years (54-77), and 60% (n = 40) and 58% (n = 55) were females, respectively. There was a higher rate of all comorbidities in the SBA group 92% (61/66) versus controls 76% (72/95) p < 0.002. Significant associations were found with: hypertension (odds ratio [OR] 2.8), ischemic heart disease (OR 4.25), arrhythmias (OR 4.36), valvular heart disease (OR 18), congestive heart failure (OR 4.22), chronic kidney disease (CKD) (OR 8.4), chronic respiratory conditions (OR 2.0), and previous venous thromboembolism (VTE) (OR 6.4). Anticoagulant use was higher in patients with SBA, 50% (n = 33) versus 27% (n = 26) of controls, p < 0.002, specifically warfarin and asasantin retard. CONCLUSIONS: SBA occurs in elderly patients with cardiovascular disease and CKD, as previously suggested. This study identifies a previously unrecognised risk in females, patients with chronic respiratory conditions and VTE, and the use of warfarin and asasantin retard. These associations should raise awareness of possible underlying SBA in risk patients with anemia.

Effectiveness and predictors of response to somatostatin analogues in patients with gastrointestinal angiodysplasias: a systematic review and individual patient data meta-analysis.

BACKGROUND: Gastrointestinal angiodysplasias are vascular malformations that often cause red blood cell transfusion-dependent anaemia. Several studies suggest that somatostatin analogues might decrease rebleeding rates, but the true effect size is unknown. We therefore aimed to investigate the efficacy of somatostatin analogues on red blood cell transfusion requirements of patients with gastrointestinal angiodysplasias and to identify subgroups that might benefit the most from somatostatin analogue therapy. METHODS: We did a systematic review and individual patient data meta-analysis. We searched MEDLINE, Embase, and Cochrane on Jan 15, 2016, with an updated search on April 25, 2021. All published randomised controlled trials and cohort studies that reported on somatostatin analogue therapy in patients with gastrointestinal angiodysplasias were eligible for screening. We excluded studies without original patient data, single case reports, small case series (ie, <10 participants), studies in which patients had a specific aetiology of gastrointestinal angiodysplasias, and studies in which somatostatin analogue therapy was initiated simultaneously with other treatment modalities. Authors of eligible studies were invited to share individual patient data. Aggregated data was used if individual patient data were not provided. The primary outcome was the mean reduction in the number of red blood cell transfusions during somatostatin analogue therapy, compared with baseline, expressed as the incidence rate ratio (IRR) and absolute mean decrease. We defined patients as either good responders (≥50% reduction in the number of red blood cell transfusions) or poor responders (<50% reduction). A mixed-effects negative binomial regression was used to account for clustering of patients and skewness in data. This study was registered in the International Prospective Register of Systematic Reviews (PROSPERO), number CRD42020213985. FINDINGS: We identified 11 eligible studies (one randomised controlled trial and ten cohort studies) of moderate-to-high quality and obtained individual patient data from the authors of nine (82%) studies. The remaining two (18%) studies provided sufficient information in the published manuscript to extract individual patient data. In total, we analysed data from 212 patients. Somatostatin analogues reduced the number of red blood cell transfusions with an IRR of 0·18 (95% CI 0·14-0·24; p<0·0001) during a median treatment duration of 12 months (IQR 6·0-12·0) and follow-up period of 12 months (12·0-12·0), correlating with a mean absolute decrease in the number of red blood cell transfusions from 12·8 (95% CI 10·4-15·8) during baseline to 2·3 (1·9-2·9) during follow-up-ie, a reduction of 10·5 red blood cell transfusions (p<0·0001). 177 (83%) of 212 patients had a good response to somatostatin analogue therapy (defined as at least a 50% reduction in the number of red blood cell transfusions). Heterogeneity across studies was moderate (I2=53%; p=0·02). Location of gastrointestinal angiodysplasias in the stomach compared with angiodysplasias in the small bowel and colon (IRR interaction 1·92 [95% CI 1·13-3·26]; p=0·02) was associated with worse treatment response. Octreotide was associated with a better treatment response than lanreotide therapy (IRR interaction 2·13 [95% CI 1·12-4·04]; p=0·02). The certainty of evidence was high for the randomised controlled trial and low for the ten cohort studies. Adverse events occurred in 38 (18%) of 212 patients receiving somatostatin analogue therapy, with ten (5%) discontinuing this therapy because of adverse events. The most common adverse events were loose stools (seven [3%] of 212), cholelithiasis (five [2%]), flatulence (four [2%]), and administration site reactions (erythema, five [2%]). INTERPRETATION: Somatostatin analogue therapy is safe and effective in most patients with red blood cell transfusion-dependent bleeding due to gastrointestinal angiodysplasias. Somatostatin analogue therapy is more effective in patients with angiodysplasias located in the small bowel and colon, and octreotide therapy seems to be more effective than lanreotide therapy. FUNDING: The Netherlands Organisation for Health Research and Development and the Radboud University Medical Center.

Shared changes in angiogenic factors across gastrointestinal vascular conditions: A pilot study.

BACKGROUND: Neovascularisation is common to a variety of gastrointestinal (GI) disorders with differing aetiologies and presentations; usually affecting adults above 60 years. Shared angiogenic factors modulated by disease specific elements could be a common denominator and represent novel diagnostic and therapeutic targets. As yet, assessment of angiogenic factors across several GI vascular disorders associated with recurrent bleeding and anaemia has not been reported. AIM: To assess serum levels of angiogenic factors in several intestinal vascular disorders. METHODS: A case control study was performed in Tallaght University Hospital in patients with endoscopically proven small bowel angiodysplasia (SBA), portal hypertensive gastropathy (PHG), gastric antral vascular ectasia (GAVE) and non-bleeding, non-anaemic controls. Using enzyme-linked immunosorbent assay, concentrations of Angiopoietin 1 (Ang-1), Ang-2 and vascular endothelial growth factor (VEGF) were measured from 2 serum tubes of blood following informed consent. The relative expression of Ang-1 and Ang-2 and Ang-1/2 ratio was calculated and compared between groups. Statistical analysis was applied using a t-test, and a P value of < 0.05 was considered significant. RESULTS: To date 44 samples were tested: 10 SBA, 11 PHG, 8 GAVE and 15 controls. Mean age 60 (range 20-85) years and 20 (45%) were males. Controls were significantly younger (49 years vs 66 years, P = 0.0005). There was no difference in VEGF levels between the groups (P = 0.6). SBA, PHG and GAVE Ang-1 levels were similar and were significantly lower than controls, (P = 0.0002, 95%CI: 241 to 701). Ang-2 levels were statistically higher in PHG and GAVE groups compared to controls (P = 0.01, 95%CI: 77.8 to 668) and as a result, also had a lower Ang-1/2 ratios compared to controls. While SBA Ang-2 levels were higher than controls, this did not reach statistical significance. Neither age nor haemoglobin level, which was similar between disease groups, could explain the difference. In addition, the median Ang-1/Ang-2 ratio for all patients was found to be significantly lower compared to controls, 8 vs 28 respectively, P = 0.001, 95%CI: -27.55 to -7.12. CONCLUSION: Our novel pilot study suggests common alterations in Ang-1 and Ang-2 levels across several GI vascular disorders. Differences in Ang-1/Ang-2 ratios among vascular disorders compared to controls suggest disease-specific modulation.

Rendu-Osler-Weber disease: a gastroenterologist's perspective.

Hereditary hemorrhagic teleangectasia (HHT, or Rendu-Osler-Weber disease) is a rare inherited syndrome, characterized by arterio-venous malformations (AVMs or Telangiectasia). The most important and common manifestation is nose bleeds (epistaxis). The telangiectasias (small AVMs) are most evident on the lips, tongue, buccal mucosa, face, chest, and fingers, however; large arterio-venous malformations can also occur in the lungs, liver, pancreas, or brain. Telangiectasias in the upper gastrointestinal tract are known to occur, however data regarding possible small-bowel involvement is limited due to technical difficulties in visualizing the entire gastrointestinal tract. The occurrence of AVMs in the stomach and small bowel can result in chronic bleeding and anaemia. Less frequently, this may occur due to bleeding from oesophageal varices, as patients with HHT can develop hepatic parenchymal AVMs or vascular shunts which cause hepatic cirrhosis and portal hypertension. Gastroenterologists have a crucial role in the management of these patients, however difficulties remain in the detection and management of complications of HHT in the gastrointestinal tract.

Assessment of Crohn's Disease Activity: Magnetic Resonance Enterography in Comparison with Clinical and Endoscopic Evaluations.

Crohn's disease (CD) is a chronic inflammatory condition characterized by continuous mucosal damage and ongoing wound healing of the intestines. The fibrinolytic system is involved in early parts of the wound healing process. Fibrin is a key mediator of primary blood clot formation and is formed by cross-linking of fibrinogen. To gain insights into the dynamics of wound healing in CD patients we investigated the conversion of fibrinogen into fibrin by the pro-peptide FPA, the amount of factor XIII cross-linked fibrin and total fibrin clot. METHODS: Serum samples of 35 CD patients, 15 non-inflammatory bowel disease (non-IBD) patients and 39 age-matched healthy controls were analyzed for three novel neo-epitope markers: D-fragment and D-dimer, reflecting the degradation of total fibrin clot and factor XIII cross-linked fibrin, as well as FPA, reflecting synthesis of fibrin. RESULTS: Crohn's disease patients had a significantly lower D-dimer level (p=0.0001) compared to healthy controls. Crohn's disease and non-IBD patients had a significantly higher level of FPA (p<0.0001) and D-fragment/D-dimer ratio (p<0.0001 and p=0.02). FPA, D-dimer and D-fragment/D-dimer ratio could distinguish CD patients from healthy controls with area under the curve of 0.92 (95% CI 0.83-0.97), 0.78 (95% CI 0.67-0.87) and 0.85 (95% CI 0.75-0.93), respectively. CONCLUSION: Wound healing parameters were clearly changed in CD patients. FPA levels were higher in CD patients as compared to healthy controls, indicating more ongoing wound healing. D-dimer levels were lower in CD patients than in healthy controls, indicating impaired wound healing due to poor quality of factor XIII cross-linked fibrin and clot resolution.

An overview of angiodysplasia: management and patient prospects.

INTRODUCTION: Gastrointestinal angiodysplasias (GIADs) have a wide variety of presentations, which can be significant and debilitating in a subset of patients. Endoscopic ablation is currently the most effective treatment for GIADs, however re-bleeding rates are high. Several medical have been used for GIADs and reported in the literature, however these medications have significant side effect profiles and randomized controlled trials are lacking. A relatively poor understanding of the pathophysiology of GIAD formation has limited the development of more effective treatments and improved diagnostic and prognostic markers for GIAD. However, recent advances in research in the area of angiogenesis have identified a potential role for certain angiogenic factors including Angiopoeitin 1 and 2, in the pathophysiology of GIAD. Areas covered: We performed an extensive pubmed search of all articles mentioning GIAD and summarized our findings focussing on patient management and prospects. We summarize the available literature regarding the medical, endoscopic, and radiological management of GIAD and the value of clinical prognostic factors. Expert commentary: Although the area of angiogenesis is a novel area of research in GIAD, it represents an exciting avenue for development with the potential to improve diagnostic and prognostic tools to improve patient outcome.

Same-day colon capsule endoscopy is a viable means to assess unexplored colonic segments after incomplete colonoscopy in selected patients.

BACKGROUND: Same-day colon capsule endoscopy (CCE) immediately following incomplete optical colonoscopy (OC) would have a number of advantages for patients, while also presenting unique procedural challenges including the effect of sedation on capsule propulsion and patient tolerance of protracted preparation and fasting. AIM: The aim of this article is to prospectively assess the efficacy of same-day CCE after incomplete OC in an unselected patient cohort. METHODS: This was an observational, prospective, single-centre study of CCE post-incomplete colonoscopies. Patients with an incomplete OC for any reason other than obstruction or inadequate bowel preparation were recruited. CCE was performed after a minimum of a one-hour fast. Once the patient was fully alert, intravenous metoclopramide was administered after capsule ingestion when possible, and a standard CCE booster protocol was then followed. Relevant clinical information was recorded. CCE completion rates, findings and their impact, and adverse events were noted. RESULTS: Fifty patients were recruited, mean age = 57 years and 66% (n = 32) were female. Seventy-six per cent (n = 38) of CCEs were complete; however, full colonic views were obtained in 84% (n = 42) of cases. Patients > 50 years of age were five times more likely to have an incomplete CCE and there was also a trend towards known comorbidities associated with hypomobility having reduced excretion rates. Overall diagnostic yield for CCE in the unexplored segments was 74% (n = 37), with 26% (n = 13) of patients requiring significant changes in management based on CCE findings. The overall incremental yield was 38%. CCE findings were normal 26% (n = 13), polyps 38% (n = 19), inflammation 22% (n = 11), diverticular disease 25 (n = 12), angiodysplasia 3% (n = 1) and cancer 3% (n = 1). Significant small bowel findings were found in three (6%) cases, including Crohn's disease and a neuroendocrine tumour. A major adverse event occurred in one patient (2%), related to capsule retention. CONCLUSION: Same-day CCE is a viable alternative means to assess unexplored segments of the colon after incomplete OC in selected patients.

Usefulness of contrast-enhanced ultrasound (CEUS) in Inflammatory Bowel Disease (IBD).

Intestinal ultrasonography has emerged as a cheap, non-invasive and readily accessible modality for the assessment of a number of gastroenterological diseases. Over the last decade, particularly due to the widespread use of biological agents in Inflammatory Bowel Disease (IBD), guidelines regarding management and follow-up advise more regular disease assessment and surveillance in order to guide treatment adjustments, and provide more personalised care. Given the young age of the majority of patients with IBD the availability of an alternative modality to harmful radiation or the risks of endoscopy for this indication offers an appealing advantage. Intestinal ultrasonography has been shown to be as sensitive and specific for detecting IBD as both computed tomography and magnetic resonance enterography, and endoscopic evaluation. More recent developments in the technology of ultrasonography equipment and the use of intravenous contrast agents (contrast enhanced ultrasonography, known as CEUS), have significantly increased the ability to both detect disease location, determine the disease activity and also potentially the difference between fibrotic and inflammatory segments. This review focusses specifically on the value of CEUS for the diagnosis of both Crohn's disease and Ulcerative Colitis, in determining disease activity, extraintestinal complications, determination of fibrosis as well as its more recent use in assessing and predicting response to biological and immunosuppressive therapies.

Assessment of serum angiogenic factors as a diagnostic aid for small bowel angiodysplasia in patients with obscure gastrointestinal bleeding and anaemia.

AIM: To assess the use of serum levels of angiopoietin-1 (Ang1), Ang2 and tumor necrosis factor-α (TNFα) as predictive factors for small bowel angiodysplasia (SBA). METHODS: Serum samples were collected from patients undergoing capsule endoscopy for any cause of obscure gastrointestinal bleeding (OGIB) or anaemia. Based on small bowel findings patients were divided into 3 groups: (1) SBA; (2) other bleeding causes; and (3) normal, according to diagnosis. Using ELISA technique we measured serum levels of Ang1, Ang2 and TNFα and compared mean and median levels between the groups based on small bowel diagnosis. Using receiver operator curve analysis we determined whether any of the factors were predictive of SBA. RESULTS: Serum samples were collected from a total of 120 patients undergoing capsule endoscopy for OGIB or anaemia: 40 with SBA, 40 with other causes of small bowel bleeding, and 40 with normal small bowel findings. Mean and median serum levels were measured and compared between groups; patients with SBA had significantly higher median serum levels of Ang2 (3759 pg/mL) compared to both other groups, with no significant differences in levels of Ang1 or TNFα based on diagnosis. There were no differences in Ang2 levels between the other bleeding causes (2261 pg/mL) and normal (2620 pg/mL) groups. Using Receiver Operator Curve analysis, an Ang2 level of > 2600 pg/mL was found to be predictive of SBA, with an area under the curve of 0.7. Neither Ang1 or TNFα were useful as predictive markers. CONCLUSION: Elevations in serum Ang2 are specific for SBA and not driven by other causes of bleeding and anaemia. Further work will determine whether Ang2 is useful as a diagnostic or prognostic marker for SBA.

The organisation and needs of young sections belonging to UEG National Societies: Results of a Europe-wide survey.

One of the aims of the Young Talent Group (YTG) is to make United European Gastroenterology (UEG) more attractive for young fellows interested in gastroenterology, and to involve them actively in UEG activities, by collaborating with young GI sections (YGIS) across Europe. Therefore, the YTG launched a survey to collect up-to-date information on YGISs belonging to UEG National Societies. The Friends of YTG were chosen as the target population and received a web-based questionnaire concerning their personal information, the structure of YGIS in their respective country, the YGIS' support mechanisms for young trainees, and ideas on how to improve them. Overall, 24 of 29 Friends answered the survey (83%). Among the Societies surveyed, only half have a young section. Typically, YGIS are supported, but not influenced, by National Societies through several initiatives. Results of the survey suggest that a lack of funding, of harmonised education, and of active roles available within National Societies, were the concerns most prevalent among young fellows. Our survey shows that the development of YGIS is being hindered by organisational, financial, and political issues. The YTG believes that a close collaboration between National Societies, UEG, and the YTG is necessary in order to offer young fellows the most productive and professionally satisfying future possible.

Gut microbiota and inflammatory bowel disease: so far so gut!

Major advances have occurred in the knowledge of the pathogenesis of inflammatory bowel disease (IBD) over the last decade, and perhaps the most major, and clinically advantageous of these advances has been the discovery of the microbiome as a key multifaceted component of inflammation. The gut microbiome is the largest known group of cells in the body, and is now recognized as an organ in its own right. Initial studies looking at a possible role of bacterial manipulation of the immune system in IBD, looked at identifying a specific bacterial species, and were not representative of a feasible model of inflammation in IBD overall. More recently there has been a shift towards the concept of dysbiosis, and the acceptance that a number of bacterial factors interact with the immune system in order for inflammation to occur. In the present review we will focus on past perspective of the role of microbiota in IBD, current evidences about dysbiosis in IBD and also the main therapeutic modalities to affect IBD by affecting gut microbiota: probiotics, prebiotics, fecal microbiota transplantation and emerging dietary intervention.