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.

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.

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.

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.

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.

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.

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.

Body mass index influences infliximab post-infusion levels and correlates with prospective loss of response to the drug in a cohort of inflammatory bowel disease patients under maintenance therapy with Infliximab.

INTRODUCTION: Infliximab is an effective treatment for inflammatory bowel disease (IBD). Studies differ regarding the influence of body mass index (BMI) on the response to infliximab, with the majority of studies indicating that increased BMI may be associated with a poorer response to Infliximab. However, the pharmacokinetic mechanisms causing this have not yet been reported. AIMS: Examine the correlation between BMI/immunosuppressant use with clinical response, trough and post-infusion levels of infliximab, tumour necrosis factor-α(TNF-α) and anti-drug antibodies(ATI), and determine if these factors can predict future response. METHODS: We collected serum from 24 patients receiving Infliximab before and 30 minutes following infusion. Clinical parameters were collected retrospectively and prospectively. ELISA measurements of infliximab, TNF-α and ATI were performed. RESULTS: We confirmed that patients with higher infliximab trough levels have a better response rate and that patients with an elevated BMI display a higher rate of loss of response (20%). Patients with a higher BMI had elevated post-infusion levels of infliximab. Additionally, the ratio of IFX/TNF-α trough levels correlated with clinical response to the following infusion. CONCLUSION: This study confirms that an elevated BMI is associated with a poorer response to infliximab. For the first time, we describe that a higher BMI correlates with higher post-infusion levels, however this does not correlate with a higher rate of response to the drug, suggesting that circulating drug levels do not correlate with tissue levels. Furthermore, in our small cohort of patients, we identified a possible predictive marker of future response to treatment which may be used to guide dose escalation and predict non-response to infliximab.

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 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 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.

Molecular detection of Helicobacter pylori antibiotic resistance in stool vs biopsy samples.

AIM: To compare (1) demographics in urea breath test (UBT) vs endoscopy patients; and (2) the molecular detection of antibiotic resistance in stool vs biopsy samples. METHODS: Six hundred and sixteen adult patients undergoing endoscopy or a UBT were prospectively recruited to the study. The GenoType HelicoDR assay was used to detect Helicobacter pylori (H. pylori) and antibiotic resistance using biopsy and/or stool samples from CLO-positive endoscopy patients and stool samples from UBT-positive patients. RESULTS: Infection rates were significantly higher in patients referred for a UBT than endoscopy (overall rates: 33% vs 19%; treatment-naïve patients: 33% vs 14.7%, respectively). H. pylori-infected UBT patients were younger than H. pylori-infected endoscopy patients (41.4 vs 48.4 years, respectively, P < 0.005), with a higher percentage of H. pylori-infected males in the endoscopy-compared to the UBT-cohort (52.6% vs 33.3%, P = 0.03). The GenoType HelicoDR assay was more accurate at detecting H. pylori infection using biopsy samples than stool samples [98.2% (n = 54/55) vs 80.3% (n =53/66), P < 0.005]. Subset analysis using stool and biopsy samples from CLO-positive endoscopy patients revealed a higher detection rate of resistance-associated mutations using stool samples compared to biopsies. The concordance rates between stool and biopsy samples for the detection of H. pylori DNA, clarithromycin and fluoroquinolone resistance were just 85%, 53% and 35%, respectively. CONCLUSION: Differences between endoscopy and UBT patients provide a rationale for non-invasive detection of H. pylori antibiotic resistance. However, the GenoType HelicoDR assay is an unsuitable approach.

Small bowel Dieulafoy lesions: An uncommon cause of obscure bleeding in cirrhosis.

Dieulafoy lesions (DLs) are an uncommon cause of gastrointestinal bleeding, accounting for up to 2% of cases overall. They are largely under recognised and difficult to treat. Up to 95% occur in the stomach, and only case reports document their occurrence in the small bowel (SB). Little is known about their pathophysiology, although there have been associations made previously with chronic liver disease, thought to be due to the erosive effects of alcohol on the mucosa overlying the abnormally dilated vessels. We present a case series of 4 patients with a long duration of obscure gastrointestinal bleeding, who were diagnosed with small intestinal DLs and incidentally diagnosed with chronic liver disease. The histories describe the challenges in both diagnosis and treatment of small intestinal DLs. Our case series suggest a previously unreported link between chronic liver disease and SB DLs which may be due to anatomical vasculature changes or a shift in angiogenic factors as a consequence of portal hypertension or liver cirrhosis.

Long-acting somatostatin analogues provide significant beneficial effect in patients with refractory small bowel angiodysplasia: Results from a proof of concept open label mono-centre trial.

INTRODUCTION: Small bowel angiodysplasias account for over 50% of causes of small bowel bleeding and carry a worse prognosis than lesions located elsewhere in the gastrointestinal tract. Re-bleeding rates are high even after first-line endoscopic therapy and are associated with high levels of morbidity for affected patients. Small trials of long-acting somatostatin analogues have shown promising results but have not yet been assessed in patients with refractory small bowel disease. AIM: The purpose of this study was to assess the effect of long-acting somatostatin analogues in reducing re-bleeding rates and transfusion requirements, and improving haemoglobin levels in patients with refractory small bowel angiodysplasia. METHODS: Patients with refractory small bowel angiodysplasia were treated with 20 mg of long-acting octreotide for a minimum of three months. Response was assessed according to: rates of re-bleeding, haemoglobin levels, transfusion requirements, and side effects. RESULTS: A total of 24 patients were initially treated and 20 received at least three doses. Rates of complete, partial and non-response were 70%, 20% and 10% respectively. Average haemoglobin rates increased from 9.19 g/dl to 11.35 g/dl (p = 0.0027, 95% confidence interval (CI) -3.5 to -1.1) in the group overall and 70% remained transfusion-free after a mean treatment duration of 8.8 months. The rate of adverse events was higher than previously reported at 30%. CONCLUSION: Long-acting somatostatin analogues offer a therapeutic advantage in a significant proportion of patients with small bowel angiodysplasia. With careful patient selection and close observation, a long-acting somatostatin analogue should be considered in all patients with persistent anaemia attributable to refractory disease in conjunction with other standard treatments.

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.

Long-term assessment of clinical response to adalimumab therapy in refractory ulcerative colitis.

INTRODUCTION: The role of antitumour necrosis factor agents, in particular infliximab in ulcerative colitis (UC) has been well established. More recently adalimumab, a fully humanized antitumour necrosis factor α monoclonal antibody, was licensed for refractory moderately active UC in 2012. Available outcome data for adalimumab from routine clinical practice is limited. AIMS: To evaluate the clinical response and remission to adalimumab in a cohort of UC patients. METHODS: Patients with UC treated with adalimumab were identified from our inflammatory bowel disease database from 2007. A retrospective chart review was undertaken. Demographic and clinical data were recorded including a Mayo score and C-reactive protein (CRP) where available. All patients received standard induction subcutaneous therapy (160/80/40 mg) followed by a maintenance dose of 40 mg fortnightly. Clinical and biochemical response was assessed at 6 and 12 months. Clinical response was defined by a reduction in Mayo score more than or equal to 3, whereas clinical remission was defined by a total score of 2 or less. Dose adjustments and adverse events were also noted. RESULTS: In all, 52 patients were identified. Of these, 65% (n=34) were male and the mean age was 45 years (range 23-72 years). A total of 65% (n=34) had left sided disease, 31% (n=16) pancolitis and 4% (n=2) proctitis. The majority commenced adalimumab due to a loss of response to immunomodulator therapy (n=45, 87%), whereas the remaining 13% (n=7) had loss of response or been intolerant to infliximab. The mean disease duration was 8 years (1-29 years). At baseline 85% (n=44) had moderate disease and 15% (n=8) had mild disease. The baseline mean CRP was 13.5 mg/l (range 1-82 mg/l) and the mean Mayo score was 6 (range 4-10). The mean duration of treatment was 18.5 months (range 4-95 months). Follow-up data was available in 46 (88%) and 37 (71%) patients at 6 and 12 months. Overall there was a statistically significant improvement in mean partial Mayo score on follow-up; 6 months=2 [P=0.0001, 95% confidence interval (CI) 2.99-4.55], 12 months=2 (P=0.0001, 95% CI 2.74-4.46). While 65% (n=34) and 52% (n=27) had a clinical response at 6 and 12 months, respectively, 52% (n=27) and 42% (n=22) were in remission. Overall mean CRP normalized at 6 months (P=0.002, 95% CI 3.31-15.1). Of note 25% (n=13) required dose escalation during follow-up, while treatment was discontinued by seven patients, five (71%) due to a loss of response, the remaining two (29%) due to an adverse event. CONCLUSION: Our study shows adalimumab is an effective and safe long-term therapy for moderately active UC refractory to other treatments. While this data is encouraging, further work is required on patient selection and to determine the impact of treatment on both natural history and quality of life.