Sonographic detection of massive colonic pseudopolyposis in inflammatory bowel diseases.

PURPOSE: Colonic pseudopolyps are a frequent finding in inflammatory bowel disease (IBD). Yet there are no published data describing the characteristics of pseudopolyposis in intestinal ultrasound (IUS). This study aimed at identifying the key features of pseudopolyposis in IUS. METHODS: This case-control study included 12 patients with ulcerative colitis or Crohn's colitis with extensive left colon pseudopolyposis and 18 matched IBD patients without pseudopolyps at colonoscopy. Luminal (diameters, thickening, stratification, margins, and vascularity) and intraluminal (vascular signals at color Doppler), and extraluminal (mesenteric fat) parameters of the left colon were compared. Anonymized still images and videos of these patients were blindly reviewed to estimate the accuracy in detecting this condition. RESULTS: Among the IUS parameters assessed, the anteroposterior diameter ≥ 12 mm and the presence of luminal vascular signals were significantly correlated with pseudopolyposis. The detection of both these findings were able to detect extensive pseudopolyposis a sensitivity of 75% (CI 95%: 42.8-94.5%) and a specificity of 100% (CI 95%: 81.5-100%). CONCLUSION: This is the first study describing the IUS features of pseudopolyposis in IBD. The potential use of IUS to assess pseudopolyposis might have an impact on IUS monitoring and surveillance of IBD patients with condition.

Prevalence of coexisting autoimmune thyroidal diseases in coeliac disease is decreasing.

BACKGROUND: Coeliac disease (CD) is associated with an increased risk of other immune-mediated conditions. Aim: To investigate the prevalence of coexistent immune-mediated diseases in CD patients, and changes in the prevalence of autoimmune thyroidal diseases over the last 50 years. METHODS: Medical record data were collected retrospectively from 749 CD patients in Ireland. Prevalence of autoimmune diseases was compared with previously published results from general populations. Patients were divided into four groups based on the year of diagnosis to analyse changes in the prevalence of autoimmune thyroidal disease over time. RESULTS: Median age at the time of CD diagnosis was 56 years (range 18-91 years). A total of 233 (31.1%) patients had a coexistent immune-mediated condition (IMC). Autoimmune thyroidal diseases were seen in 149 (19.9%) patients, hypothyroidism in 110 (14.7%), type 1 diabetes in 27 (3.6%), psoriasis in 20 (2.7%), inflammatory bowel disease in 14 (1.9%) and rheumatoid arthritis in 12 (1.6%). All conditions were more common in CD patients than in the general population. Type 1 diabetes was diagnosed mainly before CD, whereas there was no such trend in other conditions. Autoimmune thyroidal diseases became less common in female CD patients over time. CONCLUSIONS: Prevalence of autoimmune diseases is increased in adult CD patients compared with the general population. However, concomitant autoimmune thyroidal diseases became less common over time in women.

Predicting pathology on small bowel capsule endoscopy: a good FIT.

Background and study aims Small bowel capsule endoscopy [SBCE) has an established role in investigating suspected small bowel bleeding [SSBB). Identification of a biomarker to predict pathology would maximize utility of this valuable diagnostic modality. This study aimed to investigate if fecal immunochemical test [FIT) could predict likelihood of small bowel pathology on SBCE. Patients and methods Patients referred for SBCE to investigate anaemia or suspected small bowel bleeding were prospectively recruited. All patients had negative upper and lower endoscopy prior to referral. A FIT ≥ 45 ug Hb/g was considered positive. SBCE was positive if a potential source of SSBB was identified. The primary endpoint was correlation between FIT and positive SBCE. Secondary endpoints were correlation between anemia and SBCE and a combination of anemia plus FIT and SBCE. Results Fifty-one patients were included in the final study cohort. 29.4 % had a positive FIT, 33.3 % were anemic, and 25.5 % patients had significant SBCE findings. There was a statistically significant association between positive FIT and pathology on SBCE (OR 12, 95 % CI [2.8 - 51.9), P  = 0.001). Sensitivity and specificity of positive FIT in predicting SBCE findings were 69 % and 84 %, respectively. A normal Hb had an NPV of 83 % (OR 0.30, P  = 0.09). Combining Hb and FIT was statistically significant in predicting pathology on SBCE (OR 9.14, 67 % PPV, 82 % NPV, P  = 0.025). Conclusion FIT ≥ 45 ug Hb/g is a useful tool in predicting small bowel pathology on SBCE. Use of this biomarker alone, or in combination with serum haemoglobin, has value as a screening tool and may help to better triage patients referred for SBCE.

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.

Capsule endoscopy in young patients with iron deficiency anaemia and negative bidirectional gastrointestinal endoscopy.

BACKGROUND: Recent data imply young patients (age ≤50 years) undergoing small-bowel (SB) capsule endoscopy (CE) for iron deficiency anaemia (IDA) show higher diagnostic yield (DY) for sinister pathology. We aimed to investigate DY of CE in a large cohort of young IDA patients, and evaluate factors predicting significant SB pathology. MATERIALS AND METHODS: This was a retrospective, multicentre study (2010-2015) in consecutive, young patients (≤50 years) from 18 centres/12 countries, with negative bidirectional gastrointestinal (GI) endoscopy undergoing SBCE for IDA. Exclusion criteria: previous/ongoing obscure-overt GI bleeding; age <19 or >50 years; comorbidities associated with IDA. Data retrieved: SBCE indications; prior investigations; medications; SBCE findings; final diagnosis. Clinical and laboratory data were analysed by multivariate logistic regression. RESULTS: Data on 389 young IDA patients were retrieved. In total, 169 (43.4%) were excluded due to incomplete clinical data; data from 220 (122F/98M; mean age 40.5 ± 8.6 years) patients were analysed. Some 71 patients had at least one clinically significant SBCE finding (DY: 32.3%). They were divided into two groups: neoplastic pathology (10/220; 4.5%), and non-neoplastic but clinically significant pathology (61/220; 27.7%). The most common significant but non-neoplastic pathologies were angioectasias (22/61) and Crohn's disease (15/61). On multivariate analysis, weight loss and lower mean corpuscular volume(MCV) were associated with significant SB pathology (OR: 3.87; 95%CI: 1.3-11.3; p = 0.01; and OR: 0.96; 95%CI: 0.92-0.99; p = 0.03; respectively). Our model also demonstrates association between use of antiplatelets and significant SB pathology, although due to the small number of patients, definitive conclusions cannot be drawn. CONCLUSION: In IDA patients ≤50 years with negative bidirectional GI endoscopy, overall DY of SBCE for clinically significant findings was 32.3%. Some 5% of our cohort was diagnosed with SB neoplasia; lower MCV or weight loss were associated with higher DY for SB pathology.

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 Irish Helicobacter pylori Working Group consensus for the diagnosis and treatment of H. pylori infection in adult patients in Ireland.

BACKGROUND: Irish eradication rates for Helicobacter pylori are decreasing and there is an increase in the prevalence of antibiotic-resistant bacteria. These trends call into question current management strategies. OBJECTIVE: To establish an Irish Helicobacter pylori Working Group (IHPWG) to assess, revise and tailor current available recommendations. METHODS: Experts in the areas of gastroenterology and microbiology were invited to join the IHPWG. Questions of relevance to diagnosis, first-line and rescue therapy were developed using the PICO system. A literature search was performed. The 'Grading of Recommendations Assessment, Development and Evaluation' approach was then used to rate the quality of available evidence and grade the resulting recommendations. RESULTS: Key resultant IHPWG statements (S), the strength of recommendation and quality of evidence include S8: standard triple therapy for 7 days' duration can no longer be recommended (strong and moderate). S9: 14 days of clarithromycin-based triple therapy with a high-dose proton pump inhibitor (PPI) is recommended as first-line therapy. Bismuth quadruple therapy for 14 days is an alternative if available (strong and moderate). S12: second-line therapy depends on the first-line treatment and should not be the same treatment. The options are (a) 14 days of levofloxacin-based therapy with high-dose PPI, (b) 14 days of clarithromycin-based triple therapy with high-dose PPI or (c) bismuth quadruple therapy for 14 days (strong and moderate). S13: culture and antimicrobial susceptibility testing should be performed following two treatment failures (weak and low/very low). CONCLUSION: These recommendations are intended to provide the most relevant current best-practice guidelines for the management of H. pylori infection in adults in Ireland.

Changes in Presentation of Celiac Disease in Ireland From the 1960s to 2015.

BACKGROUND & AIMS: Celiac disease is an immune-mediated enteropathy characterized with high heterogeneity in presentation among genetically predisposed individuals. In recent years, a change in the phenotypic presentation of celiac disease has been reported. We studied clinical presentation, from 1960 through 2015, in Ireland, which has a high incidence of celiac disease. METHODS: We performed a retrospective analysis of medical charts from patients diagnosed with celiac disease at 5 secondary referral centers in Ireland from 1960 through 2015 (n = 749; median age, 56 years; age range, 18-91 years). The cohort was divided into 5 groups based on year of diagnosis (≤1985, 1986-1995, 1996-2005, 2006-2010, or 2011 and later). We collected findings from clinical presentation at diagnosis; serology tests; small intestinal biopsy analyses; and patients' demographic, clinical, and family data. Presentations at diagnosis were classified according to the Oslo criteria as follows: classical (patients presenting with malabsorption), nonclassical (no signs or symptoms of malabsorption at presentation), or subclinical (below the threshold of clinical detection). The primary outcome was change in clinical presentation of celiac disease over time. RESULTS: Of the 749 patients studied, 512 were female and 237 were male (ratio of 2.2:1). Female patients were diagnosed at younger ages than male patients (42 vs 47 years, respectively; P = .004), and had more immune-mediated conditions than male patients (35.7% for female patients vs 21.5% for male patients; P < .001). For patients diagnosed as adults (after the age of 18 years), the median age of diagnosis increased from 34.0 years during the period ≤1985 to median ages of 44-46 years after 1985 (P < .002). A smaller proportion of patients presented with classical features of celiac disease after 2010 (48.4%) than ≤1985 (85.2%); the proportion of patients with nonclassical or subclinical celiac disease increased from 14.8% ≤1985 to 51.6% after 2010 (P = .006 for each). Biopsies categorized as Marsh 3c decreased, from 52.2% in the period 1996-2005 to 22.5% in the period after 2010 (P = .003). The prevalence of associated thyroid disease has decreased during the study period, from 36.6% ≤1985 to 17.1% after 2010 (P = .039), whereas body mass index at diagnosis increased from 21.5 kg/m2 ≤1985 to 24.8 kg/m2 after 2010 (P < .001). CONCLUSIONS: We found the clinical presentation of celiac disease changed significantly in Ireland from 1960 through 2015. The age of presentation in adulthood increased over this time period, as did the proportions of patients with nonclassical or subclinical disease.

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-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.

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.

Long-term follow-up with stress echocardiograms of patients with Kawasaki's disease.

Patients with a history of Kawasaki's disease (KD), particularly those not treated with intravenous gamma-globulin, are at risk of coronary artery aneurysms and later obstruction. Twenty-eight patients with a history of KD (4 had coronary artery aneurysms) were examined with stress echocardiograms. Fourteen patients received gamma-globulin < or =10 days of the onset, 8 patients received gamma-globulin >10 days and 6 received no gamma-globulin. The mean age at diagnosis was 7.2 +/- 4.1 years; the median follow-up was 8.0 +/- 7.4 years. All tests were negative. Using a binomial model, a power of 0.80, a sensitivity of each test of 80% and assuming uniform risk, the individual rate of failure to detect was <7%. At least 640 patients in each group would be needed to detect a difference of 3.5% vs. 7.0% and 184 in each group would be needed to detect a difference of 1.5% vs. 7.5%. We conclude that the probability of an abnormal stress echo in asymptomatic patients with a history of KD is at most 7% and that a more precise determination of the risk of an abnormal stress echo in KD requires a much larger study.