Lyn A. Smith

A prospective single-centre evaluation of the intra-individual variability of faecal calprotectin in quiescent Crohn's disease

As a non‐invasive marker of gastrointestinal inflammation, faecal calprotectin (FC) is being increasingly used to guide the management of Crohns disease. It is therefore a concern that studies have shown variability in day to day levels.

Hemospray Application in Nonvariceal Upper Gastrointestinal Bleeding: Results of the Survey to Evaluate the Application of Hemospray in the Luminal Tract.

Background: Hemospray TM (TC-325) is a novel hemostatic agent licensed for use in nonvariceal upper gastrointestinal bleeding (NVUGIB) in Europe. Goals: We present the operating characteristics and performance of TC-325 in the largest registry to date of patients presenting with NVUGIB in everyday clinical practice. Methods: Prospective anonymized data of device performance and clinical outcomes were collected from 10 European centers using the multicentre SEAL survey (Survey to Evaluate the Application of Hemospray in the Luminal tract). TC-325 was used as a monotherapy or as second-line therapy in combination with other hemostatic modalities at the endoscopists’ discretion. Results: Sixty-three patients (44 men, 19 women), median age 69 (range, 21 to 98) years with NVUGIB requiring endoscopic hemostasis were treated with TC-325. There were 30 patients with bleeding ulcers and 33 with other NVUGIB pathology. Fifty-five (87%) were treated with TC-325 as monotherapy; 47 [85%; 95% confidence interval (CI), 76%-94%] of them achieved primary hemostasis, and rebleeding rate at 7 days was 15% (95% CI, 5%-25%). Primary hemostasis rate for TC-325 in patients with ulcer bleeds was 76% (95% CI, 59%-93%). Eight patients, who otherwise may have required either surgery or interventional radiology, were treated with TC-325 as second-line therapy after failure of other endoscopic treatments, all of whom achieved hemostasis following the adjunct of TC-325. Conclusions: This multicentre registry identifies potentially useful characteristics of Hemospray (TC-325) when used either as monotherapy or as a rescue therapy in a wide variety of ulcer and nonulcer NVUGIB.

The use of hemospray in portal hypertensive bleeding; a case series.

Hemospray is a haemostatic agent licensed for endoscopic haemostasis of non-variceal upper gastrointestinal bleeding (NVUGIB) in Europe and Canada. Hemospray has been shown to be safe and effective in achieving haemostasis in bleeding peptic ulcers in a prospective clinical study and several further case series have described the use of hemospray in other non-variceal causes of gastrointestinal bleeding. Portal hypertensive gastropathy and colopathy are common in patients with portal hypertension. As hemospray is an easy to apply, non-contact method, which can cover large areas of mucosa, it may be of benefit in acute non-variceal portal hypertensive bleeding. We present data from the first four consecutive patients presenting to our institution with acute haemorrhage secondary to non-variceal diffuse portal hypertensive bleeding treated with hemospray.

Utility of faecal calprotectin analysis in adult inflammatory bowel disease

The inflammatory bowel diseases (IBD), Crohns disease and ulcerative colitis, are chronic relapsing, remitting disorders. Diagnosis, along with assessment of disease activity and prognosis present challenges to managing clinicians. Faecal biomarkers, such as faecal calprotectin, are a non-invasive method which can be used to aid these decisions. Calprotectin is a calcium and zinc binding protein found in the cytosol of human neutrophils and macrophages. It is released extracellularly in times of cell stress or damage and can be detected within faeces and thus can be used as a sensitive marker of intestinal inflammation. Faecal calprotectin has been shown to be useful in the diagnosis of IBD, correlates with mucosal disease activity and can help to predict response to treatment or relapse. With growing evidence supporting its use, over the last decade this faecal biomarker has significantly changed the way IBD is managed.

Multicentre randomised controlled study comparing carvedilol with variceal band ligation in the prevention of variceal rebleeding.

BACKGROUND & AIMS Rebleeding after an initial oesophageal variceal haemorrhage remains a significant problem despite therapy with band ligation, non-selective β-blockers or a combination of these. Carvedilol is a vasodilating non-selective β-blocker with alpha-1 receptor and calcium channel antagonism. A recent study has suggested it is effective in the prevention of a first variceal bleed. Our aim was to compare oral carvedilol with variceal band ligation (VBL) in the prevention of rebleeding following a first variceal bleed. METHODS Patients who were stable 5 days after presentation with a first oesophageal variceal haemorrhage and had not been taking β-blockers were randomised to oral carvedilol or VBL. Patients were followed-up after one week, monthly, then every 3 months. The primary end point was variceal rebleeding on intention-to-treat analysis. RESULTS 64 patients were randomised, 33 to carvedilol and 31 to VBL. 58 (90.6%) patients had alcohol related liver disease. Age and Child-Pugh score were similar in both groups at baseline. Median follow-up was 26.3 (interquartile range [IQR] 10.2-46.6)months. Compliance was 68% and 65% for carvedilol and VBL respectively (p=0.993) and serious adverse events between the two groups were similar (p=0.968). Variceal rebleeding occurred during follow-up in 12 (36.4%) and 11 (35.5%) patients in the carvedilol and VBL groups, respectively (p=0.857), with 9 (27.3%) and 16 (51.6%) deaths in each group, respectively (p=0.110). CONCLUSIONS Carvedilol is not superior to VBL in the prevention of variceal rebleeding. The trend to a survival benefit for patients taking this drug compared with those undergoing banding requires further exploration.

A prospective evaluation of the predictive value of faecal calprotectin in quiescent Crohn's disease

BACKGROUND Faecal calprotectin (FC) is a non-invasive marker of gastrointestinal inflammation. AIM To determine whether higher FC levels in individuals with quiescent Crohns disease are associated with clinical relapse over the ensuing 12 months. METHODS A single centre prospective study was undertaken in Crohns disease patients in clinical remission. The receiver operating characteristic (ROC) curve for the primary endpoint of clinical relapse by 12 months, based on FC at baseline, was calculated. Kaplan-Meier curves of time to relapse were based on the resulting optimal FC cutoff for predicting relapse. RESULTS Of 97 patients recruited, 92 were either followed up for 12 months without relapsing, or reached the primary endpoint within that period. Of these, 10 (11%) relapsed by 12 months. Median FC was lower for non-relapsers, 96 μg/g (IQR 39-237), than for relapsers, 414 μg/g (IQR 259-590), (p=0.005). The area under the ROC curve to predict relapse using FC was 77.4%. An optimal cutoff FC value of 240 μg/g to predict relapse had sensitivity of 80.0% and specificity of 74.4%. Negative predictive value was 96.8% and positive predictive value was 27.6%, FC ≥240 μg/g was associated with likelihood of relapse by 12-months 12.18 (95% CI 2.55-58.2) times higher than lower values (p=0.002). CONCLUSIONS In this prospective dataset, FC is a useful tool to help identify quiescent Crohns disease patients at a low risk of relapse over the ensuing 12 months. FC of 240 μg/g was the optimal cutoff in this cohort.

Catastrophic gastrointestinal complication of systemic immunosuppression.

We present a case of acute upper gastrointestinal haemorrhage in a patient with systemic vasculitis immunosuppressed on cyclophosphamide and prednisolone. The patient presented with a diffuse haemorrhagic oesophagitis and a non-specific duodenitis. Biopsies taken from the oesophagus and duodenum demonstrated infection with herpes simplex virus (HSV) and cytomegalovirus (CMV) respectively. Viral infection of the upper gastrointestinal tract is a recognised complication of immunosuppression and HSV is one of the most common pathogens. CMV on the other hand most commonly causes a colitis or less commonly oesophagitis. CMV enteritis is rare as is the synchronous infection with two viral agents in an immunocompromised patient having being described in a few case series only. Viral infection of the gastrointestinal tract in immunocompromised patients should be treated with systemic anti-viral medication and consideration to withdrawal of the immunosuppressive therapy if possible and appropriate. The authors highlight the need for a high suspicion of viral infection in immunosuppressed patients presenting with upper gastrointestinal bleeding.

OC-003 Multicentre Randomised Controlled Study Comparing Carvedilol with Endoscopic Band Ligation in the Prevention of Variceal Rebleeding

Introduction Rebleeding after an initial oesophageal variceal haemorrhage remains a significant problem despite therapy with band ligation ± non-selective ß-blockers. Carvedilol is a vasodilating non-selective ß-blocker with alpha-1 receptor and calcium channel antagonism. It has a greater portal hypotensive effect than propranolol and has been shown to be effective in the prevention of a first variceal bleed. Our aim was to compare oral carvedilol with band ligation in the prevention of rebleeding following a first variceal bleed. Methods Patients who were stable 5 days after presentation with a first variceal haemorrhage and had not been taking (or had contraindications to) ß-blockers, were randomised to oral carvedilol (6.25 mg daily then 12.5 mg daily after one week if tolerated) or a band ligation programme. Patients were followed up at clinic after one week, monthly, then 3-monthly. The primary end-point was variceal rebleeding, on intention-to-treat analysis. Results 63 patients were randomised, 32 to carvedilol and 31 to banding. Fifty-six (89%) patients had alcohol related liver disease. There was no difference in baseline mean age (51 yrs ± 10.9 and 50 yrs ± 13.0) or median Childs Pugh score (9, IQR 6–11 and 9, IQR 8–11) for patients randomised to carvedilol or banding respectively. Mean follow-up was 29 months. Compliance was 72% and 90% for carvedilol and banding respectively (p = 0.14) and there was no difference in the number of serious adverse events between the two groups. Variceal rebleeding occurred during follow-up in 12 (37.5%) and 9 (29.0%) patients in the carvedilol and banding groups respectively (p = 0.72), with mortality 25.0% and 51.6% respectively (p = 0.058). The differences in outcome the between groups were similar using per protocol analysis. This interim analysis indicates that to show a significant difference in rebleeding, 482 patients would be required in each group. Conclusion Carvedilol is not clearly superior to band ligation in the prevention of variceal rebleeding. However there appears to be a survival benefit for patients taking this drug compared with those undergoing banding, which requires further exploration. Disclosure of Interest None Declared

Mediastinal node staging by positron emission tomography-computed tomography and selective endoscopic ultrasound with fine needle aspiration for patients with upper gastrointestinal cancer: Results from a regional centre

AIM To investigate the impact of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) and positron emission tomography-computed tomography (PET-CT) in the nodal staging of upper gastrointestinal (GI) cancer in a tertiary referral centre. METHODS We performed a retrospective review of prospectively recorded data held on all patients with a diagnosis of upper GI cancer made between January 2009 and December 2015. Only those patients who had both a PET-CT and EUS with FNA sampling of a mediastinal node distant from the primary tumour were included. Using a positive EUS-FNA result as the gold standard for lymph node involvement, the sensitivity, specificity, positive and negative predictive values (PPV and NPV) and accuracy of PET-CT in the staging of mediastinal lymph nodes were calculated. The impact on therapeutic strategy of adding EUS-FNA to PET-CT was assessed. RESULTS One hundred and twenty one patients were included. Sixty nine patients had a diagnosis of oesophageal adenocarcinoma (Thirty one of whom were junctional), forty eight had oesophageal squamous cell carcinoma and four had gastric adenocarcinoma. The FNA results were inadequate in eleven cases and the PET-CT findings were indeterminate in two cases, therefore thirteen patients (10.7%) were excluded from further analysis. There was concordance between PET-CT and EUS-FNA findings in seventy one of the remaining one hundred and eight patients (65.7%). The sensitivity, specificity, PPV and NPV values of PET-CT were 92.5%, 50%, 52.1% and 91.9% respectively. There was discordance between PET-CT and EUS-FNA findings in thirty seven out of one hundred and eight patients (34.3%). MDT discussion led to a radical treatment pathway in twenty seven of these cases, after the final tumour stage was altered as a direct consequence of the EUS-FNA findings. Of these patients, fourteen (51.9%) experienced clinical remission of a median of nine months (range three to forty two months). CONCLUSION EUS-FNA leads to altered staging of upper GI cancer, resulting in more patients receiving radical treatment that would have been the case using PET-CT staging alone.

PWE-029 Utility of Measurement Anti TNF Drug and Anti Drug Antibody Levels in A Cohort of Patients with Crohn’s Disease: How Does it Affect Clinical Practice?: Abstract PWE-029 Table 1

Introduction It has been recognised that the measurement of anti-TNF drug concentrations and detection of anti drug antibodies may be useful in aiding decision making and therefore optimising clinical outcomes in patients on anti-TNF drugs in whom there is incomplete clinical response or loss of drug therapy.1 Methods A total of 45 Crohn’s patients attending our tertiary referral IBD clinic had anti TNF drug concentrations and antidrug antibodies levels measured. The indications for testing were incomplete response or loss of response during therapy. We measured drug levels and Anti Drug Antibody levels using the ELISA assay (Immunodiagnostik). Reference ranges for Infliximab >2.0 ug/ml therapeutic and Adalimumab >5.0 ug/ml therapeutic. Total drug antibody levels >10 AU/ml positive. Results We present the patient demographics in Table 1.Abstract PWE-029 Table 1 Patient demographics Crohn’s cohort N = 45 Female, n (%)Male 25 (55%)20 (45%) Median age at time of testing, years 36.5 (18–75) Smoking status, n (%)CurrentNon-smokers 7 (16%)38 (84%) PanentericIleocolonicIlealPerianalColonic 18 (40%)9 (20%)8 (18%)6 (13%)4 (9%) Anti-TNF treatmentInfliximabAdalimumab 26 (58%)19 (42%) Anti TNF monotherapyThiopurinesMethotrexateCorticosteroids (>20mg/daily) 22 (49%)19 (42%)2 (4.5%)2 (4.5%) Drug and ADA levels 44% (n = 20) had therapeutic levels and negative antibodies, 18% (n = 8) had therapeutic levels and positive antibodies, 22% (n = 10) had sub-therapeutic levels and negative antibodies and 16% (n = 7) had sub-therapeutic levels and positive antibodies. Impact of results meaurement of drug and ADA led to change in management in 28/45 (62%) patients. 6 (13%) patients switched therapy,17 (38%) had dose escalation,17 (38%) no treatment change,5 (11%)other outcome. Conclusion Measurement of anti-TNF drug concentrations and antibody status in our patients on Anti TNF resulted in change of management in 28/45 (62%) patients. In the 17 patients with dose escalation in whom outcome was assessed 13 (76%) patients have responded. Measurement of drug concentration and antibody status presents an possible option in the management of patients on anti-TNF who present with loss of response or incomplete response of treatment Reference 1 Vande Casteele N, et al. The relationship between infliximab concentrations, antibodies to infliximab and disease activity in Crohn’s disease. GUT 2015 Oct;64(10):1539–45. Disclosure of Interest S. Laird: None Declared, L. Caulfield: None Declared, L. Smith Conflict with: cook, boston and allergan, almirall, J. Winter Conflict with: almirall, reckitt-Benckisaer, ferring, shire, D. Gaya: None Declared, A. Morris Conflict with: Falk,Vifor