OP054-LB1 A CONTROLLED CROSS-OVER TRIAL SHOWS BENEFIT OF PRUCALOPRIDE FOR SYMPTOM CONTROL AND GASTRIC EMPTYING IN GASTROPARESIS
F. Carbone1, A. Rotondo1, C. Andrews1, L. Holvoet2, L. Van Oudenhove1, T. Vanuytsel2, R. Bisschops2, P. Caenepeel2, J. Arts2, A. Papathanasopoulos1 and J. Tack1
1TARGID, Leuven Unversity and Leuven University Hospitals
2Gastroenterology, Leuven University Hospitals, Leuven, Belgium
Contact E-mail Address:jan.tack@med.kuleuven.be
Introduction: Gastroparesis is a chronic gastric disorder characterised by delayed gastric emptying without mechanical obstruction, and clinical symptoms such as post-prandial fullness, early satiety, bloating, nausea and vomiting. Prokinetics are considered the preferred treatment option for gastroparesis, but evidence of their efficacy is lacking. Prucalopride, a selective 5-hydroxytryptamine4 receptor (5-HT4R) agonist used in the treatment of constipation, is able to enhance gastric emptying rate.
Aims & Methods: In a single-center double-blind, randomized, placebo-controlled cross-over study we evaluated the efficacy of prucalopride to improve gastric emptying rate and symptoms in idiopathic or diabetic gastroparesis patients. 34 gastroparesis patients (28 idiopathic, mean age 43.5 ± 2.3, 8 men) underwent a 13C-octanoic acid solid gastric emptying breath test, and symptom severity assessment by the Gastroparesis Cardinal Symptoms Index (GCSI) at run-in and at the end of 4 weeks blinded cross-over treatment periods with placebo or prucalopride 2 mg q.d., separated by 2 weeks wash-out.
Results: Three patients were lost to follow-up. One serious adverse event occurred (small bowel volvulus in the prucalopride group), and 4 patients dropped out because of adverse events of nausea and headache (1 placebo, 3 prucalopride). Prucalopride significantly enhanced gastric half emptying time compared to placebo and to baseline (87.9 ± 8.2 vs 117.9 ± 14.4 and 139.2 ± 11.8 min, p < 0.05 and <0.005 respectively). In addition, prucalopride, compared to placebo and to baseline, also significantly improved the GCSI subscales of fullness/satiety (2.03 ± 0.27 vs 2.77 ± 0.28 and 3.07 ± 0.26, both p < 0.0005), nausea/vomiting (1.04 ± 0.23 vs 1.49 ± 0.27 and 1.77 ± 0.24, p = 0.01 and <0.0001 respectively) and bloating/distention (1.30 ± 0.25 vs 2.35 ± 0.30 and 2.89 ± 0.31, both p < 0.00001). With placebo, only the bloating/distention subscale differed significantly from baseline. Compared to both baseline or placebo, prucalopride significantly improved the overall PAGI-QOL score, and the domains of clothing and diet (all p < 0.01).
Conclusion: In gastroparesis patients, 4 weeks of prucalopride treatment significantly enhances gastric half emptying time and improves symptoms and quality of life compared to placebo and to baseline.
Disclosure of Interest: None declared.
OP054-LB2 GASTROINTESTINAL EVENTS AND ADVERSE REACTIONS ON SELECTIVE AND NON SELECTIVE CYCLOOXYGENASE INHIBITORS IN THE LARGE RANDOMISED CONTROLLED SCOT TRIAL
C. Hawkey1, J. Scheiman2, J. Dillon3, A. Lanas4, J. Moeller5, J. Hallas6, I. Ford7, N. Greenlaw7, I. Mackenzie3 and T. MacDonald3
1University of Nottingham, Nottingham, United Kingdom
2University of Michigan, Michigan, Canada
3Ninewells Hospital, Dundee, United Kingdom
4University of Zaragoza, Zaragoza, Spain
5Odense University Hospital
6University of Southern Denmark, Odense, Denmark
7University of Glasgow, Glasgow, United Kingdom
Contact E-mail Address:cj.hawkey@nottingham.ac.uk
Introduction: Non-selective non-steroidal anti-inflammatory drugs (nsNSAIDs) are associated with adverse gastrointestinal (GI) events which may reduce with selective cyclooxygenase-2 (COX-2) inhibitors, though both may increase cardiovascular (CV) events. We compared the COX-2 inhibitor celecoxib with nsNSAIDs in a large pragmatic trial using record linkage.
Aims & Methods: Patients aged ≥60 years, without CV disease, taking chronic nsNSAIDs in primary care, were randomised to celecoxib or continued nsNSAID. The primary endpoint was non-fatal myocardial infarction, biomarker positive acute coronary syndrome, stroke or CV death and the secondary (GI) endpoint adjudicated ulcer complications.
Results: A total of 7297 participants (38% on ulcer healing drug) were randomised and followed for median 3 years. The CV endpoint occurred at a low rate of 0.95/100 patient years on celecoxib vs 0.86/100 on nsNSAIDs (on treatment (OT) analysis; 1.14 vs 1.10/100 by intention to treat (ITT)). There were only 15 adjudicated secondary (GI) endpoints (0.10/100 patient years on celecoxib vs 0.05 on nsNSAIDs OT, 0.09 vs 0.04 ITT). There were 218 deaths (CV: 33.3% celecoxib vs 35.3% nsNSAIDs, neoplasia: 39.2% vs 29.3%, non-malignant respiratory: 14.7% vs 12.9%) with only 2 attributed to GI bleeding (celecoxib). Serious adverse events were similar for each group (celecoxib 31.7%, ns-NSAID 32.4%) but adverse reactions (ARs) attributed to trial treatment were reported in 22.0% celecoxib vs 16.1% nsNSAIDS (p < 0.001), including 10.6% vs 9.1% GI (p = 0.04). There were more GI serious ARs on nsNSAIDs than celecoxib (1.8% vs 1.0%, p = 0.007) with 10 vs 2 reports of rectal haemorrhage and 13 vs 3 of gastritis. Haematological ARs were reported in more nsNSAID than celecoxib patients (1.3% vs 0.7%) due to to more patients with anaemia or iron deficiency anaemia (1.3% vs 0.6%). During follow-up, 50.9% patients withdrew from celecoxib compared to 30.2% from all nsNSAIDs (p < 0.001).
Conclusion: Prescribing celecoxib to patients previously on nsNSAIDs did not significantly alter risk of adjudicated CV or GI endpoints. Some new ARs emerged, contributing to withdrawal, but there appeared to be fewer rectal haemorrhage and gastritis SARs and fewer ARs due to anaemia. Causes of death were similar to those seen in unselected patients and GI bleeding was an uncommon cause.
Disclosure of Interest: C. Hawkey Financial support from: Univ Dundee, NIHR, HTA, Consultancy for: Bayer, InDex Pharma, Novartis/GSK, J. Scheiman: None declared, J. Dillon: None declared, A. Lanas: None declared, J. Moeller: None declared, J. Hallas: None declared, I. Ford: None declared, N. Greenlaw: None declared, I. Mackenzie: None declared, T. MacDonald Financial support from: Novartis, Pfizer, Amgen, Ipsen, Teijin, Menarini, Consultancy for: Pfizer, Novartis, Kaiser Permanente, Takeda, Servier, Shire, Astellas, Menarini, AstraZeneca, Daiicho Sankyo, Lundbeck.
OP54-LB3 ENDOSCOPIC FULL THICKNESS RESECTION IN THE LOWER GASTROINTESTINAL TRACT USING AN OVER-THE-SCOPE DEVICE – PRELIMINARY RESULTS OF A PROSPECTIVE MULTICENTRE TRIAL
A. R. Schmidt1, B. Schumacher2, D. Albers3, H. Neuhaus4, M. Nübel4, H. Messmann5, A. Probst5, A. Meining6, M. Birk6, H.-J. Richter-Schrag7, A. Fisher7, T. Frieling8, M. Götz9 and K. Caca10
1Department of Gastroenterology, Klinikum Ludwigsburg, Ludwigsburg
2Elisabeth Krankenhaus, Essen
3Department of Gastroenterology, Elisabeth Krankenhaus, Essen
Introduction: The Full Thickness Resection Device (FTRD) (Ovesco, Tübingen, Germany) is a novel over-the-scope device which is approved for full-thickness resection in the lower gastrointestinal (GI) tract in Europe since September 2014. A recent retrospective study has suggested that device and technique is safe and effective.
Aims & Methods: We are conducting a prospective, uncontrolled, multicenter trial at 7 academic referral centers in Germany (NCT02362126). Primary endpoints of the study are technical success and R0-resection, secondary endpoints are occurrence of adverse events. Here, we report the results of an interim analysis while the study is still recruiting. Between February 2015–August 2015, 74 patients with indication for full thickness resection in the colorectum were included in the study.
Results: Indications for endoscopic full thickness resection were: recurrent, incompletely resected or untreated non-lifting adenomas (43); adenoma involving the appendix (11), T1-carcinoma (8), adenoma involving a diverticulum (2) and subepithelial tumors (10). The lesions were located as followed: coecum (19), ascending colon (15), transverse colon (13), descending colon (3), sigmoid (11), recosigmoid transition (4) and rectum (10). Reaching the target lesion with the endoscope and the mounted FTRD was possible in all patients (100%). Technical success (macroscopically complete and en bloc resection) was achieved in 64 (86.4%) patients. R0-resection rate was 80.1 %. One secondary perforation at the resection site requiring surgical therapy and two minor bleedings were observed. No other severe complications have been recorded so far.
Conclusion: The interim results of this prospective study indicate that full thickness resection in the lower GI tract with the novel FTRD is feasible, effective and safe. Final results including follow up data will be expected by mid of 2016.
Disclosure of Interest: A. Schmidt Lecture fee(s) from: Ovesco Endoscopy, B. Schumacher: None declared, D. Albers: None declared, H. Neuhaus: None declared, M. Nübel: None declared, H. Messmann: None declared, A. Probst: None declared, A. Meining: None declared, M. Birk: None declared, H.-J. Richter-Schrag: None declared, A. Fisher: None declared, T. Frieling: None declared, M. Götz: None declared, K. Caca Lecture fee(s) from: Ovesco Endoscopy.
References
SchmidtADammMCacaK. Endoscopic full thickness resection using a novel over-the-scope device. Gastroenterology2014; 47: 740–743.Schmidt A, Bauerfeind P, Gubler C, et al. Endoscopic full thickness resection in the colorectum with a novel over-the-scope device – first experience. World J Gastroenterol 2015; 21(31): 9273--9285. Published online 21 August 2015. DOI: 10.3748/wjg.v21.i31.9273. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4541380/.
OP054-LB4 A MULTICENTER, DOUBLE-BLIND, PLACEBO-CONTROLLED PH3 STUDY OF USTEKINUMAB, A HUMAN MONOCLONAL ANTIBODY TO IL-12/23P40, IN PATIENTS WITH MODERATELY-SEVERELY ACTIVE CROHN’S DISEASE WHO ARE NAÏVE OR NOT REFRACTORY TO ANTI-TNFΑ: UNITI-2
B. Feagan1, C. Gasink2, Y. Lang2, J. R. Friedman2, J. Johanns2, L.-L. Gao2, B. Sands3, S. Hanauer4, P. Rutgeerts5, S. Targan6, S. Ghosh7, W. de Villiers8, J.-F. Colombel3, Z. Tulassay9, U. Seidler10 and W. J. Sandborn11
6Cedars-Sinai Medical Center, Los Angeles, United States
7University of Calgary, Calgary, Canada
8University of of Cape Town, Cape Town, South Africa
9Semmelweis University, Budapest, Hungary
10Hannover Medical School, Hannover, Germany
11UCSD, La Jolla, United States
Contact E-mail Address:MRittenh@its.jnj.com
Introduction: In the Ph 2b Crohn's Evaluation of Response to Ustekinumab anti-IL12/23 for Induction study, a single intravenous ustekinumab induction dose was effective and safe in Crohn's disease patients (pts) previously failing anti-tumor necrosis factors,1 but efficacy in pts only failing conventional therapy is unknown. We evaluated 2 intravenous ustekinumab induction dose-regimens in a Crohn's disease population not refractory to anti-tumor necrosis factors.
Aims & Methods: Pts with moderate-severely active Crohn's disease (CDAI220-450) who failed conventional therapy but were not refractory to anti-tumor necrosis factors were randomized to a single dose of intravenous placebo, ustekinumab 130 mg, or weight-based tiered ustekinumab dosing ∼6 mg/kg. Primary endpoint was clinical response at Wk 6 (reduction in Crohn's Disease Activity Index score of ≥100 pts). At Wk 8, pts transitioned to IM-UNITI maintenance study or had safety follow-up through Wk 20.
Results: Of 628 pts randomized, median disease duration was 6.4 years; baseline (BL) mean Crohn's Disease Activity Index was 303; 39% and 35% were receiving steroids and immunomodulators, respectively at BL; 69% were naïve to anti-tumor necrosis factors. At Wk 6, 55.5% and 51.7% in ∼6 mg/kg and 130 mg ustekinumab groups were in clinical response vs 28.7% placebo (p < 0.001). At Wk 8, 40.2% and 30.6% of pts in ∼6 mg/kg and 130 mg ustekinumab groups were in clinical remission vs 19.6% placebo (p ≤ 0.009). Both ustekinumab doses showed significant improvements vs placebo in Crohn's Disease Activity Index, Inflammatory Bowel Disease Questionnaire, C reactive protein, and fecal lactoferrin and fecal calprotectin. Proportions of adverse events, serious adverse events, and infections (including serious infections) were similar in ustekinumab and placebo groups. No malignancies, deaths, opportunistic infections or tuberculosis occurred in ustekinumab-treated pts (see table).
PBO (n = 209)
UST 130 mg (n = 209)
UST ∼ 6 mg/kga (n = 209)
Clinical responseb
Wk 3
45 (21.5)
68 (32.5) p = 0.010
81 (38.8) p < 0.001
Wk 6c
60 (28.7)
108 (51.7) Delta = 23% p < 0.001
116 (55.5) Delta = 26.8% p < 0.001
Wk 8
67 (32.1)
99 (47.4) p < 0.001
121 (57.9) p < 0.001
Clinical remissiond
Wk 3
24 (11.5)
33 (15.8) p = 0.199
48 (23.0) p = 0.002
Wk 6
37 (17.7)
60 (28.7) p = 0.007
73 (34.9) p < 0.001
Wk 8
41 (19.6)
64 (30.6) Delta = 11.0% p = 0.009
84 (40.2) Delta = 20.6% p < 0.001
Data are n (%); aweight-range based UST doses ∼6 mg/kg: 260 mg (weight ≤55 kg), 390 mg (weight >55 kg and ≤85 kg), 520 mg (weight >85 kg); b≥100 pt reduction in CDAI; cprimary endpoint; dCDAI < 150.
Conclusion: IV UST induced clinical response and remission in pts with moderate-severe CD not previously failing anti-TNFs and was well-tolerated through induction.
Disclosure of Interest: B. Feagan Other conflict with: Investigator, Janssen R&D, LLC, C. Gasink Other conflict with: Employee, Janssen R&D, LLC, Y. Lang Other conflict with: Employee, Janssen R&D, LLC, J. Friedman Other conflict with: Employee, Janssen R&D, LLC, J. Johanns Other conflict with: Employee, Janssen R&D, LLC, L.-L. Gao Other conflict with: Employee, Janssen R&D, LLC, B. Sands Other conflict with: Investigator, Janssen R&D, LLC, S. Hanauer Other conflict with: Investigator, Janssen R&D, LLC, P. Rutgeerts Other conflict with: Investigator, Janssen R&D, LLC, S. Targan Other conflict with: Investigator, Janssen R&D, LLC, S. Ghosh Other conflict with: Investigator, Janssen R&D, LLC, W. de Villiers Other conflict with: Investigator, Janssen R&D, LLC, J.-F. Colombel Other conflict with: Investigator, Janssen R&D, LLC, Z. Tulassay Other conflict with: Investigator, Janssen R&D, LLC, U. Seidler Other conflict with: Investigator, Janssen R&D, LLC, W. Sandborn Other conflict with: Investigator, Janssen R&D, LLC.
Reference
Sandborn WJ, et al. N Engl J Med 2012; 367: 1519–1528.
OP054-LB5 SUSTAINED EFFICACY AFTER DUAL TOPICAL APPLICATION OF THE TOLL-LIKE RECEPTOR 9 AGONIST DIMS0150 IN CHRONIC ACTIVE ULCERATIVE COLITIS PATIENTS
R. Atreya1, F. Scaldaferri2, S. Bloom3, T. E. Knittel4, V. Gerardi5, Å. Karlsson4, J. Kowalski4, M. Lukas6, R. Löfberg7, R. Petryka8, R. Schnabel9, U. Seidler10, S. Nancey11, M. Neurath1 and C. Hawkey12
1Department of Medicine, University of Erlangen-Nuernberg, Erlangen, Germany
2Internal Medicine Department/Gastroenterology Division, Catholic University of Rome, Rome, Italy
3Gastroenterology, University College London Hospital, London, United Kingdom
4R&D, Index Pharmaceuticals, Stockholm, Sweden
5Catholic University of Rome, Rome, Italy
6IBD Clinical and Research Centre, Prague, Prague, Czech Republic
7Karolinska Institute and Sophiahemmet, Stockholm, Sweden
8NZOZ Vivamed, Warsaw, Poland
9Pannonia Maganorvosi Centrum, Budapest, Hungary
10Dept. of Gastroenterology, Hepatology and Endocrinology, MHH, Hannover, Germany
11Gastroenterology, Lyon-Sud Hospital, Pierre-Bénite, France
12Department of Gastroenterology, Nottingham University Hospitals, Nottingham, United Kingdom
Introduction: In the COLLECT study the Toll-like Receptor-9 agonist DIMS0150 was evaluated for its therapeutic efficacy in ulcerative colitis patients refractory to conventional therapy. Patients were followed up to one year after administration of two single topical doses and long term efficacy and sustained clinical effects were analysed in a post-hoc analysis.
Aims & Methods: The oligonucleotide DNA based ImmunoModulatory Sequence0150 was studied in a randomised, double blind, placebo-controlled, multicentre, pan-European phase III trial in 131 patients with moderate to severe ulcerative colitis. Patients were randomly assigned to receive two single doses of DNA based ImmunoModulatory Sequence0150 (30 mg) or placebo (in a 2:1 ratio) administered topically via endoscopy to the inflamed mucosa at baseline (week 0) and after 4 weeks (week 4). Efficacy was studied using the endpoints symptomatic remission (SR), absence of blood in stool and mean weekly stools <35) and registration remission (RR), Clinical Activity Index ≤4 and mucosal healing (MH) defined as endoscopic Mayo score of 0 or 1.
Results: SR was present in 32.1% of the DNA based ImmunoModulatory Sequence0150 vs 14.0% of the placebo treated patients (p = 0.02) 4 weeks after a single topical administration of DIMS0150. RR was achieved in 21.0% of the DNA based ImmunoModulatory Sequence0150 vs 4.7% of the placebo treated patients (p = 0.02), and MH was present in 34.6% vs 18.6% (p = 0.09), respectively after 4 weeks.
Sustained SR at weeks 4 and 12, i.e. SR both at week 4 and week 12, was achieved in 24.7% of the DNA based ImmunoModulatory Sequence0150 vs 11.6% of the placebo treated patients (p = 0.09) and for weeks 4 and 52 it was 13.6% vs 4.7% respectively (p = 0.14). The corresponding results for sustained MH was 27.2% vs 14.0% (p = 0.10) for week 4 and week 12, and 1.2% vs 2.3% for week 4 and week 52. The combined endpoint of SR and MH achieved at both weeks 4 and 12 was 14.8% in the DIMS0150 treated vs 0% in the placebo treated patients (p = 0.008) Sustained RR at weeks 4 and 12 was 14.8% in the DNA based ImmunoModulatory Sequence0150 vs 2.3% in the placebo treated patients (p = 0.06).
Conclusion: The COLLECT study demonstrates that dual topical administration of the Toll-like Receptor-9 agonist DNA based ImmunoModulatory Sequence0150 is able to induce sustained clinical effects in chronic active, moderate to severe ulcerative colitis patients even 52 weeks after initial treatment.
Disclosure of Interest: R. Atreya Financial support from: Index Pharmaceuticals, Consultancy for: Index Pharmaceuticals, F. Scaldaferri Consultancy for: InDex Pharmaceuticals, S. Bloom Financial support from: Index Pharmaceuticals, T. Knittel Consultancy for: InDex Pharmaceuticals, Shareholder of: InDex Pharmaceuticals, V. Gerardi: None declared, Å. Karlsson Consultancy for: Index Pharmaceuticals, Shareholder of: Index Pharmaceuticals, J. Kowalski Consultancy for: Index Pharmaceuticals, M. Lukas Financial support from: Index Pharmaceuticals, R. Löfberg Consultancy for: Index Pharmaceuticals, Shareholder of: Index Pharmaceuticals, R. Petryka Financial support from: Index Pharmaceuticals, R. Schnabel Financial support from: Index Pharmaceuticals, U. Seidler Financial support from: Index Pharmaceuticals, S. Nancey Financial support from: Index Pharmaceuticals, M. Neurath Consultancy for: Index Pharmaceuticals, C. Hawkey Consultancy for: Index Pharmaceuticals.
OP054-LB6 SUSTAINED RESPONSE AFTER FAECAL TRANSPLANTATION IN ULCERATIVE COLITIS IS DRIVEN BY BUTYRATE PRODUCERS
C. Ponsioen1, S. Fuentes2, N. Rossen1, G. D. Haens1, E. Zoetendal2, L. Huskonen3 and W. M. de Vos2
1Gastroenterology & Hepatology, Academic Medical Center, Amsterdam
2Laboratory of Microbiology, WUR, Wageningen, Netherlands
3RPU Immunobiology, University of Helsinki, Helsinki, Finland
Contact E-mail Address:c.y.ponsioen@amc.uva.nl
Introduction: We aimed to identify bacterial signatures that are associated with sustained remission after faecal transplantation for active ulcerative colitis (UC). To this end, we analysed the faecal and mucosal microbiota composition during and up to 3 years post transplantation.
Aims & Methods: Faeces and biopsies from UC patients and healthy donors who participated in the TURN trial were analysed. This trial compared the efficacy of two duodenal infusions of faecal homogenates after bowel preparation from a healthy donor or autologous. Microbiota profiles were determined by phylogenetic microarraying and the number of butyryl-coenzyme A (CoA)-CoA transferase genes (ButCoA) was determined by qPCR. Patients were grouped into responders (Rs) and non-responders (NRs) assessed at week 12 and further stratified by sustained remission (SR) and relapse (assessed at ≥1 year follow-up).
Results: At baseline, NR showed reduced amounts of groups from the Clostridium cluster XIVa, and significantly higher levels of bacteroidetes as compared to donors. At 12 weeks these differences were retained. Redundancy analysis showed an almost complete separation of sustained remitters and patients that relapsed at the ≥1-year follow-up. SR was highly associated with shift at 12 weeks to a clostridium IV and XIVa enriched signature, including many butyrate producers, while relapse was associated with proteobacteria and bacteroidetes. The level of ButCoA genes and proportion of known butyrate producers were shown to be enriched in responders, most prominently in patients who would achieve SR. Interestingly, when SR patients and relapsers were subdivided in placebo and donor faeces recipients, only those placebo patients who at baseline had a microbiota close to a Clostridium IV and XIVa like signature were able to retain their response, while in donor recipients this was determined by a Clostridium IV/XIVa rich signature of the donor in all cases. No differences were observed in microbiota composition of mucosal biopsies between responders and NR.
Conclusion: In UC patients a microbiota signature low in clostridium clusters IV and XIVa and rich in bacteroidetes and proteobacteria is predictive of poor sustained response to FMT, unless they receive a successful engraftment from a clostridium clusters IV and XIVa rich donor. This signature is driven by butyrate producers and durable response is associated with a restoration of the significantly reduced butyrate gene expression at baseline compared with healthy donors.
Disclosure of Interest: None declared.
Reference
Rossen, N. G. et al. Gastroenterology 2015; 149: 110–118.
OP054-LB7 A MULTI-CENTER, CLUSTER RANDOMIZED DOSE-FINDING STUDY OF FECAL MICROBIOTA TRANSPLANTATION CAPSULES FOR RECURRENT CLOSTRIDIUM DIFFICILE INFECTION
M. Fischer1, J. R. Allegretti2, M. Smith3, M. J. Klank1, G. Mendolia3, E. Vo3 and Z. Kassam3
1Gastroenterology, Indiana University, Indianapolis
2Gastroenterology, Brigham and Women's Hospital, Boston
3Openbiome, Medford, United States
Contact E-mail Address:jallegretti@partners.org
Introduction: Fecal microbiota transplantation (FMT) is a promising therapy for recurrent Clostridium difficile infection (CDI) and FMT capsules have emerged; however, the ideal dose is unknown.
Aims & Methods: We aim to evaluate the safety and resolution rate of diarrhea following low and high dose FMT capsules in patients who have suffered three or more recurrences of CDI and failed to maintain CDI cure after standard oral vancomycin therapy. Open-label, cluster dose-finding study performed at two academic hospitals. One site was randomized to low dose FMT capsules (30 pills once) and the other to high dose FMT capsules (30 pills daily for 2 consecutive days). Patients in both groups received oral proton pump inhibitor therapy daily for 48 h prior to FMT to decrease gastric acid and maintain bacterial viability. FMT capsules were generated from healthy, rigorously screened unrelated donors from a universal stool bank (mean age: 26 years, mean body mass index: 22.2 kg/m2, mean waist circumference: 32.5 in, donors pooled clinical success in CDI: 81.3%, n = 48, universal stool bank pooled clinical success in CDI: 85.2%, n = 861) using a scalable, physically stable (>30 days at 25oC) emulsion-based production protocol. The primary end points were safety assessed grade 2 or above, and clinical resolution of diarrhea with no recurrence at 8-week follow-up as per guidelines. Safety data was compared between high and low FMT dose groups by review of adverse events. Non-responders were treated with high dose FMT capsules (30 pills daily for 2 consecutive days) in either arm.
Results: Baseline characteristics of the 17 patients were similar (Figure 1). No adverse events or serious adverse events attributed to FMT were observed with either the high or low FMT dose. Resolution of diarrhea in the high dose was achieved in 5/7 (71%) patients and in 7/10 (70%) patients that received low dose FMT at 8-week follow-up (p = 0.33). Resolution of diarrhea was assessed at multiple time intervals. Clinical remission at 72 h was achieved in 7/7 in the high dose and 8/10 in the low dose (p = 0.56). All five of the non-responders were treated with a high dose FMT extension. Four out of these five patients (80%) had resolution of diarrhea. Overall, the aggregate capsule response rate was 16/17 (94%). The one patient who failed capsule extension was cured with FMT by colonoscopy.
Conclusion: To our knowledge, this study is the first randomized study of FMT capsules in recurrent CDI and provides insight into the lowest, safe, effective FMT capsule dose.
Disclosure of Interest: None declared.
High Dose FMT Capsules (n=7)
Low Dose FMT Capsules (n=10)
p-value
Age – Mean ± SD
60.8 ± 16.8
57.7 ± 20.2
0.73
Female – n (%)
5 (71%)
8 (80%)
0.39
Number of recurrences – Mean ± SD
3.85 ± 0.89
3.4 ± 0.51
0.25
Prior antibiotics – n (%)
7 (100%)
9 (90%)
0.58
Health-care acquired Clostridium difficile infection – n (%)
1 (14.2%)
5 (50%)
0.14
OP103-LB1 THE NATIONAL COLORECTAL CANCER FIT-BASED SCREENING PROGRAMME OF THE NETHERLANDS: OUTCOMES OF THE FIRST YEAR
E. Toes-Zoutendijk1, M. E. van Leerdam2, F. van Hees1, E. Dekker3, M. P. van der Meulen1, H. van Vuuren4, E. J. Kuipers4, H. Bonfrer2, F. van Kemenade5, K. Biermann5, M. Thomeer6, M. C. Spaander4, H. Veldhuizen7, S. Kroep1, M. van Ballegooijen1, H. de Koning1 and I. Lansdorp-Vogelaar1
1Public Health, Erasmus MC, University Medical Center, Rotterdam
2Antoni van Leeuwenhoek, Dutch Cancer Institute
3Gastroenterology and Hepatology, Academic Medical Center, Amsterdam
4Gastroenterology and Hepatology
5Pathology
6Radiology
7Quality improvement, Erasmus MC, University Medical Center, Rotterdam, Netherlands
Introduction: In 2014, a national program for colorectal cancer (CRC) screening with biennial faecal immunochemical testing (FIT) using the FOB-Gold (Sentinel, Italy) was initiated in the Netherlands. The programme was preceded by a period of planning, piloting and implementation of monitoring system.
Aims & Methods: To illustrate the importance of planning and monitoring of screening programmes based on the outcomes of the first year of the Dutch national CRC screening programme. Individuals in the target population received a FIT. Participants with a positive test received an appointment for colonoscopy. Participation and positivity rates, positive predictive values (PPVs) and detection rates per 1000 participants were determined, using data from the national information system for the CRC Screening Program (ScreenIT).
Results: From the 741,916 persons invited, 529,056 (71.3%, 95% confidence interval (CI): 71.2–71.4%) participated in the national programme. The age-adjusted positivity rate in the first half year of 9.6% (95% CI: 9.5–9.8%) at 15 µg Hb/g faeces was higher than anticipated. Age-adjusted detection rates for CRC and advanced adenomas (AADs) were also higher, 5.6 (95% CI: 5.3–6.0) and 28.5 (95% CI: 27.7–29.4) per 1000 respectively, but the PPV of advanced neoplasia (CRC or AAD) was lower, 42.9% (95% CI: 41.7–44.1%). To accommodate available colonoscopy capacity and balance benefits and harms of screening, the cut-off was increased to 47 µg Hb/g faeces in July 2014. This resulted in an age-adjusted positivity rate of 6.9% (95% CI: 6.8–7.0%), with associated detection rate for CRC and AAD of 4.6 (95% CI: 4.3–4.8) and 21.3 (95% CI: 20.8–21.8) per 1000 respectively and PPV of advanced neoplasia of 47.7% (95% CI: 46.6–48.7%).
Conclusion: The Dutch national colorectal cancer screening programme was successfully implemented with high participation. Real-time monitoring system allowed for instant adjustment of the programme when it was not performing as anticipated. This adjustment resulted in 28% reduction in positivity rate and associated colonoscopy capacity while maintaining 82% of CRC and 75% of AAD detection.
Disclosure of Interest: None declared.
OP103-LB2 RECURRENCE AFTER COLONIC EMR IS PREDICTABLE; THE SYDNEY EMR RECURRENCE TOOL (SERT)
D. J. Tate1, L. Desomer1, A. Klein1, G. Brown2, L. Hourigan3, A. Moss4, D. Ormonde5, S. Raftopoulos5, R. Singh6, S. Williams1, S. Zanati4, K. Byth1 and M. J. Bourke1
1Westmead Hospital, Sydney
2Alfred Hospital, Melbourne
3Greenslopes Private Hospital, Brisbane
4Western Hospital, Melbourne
5Sir Charles Gairdner Hospital, Perth
6Lyell McEwan Hospital, Adelaide, Australia
Contact E-mail Address:djtate@gmail.com
Introduction: Endoscopic mucosal resection (EMR) is now the primary treatment of large laterally spreading lesions (LSLs) in the colon, with significant cost and morbidity benefits over surgery.1 Adenoma recurrence is the major limitation of EMR.2
Aims & Methods: Prospective multicentre data on consecutive LSLs ≥20 mm removed by EMR from the Australian Colonic EMR study (ACE) was included (July 2008–June 2015). Independent predictors for endoscopic recurrence were identified by multivariate analysis. A binomial logistic regression model was then created on a random half of the cohort to yield the Sydney EMR Recurrence Tool (SERT), a four-point clinical score to estimate the probability of recurrence based on procedural and lesion factors of the index EMR. SERT was validated on the remainder of the cohort.
Results: Altogether 1975/2119 (93.2%) lesions underwent successful EMR. Analysis was performed on 1383 lesions that were eligible for first surveillance colonoscopy (SC1) at median 5 months (interquartile range (IQR) 4–6 months). Endoscopic recurrence was detected in 225/1383 patients (16.3%). LSL size ≥40 mm (odds ratio (OR) 3.25, 95% CI 2.09–5.05, p < 0.001), intra-procedural bleeding (IPB) (OR 1.86, 1.11–3.12, p = 0.018) and high-grade dysplasia (HGD) (OR 1.84, 1.17–2.90, p = 0.009) were identified as independent predictors of recurrence and were allocated scores of 2, 1 and 1 respectively based on the regression to create SERT. SERT = 0 had a negative predictive value of 92.6% for recurrence at SC1, which was commonly diminutive (<5 mm, 67%), uni-focal (75%), with no HGD. Kaplan-Meier curves were used to derive the cumulative incidence of recurrence at specific intervals after EMR (see Table).
Months follow-up
Cumulative recurrence SERT 0 lesions n = 323 (standard error)
Cumulative recurrence SERT 1–4 lesions n = 368 (standard error)
Log-rank test
6
5.6% (0.014)
14.8% (0.019)
p < 0.001
12
7.8% (0.017)
25.3% (0.026)
18
8.5% (0.018)
31.8% (0.030)
36
16.8% (0.049)
46.6% (0.051)
SERT: Sydney Endoscopic Mucosal Resection Recurrence Tool.
N° patients (%)
OR (CI 95%)
p-value
ACNDR
≥1 adenoma ≥ 10 mm
324 (57.75%)
1.984 (0.996–3.950)
0.051
9.6%
3–4 adenomas
349 (62.21%)
2.099 (1.012–4.352)
0.042 a
9.5%
High-grade dysplasia
77 (13.72%)
0.45 (0.136–1.492)
0.364
3.9%
Villous histology
120 (21.4%)
1.29 (0.630–2.642)
0.486
9.2%
3–4 adenomas and ≥1 measuring ≥ 10 mm
132 (23.53%)
3.886 (2.061–7.325)
<0.001a
16.7%
3–4 adenomas as the only finding
189 (33.69%
0.497 (0.233–1.059)
0.065
4.8%
Univariate analysis of intermediate-risk subgroups.
Conclusion: Guidelines recommend early first surveillance within 6 months of EMR in all cases.3 SERT accurately stratifies recurrence post-EMR. SERT 0 lesions can safely undergo first surveillance at 18 months, whereas SERT 1–4 lesions require follow up at 6 and 18 months. This approach eliminates a colonoscopy for almost half of patients undergoing EMR with substantial cost savings. Clinicaltrials.gov NTC01368289.
OP103-LB3 INTERMEDIATE RISK PATIENTS WITH 3-4 SMALL ADENOMAS COULD BE CONSIDERED AS LOW RISK IN COLORECTAL CANCER SCREENING
E. Pérez-Cuadrado Robles1, E. Torrella Cortés1, J. L. Rodrigo Agudo1, R. Jijón Crespín2, S. Chacón Martinez1, P. Bebia Conesa1, P. Esteban Delgado1, E. Perez-Cuadrado Martinez1 and F. Pérez Riquelme3
1Gastroenterology, Morales Meseguer Hospital
2Gastroenterology, Arrixaca Hospital
3Colorectal Cancer Prevention Program for Región de Murcia, Servicio Murciano de Salud, Murcia, Spain
Contact E-mail Address:kikemurcia@gmail.com
Introduction: Intermediate risk patients with 3–4 small adenomas could be considered as low risk in colorectal cancer screening.
Aims & Methods: The aim of our study was to comparatively assess the risk of advanced colorectal neoplasia at first follow-up colonoscopy among the different intermediate-risk subgroups according to European guidelines, with focus on patients with 3–4 adenomas. All patients recruited for a baseline screening colonoscopy between 2006–2011 were included. The number, size and histopathological characteristics of adenomas were collected. The main outcome was the advanced colorectal neoplasia detection rate (invasive carcinoma or advanced adenoma) at first follow-up colonoscopy. Low and high-risk patients were excluded.
Results: Five-hundred and sixty-one intermediate-risk patients (63.3% men, mean age: 59.01 ± 6.16 years) underwent index and follow-up colonoscopy (see table). By multivariate analysis, 3–4 adenomas (odds ratio (OR): 3.613, confidence interval (CI) 95%: 1.661–7.859, p = 0.001) and adenoma size ≥ 10 < 20 mm (OR: 3.374, CI 95%: 1.618–7.034, p = 0.001) were independent factors associated with advanced colorectal neoplasia. Advanced lesions were detected in 7.7% of cases. The 51.16% of patients with advanced colorectal neoplasia belonged to the subgroup 3–4 adenomas and ≥1 of ≥10 < 20 mm (n = 132, 23.53%). These patients were associated with a higher rate of advanced lesions (OR: 3.886, CI 95%: 2.061–7.325, p < 0.001) than those with 3–4 small adenomas <10 mm (16.7% vs 4.8%, p < 0.001). In addition, considering patients (n = 189, 33.69%) with 3–4 small adenomas as the only finding, it was not significant (OR: 0.497, CI 95%: 0.233–1.059, p = 0.065).
Conclusion: Intermediate-risk patients with 3–4 small adenomas achieved a very-low advanced lesion rate at follow-up. The surveillance interval might be lengthened considering these patients as low-risk.
Disclosure of Interest: None declared.
OP103-LB4 ENDOSCOPIC AND MOLECULAR FEATURES REVEAL PROGRESSION OF SERRATED LESIONS
H. Aoki1,2, E. Yamamoto1,3, H.-O. Yamano4, T. Endo2, T. Sugai5 and H. Suzuki1
1Department of Molecular Biology, Sapporo Medical University
2Department of Gastroenterology, Sapporo Shirakaba-dai Hospital
3Department of Gastroenterology, Rheumatology and Clinical Immunology, Sapporo Medical University, Sapporo
4Department of Gastroenterology, Akita Red Cross Hospital, Akita
5Department of Molecular Diagnostic Pathology, Iwate Medical University, Morioka, Japan
Contact Email address:hironori_a1123@yahoo.co.jp
Introduction: We have previously reported that Type II-Open (Type II-O) pit patterns, which are highly specific to sessile serrated adenoma/polyp (SSA/P) with BRAF mutation and CpG island methylator phenotype (CIMP). Type II-O pit-positive and -negative serrated lesions (SLs) appear to develop through distinct tumorigenic pathways. However, molecular and clinical features of Type II-O pit-negative SLs remain unclear.
Aims & Methods: We aimed to identify endoscopic and molecular features associated with progression of Type II-O pit-negative SLs. We characterized the methylation profile and BRAF/KRAS/TP53 mutation status in 505 premalignant colorectal tumors, which were prospectively collected between April 2009–August 2015. Surface microstructures were classified according to the Kudo’s pit pattern classification system using magnifying endoscopy. In addition, the Type II pit pattern was categorized as classical Type-II, Type II-O and Type II-Long (Type II-L).
Results: Endoscopic findings were classified as 82 Type II, 30 Type II-L, 97 Type II-O, 19 Type II plus tumor pit (Type III, Type IV or Type V), 19 Type II-L plus tumor pit, 57 Type II-O plus tumor pit and 201 tumor pit. We identified the Type II-L plus tumor pit was associated with traditional serrated adenoma (TSA) with BRAF or KRAS mutation and CIMP-Low. A subset of the Type II-L plus tumor pit SLs exhibited TP53 mutations. Our observations suggest that SLs with Type II-L plus tumor pit differ from those with Type II-O plus tumor pit, which is tightly associated with SSA/P with BRAF mutation and CIMP-High. To assess epigenetic alterations that are associated with the development of TSA, genome-wide DNA methylation was carried out using the Infinium Human Methylation450 Bead Chip array in 11 specimens from TSAs (n = 4) and SSAs (n = 3). We identified aberrant DNA methylation of a novel gene, which are predominantly observed in TSAs and was more frequently observed SLs with Type II-L plus tumor pit (65%) than SLs with Type II (0%), Type II-L (0%), Type II-O (0%) and Type II-O plus tumor pit (26%). Progression of SLs with Type II-L to TSA was associated with accumulation of aberrant DNA methylation and additional morphological changes, including Type III, Type IV or Type V pit patterns.
Conclusion: Our data suggest that Type II-L plus tumor pit is a useful hallmark of the premalignant stage of colorectal cancer with BRAF or KRAS mutation and CIMP-Low. Our findings may lead to the development of an innovative endoscopic diagnostic system for detection of premalignant serrated lesions and reduce CRC mortality.
Disclosure of Interest: None declared.
OP103-LB5 RISK FACTORS FOR CLINICAL EVENTS IN A POPULATION UNAWARE OF THEIR GALLSTONES - A COHORT STUDY
D. M. Shabanzadeh1,2, L. T. Sørensen1 and T. Jørgensen2
1Digestive Disease Center, Bispebjerg Hospital
2Research Centre for Prevention and Health, Rigshospitalet, Copenhagen, Denmark
Contact E-mail Address:dmshaban@gmail.com
Introduction: Knowledge about determinants for clinical events in gallstone carriers is limited.
Aims & Methods: The objective was to investigate the long-term associations between body mass index (BMI), lifestyle factors, mental status, social group and clinical gallstone events in a population unaware of having gallstones. A cohort study of three randomly selected groups from the general population of Copenhagen was performed. Participants (n = 6037) underwent ultrasound examinations to detect gallstones in the period 1982–1994. The study population comprised 664 persons with gallstones and they were not informed of gallstone status. Ten percent were aware of having gallstones at baseline. Follow-up for complicated and uncomplicated clinical events was performed through central registers until 31 December 2011. Independent variables were analyzed using Cox regression.
Results: A total of 130 developed clinical events during follow-up (median 17.4 years, inter quartile range 9.46–20.74). Among these, 53 were complicated and 77 were uncomplicated. All clinical events were positively associated to BMI and a poor self-rated health. Daily coffee consumption and sports were inversely associated to all events. Complicated events were positively associated to BMI (hazard ratio (HR) 1.07, 95% confidence interval (CI) 1.02–1.13) and in unadjusted analyses to a poor/bad self-rated health (HR 3.65, CI 1.23–10.85). Uncomplicated events were inversely associated to a daily coffee consumption (HR 0.48, CI 0.23–0.98). Multivariable adjusted models confirmed the significant associations for all events. No significant associations were found to smoking, alcohol, mental vulnerability, visits to general practitioner, or social group (see table).
BMI: body mass index. Multivariable Cox regression models for all gallstone events.
Adjusted for age, sex, number of visits to the general practitioner.
First 12 years of follow-up included.
Adjusted for age, sex, BMI, larger gallstone size, visiting the general practitioner.
Conclusion: Lifestyle, BMI, and self-rated health are associated with clinical events in the long-term follow-up of gallstone carriers. Randomized controlled trials are needed to investigate, whether lifestyle interventions in persons with gallstones will have any effect on the development of clinical events.
Disclosure of Interest: None declared.
OP103-LB6 ENDOSCOPIC ULTRASOUND GUIDED PORTAL PRESSURE GRADIENT MEASUREMENT WITH A SIMPLE NOVEL DEVICE – A HUMAN PILOT STUDY
J. Y. Huang1, J. B. Samarasena1, T. Tsujino1, K.-Q. Hu1, J. G. Lee1 and K. J. Chang1
1Comprehensive Digestive Disease Center, University of California Irvine, Orange, United States
Contact E-mail Address:kchang@uci.edu
Introduction: Portal hypertension (PH) is a serious complication of liver cirrhosis. The hepatic venous pressure gradient or portal pressure gradient (PPG) accurately reflects the degree of PH and is the single best prognostic factor in liver disease. The PPG can guide medical therapy and predict decompensation/cancer risk. Currently, PPG measurement (PPGM) is performed by interventional radiology (IR) via a transjugular approach. Recently, we developed a novel yet simple technique for EUS-PPGM. Our animal studies showed excellent correlation between EUS-PPG and IR-PPG with R = 0.98.1 We now present the first human pilot study of EUS-PPGM using a 25G FNA needle and a new compact manometer.
Aims & Methods: The purpose of this study was to evaluate the feasibility and safety of a novel EUS–PPGM technique and to correlate PPG with endoscopic/clinical evidence of PH in patients with liver disease. EUS-PPG was performed at a tertiary academic center by experienced endosonographers. Patients with liver disease were classified as high probability for cirrhosis if pre-procedural imaging, endoscopic or laboratory studies had evidence of PH. Feasibility was defined as successful PPGM in each patient. Safety was based on complications captured via post-procedural interview. PPGM was performed with a linear echoendoscope, a 25G FNA-needle, non-compressible tubing, and a novel compact manometer (Cook Medical, Indiana, USA). Portal vein and right hepatic vein (or IVC) were targeted via a transgastric or transduodenal transhepatic approach.
Results: Altogether 24 subjects underwent EUS-PPGM with 100% technical success. Pressure reading, identification, and access of targeted vessels was achieved in all without failure. There were no complications. PPG range was 1.5–19 mm Hg. PPG was significantly higher in patients with high probable cirrhosis, varices, and portal hypertensive gastropathy (PHG) compared to those without (Table 1). PPG and platelet count had a strong negative correlation (R = −0.45, p = 0.03). Odds for high probable cirrhosis were 19.5 times higher with PPG > 5 vs PPG ≤ 5 (95% confidence interval (CI) 2.40–432.99).
Conclusion: In this human pilot study, the novel technique of EUS-PPGM using a 25G needle and compact manometer was feasible and safe. PPG values showed excellent correlation with clinical parameters of PH. Given the wide availability of EUS and the simplicity of the manometry setup, this represents a promising breakthrough for procuring indispensable information in the management of patients with liver disease.
Disclosure of Interest: J. Huang Financial support from: Educational grants Cook Medical, Consultancy for: Cook Medical, J. Samarasena Financial support from: Educational grants Cook Medical, T. Tsujino: None declared, K.-Q. Hu: None declared, J. Lee Financial support from: Educational grants Cook Medical, K. Chang Financial support from: Educational grants Cook Medical, Lecture fee(s) from: Cook Medical, Consultancy for: Cook Medical.
Reference
AJG abstract 2015.
OP103-LB7 SAFETY AND FEASIBILITY OF AN ENDOLUMINAL-SUTURING DEVICE (ENDOMINA) AS AN AID FOR ENDOSCOPIC GASTRIC REDUCTION
V. Huberty1, M. Ibrahim1, M. Hiernaux2, A. Chau2 and J. Deviere1
Introduction: Endoscopic suturing with full thickness gastric sutures is still challenging due to the complexity of suturing maneuvers. We currently report first human experience using a suturing station assembled into the stomach.
Aims & Methods: This pilot trial explored the safety and the technical feasibility of a novel triangulation platform ENDOMINA (Endo Tools Therapeutics, Belgium) to perform full thickness endoscopic suturing and anterio-posterior apposition into the stomach. ClinicalTrials.gov NCT02534662. This single use triangulation platform, assembled on the endoscope into the stomach, adds a 5Fr bendable channel and a 5Fr nonbendable channel to an endoscope. ENDOMINA is used in combination with a Transmural Anterio- Posterior Endoscopic Stitcher (TAPES) in the bendable channel with a preloaded tag and tightening system. The procedure included performing 2 large plicatures with serosa to serosa apposition tightened to each other after mucosal ablation and resulting in antero-posterior apposition. This was repeated 4–6 times in every case.
Results: Twelve obese (body mass index (BMI) 34.6 ± 2.2 kg/m2) patients (8 women, mean age: 36 ± 10 years) were included between May 2015–July 2015. One patient was excluded because of gastric ulcers. The median (range) duration of the procedure was: 2 h 6 min (1 h 15 min–3 h 20 min) in this first human experience. No complication was observed. Mean weight loss and percentage excess weight loss were 5.8 kg (standard deviation (SD) 2.9) and 8.1% (SD 6.3), respectively at 1 month for the 11 patients treated and 9 kg (SD 5.4) and 17.6% (SD 11.5) respectively at 3 months for the 4 patients already available for follow-up.
Conclusion: This single use triangulation platform and suturing system appears to be safe and effective in the short term in creating gastric restriction and inducing weight loss. More patients and follow-up are mandatory.
Disclosure of Interest: V. Huberty Other conflict with: Stock Option Holder: Endo Tools Therapeutics (ETT), M. Ibrahim Other conflict with: Stock Option Holder: ETT, M. Hiernaux Other conflict with: Stock Option Holder: ETT, A. Chau Other conflict with: Stock Option Holder: ETT, J. Deviere Shareholder: ETT.
