Introduction Radiofrequency ablation (RFA) is the recommended therapy for flat high grade dysplasia (HGD) and residual Barrett’s oesophagus (BO) after endoscopic mucosal resection (EMR) to reduce the risk of metachronous neoplasia. We aim to assess safety and effectiveness from the East Midlands Barrett’s RFA database. Methods Data was analysed on patients referred to Nottingham University Hospital for RFA therapy to treat dysplastic BO between 2008 and 2018. The main outcome measures included complete remission of dysplasia (CRD), complete remission of intestinal metaplasia (CRIM), recurrent rates of BO, HGD and adenocarcinoma, procedural complications, treatment failure rates and median follow up prior to discharge back to the referring hospital. RFA techniques involved the use of circumferential and focal ablation every three months until the BO was obliterated. Follow up endoscopy and biopsy of original BO length was performed 3 and 12 months after the last RFA session and annually thereafter unless there was evidence of recurrent disease. Results 221 patients were included in the analysis. Median age was 67.72 (±9.2) years, the male: female ratio was 4:1, median BO length was C2 (IQR:6) M6 (IQR:5), 59.8% had EMR prior to RFA. The proportion of patients having RFA with a previous histological diagnosis of LGD, HGD and intramucosal adenocarcinoma (IMC) was 22%, 44.8% and 32.2% respectively. The median number of RFA sessions was 3 (IQR:2). The rates of CRD and CRIM were 93.2% and 91.3%. Adjuvant ablation techniques were required in less than half of patients: APC 38% with median sessions of 1(1-4) and 1 excision biopsy session in 9.4% of patients. Severe oesophagitis delayed treatment in 12.1% and hiatus hernia repair surgery was required in 1.3% of patients. Stricture rates were 5.4% requiring a median of 2 (IQR:6) dilatations and bleeding requiring hospital admission was 0.45%. RFA failed or was abandoned in 6.3% of patients. Metachronous lesions development during RFA treatment phase warranting further therapy in 14.9% patients: BO (2.7%) LGD (0.9%) HGD (5%) and IMC (6.3%). Metachronous lesions and BO developed after CRIM in 5% requiring further therapy and 0.9% developed invasive cancer. Median follow up post CRD/CRIM was 20.1 (±28.9) months. The survival rate over the 10-year study period was 94.6% with the majority of deaths due to unrelated disease. Conclusions This 10-year data demonstrates that RFA therapy is effective in achieving eradication of BO and dysplasia with a favourable safety profile.

Targeting the programmed death-1/programmed death ligand 1 (PD-1/PD-L1) pathway has improved clinical outcomes, expediting the US FDA approval of 5 agents as treatment for several tumor types. PD-L1 immunohistochemistry (IHC) diagnostic assays have been developed to guide treatment with anti–PD-1/PD-L1 agents. The Dako PD-L1 IHC 22C3 pharmDx and Ventana PD-L1 (SP142) assays are FDA-approved diagnostics for non-small cell lung cancer (NSCLC) as a companion to pembrolizumab and complementary to atezolizumab, respectively. The Dako PD-L1 IHC 28-8 pharmDx is approved for nonsquamous NSCLC, complementary to nivolumab. We sought to overcome barriers to PD-L1 testing by characterizing the use of 22C3, 28-8, and SP142 PD-L1 IHC assays on real-world lung cancer samples.

Introduction Endoscopic mucosal resection (EMR) is a widely used therapy for visible dysplastic lesions associated with Barrett’s oesophagus (BO) and intramucosal adenocarcinoma (IMC). This study evaluates the efficacy and safety of a single high-volume UK tertiary centre with 15-years experience. Methods A retrospective review was conducted of patients referred to Nottingham University Hospital between 2004–2019 for EMR with dysplastic BO visible lesions or IMC. The main outcomes were endoscopic resection success rates, long-term recurrence rates, complications during the treatment phase, surgery rates, median follow up prior to discharge from tertiary centre and tumour related deaths. Results A total of 309 lesions were resected in 212 patients, median age was 68.1±9.4 years, the male: female ratio was 5:1. Median BO length was C2(IQR:6) M4(IQR6) and 76.2% of lesions were at the 12 to 6 o’clock position. The most common lesion was Paris IIa (63.4%) and the median size was 10 mm (3–70). Most procedures were done under intravenous sedation as a day-case with the ligate and cut technique (93.2%) and the Duette® multi-band mucosectomy device (88%). APC was used in addition to EMR in 5.4% of cases. Complete resection rates were 95.5%. Prophylactic measures to prevent bleeding were undertaken in 11.3%. Significant complications requiring admission and further treatment was 3.8%: bleeding (2.3%) and perforation (0.3%) with a median length of stay of 1 day (1-8). Stricture rates were 2.6% requiring a median of 1 (IQR:1.75) dilatation. The most commonly resected histological grade was IMC (48.1%), high grade dysplasia (37%) and low grade dysplasia (6.5%). The majority of tumours were stage T1a (86.7%). 22% of patients with confirmed adenocarcinoma had an indication for surgery and over half of these underwent surgery. Post EMR 72.5% had additional therapy for the remaining BO. After a median follow up of 32 months (IQR 43.6) metachronous lesions developed in 10.7% of patients. 95% of these were successfully treated with endoscopic or surgical therapy. The survival rate over the study period was 85.7%, with cause of death attributed to unrelated disease (11.3%) and oesophageal adenocarcinoma (2.8%). Conclusions This real-world data demonstrates that EMR is a minimally invasive, safe and effective treatment for Barrett’s neoplasia that can be delivered in a day-case setting. It allows accurate local staging with the option of surgery for locally advanced disease.

Immune checkpoint inhibitors targeting the programmed death-1/programmed death ligand 1 (PD-1/PD-L1) pathway have improved clinical outcomes in patients with cancer. Testing for PD-L1 with immunohistochemistry (IHC) is performed to inform therapy decisions. Among the FDA-approved PD-L1 IHC diagnostic assays, the Dako PD-L1 IHC 22C3 pharmDx assay is approved as a companion diagnostic to pembrolizumab in non-small cell lung cancer (NSCLC) and the Dako PD-L1 IHC 28-8 pharmDx assay as a complementary diagnostic to nivolumab for nonsquamous NSCLC. Previous studies have compared the 2 assays in NSCLC and urothelial carcinoma. Here, we present a comparison of the 28-8 and 22C3 assays on the largest real-world dataset of lung cancer samples reported to date.

Introduction Randomised controlled trials have demonstrated efficacy of vedolizumab in Ulcerative Colitis (UC) and Crohn’s Disease (CD). Further data in the real-world setting is needed to inform future practice. Methods A multicentre retrospective observational chart review study was conducted with all pts initiated on vedolizumab across 7 UK hospitals between 1/11/14–30/11/16. The Health Research Authority approved the protocol (19/HRA/0008). Clinical disease activity was assessed at baseline, week 14, 30 & 52 using the Harvey Bradshaw Index (HBI) and partial Mayo Score (pMS). Clinical remission was defined as HBI≤4 or pMS <2 with a combined stool frequency and rectal bleeding subscore of ≤1. Clinical response was defined as ≥2-point decrease from baseline in pMS and ≥3-point decrease from baseline in HBI. The primary objective was to describe corticosteroid-free and clinical remission. Secondary objectives included effect on disease activity scores, biochemical markers, concomitant drug use, mucosal healing, hospital admissions and adverse effects. Results 192 patients were included: 100 CD, 87 UC and 5 IBD unclassified (grouped with CD in this analysis). 46% of UC and 10% of CD patients were anti-TNF naïve. Median age was 44 (range 18–79) years; 49% male and median BMI was 25.7 (IQR 22.5–31.4). Exposure time was 38.0 (23.7–56.7) for UC and 30.9 (21.3–49.6) weeks for CD. Corticosteroid-free remission rates for UC and CD were 46% and 45%, while clinical remission rates were 52% and 44% respectively. Clinical response rates for UC was 49% and CD was 53%. The median time to corticosteroid free remission for UC and CD was 17.6 (8.7–29.6) and 14.1 (6.0–21.7) weeks and clinical remission was 15.1 (7.4–24.9) and 10.1 (3.1–21.0) weeks respectively. Time to clinical response for UC was 9.4 (5.7–15.4) and CD was 9.5 (6.1–18.2) weeks. Disease activity decreased from baseline at 14 weeks: pMS 5 (4–6) vs 3 (1–5) p=0.025 and 30 weeks pMS 5 (4–6) vs 2(1–5.5) p=0.032. Concomitant corticosteroid and immunomodulator use decreased in UC (48% vs 15% and 41% vs 18%) and CD (27% vs 10% and 26% vs 7%), respectively. The overall rate of IBD-related hospital admissions per patient per year was 1.3 (0–18.1). Adverse events were reported in 5.2% of patients. Conclusions Results in our predominately anti-TNF experienced vedolizumab cohort mirror other published real-world data and demonstrate good clinical effectiveness and safety profile.

SummaryBackgroundThere is a great unmet clinical need for efficacious, tolerable, economical and orally administrated drugs for the treatment of inflammatory bowel disease (IBD). New therapeutic avenues have become possible including the development of medications that target specific genetic pathways found to be relevant in other immune mediated diseases.AimsTo provide an overview of recent clinical trials for new generation oral targeted medications that may have a future role in IBD management.MethodsPubmed and Medline searches were performed up to 1 March 2018 using keywords: “IBD”, “UC”, “CD”, “inflammatory bowel disease” “ulcerative colitis”, “Crohn's disease” in combination with “phase”, “study”, “trial” and “oral”. A manual search of the clinical trial register, article reference lists, abstracts from meetings of Digestive Disease Week, United European Gastroenterology Week and ECCO congress were also conducted.ResultsIn randomised controlled trials primary efficacy endpoints were met for tofacitinib (JAK 1/3 inhibitor‐phase III), upadacitinib (JAK 1 inhibitor‐phase II) and AJM300 (α4‐integrin antagonist‐phase II) in ulcerative colitis. Ozanimod (S1P receptor agonist‐phase II) also demonstrated clinical remission. For Crohn's disease, filgotinib (JAK1 inhibitor‐phase II) met primary endpoints and laquinimod (quinolone‐3‐carboxide small molecule‐phase II) was also efficacious. Trials using mongersen (SMAD7 inhibitor) and vidofludimus (dihydroorotate dehydrogenase inhibitor) have been halted.ConclusionsThis is potentially the start of an exciting new era in which multiple therapeutic options are at the disposal of physicians to treat IBD on an individualised basis. Head‐to‐head studies with existing treatments and longer term safety data are needed for this to be possible.

Introduction Variceal size is a major predictor of the risk of bleeding in patients with liver cirrhosis. Guidelines from the American Association for the Study of the Liver (AASLD) recommend the use of a simplified system (small vs large) for grading of oesophageal varices (OV), but data on the reliability of this system compared to the conventional 3- grade classification remains lacking. We aimed to assess inter-rater reliability of these two widely used grading systems for OV. Method High-resolution endoscopy recordings of 108 patients (n=8 training cohort and n=100 evaluation cohort) with chronic liver disease were prospectively collected using standardised criteria. Nine Gastroenterologists of variable experience performed independent evaluations of the videos in a random order. The cases were scored according to the presence or absence of OV. If OV were present they were scored using a 2-grade system (small and large) as well as a 3-grade system (small, medium and large). Overall agreement was analysed using intraclass correlation coefficient or kappa statistic as required. Results Agreement on the presence or absence of varices was good (k=0.6, p<0.001). Agreement between observers using the 2-grade (0.74, 95% Confidence interval (CI) 0.68–0.80) was very similar to that using the 3-grade scoring system (0.76, 95% CI 0.70–0.81). The agreement between experts (2-grade: k=0.78, 95% CI 0.71–0.84 and 3-grade: k=0.79, 95% CI 0.72–0.84) was slightly higher than that between trainees (2-grade: k=0.7, 95% CI 0.61–0.77 and 3- grade: k=0.72, 95% CI 0.637–0.792). The agreement between observers and the reference endoscopist was slightly higher for the 2-grade system (k=0.55, p<0.001) in comparison to the 3-grade system (k=0.47, p<0.001). Conclusion Observers had a good to substantial level of agreement using 2 different scoring systems of OV. We conclude that the simpler 2-grade system recommended by AASLD appears to be equivalent to the 3-grade system in terms of inter-observer agreement. This is the first study to support its use in clinical practice. Disclosure of Interest None Declared

Introduction IDA affects up to 5% of the adult population in the developing world. There is an association between H. pylori (Hp) infection and incidence of unexplained IDA, but the mechanisms remain unclear. In children it has been suggested that Hp disturbs the iron regulatory mechanism via hepicidin. This peptide hormone induces internalisation and degradation of the iron transporter protein ferroportin thus limiting iron absorption and release. Hepcidin expression is induced by inflammation, but how this relates to Hp and IDA has not been fully elucidated, particularly in adults. This pilot study aimed to characterise local and systemic iron transporter expression in IDA patients with and without Hp infection, in comparison to Hp negative dyspepsia controls. Methods Patients undergoing routine endoscopy for IDA (HpIDA and IDA groups, n = 18 and 40 respectively) or without IDA (control group, n = 18) donated blood and biopsy samples with informed consent and ethical approval. Hp status was assessed by three biopsy based tests and by serology. Duodenal and gastric biopsies were evaluated by immunohistochemistry for ferroportin and hepcidin, in addition to H&E staining for inflammation and atrophy grading. All scoring was carried out by experienced blinded histopathologists. A commercial ELISA assay was used to quantify serum Hepcidin-25. Results As expected, anaemia parameters were significantly lower in the HpIDA and IDA groups compared to the controls (P < 0.0001). Surprisingly, serum hepcidin concentrations were significantly reduced in the HpIDA and IDA groups compared to the controls (9 fold, P = 0.009 and 5 fold, P < 0.0001 respectively). Hp infection was associated with gastric expression of hepcidin, particularly in the corpus when compared to controls. This corresponded with the cytoplasmic relocalisation of ferroportin (n = 12; 67%) in the duodenal enterocytes of patients with HpIDA compared to controls, where the ferroportin was actively expressed. Hepcidin was also found to be expressed in the duodenum of both controls and HpIDA. Significant atrophy was observed in both IDA groups. Conclusion IDA was associated with significantly lower levels of serum hepcidin in contrast to previous studies. Local or systemic factors such as inflammatory mediators could be driving this response as more severe atrophy was observed in both IDA groups. We now aim to perform quantitative analysis of hepcidin in the gastric specimens using RT-qPCR to further evaluate whether local Hp transcriptionally upregulated hepcidin expression might cause these effects on iron transport. Disclosure of Interest None Declared

Background: Pulmonary arterial hypertension (PAH) is characterized by pulmonary vascular remodeling, rise in pulmonary arterial pressures, and if left untreated, right heart failure. Invasive hemodynamic assessment with right heart catheterization (RHC) has been the gold standard for the diagnosis and serial assessment of patients with PAH. However, RHC has important limitations and might be supplemented by newer technologies in the management of PAH patients.Implications for Clinicians: Implantable hemodynamic monitors (IHM) hold the promise of being able to provide accurate pulmonary artery pressure measurements, with frequent or continuous remote monitoring in the home or ambulatory setting. As such, IHMs may provide a more complete understanding of a patient's hemodynamic profile and burden of disease. IHM data may also help to provide ongoing feedback in terms of a PAH patient's response to medical therapy and other interventions and might be valuable in specific subsets of patients with borderline or exercise-induced PAH.Conclusions: Though clinical studies using IHMs in PAH patients have been limited to small series and case reports, these devices hold a great deal of promise to supplement RHC in the management of PAH patients and warrant further investigation and clinical experience.

Pulmonary arterial hypertension (PAH) remains a morbid disease requiring better markers for outcome prediction. Although invasive hemodynamics (Hemos) provides valuable prognostic information, their routine use is impractical. The CardioMEMS™ HF System (CMHFS) is indicated for wireless monitoring of PA pressure in heart failure patients (pts). It allows daily Hemo measurements reflecting the total Hemo burden of disease over time. Importantly, assessment of exercise Hemos may allow a novel modality for assessment of therapeutic interventions in PAH. We tested the feasibility of assessing exercise Hemos in PAH pts implanted with the CMHFS during the 6-minute walk distance (6MWD). 11 PAH pts had the CMHFs implanted. Device mPAP, sPAP, dPAP, HR, and CO (sensor pressure based algorithm) and CMHFS derived total pulmonary resistance (TPR), right ventricular (RV) stroke volume and index (SV, SVI), RV work (W), RV power (P) and compliance (SV/PP) were collected pre and post 6MWD and compared using paired-t tests at 1 & 4 mos. Changes in values b/t 1 and 4 mos were also analyzed. Pts consisted of newly (45%) and previously (55%) diagnosed pts with NYHA Class III or IV sxs. All Implanted pts were female, aged 57 ± 9 with IPAH (45%), scleroderma-related (45%) and anorexigen-related (5%) PAH with a mPAP 45 ± 14 mmHg and pulmonary vascular resistance of 600 ± 384 dyn.s.cm-5. There were no peri-procedural complications and no device related SAE's within the first month post implant. PAH meds were optimized per the treating MD over time. As compared to pre 6MWD Hemos, there was a significant increase (p <0.05) in post 6MWD HR, TPR, sPAP, dPAP, mPAP, RVW and RVP and a significant decrease (p<0.05) in SV, SVI and C. These changes persisted at 4 mos. When comparing changes in isolated pre and post 6MWD values between 1 and 4 mos, there were no differences in pre 6MWD values. However, significant positive changes (p<0.05) in post 6MWD SV, SVI, RVW occurred with a consequent significant decrease in TPR. Use of the CMHFS in a select group of PAH pts with advanced symptoms appears safe and demonstrated with exercise a significant increase in pulmonary pressure and resistance with a coincident decline in RV performance, coupling and efficiency that persisted over time and only marginally improved with optimization of therapy. The clinical impact on these changes will need to be further explored.

Introduction IDA is prevalent in up to 5% of the developed world and endoscopy remains the most utilised investigation. Magnified white light endoscopy has been shown to accurately identify gastric atrophy, H. pylori gastritis and coeliac disease but the role of magnified NBI endoscopy (NBI-Z) in this context has not been evaluated. The study aim was to assess the ability of NBI-Z to make a real time diagnosis of these conditions compared to histology as the gold standard. Methods This prospective cohort study recruited patients undergoing endoscopic evaluation for IDA. All procedures were performed with an Olympus video endoscopy system by clinicians with advanced imaging experience. Systematic NBI-Z imaging in parts of the duodenum and gastric mucosa were taken with corresponding biopsies. A previously validated Nottingham Type 1–4 classification system was used to classify the characteristic gastric mucosal pit pattern, and magnified morphological features were used to describe intestinal metaplasia and villous atrophy. This allowed for a real time diagnosis to be made for villous atrophy, gastric atrophy and H. pylori gastritis. The specimens were examined by a single blinded GI pathologist. Results 105 patients were recruited over 3 years. Excluding those with an obvious cause (n = 11), a total of 94 patients were included in the final analysis. Female: male ratio was 1: 0.7, median age 66 years (range 21–85). 38% had significant co-morbidities. At time of endoscopy 52% were taking iron therapy, 19% aspirin, 30% PPI and 4% NSAIDs. The median (range) anaemia parameters were: Hb 10.8g/dL (7.7–12.6), MCV 82fl (60–97), Ferritin 10g/L (1–379) and iron 7.5 µmol/L (1–22). 73% had the procedure under sedation with median doses of 2.5 mg midazolam and 25 mg pethidine. Conclusion In patients with IDA, NBI-Z is highly specific in providing a real time diagnosis of gastric atrophy and coeliac disease. It is a useful technique to exclude H. pylori gastritis. The clinical relevance is that this technique allows for targeted biopsies, reducing the miss rate and thus increasing the diagnostic yield. Disclosure of Interest J. White: None Declared, S. Sami: None Declared, J. Ortiz Fernández-Sordo: None Declared, J. Mannath: None Declared, K. Ragunath Grant/research support from: Olympus-Keymed UK, Speaker honoraria and consultancy fees from: Olympus-Keymed UK.

SummaryChronic hepatitis C virus (HCV) infection places a considerable economic burden on health services. Cost‐effectiveness analyses of antiviral treatment for patients with chronic HCV infection are dependent on assumptions about cost reductions following sustained virological response (SVR) to therapy. This study quantified the medium‐term difference in health resource usage and costs depending on treatment outcome. Retrospective chart review of patients with HCV genotype 1 infection who had received at least 2 months pegylated interferon and ribavirin therapy, with known treatment outcome was conducted. Disease status was categorized as chronic hepatitis, cirrhosis or decompensated liver disease. Health resource use was documented for each patient in each disease state. Unit costs were from the NHS ‘Payment by Results’ database and the British National Formulary. One hundred and ninety three patients (108 SVR, 85 non‐SVR) with mean follow‐up of 3.5 (SVR) and 4.9 (non‐SVR) years were enrolled. No SVR patient progressed to a more severe liver disease state. Annual transition rates for non‐SVR patients were 7.4% (chronic hepatitis to cirrhosis) and 4.9% (cirrhosis to decompensated liver disease). By extrapolation of modelled data over a 5‐year post‐treatment period, failure of patients with chronic hepatitis to achieve SVR was associated with a 13‐fold increase (roughly £2300) in costs, whilst for patients who were retreated, the increase was 56‐fold, equating to more than £10 000. Achievement of an SVR has significant effects on health service usage and costs. This work provides real‐life data for future cost‐effectiveness analyses related to the treatment for chronic HCV infection.