Rishi M. Goel

Budd-Chiari syndrome: investigation, treatment and outcomes.

Budd–Chiari syndrome is a rare disorder characterised by hepatic venous outflow obstruction. It affects 1.4 per million people, and presentation depends upon the extent and rapidity of hepatic vein occlusion. An underlying myeloproliferative neoplasm is present in 50% of cases with other causes including infection and malignancy. Common symptoms are abdominal pain, hepatomegaly and ascites; however, up to 20% of cases are asymptomatic, indicating a chronic onset of hepatic venous obstruction and the formation of large hepatic vein collaterals. Doppler ultrasonography usually confirms diagnosis with cross-sectional imaging used for complex cases and to allow temporal comparison. Myeloproliferative neoplasms should be tested for even if a clear causative factor has been identified. Management focuses on anticoagulation with low-molecular-weight heparin and warfarin, with the new oral anticoagulants offering an exciting prospect for the future, but their current effectiveness in Budd–Chiari syndrome is unknown. A third of patients require further intervention in addition to anticoagulation, commonly due to deteriorating liver function or patients identified as having a poorer prognosis. Prognostic scoring systems help guide treatment, but management is complex and patients should be referred to a specialist liver centre. Recent studies have shown comparable procedure-related complications and long-term survival in patients who undergo transjugular intrahepatic portosystemic shunting and liver transplantation in Budd–Chiari syndrome compared with other liver disease aetiologies. Also, the optimal timing of these interventions and which patients benefit from liver transplantation instead of portosystemic shunting remains to be answered.

Diffuse Large B-Cell Lymphoma Recurrence Complicating Primary Intestinal Lymphangiectasia

m p l A man presented with abdominal pain, diarrhea, and 6-kg weight loss. His medical history included priary intestinal lymphangiectasia (PIL), which was diagnosed hen he was 6 years old. Three years ago, he presented with similar symptoms that ere investigated with computed tomography scan of abdomen Figure A; marked mural thickening in multiple small bowel oops and moderate ascites) and small bowel meal (Figure B; iffuse mucosal fold thickening, increased nodularity in muliple small bowel loops, and tiny nodules representing dilated acteal vessels in the lamina propria), with findings typical for ymphangiectasia. Gastroscopy and ileocolonoscopy were performed. Duodenal iopsies showed dilated lymphatic channels characteristic for ymphangiectasia. Terminal ileum biopsies confirmed multifoal diffuse large B-cell lymphoma (DLBCL). Clinical remission as achieved with multiple cycles of rituximab, cyclophosphmide, doxorubicin, vincristine, and prednisolone. Parenteral utrition was required during chemotherapy. Annual surveilance with positron emission tomography– computed tomograhy (PET-CT) up to representation confirmed remission of LBCL. At this presentation, PET-CT showed multiple foci of inreased metabolic activity within the proximal small bowel. astroscopy showed numerous smooth soft cystic lesions inerspersed with whitish spotty lesions in the duodenum (Figure ). Endoscopic appearances and biopsies confirmed these alost entirely replaced the duodenal folds, which was consistent ith lymphangiectasia. To exclude DLBCL recurrence, enterosopy was performed, revealing lymphangiectasia from the dudenum to the proximal jejunum. The jejunum was interpersed with more suspicious-looking lesions (Figure D), with iopsies confirming relapse of DLBCL. Salvage chemotherapy was commenced with rituximab, ytarabine, cisplatin, and dexamethasone. PET-CT confirmed

OC-045 Faecal microbiota transplantation: implementing a new treatment for recurrent/refractory clostridium difficile infection using banked stool in a tertiary uk centre

Introduction Faecal microbiota transplantation is an effective treatment for recurrent/refractory Clostridium difficileinfection (CDI). A randomised controlled trial reported sustained response in greater than 90% of patients, with an excellent safety profile. NICE approved the treatment as of March 2014. We introduced this new service in January 2015, setting up a stool bank to treat patients with recurrent CDI. We describe the process of initiating this service. Method Stool donors are recruited from non-clinical members of hospital staff or patient selected donors. Donors must be healthy with a BMI <30, not taking oral medication, not received antibiotics in the previous 3 months and not be infected or at risk of any blood-borne viruses or transmissible infectious diseases. Donors are screened for diseases including Hepatitis A, B, C, E, HIV, HTLV, syphilis, CMV, EBV, Entamoeba histolytica, Strongyloides sterocaralis, Cryptosporidium, Giardia, C.difficile, H. Pylori, Norovirus, Campylobacter, Salmonella, Shigella, E.coli O:157, MRSA and multi-drug resistant coliforms. All transplant material has a batch number allowing full traceability. After screening, donors can provide stool for transplant for up to 3 months. >50 g of fresh donated stool is diluted with 250 mls 0.9% normal saline and 12.5% glycerol, filtered to remove large particles and immediately frozen at –800C. Frozen stool can be stored for up to 6 months, offers the benefit of being available on demand, and is as effective as freshly used stool. Recipients are informed of the risks of colonoscopy and the risk of acquiring an unrecognised transmissible disease. Standard bowel preparation is given and the transplant is delivered through the endoscope channel with 75% of the donor stool placed in the caecum, and the remainder in the right colon. Alternatively, infusion can be performed via a nasoduodenal tube. Results This pathway has been successfully implemented. Procedures are performed at the end of a list to allow subsequent deep cleaning of the endoscopy room, and donor stool is available in an ice box 30 min prior to procedure. Individuals are discharged home the day after the procedure, and contacted a week later to ascertain improvement in symptoms, and at 3-months for a second assessment including laboratory testing for C. difficile. Preliminary experience is promising with 100% of patients achieving clinical remission within a week of a single procedure. Conclusion Introduction of a faecal transplant service for CDI is feasible. As with all new treatments safety is paramount. Thorough screening of donors, traceability of transplants and long term follow up is essential. Disclosure of interest None Declared.

Sa1255 Higher Red Blood Cell Methotrexate Polyglutamates Correlate With Increased Disease Activity, and Are Useful in Assessing Adherence

Introduction Methotrexate (MTX) is commonly used in patients with inflammatory bowel disease (IBD). Within red blood cells (RBC), MTX is activated by sequential addition of glutamic acid residues to form polyglutamates (MTXPG 1–5 ). In rheumatoid arthritis, low [MTXPG] has been associated with active disease, whereas other studies have demonstrated an inverse relationship, including the only published data in IBD. The aim of this study was to determine if RBC [MTXPG] reflect clinical response in IBD patients and whether they are useful in assessing adherence. Methods This was a single-centre, retrospective pilot study of 21 IBD patients treated with weekly MTX. RBC MTXPG 1–5 was measured using high-performance liquid chromatography. Clinical status (active disease or remission) was assessed by 2 IBD physicians blinded to [MTXPG], using a combination of prospectively recorded clinical activity indices (Simple Colitis Activity Index, Harvey Bradshaw Index), endoscopy, faecal calprotectin and C reactive protein (CRP). Pearson correlation coefficient, r was calculated to assess the relationship between MTX dose and [MTXPG]. Association between [MTXPG] and clinical response was analysed with unpaired t-test. Results 4/21(22%) patients (3 of whom admitted non-adherence) had undetectable MTXPGs and were excluded from further analysis. MTXPG 2–4 were detected in all adherent patients. PG 3 was the predominant polyglutamate accounting for a mean of 43% of total MTXPG. A linear relationship between dose of MTX and PG 1–5 was observed. 12/21(57%) patients were assessed as having active disease. No significant difference in mean [MTXPG n ] was observed between those with active disease and remission. For each MTXPG n , a non-significant trend towards a higher concentration was observed in patients with active disease. Conclusion In this study, the largest to date in IBD, measuring RBC MTXPG was useful in assessing adherence to MTX. A trend towards higher PG concentrations was associated with active disease confirming the findings in the only other study in IBD. Whether this is confounded by higher doses being used in patients with more active disease warrants further study in larger, prospective trials. Reference Disclosure of Interest None Declared.

Su1101 Indeterminate and Inconclusive Results Are Common When Using Interferon Gamma Release Assay As Screening for TB in Patients With IBD

Introduction Anti-TNF treatment is widely used in inflammatory bowel disease (IBD) but has been linked with reactivation of tuberculosis (TB). Screening for active and latent TB prior to initiation of anti-TNF therapy is therefore mandated. ECCO recommends interferon gamma release assays (IGRAs) as, unlike tuberculin skin test, positive tests are not caused by previous Bacillus Calmette–Guerin (BCG) vaccine. However, immunosuppressive agents can result in indeterminate or unreportable results[i] and there is no clear guidance on managing them. We quantified the prevalence of indeterminate or unreportable TB IGRA Elispot results in a large tertiary centre cohort of patients with IBD. Methods A single centre retrospective study of IGRA tests performed on IBD patients prior to commencement of anti-TNF therapy between Oct 2010 and Oct 2013. Results We included 140 patients (median age 34, range 24–86, 50% males). 92% had Crohn’s disease, 4% ulcerative colitis, and 4% IBD-unclassified. At the time of IGRA testing, 115 patients were on immunomodulators and 6 on prednisolone. 3 were positive for latent TB and were referred to infectious disease (ID) department prior to anti-TNF therapy. 3 had indeterminate results; all were on immunosuppressants (2=azathioprine, 1=methotrexate). 2 had a lymphocyte count 10 had unreportable results, 9 of whom were on azathioprine. On repeat testing, 4 were negative, and the remainder were still unreportable, one of whom had risk factors for TB and was treated with isoniazid chemoprophylaxis on the advice of the ID team. The remaining 5 patients started anti-TNF based on the absence of risk factors for TB. No patient had reactivation of latent TB at follow up (range 1–18 months). Lymphopaenia was found to be associated with non-reportable cases as compared to the reported cases (median lymphocyte count unreportable = 0.4, reportable = 1.2; p = 0.015). Conclusion Our results demonstrate TB IGRA is a useful test to screen for latent infection before initiating anti-TNF therapy. However, a minority of results are indeterminate or unreportable. In such cases repeat testing can produce definitive results. Low lymphocyte counts in association with immunosuppression may contribute to unreportable and indeterminate results; clinical risk stratification appears to be a safe way of managing such cases in this small cohort. Reference Papay P et al . Predictors of indeterminate IFN-γ release assay in screening for latent TB in inflammatory bowel diseases. Eur J Clin Invest. 2011 Disclosure of Interest None Declared.

OC-015 The Influence of Gender and Haemoglobin on TPMT Activity

Introduction Pre-treatment measurement of red blood cell (RBC) thiopurine-S-methyltransferase (TPMT) activity is recommended to guide initial dosing of azathioprine (AZA) and mercaptopurine (MP). TPMT exhibits a trimodal distribution, with low and intermediate activities predicting myelotoxicity at standard drug doses. There is a high concordance between TPMT genotype and normal or low enzyme activity (93–100%); however the relationship is poor in the intermediate range (53–100%) [1]. Furthermore, there are few explanations for the wide variation in inter-individual TPMT activities in the wild-type range. Bioavailability of the cofactor S-adenosylmethionine (SAM) and RBC age may play a role. The aim of this study was to determine if gender or anaemia influences RBC TPMT activity. Methods We analysed a retrospective cohort of 6,496 RBC TPMT samples (n = 3804 females, n = 2692 males) measured in the PRL since 2004 and correlated enzyme activity with gender and haemoglobin concentrations. Results A greater portion of females exhibited intermediate TPMT activity (13.46%) as compared to males (11.07%). The mean TPMT activity was also significantly lower in females (32.94 pmol/mg Hb/h) versus males (34.13 pmol/mg Hb/h; p = < 0.0001, 95% CI 0.7950–1.589). When separated by low, intermediate or normal TPMT activity, this relationship only remained in patients with normal TPMT activity. TPMT activity was significantly higher in female patients with an Hb < 10g/dl (n = 250, mean TPMT 38.06 pmol/mg Hb/h) versus females with an Hb > 12g/dl (n = 2192, mean TPMT 32.46 pmol/mg Hb/h; p = < 0.0001). Similarly TPMT activity was significantly higher in male patients with an Hb < 10g/dl (n = 123, mean TPMT 38.14) versus males with an Hb > 12g/dl (n = 1901, mean TPMT 33.76; p = < 0.0001). Conclusion TPMT activity in the wild-type range is lower in females than males, suggesting a post-translational influence on TPMT activity related to gender. Lower levels of SAM have been reported in females, which may explain this observation[2]. Re-appraisal of the concordance between TPMT genotype and phenotype, adjusting for gender is therefore indicated. The finding of higher TPMT activity with anaemia may be due to a younger red cell population in this group. The difference in TPMT activities between patients with or without anaemia is clinically relevant, particularly where the TPMT activity is around the cut-off between intermediate (10–25 pmol/mg Hb/h) and normal (≥26 pmol/mg Hb/h) ranges. TPMT genotyping should be considered in such patients. Disclosure of Interest None Declared References Karas-Kuzelicki, et al. Pharmacogenomics 2009. 10:1309–22. Poirier, et al. Cancer epidemiology, biomarkers & prevention 2001. 10:649–655.

Recommended drug therapies for inflammatory bowel disease

The treatment of inflammatory bowel disease (ulcerative colitis and Crohns disease) has been revolutionised in recent years with the advent of biological therapies. This article discusses the current role of both conventional and biological treatments in the management of these conditions.

Causes and treatment of nausea and vomiting

Nausea and vomiting are associated with a range of underlying causes, and a full history and clinical examination are essential in order to yield a diagnosis and commence appropriate treatment. This article discusses the various causes of nausea and vomiting and the treatment options available.

PTU-044 Tertiary Centre Experience Of 360 Degree Side-viewing Video Capsule Endoscopy

Introduction Since it’s development in 1999, video capsule endoscopy (VCE) has become the investigation of choice for examining the small bowel. Recently, a novel panoramic 360 degree side-viewing VCE (Capsovision, Medical Innovations, USA) was launched. It differs from previous capsules in that no data recorder or sensors are required. The images are stored on the capsule itself, which when passed, must be retrieved and sent to the endoscopy reader for analysis. We report our initial experience of this novel VCE. Methods We retrospectively analysed the first 51 side-viewing VCE over a 6-month period at our institution. All patients had a clear liquid diet as preparation the day before. Results 51 patients (26 males) underwent examination with the side-viewing VCE. 39 (76.4%) examinations were completed and 12 were incomplete. This included 4 which were lost due to being flushed away. Over the same time period, forward-viewing VCE complete results were available in 83.2% patients. 1 of the incomplete examinations was due to a NSAID-induced stricture, subsequently diagnosed with a forward-viewing VCE. 31 patients had good bowel preparation, 11 satisfactory preparation and 6 were reported as having poor bowel preparation. The duodenal ampulla was reliably identified in 3/47 (6.4%) examinations. Pathology was identified in 11/47 (23.4%) examinations. Conclusion Side-viewing VCE was well tolerated and completed examination results were available for 76.4% of patients examined. Our findings did not correlate with previous reported results (71%) regarding the identification rate of the duodenal papilla as a small bowel landmark with side-viewing VCE. Advantages of the side-viewing VCE are not needing the patient to wear a recorder, with the data being stored in the capsule itself. This enables multiple patients to be examined on the same day and the number of examinations is not limited by available data recorders. Patients can also take the capsule home and take the capsule at any time which can be useful in the investigation of obscure GI bleeding. Side-viewing VCE is comparable to forward viewing VCE with respect to cost and accuracy. Disclosure of Interest None Declared.

PWE-080 Prevalence of Faecal Incontinence in Adults with Inflammatory Bowel Disease

Introduction The prevalence of faecal incontinence (FI) in people with inflammatory bowel disease (IBD) has not been fully explored. FI is not only associated with social stigma but also with decreased quality of life. In the general population prevalence is estimated at between 1–10%. Awareness of the prevalence of FI in IBD is important to aid management strategies and resource allocation. Methods Aim: To investigate the prevalence of FI in adults with IBD in a tertiary care setting. Methods: We performed a cross sectional questionnaire survey of 380 adults attending IBD outpatients at Guy’s & St.Thomas’ Hospitals. Patient surveys were: the validated International Consultation on Incontinence – Bowels (ICIQ-B) questionnaire, detailing frequency and severity of bowel pattern, control and quality of life; and the non-validated Bowel Leakage questionnaire, detailing any prior interventions by health care professionals. Demographics of age, gender, diagnosis, Montreal classification, St Mark’s Continence Score and disease activity were also recorded. Data was entered into a database and analysed using a SPSS statistical package. Results Median age was 38 years (IQR 31–50) and 180/380 (47%) were female. The mean duration of IBD diagnosis was 8.7 years (3.4–15.1). 151/380 (40%) had UC vs 229/380 (60%) CD. Overall, 255/380 (67%) reported FI as defined by any episode of uncontrolled bowel opening in the preceding three months, while 343/380 (90%) reported anal incontinence of flatus or faeces. Incontinence was strongly associated with disease activity, occurring during disease flares in 57% of people. However, 37% experienced incontinence both during relapse and remission, whilst only 5% experienced incontinence uniquely when in remission. The ICIQ-B control score was associated with current disease activity in CD (r = 0.29, p < 0.0001) but not in UC. There was no significant difference in FI prevalence between patients with Crohn’s Disease (CD) or Ulcerative Colitis (UC), (66% vs 68%, p = 0.74). Conclusion Faecal incontinence in IBD increases in proportion to disease activity. Given the availability of specialist FI interventions and support, we recommend that sensitive questioning regarding FI should be part of routine disease surveillance in the outpatient setting to cater for this unmet need. Disclosure of Interest None Declared.