British Society Of Paediatric Gastroenterology Hepatology

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British Society Of Paediatric Gastroenterology Hepatology

Transcript Of British Society Of Paediatric Gastroenterology Hepatology

January 23rd –25th 2008

Botley Park Hotel and Golf Club Southampton SO32 2UA
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Dear Colleagues
We would like to welcome you to Southampton and to the Winter Meeting of the BSPGHAN.
We have made clinical practice the main focus of the meeting covering a wide variety of topics across all three of the society’s specialist areas including global malnutrition, obesity, surgical practice and the interface between paediatric and adult specialist practice. We have been fortunate to attract top quality speakers and hope you will enjoy the sessions. Good clinical practice comes from quality research and we are pleased to have Professor Sally Davies to talk on research in the modern NHS.
We were pleased to have more than 50 abstracts submitted and hope you will enjoy the plenary abstract and poster sessions.
We are grateful for all the practical help we have had with the organisation of the meeting. We have had considerable support from the BSPGHAN council. Sue Protheroe’s help has been invaluable organising the abstract adjudication and advising on the postgraduate programme including the introduction of trainee case presentation.
We are also grateful for the support of industry without which it would be difficult for a meeting like this to go ahead.
Carla Lloyd, as part of the organising committee has been invaluable
Mark Beattie
On behalf of the Organising Committee
Winter Meeting Organising Committee Dr Mark Beattie Mr Mervyn Griffiths Dr Nadeem Afzal Mrs Carla Lloyd
Supported by Dr Huw Jenkins Dr Stephen Murphy Dr Muftah Eltumi Dr Sue Protheroe Dr Richard Russell
Abstract Selection Committee Dr Sue Protheroe (chair) Dr Sue Beath Dr Richard Russell Mr Mervyn Griffiths
Social Committee Mr Mick Cullen Dr Richard Russell
Sponsorship: We wish to also thank the following sponsors for their generous support

Wednesday 23rd January 2008 – Postgraduate Course

10.00 – 10.30 Registration and Coffee

Chair Dr Sue Protheroe and Mr Mervyn Griffiths

Session One : Theme Therapeutic Options in Inflammatory Bowel Disease

10.30 – 11.00

Cochrane Methodology with specific reference to Inflammatory Bowel Disease Dr Tony Akobeng - Consultant Paediatric Gastroenterologist, Manchester

11.00 – 11.30

New Therapeutic Approaches in Inflammatory Bowel Disease Dr Ronald Bremner, Birmingham

11.30 – 12.30 Case presentations with Panel Discussion

11.30 – 11.45

Azathioprine: Friend or Foe? Presenter: Dr Sherina Ross S Ross, S Rajwal, I Sugarman, S Davison, S Picton, P McCLean. St. James’s University Hospital, Beckett Street, Leeds, LS9 7TF.

11.45 – 12.00

Crohn’s disease presenting as gastric outlet obstruction Presenter: Dr Sabarinathan Loganathan Loganathan S, Casson D Alderhey Children’s Hospital, Liverpool.

12.00 – 12.15

Diagnostic and management dilemma in a case of Inflammatory bowel disease Presenter: Dr Viswa Sivaramakrishnan VM Sivaramakrishnan, S Protheroe Department of Paediatric Gastroenterology Birmingham Children’s Hospital, Birmingham, United Kingdom

12.15 – 12.30

Pre-pouch ileitis after colectomy in paediatric ulcerative colitis Presenter: Dr Wael El-Matary Carrie Slatter, Safwat Girgis+, Hien Huynh, Wael El-Matary Division of Pediatric Gastroenterology, Hepatology and Nutrition, Stollery Children’s Hospital and +Department of Pathology, University Hospital, University of Alberta, Edmonton, Canada

12.30 – 13.30 Lunch

Chair: Dr Jane Hartley and Dr Jenny Gordon

Session Two : Theme Liver Transplantation : Update on Transplant Issues

13.30 – 14.00

Case presentation with discussion of the long term complications of transplantation. Dr Venkatesh Karthik - Specialist Registrar, Leeds

14.00- 14.30

Organ donation issues Professor Nigel Heaton - Consultant Transplant Surgeon, London

14.30 – 15.00

Update on immunosuppressive agents including the monoclonal antibodies and newer immunosuppressive agents. Dr Sue Beath - Consultant Paediatric Hepatologist, Birmingham

Chair Dr Steve Wootton and Dr John Puntis

Session Three: Nutritional Assessment of Children with Chronic Disease

15.30 – 16.00

Introduction to Nutritional Assessment Dr Steve Wootton - Senior Lecturer in Nutrition, Southampton

16.00 – 16.20

Nutritional assessment in Cystic Fibrosis Mrs Teresa Hannan - Paediatric Dietician, Southampton

16.20 – 16.40 16.40 – 17.10 17.10-17.30 17.30 – 18.30
19.00 – 20.30 21.00

Nutritional assessment in IBD Mrs N Heather - Paediatric Dietician, Southampton
Feeding children with neurodisability – the evidence base Dr Peter Sullivan - Consultant Paediatric Gastroenterologist, Oxford
Panel discussion led by Chair
Endoscopy Steering Group Dr Mike Thomson (Open to all members)

Thursday 24th January 2008

Registration 9.30 – 12.00

Working Group/Specialist group meetings

Meetings open to all delegates



9.00 – 10.15

Hepatology DGH IBD Associates

Dr Patricia McClean Dr Graham Briars Dr Sally Mitton Dr Jenny Gordon

10.30 - 11.45

Clinical Standards Trainees Research Education Nutrition

Dr Nigel Meadows Dr Richard Russell Dr Nikhil Thapar Dr Sue Protheroe Dr Sue Beath

Poster session I viewing from 10.30

24th BSPGHAN Meeting

12.00 – 13.00

Buffet Lunch Poster session I and judging

13.00 – 13.05

Opening and welcome on behalf of the organising committee Dr Mark Beattie - Consultant Paediatric Gastroenterologist, Southampton

Session I

Chair: Dr Huw Jenkins and Dr Stephen Murphy

13.05 – 13.50

Research opportunities in the NHS Professor Sally Davies - Director General for Research and Development, Department of Health

13.50 – 15.20

Plenary session I with abstracts from Gastroenterology, Hepatology and Nutrition

13.50 – 14.05

Polymeric versus elemental feeding a in newly diagnosed paediatric Crohn’s disease : a single blind randomised control trial Grogan J, Terry A, Casson D, Dalzell AM Dept. Nutrition and Dietetics. RLCH NHS Trust, Eaton Road, Liverpool L12 2AP

14.05 – 14.20

A prospective audit of liver biopsies in children SV Karthik1, S Davison1, P McClean1, S Rajwal1, W Ramsden2,

M Stringer1, H Woodley2, J Wyatt3. Children’s Liver and GI unit1, Departments of Radiology2 and Histopathology3, St James’s University Hospital, Leeds, UK.

14.20 – 14.35

UK regional paediatric HPN data suggest a national underestimate in service requirements A.R. Barclay1, C.E. Paxton1, J. LIvingstone2, D. Hoole3, F. Munro4, P. Gillett1, D.C. Wilson1,5, Departments of 1Paediatric Gastroenterology and Nutrition, 2Dietetics, 3Pharmacy and 4Surgery, Royal Hospital for Sick Children, Edinburgh, EH9 1LF, 5Child life and Health, University of Edinburgh, EH9 1UW

14.35 – 14.50

Feasibility of confocal laser endomicroscopy in the diagnosis of paediatric gastrointestinal disorders: the first human studies Venkatesh K1, Hurlstone DP2, Cohen M3, Evans C3, Tiffin N4, Delaney P5, Thomas S5, Taylor C1, Aboutaleb A1, Kiesslich R6, Thomson M1 1 Centre for Paediatric Gastroenterology, Sheffield Children’s NHS Foundation Trust, Sheffield, United Kingdom 2 Department of Gastroenterology, Royal Hallamshire Hospital, Sheffield, United Kingdom 3 Department of Histopathology, Sheffield Children’s NHS Foundation Trust, Sheffield, United Kingdom 4 Department of Histopathology, Royal Hallamshire Hospital, Sheffield, United Kingdom 5Optiscan, Melbourne, Australia. 6 I. Med. Klink und Poliklinik, Johannes Gutenberg University of Mainz, Mainz, Germany.

14.50 – 15.05

Impact of an improved national paediatric donor organ allocation policy for children waiting for intestinal transplantation (ITx) Giovanelli M1, Gupte GL1, Pocock P3, Lloyd C1, McKiernan P1, Richards S4, Sharif K1, Mirza DF2 1Liver Unit, Birmingham Children’s Hospital, 2Liver Unit, Queen Elizabeth Hospital, 3UK Transplant, Bristol, 4Transplant Co-ordinator, Queen Elizabeth Hospital

15.05 – 15.20

Small bowel histology in screening identified vs symptomatic children diagnosed with coeliac disease Srinivasan R, Rawat D, Spray CS, Ramani P* Dept of Paediatric Gastroenterology, Bristol Royal Hospital for Children and Dept of Histopathology *, United Bristol health Care NHS Trust, Upper Maudlin Street, Bristol, UK

15.20 – 15.45 Tea

Session II

Chair: Professor Bhu Sandhu

15.45 – 16.30

WHO Feeding children with malnutrition Professor Anne Ashworth Hill, London

16.30 – 17.15

Nutrition in the 21st century Professor Alan Jackson - Professor of Nutrition, Southampton

17.30 – 19.00 Annual General Meeting



21.00 – late

Conference dinner and entertainment with the band EMD

Friday 25th January 2008

Breakfast symposium sponsored by Nutricia

Cow’s Milk Allergy

Chair: Dr Martin Brueton

8.00 – 8.15

Update on European Protocol for Cow’s Milk Allergy Dr Martin Brueton - Consultant Gastroenterologist, Chelsea and Westminster

8.15 – 8.35

Practical Management of Cow’s Milk Allergy Patients Jonathan Hourihane

8.35 – 8.55

Prebiotics in Infancy – a two year follow up Dr Sertac Arslanoglu - Centre for Infant Nutrition, Macedonio Melloni Hospital, Milan

Session III

Chair: Dr Sally Mitton and Dr John Fell

9.00 - 9.45

Management of Ulcerative Colitis Dr Simon Travis - Consultant Gastroenterologist, Oxford

9.45 – 10.15

Modern Management of Gastroschisis Mr David Burge - Consultant Paediatric Surgeon, Southampton

Session IV

Sponsored by Children’s Liver Disease Foundation

Chair: Dr Patricia McClean and Dr Nadeem Afzal

10.15 – 10.45

Adolescent Liver Disease Dr Mark Wright - Consultant Hepatologist, Southampton

10.45 – 11.15

Outcome of Liver Disease in Childhood Professor Anil Dhawan, Consultant Paediatric Hepatologist King’s College Hospital, London

11.15 – 11.45 COFFEE

Poster Session II Viewing

Session V

Chair: Dr Ulrich Baumann and Dr Justin Davis

11.45 – 12.15

Metabolic syndrome Dr Julian Shields - Consultant Paediatric Gastroenterologist, Bristol

12.15 – 12.45

Bariatric Surgery Mr James Byrne - Consultant Surgeon, Southampton

12.45 – 13.30

BUFFET LUNCH Poster Session II and judging

Session VI

Chair: Professor David Candy and Dr Mike Bisset

13.30 – 15.00 Plenary abstract session II

13.30 – 13.45

Stable isotope probing of the gut microbiota can link bacterial activity to diversity across varying media, timeframes and bacterial species. A R Barclay1, L T Weaver1, D J Morrison2 1Division of Developmental Medicine, 2SUERC, University of Glasgow, Glasgow, United Kingdom

13.45 – 14.00 4.00 – 14.15 14.15 – 14.30 14.30 – 14.45

The early stool patterns of young children with autistic spectrum disorder Sandhu BK , Steer C, Golding J, Emond A Centre for Child and Adolescent Health, Hampton House, Bristol BS6 6JS
Exclusive enteral nutrition for induction of remission in children with Crohn's disease: Single centre experience of treating more than 100 children Buchanan E, Cardigan T, Hassan K, Young D, McGrogan P, Russell RK. Department of Paediatric Gastroenterology, Hepatology and Nutrition, Yorkhill Hospital, Glasgow
Gastric Electrical Stimulation for treatment of severe idiopathic gastroparesis in a child *C Ong, *S Robertson, F Torrente, C Salvestrini, JWL Puntis, M Winslet, O Epstein, RB Heuschkel . Paediatric Gatroenterology Department, Royal Free Hospital, Pond Street, London NW3 2QG (* joint first authors)
Eosinophilic colitis in children: a retrospective case series Sam Behjati*, Alan Bates*, Robert Heuschkel#, Alan Phillips#, Camilla Salvestrini#, Franco Torrente# *Department of Histopathology and #Centre for Paediatric Gastroenterology, Royal Free Hampstead NHS Trust, Royal Free & University College Medical School

14.45 – 15.00

Adalimumab usage in early-onset Crohn’s disease – results of a regional cohort study DC Wilson, GT Ho, PM Rogers, A Tybulewicz, J Satsangi Department of Paediatric Gastroenterology and Nutrition,Royal Hospital for Sick Children, Edinburgh EH9 1LF

15.00 - 15.30

Peri-anal disease Mr Paul Nichols - Consultant Surgeon, Southampton

15.30 – 16.00

Cyclical Vomiting Syndrome Dr Marion Rowland - Lecturer in Epidemiology, Dublin


Presentation of prizes and Close of Meeting Dr Huw Jenkins - President BSPGHAN

25th BSPGHAN Winter Meeting

28th – 30th January 2009, Sheffield

Local organiser: Dr Mike Thomson

How Cochrane Systematic Reviews Guide Therapy in IBD: Maintaining Remission in Crohn’s Disease
Tony Akobeng, Booth Hall Children’s Hospital, Manchester, UK
Background: Systematic reviews of randomised controlled trials (RCTs) are considered to be evidence of the highest level in the hierarchy of research designs evaluating effectiveness of interventions. Systematic reviews allow us to take account of the whole range of relevant findings from research on a particular topic, and not just the results of one or two studies. Systematic reviews can be used to establish whether scientific findings are consistent and generalisable across populations, settings, and treatment variations, or whether findings vary significantly by particular subgroups.
Aim: In this presentation, I will talk about the general principles of systematic reviews and meta-analyses and briefly talk about the work of the Cochrane collaboration in general and the Cochrane IBD review group in particular. I will discuss the important role that Cochrane systematic reviews play in helping to promote understanding of the current evidence on existing interventions for maintaining remission in Crohn’s disease (CD) and discuss interventions on which there are Cochrane reviews. Where no Cochrane review was available on an intervention, relevant RCT’s will be briefly mentioned.
Methods: The Cochrane Library and Medline (Pubmed) were searched for level 1 evidence on specific interventions. Search terms included “Crohn’s disease or synonyms”, “remission or synonyms” and the names of specific interventions.
Results: Azathioprine, infliximab and adalimumab are effective at maintaining remission in Crohn’s disease. Natalizumab is also effective but there are concerns about its potential association with progressive multifocal leukoencephalopathy. Long term enteral nutritional supplementation, enteric-coated omega-3 fatty acids and intramuscular methotrexate may also be effective but the evidence on these is based on relatively small studies. The available evidence does not support the use of oral 5-ASA agents, corticosteroids, anti-mycobacterial agents, probiotics or ciclosporin as maintenance therapy in Crohn’s disease.
Conclusions: A better understanding of the evidence base of existing interventions for maintaining remission in CD could result in the use of treatments which are more likely to lead to improved patient outcomes.

New Therapies in Crohn’s Disease
Ronald Bremner, Specialist Registrar in Paediatric Gastroenterology, Birmingham
Crohn’s disease is characterised by an ongoing inflammatory response in the absence of an obvious trigger. Laboratory, genetic and clinical studies have added to the understanding of the mechanisms of this immune dysregulation. Interactions between the innate and adaptive immune system at the mucosal level appear central to pathogenesis, directing the polarisation of lymphocytes towards the Th1/Th17 phenotypes. The multilayer defence within the gut and systemic immune system provides many potential targets for therapy.
Since infliximab, several other specific anti-TNF therapies have been developed. These include adalimumab and certolizumab-pegol. Adalimumab is a fully human monoclonal anti-TNF antibody, with efficacy similar to Infliximab in anti-TNF-naïve subjects for induction and maintenance of remission. Efficacy is less, but still significantly better than placebo in those unresponsive or intolerant of inlfiximab. Certolizumab-pegol can be given monthly and appears more effective in those patients with raised inflammatory markers. Reports of hepatosplenic lymphoma after exposure to infliximab have highlighted long-term safety issues with biological therapies.
There are preliminary data suggesting efficacy of agents directed against other pro-inflammatory mediators, including interleukins 6 and 12, interferon-? and MAP kinases. Anti-inflammatory IL-11 and inhibitors of leucocyte adhesion have shown only moderate clinical benefit. Other strategies under investigation include methods to stimulate the innate immune defence systems at the mucosal level using probiotics, prebiotics or non-pathogenic helminths.
Trials examining the “top-down” approach to treatment compared to traditional “step-up” management strategies are reviewed.

Azathioprine. Friend or Foe?
S Ross, S Rajwal, I Sugarman, S Davison, S Picton, P McCLean. St. James’s University Hospital, Beckett Street, Leeds, LS9 7TF.
Azathioprine is an effective treatment for steroid dependent Inflammatory Bowel Disease (IBD) .Recently concerns emerged in regard to long term risk of neoplasia in patients with IBD treated with azathioprine or its metabolite, 6-mercaptopurine.
To date, studies have been inconclusive in confirming any association between azathioprine and haematopoietic malignancies. This risk is deemed insignificant and does not preclude the use of azathioprine and/or 6-MP in the treatment of IBD, especially in young patients where cancer risk is at a minimum.
We report an unusual case of EBV associated lymphoproliferative disease in a fifteen year old boy who was initially diagnosed with Crohn’s disease at the age of ten. His disease activity was initially mild but proved to be difficult to control three years into his diagnosis when he persistently required systemic steroid to induce and maintain remission. This prompted treatment with azathioprine, with a maximum dose of 3mg/kg/day.
Eighteen months later, he presented with bilateral painless cervical lymphadenopathy. Initial blood investigations showed pancytopaenia but normal biochemistry.EBV IgM, IgG and PCR were positive with titres in excess of 100,000 copies/ml. Lymph node biopsy was consistent with EBV associated B-cell lymphoproliferation and immunohistochemistry was CD20+ Bone marrow examination only showed reactive changes. Chest radiograph and abdominal sonography at presentation were also normal. Azathioprine was therefore stopped . He deteriorated two weeks later with profuse bloody diarrhoea, hepatosplenomegaly,jaundice and hypoalbuminaemia.Clotting was deranged with prothrombin time of 46 seconds which corrected with intravenous vitamin K. Antiviral therapy with intravenous ganciclovir was commenced with no response. He continued to deteriorate clinically and biochemically with increasing hepatosplenomegaly, ascites and steady decline in liver and renal functions. Computed tomography of neck , thorax and abdomen showed evidence of large necrotic bilateral cervical lymphadenopathies, bilateral nodular consolidation of lungs, worsening abdominal lymphadenopathy with multiple focal abnormalities of poor echogenicity in the spleen. As a result, antimonoclonal antibody treatment with rituximab and COP chemotherapy (cyclophosphamide, vincristine and prednisolone) were initiated.
His initial response to treatment was poor inspite of three cycles of rituximab and chemotherapy. He deteriorated further with persistent diffuse per-rectal bleeding and eventually had a sub-total colectomy for bowel perforation. Remarkably, he was clinically much improved post bowel resection and EBV titres showed a downward trend for the first time. Histology confirmed atypical lymphoid infiltrate consistent with lymphoproliferative disease as the cause of gastrointestinal haemorrhage and perforation. Unfortunately, shortly after completing four cycles of chemotherapy and rituximab, he succumbed to necrotising enterocolitis and sepsis.
Even though previous studies of the risk of lymphoma in IBD patients treated with immunosuppressants have provided conflicting results, there is a common and real concern among patients and physicians who are considering its use. General consensus is that this risk is probably insignificant and more so in the paediatric population.This case demonstrates that even though it is rare, azathioprine associated lymphoproliferative disease is a real entity and will always pose a concern for patients and paediatricians alike.

Crohn’s Disease Presenting As Gastric Outlet Obstruction
Loganathan S, Casson D Alderhey Children’s Hospital, Liverpool.
We describe a 14 year old girl with Crohn’s disease in whom the diagnosis, anatomical localization and management presented significant dilemmas.
Case report: At 5 year of age she was diagnosed with a cutaneous anaplastic large cell non-Hodgkins’s lymphoma which responded well to treatment. She remained well for 7 years and then presented with persistent nonbilious vomiting and weight loss of 5 kgs over the previous 6 months. There was no history of oral manifestations, diarrhoea or blood in stools. She has attained menarche and there was no family history of bowel disorders.
She had Barium follow through which demonstrated a dilated stomach and an abnormal and featureless duodenum. Inflammatory markers were normal. We were concerned that the obstruction represented a recurrence of her original malignancy however a CT scan of abdomen did not show characteristic appearances of small bowel lymphoma. At endoscopy passage through the pylorus could only be
achieved by use of the neonatal scope. A 3-4 cm narrowing of the first part of the duodenum was identified with normal mucosa beyond. There were no other endoscopic abnormalities. Histology demonstrated granulomatous inflammation of stomach, duodenum and colon in keeping with Crohn’s disease.
She responded well to enteral feeds but on each occasion, including one course of steroids, the vomiting recurred within a week of finishing. In view of the previous lymphoma there was dilemma about commencing azathioprine. On discussion with the oncologists it was felt that this represented an acceptable risk and it was commenced. Further contrast studies showed featureless duodenum but no evidence of stricture. We faced a dilemma over progression to surgery in view of concerns over the possible involvement of the ampullary region and discrepancy between radiological and endoscopic disease localization. With this uncertainty we proceeded to surgical intervention at which disease distribution was as had been described endoscopically involving D1 only. The on-table surgical dilemma was between stricturoplasty, balloon dilataton and a Roux-EN-Y gastric bypass. The latter was performed and she has remained well for past 1 year.
Summary: We present a complex case of Crohn’s disease which presented several dilemmas: there was initial difficulty at distinguishing Crohn’s from relapse of lymphoma, subsequent treatment was ineffective at inducing remission, the decision to start azathioprine in view of previous malignancy was fraught, the anatomy of the stricture was difficult to establish and the optimal surgical procedure was uncertain.

Diagnostic and management dilemma in a case of Inflammatory bowel disease
VM Sivaramakrishnan, S Protheroe Department of Paediatric Gastroenterology, Birmingham Children’s Hospital, Birmingham, United Kingdom
Background: Classical clinical features of inflammatory bowel disease can be mimicked by infective diseases including tuberculosis. Annual incidence of tuberculosis in children (Asian ethnic group) is 21/100,000, whereas incidence of Crohn’s disease is perhaps 4/100,000.
Case Summary: A 14 year old British Asian girl presented with pyrexia of unknown origin, bilateral hip and left elbow pain to the Rheumatology team. She did not respond to the anti inflammatory medication. She had a positive Mantoux test and noted to have a family contact of tuberculosis. She has had BCG vaccine at birth. Despite a negative synovial biopsy, she was given a 6-month course of antituberculous therapy (ATT) for synovitis with minimal improvement in clinical symptoms.
A gastroenterologist opinion was sought in Oct-06 for intermittent abdominal pain with fever, diarrhoea and arthralgia all of which were present since first seen. She was also noticed to have blood in the stools for 2 months prior to the referral. On examination she had no generalized lymphadenopathy or hepatosplenomegaly. Small bowel contrast studies showed ulceration of distal ileum with irregular mucosa, indistinct ileocaecal valve with caecal involvement. Colonoscopy revealed patchy ulceration in caecum and terminal ileum. Ileocaecal biopsies showed severe, chronic active inflammation in keeping with Crohn’s disease. The biopsy material was negative for acid & alcohol fast bacilli staining and TB cultures were negative. Early morning urine sample for TB was also negative. Abdominal sonography excluded lymphadenopathy. Elispot test done in Oct 2006 was negative. Management with liquid diet and Mesalazine yielded improvement both clinically and histologically.
Her symptoms recurred within two months and she declined further liquid diet therapy. She was found to be steroid dependant and she has been referred to the surgeons for an opinion regarding ileocaecal resection. She may not be a good candidate for further immune-suppression and certainly would not qualify for infliximab as she has had evidence of exposure to TB infection in the past.
Conclusion: Our case serves to highlight the difficulties that can be encountered in differentiating Crohn’s disease from tuberculosis. A positive Mantoux could be misleading towards a diagnosis of tuberculosis and false positivity is well recognised when there has been prior tuberculosis contact. Accurate diagnosis is essential prior to any proposed pharmacological and/or immune therapy.

Pre-pouch ileitis after colectomy in pediatric ulcerative colitis
Carrie Slatter, Safwat Girgis+, Hien Huynh, Wael El-Matary Division of Pediatric Gastroenterology, Hepatology and Nutrition, Stollery Children’s Hospital and +Department of Pathology, University Hospital, University of Alberta, Edmonton, Canada
Background: Colectomy and ileal pouch anal anastomosis (IPAA) is a potentially curative option for patients with ulcerative colitis. A rare, post-operative complication is terminal ileitis, which arises when the ileum is colitis.
reanastomosted into a non-physiologic environment. Terminal ileitis is well described in adults, but has been poorly documented in pediatric patients.
Aim: To describe our experience of children with ulcerative colitis who developed terminal ileitis following colectomy and IPAA.
Methods and Results: A search of our pediatric inflammatory bowel disease database of patients we are currently following revealed two boys (initially presenting at ages 4 and 9) diagnosed with ulcerative colitis on the basis of clinical presentation, investigations including endoscopy and colonoscopy and biopsies. As they were resistant to medical therapy, including steroids, 5-ASA preparations (oral and rectal), azathioprine, tacrolimus and various antibiotics, they each underwent colectomy with IPAA. Pathological examination of the surgical specimens confirmed the diagnosis of ulcerative colitis.
One year later, both children had recurrence of symptoms, including watery, bloody diarrhea and weight loss. Several endoscopies and biopsies showed acute on chronic mucosal inflammation, ulceration, friability and granularity in the pouch and up to 50cm into the terminal ileum. Biopsies revealed mixed inflammatory infiltrate rich in eosinophils, plasma cells and neutrophils. No granulomas were seen. Stomach and duodenal biopsies were normal. Both children were diagnosed with pouchitis and terminal ileitis. At present, their symptoms are well controlled using 5-ASA preparations in one child and azathioprine in the other.
Conclusion: Development of terminal ileitis after colectomy and IPAA can occur in children with ulcerative colitis. Although every effort should be made to exclude Crohn’s disease as a cause of the terminal ileitis, this unique and poorly defined condition should not be considered to be against the diagnosis of ulcerative colitis. More research is needed to develop a better understanding of the aetiopathogenesis of this uncommon condition.

Update on immunesuppressive agents including the monoclonal antibodies and newer immunosuppressive agents.
Dr Sue Beath Paediatric Heptologist Birmingham Children’s Hospital
Immune suppressants agents have developed from general anti-inflammatory agents such as aspirin and steroids to highly specific molecules targeted on a specific cell type or enzyme system within the immune system. The increasing expansion in indications for organ and tissue transplantation is driving pharmacological innovation rapidly as knowledge about fundamental controls of the immune system begin to emerge.
There are several parallel strategies for controlling the immune system in the context of organ transplantation:
• Drugs with a wide range of effects mediated via actions on the nucleus ie protein translation and transcription, eg) steroids which are effective but have many unwanted effects in addition to attenuation of inflammatory mediators. And inhibitors of purine or pyrimidine synthesis, so called anti-metabolites, e.g. azathioprine, mycophenolate and leflunomide, but which are often toxic to bone marrow.
• Drugs acting on specific pathways and sites within the cytosol – extra nuclear actions e.g.. tacrolimus and sirolimus. But such pathways feed into other cellular control systems, thus a cascade of side effects often seen in a dose dependant way e.g. Tacrolimus up-regulates endothelium receptors which is one mechanism whereby arteriolar blood flow including renal arterioles is restricted leading to hypertension and renal impairment.
• Drugs with a specific receptor-ligand interaction – such simple interactions are often to be found on the cell surface and are particularly suitable for monoclonal antibody blockage – has led to an exponential proliferation in designer antibodies active against a variety of ligands from inflammatory mediators such as TNF to receptors for IL-2 activation.
• Nutritionals – the role of omega 6 fatty acids in the production of inflammatory mediators such as prostaglandins & arachondonic acid opens the possibility of a tolerogenic diet rather than simply a hypoantigenic diet. The effect of chronic undernutrition and reduced glutathione stores has been the scientific basis of N-acetylcystein studies in liver transplant recipients.
Intracellular signaling pathways Trans-membrane proteins/receptors are the means whereby drugs, viruses, hormones proteins, fatty acids stimulate different intracellular pathways. These pathways can be affected directly by binding with pharmacological agents; e.g calcineurin inhibition by tacrolimus; inhibition by sirolimus of the phyllogenetically ancient Toll like recepter pathway, steroids bind to the nuclear transcription molecule NFkappa B. The end result of these actions is to reduce the transcription of interleukin-2.
NF-kappaB is a pleiotropic transcription factor implicated in the regulation of diverse biological phenomena, including apoptosis, cell survival, cell growth, cell division, innate immunity, cellular differentiation, and the cellular responses to stress, hypoxia, stretch and ischemia. Cyclosporine and tacrolimus prevent NF-kappa B activation by inhibiting the action of calcineurin, a phosphatase that indirectly induces I kappa B degradation.
Another pathway which may be important in future therapeutic targeting is the Rho-ROCK-VEGF. There are animal models suggesting that sirolimus reduces the effects of ischaemia in transplated organs by acting on this pathway. The Rho effectors such as the Rho-associated coiled-coil forming kinase (ROCK) may be a common cellular mechanism for interstitial fibrosis.
Arachidonic acid, which is derived from essential long chain fatty acids, has been shown to activate the mitogen activated protein kinase (MAPK) signaling pathways. MAPKs mediate the effect of reactive oxygen species which in turn stimulate pathways leading to programmed cell death. However, NF-kappB exerts a negative control on reactive oxygen species and MAPK. Thus the interaction between MAPK siagnalling and NF-kappaB may be key to developing new therapies for the treatment of widespread human illnesses, such as cancer and chronic inflammatory conditions including rejection.
Cytokines Cytokines are important mediators of immune cells and have been the focus of attempts to produce a more selective form of immune suppression with minimal adverse effects. This has led to numerous monoclonal antibodies active against various cytokines.
Macrophages produce are large number of cytokines of which IL-1 (causes the release of prostaglandins, thromboxane and platelet activating factors from inflammatory cells) and Phospholipase A2 (contributes to synthesis of arachondonic acid and derived mediators including prostaglandins and leukotrienes) and TNF? (induces synthesis of acute phase proteins by the liver and attacks gastrointestinal epithelium) are important examples. All 3 of these macrophage cytokines are inhibited by cortico-steroids.

Thymocytes also produce cytokines and are often categorized into 2 main types according to cytokine profile: Th-1 which is associated delayed type hypersensitivity including rejection and Th-2 which is associated with a more immediate response including allergy and anaphylaxis. The Th-1 cytokines are IL-2 and IFN????IL?? is produced by T lymphocytes and is pivotal in the immune response leading to clonal expansion of activated T cells. Cyclosporin and tacrolimus block gene transcription of IL-2 via calcineurin pathway inhibition and NF-kappaB . Sirolimus blocks transcription of IL-2 via the inhibition of the Toll pathway. The Th-2 cytokines are IL-2, IL-5, IL-6 and IL-10. IL-10 is produced by Th-2 T lymphocytes and B lymphocytes and it acts on on macrophages to down regulate expression of MHC. A viral analogue for IL-10 exists in some viruses eg EBV – may allow evasion of host immune response by down regulating the MHC molecules on the cell surface. This is in contrast to the effects of IFNg which up regulates MHC expression by epithelial cells. Thus the two type of thymocyte antagonise each others actions to provide a balance within the immune system.

Monoclonal antibodies The latest range of monoclonal antibodies are humanized and well tolerated, although it is still possible to induce a cytokine release syndrome and repeated use can induce allo-antibodies which reduce the efficacy of the monoclonal antibody. The mechanism of action is one of inhibition either by masking/blocking the cytokine/ cell surface receptor, or by cell destruction via a lytic effect. Monoclonals are often referred to by the cytokine being targeted, or by the cellular immunophenotyping which is a classification based on the cell differentiation receptor. The range of cell receptors, their receptors are shown in the table below.

Table showing Cellular differentiation (CD) receptors and their role in disease and immuno-suppression via monoclonals

CD receptor CD 3 CD 4 CD 8




T cell receptor (all T cells)

ATG and Orthoclone/OKT3

Pre-transplant depletion therapy, rescue in severe
rejection episodes

Subset of T cells (cytotoxic/helper)

receptor for HIV as well

Subset of T cells (suppressor)

IL-2 receptor found on cytotoxic T lymphocytes

blocked by basiliximab, also daclizumab both prevent IL-2 stimulating a proliferating immune

used in induction regimens to reduce intensity of rejection, allow lower doses of steroids and calcineurin inhibitors

CD 20

carried almost exclusively by nearly all
B cells

rituximab attaches to receptor and induces lysis, results in none, or very few, B cells and a deficit in

used to treat tumours in B cells especially posttransplant lymphoproliferative disease.

numerous tissue types


infliximab, adalimumab are blocking monoclonal antibodies which bind to active molecule, Etanercept has similar effect but is a fusion protein with p75 receptor

used to treat inflammatory conditions especially
necrotic fistulising disorders e.g.Crohn’s disease

CD 52

Found on most B cells

Alemtuzamb (Aka Campath-H1) induces lysis on mainly B cells and
some T cells also neutrophils

Pre-transplant depletion therapy, also conditioning
before BMT

Summary In organ transplantation, no single immunosuppressive agent is sufficient to achieve induction of tolerance, but the combination of calcineurin inhibitors with antibodies restricting stimulation of IL-2 via its CD25 receptor and low dose steroid have combined to produce a lower frequency of rejection in liver, kidney and small bowel allografts. In the long term, new modalities targeting adhesion of immune cells, and, manipulation of the diet to limit the availability of reactive oxygen species and pro-inflammatory cytokines like arachodonic acid, and, molecules influencing the intracellular signaling pathways especially those connected with fibrosis such as the Rh—ROCK-VEGF pathway, may be available to clinicians to achieve the goal of induction of tolerance and effective treatment of chronic rejection, without unacceptable side effects.

Introduction to Nutritional Assessment Dr Steve Wootton, Senior Lecturer in Human Nutrition Southampton Awaiting Abstract

Nutrition Assessment in Inflammatory Bowel Disease
Nicky Heather - Paediatric Gastroenterology Dietitian, Southampton General Hospital
Twenty–five percent of cases of inflammatory bowel disease (IBD) present in childhood with Crohn’s disease being the most common type. A significant feature at presentation is poor nutritional status which may worsen during the clinical course. As a result poor linear growth can lead to permanent growth retardation and failure to reach predicted adult height. Factors contributing include inadequate intake, malabsorption, altered energy demands and stool losses particularly evident in colitis. Nutrition is therefore central to the medical management of the disease in aiming to induce and maintain remission.
Managing nutritional status and prescribing enteral nutrition (EN) requires assessment of energy requirements. At present there is very little data published on making accurate predictions of an individual’s energy needs during the course of the disease.
In a study of 40 children newly diagnosed with Crohn’s disease energy intakes exceeded the Estimated Average Requirements (EAR) values for age in 82% of the patients with a median of 117.5% of EAR values (Gavin et al, 2005). The group with ileocolonic disease had the highest intakes compared to isolated small bowel or colonic disease (not statistically significant). In the absence of energy balance studies this study concluded that energy intakes in the range of 100-149% of EAR for age may be required.
In inactive Crohn’s disease a study (Hart et al, 2005) compared measured versus predicted energy expenditure in 23 patients. Resting energy expenditure (REE) was measured with indirect calorimetry and compared with predicted basal metabolic rate (BMR) using the Schofield equation. Total energy intake was compared with EAR values. Results showed that REE was higher than predicted BMR values ranging from 79%-136%. Total energy requirements (TEE) ranged from 72%-163% of EAR values. Conclusions made were that the Schofield equation and EAR values are unreliable in predicting energy requirements in inactive Crohn’s disease and may result in underestimating their true energy needs.
More reliable methods of assessing nutritional requirements are needed on the changing requirements throughout the disease process which also accounts for growth and changes in body composition.

Nutritional assessment in cystic fibrosis
Teresa Curbishley Paediatric Gastroenterology Dietitian, Southampton General Hospital
For many patients with cystic fibrosis (CF) and pancreatic insufficiency, good nutritional status can be achieved by taking a high calorie diet with an adequate use of pancreatic enzyme replacement therapy (PERT). However, suboptimal growth in some children with CF can remain a problem. As malnutrition in CF is linked to poorer pulmonary function, reduced survival and quality of life, prevention of malnutrition is essential.
Poor weight gain and growth observed in some children with CF suggests a chronic negative balance between energy intake and energy expenditure. To plan effective malnutrition prevention and treatment interventions, an understanding of energy balance is needed. Energy balance depends on the following contributing factors; energy intake, energy expenditure, energy loss in stool due to maldigestion and malabsorption, and energy storage for tissue accretion.
Energy intakes of CF patients may be affected by several factors, including recurrent vomiting from coughing, gastroesophageal reflux, chronic respiratory infections and psychosocial stresses. In CF children, it has been reported that despite energy intakes being significantly higher than that of healthy children, energy intakes are often not able to meet the clinical demands of the disease, particularly during puberty, and hence this age group may require greater nutritional targeting (White et al, 2007).
Clinical practice has shown that energy requirements of patients with CF can vary widely, however it has been estimated that energy requirements can be as high as 120-150% of the Estimated Average Requirement (EAR) for age. This increase in requirement is thought to be attributed to a higher basal metabolic rate as a result of catabolic lung inflammation and increased work of breathing (Levison & Cherniak, 1968). However in the stable CF patient, there are conflicting thoughts as to whether total energy expenditure (TEE) is higher than that of healthy individuals.
TEE of individuals with CF can also be increased by uncontrolled maldigestion and malabsorption despite optimal use of PERT. In 1991, Murphy et al reported that raised stool energy losses may contribute towards an energy deficit sufficient to limit growth in CF. Increased maldigested and malabsorbed dietary nutrients, endogenous secretions and cellular debris, and colonic bacterial micro flora lead to increased stool energy losses. A simple measure of stool lipid losses may not be the most accurate way of assessing the adequacy of PERT, as total energy losses will not be detected. A more novel way of measuring total stool energy loss would be to do a three day stool collection, estimating energy loss from stool weight.
In clinical practice, by accurately assessing the different factors that contribute to energy balance in individuals, this will lead to a more effective way of preventing and treating malnutrition in CF.

Nutrition In Children With Neurodisability
Peter B. Sullivan,Reader in Paediatric Gastroenterology,University of Oxford
Children with severe cerebral palsy (CP) have oral-motor impairment; this impairs nutritional intake and leads to malnutrition (short stature, low fat stores and reduced muscle mass) and ill health. The body composition of the child with severe CP differs from that of the average child; a decrease in body cell mass accompanies an expansion of the extra-cellular fluid volume. Their relative immobility reduces fat free mass (largely muscle but also skeletal mass) as well as energy expenditure. The reduced energy expenditure of children with CP is reflected in a lower dietary energy requirement - around 80% of current recommendations for neurologically normal children. These differences in body composition and energy expenditure, therefore, mean that standard reference data for ideal nutritional input and optimal growth do not apply to children with CP. Once malnutrition is identified the next problem is to decide how much to feed the child. The central consideration here is the amount of energy that the child requires to grow optimally. There is a wide variation in total energy expenditure (largely attributable to variations in physical activity levels) in immobile CP children. This individual variation, together with the lack of any suitable reference standards, compounds the difficulties in writing an accurate dietetic prescription. Insertion of a gastrostomy feeding tube is an increasingly common intervention in neurologically impaired children who: have an unsafe swallow; are unable to maintain a satisfactory nutritional state by oral feeding alone; have an inordinately long (> 3 hours per day) oral feeding time; is dependant on nasogastric tube feeding. Gastrostomy tube feeding has been shown to lead to improved weight gain (1;2), reduced feeding time (3) and improved quality of life for carers (3).
(1) Samson-Fang L, Butler C, O'Donnell M. Effects of gastrostomy feeding in children with cerebral palsy: an AACPDM evidence report. Dev Med Child Neurol 2003 Jun;45:415-26.
(2) Sullivan PB, Juszczak E, Bachlet AM, Lambert B, Vernon-Roberts A, Grant HW, et al. Gastrostomy tube feeding in children with cerebral palsy: a prospective, longitudinal study. Dev Med Child Neurol 2005 Feb;47(2):77-85.
(3) Sullivan PB, Juszczak E, Bachlet AM, Thomas AG, Lambert B, Vernon-Roberts A, et al. Impact of gastrostomy tube feeding on the quality of life of carers of children with cerebral palsy. Dev Med Child Neurol 2004 Dec;46(12):796-800.