To the ileum ……. and beyond Dr. Matt W. Johnson BSc MBBS MRCP (??MD!!) Consultant Gastroenterologist

1909 Royal Military Asylum

1733 – Hyde Park

1976 - Tooting

St. George’s Hospital

Achievements First Class BSc Degree MBBS (University of London) Medical Sciences with Physiology Physiology research project: Effects of alpha and beta sympathetic adrenoreceptors on mucus content and quantity. MBBS (University of London) Eating in every one of the 28 Indian restaurants from Tooting Broadway to Tooting Bec

HO + SHO Posts MEDICAL SHO POSTS St. Helier Hospital, Gastro and GIM Hemel Hempstead Hospital, Gastro, Haem and GIM Royal Free Hospital, Specialist Liver Unit and GIM St. Thomas’ Hospital, Cardiology Lewisham Hospital, Endocrine and GIM Lewisham Hospital, Care of the Elderly Guy’s Hospital, Accident and Emergency PRE REGISTRATION HOUSE OFFICER Mayday Hospital, General Surgery and ENT St. George’s Hospital, GIM and Care of the Elderly

St. Thomas’s Hospital

South East Thames SpR Rotation QUEEN ELIZABETH THE QUEEN MOTHER (MARGATE) HOSPITAL Dr. A. Piotrowicz, Dr. K. Hills DARENT VALLEY HOSPITAL Dr. W. Melia, Dr. R. Ede, Dr. P. Mairs KINGS COLLEGE HOSPITAL - LIVER UNIT General Hepatopancreatobiliary / Liver ITU / Transplant Medicine Dr. J. O’Grady, Dr. M. Heneghan, Dr. J. Devlin, Dr. P. Harrison, Dr. V. Aluvihare, Dr. K. Agarwal, Dr. E. Sizer, Dr. W. Bernal. Dr. G. Auzinger, Dr. J. Wendon. St. MARK’S and St. THOMAS’S HOSPITAL Research Fellowship, Specialist Surgical Gastroenterology Prof R.J. Nicholls, Prof P.J. Ciclitira and Prof A. Forbes St. THOMAS’ and GUYS’ NHS TRUST Sir R. Thompson, Prof P.J. Ciclitira, Dr. J. Meenan, Dr. J. Sanderson, Dr. T. Wong, Dr. M. Wilkinson, Dr. R.Ede BROMLEY NHS TRUST Dr. J. Hunt, Dr. A. Jenkins, Dr. M. Asante ROYAL SURREY COUNTY HOSPITAL Dr. M. Smith FRIMLEY PARK HOSPITAL - LAS Col. Fabricius, Col. Ineson

Specialty Areas of Interest Inflammatory Bowel Disease – including tertiary referral clinics at St. Mark’s and St. Thomas’s hospitals. Surgical Gastroenterology - National Referral Unit for ileoanal pouches, faecal incontinence, complex anorectal fistula disease at St. Mark’s Small bowel pathology + Coeliac disease tertiary referral clinics for complicated and non-responsive cases. Hepatology (General hepatopancreatobiliary medicine, Hepatitis clinics, Liver ITU, pre/post liver transplant medicine)

17 Publications 2009 Coeliac disease in the elderly. Nat Clin Pract Gastroenterol Hepatol. 2008 Dec; 5(12): 697-706 Bacterial community diversity in cultures derived from healthy and inflamed ileal pouches after restorative proctocolectomy. IBD. 2009 Nov The bacteriology of pouchitis: A molecular phylogenetic analysis. GUT. 2009. Dec The prevalence of osteoporosis and osteopenia in ileal pouch patients post-restorative proctocolectomy. IBD. 2009. Sept Prolonged toxic megacolon secondary to Salmonella. [Submitted to Diseases of the Colon and Rectum] 2008 Coeliac disease in the older patient: Are we ageist in our practice. [Awaiting publication in Gastroenterolgy CME Journal] The medical management of patients with an ileal pouch anal anastomosis after restorative proctocolectomy. EJoGH. Faecal M2-pyruvate kinase; a novel, non-invasive marker of ileal pouch inflammation. EJoGH 2007 Faecal calprotectin: A non-invasive diagnostic tool and marker of severity in pouchitis. Eur J Gastroentero Hepatol. 2008 March; 20(3): 174-179 2006 Hyperbaric oxygen as a treatment for malabsorption in a radiation damaged short bowel. June 2006; 18(6):685-688 Risk of dysplasia and adenocarcinoma following restorative procto-colectomy for ulcerative colitis. Colorectal Disease. CDI-00256-2005.R1. 03/05/06 2005 Use of fecal lactoferrin to diagnose irritable pouch syndrome: A word of caution. Gastroenterology. 2004. 127(5):1647-8 Presentation, diagnosis and management of inflammatory bowel disease in older people. CME Geriatric Medicine, 2005; 7(3): 149-153 The pathogenesis of coeliac disease. Molecular Aspects of Medicine, Dec 2005: 26 (6); 421-458 2004 11th International Symposium on Coeliac Disease: A report. Gastroenterology Today. Summer 2004; 14 (2): 46-7 Clinical toxicity of HMW glutenin subunits of wheat to patients with celiac disease. Proceedings of the 19th Meeting of the Working Group on the prolamin analysis and toxicity, 2004; III Symposium: 147-9 2002 Malaria: The dilemmas of malarial diagnostics. J R Army Med Corps 2002; 148: 122-126

Research Fellowship St. Marks’ and St. Thomas’ Hospital The Bacterial Pathogenesis of Pouchitis and Development of Novel Probiotic Therapies Prof PJ. Ciclitira, Prof RJ. Nicholls and Prof A. Forbes MD – Awaiting Examination

Aims IBD Centre of Excellence SBCE HRM EUS

Luminology

To the ileum …and beyond

Oesophagus

High Resolution Manometry Spatiotemoral plots derived from >36 closely spaced pressure sensors Reveals complex functional anatomy Increased our understanding of dysmotility Looks beautiful

Normal

Achalasia

Mid-oesophageal submucosal Ca

Herniation of Lap Wrap

Stomach

Management of Dyspepsia BSG Guidelines 1996 Updated 2002 By Matt Johnson St. Thomas’s and East Surrey

Dyspepsia Introduction Prevalence = 23 – 41% in UK 4% of GP consultations 10% of these are referred to hospital 2% of entire adult population receive either an OGD or a barium meal each year

Rationing of Endoscopy Morbidity = 1:1,000 (Haemorrhage) Death = 1:10,000 (Perforation) OGD is recommended in all patients >55y D with new onset uncomplicated dyspepsia for > 1/12 duration < 55y with “alarm symptoms” C

Alarm Symptoms These include dyspeptic patients with: Unintentional weight loss GI Bleeding Previous gastric surgery Epigastric mass Previous gastric ulcer Unexplained Fe deficiency Dysphagia or Odynophagia Persistent continous vomiting Suspicious barium meal

Investigation of dyspepsia in patients <55 years NICE guidelines www.nice.org CG17 Test and treat Helicobacter Empirical PPI therapy Reduce role of endoscopy in the <55 yrs Manage uninvestigated reflux as dyspepsia Alarm symptoms via TWW February Surrey and Sussex Healthcare 2008 NHS Trust

Investigation of dyspepsia in patients <55 years 724 endoscopies performed 54% normal 13% major abnormalities 33% minor abnormalities 42% recommended PPI therapy 8.1% helicobacter eradication resulting 1 oesophageal cancer discovered (aged 52) *

Investigation of dyspepsia in patients <55 years Conclusions: Three weeks out of year spend endoscoping this group Findings in line with other studies Very low prevalence of cancer in this group Minimal evidence of change in management

Iron Deficiency Anaemia

Causes of Fe deficiency Anaemia Occult GI Blood Loss Aspirin/NSAID use 10–15% Colonic carcinoma 5–10% Gastric carcinoma 5% Gastric ulceration 5% Angiodysplasia 5% Oesophagitis 2–4% Oesophageal Ca 1–2% GAVE (ectasia) 1–2% Small bowel tumours 1–2% Ampullary Ca. <1% Ancylomasta duodenale <1% Malabsorption Coeliac disease 4–6% Gastrectomy <5% H. pylori colonisation <5% Gut resection <1% Bacterial overgrowth <1% Non-GI blood loss Menstruation 20–30% Blood donation 5% Haematuria 1% Epistaxis <1%

Iron Deficiency Anaemia Haemoglobin <12 or <13 nmg/L MCV <76 Ferritin <15nmg/L Coeliac serology TFT Sickle cell and Thalassaemia screen Non-vegetarian No menorrhoea

Small Bowel

COELIAC DISEASE Matt Johnson + David Dewar Professor Paul Ciclitira St Thomas’s Hospital, London

Prevalence of coeliac disease Sweden 1:67 antibody positive Ireland 1:100 England 1:150 Europe 1:300 N America 1:300 Australia 1:300

DERMATITIS HERPETIFORMIS

Associations Dermatitis herpetiformis IgA deficiency 2-3% SBBO 8% of NRCD Hyposplenism ?80% Microcytic colitis 5% Autoimmune conditions 25% Thyroid disease Type 1 diabetes Addison’s Sjogrens syndrome

AD and age at diagnosis: Group Prevalence AD A1 – age<2yrs 5.1% A2 – age 2-10yrs 17% A3 – age>10yrs 23.6% Prevalence of autoimmune disease is related to duration of gluten exposure Ventura A (1999) Gastroenterology 117:297-303

Osteoporosis 47% women < 50% men on GFD have osteopenia / osteoporosisa Improvement 1 year post treatmentb aMcFarlane (1995) Gut 36:710-14 bValdimarsson (1996) Gut 38:322-7

Mortality Almost all mortality in CD is due to malignancy >50% due to EATCL Other tumours = mouth, oesophagus, sb,lb Mortality 1.9-3.4x control population Holmes et al : 2x control pop1 Mortality normal after 5 yrs on GFD2 1Holmes GK et al (1976) Gut 17(8): 612-9 2Holmes GK et al (1989) Gut 30(3): 333-8

Ulcerative jejunitis Rare (6th decade) pre-malignant state Related to Enteropathy-associated T cell lymphoma (EATL) T Cell receptor PCR monoclonality UCL – Prof. Isaacson Atypical gTcell receptor abnormalities Steroids, nutritional support, close observation

Treatment of coeliac disease Gluten-free diet Avoidance of wheat, rye and barley Oats (probably OK) Dietician Codex Alimentarius Coeliac societies handbook BUT NOT CORNFLAKES

Using Serology to Monitor Patients IgA gliadin and TTG normalise on a strict GFD after 3-6/12 Must have pre-treatment levels IgG gliadin can be used but takes longer to normalise IgA endomyseal is costly and more difficult to quantify

Dewar D, Johnson MW, Ciclitira PJ, GUT 2005

Small Bowel UGI tract 0.8m LGI tract 1m Sb 5.6m 95% absorption capacity

Capsule Endoscope A small disposable capsule about the size of a jelly bean. Has own light source and video camera. Suitable for adults and older children. Transmits data to recorder worn at waist. Patient swallows capsule with glass of water after a simple overnight fast. Carries on with normal activities and returns data recorder after 8 hours. At the American College of Gastroenterology (ACG) 2004 meeting, Drs Jamie Barkin and Gregory Schwartz (USA) reported that patients with SBT had an average of 4.6 procedures before definitive diagnosis with capsule endoscopy.

BSG Indications for SBCE Guidelines April 2008 1) Obscure gastrointestinal bleeding 2) Suspected sb Crohn’s disease 3) Assessment of Coeliac disease 4) Screening for Polyps / FAP Suspected small bowel malignancy Evaluation of side-effects of NSAIDs

Dartford SBCE Service A review of the first 37 small bowel capsule enteroscopies performed at Darent Valley Hospital. Stomach Gastritis (5) Erosions (6) Angiectasia (4) Polyps (1) Small bowel NSAID induced enteropathy (9) Angiodysplasia (2) Coeliac disease (7) - UCH pre-malignant ulcerative jejunitis Gastrointestinal stromal tumours (GISTs) (2) - 2x St. Mark’ for D-balloon enteroscopy Crohn’s disease (5) Juvenile polyposis (1) - GOS Bacterial overgrowth secondary to small bowel diverticulae (1) Parasitic infestation (1) Multiple cystic lymphangiectasia (1)

Coeliac Disease Celiac disease is an immune-mediated disorder that primarily affects the GI tract. It is characterized by chronic inflammation of the small intestine mucosa that may result in atrophy of intestinal villi, malabsorption, and a variety of clinical manifestations, which may begin in either childhood or adult life. Patients with celiac disease may also have diabetes, anemia, osteoporosis, neurological problems, malignancies, and show behavioral changes. Family members may also be positive for celiac disease Sero + (EMA or tTG) patients unwilling or unable to undergo upper GI endoscopy Sero + (EMA or tTG) patients with negative histology to rule out patchy disease For alarm symptoms in known CD patients on a strict GFD (risk of malignancy) Obstruction Weight loss Bleeding Pain Fever

Using SBCE in Crohn’s 10-30% sb only 66% ileocaecal disease 20% colonic Wireless capsule endoscopy and Crohn’s disease. P Swain Gut: March 2005 vol 54 no 3 Costamagna Gastroenterology 2002;123:999-1005

Suspected Crohn’s

Obscure Intestinal Bleeding 5% of all UGI haemorrhages Benefits Safe, well tolerated, able to view entire small bowel, clarity of image + Share images; patient preference; Reduced diagnostic cost and utilization If bleeding source identified = Less need for transfusions Reduced treatment cost and utilization The first main use of SBCE was in the investigation of patients with obscure intestinal bleeding. So called because patient’s had chronic anaemia or obvious bleeding but the gastroscopy and colonoscopy were normal. CE is a valuable tool in the diagnostic tool kit Key advantages of CE include: ability to review and share images; patient preference; safety profile; ability to conduct in variety of settings; clarity of image comparable to other endoscopy; ability to image entire small bowel Bleeding stops/anemia resolves Less need for transfusions Reduced diagnostic cost and utilization Reduced treatment cost and utilization Patient satisfaction and quality of life (QoL) Improved outcome of earlier diagnosed tumors in the small bowel

Small bowel malignancies Prior to SBCE sb tumours = 1 - 2% of all GI malignancies Now it is thought to compromise 5% PillCam™ Trial = incidence of small bowel tumors among 1,235 patients – 6% - 9% (Corbin, Bailey, Keuchel) 60% of SBTs are malignant - adenocarcinomas, carcinomas, melanomas, lymphomas and sarcomas 40% of SBTs are benign GISTs, hemangiomas, hamartomas, and adenomas Prior to capsule endoscopy SB tumors comprise 1% - 2% of GI malignancies PillCam™ incidence of small bowel tumors among 1,235 patients – 6% - 9% (Corbin, Bailey, Keuchel) Malignant tumors of small bowel (poor prognosis) Metastases - 45% - 75% Unresectable - 20% - 50% Often diagnosed late in course or incidentally at laparotomy or biopsy If a lesion leads to symptoms, presentation depends on the pathology of the neoplasm and location At least 50% of benign lesions remain asymptomatic, while approximately 80% of malignant lesions are associated with symptoms Not clear if symptoms or signs are specific for either benign or malignant tumors The most common indication for PillCam™ endoscopy in patients with SBTs was obscure GI bleeding/anemia (80%) PillCam™ endoscopy detected SBTs after patients had undergone an average of 4.6 negative procedures The majority of SBTs were malignant (60%), consisting of adenocarcinomas, carcinomas, melanomas, lymphomas, and sarcomas The benign SBTs (40%) were GISTs, hemangiomas, hamartomas, and adenomas

Small Bowel malignancies Often diagnosed late or incidentally at laparotomy Malignant tumors of small bowel (poor prognosis) Metastases - 45% - 75% Unresectable - 20% - 50% 80% of SBTs undergoing SBCE present with obscure GI bleeding/anemia Improved outcome of earlier diagnosed tumors in the small bowel On average patients with SBTs who present for SBCEs have already undergone detected SBTs after patients had undergone an average of 4.6 negative endoscopic procedures PillCam™ Trial (Corbin, Bailey, Keuchel) If a lesion leads to symptoms, presentation depends on the pathology of the neoplasm and location At least 50% of benign lesions remain asymptomatic, while approximately 80% of malignant lesions are associated with symptoms Not clear if symptoms or signs are specific for either benign or malignant tumors The most common indication for PillCam™ endoscopy in patients with SBTs was obscure GI bleeding/anemia (80%) PillCam™ endoscopy detected SBTs after patients had undergone an average of 4.6 negative procedures The majority of SBTs were malignant (60%), consisting of adenocarcinomas, carcinomas, melanomas, lymphomas, and sarcomas The benign SBTs (40%) were GISTs, hemangiomas, hamartomas, and adenomas

Final points Safe + Well tolerated Cost-effective in economic analysis. This is now standard practice throughout UK Watford, Stevenage, Wellen Garden City, Cambridge, ?Aylesbury Presently the paediatricians refer to GOS Adult medicine is under-referring St.Mark’s External referral = £800-1200 Cost of service = £13,000 Cost of capsule = £340

Colon

Operative Picture

Complications Obstruction Bleeding Inflammation “itis” Fistula Sepsis Perforation May co-exist with IBD Specimen showing blood in diverticulae

Criteria for Toxic Megacolon (Jalan et al) 1) Radiographic evidence Total or segmental non-obstructive colonic dilatation of > 6cm 2) 3 or more of: Fever > 38 C PR > 120 / min Neutrophils > 10.5 Hb <12.5 3) At least 1 of: Dehydration Hypotension Electrolyte imbalance Altered consciousness

Probiotics are sooo outdated Prebiotics = “functional foods” Inulin / Fructo-oligosaccharides / Lactulose Transgalacto-oilgosaccharides Chicory (boiled root = 90% inulin) Jerusalem artichoke Onion Leek Garlic Asparagus Banana (cereals eg. Oatmeal)