title: Prospective study of immunological factors in non-inflammatory bowel disease enterocutaneous fistulas.
abstract: BACKGROUND
  Enterocutaneous fistulas (ECF) are debilitating and usually result following complex abdominal surgery. While there is an association with inflammatory bowel disease (IBD), a large number of fistulas occur after surgery not related to IBD. The consequences of ECF include short bowel syndrome and the need for long term parenteral nutrition.ECF can heal spontaneously and in the case of IBD can be cured by medical therapy in some instances. Those that do not resolve spontaneously have to be cured by surgery which is complex and associated with a high morbidity. It is not considered traditional treatment to use the same medical therapy as in IBD to cure ECF caused by other conditions.A small case series has reported three patients with persistent ECF not related to IBD to have healed following use of Infliximab which is the treatment commonly used for ECF caused by IBD. Infliximab acts by inhibiting the activity of the inflammatory cytokine TNF- alpha. It is not known if this cytokine is present in ECF tissue in the absence of IBD.The aim of this study is to demonstrate the presence of inflammatory markers in tissue surrounding non-IBD ECF and in particular to quantify the presence of the cytokine TNF- alpha. We hypothesise that TNF - alpha levels are raised in non-IBD ECF.
  
  
  METHODS
  Tissue and serum from ECF of IBD and non-IBD patients will be prospectively collected at St. Mark's Hospital Intestinal Failure Unit. The control group will consist of patients undergoing colonoscopy for bowel cancer screening, with normal findings. Biopsies of the terminal ileum will be obtained from this group during colonoscopy. The fistula tract and serum cytokine profiles of interleukins (IL)-1a, IL-1b, IL-2, IL-4, IL-6, IL-8, IL-10, TNF- alpha, IFN-y, MCP-1, EGF and VEGF will be assessed.
  
  
  CONCLUSIONS
  This study aims to assess the presence or absence of TNF- alpha expression in the ECF tissue in non-IBD origin. If our hypothesis is correct we would then be able to study the use of the TNF- alpha inhibitor Infliximab as a therapeutic option in the treatment of non-IBD ECF. Secondary aims include assessing the spectrum of inflammatory cytokines and markers present in tissue and serum of non-IBD ECF when compared with IBD ECF and normal controls.
  
  
  BACKGROUND
  ISRCTN44000447.
authors: Colorectal and Intestinal Failure Surgery, St, Mark's Hospital and Academic Institute Watford Road, Harrow, Middlesex, HA1 3UJ, UK. g.rahbour10@imperial.ac.uk
authors: Goher
authors: G
authors: Rahbour
authors: Ailsa L
authors: AL
authors: Hart
authors: Hafid O
authors: HO
authors: Al-Hassi
authors: Mohammad R
authors: MR
authors: Ullah
authors: Simon M
authors: SM
authors: Gabe
authors: Stella C
authors: SC
authors: Knight
authors: Janindra
authors: J
authors: Warusavitarne
authors: Carolynne J
authors: CJ
authors: Vaizey
references: Int J Colorectal Dis. 2004 Nov;19(6):603-6
references: 15175888
references: J Am Coll Surg. 1999 May;188(5):483-90
references: 10235575
references: Spine (Phila Pa 1976). 2004 Oct 1;29(19):2115-9
references: 15454701
references: J Exp Med. 1996 Jul 1;184(1):241-51
references: 8691138
references: Ann Surg. 1978 Oct;188(4):460-7
references: 697430
references: Gut. 2001 Dec;49 Suppl 4:iv2-10
references: 11878790
references: Annu Rev Immunol. 1989;7:145-73
references: 2523712
references: Ann Rheum Dis. 2002 Nov;61 Suppl 2:ii51-3
references: 12379622
references: N Engl J Med. 2004 Feb 26;350(9):876-85
references: 14985485
references: Br J Surg. 2004 Dec;91(12):1646-51
references: 15505866
references: Gut. 2001 Dec;49 Suppl 4:iv22-31
references: 11878791
references: N Engl J Med. 1999 May 6;340(18):1398-405
references: 10228190
references: J Clin Invest. 1993 Apr;91(4):1390-5
references: 8473490
references: Ann Surg. 1960 Sep;152:445-71
references: 13725742
references: Immunity. 1994 Oct;1(7):553-62
references: 7600284
references: Br J Surg. 2006 Sep;93(9):1045-55
references: 16804873
references: J Exp Med. 1996 Jun 1;183(6):2605-16
references: 8676081
references: World J Surg. 1983 Jul;7(4):495-501
references: 6414191
references: N Engl J Med. 1997 Oct 9;337(15):1029-35
references: 9321530
references: Chin Med J (Engl). 2003 Feb;116(2):171-5
references: 12775223
references: Inflamm Bowel Dis. 2010 Oct;16(10):1787-807
references: 20222140
references: Ann Surg. 2004 Nov;240(5):825-31
references: 15492564
references: Curr Opin Clin Nutr Metab Care. 2004 May;7(3):309-16
references: 15075923