Pilot study of immunological factors in non-inflammatory bowel disease enterocutaneous fistulas.

BACKGROUND: Tumour necrosis factor alpha (TNF-α) is a cytokine elevated in inflammatory bowel disease enterocutaneous fistula (IBD ECF). Dendritic cells are antigen presenting cells that orchestrate the immune responses and regulate the production of cytokines by immune cells including T cells. No study to date has assessed the level of TNF-α or the presence of dendritic cells in non-IBD ECF. The aim of this study was to assess the inflammatory activity, with a particular emphasis on TNF-α in non-IBD ECF when compared with control small bowel tissue. METHODS: Tissue biopsies were obtained from ECF at operation from non-IBD patients and from terminal ileum in normal colonoscopy control patients. After overnight culture, accumulation of intracellular TNF-α was measured by flow cytometry in cells treated with monensin to assess the on-going cytokine production. Data were acquired using FACS Canto II. Unpaired Student's t-test was used to compare variables between groups and p < 0.05 was regarded as significant. RESULTS: The on-going production of TNF-α from dendritic cells (p = 0.0007), putative monocyte and B cell populations (p = 0.04) and CD3+ T cells (p = 0.04) was significantly higher in non-IBD ECF tissue than that from control tissue. CONCLUSIONS: This study reveals results which provide evidence for the potential use of anti-TNF-α agents in the treatment of non-IBD ECF. A pilot study to evaluate this treatment as an alternative option in an already surgically challenging group of patients is planned. Positive findings would be a major medical advance with a new use for anti-TNF-α agents.

A meta-analysis of outcomes following use of somatostatin and its analogues for the management of enterocutaneous fistulas.

OBJECTIVE: Several randomized control trials (RCTs) have compared somatostatin and its analogues versus a control group in patients with enterocutaneous fistulas (ECF). This study meta-analyzes the literature and establishes whether it shows a beneficial effect on ECF closure. METHODS: We searched MEDLINE, EMBASE, CINAHL, Cochrane, and PubMed databases according to PRISMA guidelines. Seventy-nine articles were screened. Nine RCTs met the inclusion criteria. Statistical analyses were performed using Review Manager 5.1. RESULTS: Somatostatin analogues versus control. Number of fistula closed: A significant number of ECF closed in the somatostatin analogue group compared to control group, P = 0.002.Time to closure: ECF closed significantly faster with somatostatin analogues compared to controls, P < 0.0001.Mortality: No significant difference between somatostatin analogues and controls, P = 0.68.Somatostatin versus control. Number of fistula closed: A significant number of ECF closed with somatostatin as compared to control, P = 0.04.Time to closure: ECF closed significantly faster with somatostatin than controls, P < 0.00001.Mortality: No significant difference between somatostatin and controls, P = 0.63 CONCLUSIONS: Somatostatin and octreotide increase the likelihood of fistula closure. Both are beneficial in reducing the time to fistula closure. Neither has an effect on mortality. The risk ratio (RR) for somatostatin was higher than the RR for analogues. This may suggest that somatostatin could be better than analogues in relation to the number of fistulas closed and time to closure. Further studies are required to corroborate these apparent findings.

Cullen's sign - Case report with a review of the literature.

INTRODUCTION: Cullen's sign is described as superficial oedema with bruising in the subcutaneous fatty tissue around the peri-umbilical region. It is also known as peri-umbilical ecchymosis. PRESENTATION OF CASE: We report a case of a fifty-three year old gentleman who presented with non-specific abdominal pain. Significant bruising was present within the subcutaneous fatty tissue on the anterior abdominal wall in keeping with 'Cullen's sign.' Of note he denied any alcohol intake and his amylase was normal. A diagnosis of pancreatitis was made following a CT scan of his abdomen. DISCUSSION: A search of the entire English literature using PubMed with the phrase 'Cullen's sign' has been performed. Papers were reviewed in relation to recognition of this clinical sign, differential diagnosis, and management. CONCLUSION: Our case and review of the literature highlights the rarity of this clinical sign which a clinician may encounter. In addition we draw to attention the importance of having knowledge of the underlying possible conditions which may lead to this sign, and can be vital in successful acute management.

Dieulafoy lesion endoscopically rubber banded, with further severe haematemesis requiring emergency laparotomy - Case report.

Dieulafoy lesion is a rare cause of massive gastrointestinal haemorrhage that can be fatal. We report a case of a sixty-year-old lady who presented to the emergency department with haematemesis and melaena. During oesophagogastroduodenoscopy (OGD), an active bleeding vessel was seen on the lesser curvature of the stomach, near the gastro-oesophageal junction and a diagnosis of Dieulafoy's lesion made. The lesion was managed with the application of two rubber bands. Our patient re-presented to the emergency department ten days later with severe haematemesis requiring an emergency laparotomy.A search of the entire English literature using PubMed with the phrase 'Dieulafoy' has been performed. Papers were reviewed in relation to management of this lesion with rubber banding via endoscopy. The current available haemostatic methods are described.

Prospective study of immunological factors in non-inflammatory bowel disease enterocutaneous fistulas.

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/DESIGN: 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. DISCUSSION: 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. TRIAL REGISTRATION: ISRCTN44000447.

Transverse colon volvulus in a 15 year old boy and the review of the literature.

We report a rare case of transverse colon volvulus in a fifteen year old boy with a review of the literature. This brings the total number of pediatric cases reported in the English literature to fifteen. This case is unusual in that no aetiological factor has been found, in contrast to the majority of the pediatric cases. Diagnosis can be challenging and the effective management remains controversial. The various radiological imaging modalities are presented. The epidemiology, aetiology, diagnosis and management of transverse colon volvulus are discussed. It is important to highlight this case and those in the literature, as many surgeons may never have seen a single case of transverse colon volvulus. It may therefore not be considered in the differential diagnosis of recurrent intermittent abdominal pain or acute intestinal obstruction.