As a national referral centre, the Intestinal Failure Unit at St Mark’s cares for the largest cohort of patient with Type 3 IF in the UK and possibly in Europe. A large database incorporating all patients has developed over time. The aims of this research were to analyse factors affecting survival in patients with intestinal failure and evaluate possible novel therapeutic avenues.
In order to address this broad question, four retrospective studies were undertaken. The first looked at changes in underlying aetiology leading to intestinal failure and assessed in particular whether the pathophysiological mechanism of intestinal failure was a predictor of survival. While the effect of the pathophysiological mechanism on survival has been described in the literature previously [1][2], it has not covered the number of patients or study period of my study. In addition, it is the first time the exact mechanistic categories as defined by the ESPEN consensus document have been used as a predictor of survival. The second study looked at the effect on survival and parenteral support requirements of restoration of intestinal continuity surgery. The third study looked at the effect of fungal catheter related blood stream infections on survival in patients with intestinal failure. The fourth study looked at the effect of CT defined sarcopenia on survival in intestinal failure.
The functionality of healthy small intestinal tissue is reliant on the coordination of multicellular processes, which in turn depend upon complex intracellular signalling. This signalling is mediated by a host of growth factors and cytokines. There is now evidence to suggest the therapeutic manipulation of these factors can restore functionality of intestinal tissue. An example of this is the GLP-2 which has been shown to cause mucosal proliferation and this increase functional surface area of the bowel and improve intestinal absorption. This has led to the development of analogues which have now been licenced for use in short bowel. To evaluate the effect of this I undertook an in-vitro study developing a protocol for culture and maturation of porcine intestinal organoid units and assessing the effect of two growth factors, the glucagon like peptides GLP-1 and GLP-2. My final chapter describes the successful set up and protocol for a phase 2b clinical trial of the GLP-1 analogue liraglutide on patients with intestinal failure and our difficulties recruiting to this trial with the eventual closure of the trial due to the COVID-19 pandemic.