The role of circulating fibrocytes in the diagnosis of appendicitis

Circulating fibrocytes play a role in healing and fibrotic processes. They promote tissue  healing by secreting collagen and extracellular matrix molecules. They also contribute to scar formation by producing a –SMA which provides a contractile force. As fibrocytes are  monocyte-derived cells, they have features of macrophages, and therefore play a role in the  inflammatory process. They are known to be an active source of cytokines.

Circulating fibrocytes are involved in many fibrotic and inflammatory conditions. The  circulating fibrocyte percentage increases in some intestinal diseases such as Crohn’s disease.  Fibrocytes are diffusely distributed throughout the connective tissue platform shared by mesentery and adjacent intestine. This thesis aimed to investigate the role of circulating  fibrocytes in acute appendicitis. 

In the first work of the thesis we examined the diagnostic accuracy of available biomarkers in the diagnosis of acute appendicitis in patients with right iliac fossa pain. The findings showed  there is a lack of biomarkers that accurately identify acute appendicitis in patients who present with right iliac fossa pain. These findings prompted further investigation of the possibility that the proportion of fibrocytes in circulating monocytes may identify an accurate  marker of acute appendicitis. 

Patients presenting with suspected acute appendicitis at University Hospital Limerick were recruited in a prospective cohort study. Pre-operative blood samples and the post-operative  histological analysis of the appendix facilitated an investigation of the role of the circulating fibrocytes in the diagnosis of acute appendicitis using techniques such as flow cytometry analysis. Relevant clinical data were collected for all patients. 

The circulating fibrocyte percentage was increased in patients with histologically proven acute appendicitis when compared with healthy controls. Also, the circulating fibrocyte percentage was increased in patients with histologically proven acute appendicitis when  compared with patients with histologically proven normal appendix. The diagnostic accuracy  of the circulating fibrocyte percentage was equally accurate as standard serological biomarkers (i.e., white cell count, C-reactive protein and neutrophil-lymphocyte ratio) in  terms of the diagnosis. The circulating fibrocyte percentage was increased in patients with histologically proven uncomplicated appendicitis when compared with patients with histologically proven normal appendix. The neutrophil-lymphocyte ratio was increased in patients with histologically proven complicated appendicitis when compared with patients  with histologically proven normal appendix. The circulating fibrocyte percentage was included in a diagnostic prediction model for patients presenting with suspected acute appendicitis. The diagnostic accuracy of the new prediction model outperformed the Alvarado model in the diagnosis of acute appendicitis in patients at high-risk of having acute appendicitis. The diagnostic accuracy of the Alvarado model outperformed the new prediction model in the diagnosis of a normal appendix in patients at low-risk of having acute appendicitis.

The thesis concludes with a summary of the work undertaken and a discussion of the findings in the context of available literature on the topic. The limitations of the study and future directions are also discussed.