Immunohistochemical characterisation of inflammatory, neuroimmune and histologically "normal" appendicitis

Psaltis, Emmanouil (2021) Immunohistochemical characterisation of inflammatory, neuroimmune and histologically "normal" appendicitis. PhD thesis, University of Nottingham.

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Appendicitis is the most common surgical condition, but its diagnosis can be challenging. The practice of early appendicectomy to minimise morbidity and mortality has resulted in an increase of histologically "normal" appendices (HNA) being resected. Even, in the laparoscopic era, the removal of a macroscopically normal appendix in a symptomatic patient remains a clinical dilemma. The discrepancy between the clinical and histological diagnosis could suggest that an unknown pathology exists. This study compared the in-situ expression of key inflammatory markers in HNA resected from symptomatic patients with histologically inflamed samples.


The study retrospectively included 448 appendix specimens allocated in 4 groups. Group I (n=120) included specimens with histologically confirmed uncomplicated appendicitis, Group II (n=118) included samples with histologically confirmed complicated appendicitis (gangrene/perforation), and Group III (n=104) included appendices with no evidence of inflammation on conventional histology (HNA). The control group (n=106) consisted of appendices removed as part of the resected colon following elective colectomy. The expressions of TNF-α, IL-6, IL-2R and serotonin were studied with immunohistochemistry. Clinical data on signs and symptoms, routine laboratory tests and intraoperative findings were collected from the patient notes. Statistical analysis was carried out in SPSS version 21.


TNF-α expression in HNA was significantly increased compared with the control and inflamed appendices (p<0.05). HNA also demonstrated significantly increased IL-6 expression in the epithelial cells compared with the control as well as inflamed samples (p<0.05). The IL-2R expression of the HNA was significantly increased compared with the control appendices (p<0.05) but not as high as in the inflamed samples (p<0.05). HNA did not demonstrate significantly different serotonin contents of enterochromaffin cells compared with the control group (p=0.60). The inflamed samples were significantly depleted (p<0.05). Patients with HNA demonstrated significantly elevated white cell count compared with the control group (p<0.05) but not as high as in patients with inflamed samples (p<0.05). Of patients with HNA 23% reported previous episodes of RIF pain compared with 14% and 4% of patients with uncomplicated and complicated appendicitis respectively, whereas the severity of RIF pain did not vary between the three groups of patients. Localised peritonism was present in 56% of patients with HNA compared with 73% of patients with inflamed samples. The neutrophil to lymphocyte ratio and C-reactive protein concentrations of patients with HNA were significantly lower compared with the control group as well as patients with inflamed appendices (p<0.05). Faecoliths were found in 27% of HNA compared with 11% and 28% of uncomplicated and complicated appendicitis samples respectively. Intraoperatively, 51% of the HNA were thought to be inflamed. The expression of the studied markers between samples with and without faecolith and between those that appeared normal and those that appeared inflamed was not statistically significant.


It was demonstrated that histologically "normal" appendices resected following a clinical diagnosis of acute appendicitis exhibited increased levels of TNF-α, IL-6 and IL-2R that could indicate an active inflammatory response. Signs and symptoms as well as routine laboratory results that help clinicians in the diagnosis of appendicitis were also abnormal in patients with HNA. These observations could either represent an inflammatory response at such an early stage that could not be detected with conventional microscopy or could indicate an abnormally long inflammatory response with features of chronicity. In addition to this, the fundamental differences between samples with complicated and uncomplicated appendicitis could suggest that the different degrees of inflammation in the appendicitis spectrum could be due to differences in the underlying immunopathogenesis and not just disease progression.

Item Type: Thesis (University of Nottingham only) (PhD)
Supervisors: Lobo, Dileep
Zaitoun, Abed
Keywords: acute appendicitis; right iliac fossa pain; histologically normal; immunohistochemistry; inflammatory mediators
Subjects: W Medicine and related subjects (NLM Classification) > WI Digestive system
Faculties/Schools: UK Campuses > Faculty of Medicine and Health Sciences > School of Medicine
Item ID: 64816
Depositing User: Psaltis, Emmanouil
Date Deposited: 04 Aug 2021 04:41
Last Modified: 04 Aug 2021 04:41

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