Neuronal hypertrophy in acute appendicitis.
OBJECTIVE
The pathogenesis of appendicitis remains poorly understood. However, there is increasing evidence of involvement of the enteric nervous system in immune regulation and in inflammatory responses. This study was set up to characterize the status of the enteric nervous system in normal and in inflamed appendixes.


METHODS
S100- and 2',2'-cyclic nucleotide 3' phosphodiesterase-positive Schwann cells, synaptophysin, and neuron-specific, enolase-positive nerve fibers and tryptase-positive mast cells were evaluated with immunohistochemical staining in surgically resected appendixes from 20 children with histologically proven acute appendicitis (HA), 10 histologically normal appendixes (HN) from patients with a clinical diagnosis of appendicitis, and 10 normal appendixes from patients undergoing elective abdominal surgery. Immunostained sections were subjected to quantitative image analysis. The number and size of ganglia and the number of nerve fibers, Schwann cells, and mast cells in each tissue compartment was quantitatively or semiquantitatively measured.


RESULTS
Increased numbers of fibers, Schwann cells, and enlarged ganglia, widely distributed in the muscularis externa and submucosa, were seen in all HA appendixes and in 4 of 10 HN appendixes. The number and size of ganglia in muscularis externa and in the submucosa of appendixes with HA were significantly greater compared with those in control appendixes (P <.001). A significantly increased number of individually stained nerve fibers and Schwann cells (P <.05) were present in the muscularis externa in HA appendixes compared with control appendixes. Significantly increased numbers of tryptase-positive mast cells (P <.05) were present in the submucosa, muscularis, and especially in the lamina propria in HA specimens, compared with that of control tissue.


CONCLUSIONS
The significant increase in neural components and mast cells in acute appendicitis is unlikely to develop during a single acute inflammatory episode. This suggests an underlying chronic abnormality as a secondary reaction to repeated bouts of inflammation, obstruction, or both. These results challenge our current understanding of the pathophysiological processes that give rise to acute appendicitis.
Xiong
S
S
Children's Research Centre, Our Lady's Hospital for Sick Children, Crumlin, Dublin 12, Ireland.
Puri
P
P
Nemeth
L
L
O'Briain
D S
DS
Reen
D J
DJ
D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases / Q000378:metabolism; D000208:Acute Disease; D001064:Appendicitis / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D002648:Child; D053818:Chymases; D017615:Enteric Nervous System / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D006984:Hypertrophy; D007124:Immunoenzyme Techniques; D008297:Male; D009412:Nerve Fibers / Q000378:metabolism / Q000473:pathology; D010523:Peripheral Nervous System Diseases / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D009418:S100 Proteins / Q000378:metabolism; D012583:Schwann Cells / Q000378:metabolism / Q000473:pathology; D012697:Serine Endopeptidases / Q000378:metabolism; D016708:Synaptophysin / Q000378:metabolism; D053802:Tryptases
D009418:S100 Proteins; D016708:Synaptophysin; D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases; D012697:Serine Endopeptidases; C083294:chymase 2; D053818:Chymases; D053802:Tryptases; D010751:Phosphopyruvate Hydratase