Mucosal Neuroendocrine Cell Abnormalities in Patients with Chronic Constipation

Abstract

The aim of this study was to examine the distribution of neuroendocrine cells (NEC) in patients with chronic constipation (CC) as a means of establishing a relationship between pathology, symptomatology and treatment. Methods: Rectal biopsy specimens from 43 patients with CC (aged 17–82 years) and 20 age-matched normal controls were examined histopathologically using haematoxylin and eosin, and immunohistochemically using antibodies against chromogranin-A (Ch-A) and serotonin (5-HT) to detect NEC. The number of positive NEC per 70 crypts (CR) was counted and expressed as the ratio of NEC/CR. CC patients were divided into groups based on management, then compared using NEC/CR. Results: CC was managed conservatively in 29 patients (group A) and invasively in 14. Of these 14, 10 had normal histology (group B) and four had typical histopathological signs of intestinal neuronal dysplasia (IND; group C). All control specimens were unremarkable. In controls, NEC/CR was 0.94 ± 0.33 for Ch-A and 0.32 ± 0.08 for 5-HT. In group A, NEC/CR was 2.23 ± 0.13 for Ch-A and 1.02 ± 0.06 for 5-HT. In group B, it was 2.79 ± 0.18 for Ch-A and 1.72 ± 0.33 for 5-HT. In group C, it was 3.12 ± 0.22 for Ch-A and 2.32 ± 0.14 for 5-HT. The increase in Ch-A and 5-HT immunoreactive cells in groups B and C compared with controls was greater (p < 0.01, p < 0.05) than the increase seen in group A compared with controls (p < 0.01, p < 0.05). Conclusions: These results demonstrate that increased numbers of NEC may play a role in the abnormal bowel function seen in CC, and may have some relationship with the development of giant submucosal ganglia in IND.