vasoactive-intestinal-peptide and Adenomatous-Polyposis-Coli

In children with severe chronic constipation, abnormal distribution of substance P (SP) and vasoactive intestinal peptide (VIP), which represent excitatory and inhibitory nerves, respectively, has been reported. The normal distribution of these neuropeptides, however, is not well known. The aim of this study was to determine the populations of SP- and VIP-immunoreactive nerve fibres in the circular muscle of the colon in children. Surgically resected specimens were collected from a 6-year-old girl with familial polyposis coli (total colon) and nine patients with anorectal malformations aged 0-4 years (sigmoid colon). Double-labelling immunofluorescence was employed using neuron-specific enolase (NSE) with SP and NSE with VIP to count the percentage of SP- or VIP-labelled nerve fibres. These specimens showed normal submucous and myenteric plexuses stained with NSE. The population of SP- immunoreactive fibres was 15%-21% throughout the colon, and VIP was 39% in the caecum and 63%-65% in the transverse, descending, and sigmoid colon. In the four neonatal specimens (day 1 to 4), the SP population was only 1%-6% and the VIP population was also low (22%-33%). After 3 weeks of age, the populations had stabilised at 18%-26% for SP and 52%-62% for VIP. SP-immunoreactive nerve fibres were scarce in the neonatal period, and showed a rapid increase by 3 weeks and a similar though less dramatic increase in VIP-immunoreactive fibres. VIP-immunoreactive fibres were fewer in the caecum that at other colonic levels, where they accounted for 60% of NSE-labelled fibres; the SP population, however, was comparable at all levels of the colon at about 20% of NSE-labelled fibres.

Topics: Adenomatous Polyposis Coli; Anal Canal; Child, Preschool; Colon; Colon, Sigmoid; Enteric Nervous System; Female; Humans; Infant; Infant, Newborn; Male; Motor Neurons; Nerve Fibers; Rectum; Substance P; Vasoactive Intestinal Peptide

After Hirschsprung's disease was ruled out for 25 children who had severe chronic constipation, the authors studied the distribution of immunoreactivity for substance P (SP) and vasoactive intestinal peptide (VIP) in the intestinal wall, using immunofluorescence. SP and VIP immunoreactivity identify excitatory and inhibitory nerve fibres, respectively. Full-thickness rectal biopsy specimens were unsatisfactory, so seromuscular biopsies of the caecum, transverse colon, and sigmoid colon were obtained (by laparoscopy and laparotomy; n = 10 patients). SP-immunoreactive fibres were markedly reduced in seven, with concomitant reduction of VIP-immunoreactive fibres in four. In two other patients, there was no obvious reduction in SP- or VIP-immunoreactive fibres. In a patient who subsequently was found to have multiple endocrine neoplasia type 2b, the myenteric plexus was markedly hyperplastic, with an increase in nerve cells and nerve fibres. VIP-immunoreactive fibres were increased, but SP-immunoreactive fibres were markedly decreased. Surgical options included proximal stoma, Malone operation, and subtotal colectomy with preservation of the rectum. Three children with subtotal colectomy have had improvement over short-term follow-up. The combination of seromuscular laparoscopic biopsies and immunofluorescence demonstration of neuropeptides may identify new variants of intestinal neuronal dysplasia than can be treated successfully with surgery.

Topics: Adenomatous Polyposis Coli; Biopsy; Child; Child, Preschool; Colectomy; Colon; Colonic Pseudo-Obstruction; Constipation; Female; Fluorescent Antibody Technique; Hirschsprung Disease; Humans; Male; Nerve Fibers; Substance P; Vasoactive Intestinal Peptide