This study suggests patients who present with asymptomatic CCAM will subsequently become symptomatic. Early surgical referral and intervention may be beneficial to avoid the development of complications.

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Necrotising enterocolitis (NEC) remains an overwhelming gastrointestinal (GI) emergency in premature infants, with an annual incidence of 350 cases and a mortality of 23% in the United Kingdom. The aetiology of NEC is multifactorial and its pathogenesis poorly understood. It is characterised by severe necrotic damage to the intestine. Mucus is an adherent, viscoelastic gel layer protecting the delicate underlying epithelium from lumenal aggressors such as digestive enzymes and bacterial toxins. The group of trefoil factor peptides (TFF1-3) are part of the protective mechanism operating in the intestinal mucosa and play a fundamental role in epithelial protection, repair, and restitution. These secreted peptides have been identified in a site-specific pattern in the GI mucosa, and their expression has been shown to be upregulated in early stages of mucosal repair. The role of trefoil peptides in neonatal mucosal protection has not been well investigated. Impaired mucosal regeneration due in part to failure of upregulation of TFF expression may contribute to the pathogenesis of NEC. The aim of this study was to investigate TFF1-3 mRNA expression and to identify the gene product in the GI tracts of normal neonatal controls and infants with NEC. Parents of all babies having a laparotomy in the neonatal period (defined as up to 44 weeks' gestation) and bowel resection were approached for written consent. Bowel samples were fixed in formalin and then embedded in paraffin in an RNAse-free manner. In situ hybridisation and immunohistochemistry were performed to examine the pattern of trefoil mRNA expression and to localise the peptides in the neonatal GI tract. Forty neonatal bowel specimens were examined. Twelve patients had NEC, eight were recovering from NEC, and 20 control specimens were obtained. TFF1 and TFF2 mRNA expression were not detected in the majority of NEC specimens, and there was a relative downregulation of TFF3 expression in 83% of NEC patients. TFF1 and TFF2 expression were noted in the recovery phase from NEC. Immunohistochemistry revealed a decrease in TFF3 gene product in sites adjacent to mucosal damage secondary to NEC. In acute NEC there was no apparent expression of TFF1 and 2 protein. In the group of patients recovering from NEC, TFF1 and 2 expression were seen in association with regenerative changes in the mucosa. Previous data has shown TFF1-3 to be upregulated in the acute phase response to mucosal injury in the gut. Trefoil peptides have been shown to promote epithelial cell migration and protect against apoptosis. Our results suggest that there is a lack of TFF expression in response to NEC in the premature gut. This may lead to impaired restitution of the mucosa and contribute to the cascade of bowel necrosis and generalised sepsis characteristic of NEC.

Patients who have an APER are over 10 times more likely to have a perineal wound complication if they have SCPRT than not. Two-thirds of these will not have healed by 1 month, half by 3 months and over a quarter will still remain unhealed at 1 year. This has important implications for patient management decisions. Large prospective studies are needed to evaluate the effects of a selective policy for radiotherapy administered to patients requiring APER.

Necrotising enterocolitis (NEC) is characterised by severe mucosal loss and therefore gastrointestinal (GI) cell proliferation is essential for survival, epithelial repair and recovery of function. Trefoil peptides play a key role in epithelial restitution and repair, and we previously reported a down-regulation of these peptides in NEC. Oral administration of epidermal growth factor has a protective effect in a rat model of colitis. These observations raised the question of a link between the pathogenesis of NEC and decreased mucosal cell proliferation. This study investigates the pattern of mucosal cell proliferation in the GI tract of fetuses, normal neonatal controls, infants with NEC and those recovering from NEC. Parents of neonates up to 44 weeks' gestation undergoing laparotomy and bowel resection were approached for consent. Bowel samples from resection specimens, and GI tract extractions from products of conception at termination of pregnancy, were fixed in formalin and then embedded in paraffin blocks. Patterns of small and large bowel mucosal proliferation were assessed by immunohistochemical staining for Ki67. Seventeen foetal and 58 postnatal bowel samples [34 with NEC (22 acute, 12 recovery) and 24 controls] were analysed. The pattern of proliferation seen in the fetus and normal neonate was identical to that in mature bowel. In NEC severe mucosal necrosis was observed, but in viable crypts remaining, there was crypt hyperplasia and a relative increase in the proportion of cells staining positive for Ki67. In those patients recovering from NEC the pattern of proliferation was returning towards the normal range. In those patients with post-NEC strictures the recovery of normal bowel morphology was delayed. In NEC there is massive loss of potential proliferative tissue. The remaining viable tissue shows an increase in proliferative activity in the small and large bowel. Failure of rapid regeneration of functional mucosa may therefore be related to an inability of increased proliferative activity to match the losses from the surface; alternatively there may be rapid production of immature, short-lived cells. This study shows that the proliferative response, although present, is insufficient to rapidly reverse the mucosal insult observed in NEC.

Background The pivotal role of epidermal growth factor receptor (EGFR) in transducing signalling by multiple ligands involved in proliferation, differentiation and migration is evidenced by the fact that EGFR-null mice invariably die in utero or early post-natal life. Inactivation of EGFR in knockout mice results in a haemorrhagic enterocolitis similar to necrotising enterocolitis (NEC). Aims This study aims to define the pattern of expression and localisation of the EGFR in foetal bowel, normal neonatal gastrointestinal tract (GIT) and in NEC. Methods Foetal bowel samples and bowel resection specimens from neonates undergoing laparotomy were collected with parental consent. Immunohistochemistry was performed to examine EGFR expression and localisation in the GI tract. Results 15 foetal and 58 neonatal bowel specimens were examined (NEC n = 22, recovering from NEC n = 12, normal neonatal controls n = 24). EGFR was detected in all foetal bowel samples from 10+3 weeks gestation and was localised to the apical membrane of GI epithelial cells. In acute NEC an increase in EGFR expression and a partial shift in localisation to the apical surface of GI epithelial cells was observed when compared to normal neonatal controls. Conclusions It has been proposed that EGFR forms part of an essential defence mechanism of intestinal epithelial integrity, wherein peptide growth factors play critical protective and reparative roles. This study demonstrates apical expression of EGFR protein in the GI epithelium during acute NEC, which may enhance the ability of luminally delivered growth factors and protective peptides to exert their restitutive effects in acute mucosal injury.

Background The aetiology of necrotizing enterocolitis (NEC) is multifactorial and its pathogenesis poorly understood. The trefoil factor peptides (TFF1–3) contribute to protective mechanisms operating in the gastro-intestinal (GI) mucosa and play a fundamental role in epithelial protection, restitution and repair. The role of TFF1–3 in neonatal mucosal protection has not been well investigated. Aims This study aims to investigate alterations in TFF 13 mRNA and protein expression in the GI tract of infants with NEC compared to normal neonatal controls. Methods Bowel resection specimens were collected with parental consent from neonates undergoing laparotomy. In situ hybridisation, real time PCR and immunohistochemistry were performed to examine trefoil mRNA and peptide expression in the neonatal GI tract. Results 77 neonatal bowel specimens were examined (NEC n = 27, recovering from NEC n = 16, normal neonatal controls n = 29). There was no upregulation of TFF 1 and 2 mRNA and protein expression in acute NEC and there was significant down-regulation of TFF3 protein and mRNA expression. Adjacent to areas of mucosal necrosis there was an inverse relationship in the number of TFF3-positive goblet cells and proximity to the ulceration. Conclusions A number of studies have shown up-regulation of TFF 1–3 in the acute phase response to GI mucosal injury, promotion of epithelial cell migration and protection against apoptosis. Our results suggest a lack of TFF expression in response to NEC in the premature gut. This may lead to impaired restitution of the mucosa and contribute to the cascade of bowel necrosis and generalised sepsis characteristic of NEC.

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