Preliminary identification of key miRNAs, signaling pathways, and genes associated with Hirschsprung's disease by analysis of tissue microRNA expression profiles.

BACKGROUND: Hirschsprung's disease (HSCR) is a congenital gut motility disorder of infants, and if left untreated, it is fatal to the affected infants. This study aimed to identify key microRNAs (miRNAs), signaling pathways and genes involved in the pathogenesis of HSCR. METHODS: The miRNA microarray dataset GSE77296 was downloaded. Nine colon tissue samples were available: six from HSCR patients and three matched control samples. Differentially expressed miRNAs (DEMs) were identified after data preprocessing. Target genes of the selected upregulated and downregulated DEMs were predicted. In addition, functional enrichment analyses for the selected DEMs and target genes were conducted. Finally, interaction networks between the DEMs and target genes were constructed. RESULTS: A total of 162 DEMs (73 upregulated and 89 downregulated) were obtained. A total of 2511 DEM-target gene pairs for the 40 selected DEMs were identified, including 1645 pairs for the upregulated DEMs and 866 pairs for the downregulated DEMs. The upregulated DEM miR-141-3p and down-regulated DEM miR-30a-3p were identified as key miRNAs by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment and network analyses. Besides, KEGG pathway enrichment analysis revealed that pathways in cancer and the mitogen-activated protein kinase (MAPK) signaling pathway were key pathways. The key genes frizzled class receptor 3 (FZD3) and docking protein 6 (DOK6) were obtained through the DEM-target gene interaction networks. CONCLUSION: Two key miRNAs (miR-141-3p and miR-30a-3p), the MAPK signaling pathway and two key genes (FZD3 and DOK6) were implicated in the pathogenesis of HSCR.

[The relationship between postoperative complication and pathological features of 324 patients with neuronal intestinal malformations].

OBJECTIVE: To investigate the relationship between the morphological features of different types of neuronal intestinal malformations (NIM) and their postoperative complications. METHODS: The data of morphological and clinical features of 324 cases with NIM were analyzed retrospectively. RESULTS: In all 324 patients, 210 cases were Hirschsprung's disease (HD), 38 intestinal neuronal dysplasia (IND), 45 mixed HD/IND, 8 hypoganglionosis, 22 combined HD/hypoganglionosis and 1 immaturity of ganglion cells. The percentages of normal neuron in bowel of different NIM were 88.1%, 24.4%, 18.4%, 4/8, 27.7% and 0/1 in HD, HD/IND, IND, hypoganglionosis, HD/hypoganglionosis and immaturity of ganglion cells respectively. There were totally 46 cases complicated with recurrent postoperative enterocolitis (EC). Incidence of recurrent postoperative EC in HD patients was 6.7% while in IND/HD and IND patients was 35.6% and 28.9%, respectively. Incidences of EC in cases with the residual IND margins and with the normal margins were 38.2% and 8.7%, respectively. Incidence of EC in cases with transanal endorectal pull-through procedure and with transabdominal procedure was 18.0% and 8.3%, respectively. Nine cases underwent another procedure because of severe persistent constipation or EC after operation, including 4 cases HD/IND, 1 case IND, 3 cases HD and 1 case HD/hypoganglionosis. CONCLUSIONS: Neuron distribution is inconsistent with pathology of NIM. Postoperative EC are rare in the patients only with isolated HD. Furthermore, margins with residual IND and transanal endorectal pull-through procedure are risk factors to recurrent EC. However, the extension of excision about IND is uncertain and need further study.

Congenital duodenal obstruction in neonates: a decade's experience from one center.

BACKGROUND: Congenital duodenal obstruction (CDO) is one of the most common anomalies in newborns, and accounting for nearly half of all cases of neonatal intestinal obstruction. This study aimed to review our single-center experience in managing congenital duodenal obstruction while evaluate the outcomes. METHODS: We conducted a retrospective analysis of the records of all neonates dianogsed with congenital duodenal obstruction admitted to our center between January 2003 and December 2012. We analyzed demographic criteria, clinical manifestations, associated anomalies, radiologic findings, surgical methods, postoperative complications, and final outcomes. RESULTS: The study comprised 287 newborns (193 boys and 94 girls). Birth weight ranged from 950 g to 4850 g. Fifty-three patients were born prematurely between 28 and 36 weeks' gestation. Malrotation was diagnosed in 174 patients, annular pancreas in 66, duodenal web in 55, duodenal atresia or stenosis in 9, preduodenal portal vein in 2, and congenital band compression in 1. Twenty patients had various combinations of these conditions. Presenting symptoms included bilious vomiting, dehydration, and weight loss. X-rays of the upper abdomen demonstrated the presence of a typical double-bubble sign or air-fluid levels in 68.64% of patients, and confirmatory upper and/or lower gastrointestinal contrast studies were obtained in 64.11%. Multiple associated abnormalities were observed in 50.52% of the patients. Various surgical approaches were used, including Ladd's procedure, duodenoplasty, duodenoduodenostomy, duodenojejunostomy, or a combination of these. Seventeen patients died postoperatively and 14 required re-operation. CONCLUSIONS: Congenital duodenal obstruction is a complex entity with various etiologies and often includes multiple concomitant disorders. Timely diagnosis and aggressive surgery are key to improving prognosis. Care should be taken to address all of the causes of duodenal obstruction and/or associated alimentary tract anomalies during surgery.