Colonic atresia without mesenteric vascular occlusion. The role of the fibroblast growth factor 10 signaling pathway.

BACKGROUND/PURPOSE: Colonic atresia occurs in 1:20,000 live births, offering a neonatal surgical challenge. Prenatal expression of fibroblast growth factor 10 (Fgf10), acting through fibroblast growth factor receptor 2b (Fgfr2b), is critical to the normal development of the colon. Invalidation of the Fgf10 pathway results in colonic atresia, inherited in an autosomal recessive pattern. Classically, disturbance of the mesenteric vasculature has been thought to cause many forms of intestinal atresia. The purpose of this study was to evaluate the role of vascular occlusion in the pathogenesis of colonic atresia. METHODS: Wild type (Wt), Fgf10(-/-), and Fgfr2b(-/-) mutant mouse embryos were harvested from timed pregnant mothers. Immediately following harvest, filtered India ink was infused via intracardiac microinjection. The gastrointestinal tract was dissected, and photomicrographs of the mesenteric arterial anatomy were taken at key developmental time points. RESULTS: Photomicrographs after India ink microinjections demonstrate normal, patent mesenteric cascades to the atretic colon at the time points corresponding to the failure of colonic development in the Fgf10(-/-) and Fgfr2b(-/-) mutants. The mesenteric arterial anatomy of the colon demonstrates no difference between the Wt and mutant colonic atresia. CONCLUSIONS: The absence of embryonic expression of Fgf10 or its receptor Fgfr2b results in colonic atresia in mice. India ink microinjection is a direct measure of mesenteric arterial patency. Colonic atresia in the Fgf10(-/-) and Fgfr2b(-/-) mutants occurs despite normal mesenteric vascular development. Thus the atresia is not the result of a mesenteric vascular occlusion. The patent colonic mesentery of the Fgf10(-/-) and Fgfr2b(-/-) mutants challenges an accepted pathogenesis of intestinal atresia. Although colonic atresia can occur as a result of vascular occlusion, new evidence exists to suggest that a genetic mechanism may play a role in the pathogenesis of this disease.

Congenital segmental dilatation of the colon with anorectal malformation.

Segmental dilatation of the colon is a rare entity. The authors report unique case of segmental dilatation of the cecum and ascending colon with high anorectal malformation in a newborn, and the possible embryogenesis of this condition is discussed.

The clinical relevance of non-classified dysganglionoses and implications for a new grading system.

In addition to the classified types of dysganglionosis, certain non-classified dysganglionoses (NCD) (types 1-4) were introduced by Meier-Ruge in 1992. Clinical data on these conditions are limited. Among 134 children with intestinal dysganglionoses (ID) treated from 1979 to 1999, 12 were identified to have a NCD. Their clinical course is presented. The existence of mild ID (type 1) is difficult to demonstrate. Current definitions and data on clinical relevance are not convincing. An indication for surgical treatment is not present. Isolated hypogenesis of the submucous plexus (SMP) (type 2, n = 8) is clinically a more severe kind of intestinal neuronal dysplasia type B and often requires early surgical intervention, but not resection. When associated with aganglionosis, its recognition is important for surgical strategy, to avoid complicated clinical courses, which are frequent if total or nearly-total resection is not performed. Hypogenesis of the myenteric plexus (MP) (type 5, n = 1) has received little attention so far. The sporadic appearance of heterotopic nerve cells of the SMP in the mucosa (type 3, n = 1) is physiologic; clusters of such cells, however, are probably of pathologic value, especially in combination with other types of ID in the same patient. Heterotopic nerve cells of the MP (type 4, n = 3) in the circular and longitudinal muscle layers are highly pathologic. This clearly-defined type is of major clinical relevance and requires complete resection. A severe disturbance of the migration process is the underlying cause. To simplify the terminology of IDs, a grading system based on the anatomic structures and clinical findings is proposed: innervation disturbances of the mucosa (grade I) are of limited clinical significance. Isolated malformations of the SMP (grade II) may require an enterostomy, but do not require resection except in certain cases associated with distal aganglionosis. Dysganglionosis of the MP (grade III) usually exhibits more severe symptoms and resection is indicated, especially with associated hypo- or aganglionosis. In aganglionic bowel (grade IV) resection is mandatory.

[Meconium peritonitis and feto-fetal transfusion syndrome]. / Peritonite da meconio e sindrome da trasfusione feto-fetale.

A case of twin-to-twin transfusion syndrome with intrauterine death of one twin and meconium peritonitis and intravascular disseminated coagulation in the other twin is reported. Meconium peritonitis follows to bowel perforation, caused by segmental severe hypoplasia of muscular layer. The Authors suggest that this structural alteration of bowel wall could be an expression of inequal distribution of some cells between the two twins, during embrional development.

Colonic hamartoma development by anomalous duplication in Cdx2 knockout mice.

To determine the biological role of caudal-like homeobox gene CDX2, we constructed knockout mice in which its mouse homologue Cdx2 was inactivated by homologous recombination, placing a bacterial lacZ gene under the control of the Cdx2 promoter. Although the homozygous mutants died in utero around implantation, the heterozygotes were viable and fertile and expressed lacZ in the caudal region in early embryos and in the gut tissues in adults. The heterozygotes developed cecal and colonic villi by anteriorization and formed hamartomatous polyps in the proximal colon. The hamartoma started to develop at 11.5 days of gestation as an outpocket of the gut epithelium, which ceased to express the remaining Cdx2 allele. The outpocket then expanded as a partially duplicated gut but was contained as a hamartoma after birth. In adult mice, these hamartomas grew very slowly and took a benign course. None of them progressed into invasive adenocarcinomas, even at 1.5 years of age. Whereas the cecal and colonic villi expressed lacZ, the hamartoma epithelium did not, nor did it express Cdx2 mRNA from the wild-type allele. However, genomic DNA analysis of the polyp epithelium did not show a loss of heterozygosity of the Cdx2 gene, suggesting a mechanism of biallelic Cdx2 inactivation other than loss of heterozygosity. These results indicate that the Cdx2 haploin-sufficiency caused cecal and colonic villi, whereas the biallelic inactivation of Cdx2 triggered anomalous duplications of the embryonic gut epithelium, which were contained as hamartomas after birth.

The retropancreatic colon: a congenital anomaly.

We report the first case of a retropancreatic colon. This condition appears to be a congenital internal intra-abdominal hernia secondary to abnormal intestinal rotation in the embryo.

Malrotation of the intestine.

Malrotation of the intestinal tract is a product of a well defined aberrant embryology. Because the consequences of malrotation associated with a midgut volvulus may be catastrophic, an understanding of the anatomy, diagnostic criteria, and appropriate therapy for this putative emergency illness is imperative. This report summarizes a recent 18-month experience with this diagnosis and contrasts this experience with that in the published literature. More than half (14/22) of the patients presented during the first month of life, and all had vomiting, which in most cases was bilious. The barium upper gastrointestinal series was the preferred diagnostic study, being both sensitive (18/19, 95%) and accurate (18/21, 86%). In this series two-thirds of the patients presented with volvulus (15/22, 68%) of whom five had ischemic intestine requiring resection. One of these children died of overwhelming sepsis. A Ladd procedure was the preferred treatment, which as defined by us includes evisceration and inspection of the mesenteric root, counterclockwise derotation of a midgut volvulus, lysis of Ladd's bands with straightening of the duodenum along the right abdominal gutter, inversion-ligation appendectomy, and placement of the cecum into the left lower quadrant. A high index of suspicion in the neonate with vomiting, rapid diagnosis, and appropriate operative therapy results in a predictable favorable outcome for children with intestinal malrotation.

Three cases of spontaneous duodeno-colic fistula.

Three cases of duodeno-colic fistula are presented, where a communication was demonstrated between the anterior aspect of the third part of the duodenum and the transverse colon at the point of mesocolic attachment. At operation the fistulae were found to be some 6 to 9 cm in length, and histological examination showed a well marked muscular layer with an intact epithelium. In view of the absence of any explanatory pathology, an embryological basis is suggested as the likeliest explanation for their origin.