New observations on the pathogenesis of multiple intestinal atresias

It has been suggested that multiple intestinal atresias result from multiple ischemic infarctions of the intestinal tract. We have studied surgical material from 59 neonates with intestinal atresias seen at our hospital between 1975 and 1986. Forty (68%) patients had single intestinal atresias and 19 (32%) had multiple atresias. There were seven cases of hereditary multiple atresias seen in three families and 12 cases of nonhereditary multiple atresias. All hereditary cases had numerous type I or type II gastrointestinal atresias but none had type IIIa atresia. Six of the seven hereditary cases had multiple atresias in the small as well as large bowel. The 12 patients with nonhereditary atresias had various types of atresias but mesenteric or intestinal interruption was observed in only two patients. All patients with hereditary multiple intestinal atresias showed identical microscopic appearances in the small and large intestine, consisting of sieve-like multiple lumina, each surrounded by its own mucosa and muscularis mucosae but sharing a common muscle coat. There was no evidence of lanugo, bile pigments, or squames within the lumen distal to atretic segments in any of these patients. Six nonhereditary cases who had multiple septal atresias affecting only the small bowel demonstrated essentially similar lesions on microscopic examination as seen in hereditary cases. There was no evidence of arterial occlusion in the mesentery and lanugo, bile pigments, and squames could not be found distally in the intestinal contents in any of these cases. These pathologic findings suggest that all cases of hereditary multiple intestinal atresias and some cases of nonhereditary multiple intestinal atresias are a consequence of a malformative process of the gastrointestinal tract rather than an ischemic process.     

Complicated Intestinal Atresias

In this group of 45 intestinal atresia patients (duodenum, 16; jejunum, 24; ileum five) at the University of Mississippi Medical Center, individual hospitalizations ranged up to 245 days. Twelve patients required multiple operations, and the overall mortality rate was 22% (ten patients). While the patients with duodenal atresia had the greatest incidence of other congenital anomalies, including Down's syndrome, the patients with jejunal atresia presented with the most challenging surgical problems. Of the 24 jejunal atresia patients, only three had a single, simple area of obstruction. The remainder were complicated by other gastrointestinal lesions (five patients), by multiple areas of atresia (seven patients) including those in one surviving patient with 22 separate atretic segments, and by the Christmas tree deformity (nine patients). Intraoperative management of the complicated atresia should include: 1) grouping of multiple atresias during resection, 2) adequate resection of the dilated proximal atonic loop, 3) end-to-end anastomoses, 4) avoidance of intraluminal catheters, 5) additional resection of a segment of the distal loop in the Christmas tree deformity and 6) consideration of the shish kebab technique for multiple atretic webs. Postoperative management should involve early intravenous nutrition and repeated exploration for continued obstruction.     

Hereditary multiple intestinal atresias: 2 new cases and review of the literature

Intestinal atresias are a common cause of newborn bowel obstruction (Dalla Vecchia LK, Grosfeld JL, West KW, et al, Intestinal atresia and stenosis: a 25-year experience with 277 cases. Arch Surg 1998; 133[5]:490-496). Hereditary multiple intestinal atresias, first reported by Guttman et al in 1973, is the rarest form of multiple atresias (Guttman FM, Braun P, Garance PH, et al, Multiple atresias and a new syndrome of hereditary multiple atresias involving the gastrointestinal tract from stomach to rectum. J Pediatr Surg 1973;8:633-640; Bass J, Pyloric atresia associated with multiple intestinal atresias and immune deficiency. J Pediatr Surg 2002;37:941-942.). It has been proposed to be autosomal recessive, to involve atresias in a variable combination of sites from stomach to rectum, and to be universally fatal (Bilodeau A, Prasil P, Cloutier R, et al, Hereditary multiple intestinal atresia: thirty years later. J Pediatr Surg 2004;39:726-730; Moreno LA, Gottrand F, Turck D, et al, Severe combined immunodeficiency syndrome associated with autosomal recessive familial multiple gastrointestinal atresias: study of a family. Am J Med Genet 1990;37:143-146). Patients have significant intestinal dysfunction and unrelenting sepsis stemming from a poorly defined, severe immunologic defect. Our case report presents 2 full siblings to nonconsanguineous parents with pyloric atresia, multiple small bowel and colonic atresias, and severe immune dysfunction. Care was withdrawn within 3 months of life on both siblings after multiple bouts of sepsis. Data suggest that the immune defect may not be primary, but in fact be secondary to intestinal dysfunction. Although the subjects in this article ultimately had fatal outcomes, a comprehensive immunologic/physiologic picture is presented in hopes of furthering the understanding of this grave disease.     

Surgical management of multiple intestinal atresias

The unusual problem of multiple intestinal atresias associated with jejunal atresia has been reviewed and seven cases have been summarized. Maintaining maximal bowel length without jeopardizing the patient is of utmost importance. The shish kebob technique has been illustrated in a patient with 15 obstructions. The other cases include one patient with the apple peel deformity and two with atresias associated with gastroschisis. Although these children are small in general, they are bright and otherwise healthy. The 90 percent mortality reported previously has been reversed by a combination of techniques and lessons learned from the leaders in pediatric surgery.     

Multiple atresias in a low-birth-weight twin.

This report describes a case of 16 small bowel atresias in a twin who was born at 31 weeks' gestation, weighing 1,690 g. All atresias and intestinal segments of 5 cm or less in length were resected, resulting in nine primary anastomoses, preserving 75% (107 cm) of his initial small bowel length. The baby went home on full oral feedings after 10 weeks. Multiple anastomoses in the low-birth-weight neonate can be tolerated with the functional benefit of maximal bowel length. The time taken to tolerate feedings appears to be independent of the number of anastomoses. Vascular anastomoses associated with monochorionic twinning may place both fetuses at risk of intestinal atresia in the event of an ischemic insult, either concurrently or with the demise of one affecting the other. Prenatal ultrasound scan appears to be useful for monitoring the evolution of intestinal atresia. However, the risks of extreme prematurity preclude the delivery of the affected baby at the time of initial diagnosis, and as yet it is unknown whether early delivery will alter the number, type, or prognosis of multiple atresias.     

Atresia of jejunum and ileum: is it the same disease?

A retrospective analysis of 21 patients with jejunal atresia and 24 with ileal atresia showed more differences than similarities between the two categories. The incidence of jejunal atresia appeared to be increasing during the period of observation (1978 to 1987). In the past 2 years, many children with jejunal atresia, who belonged to a set of heterozygotic twins, were admitted to this institution. The mean birth weight and gestational age in jejunal atresia were significantly lower than in ileal atresia. The majority of jejunal atresias were multiple, whereas most ileal atresias were single. Antenatal perforation occurred rather frequently (10 cases) in ileal atresia but only twice in jejunal atresia. The postoperative course was more often prolonged in jejunal than in ileal atresia. Mortality was higher in jejunal atresia: three deaths, all in apple peel atresia, versus one death in ileal atresia. An explanation for some of these observations can be found in a difference of compliance of the bowel wall between jejunum and ileum: the more compliant jejunal wall allows for massive dilatation with subsequent loss of peristaltic activity. It is postulated that because of the many differences, jejunal and ileal atresia may be considered as separate diseases.     

Formation of intestinal atresias in the Fgfr2IIIb-/- mice is not associated with defects in notochord development or alterations in Shh expression

PurposeThe etiology of intestinal atresia remains elusive but has been ascribed to a number of possible events including in utero vascular accidents, failure of recanalization of the intestinal lumen, and mechanical compression. Another such event that has been postulated to be a cause in atresia formation is disruption in notochord development. This hypothesis arose from clinical observations of notochord abnormalities in patients with intestinal atresias as well as abnormal notochord development observed in a pharmacologic animal model of intestinal atresia. Atresias in this model result from in utero exposure to Adriamycin, wherein notochord defects were noted in up to 80% of embryos that manifested intestinal atresias. Embryos with notochord abnormalities were observed to have ectopic expression of Sonic Hedgehog (Shh), which in turn was postulated to be causative in atresia formation. We were interested in determining whether disruptions in notochord development or Shh expression occurred in an established genetic model of intestinal atresia and used the fibroblast growth factor receptor 2IIIb homozygous mutant (Fgfr2IIIb?/?) mouse model. These embryos develop colonic atresias (100% penetrance) and duodenal atresias (42% penetrance).MethodsWild-type and Fgfr2IIIb?/? mouse embryos were harvested at embryonic day (E) 10.5, E11.5, E12.5, and E13.5. Whole-mount in situ hybridization was performed on E10.5 embryos for Shh. Embryos at each time point were harvested and sectioned for hematoxylin-eosin staining. Sections were photographed specifically for the notochord and resulting images reconstructed in 3-D using Amira software. Colons were isolated from wild-type and Fgfr2IIIb?/? embryos at E10.5, then cultured for 48 hours in Matrigel with FGF10 in the presence or absence of exogenous Shh protein. Explants were harvested, fixed in formalin, and photographed.ResultsFgfr2IIIb?/? mouse embryos exhibit no disruptions in Shh expression at E10.5, when the first events in atresia formation are known to occur. Three-dimensional reconstructions failed to demonstrate any anatomical disruptions in the notochord by discontinuity or excessive branching. Culture of wild-type intestines in the presence of Shh failed to induce atresia formation in either the duodenum or colon. Cultured Fgfr2IIIb?/? intestines developed atresias of the colon in either the presence or absence of Shh protein.ConclusionsAlthough disruptions in notochord development can be associated with intestinal atresia formation, in the Fgfr2IIIb?/? genetic animal model neither disruptions in notochord development nor the presence of exogenous Shh protein are causative in the formation of these defects.     

Pyloric atresia associated with multiple intestinal atresias and pylorocholedochal fistula

Although congenital pyloric atresia commonly occurs in isolation, it has rarely been reported in association with other alimentary tract atresias. This is a report of a newborn with congenital pyloric atresia associated with duodenal atresia, jejunal atresia, apple-peel ileal atresia, and pylorocholedochal fistula. Preoperative diagnosis was duodenal atresia because of bilious vomiting, and erect radiogram showed double bubble sign. The presented case is the first report of such an association. J Pediatr Surg 37:1223-1224.     

Atresia of the colon.

Eleven infants with colon atresia have been managed by staged procedure with survival and good health in ten. Complications have been relatively few. At the initial operation the proximal atretic segment is exteriorized as an end colostomy. Such a procedure is simple and safe, results in rapid relief of the obstruction, and permits normal feeding by mouth within a few days. At a second procedure several weeks or months later, intestinal continuity is established by an end-to-end or end-to-side anastomosis. Gastroschisis has been an associated anomaly in four of these cases. This association gives additional support to the concept that intrauterine interference to the blood supply to a segment of intestines is the etiologic factor responsible for such atresias.     

Intestinal atresias: factors affecting clinical outcomes

Background

Despite improvements in care, intestinal atresias are associated with prolonged hospitalization and occasionally mortality. Although each type of atresia is distinct, it is unclear which factors impact clinical course. This study seeks to identify predictors of untoward outcome.

Methods

Neonates with duodenal, jejunal/ileal, and colonic atresia, treated at 1 institution from 1982 to 2005 were reviewed. Data were evaluated using nonparametric analysis of variance and logistic regression. Nonparametric data were expressed as medians with interquartile range (IQR).

Results

A total of 132 infants were evaluated including 63 with duodenal, 60 with jejunal/ileal, and 9 with colonic atresias. Overall mortality was 7% with associated congenital anomalies identified as an independent risk factor (P = .01). Infants with associated anomalies were more likely to have low birth weight (2.3 ± 0.8 vs 3.0 ± 0.8 kg, P = .01), which further increased mortality risk. Atresia location did not affect mortality or length of stay; however it did impact the time to full enteral nutrition with jejunal atresia requiring longer than duodenal (17 [IQR, 9-40 days] vs 10 [IQR, 7-70 days]; P = .01).

Conclusion

Overall mortality from intestinal atresia is low and is not dependent on the location of obstruction. Infants with birth weight less than 2 kg and associated anomalies are at an increased risk for prolonged hospital stay and mortality.     

Jejunoileal atresia and associated malformations: correlation with the timing of in utero insult

PURPOSE: Duodenal atresia is associated with a higher incidence of associated congenital malformations than jejunoileal atresia, supporting the hypothesis that the duodenal obstruction occurs early in fetal life. In this study, the authors analyzed the incidence of major associated malformations in jejunal atresia (JA) and ileal atresia (IA) to determine if there is a positive correlation between the proximity of the intestinal atresia and the association of other major anomalies. METHODS: Records of all patients with jejunoileal atresias treated at the authors' institution between 1980 and 1997 were examined. RESULTS: There were 83 patients with jejunoileal atresias, 38 with JA, and 45 with IA. Sixteen (42%) of the JA patients had an associated major congenital malformation, whereas only 1 (2%) of the IA patients had an associated malformation. A single atresia was found in 18 (47%) of JA patients and 41 (91%) of IA patients. Twenty (53%) of the JA patients had either multiple or apple-peel atresia. Thirteen patients (16%) died, 11 with JA, and 2 with IA. Of the 11 patients with JA who died, 6 had multiple atresias, 4 had cystic fibrosis, and 1 had small bowel volvulus. CONCLUSION: The higher incidence of associated major congenital extraintestinal malformations in JA compared with IA patients suggests that some cases of JA may arise from a malformative process.     

Mechanical compression with secondary ischemia as a possible cause of atresias associated with omphalocele

We report 2 cases of omphalocele associated with intestinal atresia. In the context of this unusual sequence, we discuss the etiopathogenesis of intestinal atresias in association with tight abdominal wall defects.     

Duodenal and small intestinal atresias and stenosis

Intestinal atresias and stenoses are common causes of intestinal obstruction in the neonate. The diagnosis and treatment of the various types of intestinal atresia are discussed. The aetiology, associated anomalies, presentation, surgery and postoperative care differ depending on the site of the lesion.     

Individualized management of colonic atresia

Atresia of the colon represents the least common cause of neonatal intestinal obstruction, comprising less than 10 percent of gastrointestinal atresias. Eleven patients underwent surgical repair of colonic atresia during a 5 year period. Five of the patients were premature. Two had associated gastroschisis and other congenital anomalies were present in three patients. Hypaque enema was utilized to diagnose intestinal atresia and laparotomy was then undertaken. Primary repair could be performed in four patients, one with type I and three with type 3 atresias. These four patients did well and were discharged within 13 days after operation. Three deaths occurred in patients with associated anomalies, yielding a mortality rate of 28 percent. Operative therapy of colonic atresia should be individualized, based on the condition of the patient at presentation and the presence of associated birth defects.     

Intestinal atresia with gastroschisis: a selective approach to management

BACKGROUND: The association of bowel atresia with gastroschisis is well recognized, but the ideal management is less certain. METHODS: The records of 10 infants with gastroschisis and intestinal atresia treated between 1991 and 1997 in a single neonatal surgical unit were reviewed. RESULTS: Ten infants had midgut atresias: 5 small intestine, 1 jejunum and colon, and 4 colonic. Of the 6 with small bowel atresias, 4 had primary abdominal wall repair with electively delayed primary anastomosis at 21 to 46 days, 1 had decompressing tube jejunostomy at 11 days at the time of secondary abdominal closure, and 1 initial jejunostomy. Of the 4 with colonic atresia alone, 3 had perforation or infarction of the proximal colon at birth, 2 had a primary stoma, and 2, who did not have initial colostomy or anastomosis, required reoperation for increasing abdominal distension at 11 and 23 days. Complications were recorded in 6 patients: 2 had necrotizing enterocolitis after which 1 developed malabsorption, 1 had distal bowel obstruction after delayed primary anastomosis treated with a Bishop-Koop ileostomy at 50 days, 2 had stoma stenosis, and 1 had stoma prolapse. None died, and at 1 year 9 were within the normal range for body weight, and details of 1 are not known. CONCLUSIONS: At birth, diagnosis of atresia often is uncertain, and the bowel is difficult to repair or exteriorize. For proximal atresias, delayed primary repair is a safe satisfactory approach. At birth, distal atresias are more obvious, often complicated by perforation or infarction, and may benefit from early enterostomy.     

Vertebral anomalies associated with esophageal atresia and tracheoesophageal fistula with reference to the initial operative mortality

In a series of 40 patients with esophageal atresia and tracheoesophageal fistula, the incidence of musculoskeletal anomalies was 45% (18 patients). An extra mesodermal segment was found in 15 patients (13 paired thoracic vertebrae and 13 paired ribs in nine patients; six lumbar vertebrae in 6 patients). The mortality in grade A infants with an extra mesodermal segment was significantly higher than in those infants with a normal spine (p > 0.01). It is suggested that segmentation or abnormal segmentation of the embryo may be important as a cause of esophageal atresia.     

Congenital multiple intestinal atresia successfully treated with multiple anastomoses in a premature neonate: Report of a case

We report herein the case of a 2080-g premature male infant born at 34 weeks' gestation with multiple intestinal atresia, for whom multiple anastomoses were successfully performed. A total of 11 atresias were found in the small bowel, and five anastomoses were performed to preserve 59cm of small bowel and the ileocecal valve. Postoperatively, he developed several episodes of sepsis caused by persistent enterostasis, but was able to be weaned from total parenteral nutrition (TPN) by postoperative day (POD) 106. Thus, multiple anastomoses may be the appropriate procedure to prevent short-gut syndrome for congenital multiple intestinal atresia, even in premature infants.     

Portal decompression by interposition mesocaval shunt in patients with biliary atresia

Surgical correction of portal hypertension in infants and children has often been frustrated by limitations imposed by the diminutive vessel size. During the past 18 mo, five patients from 1 to 7 yr of age and weighing between 9 and 19 kg, have required portal decompression for bleeding from esophageal varices. In two patients, a previous dissection in the area of the porta hepatis imposed a further technical obstacle. Both of these patients had biliary atresia and one had undergone a successful portoenterostomy (Kasai).¹ Success of the interposition mesocaval graft in adult patients led us to adopt this procedure in our five patients. Autogenous jugular vein was utilized for construction of the shunt in the smaller patients. Radiographic confirmation of shunt patency has been obtained 1 yr postoperatively.     

Multiple gastrointestinal atresias in three consecutive siblings: observations on pathogenesis

Three consecutive siblings with innumerable membranous gastrointestinal atresias, beginning at the prepyloric region and ending in the rectum, are reported. Microscopic examination of the small and large intestine showed multiple, tiny lumina each surrounded by a separate mucosa and muscularis mucosae but by a single muscular layer at the periphery. The pathological findings and hereditary character of these atresias suggest that a defect in recanalization during a solid stage of development involving the whole of the gastrointestinal tract may be the cause of these atresias.     

Midgut atresias result from abnormal development of the notochord in an Adriamycin rat model

Background/Purpose: Prenatal exposure to Adriamycin in a rat model (ARM) has been reported to lead to a spectrum of tracheoesophageal and associated malformations of the gastrointestinal tract, including multiple intestinal atresias. An abnormal relationship of the notochord with the foregut has been implicated in the formation of esophageal atresias. The authors hypothesised that midgut atresias arise from abnormal notochord development in the region of the midgut. This study was designed to examine the gut-notochord relationship during early embryonic development. Methods: Timed pregnant Wistar rats were given 1.75 mg/kg of Adriamycin intraperitoneally on days 7, 8, and 9 of gestation. Embryos were recovered at 12-hour intervals from days 9.5 to 14, and at term. A control group was given saline instead of Adriamycin. Embryos were embedded in resin or wax, sectioned, and studied using light microscopy, paying particular attention to the notochord and surrounding structures. Results: The notochord appeared identical in controls and experimental embryos on day 9.5. However, on day 10.5 the notochord was diffusely abnormal in ARM, distorted, and tethered to foregut as well as midgut compared with controls. This abnormality was not seen in control embryos. On day 12 the notochord abnormalities were more exaggerated in the region of the midgut in ARM embryos. Full-term ARM animals had esophageal and multiple intestinal atresias. Conclusions: The notochord is abnormal in the region of the developing midgut, and this may account for the occurrence of atresias found in this region.