Small Intestinal Atresia and Stenosis

The pathophysiology of duodenal stenosis and atresia differs from that of obstructions located more distally in the jejunoileal area; the importance of this difference cannot be overstated. In duodenal atresias, a failure of recanalization of intestinal tube occurs at 8-10 weeks' gestation after obliteration of the lumen by epithelial proliferation at 6-7 weeks; it usually occurs in the second part of the duodenum. Incomplete recanalization can lead to duodenal stenosis or the presence of a duodenal web. ^{[4, 5]}

In jejunoileal atresias, however, the underlying process is an ischemic injury to the gut, usually secondary to malrotation with volvulus or intestinal strangulation with the umbilical ring, intestinal perforations, or vasoconstrictive drugs (eg, cocaine, ephedrine, and nicotine). Jejunoileal atresias occur after intestinal development because of the presence of bile droplets, meconium, or lanugo distal to the atresia. ^[6]

Dalla Vecchia et al performed a 25-year retrospective review and found 277 neonates with intestinal atresia. ^[7] The level of obstruction was duodenal in 138 patients, jejunoileal in 128, and colonic in 21. Of the 277 neonates, 10 had obstruction at more than one site. Jejunoileal atresia was associated with intrauterine volvulus (27%), gastroschisis (16%), and meconium ileus (11.7%).

In atresias of the small intestine, the jejunum and ileum are equally affected. ^{[8, 9]}  The proximal jejunum is the site of atresia in 31% of cases, the distal jejunum in 20%, the proximal ileum in 13%, and the distal ileum in 36%. In more than 90% of patients, the atresia is single; however, multiple atresias are reported in 6-20% of cases. ^[10]

Stollman et al published a large series of jejunoileal atresias as a retrospective review at a large pediatric referral center in the Netherlands. ^[11] Between 1974 and 2004, they found 114 infants with jejunoileal atresia. In all, 62% of atresia and stenosis cases were noted in the jejunum, 30% in the ileum, and 8% in both the jejunum and the ileum; 7% of patients had intestinal stenosis, 16% had type I atresia, 21% had type II, 24% had type IIIa, 10% had type IIIb, and 22% had type IV (see Classification below).

Heij et al performed a retrospective analysis of 21 patients with jejunal atresia and 24 with ileal atresia and found more differences than similarities between the groups (see Table 1 below). ^{[12, 13, 14, 2, 15]}

Table 1. Differences Between Jejunal and Ileal Atresia ^{[12, 13, 14, 2, 15]} (Open Table in a new window)

In this analysis, mean birth weight and gestational age were significantly lower in patients with jejunal atresia than in those with ileal atresia. ^[12] Most jejunal atresias were multiple, whereas most ileal atresias were single. Antenatal perforation was frequent (10 cases) in ileal atresia but infrequent (two cases) in jejunal atresia. The postoperative course was often prolonged, and mortality increased in patients with jejunal atresia, three of whom died (all of them patients with apple-peel deformity); by comparison, one patient with ileal atresia died.

Heij et al suggested that some of their findings may be explained by a difference in bowel-wall compliance between the jejunum and the ileum. ^[12] The compliant jejunal wall allows massive dilatation with subsequent loss of peristalsis, accounting for the prolonged postoperative course and the relatively high rate of perforation in ileal atresia.

Classification

Duodenal atresias have several basic morphologies, as follows:

• Type I atresias constitute luminal webs or membranes, some of which contain a central defect or fenestration of variable size, and result in a marked size discrepancy with mural continuity
• Type II atresias have dilated proximal and diminutive distal segments connected by a fibrous cord
• Type III atresias are characterized by a complete discontinuity between the segments

The relation between the point of obstruction and the ampulla of Vater is important. Most series document a predominance of postampullary obstructions. Obstructions caused by type I membranes are frequently associated with anomalies of the common bile duct (CBD) in which the CBD may terminate within the membrane itself. ^[16]

The maximal dilatation of the proximal segment occurs at the point of obstruction. This segment is commonly aperistaltic, of questionable viability, or both. ^[3] Grosfeld et al modified Louw’s original classification into the following description of intestinal atresia, which is currently the most commonly used classification scheme ^[9] :

• Type I – Membrane
• Type II – Blind ends joined by fibrous cord
• Type IIIa – Disconnected blind end
• Type IIIb – Apple-peel deformity
• Type IV – Multiple, string of sausages

Stenosis

The proximal dilated intestine is in continuity with the distal nondilated bowel, and the mesentery is intact. Between these portions, a narrow, semirigid segment with a minute lumen is present. The small-bowel length is normal. This lesion might simulate a type I atresia (see the image below).

Atresia type I

Type I is a mucosal (septal) atresia with an intact bowel wall. The proximal dilated intestine is continuous with the distal narrow one. The mesentery is intact, and the intestinal length is normal. The pressure generated on the internal membrane may elongate it as a windsock, giving a conical appearance to the transition. The distal intestine is collapsed (see the image below) but may contain meconium.

Atresia type II

In type II, a fibrous cord separates the proximal bowel from the distal segment. The mesentery is usually intact, but a small V-shaped defect may be present. Intestinal length is normal. The proximal blind pouch is grossly dilated, often aperistaltic and cyanotic. Perforations may be noted in patients who present late. Dilatation usually extends 10-15 cm proximally, after which point the intestine appears relatively normal. The distal blind pouch may be mildly distended because of retained cellular debris (as in fetal intussusception) (see the image below).

Atresia type IIIa

Type III atresias seem to be the most common. ^{[8, 17]} Intrauterine resorption of fetal gut subjected to a vascular insult explains the reduced bowel length commonly seen in this type of atresia. The distal bowel is small and decompressed.

In type IIIa atresia, the two blind ends are completely separated without a fibrous cord between them. The atresia has a V-shaped mesenteric gap, and the intestine is shortened (see the images below). The proximal dilated pouch may have questionable viability and undergo torsion.

Atresia type IIIb

In type IIIb atresia (Christmas-tree or apple-peel deformity), the two intestinal segments are separated as in type IIIa, and the mesenteric defect is large. The proximal atretic segment is in the upper jejunum, near the ligament of Treitz; the pouch is distended and lacks dorsal mesentery. The superior mesenteric artery distal to the middle colic branch is absent. The collapsed distal intestine helically encircles a small vessel (marginal artery) arising from the ileocolic or right colic arcades, or the inferior mesenteric artery, and its vascularity may be impaired.

Type I and type II atresias may coexist in the distal segment. The intestine is always substantially shortened (see the image below). Many patients with this variant have low birth weight (70%) and were born premature (70%); they may also have malrotation (54%), multiple atresias, and an increased number of other associated anomalies that raise the prevalence of complications (63%) and increase the mortality (54-71%). ^{[18, 19]}

Atresia type IV

Type IV atresia refers to any number and combination of type I, II, or III atresias that present simultaneously, creating a string-of-sausages appearance (see the image below). A possible cause is intrauterine inflammation. However, findings of this type of atresia in family members suggest possible autosomal recessive transmission. ^{[20, 10, 21]}

The presence of multiple GI atresias with cystic dilatation of the bile duct is rare; the association has been described in only a few dozen patients, with no recorded survivors in the world literature. ^{[22, 23]} The dilatation of the bile duct seems to be due to normal drainage of bile into a closed-loop duodenal obstruction. Patients present with multiple atresias and die of short-bowel syndrome and complications related to total parenteral nutrition (TPN).

Intrinsic duodenal obstructions and anular pancreas result from events that occur during early development of the foregut. Duodenal atresia and stenosis are believed to result from a failure of recanalization of the embryonic duodenum, which becomes solid as a result of early epithelial proliferation.

Anular pancreas occurs when the ventral pancreatic bud fails to rotate behind the duodenum, leaving a nondistensible ring of pancreatic tissue fully encircling the second portion of the duodenum. It frequently coexists with intrinsic duodenal anomalies and anomalies of the pancreaticobiliary ductal system, suggesting closely linked mechanisms of pancreatic, duodenal, and biliary development during this stage. ^[16]

That associated congenital malformations are more prevalent with duodenal atresia than with jejunoileal atresia suggests that proximal obstructions occur earlier in fetal life. ^{[7, 24]}

Unlike duodenal atresias, many jejunoileal atresias are separated by a cordlike segment or a V-shaped mesenteric gap. This finding and the usual finding of bile pigments and lanugo distal to the atretic segment indicate that an in-utero vascular accident occurring relatively late in gestation (>11-12 wk) is the likely origin of these atresias, rather than failure of GI tract recanalization. A localized intrauterine vascular accident with ischemic necrosis of the bowel and subsequent reabsorption of the affected segment has been the favored theory. ^{[25, 1, 3, 26]}

De Chadarevian et al reported on an infant with inherited thrombophilia that created a hypercoagulable state, favoring a segmental intestinal thrombosis and resulting in terminal ileal atresia. ^[27] This patient was also found to have Hirschsprung disease, which is rarely associated with intestinal atresia.

The localized nature of a vascular insult explains the low (10%) prevalence of coexisting conditions. Intestinal atresia associated with in-utero intussusception or perforation, malrotation, volvulus, internal hernias, gastroschisis, and omphalocele further corroborates a vascular event as the etiology of most jejunoileal atresias. ^{[28, 26, 29, 30]}

Only one case of a newborn patient has been reported to date with multiple intestinal atresias associated with multifocal angiodysplasia of the intestinal wall. ^[31]

Sweeney et al examined 38 patients with jejunal atresia and 45 patients with ileal atresia at the Children's Research Center in Dublin, Ireland. ^[24] Compared with patients with ileal atresia, patients with high jejunal atresia had a higher rate of associated congenital malformations (42% vs 2%), a higher rate of multiple or apple-peel (type IIIb) atresias (53% vs 9%), and a higher mortality. These results suggest that jejunal atresia may also develop from a malformative process.

In a collaborative study in France, Gaillard et al reviewed 102 cases from 42 induced abortions and 22 stillborns, as well as surgical findings in 38 neonates. ^[32] Abnormalities such as meconium ileus (associated with cystic fibrosis) and chromosomal aberrations (eg, Down syndrome) were present during the second trimester of gestation. Intestinal atresia and stenosis were detected in the third trimester of pregnancy and were associated with ischemic conditions.

Although most infants have only one atretic segment, multiple atresias have been described in infants of mothers who ingested ergotamine and caffeine or pseudoephedrine (alone or with acetaminophen) during pregnancy. ^{[33, 34]} Other vasoconstrictive factors (eg, cocaine abuse and smoking during pregnancy) have also been linked with increased risk for intestinal atresia. ^[34] The risk is also higher in patients with graft-versus-host disease and immunosuppression and those with malformative processes that are likely due to autosomal recessive transmission. ^{[35, 21]}

Multiple intestinal atresias have been reported in rare association with pyloric atresia and pylorocholedochal fistula. ^[36]

In a study of 114 cases of jejunoileal atresia in the Netherlands, Stollman et al found other GI anomalies in 24% of patients, genitourinary malformations in 9%, cystic fibrosis in 9%, neurologic anomalies in 6%, and congenital heart disease in 4%. ^[11]

Duodenal obstructions of congenital origin are often associated with other congenital anomalies, which account for most of the morbidity and mortality in these patients. Various publications report a 50-80% incidence of associated conditions. Congenital heart disease and trisomy 21 ^[37] are the most common of these associated conditions, each occurring in about 30% of cases. ^[38] All three conditions may coexist in the same patient. ^[39]

In a study of patients with trisomy 21 who underwent antenatal ultrasonography (US), about 4% showed antenatal evidence of duodenal atresia. ^[40] Other associated anomalies include intestinal malrotation (20%), esophageal atresia, ^[41]  imperforate anus (10-20%), thoracoabdominal heterotaxia, and gallbladder agenesis.

One of the most important factors to keep in mind is that in duodenal atresia, as in other neonatal diseases, the outcome for patients depends more on the severity of the associated anomalies and the ease with which they can be corrected than on the surgical management of the obstruction itself. ^[16]

Familial cases of various types of atresia have been described. ^[42] In one family, familial type I jejunal atresia affected three members from two generations. Proximal atresia was associated with renal dysplasia. Knowledge of the familial form of the disease indicates that most cases of jejunoileal atresia actually result from disruption of a normal embryologic pathway, most likely the development of the superior mesenteric artery and its branches. They should be considered to be true embryologic malformations rather than acquired lesions. ^[42]

This association is presumably an autosomal dominant condition. ^[22] Matsumoto et al reported a case in Japan and reviewed the literature, finding six other cases of small intestinal atresia occurring in twins. ^[43] All published cases except one involved identical twins. Three pairs of twins had different types of atresia, and four pairs had no other anomalies. The other members of these families were not affected; this finding suggested that such cases may be due to environmental influences during gestation.

Another report of different intestinal atresias in identical twins suggested them to be either the consequence of linkage of two genes or a pleiotropic expression of a single gene. ^[44]

Congenital duodenal obstruction may be complete or partial, intrinsic or extrinsic. Intrinsic obstruction occurs in about 1 of 7000 live births and accounts for about half of all small-bowel atresias. Extrinsic obstruction has many causes, including malrotation with Ladd bands, other congenital bands not associated with malrotation, ^[45] preduodenal portal vein, gastroduodenal duplications, cysts or pseudocysts of the pancreas and biliary tree, and anular pancreas (which is commonly associated with a duodenal web, an intrinsic cause of duodenal obstruction ^[16] ).

In West Africa, intestinal atresia is the fourth most common cause of neonatal intestinal obstruction, after anorectal malformations, Hirschsprung disease, and strangulated inguinal hernias. ^[46] In an 11-year retrospective review of 500 children in India, Ranan et al found intestinal atresias to be the most common cause of intestinal obstruction in newborns and the second most common cause (11.8%) after intussusception (20.8%) in all age groups. ^[47]

Boys and girls are equally affected. ^[8] In most studies, jejunoileal atresias seem to be more common than duodenal atresias, and colonic atresias account for the fewest cases.

Unlike duodenal atresia, jejunoileal atresia associated with Down syndrome is uncommon. Patients with intestinal atresia are epidemiologically characterized by young gestational age and low birth weight. In addition, the atresia is associated with twinning, the parents are more often consanguineous compared with parents of healthy neonates, and vaginal bleeding frequently complicates the pregnancies.

No correlation between jejunoileal atresia and parental age or disease has been proved. ^{[14, 13, 2]} However, one study from France reported an increased prevalence of intestinal atresias in infants born to teenagers. ^[14] Some maternal infections may be associated with ileal atresia. ^[13]

Before the mid-20th century, the mortality associated with small-bowel atresias was prohibitive (>90%). By the late 1950s, the survival rate had risen to 78%. Survival rates improve with distal atresias, whereas mortality is high in instances of multiple atresia (57%); apple-peel deformity (54-71%); and atresias associated with meconium ileus (65%), meconium peritonitis (50%), or gastroschisis (66%). ^{[18, 4, 19, 26]}

Overall survival rates (including preterm babies) have reached 90%, with a surgical mortality of less than 1%. ^{[18, 7, 19]}  Mortality is related to sepsis, associated anomalies, prematurity, malrotation, meconium peritonitis, and long-term TPN complications in patients with short-bowel syndrome.

The most common cause of death in infants with jejunoileal atresia is infection related to pneumonia, peritonitis, or sepsis. ^[8]  Sato et al reported on an infant with ileal atresia and meconium peritonitis after a perforation who presented with pylephlebitis (air in the portal system) and a pulmonary gas embolism. ^[48]  The patient had respiratory distress, shock, disseminated intravascular coagulation, and intractable diarrhea but eventually recovered and was discharged from the hospital after 4 months.

The most important surgical complications are anastomotic leaks and functional obstruction at the level of the anastomosis; these occur in as many as 15% of patients. ^{[8, 17]}  In 84 patients with congenital jejunoileal or colonic atresia who were treated in New South Wales, Australia, mortality was higher in infants who underwent stoma formation than in those who received a primary anastomosis. ^[49]  Reoperation may be required to prevent complications. ^[50]

Short-bowel syndrome refers to a spectrum of malnutrition problems that result from inadequate bowel length, which may occur in patients born with multiple atresias or in those with the apple-peel deformity. It is a cause of intestinal failure, together with other congenital diseases of enterocyte development, and severe motility disorders (total or subtotal aganglionosis or chronic intestinal pseudo-obstruction syndrome). ^[51]  Other common causes of short-bowel syndrome include necrotizing enterocolitis and midgut volvulus. ^[52]

Of the 114 patients involved in the study by Stollman et al, 28% developed early postoperative complications, whereas 17% experienced late postoperative complications; mortality was 11%. ^[11]  Short-bowel syndrome seems to be the biggest problem, resulting in longer hospital stay, more feeding problems, and higher morbidity and mortality.

Today, the survival rate for patients with short-bowel syndrome is 80-94%. The presence or absence of the ileocecal valve appears not to affect mortality but does affect the length of time for which TPN is required and thus affects the complications related to its use (eg, predisposition to infection, central line sepsis, and TPN-related cholestasis). ^[7]  Malabsorption and steatorrhea are most severe in patients with terminal ileal resection, particularly when the ileocecal valve is excised. Vitamin B supplements are useful in such patients.

Overall mortality due to intestinal atresia does not seem to depend on the location of obstruction. Prematurity, birth weight less than 2 kg, and associated anomalies are independent risk factors for prolonged hospital stay and higher mortality. ^{[53, 54]}

A study comparing postoperative outcomes of 50 patients with complete congenital duodenal obstruction (CCDO; n = 27) or incomplete congenital duodenal obstruction (ICDO; n = 23) found that outcomes in these two groups differed greatly. ^[55] The overall antenatal detection rate of CDO was 49%; however, the rate for CCDO was significantly higher than that for ICDO (88% vs 4%). Despite the high detection rate, the CCDO group was significantly associated with the following:

• Lower gestational age at birth
• Lower age and weight on operation
• Higher rate of associated congenital heart disease (CHD)
• More extensive preoperative radiologic diagnostics
• Higher morbidity according to Clavien-Dindo classification
• Higher comprehensive complication index

In addition, CCDO patients had a longer hospital stay that was associated with more adverse events. ^[55] On the other hand, patients with ICDO often experienced considerable delays in diagnosis and operative repair of their congenital malformation. Although this study focused specifically on postoperative outcomes of CCDO and ICDO, it also identified important factors during the antenatal and postnatal periods that could have a significant impact on prognosis.

Lack of sufficient residual bowel is responsible for considerable morbidity or a poor quality of life. In most instances, maximal intestinal adaptation occurs within 6-12 months, but it may take longer. ^[26]  The use of the longitudinal intestinal lengthening and tailoring (LILT) procedure, proposed by Bianchi and modified by Aigrain, can allow the child to be weaned from parenteral nutrition. ^[56]

As a consequence of advances in medical care, such as improved surgical techniques and parenteral nutrition, the survival of neonates with intestinal atresias improved dramatically in the 20th century. ^[57]

The presence of multiple intestinal atresias necessitates repeated surgical interventions and sometimes small-bowel transplantation; the development of short-bowel syndrome in these patients is associated with increased risk of cholestasis, liver cirrhosis, and hepatic failure. The prognosis is poor, with most infants dying early in life. ^[58]  Patients with this condition often have immunodeficiency. ^[59]  Thymic dysplasia and lymphoid depletion are key findings in patients with mutations in the TTC7A gene who have multiple intestinal atresias.