Treatment

The management of bowel obstruction from malrotation or an internal hernia is operative. Initial

assessment, resuscitation, and preoperative preparation in a symptomatic newborn should be conducted

simultaneously so that confirmation of malrotation can be followed immediately by laparotomy. Urgent

laparotomy is required to reduce the ischemic injury to the intestine. Shock, if present, must be treated

aggressively by insuring adequate gas exchange and establishing restoration of intravascular volume

prior to the induction of general anesthesia. Volvulus with complete infarction of the midgut, if not

immediately lethal, is survivable only with enterectomy, followed by permanent or long-term TPN

support. In older, asymptomatic children with incidentally discovered malrotation, operative repair

remains controversial. Given the devastating consequences of midgut volvulus, however, elective

surgical correction appears warranted in most asymptomatic individuals as well.

Operative repair of malrotation is performed by Ladd procedure.107 The first objective is to relieve

the midgut volvulus, if present. This is accomplished by delivery and detorsion of the affected midgut,

usually in a counterclockwise direction. Recurrent volvulus is prevented by broadening the base of the

mesenteric vascular pedicle by dividing the peritoneal bands that tether the cecum, small bowel

mesentery, mesocolon, and duodenum around the base of the SMA (Fig. 103-30). Once completed, the

mesentery and the mesocolon open widely and the mesenteric pedicle is at low risk for recurrent

volvulus.

Figure 103-29. A: Plain radiograph of an infant with malrotation. There is a paucity of small bowel gas. B: Upper gastrointestinal

contrast study demonstrating malrotation with midgut volvulus and duodenal obstruction. The position of the duodenojejunal

junction is abnormal. C: Plain film showing a contrast-filled colon and cecum on the patient’s left (asterisks). The entire small

bowel is to the right of midline. These are typical radiographic findings of malrotation.

The second objective of Ladd procedure is to divide the abnormal peritoneal attachments between the

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cecum and the abdominal wall. A modified Kocher maneuver involving meticulous and complete

mobilization of the entire duodenum with division of all anterior, lateral, and posterior attachments is

performed. Duodenal and distal small bowel patency should be demonstrated using intraluminal air or

saline because synchronous intestinal webs and atresia have been reported. An appendectomy is

performed to eliminate potential confusion from acute appendicitis developing in an abnormally

positioned appendix. Performance of laparoscopic Ladd procedure has been demonstrated to be feasible

and may help reduce time to enteral feeding and hospital length of stay; however, the long-term

efficacy of this approach has been debated.108 Fixation of the mesentery by cecal or duodenal plication

to the body wall has been abandoned for lack of data supporting efficacy. Postoperative small bowel

obstruction secondary to adhesions is reported in about 10% of patients.

Volvulus with intestinal necrosis is treated by preserving as much bowel length as possible. If bowel

viability is unclear during initial exploration, a second-look procedure may be helpful to delineate

reversible from irreversible injury. The management of nonviable bowel from volvulus is not different

from other situations in which intestinal necrosis is encountered, and clinical decisions regarding

resection and anastomosis are individualized. In situations in which the entire small intestine is lost and

long-term survival is doubtful, treatment decisions must be made with the family.

Surgical management of right mesocolic hernia is directed at dividing the lateral peritoneal

attachments of the cecum and right colon to eliminate the hernia. In addition, given the associated

nonrotation of the proximal bowel, the vascular pedicle should be broadened as much as possible. Left

mesocolic hernia is treated by mobilization of the inferior mesenteric vein, reduction of the small bowel

from the hernia sac, and closure of the neck of the hernia sac to eliminate the potential space.

Results and Complications

Results following surgical correction of intestinal rotational abnormalities should be excellent, and life

expectancy should be normal in the absence of intestinal necrosis. Recurrent volvulus and recurrent

duodenal obstruction are distinctly unusual if the initial procedure is technically complete. Adhesive

small bowel obstruction following Ladd procedure is reported in 1% to 10% of patients. Long-term

outcome is obviously less favorable in patients with intestinal necrosis at the time of exploration.

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Figure 103-30. Correction of malrotation. A,B: Detorsion of midgut. C,D: Division of peritoneal attachments (Ladd bands) of

cecum to abdominal cavity.

Congenital Aganglionosis (Hirschsprung Disease)

Embryology

5 Congenital aganglionosis of the intestine (Hirschsprung disease) is characterized by the absence of

intestinal ganglion cells. The pathogenesis of aganglionosis remains unknown. In normal development,

neuroblasts derived from neural crest precursors become evident by week 5 of gestation. The

neuroblasts begin maturation and caudal migration along with vagal nerve fibers. The initial caudal

migration in an intermuscular plane is followed by intramural dispersal into both superficial and deep

submucosal nerve plexuses. Ultimately, the neuroblasts give rise to the ganglion cells of the myenteric

nervous system, with functional maturation continuing well into infancy. The orderly migration

pathway of myenteric innervation has been documented in human embryos; normally, ganglion cells

can be identified in the esophagus at week 6 of gestation, in the transverse colon at week 8 of gestation,

and in the rectum by week 12 of gestation.109

Anatomy

Hirschsprung disease is characterized by a lack of ganglion cells in the distal intestine. The length of

aganglionosis is variable but most commonly involves the distal rectosigmoid colon in 75% to 80% of

affected infants. In about 5% of cases, the transition zone between the normal, proximal bowel and the

distal, aganglionic segment occurs in the small intestine.110 Discontinuous aganglionosis has been

reported but should be considered distinctly unusual. Therefore, in virtually all cases, the aganglionic

intestinal segment is continuous with the distal rectum to the anal verge and also includes the internal

sphincter. Because of this distribution, the pathogenesis of congenital aganglionosis is often attributed

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to failure of neuroblast migration. The characteristic lesion in the distal bowel is the aganglionosis in

the intermuscular and submucosal plexuses. Large, hypertrophied, nonmyelinated nerve fibers are

present within the muscularis mucosa, lamina propria, submucosa, and Auerbach intermuscular plexus.

Both adrenergic and cholinergic fibers are prominent in the aganglionic segment, and

acetylcholinesterase staining is useful diagnostically. Abnormalities in the peptidergic nervous system,

including vasoactive intestinal peptide, substance P, and neurotensin immunoreactive fibers, are also

described in the aganglionic bowel segment.111 Deficient neuronal nitric oxide synthase mRNA and

subsequent decreased local nitric oxide synthase activity in the aganglionic bowel have also been

described.112 These experimental data are consistent with the concept that a defect in nitric oxide–

mediated smooth-muscle relaxation may account for some of the characteristic clinical features of

Hirschsprung disease.

The transition zone between the normal, proximal bowel and the aganglionic distal bowel is

distinguished grossly by distention of the proximal bowel with histologic evidence of muscular

hypertrophy. The transition zone often becomes evident to direct inspection or on contrast enema

during the first few weeks of life as functional obstruction leads to progressive proximal dilatation. On

gross inspection, the transition zone may appear as a short funnel or cone-shaped colonic segment. The

discrepancy in bowel lumen diameter is somewhat age dependent and may be subtle in a newborn or in

a child with total colonic aganglionosis. Therefore, it may be difficult for the surgeon or the radiologist

to define the exact transition zone site based on gross inspection or contrast enema. Gross examination

alone is not sufficient for surgical decision making, and histologic confirmation of the level of ganglion

cell transition is required. Given the continuous nature of aganglionosis, a rectal biopsy performed 1 to

1.5 cm above the dentate line demonstrating ganglion cells effectively excludes Hirschsprung disease.

Neuronal intestinal dysplasia is a clinically described entity similar to or associated with Hirschsprung

disease.113,114 Despite the presence of ganglion cells, dysplastic changes in the myenteric nervous

system affect bowel motility in similar fashion to aganglionosis. Clinical presentation and treatment are

similar to those of classic Hirschsprung disease. There is considerable controversy regarding neuronal

intestinal dysplasia, but it is reasonable to suggest that this represents an entity within the spectrum of

abnormalities found in the intestinal myenteric nervous system.

Pathophysiology

Normal intestinal motility depends on coordinated propagation of segmental contraction waves

immediately preceded by relaxation of the enteric smooth muscle. Patients with Hirschsprung disease

lack a functional myenteric nervous system in the aganglionic segment; therefore, both propulsion and

reflexive relaxation are disordered or absent in the distal bowel. Loss of neuronal nitric oxide synthase

activity appears to play an important role. The internal sphincter is aganglionic and lacks the normal

reflexive relaxation following rectal distention. In fact, patients with Hirschsprung disease may exhibit a

paradoxical increase in sphincter tone in response to rectal distention. The functional result is tonic

contraction of the aganglionic segment of bowel with ineffective peristalsis. Clinically, this presents as

incomplete, distal intestinal obstruction in the newborn or as chronic constipation in the older child or

adult.

Hirschsprung disease has been associated with mutations in at least three specific genes: the RET

protooncogene, the endothelin B receptor (EDNRB) gene,115 and the endothelin 3 (EDN3) gene. In

addition, several other candidate genes are under investigation. In mice, natural and in vitro induced

mutations affecting the RET, EDNRB, and EDN3 genes generate intestinal aganglionosis identical to

Hirschsprung disease.116,117 Although widely accepted, it is still unknown whether the primary event in

aganglionosis is failure of neuroblast migration to the distal bowel. Alternatively, ineffective

microenvironmental support of neuroblasts that have already migrated may fail to promote normal

neuroblast development and survival.118

Clinical Features

Incidence and Associations. The incidence rate of Hirsch-sprung disease is estimated at 1 per 5,000

live births with a marked male-to-female (4:1) preponderance. Most cases are sporadic, but longsegment, total colonic aganglionosis and female gender are strongly associated with familial

inheritance. Genetic chromosomal analysis suggests that multiple loci may be involved, including

chromosomes 13q22, 21q22, and 10q, among others.119 Familial Hirschsprung disease has been clearly

associated with RET protooncogene mutations. From a clinical standpoint, mutations of the RET

protooncogene are associated with disorders of neural crest development, namely, multiple endocrine

neoplasia (MEN) types IIA and IIB as well as familial medullary thyroid carcinoma, and patients with

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familial Hirschsprung disease associated with RET mutation are at risk for the development of

medullary thyroid carcinoma.120 Congenital cardiac defects are present in 2% to 5% of patients with

Hirschsprung disease. Other rare congenital anomalies have been reported, but a consistent and

important association is a 5% to 15% incidence of trisomy 21.108 Infants presenting with meconium plug

syndrome should undergo rectal suction biopsy to exclude aganglionosis.

Presentation. Most infants with Hirschsprung disease fail to pass meconium within the first 24 to 48

hours of life. Nonspecific signs of neonatal intestinal obstruction (feeding intolerance, abdominal

distention, and bilious emesis) may develop. About half of the patients with Hirschsprung disease are

diagnosed as neonates. Infrequently, older children or adults are diagnosed with aganglionosis during

evaluation for chronic constipation. In this setting, symptoms may be minimal to disabling, and parents

or patients often develop elaborate strategies to deal with chronic constipation. Abdominal distention is

characteristic, and sometimes failure to thrive and malnutrition may occur. Digital rectal examination

may demonstrate spasm, and, in the presence of enterocolitis, forceful expulsion of foul-smelling, liquid

stool may occur.

Enterocolitis occurs in about 10% to 30% of infants and children with Hirschsprung disease and may

be the presenting clinical manifestation. Enterocolitis associated with Hirschsprung disease has an

unknown pathophysiology, but obstructive stasis and bacterial overgrowth are thought to be important

factors. Clostridium difficile and rotavirus have been implicated as important pathogenic organisms;

diagnostic and treatment plans should consider these possibilities. The early presenting symptoms and

signs of enterocolitis include fever, abdominal distention, and diarrhea, which may be explosive, foul

smelling, and bloody. Systemic sepsis, transmural intestinal necrosis, and perforation are all possible

later findings. The clinical progression can be rapid, with death occurring in as few as 12 to 24 hours if

treatment is not initiated. Infants are particularly vulnerable to this complication and enterocolitis

accounts for virtually all mortality directly related to Hirschsprung disease in modern pediatric surgical

practice. Infants with known Hirschsprung disease and suspected enterocolitis should be treated

aggressively. Initial treatment includes resuscitation, broad-spectrum antibiotics, cessation of feeding,

and rectal irrigation. If the enterocolitis does not respond promptly, emergent intestinal decompression

with an enterostomy proximal to the transition zone is indicated.

Diagnosis

A high index of suspicion for Hirschsprung disease should be maintained for any newborn infant with

abdominal distention failing to pass meconium in 24 to 48 hours. The signs of neonatal intestinal

obstruction should lead to a stereotypical workup. In the presence of characteristic findings on history,

examination, or radiographic studies, any infant suspected of having Hirschsprung disease should

undergo rectal biopsy.

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Figure 103-31. A: Contrast enema demonstrating a classic rectosigmoid transition zone (arrow) in Hirschsprung disease. B: Lateral

view of rectum illustrates typical distal spasm of rectum. C: Operative photograph of rectosigmoid transition zone.

Plain Abdominal Radiographs. Plain film radiographs of the neonate with Hirschsprung disease are

nonspecific and typically demonstrate distended, air-filled loops of bowel throughout the abdomen. It is

often difficult to discriminate between small intestine and large intestine on plain films at this age, but

the pattern is consistent with distal intestinal obstruction. Older children or adults may have a stoolfilled megacolon on plain radiographs. In the presence of enterocolitis, thickened, dilated intestinal

loops and pneumatosis intestinalis may be present.

Contrast Enema. When distal neonatal intestinal obstruction is suspected on plain abdominal films, a

contrast enema should be performed. With an experienced pediatric radiologist, findings consistent with

Hirschsprung disease can be accurately detected in most instances. The classic radiographic finding in

Hirschsprung disease is a transition zone (Fig. 103-31A). A definitive transition zone may not be

apparent in a neonate because proximal dilatation takes some time to develop. In addition, infants with

short-segment disease or total colonic aganglionosis may not have obvious transition zones on contrast

enema. In these instances, a lateral view of the rectum may show abnormal spasm (Fig. 103-31B).

Contrast remaining in the rectum more than 24 hours following a study is suggestive of Hirschsprung

disease.

Rectal Biopsy. The diagnostic standard for aganglionosis is the rectal biopsy. Several commercially

available instruments capable of performing rectal suction biopsies are in widespread use. The rectal

suction biopsy can be performed at bedside or in clinic without anesthesia in all newborns and most

children up to several months of age. The desire for early diagnosis and the technical simplicity of the

procedure allow liberal use of this technique. When applied liberally, the vast majority (85% to 90%) of

infants undergoing this procedure have normal ganglion cells on biopsy, effectively excluding

Hirschsprung disease. Using the rectal suction biopsy technique, a biopsy of the mucosa and the

submucosa is obtained. This is sufficient to establish the diagnosis because ganglion cells are absent

from all intramural plexuses in Hirschsprung disease. The biopsy must be taken 1 to 1.5 cm proximal to

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the dentate line. Complications of infection, perforation, and bleeding with rectal suction biopsy are

infrequent. Full-thickness rectal biopsy under general anesthesia is reserved for older children and in

infants in whom suction biopsy is inadequate. An experienced pediatric pathologist must read the

biopsies for maximal diagnostic accuracy. Evaluation for ganglion cells and the axons of the myenteric

neurons is performed (Fig. 103-32), which may be accomplished using conventional hematoxylin-eosin

staining or histochemical staining for acetylcholinesterase. Similar histochemical staining for nitric oxide

synthase can be performed. These adjunctive techniques are used routinely in some centers and can help

provide additional evidence of Hirschsprung disease rather than simply demonstrating aganglionosis in

the biopsy specimen. Diagnostic accuracy for Hirschsprung disease is excellent with a correctly obtained

rectal suction biopsy and an experienced pediatric pathologist.121,122

Figure 103-32. A: Normal rectal biopsy with ganglion cells indicated by arrow (hematoxylin-eosin). B: Rectal biopsy specimen

with aganglionosis (hematoxylin-eosin). Note the characteristic thickened nerve fiber (arrow). C: Normal rectal biopsy using

acetylcholinesterase histochemical staining. D: Similarly stained specimen from a patient with Hirschsprung disease. Many

thickened submucosal nerve fibers stain densely black.

Anorectal Manometry. The absence of sphincter relaxation in response to rectal dilatation is consistent

with Hirschsprung disease. Because of the relative ease and accuracy of rectal suction biopsy, anorectal

manometry is not widely used in the United States for the primary diagnosis of Hirschsprung disease in

infancy; however, this is used in some centers around the world and, when applied carefully with an

appropriate transduction probe, accurate manometric diagnosis is achievable in 85% to 90% of cases.

Treatment

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Diverting colostomy should be considered for a newborn infant with Hirschsprung disease who has

enterocolitis or multiple associated medical problems or anomalies. In the presence of enterocolitis,

rectal irrigation and decompression can be an effective temporizing measure while resuscitation and

broad-spectrum antibiotics are being instituted. Prompt proximal diversion will be required once the

patient has stabilized. In the neonate, one approach following diagnosis is to perform proximal

diversion by means of a colostomy (or enterostomy) placed in normal, ganglionated intestine. The

diverting colostomy must be proximal to the histologic transition zone, and a series of biopsies

examined by frozen section may be necessary to find the correct level for diversion. For classic

rectosigmoid disease, a leveling colostomy is placed just proximal to the transition zone. This approach

is generally done in two stages, with takedown of the stoma and definitive pull-through operation

performed together weeks to months later, typically when the infant reaches 9 to 12 months of age. In

older children, definitive pull-through is deferred until the colon has decompressed to relatively normal

caliber.

For many infants and children without enterocolitis, a single-stage approach that eliminates the

diverting colostomy has been advocated.123,124 Despite a number of different operative techniques in

performing a single-stage pull-through, results and outcomes appear nearly equivalent. Definitive repair

of Hirschsprung disease with a single operation is desirable from technical and economical standpoint

and essentially eliminates the complications associated with neonatal stomas. As with most aspects of

pediatric surgery, an increasing experience with laparoscopically assisted, single-stage pull-through

operations has been reported.125 The contemporary, laparoscopic single-stage approach in the

management of Hirschsprung disease has gained wide acceptance in the pediatric surgical community

and is considered by many surgeons as the current standard of care for most infants and children.

Definitive Operations for Hirschsprung Disease

The major goal of operative therapy in the treatment of Hirschsprung disease is to provide resection or

bypass of the distal aganglionic rectum with the performance of a low rectal anastomosis with normally

innervated proximal intestine. Numerous definitive procedures were designed to treat Hirschsprung

disease, and a brief description of the principal procedures in use follows. In general, the selection of a

procedure depends on a surgeon’s individual training and preference rather than compelling differences

in outcome.126,127

Duhamel Procedure (Martin Modification). The key elements of the Duhamel procedure are

illustrated in Figure 103-33. After minimal pelvic dissection, resection of the aganglionic colon is

performed. The aganglionic rectum is left in situ. Normal proximal colon is brought caudad into the

retrorectal space, and a colorectal anastomosis is performed 1 cm above the dentate line. The original

operation left the defunctionalized rectal pouch as shown, which proved problematic. The procedure has

been modified by Martin to include a longer side-to-side colorectal anastomosis. Advantages of this

procedure include its relative technical ease and limited pelvic dissection. Adoption of the stapled

anastomosis has simplified this procedure significantly.

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Figure 103-33. Duhamel procedure (Martin modification). A: Blunt retrorectal dissection. B: Incision in the posterior wall of the

aganglionic rectum. C: Retrorectal pull-through after resection of the proximal aganglionic segment. D: End-to-side colorectal

anastomosis preserving aganglionic rectum (as originally described). E: Stapled conversion of anastomosis into an extended side-toside colorectal anastomosis (Martin modification). F: Completed procedure.

Soave Procedure. The Soave procedure is illustrated in Figure 103-34. Following resection of

aganglionic colon, an endorectal dissection in the submucosal plane is performed from proximal rectum

to anus. The endorectal dissection is started in the extraperitoneal rectum. This dissection is typically

much easier than similar dissection for ulcerative colitis given the lack of mucosal inflammation. The

dissected rectal mucosal tube is everted through the anus, excised, and normal proximal bowel is pulled

through the rectal muscular cuff. The original operation did not suture the pull-through segment of

proximal bowel to the rectum. A formal sutured colorectal anastomosis is now universally performed.

Care must be taken to ensure that the pull-through segment is not obstructed by the muscular cuff.

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