An Approach to the Vomiting Infant
The majority of infants vomit. Because infant vomiting is so common, it is important to differentiate between normal vomiting, which occurs in almost all babies, to some degree, and abnormal vomiting, which may be indicative of a potentially serious underlying disorder. To determine the seriousness of a particular infant’s bouts of emesis, one needs to characterize what the vomit looks like and how sick the baby is. Vomit that looks like feeds and comes up immediately after a feeding is almost always gastroesophageal reflux. This may or may not be of concern, as described earlier. Vomiting that occurs a short while after feeding or vomiting that projects out of the baby’s mouth may be indicative of pyloric stenosis. By contrast, vomit that has any green color in it is always worrisome. This may be reflective of intestinal volvulus, an underlying infection, or some other cause of intestinal obstruction. A more detailed description of the management of these conditions is provided in the following sections.
Hypertrophic Pyloric Stenosis
Infants with hypertrophic pyloric stenosis (HPS) typically present with nonbilious vomiting that becomes increasingly projectile over the course of several days to weeks due to progressive thickening of the pylorus muscle. HPS occurs in approximately 1 in 300 live births and commonly in infants between 3 and 6 weeks of age. Male-to-female ratio is nearly 5:1.
Eventually, as the pyloric muscle thickening progresses, the infant develops a complete gastric outlet obstruction and is no longer able to tolerate any feeds. Over time, the infant becomes increasingly hungry, unsuccessfully feeds repeatedly, and becomes increasingly dehydrated. Wet diapers become less frequent, and there may even be a perception of less passage of flatus. HPS may be associated with jaundice due to an indirect hyperbilirubinemia, although the nature of this relationship is unclear.
The cause of HPS has not been determined. Studies have shown that HPS is found in several generations of the same family, suggesting a familial link. Administration of erythromycin in early infancy has been linked to the subsequent development of HPS, although the cause is unclear. Infant positioning in the prone position was implicated as a cause of HPS particularly when, in Denmark and Sweden, a drop in both cases of sudden infant death syndrome (SIDS) and HPS were reported. More recently, a similar drop in both SIDS and HPS was noted in Germany, although the distribution of case rate declines were different across regions in Germany, suggesting that the etiology of HPS is not likely simply due to positioning.
Infants with HPS develop a hypochloremic, hypokalemic metabolic alkalosis. The urine pH level is high initially, but eventually drops because hydrogen ions are preferentially exchanged for sodium ions in the distal tubule of the kidney as the hypochloremia becomes severe (paradoxical aciduria). The diagnosis of pyloric stenosis usually can be made on physical examination by palpation of the typical “olive” in the right upper quadrant and the presence of visible gastric waves on the abdomen. When the olive cannot be palpated, US can diagnose the condition accurately in 95% of patients. Criteria for US diagnosis include a channel length of over 16 mm and pyloric thickness over 4 mm.
Given frequent fluid and electrolyte abnormalities at time of presentation, pyloric stenosis is never a surgical emergency. Fluid resuscitation with correction of electrolyte abnormalities and metabolic alkalosis is essential prior to induction of general anesthesia for operation. For most infants, fluid containing 5% dextrose and 0.45% saline with added potassium of 2 to 4 mEq/kg over 24 hours at a rate of approximately 150 to 175 mL/kg per 24 hours will correct the underlying deficit. It is important to ensure that the child has an adequate urine output (>2 cc/kg/h) as further evidence that rehydration has occurred. After resuscitation, a Fredet-Ramstedt pyloromyotomy is performed (Fig. 39-12). It may be performed using an open or laparoscopic approach. The open pyloromyotomy is performed through either an umbilical or a right upper quadrant transverse abdominal incision. The former route is cosmetically more appealing, although the transverse incision provides easier access to the antrum and pylorus. In recent years, the laparoscopic approach has gained great popularity. Two randomized trials have demonstrated that both the open and laparoscopic approaches may be performed safely with equal incidence of postoperative complications, although the cosmetic result is clearly superior with the laparoscopic approach. Whether done through an open or laparoscopic approach, surgical treatment of pyloric stenosis involves splitting the pyloric muscle while leaving the underlying submucosa intact. The incision extends from just proximal to the pyloric vein of Mayo to the gastric antrum; it typically measures between 1 and 2 cm in length. Postoperatively, IV fluids are continued for several hours, after which Pedialyte is offered, followed by formula or breast milk, which is gradually increased to 60 cc every 3 hours. Most infants can be discharged home within 24–48 hours following surgery. Recently, several authors have shown that ad lib feeds are safely tolerated by the neonate and result in a shorter hospital stay.
Fredet-Ramstedt pyloromyotomy. A. Pylorus delivered into wound and seromuscular layer incised. B. Seromuscular layer separated down to submucosal base to permit herniation of mucosa through pyloric incision. C. Cross-section demonstrating hypertrophied pylorus, depth of incision, and spreading of muscle to permit mucosa to herniate through incision.
The complications of pyloromyotomy include perforation of the mucosa (1%–3%), bleeding, wound infection, and recurrent symptoms due to inadequate myotomy. When perforation occurs, the mucosa is repaired with a stitch that is placed to tack the mucosa down and reapproximate the serosa in the region of the tear. A nasogastric tube is left in place for 24 hours. The outcome is generally very good.
Intestinal Obstruction in the Newborn
The cardinal symptom of intestinal obstruction in the newborn is bilious emesis. Prompt recognition and treatment of neonatal intestinal obstruction can truly be life saving.
The incidence of neonatal intestinal obstruction is 1 in 2000 live births. The approach to intestinal obstruction in the newborn infant is critical for timely and appropriate intervention. When a neonate develops bilious vomiting, one must consider a surgical etiology. Indeed, the majority of newborns with bilious emesis have a surgical condition. In evaluating a potential intestinal obstruction, it is helpful to determine whether the intestinal obstruction is either proximal or distal to the ligament of Treitz. One must conduct a detailed prenatal and immediate postnatal history and a thorough physical examination. In all cases of intestinal obstruction, it is vital to obtain abdominal films in the supine and upright (or lateral decubitus) views to assess the presence of air-fluid levels or free air as well as how far downstream air has managed to travel. Importantly, one should recognize that it is difficult to determine whether a loop of bowel is part of either the small or large intestine, as neonatal bowel lacks clear features, such as haustra or plica circulares, normally present in older children or adults. As such, contrast imaging may be necessary for diagnosis in some instances.
Proximal intestinal obstructions typically present with bilious emesis and minimal abdominal distention. The normal neonate should have a rounded, soft abdomen; in contrast, a neonate with a proximal intestinal obstruction typically exhibits a flat or scaphoid abdomen. On a series of upright and supine abdominal radiographs, one may see a paucity or absence of bowel gas, which normally should be present throughout the gastrointestinal tract within 24 hours. Of utmost importance is the exclusion of a malrotation with midgut volvulus from all other intestinal obstructions as this is a surgical emergency.
Distal obstructions typically presents with bilious emesis and abdominal distention. Passage of black-green meconium should have occurred within the first 24 to 38 hours. Of great importance, one should determine whether or not there is tenderness or discoloration of the abdomen, visible or palpable loops of intestine, and presence or absence of a mass, and whether or not the anus is patent and in the appropriate location. Abdominal radiographs may demonstrate calcifications, which may indicate complicated meconium ileus; pneumatosis and/or pneumoperitoneum may indicate necrotizing enterocolitis. A contrast enema may show whether there is a microcolon indicative of jejunoileal atresia or meconium ileus. If a microcolon is not present, then the diagnoses of Hirschsprung’s disease, small left colon syndrome, or meconium plug syndrome should be considered.
Whenever the diagnosis of duodenal obstruction is entertained, malrotation and midgut volvulus must be excluded. This topic is covered in further detail later in this chapter. Other causes of duodenal obstruction include duodenal atresia, duodenal web, stenosis, annular pancreas, or duodenal duplication cyst. Duodenal obstruction is easily diagnosed on prenatal US, which demonstrates the fluid-filled stomach and proximal duodenum as two discrete cystic structures in the upper abdomen. Associated polyhydramnios is common and presents in the third trimester. In 85% of infants with duodenal obstruction, the entry of the bile duct is proximal to the level of obstruction, such that vomiting is bilious. Abdominal distention is typically not present because of the proximal level of obstruction. In infants with obstruction proximal to the bile duct entry, the vomiting is nonbilious. The classic finding on abdominal radiography is the “double bubble” sign, which represents the dilated stomach and duodenum (Fig. 39-13). In association with the appropriate clinical picture, this finding is sufficient to confirm the diagnosis of duodenal obstruction. However, if there is any uncertainty, particularly when a partial obstruction is suspected, a contrast upper gastrointestinal series is diagnostic.
Abdominal x-ray showing "double bubble" sign in a newborn infant with duodenal atresia. The two "bubbles" are numbered.
An orogastric tube is inserted to decompress the stomach and duodenum, and the infant is given IV fluids to maintain adequate urine output. If the infant appears ill or if abdominal tenderness is present, a diagnosis of malrotation and midgut volvulus should be considered, and surgery should not be delayed. Typically, the abdomen is soft, and the infant is very stable. Under these circumstances, the infant should be evaluated thoroughly for other associated anomalies. Approximately one third of newborns with duodenal atresia have associated Down syndrome (trisomy 21). These patients should be evaluated for associated cardiac anomalies. Once the workup is complete and the infant is stable, he or she is taken to the operating room, and the abdomen is entered through a transverse right upper quadrant supraumbilical incision under general endotracheal anesthesia. Associated anomalies should be searched for at the time of the operation. These include malrotation, anterior portal vein, a second distal web, and biliary atresia. The surgical treatment of choice for duodenal obstruction due to duodenal stenosis or atresia or annular pancreas is a duodeno-duodenostomy. This procedure can be most easily performed using a proximal transverse-to-distal longitudinal (diamond-shaped) anastomosis. In cases where the duodenum is extremely dilated, the lumen may be tapered using a linear stapler with a large Foley catheter (24 F or greater) in the duodenal lumen. It is important to emphasize that an annular pancreas is never divided but rather is bypassed to avoid injury to the pancreatic ducts. Treatment of duodenal web includes vertical duodenotomy, excision of the web, oversewing of the mucosa, and closing the duodenotomy horizontally. Gastrostomy tube placement is not routinely performed. Recently reported survival rates exceed 90%. Late complications from repair of duodenal atresia occur in approximately 12% to 15% of patients and include megaduodenum, intestinal motility disorders, and GER.
Obstruction due to intestinal atresia can occur at any point along the intestinal tract. Intestinal atresias were previously thought to be the result of in utero mesenteric vascular accidents leading to segmental loss of the intestinal lumen, although, more likely they are due to developmental defects in normal intestinal organogenesis due to disruption of various signaling pathways such as fibroblast growth factor, bone morphogenic protein, and β-catenin pathways. The incidence of intestinal atresia has been estimated to be between 1 in 2000 and 1 in 5000 live births, with equal representation of the sexes. Infants with jejunal or ileal atresia present with bilious vomiting and progressive abdominal distention. The more distal the obstruction, the more distended the abdomen becomes, and the greater is the number of obstructed loops on upright abdominal films (Fig. 39-14).
Intestinal obstruction in the newborn showing several loops of distended bowel with air-fluid levels. This child has jejunal atresia.
In cases where the diagnosis of complete intestinal obstruction is ascertained by the clinical picture and the presence of staggered air-fluid levels on plain abdominal films, the child can be brought to the operating room after appropriate resuscitation. In these circumstances, there is little extra information to be gained by performing a barium enema. By contrast, when there is diagnostic uncertainty or when distal intestinal obstruction is apparent, a barium enema is useful to establish whether a microcolon is present and to diagnose the presence of meconium plugs, small left colon syndrome, Hirschsprung’s disease, or meconium ileus. Judicious use of barium enema is therefore required in order to safely manage neonatal intestinal obstruction, based on an understanding of the expected level of obstruction.
Surgical correction of the small intestinal atresia should be performed urgently. At laparotomy, one of several types of atresia will be encountered. In type 1, there is a mucosal atresia with intact muscularis. In type 2, the atretic ends are connected by a fibrous band. In type 3A, the two ends of the atresia are separated by a V-shaped defect in the mesentery. Type 3B is an “apple peel” deformity or “Christmas tree” deformity in which the bowel distal to the atresia receives its blood supply in a retrograde fashion from the ileocolic or right colic artery (Fig. 39-15). In type 4 atresia, there are multiple atresias with a “string of sausage” or “string of beads” appearance. Disparity in lumen size between the proximal distended bowel and the small diameter of collapsed bowel distal to the atresia has led to a number of innovative techniques of anastomosis. However, under most circumstances, an anastomosis can be performed using the end-to-back technique in which the distal, compressed loop is “fish-mouthed” along its antimesenteric border. The proximal distended loop can be tapered as described earlier. Because the distended proximal bowel rarely has normal motility, the extremely dilated portion should be resected prior to performing the anastomosis.
Operative photograph of newborn with “Christmas tree” type of ileal atresia.
Occasionally the infant with intestinal atresia will develop ischemia or necrosis of the proximal segment secondary to volvulus of the dilated, bulbous, blind-ending proximal bowel. Under these conditions, an end ileostomy and mucus fistula should be created, and the anastomosis should be deferred to another time after the infant stabilizes.
Malrotation and Midgut Volvulus
During the sixth week of fetal development, the midgut grows too rapidly to be accommodated in the abdominal cavity and therefore herniates into the umbilical cord. Between the tenth and twelfth weeks, the midgut returns to the abdominal cavity, undergoing a 270° counterclockwise rotation around the superior mesenteric artery. Because the duodenum also rotates caudal to the artery, it acquires a C-loop that traces this path. The cecum rotates cephalad to the artery, which determines the location of the transverse and ascending colon. Subsequently, the duodenum becomes fixed retroperitoneally in its third portion and at the ligament of Treitz, while the cecum becomes fixed to the lateral abdominal wall by peritoneal bands. The takeoff of the branches of the superior mesenteric artery elongates and becomes fixed along a line extending from its emergence from the aorta to the cecum in the right lower quadrant. Genetic mutations likely disrupt the signaling critical for normal intestinal rotation. For instance, mutations in the gene BCL6 resulting in absence of left-sided expression of its transcript lead to reversed cardiac orientation, defective ocular development, and malrotation. The essential role of the dorsal gut mesentery in mediating normal intestinal rotation and the role of the forkhead box transcription factor Foxf1 in formation of the dorsal mesentery in mice are consistent with the noted association of intestinal malrotation with alveolar capillary dysplasia, caused by mutations in FOXF1. If rotation is incomplete, the cecum remains in the epigastrium, but the bands fixing the duodenum to the retroperitoneum and cecum continue to form. This results in (Ladd’s) bands extending from the cecum to the lateral abdominal wall and crossing the duodenum, which creates the potential for obstruction. The mesenteric takeoff remains confined to the epigastrium, resulting in a narrow pedicle suspending all the branches of the superior mesenteric artery and the entire midgut. A volvulus may therefore occur around the mesentery. This twist not only obstructs the proximal jejunum, but also cuts off the blood supply to the midgut. Intestinal obstruction and complete infarction of the midgut occur unless the problem is promptly corrected surgically.
Presentation and Management
Midgut volvulus can occur at any age, although it is seen most often in the first few weeks of life. Bilious vomiting is usually the first sign of volvulus, and all infants with bilious vomiting must be evaluated rapidly to ensure that they do not have intestinal malrotation with volvulus. The child with irritability and bilious emesis should raise particular suspicions for this diagnosis. If left untreated, vascular compromise of the midgut initially causes bloody stools, but eventually results in circulatory collapse. Additional clues to the presence of advanced ischemia of the intestine include erythema and edema of the abdominal wall, which progresses to shock and death. It must be re-emphasized that the index of suspicion for this condition must be high, since abdominal signs are minimal in the early stages. Abdominal films show a paucity of gas throughout the intestine with a few scattered air-fluid levels (Fig. 39-16). When these findings are present, the patient should undergo immediate fluid resuscitation to ensure adequate perfusion and urine output followed by prompt exploratory laparotomy. In cases where the child is stable, laparoscopy may be considered.
Abdominal x-ray of a 10-day-old infant with bilious emesis. Note the dilated proximal bowel and the paucity of distal bowel gas, characteristic of a volvulus.
Often the patient will not appear ill, and the plain films may suggest partial duodenal obstruction. Under these conditions, the patient may have malrotation without volvulus. This is best diagnosed by an upper gastrointestinal series that shows incomplete rotation with the duodenojejunal junction displaced to the right. The duodenum may show a corkscrew effect diagnosing volvulus or complete duodenal obstruction, with the small bowel loops entirely in the right side of the abdomen. Barium enema may show a displaced cecum, but this sign is unreliable, especially in the small infant in whom the cecum is normally in a somewhat higher position than in the older child.
When volvulus is suspected, early surgical intervention is mandatory if the ischemic process is to be avoided or reversed. Volvulus occurs clockwise and is therefore untwisted counterclockwise. This can be remembered using the memory aid “turn back the hands of time.” Subsequently, a Ladd procedure is performed. This operation does not correct the malrotation, but does broaden the narrow mesenteric pedicle to prevent volvulus from recurring. This procedure is performed as follows (Fig. 39-17). The bands between the cecum and the abdominal wall and between the duodenum and terminal ileum are divided sharply to splay out the superior mesenteric artery and its branches. This maneuver brings the straightened duodenum into the right lower quadrant and the cecum into the left lower quadrant. The appendix is removed to avoid diagnostic errors in later life. No attempt is made to suture the cecum or duodenum in place. With advanced ischemia, reduction of the volvulus without the Ladd procedure is accomplished, and a “second look” 24 to 36 hours later often will show some vascular recovery. A plastic transparent silo may be placed to facilitate constant evaluation of the intestine and to plan for the timing of re-exploration. Frankly necrotic bowel can then be resected conservatively. With early diagnosis and correction the prognosis is excellent. However, diagnostic delay can lead to mortality or to short-gut syndrome requiring intestinal transplantation.
Ladd procedure for malrotation. A. Lysis of cecal and duodenal bands. B. Broadening the mesentery. C. Appendectomy.
A subset of patients with malrotation will demonstrate chronic obstructive symptoms. These symptoms may result from Ladd’s bands across the duodenum or, occasionally, from intermittent volvulus. Symptoms include intermittent abdominal pain and intermittent vomiting, which may occasionally be bilious. Infants with malrotation may demonstrate failure to thrive, and they may be diagnosed initially as having GERD. Surgical correction using the Ladd procedure, as described earlier, can prevent volvulus from occurring and improve symptoms in many instances.
Pathogenesis and Clinical Presentation
Infants with cystic fibrosis have characteristic pancreatic enzyme deficiencies and abnormal chloride secretion in the intestine that result in the production of viscous, water-poor meconium. This phenotype is explained by the presence of mutations in the CFTR gene. Meconium ileus occurs when this thick, highly viscous meconium becomes impacted in the ileum and leads to high-grade intestinal obstruction. Recently, additional mutations were recently identified in genes encoding multiple apical plasma membrane proteins of infants with meconium ileus. Meconium ileus can be either uncomplicated, in which there is no intestinal perforation, or complicated, in which prenatal perforation of the intestine has occurred or vascular compromise of the distended ileum develops. Antenatal US may reveal the presence of intra-abdominal or scrotal calcifications or distended bowel loops. These infants present shortly after birth with progressive abdominal distention and failure to pass meconium with intermittent bilious emesis. Abdominal radiographs show dilated loops of intestine. Because the enteric contents are so viscous, air-fluid levels do not form, even when obstruction is complete. Small bubbles of gas become entrapped in the inspissated meconium in the distal ileum, where they produce a characteristic “ground glass” appearance.
The diagnosis of meconium ileus is confirmed by a contrast enema, which typically demonstrates a microcolon. In patients with uncomplicated meconium ileus, the terminal ileum is filled with pellets of meconium. In patients with complicated meconium ileus, intraperitoneal calcifications form, producing an eggshell pattern on plain abdominal x-ray.
The treatment strategy depends on whether the patient has complicated or uncomplicated meconium ileus. Patients with uncomplicated meconium ileus can be treated nonoperatively. Either dilute water-soluble contrast or N-acetylcysteine (Mucomyst¯) is infused transanally via catheter under fluoroscopic control into the dilated portion of the ileum. Because these agents act by absorbing fluid from the bowel wall into the intestinal lumen, infants undergoing treatment are at risk of fluid and electrolyte abnormalities, so appropriate resuscitation of the infant during this maneuver is extremely important. The enema may be repeated at 12-hour intervals over several days until all the meconium is evacuated. Inability to reflux the contrast into the dilated portion of the ileum signifies the presence of an associated atresia or complicated meconium ileus, and thus warrants exploratory laparotomy. If surgical intervention is required because of failure of contrast enemas to relieve obstruction, operative irrigation with dilute contrast agent, N-acetylcysteine, or saline through a purse-string suture may be successful. Alternatively, resection of the distended terminal ileum is performed, and the meconium pellets are flushed from the distal small bowel. At this point, an end ileostomy may be created. The distal bowel may be brought up as a mucus fistula or sewn to the side of the ileum as a Bishop-Koop anastomosis. An end-to-end anastomosis may also be considered in the appropriate setting (Fig. 39-18).
Techniques of intestinal anastomosis for infants with small bowel obstruction. A. End to back: distal limb has been incised, creating “fish mouth” to enlarge the lumen. B. Bishop-Koop: proximal distended limb joined to side of distal small bowel, which is vented by “chimney” to the abdominal wall. C. Tapering: portion of antimesenteric wall of proximal bowel excised, with longitudinal closure to minimize disparity in the limbs. D. Mikulicz double-barreled enterostomy is constructed by suturing the two limbs together and then exteriorizing the double stoma. The common wall can be crushed with a special clamp to create a large stoma. The stoma can be closed in an extraperitoneal manner.
Necrotizing enterocolitis (NEC) is the most frequent and lethal gastrointestinal disorder affecting the intestine of the stressed, preterm neonate. Over 25,000 cases of NEC are reported annually. The overall mortality ranges between 10% and 50%. Advances in neonatal care such as surfactant therapy and improved methods of mechanical ventilation have resulted in increasing numbers of low birth weight infants surviving neonatal hyaline membrane disease. An increasing proportion of survivors of neonatal respiratory distress syndrome will therefore be at risk for developing NEC. Consequently, it is estimated that NEC soon will surpass respiratory distress syndrome as the principal cause of death in the preterm infant.
Multiple risk factors have been associated with the development of NEC. These include prematurity, initiation of enteral feeding, bacterial infection, intestinal ischemia resulting from birth asphyxia, umbilical artery cannulation, persistence of a patent ductus arteriosus, cyanotic heart disease, and maternal cocaine abuse. Nonetheless, the mechanisms by which these complex interacting etiologies lead to the development of the disease remain undefined. The only consistent epidemiologic precursors for NEC are prematurity and enteral alimentation, representing the commonly encountered clinical situation of a stressed infant who is fed enterally. Of note, there is some debate regarding the type and strategy of enteral alimentation in the pathogenesis of NEC. A prospective randomized study showed no increase in the incidence of NEC despite an aggressive feeding strategy.
The indigenous intestinal microbial flora has been postulated to play a central role in the pathogenesis of NEC. Bacterial colonization may be a prerequisite for the development of this disease because oral prophylaxis with vancomycin or gentamicin reduced the incidence of NEC. The importance of bacteria in the pathogenesis of NEC is further supported by the finding that NEC occurs in episodic waves that can be abrogated by infection control measures and the fact that NEC usually develops at least 10 days postnatally, when the gastrointestinal tract is colonized by coliforms. More recently, outbreaks of NEC have been reported in infants fed formula contaminated with Cronobacter sakazakii. Common bacterial isolates from the blood, peritoneal fluid, and stool of infants with advanced NEC include Escherichia coli, Enterobacter, Klebsiella, and occasionally, coagulase-negative Staphylococcus species.
NEC may involve single or multiple segments of the intestine, most commonly the terminal ileum, followed by the colon. The gross findings in NEC include bowel distention with patchy areas of thinning, pneumatosis, gangrene, or frank perforation. The microscopic features include the appearance of a “bland infarct” characterized by full-thickness necrosis.
Infants with NEC present with a spectrum of disease. In general, the infants are premature and may have sustained one or more episodes of stress, such as birth asphyxia, or they may have congenital cardiac disease. The clinical picture of NEC has been characterized by Bell and colleagues as progressing from a period of mild illness to that of severe, life-threatening sepsis. Although not all infants progress through the various “Bell stages,” this classification scheme provides a useful format to describe the clinical picture associated with the development of NEC. In the earliest stage (Bell stage I), infants present with feeding intolerance. This is suggested by vomiting or by the presence of a large residual volume from a previous feeding in the stomach at the time of the next feeding. Following appropriate treatment, which consists of bowel rest and IV antibiotics, many of these infants will not progress to more advanced stages of NEC. These infants are colloquially described as suffering from a “NEC scare” and represent a population of neonates who are at risk of developing more severe NEC if a more prolonged period of stress supervenes.
Infants with Bell stage II have established NEC that is not immediately life threatening. Clinical findings include abdominal distention and tenderness, bilious nasogastric aspirate, and bloody stools. These findings indicate the development of intestinal ileus and mucosal ischemia, respectively. Abdominal examination may reveal a palpable mass indicating the presence of an inflamed loop of bowel, diffuse abdominal tenderness, cellulitis, and edema of the anterior abdominal wall. The infant may appear systemically ill, with decreased urine output, hypotension, tachycardia, and noncardiac pulmonary edema. Hematologic evaluation reveals either leukocytosis or leukopenia, an increase in the number of bands, and thrombocytopenia. An increase in the blood urea nitrogen and plasma creatinine levels may be found, which signifies the development of renal dysfunction. The diagnosis of NEC may be confirmed by abdominal radiography. The pathognomonic radiographic finding in NEC is pneumatosis intestinalis, which represents invasion of the ischemic mucosa by gas-producing microbes (Fig. 39-19). Other findings include the presence of ileus or portal venous gas. The latter is a transient finding that indicates the presence of severe NEC with intestinal necrosis. A fixed loop of bowel may be seen on serial abdominal radiographs, which suggests the possibility that a diseased loop of bowel, potentially with a localized perforation, is present. Although these infants are at risk of progressing to more severe disease, with timely and appropriate treatment, they often recover.
Abdominal radiograph of infant with necrotizing enterocolitis. Arrows point to area of pneumatosis intestinalis.
Infants with Bell stage III have the most advanced form of NEC. Abdominal radiographs often demonstrate the presence of pneumoperitoneum, indicating that intestinal perforation has occurred. These patients may develop a fulminant course with progressive peritonitis, acidosis, sepsis, disseminated intravascular coagulopathy, and death.
Pathogenesis of Necrotizing Enterocolitis
Several theories have been proposed to explain the development of NEC. To more precisely understand the mechanisms that contribute to the pathogenesis of NEC, several groups have focused on understanding the potential clues that may be revealed by studying patients who have progressed from Bell stage I to Bell stage III disease. In general terms, the development of diffuse pneumatosis intestinalis, which is associated with the development of stage II NEC, is thought to be due to the presence of gas within the wall of the intestine from enteric bacteria, suggesting the causative role of bacteria in the pathogenesis of NEC. Furthermore, the development of pneumoperitoneum indicates disease progression with severe disruption of the intestinal barrier (intestinal perforation). Finally, systemic sepsis with diffuse multisystem organ dysfunction suggests the role for circulating proinflammatory cytokines in the pathogenesis of NEC. It has also been demonstrated that the premature intestine responds in an exaggerated fashion to bacterial products, rendering the host susceptible to barrier dysfunction and the development of NEC. As was recently summarized by the 2006 National Institute of Child Health and Development (NICHD) workshop on NEC research, “NEC can be thought to arise from an uncontrolled exuberant inflammatory response to bacterial colonization that characterizes the intestine of premature infants.”
In all infants suspected of having NEC, feedings are discontinued, a nasogastric tube is placed, and broad-spectrum parenteral antibiotics are given. The infant is resuscitated, and inotropes are administered to maintain perfusion as needed. Intubation and mechanical ventilation may be required to maintain oxygenation. TPN is started. Subsequent treatment may be influenced by the particular stage of NEC that is present. Patients with Bell stage I are closely monitored and generally remain NPO (nothing by mouth) and on IV antibiotics for 5 to 7 days, prior to reinitiating enteral nutrition. If the infant fully recovers, feedings may be reinitiated.
Patients with Bell stage II disease merit close observation. Serial physical examinations are performed looking for the development of diffuse peritonitis, a fixed mass, progressive abdominal wall cellulitis, or systemic sepsis. Serial abdominal radiographs are obtained at regular intervals to look for the presence of pneumoperitoneum or a fixed loop of bowel. If infants fail to improve after several days of treatment or if abdominal radiographs show a fixed intestinal loop, consideration should be given to exploratory laparotomy. Paracentesis may be performed, and if the Gram stain demonstrates multiple organisms and leukocytes, perforation of the bowel should be suspected, and patients should undergo laparotomy.
In the most severe form of NEC (Bell stage III), patients have definite intestinal perforation or have not responded to nonoperative therapy. Two schools of thought direct further management. One group favors exploratory laparotomy. At laparotomy, frankly gangrenous or perforated bowel is resected, and the intestinal ends are brought out as stomas. When there is massive intestinal involvement, marginally viable bowel is retained, and a “second look” procedure is carried out after the infant stabilizes (24–48 hours). Patients with extensive necrosis at the second look may be managed by placing a proximal diverting stoma, resecting bowel that is definitely not viable, and leaving questionably viable bowel behind, distal to the diverted segment. When the intestine is viable except for a localized perforation without diffuse peritonitis and if the infant’s clinical condition permits, intestinal anastomosis may be performed. In cases where the diseased, perforated segment cannot be safely resected, drainage catheters may be left in the region of the diseased bowel, and the infant is allowed to stabilize.
An alternative approach to the management of infants with perforated NEC involves drainage of the peritoneal cavity. This may be performed under local anesthesia at the bedside and can be an effective means of stabilizing the desperately ill infant by relieving increased intra-abdominal pressure and allowing ventilation. When successful, this method also allows for drainage of perforated bowel by establishing a controlled fistula. Approximately one third of infants treated with drainage alone survive without requiring additional operations. Infants who do not respond to peritoneal drainage alone after 48 to 72 hours should undergo laparotomy. This procedure allows for the resection of frankly necrotic bowel diversion of the fecal stream and facilitates more effective drainage. It is noteworthy that a recent randomized controlled trial demonstrated that outcomes were similar in infants with NEC who were treated either with primary peritoneal drainage or laparotomy.
Necrotizing Enterocolitis in Older Infants
Although NEC is typically a disease that affects preterm infants, several independent groups have reported a tendency for early onset of NEC in term and near-term infants. In these patients, the pattern of disease was found to be different from that found in premature infants. Specifically, NEC in older infants typically is localized to the end of the small intestine and beginning of the colon, suggestive of an ischemic pathophysiology. There are four pertinent associations that are observed in term infants who develop NEC: congenital heart disease, in utero growth restriction, polycythemia, and perinatal hypoxic-ischemic events. As with NEC in preterm infants, NEC in older patients is also associated with formula consumption and is very rare in exclusively breast-fed infants. Patients with NEC at full term typically present with bloody stools and may be characterized by rapid onset of symptoms and a fulminant course. Thus, although it is true that NEC is typically a disease of premature babies, in the appropriate setting, NEC can develop at any age.
Spontaneous Intestinal Perforation Versus Necrotizing Enterocolitis
In addition to NEC, preterm infants with intestinal pathology may develop spontaneous intestinal perforation (SIP). SIP is a distinct clinical entity from NEC and is essentially a perforation in the terminal ileum. The histopathology of SIP is different from NEC. Specifically, the mucosa is intact and not necrotic, there is no sign of ischemia, and the submucosa is thinned at the site of perforation. In contrast to NEC, pneumatosis intestinalis is absent in SIP. Moreover, the demographics of NEC and SIP are slightly different, in that patients with SIP tend to be slightly more premature, smaller, and more likely to have been on inotropic support. However, both NEC and SIP occur with similar frequency in low birth weight infants. The outcome of patients in the two groups is slightly different. Because patients with SIP have isolated disease without necrosis or systemic inflammation, they tend to have a better outcome. In short, the diagnosis of SIP versus NEC has important prognostic significance. The treatment strategies, however, are essentially the same.
Survival in patients with NEC is dependent on the stage of disease, the extent of prematurity, and the presence of associated comorbidities. Survival by stage has recently been shown to be approximately 85%, 65%, and 35% for stages I, II, and III, respectively. Strictures develop in 20% of medically or surgically treated patients, and a contrast enema is mandatory before re-establishing intestinal continuity. If all other factors are favorable, the ileostomy is closed when the child is between 2 and 2.5 kg. At the time of stoma closure, the entire intestine should be examined to search for strictures. Patients who develop massive intestinal necrosis are at risk of developing short bowel syndrome, particularly when the total length of the viable intestinal segment is less than 40 cm. These patients require TPN to provide adequate calories for growth and development and may develop parenteral nutrition–associated cholestasis and hepatic fibrosis. In a significant number of these patients, transplantation of the liver and small bowel may be required.
Short bowel syndrome (SBS) is an expensive, morbid condition with an increasing incidence. Various congenital and perinatal acquired conditions such as gastroschisis, malrotation, atresia, and NEC may lead to SBS. NEC is the most common gastrointestinal emergency in neonates and primarily occurs in premature infants. As rates of prematurity are increasing, so are the numbers of children with SBS. Medical and surgical treatment options carry high dollar and human costs and morbidities including multiple infections and hospitalizations for vascular access, liver failure in conjunction with parenteral nutrition-associated cholestasis, and death. Small bowel transplant has a reported 5-year graft survival of 48%, but is attended by rejection, the morbidity of major surgery, and a lifelong need for antirejection medication. A report on 989 grafts in 923 patients by the Intestine Transplant Registry reveals improving outcomes, but 1-year graft and patient survival rates are 65% and 77%, respectively. If successful in the human, engineered intestine from autologous cells could avoid the problems of transplantation: donor supply and immunosuppression. Because engineered small and large intestine, esophagus, stomach, and specific portions of the gastrointestinal tract such as the gastroesophageal junction form by the same process, other intestinal deficiencies may possibly be addressed.
Intussusception is the leading cause of intestinal obstruction in the young child. It refers to the condition whereby a segment of intestine becomes drawn into the lumen of the more proximal bowel. The process usually begins in the region of the terminal ileum and extends distally into the ascending, transverse, or descending colon. Rarely, an intussusception may prolapse through the rectum.
The cause of intussusception is not clear, although one hypothesis suggests that hypertrophy of the Peyer’s patches in the terminal ileum from an antecedent viral infection acts as a lead point. Peristaltic action of the intestine then causes the bowel distal to the lead point to invaginate into itself. Idiopathic intussusception occurs in children between the ages of approximately 6 and 24 months of age. Beyond this age group, one should consider the possibility that a pathologic lead point may be present. These include polyps, malignant tumors such as lymphoma, enteric duplication cysts, or Meckel’s diverticulum. Such intussusceptions are rarely reduced by air or contrast enema, and thus the lead point is identified when operative reduction of the intussusception is performed.
Since intussusception is frequently preceded by a gastrointestinal viral illness, the onset may not be easily determined. Typically, the infant develops paroxysms of crampy abdominal pain and intermittent vomiting. Between attacks, the infant may act normally, but as symptoms progress, increasing lethargy develops. Bloody mucus (“currant jelly” stool) may be passed per rectum. Ultimately, if reduction is not accomplished, gangrene of the intussusceptum occurs, and perforation may ensue. On physical examination, an elongated mass is detected in the right upper quadrant or epigastrium with an absence of bowel in the right lower quadrant (Dance’s sign). The mass may be seen on plain abdominal x-ray but is more easily demonstrated on air or contrast enema.
Patients with intussusception should be assessed for the presence of peritonitis and for the severity of systemic illness. Following resuscitation and administration of IV antibiotics, the child is assessed for suitability to proceed with radiographic versus surgical reduction. In the absence of peritonitis, the child should undergo radiographic reduction. If peritonitis is present or if the child appears systemically ill, urgent laparotomy is indicated.
In the stable patient, the air enema is diagnostic and may also be curative, and it is the preferred method of diagnosis and treatment of intussusception. Air is introduced with a manometer, and the pressure that is administered is carefully monitored. Under most instances, this should not exceed 120 mmHg. Successful reduction is marked by free reflux of air into multiple loops of small bowel and symptomatic improvement as the infant suddenly becomes pain free. Unless both of these signs are observed, it cannot be assumed that the intussusception is reduced. If reduction is unsuccessful and the infant remains stable, the infant should be brought back to the radiology suite for a repeat attempt at reduction after a few hours. This strategy has improved the success rate of nonoperative reduction in many centers. In addition, hydrostatic reduction with barium may be useful if pneumatic reduction is unsuccessful. The overall success rate of radiographic reduction varies based on the experience of the center and is typically between 60% and 90%.
If nonoperative reduction is successful, the infant may be given oral fluids after a period of observation. Failure to reduce the intussusception mandates surgery. Two approaches are used. In an open procedure, exploration is carried out through a right lower quadrant incision, delivering the intussuscepted mass into the wound. Reduction usually can be accomplished by gentle distal pressure, where the intussusceptum is gently milked out of the intussuscipiens (Fig. 39-20). Care should be taken not to pull the bowel out, as this can cause damage to the bowel wall. The blood supply to the appendix is often compromised, and appendectomy is performed. If the bowel is frankly gangrenous, resection and primary anastomosis are performed. In experienced hands, laparoscopic reduction may be performed, even in very young infants. This is performed using a 5-mm laparoscope placed in the umbilicus and two additional 5-mm ports in the left and right lower quadrants. The bowel is inspected, and if it appears to be viable, reduction is performed by milking the bowel or using gentle traction, although this approach is normally discouraged during manual reduction. Atraumatic bowel graspers allow the bowel to be handled without injuring it.
Open reduction of intussusception showing how the bowel is milked backward to relieve the obstruction.
IV fluids are continued until the postoperative ileus subsides. Patients are started on clear liquids, and their diet is advanced as tolerated. Of note, recurrent intussusception occurs in 5% to 10% of patients, independent of whether the bowel is reduced radiographically or surgically. Patients present with recurrent symptoms in the immediate postoperative period. Treatment involves repeat air enema, which is successful in most cases. In patients who experience three or more episodes of intussusception, the presence of a pathologic lead point should be suspected and carefully evaluated using contrast studies. After the third episode of intussusception, many pediatric surgeons will perform an exploratory laparotomy to reduce the bowel and to resect a pathologic lead point if identified.
Correct diagnosis of appendicitis in children can be one of the most humbling and challenging tasks facing the pediatric surgeon. The classical presentation is known to all students and practitioners of surgery: generalized abdominal pain that localizes to the right lower quadrant followed by nausea, vomiting, fever, and localized peritoneal irritation in the region of McBurney’s point. When children present in this manner, there should be little diagnostic delay. The child should be made NPO, administered IV fluids and broad-spectrum antibiotics, and brought to the operating room for an appendectomy. However, children often do not present in this manner. The coexistence of nonspecific viral syndromes and the inability of young children to describe the location and quality of their pain often result in diagnostic delay. As a result, children with appendicitis often present with perforation, particularly those who are under 5 years of age. Perforation increases the length of hospital stay and makes the overall course of the illness significantly more complex.
Diagnosis of Appendicitis in Children
Controversy exists regarding the role of radiographic studies in the diagnosis of acute appendicitis. Because children have less periappendiceal fat than adults, CT is less reliable in making the diagnosis. In addition, radiation exposure resulting from the CT scan may have potentially long-term adverse effects. Likewise, US is neither sufficiently sensitive nor specific to accurately make the diagnosis of appendicitis, although it is very useful for excluding ovarian causes of abdominal pain. Therefore, the diagnosis of appendicitis remains largely clinical, and each clinician should develop his or her own threshold to operate or to observe the patient. A reasonable practice guideline is as follows: When the diagnosis is clinically apparent, appendectomy should obviously be performed with minimal delay. Localized right lower quadrant tenderness associated with low-grade fever and leukocytosis in boys should prompt surgical exploration. In girls, ovarian or uterine pathology must also be considered. When there is diagnostic uncertainty, the child may be observed, rehydrated, and reassessed. In girls of menstruating age, US may be performed to exclude ovarian pathology (cysts, torsion, or tumor). If all studies are negative, yet the pain persists, and the abdominal findings remain equivocal, diagnostic laparoscopy may be employed to determine the etiology of the abdominal pain. The appendix should be removed even if it appears to be normal, unless another pathologic cause of the abdominal pain is definitively identified and the appendectomy would substantially increase morbidity.
Surgical Treatment of Appendicitis
The definitive treatment for acute appendicitis is appendectomy. Prior to surgery, it is important that patients receive adequate IV fluids in order to correct dehydration that commonly develops as a result of fever and vomiting in patients with appendicitis. Patients should also be started on antibiotics (such as a second-generation cephalosporin). Most surgeons will perform a laparoscopic appendectomy, which may have some advantage over removing the appendix through a single larger incision. During the laparoscopic appendectomy, a small incision is made at the umbilicus, and two additional incisions are made in the lower abdomen. The appendix is typically delivered through the umbilicus, and all incisions are then closed with dissolvable sutures. If the appendix is not ruptured, the patient may start drinking liquids shortly after waking up from the operation and may be advanced to a solid diet the next day. In general, the same steps are taken when appendectomy is performed through an open approach. The most common complication after appendectomy is a surgical site infection. Other risks, including bleeding or damage to other structures inside the abdomen, are extremely rare. Recovery from surgery is dependent on the individual patient. Most children are back to school approximately 1 week after surgery and usually are allowed to return to full physical activity after 2 to 3 weeks. During the recovery period, over-the-counter pain medication may be required. Older patients tend to require a longer time for full recovery.
Management of the Child with Perforated Appendicitis
The signs and symptoms of perforated appendicitis can closely mimic those of gastroenteritis and include abdominal pain, vomiting, and diarrhea. Alternatively, the child may present with symptoms of intestinal obstruction. An abdominal mass may be present in the lower abdomen. When the symptoms have been present for more than 4 or 5 days and an abscess is suspected, it is reasonable to obtain a CT of the abdomen and pelvis with IV, oral, and rectal contrast to visualize the appendix and the presence of an associated abscess, phlegmon, or fecalith (Fig. 39-21).
Computed tomography scan of the abdomen showing the presence of a ruptured appendix with pelvic fluid and a fecalith (arrow).
An individualized approach is necessary for the child who presents with perforated appendicitis. When there is evidence of generalized peritonitis, intestinal obstruction, or systemic toxicity, the child should undergo appendectomy. This should be delayed only for as long as is required to ensure adequate fluid resuscitation and administration of broad-spectrum antibiotics. The operation can be performed through an open or laparoscopic approach. One distinct advantage of the laparoscopic approach is that it provides excellent visualization of the pelvis and all four quadrants of the abdomen. At the time of surgery, adhesions are gently lysed, abscess cavities are drained, and the appendix is removed. Drains are seldom used, and the skin incisions can be closed primarily. If a fecalith is identified outside the appendix on CT, every effort should be made to retrieve it and to remove it along with the appendix, if at all possible. Often, the child in whom symptoms have been present for more than 4 or 5 days will present with an abscess without evidence of generalized peritonitis. Under these circumstances, it is appropriate to perform image-guided percutaneous drainage of the abscess followed by broad-spectrum antibiotic therapy. The inflammation will generally subside within several days, and the appendix can be safely removed as an outpatient 6 to 8 weeks later. If the child’s symptoms do not improve or if the abscess is not amenable to percutaneous drainage, then laparoscopic or open appendectomy and abscess drainage is required. Patients who present with a phlegmon in the region of a perforated appendix may be managed in a similar manner. In general, children who are younger than 4 or 5 years of age do not respond as well to initial nonoperative approach because their bodies do not localize or isolate the inflammatory process. Thus, these patients are more likely to require early surgical intervention. Patients who have had symptoms of appendicitis for no more than 4 days should probably undergo “early” appendectomy, since the inflammatory response is not as excessive during that initial period and the procedure can be performed safely.
Other Causes of Abdominal Pain That Mimic Appendicitis in Children
As mentioned earlier, appendicitis can be one of the most difficult diagnoses to establish in children with abdominal pain, in part because of the large number of diseases that present in a similar fashion. Patients with urinary tract infection can present very similar to those with appendicitis. However, patients with urinary tract infection are less likely to present with vomiting and are likely to also experience difficulty with urination, characterized by pressure, burning, and frequency. Constipation may be commonly confused with appendicitis in its earliest stages. However, patients with constipation rarely have fever and will not have abnormalities in their blood work. Ovarian torsion can mimic appendicitis, given the severe abdominal pain that accompanies this condition. However, patients with ovarian torsion are generally asymptomatic until the acute onset of severe pain. By contrast, patients with appendicitis generally experience gradual onset of pain associated with nausea and vomiting. Finally, children and young adults are always at risk for the development of gastroenteritis. However, unlike appendicitis, patients with gastroenteritis generally present with persistent vomiting and occasionally diarrhea, which precedes the onset of the abdominal pain.
Duplications represent mucosa-lined structures that are in continuity with the gastrointestinal tract. Although they can occur at any level in the gastrointestinal tract, duplications are found most commonly in the ileum within the leaves of the mesentery. Duplications may be long and tubular, but usually, they are cystic masses. In all cases, they share a common wall with the intestine. Symptoms associated with enteric duplication cysts include recurrent abdominal pain, emesis from intestinal obstruction, or hematochezia. Such bleeding typically results from ulceration in the duplication or in the adjacent intestine if the duplication contains ectopic gastric mucosa. On examination, a palpable mass is often identified. Children may also develop intestinal obstruction. Torsion may produce gangrene and perforation.
The ability to make a preoperative diagnosis of enteric duplication cyst usually depends on the presentation. CT, US, and technetium pertechnetate scanning can be very helpful. Occasionally, a duplication can be seen on small bowel follow-through or barium enema. In the case of short duplications, resection of the cyst and adjacent intestine with end-to-end anastomosis can be performed. If resection of long duplications would compromise intestinal length, multiple enterotomies and mucosal stripping in the duplicated segment will allow the walls to collapse and become adherent. An alternative method is to divide the common wall using the GIA stapler, forming a common lumen. Patients with duplications who undergo complete excision without compromise of the length of remaining intestine have an excellent prognosis.
A Meckel’s diverticulum is a remnant of a portion of the embryonic omphalomesenteric (vitelline) duct. It is located on the antimesenteric border of the ileum, usually within 2 ft of the ileocecal valve (Fig. 39-22). It may be found incidentally at surgery or may present with inflammation masquerading as appendicitis. Perforation of a Meckel’s diverticulum may occur if the outpouching becomes impacted with food, leading to distention and necrosis. Occasionally, bands of tissue extend from the Meckel’s diverticulum to the anterior abdominal wall, and these may represent lead points around which internal hernias may develop. This is an important cause of intestinal obstruction in the older child who has a scarless abdomen. Similar to duplications, ectopic gastric mucosa may produce ileal ulcerations that bleed and lead to the passage of maroon-colored stools. Pancreatic mucosa may also be present. Diagnosis may be made by technetium pertechnetate scans when the patient presents with bleeding. Treatment is surgical. If the base is narrow and there is no mass present in the lumen of the diverticulum, a wedge resection of the diverticulum with transverse closure of the ileum can be performed. A linear stapler is especially useful in this circumstance. When a mass of ectopic tissue is palpable, if the base is wide, or when there is inflammation, it is preferable to perform a resection of the involved bowel and end-to-end ileoileostomy.
Operative photograph showing the presence of a Meckel’s diverticulum (arrow).
Mesenteric cysts are similar to duplications in their location within the mesentery. However, they do not contain any mucosa or muscular wall. Chylous cysts may result from congenital lymphatic obstruction. Mesenteric cysts can cause intestinal obstruction or may present as an abdominal mass. The diagnosis may be made by abdominal US or CT. Treatment involves surgical excision. This may require resection of the adjacent intestine, particularly for extensive, multicystic lesions. In cases where complete excision is not possible due to the close proximity to vital structures, partial excision or marsupialization should be performed.
In his classic textbook entitled Pediatric Surgery, Dr. Orvar Swenson, who is eponymously associated with one of the classic surgical treatments for Hirschsprung’s disease, described this condition as follows: “Congenital megacolon is caused by a malformation in the pelvic parasympathetic system which results in the absence of ganglion cells in Auerbach’s plexus of a segment of distal colon. Not only is there an absence of ganglion cells, but the nerve fibers are large and excessive in number, indicating that the anomaly may be more extensive than the absence of ganglion cells.” This narrative of Hirschsprung’s disease is as accurate today as it was more than 50 years ago and summarizes the essential pathologic features of this disease: absence of ganglion cells in Auerbach’s plexus and hypertrophy of associated nerve trunks. The cause of Hirschsprung’s disease remains incompletely understood, although current thinking suggests that the disease results from a defect in the migration of neural crest cells, which are the embryonic precursors of the intestinal ganglion cell. Under normal conditions, the neural crest cells migrate into the intestine from cephalad to caudad. The process is completed by the twelfth week of gestation, but the migration from midtransverse colon to anus takes 4 weeks. During this latter period, the fetus is most vulnerable to defects in migration of neural crest cells. This may explain why most cases of aganglionosis involve the rectum and rectosigmoid. The length of the aganglionic segment of bowel is therefore determined by the most distal region that the migrating neural crest cells reach. In rare instances, total colonic aganglionosis may occur.
Recent studies have shed light on the molecular basis for Hirschsprung’s disease. Patients with Hirschsprung’s disease have an increased frequency of mutations in several genes, including GDNF, its receptor Ret, or its coreceptor Gfra-1. Moreover, mutations in these genes also lead to aganglionic megacolon in mice, which provides the opportunity to study the function of the encoded proteins. Initial investigations indicate that GDNF promotes the survival, proliferation, and migration of mixed populations of neural crest cells in culture. Other studies have revealed that GDNF is expressed in the gut in advance of migrating neural crest cells and is chemoattractive for neural crest cells in culture. These findings raise the possibility that mutations in the GDNF or Ret genes could lead to impaired neural crest migration in utero and the development of Hirschsprung’s disease.
The incidence of sporadic Hirschsprung’s disease is 1 in 5000 live births. There are reports of increased frequency of Hirschsprung’s disease in multiple generations of the same family. Occasionally such families have mutations in the genes described earlier, including the Ret gene. Because the aganglionic colon does not permit normal peristalsis to occur, the presentation of children with Hirschsprung’s disease is characterized by a functional distal intestinal obstruction. In the newborn period, the most common symptoms are abdominal distention, failure to pass meconium, and bilious emesis. Any infant who does not pass meconium beyond 48 hours of life must be investigated for the presence of Hirschsprung’s disease. Occasionally, infants present with a dramatic complication of Hirschsprung’s disease called enterocolitis. This pattern of presentation is characterized by abdominal distention and tenderness and is associated with manifestations of systemic toxicity that include fever, failure to thrive, and lethargy. Infants are often dehydrated and demonstrate a leukocytosis or increase in circulating band forms on hematologic evaluation. On rectal examination, forceful expulsion of foul-smelling liquid feces is typically observed and represents the accumulation of stool under pressure in an obstructed distal colon. Treatment includes rehydration, systemic antibiotics, nasogastric decompression, and rectal irrigations while the diagnosis of Hirschsprung’s disease is being confirmed. In children who do not respond to nonoperative management, a decompressive stoma is required. It is important to ensure that this stoma is placed in ganglion-containing bowel, which must be confirmed by frozen section at the time of stoma creation.
In approximately 20% of cases, the diagnosis of Hirschsprung’s disease is made beyond the newborn period. These children have severe constipation, which has usually been treated with laxatives and enemas. Abdominal distention and failure to thrive may also be present at diagnosis.
The definitive diagnosis of Hirschsprung’s disease is made by rectal biopsy. Samples of mucosa and submucosa are obtained at 1, 2, and 3 cm from the dentate line. This can be performed at the bedside in the neonatal period without anesthesia, as samples are taken in bowel that does not have somatic innervation and is thus not painful to the child. In older children, the procedure should be performed using IV sedation. The histopathology of Hirschsprung’s disease is the absence of ganglion cells in the myenteric plexuses, increased acetylcholinesterase staining, and the presence of hypertrophied nerve bundles.
It is important to obtain a barium enema in children in whom the diagnosis of Hirschsprung’s disease is suspected. This test may demonstrate the location of the transition zone between the dilated ganglionic colon and the distal constricted aganglionic rectal segment. Our practice is to obtain this test before instituting rectal irrigations if possible, so that the difference in size between the proximal and distal bowel is preserved. Although the barium enema can only suggest, but not reliably establish, the diagnosis of Hirschsprung’s disease, it is very useful in excluding other causes of distal intestinal obstruction. These include small left colon syndrome (as occurs in infants of diabetic mothers), colonic atresia, meconium plug syndrome, or the unused colon observed in infants after the administration of magnesium or tocolytic agents. The barium enema in total colonic aganglionosis may show a markedly shortened colon. Some surgeons have found the use of rectal manometry helpful, particularly in older children, although it is relatively inaccurate.
The diagnosis of Hirschsprung’s disease requires surgery in all cases. The classic surgical approach consisted of a multiple-stage procedure. This included a colostomy in the newborn period, followed by a definitive pull-through operation after the child was over 10 kg. There are three viable options for the definitive pull-through procedure that are currently used. Although individual surgeons may advocate one procedure over another, studies have demonstrated that the outcome after each type of operation is similar. For each of the operations that is performed, the principles of treatment include confirming the location in the bowel where the transition zone between ganglionic and aganglionic bowel exists, resecting the aganglionic segment of bowel, and performing an anastomosis of ganglionated bowel to either the anus or a cuff of rectal mucosa (Fig. 39-23).
The three operations for surgical correction of Hirschsprung’s disease. A. The Duhamel procedure leaves the rectum in place and brings ganglionic bowel into the retrorectal space. B. The Swenson procedure is a resection with end-to-end anastomosis performed by exteriorizing bowel ends through the anus. C. The Soave operation is performed by endorectal dissection and removal of mucosa from the aganglionic distal segment and bringing the ganglionic bowel down to the anus within the seromuscular tunnel.
It is now well established that a primary pull-through procedure can be performed safely, even in the newborn period. This approach follows the same treatment principles as a staged procedure and saves the patient from an additional surgical procedure. Many surgeons perform the intra-abdominal dissection using the laparoscope. This approach is especially useful in the newborn period, as this provides excellent visualization of the pelvis. In children with significant colonic distention, it is important to allow for a period of decompression using a rectal tube if a single-staged pull-through is to be performed. In older children with very distended, hypertrophied colon, it may be prudent to perform a colostomy to allow the bowel to decompress, prior to performing a pull-through procedure. However, it should be emphasized that there is no upper age limit for performing a primary pull-through.
Of the three pull-through procedures performed for Hirschsprung’s disease, the first is the original Swenson procedure. In this operation, the aganglionic rectum is dissected in the pelvis and removed down to the anus. The ganglionic colon is then anastomosed to the anus via a perineal approach. In the Duhamel procedure, dissection outside the rectum is confined to the retrorectal space, and the ganglionic colon is anastomosed posteriorly just above the anus. The anterior wall of the ganglionic colon and the posterior wall of the aganglionic rectum are anastomosed using a stapler. Although both of these procedures are extremely effective, they are limited by the possibility of damage to the parasympathetic nerves that are adjacent to the rectum. To circumvent this potential problem, the Soave procedure involves dissection entirely within the rectum. The rectal mucosa is stripped from the muscular sleeve, and the ganglionic colon is brought through this sleeve and anastomosed to the anus. This operation may be performed completely from below. In all cases, it is critical that the level at which ganglionated bowel exists be determined. Most surgeons believe that the anastomosis should be performed at least 5 cm from the point at which ganglion cells are found. This avoids performing a pull-through in the transition zone, which is associated with a high incidence of complications due to inadequate emptying of the pull-through segment. Up to one third of patients who undergo a transition zone pull-through will require a reoperation.
The main complications of all of the procedures include postoperative enterocolitis, constipation, and anastomotic stricture. As mentioned, long-term results with the three procedures are comparable and generally excellent in experienced hands. These three procedures also can be adapted for total colonic aganglionosis in which the ileum is used for the pull-through segment.
Anorectal malformations describe a spectrum of congenital anomalies that include imperforate anus and persistent cloaca. Anorectal malformations occur in approximately 1 in 5000 live births and affect males and females almost equally. The embryologic basis includes failure of descent of the urorectal septum. The level to which this septum descends determines the type of anomaly that is present, which subsequently influences the surgical approach.
In patients with imperforate anus, the rectum fails to descend through the external sphincter complex. Instead, the rectal pouch ends “blindly” in the pelvis, above or below the levator ani muscle. In most cases, the blind rectal pouch communicates more distally with the genitourinary system or with the perineum through a fistulous tract. Traditionally, anatomic description of imperforate anus has been characterized as either “high” or “low” depending on whether the rectum ends above the levator ani muscle complex or partially descends through this muscle (Fig. 39-24). Based on this classification system, in male patients with high imperforate anus, the rectum usually ends as a fistula into the membranous urethra. In females, high imperforate anus often occurs in the context of a persistent cloaca. In both males and females, low lesions are associated with a fistula to the perineum. In males, the fistula connects with the median raphe of the scrotum or penis. In females, the fistula may end within the vestibule of the vagina, which is located immediately outside the hymen or at the perineum.
Low imperforate anus in a male. Note the well-developed buttocks. The perineal fistula was found at the midline raphe.
Because this classification system is somewhat arbitrary, Peña proposed a classification system that specifically and unambiguously describes the location of the fistulous opening. In males, the fistula may communicate with: (a) the perineum (cutaneous perineal fistula); (b) the lowest portion of the posterior urethra (rectourethral bulbar fistula); (c) the upper portion of the posterior urethra (rectourethral prostatic fistula); or (d) the bladder neck (rectovesicular fistula). In females, the fistula may open to the perineum between the female genitalia and the center of the sphincter (cutaneous perineal fistula) or into the vestibule of the vagina (vestibular fistula) (Fig. 39-25). In both sexes, the rectum may end in a completely blind fashion (imperforate anus without fistula). In rare cases, patients may have a normal anal canal, yet there may be total atresia or severe stenosis of the rectum.
Imperforate anus in a female. A catheter has been placed into the fistula, which is in the vestibule of the vagina.
The most frequent defect in males is imperforate anus with rectourethral fistula, followed by rectoperineal fistula then rectovesical or rectobladder neck fistula. In females, the most frequent defect is the rectovestibular fistula, followed by the cutaneous perineal fistula. The third most common defect in females is the persistent cloaca. This lesion represents a wide spectrum of malformations in which the rectum, vagina, and urinary tract meet and fuse into a single common channel. On physical examination, a single perineal orifice is observed and is located at the place where the urethra normally opens. Typically, the external genitalia are hypoplastic.
Approximately 60% of patients have an associated malformation. The most common is a urinary tract defect, which occurs in approximately 50% of patients. Skeletal defects are also seen, and the sacrum is most commonly involved. Spinal cord anomalies, especially tethered cored, are common, particularly in children with high lesions. Gastrointestinal anomalies occur, most commonly EA. Cardiac anomalies may be noted, and occasionally patients present with a constellation of defects as part of the VACTERLL syndrome (described earlier).
Management of Patients with Imperforate Anus
Patients with imperforate anus are usually stable, and the diagnosis is readily apparent. Despite the obstruction, the abdomen is initially not distended, and there is rarely any urgency to intervene. The principles of management center around diagnosing the type of defect that is present (high vs. low) and evaluating the presence of associated anomalies. It may take up to 24 hours before the presence of a fistula on the skin is noted, and thus it is important to observe the neonate for some period before definitive surgery is undertaken. All patients should therefore have an orogastric tube placed and be monitored for the appearance of meconium in or around the perineum or in the urine. Investigation for associated defects should include an US of the abdomen to assess for the presence of urinary tract anomaly. Other tests should include an echocardiogram and spinal radiographs. A US of the spine should be performed to look for the presence of a tethered cord. To further classify the location of the fistula as either “high” vs. “low,” a lateral abdominal radiograph can be obtained with a radiopaque marker on the perineum. By placing the infant in the inverted position, the distance between the most distal extent of air in the rectum and the perineal surface can be measured. This study is imprecise, however, and may add little to the overall management of these patients.
The surgical management of infants with imperforate anus is determined by the anatomic defect. In general, when a low lesion is present, only a perineal operation is required without a colostomy. Infants with a high lesion require a colostomy in the newborn period, followed by a pull-through procedure at approximately 2 months of age. When a persistent cloaca is present, the urinary tract needs to be carefully evaluated at the time of colostomy formation to ensure that normal emptying can occur and to determine whether the bladder needs to be drained by means of a vesicostomy. If there is any doubt about the type of lesion, it is safer to perform a colostomy rather than jeopardize the infant’s long-term chances for continence by an injudicious perineal operation.
The type of pull-through procedure favored by most pediatric surgeons today is the posterior sagittal anorectoplasty (PSARP) procedure, as described by Peña and DeVries. This involves placing the patient in the prone jackknife position, dividing the levator ani and external sphincter complex in the midline posteriorly, dividing the communication between the gastrointestinal tract and the urinary tract, and bringing down the rectum after sufficient length is achieved. The muscles are then reconstructed and sutured to the rectum. The outcome of 1192 patients who had undergone this procedure has been reviewed by Peña and Hong. Seventy-five percent of patients were found to have voluntary bowel movements, and nearly 40% were considered totally continent. As a rule, patients with high lesions demonstrate an increased incidence of incontinence, whereas those with low lesions are more likely to be constipated. Management of patients with high imperforate anus can be greatly facilitated using a laparoscopic-assisted approach, in which the patient is operated on in the supine position, and the rectum is mobilized down to the fistulous connection to the bladder neck. This fistulous connection is then divided, and the rectum is completely mobilized down to below the peritoneal reflection. The operation then proceeds at the perineum, and the location of the muscle complex is determined using the nerve stimulator. A Veress needle is then advanced through the skin at the indicated site, with the laparoscope providing guidance to the exact intrapelvic orientation. Dilators are then placed over the Veress needle, the rectum is pulled through this peritoneal opening, and an anoplasty is performed.