Hirschsprung Disease 

Updated: May 13, 2020
Author: Justin P Wagner, MD; Chief Editor: BS Anand, MD 

Overview

Background

Hirschsprung disease is a developmental disorder characterized by the absence of ganglia in the distal colon, resulting in a functional obstruction.[1] See the images below.

A: Plain abdominal radiograph showing a transition A: Plain abdominal radiograph showing a transition zone (PARTZ) at the rectosigmoid. B: Plain abdominal radiograph showing a PARTZ at the midsigmoid. C: Plain abdominal radiograph showing a PARTZ at the descending colon. D: Contrast enema showing a contrast enema transition zone (CETZ) at the rectosigmoid. E: Contrast enema showing a CETZ at the midsigmoid. F: Contrast enema showing a CETZ at descending colon. Images courtesy of Pratap A, Gupta DK, Tiwari A, et al. BMC Pediatr. 2007 Jan 27;7:5. [Open access.] PMID: 17257439, PMCID: PMC1790893.

Most cases of Hirschsprung disease are diagnosed in the newborn period. Hirschsprung disease should be considered in any newborn who fails to pass meconium within 24-48 hours of birth. Although contrast enema is useful in establishing the diagnosis, full-thickness rectal biopsy remains the criterion standard. Once the diagnosis is confirmed, the definitive treatment is to remove the aganglionic bowel and to restore continuity of the healthy bowel with the distal rectum, with or without an initial intestinal diversion.

Historical notes

Although this condition was described by Ruysch in 1691 and popularized by Hirschsprung in 1886, the pathophysiology was not clearly determined until the middle of the 20th century, when Whitehouse and Kernohan reported aganglionosis of the distal colon as the cause of obstruction in a case series.[2]

In 1949, Swenson described the first consistent definitive procedure for Hirschsprung disease, rectosigmoidectomy with coloanal anastomosis. Since then, other operations have been described, including the Duhamel and Soave techniques. More recently, earlier diagnosis and advances in surgical techniques have resulted in decreased morbidity and mortality in patients with Hirschsprung disease.

Also see Pediatric Hirschsprung Disease and Hirschsprung Disease Imaging.

Pathophysiology

Three nerve plexuses innervate the intestine: the submucosal (Meissner) plexus, the myenteric (Auerbach) plexus (between the longitudinal and circular muscle layers), and the smaller mucosal plexus. All of these plexuses are finely integrated and are involved in all aspects of bowel function, including absorption, secretion, motility, and blood-flow regulation.

Normal motility is primarily under the control of intrinsic neurons. In the absence of extrinsic signals, bowel function remains adequate, owing to the complex reflexive architecture of the enteric nervous system (ENS). For this reason, the ENS is often referred to as the “second brain.” Intestinal smooth muscle contraction and relaxation are under the control of enteric ganglia. Most enteric nervous activation causes muscle relaxation, mediated by nitric oxide and other enteric neurotransmitters. Extrinsic neural afferents to the ENS contain cholinergic and adrenergic fibers. The cholinergic fibers generally cause contraction, whereas the adrenergic fibers mainly cause inhibition.

In patients with Hirschsprung disease, both myenteric and submucosal plexuses are absent. The anus is invariably affected, and aganglionosis continues proximally for a variable distance. In the absence of ENS reflexes, control of the intestinal smooth muscle is overwhelmingly extrinsic. The activity of both the cholinergic system and the adrenergic system is 2-3 times that of normal intestine. The cholinergic (excitatory) system is thought to predominate over the adrenergic (inhibitory) system, leading to an increase in smooth muscle tone. With the loss of the intrinsic enteric relaxing impulses, the increased muscle tone is unopposed. This phenomenon leads to an imbalance of smooth muscle contractility, uncoordinated peristalsis, and a functional obstruction.

Enteric ganglion cells are derived from the neural crest during embryonic development. In normal development, the neuroblasts are found in the esophagus by the fifth week of gestation, and they migrate to the small intestine by the seventh week and to the colon by the twelfth week.[3] One possible etiology of Hirschsprung disease is the arrest of aboral neuroblast migration. Alternatively, although normal cell migration may occur, neuroblasts may be subject to apoptosis, failure of proliferation, or improper differentiation within the affected distal intestinal segment. Fibronectin, laminin, neural cell adhesion molecule (NCAM), and neurotrophic factors present in the intestinal stroma are necessary for normal enteric ganglion development, whereas their absence or dysfunction may also have a role in the etiology of Hirschsprung disease.[4, 5, 6]

Investigators have also identified several genes whose improper expression results in a Hirschsprung disease phenotype. Genome-wide association studies (GWAS) in Europeans and Asians have identified three common disease-susceptibility variants at the RET, SEMA3, and NRG1 loci.[7] Rs80227144 is a low-frequency variant of SEMA3 that has been associated with Europeans, and a conditional analysis indicates that rs9282834, low-frequency missense variant encoding RET p.Asp489Asn, is specific to Asians.[7]

The RET protooncogene has been implicated in several studies of Hirschsprung pathogenesis.

So and colleagues discovered that rare variants of RET were associated with more severe phenotypes among Chinese Hirschsprung patients.[8] Leon and colleagues determined that sporadic RET coding sequence mutations in Hirschsprung patients resulted in protein truncations that would deter cell membrane translocation and anchoring.[9]

Qin and colleagues performed microarray analyses of aganglionic colon and normal tissue; they discovered 622 genes with anomalous expression in the aganglionic tissue, and myenteric HAND2 expression was significantly attenuated.[10]

In a comparison of gene expression among normal and aganglionic colon, Chen and colleagues determined that overexpression of DVL1 and DVL3 genes was associated with the Hirschsprung phenotype.[11]

In a review, Butler Tjaden and Trainor reported that mutations in the genes, RET, GDNF, GFRα1, NRTN, EDNRB, ET3, ZFHX1B, PHOX2b, SOX10, and SHH are present in approximately 50% of Hirschsprung disease patients.[12]

These studies indicate the complexity of Hirschsprung pathogenesis. Ongoing studies of genetic and environmental factors will continue to elucidate this problematic disease in the future.

Although enteric ganglion cells are the primary pathogenic entity in Hirschsprung disease, some studies suggest that other cell types may also be implicated.[13, 14, 15, 16, 17] When extrinsically stimulated, smooth muscle cells in aganglionic colon are electrically inactive.[13] Furthermore, interstitial cells of Cajal, pacemaker cells connecting enteric nerves and intestinal smooth muscle, have also been postulated as an important contributing factor.[14, 15, 16] These findings suggests that Hirschsprung pathophysiology is not limited to cells normally present within the enteric ganglia, alone.

Epidemiology

United States statistics

Hirschsprung disease affects approximately 1 case per 5400-7200 newborns annually.

International statistics

Although the exact worldwide incidence is unknown, international studies have reported rates ranging from approximately 1 case per 1500-7000 newborns.[18, 19]

Race-, sex-, and age-related demographics

Hirschsprung disease affects all races; however, it is roughly 3 times more common among Asian-Americans.[20]

This disease occurs more often in males than in females, with a male-to-female ratio of approximately 4:1; however, the ratio in long-segment disease decreases to 2:1.

Hirschsprung disease is uncommon in premature infants. However, the age at which Hirschsprung disease is diagnosed has progressively decreased over the past century. In the early 1900s, the median age at diagnosis was 2-3 years; from the 1950s to 1970s, the median age was 2-6 months. Currently, approximately 90% of patients with Hirschsprung disease are diagnosed in the newborn period.[21]

Prognosis

Reports of long-term outcomes after definitive repair for Hirschsprung disease are conflicting. Some investigators report a high degree of satisfaction, whereas others report a significant incidence of constipation and incontinence. In general, more than 90% of patients with Hirschsprung disease report satisfactory outcomes; however, many patients experience disturbances of bowel function for several years before normal continence is established. Approximately 1% of patients with Hirschsprung disease have debilitating incontinence requiring a permanent colostomy.

Total colonic aganglionosis is associated with a poorer outcome, with 33% of patients experiencing persistent incontinence and 14% requiring a permanent ileostomy. Patients with associated chromosomal abnormalities and syndromes also have poorer clinical outcomes.

Morbidity/mortality

Hirschsprung disease is confined to the rectosigmoid region in about 75% of cases. Approximately 60% of infants with Hirschsprung disease have an associated condition, ranging from subtle to severe. Ophthalmologic problems affect 43% of infants, 20% have congenital anomalies of the genitourinary tract, 5% have congenital heart disease, 5% have hearing impairment, and 2% have central nervous system anomalies.[22, 23]

Hirschsprung disease is associated with chromosomal abnormalities or syndromes in approximately 9% of cases.[23] It may be associated with the following syndromes:

  • Down syndrome: Trisomy 21 is characterized by physical growth delays, characteristic facial features, and varying degrees of intellectual disability.

  • Neurocristopathy syndromes: Neurocristopathies represent a broad range of disorders characterized by aberrant neural crest development.

  • Waardenburg-Shah syndrome: Patients have a sensorineural hearing deficit and hypopigmentation of the iris and hair.

  • Yemenite deaf-blind syndrome: Affected patients have a mutation in the SRY-related HMG-box gene. The syndrome is characterized by a severe hearing deficit, nystagmus, patchy pigmentation abnormalities, and defects of the iris and cornea.

  • Piebaldism: Patients have patches of hypopigmentation due to a congenital disorder of melanocytes. Underlying pathology in the neural crest development is also common to Hirschsprung disease.

  • Multiple endocrine neoplasia type II (MEN2): Mutations in the RET protooncogene are associated with medullary thyroid cancer in MEN2 and Hirschsprung disease.

  • Congenital central hypoventilation syndrome (CCHS): CCHS is characterized by absent autonomic control of ventilation. PHOX2B transcription factor mutations may be associated in both CCHS and Hirschsprung disease.

Untreated aganglionic megacolon in infancy may result in a mortality rate as high as 80%. Operative mortality rates for any of the interventional procedures are very low. Even in cases of treated Hirschsprung disease, the mortality rate may approach 30% as a result of severe enterocolitis.

Possible complications of surgery include anastomotic leak (5%), anastomotic stricture (5%-10%), intestinal obstruction (5%), pelvic abscess (5%), and wound infection (10%). Long-term complications mostly affect patients with long-segment disease. These include chronic obstructive symptoms, incontinence, chronic constipation, enterocolitis, and late mortality. Although many patients encounter one or more of these problems postoperatively, long-term follow-up studies have shown that greater than 90% of children experience significant improvement.[24] Patients with a syndromic association and those with long-segment disease have poorer outcomes.[25, 26, 27]

Complications

Potential complications for the complex operations associated with Hirschsprung disease encompass the entire spectrum of gastrointestinal surgical complications. The incidence rates of these complications do not appear to vary significantly with the surgeon’s experience.

The most frequent postoperative complications include enterocolitis after the Swenson procedure, constipation following the Duhamel repair, and diarrhea and incontinence after the Soave pull-through procedure.

Overall, the most common complications are anastomotic leakage and stricture formation in 5%-15%, wound infection in 10%, intestinal obstruction in 5%, pelvic abscess in 5%, and reoperation in 5% of patients. After intestinal diversion, patients may also develop enterostomal complications, such as prolapse, herniation, or stricture.

In a retrospective (1979-2016) study of medical chart information from 657 Korean patients with Hirschsprung disease who underwent pull-through surgeries, investigators found 49 patients (7.5%) had redo pull-through procedures.[28] Causes of redo included pathologic problems (aganglionosis, hypoganglionosis, immature ganglion cell) and anatomic problems (stricture, fistula and/or abscess at anastomosis), with those who had anatomic problems undergoing third redo procedures more than the group with pathologic problems.[28]

Enterocolitis, chronic obstruction, incontinence, constipation, and late mortality may occur late after surgery. Rectovesical fistulas have also been reported in the literature.[29]

Enterocolitis accounts for significant morbidity and mortality in patients with Hirschsprung disease and can progress into toxic megacolon.[30] Enterocolitis is characterized by inflammation of the colon or the small intestinal mucosa. As the disease progresses, the intestinal lumen fills with a fibrinous exudate, and the risk of perforation increases. This process may occur in either aganglionic or ganglionic segments of the bowel. Patients typically present with explosive diarrhea, abdominal distention, fever, emesis, and lethargy. Approximately 10%-30% of patients with Hirschsprung disease develop enterocolitis. Long-segment disease is associated with an increased incidence of enterocolitis. The risk of enterocolitis does not decrease with surgical correction.

Patients may present postoperatively with abdominal distention, emesis, or constipation indicative of ongoing obstruction.[31] Mechanical obstruction can be diagnosed with digital rectal examination and barium enema. Serial anorectal dilatations or surgical revision of the pull-through may be required.[4]

Persistent aganglionosis occurs rarely and may be due to pathologic error, inadequate resection, or loss of ganglion cells after the pull-through procedure.[32] If a rectal biopsy does not show ganglion cells, revision of the pull-through must be done.[33, 34, 35, 36]

Hirschsprung disease may be associated with other disorders of intestinal motility. Contrast studies, manometry, and biopsy may be necessary to evaluate for intestinal neuronal dysplasia.[37, 38]

Internal sphincter achalasia may result in persistent obstruction. This can be treated with internal sphincterotomy, intrasphincteric botulinum toxin, or nitroglycerin paste. Most cases resolve by age 5 years.[39, 40]

Functional megacolon may be present due to stool-holding behavior. Bowel management regimens may be implemented with cecostomy and antegrade enemas reserved for refractory cases.[41]

Incontinence may be the result of abnormal sphincter function, decreased sensation, or overflow incontinence secondary to constipation.[31] Anorectal manometry and ultrasonography are useful to distinguish between these entities.

 

Presentation

History

The majority of Hirschsprung cases are sporadic. Approximately 10% of Hirschsprung patients have a family member who was also affected. This predisposition is more common in patients with longer-segment disease.

Prenatal ultrasonography demonstrating bowel obstruction is rare, except in cases of total colonic involvement.[42]

Hirschsprung disease should be considered in any newborn with delayed passage of meconium or in any child with a history of chronic constipation since birth. Other symptoms include bowel obstruction with bilious vomiting, abdominal distention, poor feeding, and failure to thrive.

Older children with Hirschsprung disease usually have chronic constipation since birth. They may also show evidence of poor weight gain.

Older presentation is more common in breastfed infants who will typically develop constipation around the time of weaning.

Despite significant constipation and abdominal distention, children with Hirschsprung disease rarely develop encopresis (fecal incontinence secondary to impacted stools). In contrast, children with functional constipation or stool-withholding behaviors more commonly develop encopresis.

About 10% of children present with diarrhea caused by enterocolitis, which is hypothesized to stem from stasis and bacterial overgrowth. This may progress to colonic perforation, causing life-threatening sepsis.[43]

In a study of 259 consecutive patients, Menezes and colleagues reported that 57% of patients presented with intestinal obstruction, 30% with constipation, 11% with enterocolitis, and 2% with intestinal perforation.[29]

Wu and colleagues developed a diagnostic scoring system for elements of the patient’s history. Risk factors identified include age younger than 3 years, failed or delayed passage of meconium, and male sex. Scaled scores indicating Hirschsprung disease predict the disease with a sensitivity of 83%, specificity of 90%, and accuracy of 86%.[44]

Physical Examination

Physical examination in the newborn period is often nondiagnostic; however, it may reveal a distended abdomen and/or anal spasm. In older children, abdominal distention may result from the inability to release flatus.

A low imperforate anus with a perineal orifice may have a similar presentation to that of a patient with Hirschsprung disease. Meticulous physical examination is compulsory to distinguish the two.

 

DDx

 

Workup

Laboratory Studies

Chemistry panel

For most patients, electrolyte and renal panel findings are within the reference ranges. Children presenting with diarrhea may have findings consistent with dehydration. Test results may aid in directing fluid and electrolyte management.

Complete blood cell (CBC) count

This test is obtained to ensure that the preoperative hematocrit and platelet count are suitable for surgery. In most cases, values are within the reference ranges.

Coagulation studies

These studies are obtained to ensure that clotting disorders are corrected before surgery. Coagulation parameters are expected to be within the reference ranges.

Imaging Studies

Plain abdominal radiographs may show distended bowel loops with a paucity of air in the rectum.

With regard to barium enema, avoid washing out the distal colon with enemas before obtaining the contrast enema because this may distort a low transition zone. The catheter is placed just inside the anus without inflation of the balloon to avoid distortion of a low transition zone and perforation. Radiographs are taken immediately after hand injection of the contrast and again 24 hours later.

The classic finding of Hirschsprung disease is a narrowed distal colon with proximal dilation; however, the findings are difficult to interpret in neonates (age < 1 mo) and do not demonstrate this transition zone in approximately 25% of the time.[45] Retention of rectal contrast for longer than 24 hours after the barium enema also suggests a diagnosis of Hirschsprung disease.

Other Tests

Anorectal manometry detects the relaxation reflex of the internal sphincter after distention of the rectal lumen. This normal inhibitory reflex is presumed absent in patients with Hirschsprung disease.[46] Swenson initially used this test. In the 1960s, it was refined but has fallen out of favor because of its many limitations. Sedation is usually necessary. Although some authors find this test useful, false-positive results have been reported in up to 62% and false-negative results have been reported in up to 24% of cases. Because of these limitations, anorectal manometry is not commonly performed in the United States.

Echocardiography and chromosomal analyses may be warranted to evaluate for any associated congenital conditions.

Procedures

Full-thickness rectal biopsy

The definitive diagnosis of Hirschsprung disease is confirmed by a full-thickness rectal biopsy demonstrating the absence of ganglion cells. The specimen must be obtained at least 1.5 cm above the dentate line because aganglionosis may normally be present below this level. Disadvantages of full-thickness rectal biopsy include the necessity of general anesthesia and the risks of bleeding and scarring.

Suction rectal biopsy

Simple suction rectal biopsy has been used to obtain tissue for histologic examination. Rectal mucosa and submucosa are sucked into the suction device, and a self-contained cylindrical blade excises the tissue. The distinct advantage of the suction biopsy is that it can be easily performed at the bedside. The diagnostic yield of the full-thickness rectal biopsy is significantly better than that of the suction biopsy.

Histologic Findings

Acetylcholinesterase staining reveals hypertrophied nerve trunks throughout the lamina propria and muscularis propria layers of the bowel wall. Although acetylcholinesterase histochemistry can be a useful ancillary technique to help in the diagnosis and preoperative planning,[47] studies have suggested that immunohistochemical (IHC) staining for calretinin might be more accurate than acetylcholinesterase staining in diagnosing congenital aganglionosis in suction biopsy specimens.[48, 49]

Guinard-Samuel and colleagues evaluated the diagnostic value of calretinin IHC for Hirschsprung disease in 131 pediatric rectal biopsies. Of the 131 biopsies, 130 were accurately diagnosed based on calretinin staining. When an additional 12 cases were considered doubtful based on the standard evaluation method, they were accurately diagnosed with calretinin IHC. The investigators found calretinin superior to acetylcholinesterase to complete histology.[49]

In another study that evaluated the diagnostic value of calretinin IHC staining compared with standard hematology and eosin (H&E) staining of rectal suction biopsies over 1 year in 188 children with Hirschsprung disease, Tran et al confirmed the disease in 80 children (42.6%), with 1 false positive, no false negatives, and no serious complications associated with the procedure.[50] Calretinin and H&E staining both had a 100% sensitivity, but whereas the specificity was 99.1% for calretinin staining, it was 85.2% for H&E.

Yang and colleagues identified the presence or absence of ganglion cells via IHC staining for calretinin and microtubule associated protein-2 (MAP-2) in 52 samples of normal and aganglionic bowel. Calretinin IHC correctly identified ganglia in 11 samples originally reported as false positives from surgical pathology reports.[51]

 

Treatment

Approach Considerations

If Hirschsprung disease is suspected, neonates and children should be assigned to a center where pediatric specialists are available to make the diagnosis and to provide definitive care.[52]

Consult with pediatric surgeons and pediatric gastroenterologists. Genetic consultation may be indicated (if a heritable or chromosomal anomaly is suspected).

It is important that conversations between patients and/or caregivers and clinicians take place regarding transitions in care from pediatric providers to adult providers, and that plans for transitional care be implemented early.[53]

Hirschsprung disease cannot be prevented; however, perceptive clinical acumen may prevent delays in the diagnosis.

Medical Care

The general goals of medical care are three-fold: (1) to treat the manifestations and complications of untreated Hirschsprung disease, (2) to institute temporizing measures until definitive reconstructive surgery, and (3) to manage the postoperative bowel function.

The objectives of medical care are to maintain normal fluid and electrolyte balance, to minimize bowel distention and prevent perforation, and to manage complications. Intravenous fluid resuscitation and maintenance, nasogastric decompression, and administration of intravenous antibiotics (as indicated) remain the cornerstones of initial medical management.

Colonic lavage, consisting of mechanical irrigation with a large-bore rectal tube and large volumes of irrigant, may be required.

Intravenous administration of balanced salt solutions may help prevent electrolyte imbalances.

Postoperative medical management

Postoperatively, routine colonic irrigation and prophylactic antibiotic therapy may decrease the risk of developing enterocolitis.[54, 55] For patients who do develop enterocolitis, nasogastric decompression, intravenous fluids, antibiotics, and colonic lavage may be necessary. Sodium cromoglycate, a mast cell stabilizer, has also been reported to benefit these patients.[56]

Botulinum toxin injections within the contracted internal sphincter mechanism have been reported to induce more normal patterns of bowel movements in postoperative patients with obstruction[57] or enterocolitis.[58]

In 2017, the American Pediatric Surgical Association (APSA) Hirschsprung Disease Interest Group released guidelines for managing Hirschsprung-associated enterocolitis.[59] In general, treatment of enterocolitis consists of intravenous antibiotics and aggressive colonic irrigations.[59] Some experts advocate decompression of the bowel, especially in patients with long-segment disease, by placing an enterostomy proximal to the transition zone.

Diet and activity

The patient should have nothing by mouth for 6-8 hours prior to operation.

Postoperatively, the patient will receive intravenous fluids and antibiotics; however, nothing may be administered by mouth until the passage of flatus or stool signifies return of bowel function. If a newborn undergoes creation of a diverting colostomy, the passage of flatus or stool from the stoma is necessary prior to the institution of oral feeding.

Upon resumption of bowel function, tube feeding or formula/breast milk may resume. Clear liquids are delivered by mouth, and the diet may be advanced until the feeding goals are met. Feedings are usually initiated 24-48 hours after the creation of a colostomy. The patient may be discharged from the hospital upon attaining full feedings.

Diets consisting of fresh fruits, vegetables, and high-fiber articles may improve postoperative bowel function.

With regard to activity, limit physical activity for about 6 weeks to allow the incisions to heal properly (applies more to older children).

Also see Pediatric Hirschsprung Disease and Hirschsprung Disease Imaging.

Surgical Care

Surgical management of Hirschsprung disease begins with the initial diagnosis, which often requires a full-thickness rectal biopsy. Traditionally, a diverting colostomy was created at the time of diagnosis, and definitive repair was delayed until the child grew to a weight of 10 kilograms.

This standard of treatment was developed in the 1950s after Swenson reported relatively high leak and stricture rates with a single-stage operation.

Advancements in anesthesia administration and hemodynamic monitoring have led many surgeons to advocate a single-stage pull-through procedure without initial diversion. Contraindications to a single-stage procedure include severely dilated proximal bowel, severe enterocolitis, perforation, malnutrition, and inability to accurately determine the zone of transition between healthy and aganglionic bowel, intraoperatively.

For neonates undergoing creation of a diverting colostomy, the transition zone is identified and the colostomy is placed proximal to this area. The presence of ganglion cells at the colostomy site must be unequivocally confirmed by histological evaluation of a frozen-section biopsy. Either a loop- or end-colostomy is created at the surgeon’s discretion.

A number of definitive procedures have demonstrated excellent results when performed by experienced surgeons. The most commonly performed repairs are the Swenson, Duhamel, and Soave procedures. In any elective operation for Hirschsprung disease, a robust preoperative colon cleansing must be performed.[60] Intraoperatively, histological examination of a frozen-section biopsy must confirm the presence of ganglion cells at the proximal margin of bowel intended for anastomosis. A meta-analysis performed by Friedmacher and Puri in 2011 reported that residual aganglionosis and transition-zone tissue account for persistent bowel symptoms in one third of patients undergoing a second, corrective pull-through procedure.[32]

However, long-term complications of pull-through procedures may include intermittent enterocolitis, severe stool retention, as well as intestinal obstruction.[52]

In 2017, the American Pediatric Surgical Association (APSA) Hirschsprung Disease Interest Group released guidelines for managing postoperative obstructive symptoms that include an algorithm to aid in the diagnosis and treatment of such symptoms following pull-through procedures.[61] They indicated that the causes of postprocedure obstructive symptoms include the following and should be ruled out to determine treatment[61] :

  • Mechanical obstruction

  • Persistent/acquired aganglionosis, hypoganglionosis, or transition zone in the pull-through bowel

  • Internal sphincter achalasia

  • Motility disorder in the proximal intestine that contains ganglion cells

  • Functional megacolon caused by stool-holding behavior

In 2019, the APSA Hirschsprung Disease Interest Group released guidelines for managing postoperative soiling in children with Hirschsprung disease.[62] In the small group of patients who do not fare well following pull-through surgery, the most common problems include soiling, obstructive symptoms, enterocolitis, and failure to thrive. Management includes a combination of bowel management, dietary changes, and laxatives. If indicated, a redo operation may be considered.[62]

Also see Pediatric Hirschsprung Disease and Hirschsprung Disease Imaging.

Swenson procedure

The Swenson procedure was the original pull-through procedure used to treat Hirschsprung disease. The aganglionic segment is resected down to the sigmoid colon and rectum, and an oblique anastomosis is performed between the normal colon and the low rectum.

Duhamel procedure

The Duhamel procedure was first described in 1956 as a modification to the Swenson procedure. A retrorectal approach is used, and a significant segment of aganglionic rectum is retained.

The aganglionic bowel is resected down to the rectum, and the rectum is oversewn. The proximal bowel is then brought through the retrorectal space (between rectum and sacrum), and an end-to-side anastomosis is performed with the remaining rectum.

A single-institution retrospective review (2002-2014) of 72 children who underwent surgical intervention for Hirschsprung disease found satisfactory outcomes with the Duhamel procedure, but 40% of the patients had to undergo further surgery.[63] The early complication rate was 15%, with 11 patients (15%) experiencing Hirschsprung associated enterocolitis (HAEC).

Soave (endorectal) procedure

The Soave procedure was introduced in the 1960s. The mucosa and submucosa of the rectum are resected, and the ganglionic bowel is pulled through the aganglionic muscular cuff of the rectum.

The original operation did not include a formal anastomosis, relying on scar tissue formation between the pull-through segment and the surrounding aganglionic bowel. The procedure has since been modified by Boley to include a primary anastomosis at the anus.

Anorectal myomectomy

For patients with extremely short-segment Hirschsprung disease, anorectal myomectomy is an alternative surgical option.

The surgeon removes a 1-cm-wide strip of extramucosal rectal wall, beginning immediately proximal to the dentate line and extending to the normal ganglionic rectum. The mucosa and submucosa are preserved and closed.

Procedures for long-segment Hirschsprung disease

Patients with total colonic involvement require modified procedures to exclude the aganglionic colon while preserving maximal absorptive epithelium. The goal of these procedures is to bypass the dysfunctional bowel while maximizing the chance of postoperative nutritional function and growth.

Most procedures include a side-to-side anastomosis of healthy small bowel with a short segment of the aganglionic/absorptive colon. Either a short right colonic patch or the small bowel is anastomosed to the rectal wall, similar to a Duhamel procedure. Importantly, a short patch (< 10 cm) is maintained.

Long-segment anastomoses, such as the Martin procedure, are no longer advocated.

Laparoscopic approach

A laparoscopic approach to the surgical treatment of Hirschsprung disease was first described in 1999 by Georgeson.[64] The transition zone is first identified laparoscopically, after which the rectum is mobilized below the peritoneal reflection. A transanal mucosal dissection is performed, and the rectum and aganglionic bowel is prolapsed through the anus. The healthy proximal bowel is anastomosed to the rectal cuff. Functional outcomes of this laparoscopic approach appear to be equivalent to open techniques based on short-term results.[64, 65, 66]

A long-term institutional study of outcomes following laparoscopic Duhamel procedure for extended Hirschsprung disease (extended aganglionosis) in 30 French children over 22 years (1991-2013) showed the procedure to be safe and effective but also revealed an association between late outcomes and late enterocolitis with Crohn-like ulcerations.[67] Over the short term, repeat intervention was required in 13% of children, but satisfactory bowel control was achieved in 53% of patients. Unfortunately, 22% of children suffered late enterocolitis, with all of these patients demonstrating Crohn-like ulcerations on endoscopy.[67]

Transanal pull-through procedures

Transanal pull-through procedures have been described in which no intra-abdominal dissection is performed.[25, 33] The entire procedure is performed transanally in a manner similar to perineal rectosigmoidectomy.

The mucosa is incised circumferentially above the dentate line, and a submucosal dissection is directed proximally. The muscularis is incised circumferentially, and the remainder of the dissection is carried external to the rectal wall until the transition zone is identified. Upon confirmation of ganglion cells on frozen section, the aganglionic bowel is resected and an anastomosis is performed.

Outcomes of the transanal pull-through procedure have been similar to open single-stage approaches, and analgesia requirements and hospital stays are decreased.[25, 68, 69] Studies have also reported lower rates of postoperative incontinence and shorter operating times in transanal pull-through procedures.[70, 71]

A long-term institutional study of bowel function outcomes that compared the transanal endorectal pull-through approach with that of the Soave-Denda abdominal approach over 30 years (1984-2015) in 110 Japanese children with Hirschsprung disease revealed that both procedures improved the evacuation score, with satisfactory postoperative results at a minimum of 10 years.[72] However, although the transanal approach was less complex, less invasive, and adaptive for neonates/small infants, its scores for incontinence and bowel movement frequency were significantly lower than those for the abdominal approach.

Novel strategies

Several other creative approaches have been described, including a modification of the transanal approach with transabdominal open or laparoscopic assistance, single-incision laparoscopic endorectal pull-through (SILEP), and natural orifice transluminal endoscopic surgery (NOTES).[73, 74, 75, 76]

Regenerative strategies are under investigation to restore function in the aganglionic intestine. Stem cell transplantation to regenerate the enteric nervous system is the subject of many recent experimental series.[77] Stem cells derived from the neural crest persist into adulthood, and several are capable of proliferation and differentiation within the intestine. Hotta and colleagues reported successful generation of functional enteric neurons from precursor cells transplanted into the recipient colon.[78] Though auspicious, these discoveries warrant further study to translate cell-based therapies into clinical practice.

Outpatient Monitoring

After a definitive pull-through procedure is performed, the patient should achieve normal growth and development.

Patients should be monitored for their bowel habit. Patients with no other underlying disorders and no postoperative complications often develop improved bowel function; however, normal bowel habit may take years to develop.

After definitive surgical repair, patients may experience persistent abnormal gastrointestinal motility. Postoperative hypomotility is relatively common, and many patients require a prolonged course of laxative treatment. Patients who retain stool despite laxative therapy may require enemas.[79]

 

Medication

Medication Summary

The goals of pharmacotherapy are to eradicate infection, to reduce morbidity, and to prevent complications.

Immediately after the diverting colostomy is created or a definitive pull-through procedure is performed, patients often remain on broad-spectrum intravenous antibiotics (eg, ampicillin, gentamicin, and metronidazole) until bowel function has returned and feeding goals are achieved.

After a definitive pull-through procedure is performed and normal bowel function is obtained, no additional medication is required.

Antibiotics

Class Summary

Empiric antimicrobial therapy must be comprehensive and cover all likely pathogens in the context of this clinical setting. Antibiotic selection should be guided by blood culture sensitivity whenever feasible.

Ampicillin (Marcillin, Omnipen, Principen)

Bactericidal activity against susceptible organisms. Alternative to amoxicillin when unable to take medication orally.

Gentamicin (Garamycin, Jenamicin)

Aminoglycoside antibiotic for gram-negative coverage. Used in combination with both an agent against gram-positive organisms and one that covers anaerobes. Not the DOC. Consider if penicillins or other less-toxic drugs are contraindicated, when clinically indicated, and in mixed infections caused by susceptible staphylococci and gram-negative organisms.

Dosing regimens are numerous; adjust dose based on CrCl and changes in volume of distribution. May be administered IV/IM.

Metronidazole (Flagyl)

Imidazole ring-based antibiotic active against various anaerobic bacteria and protozoa. Used in combination with other antimicrobial agents (except for Clostridium difficile enterocolitis).

Toxins

Class Summary

Induce more normal patterns of bowel movements in postoperative patients with enterocolitis.

OnabotulinumtoxinA (BOTOX®)

Binds to receptor sites on motor nerve terminals and inhibits the release of acetylcholine, which in turn inhibits the transmission of impulses in neuromuscular tissue.

 

Questions & Answers

Overview

What is Hirschsprung disease?

When was Hirschsprung disease first identified?

What is the pathophysiology of Hirschsprung disease?

How prevalent is Hirschsprung disease within the US?

How prevalent is Hirschsprung disease globally?

What are the racial predilections for Hirschsprung disease?

How does the prevalence of Hirschsprung disease vary by sex?

At what age is Hirschsprung disease diagnosed?

What is the prognosis of Hirschsprung disease?

What is the mortality and morbidity for Hirschsprung disease?

What are possible complications of Hirschsprung disease?

Presentation

What are the signs and symptoms of Hirschsprung disease?

Which physical findings suggest Hirschsprung disease in newborns?

DDX

What are the differential diagnoses for Hirschsprung Disease?

Workup

What is the role of a chemistry panel in the diagnosis of Hirschsprung disease?

What is the role of CBC count in the diagnosis of Hirschsprung disease?

What is the role of coagulation studies in the diagnosis of Hirschsprung disease?

What is the role of imaging studies in the diagnosis of Hirschsprung disease?

What is the role of anorectal manometry in the diagnosis of Hirschsprung disease?

What is the role of rectal biopsy in the diagnosis of Hirschsprung disease?

What is the role of suction rectal biopsy in the diagnosis of Hirschsprung disease?

Which histologic findings suggest Hirschsprung disease?

Treatment

Which specialists should be consulted if Hirschsprung disease is suspected?

What are the goals of medical care for Hirschsprung disease?

How should Hirschsprung disease be managed postoperatively?

What dietary restrictions should be implemented following surgery for Hirschsprung disease?

What activity restrictions should be implemented following surgery for Hirschsprung disease?

What is included in surgical management of Hirschsprung disease?

What are the American Pediatric Surgical Association (APSA) guidelines for managing postoperative obstructive symptoms in Hirschsprung disease?

What is the Swenson procedure for surgical treatment of Hirschsprung disease?

What is the Duhamel procedure for surgical treatment of Hirschsprung disease?

What is the Soave procedure for surgical treatment of Hirschsprung disease?

What is the role of anorectal myomectomy in the treatment of Hirschsprung disease?

Which surgical procedures are used for treatment of long-segment Hirschsprung disease?

What is the role of laparoscopy in the treatment of Hirschsprung disease?

How is a transanal pull-through procedure performed in the treatment of Hirschsprung disease?

Which treatments for Hirschsprung disease are under investigation?

What is included in postoperative monitoring for Hirschsprung disease?

Medications

Which medications are used in the treatment of Hirschsprung disease?

Which medications in the drug class Toxins are used in the treatment of Hirschsprung Disease?

Which medications in the drug class Antibiotics are used in the treatment of Hirschsprung Disease?