Hirschsprungs Disease

Dr Rajneesh Varshney
Consultant Surgical Gastroenterologist

definitions
Congenital megacolon HD is characterized by the absence of myenteric and submucosal ganglion cells in the distal alimentary tract; resulting in decreased motility in the affected bowel segment

Introduction
1887 description on postmortem by Hirschsprung 1901 histologic absence of ganglionic cells described 1896 surgery for left colectomy and pullthrough 1940s Swenson developed pull-through technique

Etiology
Enteric ganglion cells derived from neuroblasts from neural crest Neuroblasts start by pharynx with vagi and 6-8 descend to distal rectum

Seen in Auerbachs plexus Afterwards seen in Henles and Meissners plexi

Then neuroblasts mature into ganglion cells

Maturation from cephalad to caudad and from Auerbachs to Meissners plexus Maturation process not complete at birth Halting of migration or local microenvironment doesnt allow maturation Not known how pelvic neuroblasts migrate Other possible etiologies

Abnormal maturation of neuroblasts Immunologic destruction of ganglion cells

Pathogenesis

Epidemiology
Incidence 1/5000 live births Short segment(rectosigmoid)

male:female = 3.9:1 Multifactorial inheritance - ?recessive Decreased sex ratio Increased sibling risk ? Dominant

Longer segment

HD can be classified by the extension of the aganglionosis as follows:

Classical HD (75% of cases): Rectosegmoid Long segment HD (20% of cases) Total colonic aganglionosis (3-12% of cases) rare variants include the following:

Total intestinal aganglionosis Ultra-short-segment HD (involving the distal rectum below the pelvic floor and the anus)

Associated anomalies

CHD 4-5% Downs 4-5% Neurofibromatosis Ganglioneuromatosis Neuroblastoma Smith-Lemli-Opitz Syndrome Waardenburgs Syndrome

Pathophysiology
Abnormal function of aganglionic bowel

Etiology largely unknown Absence of progression of peristalsis Inability of internal sphincter to relax with rectal distention

Normal cholinergic and adrenergic nerves in aganglionic segment Normal Ach Increased Ach esterase and catecholamines No VIP, substance P, SS, met-enkephalin

RET proto-oncogene

Encodes transmembrane tyrosine kinase at 10q11.2 encoding 20 exons Defeciency causes migration arrest of neural crest cells in mice Mutation found in 17-38% of short segment and 70-80% of long segment disease

Other factors like glial cell line-derived neurotrophic factor(GDNF), endothelin 3, SIP1

Clinical Presentation
Depends on extent and age of patient Usually presents as incomplete bowel obstruction Bilious emesis Abdominal distention Infrequent/delayed defecation Diarrhea sepsis

Presentation

No correlation between length of aganglionsis and age of presentation Usually diagnosed in neonatal period DRE important to rule out anorectal malformations Delayed meconium passage

95% of normal children pass meconium within 24 hours 10% of children with Hirschsprungs pass meconium within 24 hours

May see as infant as diet consistency increases

Decreased defecation frequency Requires digital stimulation/suppositories Decreased appetite Intermittent episodes of obstruction

Older patient

Lifelong history of infrequent stool Abd distention Malnutrition Large fecal masses Do not soil, bleed or have anal pain more consistent with functional constipation Often have extensive enema programs

Enterocolitis

Not known why it happens Theory of stasis and bacterial overgrowth Can be life threatening Characterized by fever, abdominal distention and diarrhea C. diff toxin positive often 10% of children with HD present with enterocolitis Diagnosis of HD can be missed

The risk is greatest:

before HD is diagnosed after the definitive pull-through operation. children with Down syndrome

diagnostic workup
Plain abdominal radiography Contrast enema Manometry Biopsy

Abdominal X-Ray
Dilated bowel Air-fluid levels. Empty rectum

AXR

Diagnosis
Ba enema

Rule out obstructing lesion Rectal calibre < calibre of rest of colon Hallmark conical transition from prox dilated to distal collapsed colon Small colonic calibre with rounded flexures suggests aganglionosis Tertiary contractions or retained Ba

Ba-enema

Barium Enema

Anorectal manometry

Characterized by high pressure Progressive peristalsis to an aperistaltic segment Inability of internal sphincter to relax Helpful for evaluation after reconstruction Needs ++equipment and time Less reliable in neonates

Biopsy
Types:

rectal suction biopsy full-thickness rectal biopsy.

In HD, the biopsy reveals:

absence of ganglion cells hypertrophy and hyperplasia of nerve fibers, increase in acetylcholinesterase-positive nerve fibers in the lamina propria and muscularis mucosa.

Rectal biopsy

Full thickness gold standard Looks at the plexi Important to get biopsy 2-3cm above dentate line Disadvantage: GA, presacral abscess Alternatives punch biopsy, suction biopsy Looks at H&E, Ach esterase staining, stains for subsance P, S-100 protein and neuron specific enolase

Differential Diagnosis
Neonates

Small left colon Meconium plug Meconium ileus Megacystis-megacolon-intestinal hypoperistalsis syndrome Intestinal dysmotility Hollow viscous myopathy Chronic intestinal pseudo-obstruction

Infants and children

Functional constipation May need to evaluate for hypothyroidism and hypercalcemia

Treatment
Surgery remove aganglionic segment and anastamose normally innervated bowel to anus and preserve sphincter function May need to use frozen sections to identify transition area Used to be done as multiple staged procedures but now often one stage Commonly preferred procedures

Swenson Duhamel Soave

Swenson procedure

Low anterior resection of rectum with end-toend anastamosis performed by prolapsing the rectum and pulled-through bowel outside anus Described in 1949 by Swenson

Swenson Procedure

Duhamel procedure

Leaves native rectum in situ Normally innervated colon is brought into presacral space and an end-to-side anastamosis is performed to rectum

Duhamel Procedure

Soave procedure

Described in 1964 Used to avoid injury to pelvic vessels and nerves and protect internal sphincter Mucosal proctectomy with preservation of rectal muscular cuff and end-to-end anastamosis just above dentate line Can be done transanally for short segment

Soave Procedure

One vs Two Stage procedure

Historically, two stage procedure performed: preliminary colostomy, then completion pull through Delicate muscular sphincters of newborn may be injured 1980s, 1 stage procedures became more popular

One vs Two Stage procedure

Early complications: No difference in incidence of anastomotic leak, pelvic infection, prolonged ileus, wound infection, wound dehiscence Late complications: No difference in incidence of anastomonic stricture, late obstruction, constipation, incontinence, urgency

Postoperative enterocolitis higher in 1 stage (42% vs 22%)

Can be done laparascopically described by Georgeson

Post operative complications

anastomotic leak anastomotic stricture intestinal obstruction pelvic abscess wound infection

Prognosis
The long-term outcome is difficult to determine because of conflicting reports in the literature. Some investigators report a high degree of satisfaction, while others report a significant incidence of constipation and incontinence. approximately 1% of patients with Hirschsprung disease require a permanent colostomy to correct incontinence. patients with associated trisomy 21 have poorer clinical outcomes.

Conclusion
Hirschsprungs disease is uncommon but can present at any stage of life Most commonly in neonatal period Delayed passage of meconium Aganglionosis Diagnosed by rectal biopsy Needs surgery to bypass or resect aganglionic segment Enterocolitis can be a fatal complication