Hirschsprung Disease Flashcards

Question

What finding on anorectal manometry suggests a diagnosis of Hirschsprung Disease?

Answer 1

Absence of the recto anal inhibitory reflex (RAIR). The physiology of voluntary bowel evacuation relies on the RAIR. The normal internal sphincter relaxation in response to distention of the rectum is absent in Hirschsprung disease. When a bolus of fecal material is delivered to the rectum, increased rectal pressure and distension causes transient relaxation of the internal anal sphincter, allowing a small sample of the rectal contents to come in contact with the sensory afferent somatic nerves innervating the anorectum. Then the individual can choose if and when to tighten the external (voluntary) sphincters.

Answer 2

H + E or hematoxylin and eosin—one of the principal stains in histology. Acetylcholinesterase (AChE)—only good for the distal colon. Calretinin—stains thin nerve fibrils (neurites) and can add diagnostic value to specimens with inadequate submucosa or rarely seen ganglion cells.

Answer 3

It is significantly increased, and is one of the essential points of diagnosis in some institutions when assessing a rectal biopsy for HD. However, it is useful only in rectal biopsies and in biopsies of the left colon because there usually is no acetylcholinesterase activity proximal to the splenic flexure.

Answer 4

The appendix should not be utilized to determine whether there is Hirschsprung disease as many normal appendices have no ganglion cells [4].

Answer 5

Constipation is defined as infrequent bowel movements (2 or fewer per week) that are painful, or large in caliber stools that require excessive straining. The Rome III criteria for constipation are utilized in infants and children up to 4 years of age. This includes one month of at least 2 of the following: 2 or fewer defecations per week, at least 1 episode per week of incontinence after acquiring toileting skills, history of excessive stool retention, history of painful or hard bowel movements, presence of a large fecal mass in the rectum, history of large diameter stools that may obstruct the toilet. Accompanying symptoms include irritability with decreased appetite and/or early satiety. The accompanying symptoms disappear immediately following passage of a large stool.

Answer 6

A thorough understanding of which laxatives or enemas have been utilized and to what effect, as well as anorectal examination, contrast enema, anorectal manometry, and colonic motility testing. Colonic motility testing (sitzmarkers, radionuclides, or colonic manometry) is reserved only for those patients who have failed medical management (laxative or enema therapy).

Answer 7

The most common indication for surgical intervention in a child with functional constipation is for one who has failed medical management; high dose laxatives do not work or cause intolerable cramping and enemas do not empty the colon or are not tolerated. For these patients, anal manometry (AMAN) is performed to see if Botox or pelvic floor biofeedback is indicated and colonic manometry (CMAN) is performed to determine whether motility is normal, diffusely abnormal or seg- mentally (usually the sigmoid) abnormal. Based on the motility testing an antegrade option can be offered which is usually successful, but if flushes do not work a colonic resection may be required.

Answer 8

Through a combined multidisciplinary approach with the implementation of laxatives, dietary modifications, defecation trials, psychosocial support and appropriate testing. Psychosocial counseling often benefits the patient and family as part of a multimodality management.

Answer 9

A number of surgical procedures have been proposed that include anal and pelvic floor procedures (such as Botox and biofeedback training), antegrade continence enema procedures (Malone antegrade continence enemas or cecostomy), colonic resections and sacral nerve stimulation (SNS) [5].

Answer 10

The absence of high amplitude propagating contractions (HAPC) in response to a stimulant medication.

Answer 11

Children with poor motility that is limited to the sigmoid as well as children with normal colon motility.

Answer 12

>95% of children.

Answer 13

E. Increased recto-sigmoid index.

Answer 14

D. Martin’s modification is for ultra-short segment Hirschsprung disease.

Answer 15

A. It is an established manner of diagnosis.

Answer 16

E. None of the above.

Answer 17

A. It is easy to identify the transitional zone in neonate.

Answer 18

C. Specimen is usually taken from anterior wall.

Answer 19

E. Hyperthyroidism

Answer 20

E Statements A, B, C, D are true. — The ultrashort segment HD, which is a rare condition, is characterized by an aganglionic segment of 1 to 3 cm long and normal acetylcholinesterase (AChE) activity in the lamina propria and increased AChE activity in the muscularis mucosae. Many patients who are considered to have ultrashort HD on abnormal anorectal manometric findings show presence of ganglion cells and normal acetylcholinesterase (AChE) activity in suction rectal biopsies. Coran — Some surgeons use this term to describe children with normal ganglion cells on rectal biopsy, but with absence of the RAIR, which is synonymous with the definition of internal sphincter achalasia. We prefer to reserve this term for children who have a documented aganglionic segment of <3–4 cm. In children with this condition, the findings of hypertrophic nerves and abnormal cholinesterase staining may be absent. The treatment of ultra-short segment HD is controversial. Some authors advocate simple anal sphincter myectomy, whereas others prefer excision of the aganglionic segment with a pull-through. H&A

Answer 21

1) Absence of ganglion cells in the submucosal and myenteric plexus 2) Hypertrophied nerve trunks 3) Stains: H&E, characteristic pattern of increased acetylcholinesterase in submucosa and mucosa, absent calretinin

Answer 22

White bread, pasta, rice, bagels Apples, applesauce, bananas

Answer 23

Milk, cheese, ice cream Strawberries, watermelon, oranges French fries, potato crisps

Answer 24

Idiopathic constipation Patients with idiopathic constipation are usually physically ﬁt and have no evidence of illness except for the soiling of underwear that occurs in some children (encopresis). Idiopathic constipation may be present at birth but the parents may not notice the symptoms until much later, usually at the time of toilet-training. Physical examination does not yield much except that abdominal examination may reveal a mass in the lower abdomen consistent with an impacted rectosigmoid. Rectal examination conﬁrms a large amount of rock-hard faeces very low in the rectum.

Answer 25

Hirschsprung Disease Untreated Hirschsprung’s disease causes failure to thrive and the patient becomes malnourished because of poor absorption of nutrients. Episodes of enterocolitis may occur as a result of stasis of stool and bacterial overgrowth. The history of delayed passage of meconium is commonly encountered in children with Hirschsprung’s disease. Most (95%) full-term neonates will pass meconium within the ﬁrst 24 hours of life.

Answer 26

1) Aberrant/aborted migration of enteric nerves during development. Neural crest cells, from which ganglion cells are derived, never reach the distal intestine due to early maturation or differentiation into ganglion cells. 2) Neural crest cells reach their destination, but fail to survive or differentiate into ganglion cells due to an inhospitable microenvironment. (Abnormality in constitution of ECM, impaired interaction of progenitor cells with glycoprotein receptors) Normal embryology: Ganglion cells are derived from the neural crest. By 13 weeks postconception, the neural crest cells have migrated from proximal to distal through the gastrointestinal tract, through some interaction with glycoprotein receptors, after which they differentiate into mature ganglion cells.

Answer 27

Meconium ileus Meconium ileus is one of the differential diagnoses of abdominal distension in the newborn period. It is manifested by a clinical picture of intestinal obstruction and a characteristic image of a ‘ground glass’ appearance, sometimes representing an in utero perforation, on abdominal radiograph. There may be a family history of cystic ﬁbrosis. Rectal examination may yield inspissated meconium. Symptoms tend to resolve once the meconium is cleared. Repeated water-soluble enemas may be needed for a complete resolution, and occasionally surgery is required to manage the obstruction.

Answer 28

1) Mechanical obstruction 2) Recurrent or acquired aganglionosis 3) Disordered motility In the proximal colon or small bowel 4) Internal sphincter achalasia 5) Functional megacolon caused by stool-holding behavior

Answer 29

In normal individuals, one to five ganglion cells are present in clusters for every 1 mm length of rectum.

Answer 30

Variant HD is the term often used to describe children who present with a clinical picture suggestive of HD, but with ganglion cells on rectal biopsy. There is a significant amount of controversy surrounding the definitions and features of many of these conditions. In some cases, their existence has even been questioned. INTESTINAL NEURONAL DYSPLASIA Intestinal neuronal dysplasia (IND) was first described by Meier-Ruge in 1971. Two types are usually described. Type A is less common and is characterized by diminished or absent sympathetic innervation of the myenteric and submucosal plexuses, along with hyperplasia of the myenteric plexus. Type B consists of dysplasia of the submucous plexus with thickened nerve fibers and giant ganglia, increased acetylcholinesterase staining, and identification of ectopic ganglion cells in the lamina propria. Type B can occur independently or concomitant with HD. In addition, IND may be either diffuse or focal. Despite multiple publications, the topic of IND continues to stimulate a lot of controversy among pediatric surgeons and pediatric pathologists. Sophisticated histologic techniques, including special stains and the use of thick sections, are often necessary for an accurate diagnosis. In addition, there is some evidence that the histologic finding of IND may in some cases be secondary to chronic obstruction rather than the cause of it. In many cases, there may not be good correlation between the histologic finding of IND and the bowel motility. HYPOGANGLIONOSIS Hypoganglionosis is characterized by sparse and small ganglia, usually in the distal bowel, often associated with abnormalities in acetylcholinesterase distribution. The appropriate treatment is resection of the abnormal colon with a pull-through procedure as one would do for a child with HD, although it is best to also document a focal area of abnormal motility using a functional study prior to subjecting the child to operation. This condition must be differentiated from immature ganglia, which are seen in preterm children, and should not be treated surgically. INTERNAL SPHINCTER ACHALASIA There are some children who have normal ganglion cells on rectal biopsy, but who lack the RAIR on anorectal manometry and develop symptoms of HD. This condition has been termed internal sphincter achalasia. The initial treatment is a bowel management regimen consisting of diet, laxatives, and enemas or irrigations. If this is unsuccessful, some surgeons have advocated anal sphincter myectomy. Because the constipation associated with this condition usually improves over the first five years of life, treatment includes temporary or reversible sphincterrelaxing measures such as botulinum toxin, nitroglycerine paste, or topical nifedipine, as previously discussed. “ULTRA-SHORT SEGMENT” HIRSCHSPRUNG DISEASE Some surgeons use this term to describe children with normal ganglion cells on rectal biopsy, but with absence of the RAIR, which is synonymous with the definition of internal sphincter achalasia. We prefer to reserve this term for children who have a documented aganglionic segment of <3–4 cm. In children with this condition, the findings of hypertrophic nerves and abnormal cholinesterase staining may be absent. The treatment of ultra-short segment HD is controversial. Some authors advocate simple anal sphincter myectomy, whereas others prefer excision of the aganglionic segment with a pull-through. DESMOSIS COLI This is a rare condition characterized by chronic constipation associated with total or a focal lack of the connective tissue net in the circular and longitudinal muscles as well as the connective tissue layer of the myenteric plexus, without any abnormalities in the enteric nervous system. One family has been described in which HD and desmosis coli coexisted, although they are separate entities in most cases.

Answer 31

C Hirschsprung’s disease occurs in 1 in 5000 live births, and is more common in males with a male-to-female ratio of 4 : 1. In long-segment disease, this ratio decreases. A higher incidence has been reported in white people and in Asian children. Harald Hirschsprung is credited with the first classic description of the disease. He was a Danish paediatrician and presented the cases of two children with the clinical and anatomical characteristics of the condition in Berlin, in 1886. The first surgical approach was reported by Swenson and Bill in 1949. The commonest cause of constipation in children is idiopathic constipation, which affects 3% of the paediatric population. SPSE 1

Answer 32

D There is evidence of familial involvement in Hirschsprung’s disease. The incidence of familial occurrence ranges from 2% to 18%. The risk of familial involvement increases with the length of aganglionosis. The chances that a male sibling will be affected (5%) are greater than those of a female (1%) in shortsegment Hirschsprung’s disease. male relatives of females with long-segment Hirschsprung’s disease have the greatest risk of being affected (25% for brothers and 30% for sons). SPSE 1

Answer 33

C Failure of passage of meconium within the first 48 hours of life is the commonest feature of patients with Hirschsprung’s disease. Ninety-five per cent of full-term neonates will pass meconium within the first 24 hours of life and 10%–40% of patients with Hirschsprung’s disease, in various reports, successfully pass meconium, so it is not always helpful as a clinical feature. A water-soluble contrast enema is preferred to barium in neonates to avoid barium peritonitis in cases of occult perforation. Water-soluble enemas are also therapeutically better at dislodging meconium plugs. A bedside suction biopsy is the key diagnostic study. SPSE 1

Answer 34

B To make the diagnosis of Hirschsprung’s disease, a rectal biopsy for histology is vital. A suction biopsy at the bedside or in clinic offers a rapid way of obtaining the specimen without the need for anaesthesia but is difficult to do in infants after 1 year of age. The sensitivity of rectal suction biopsy is >90% and specificity is >95%. The pathological evaluation, however, is more technically difficult for a suction biopsy specimen than for a full-thickness rectal biopsy specimen. In older children or in patients with indeterminate suction biopsy results, a full-thickness biopsy is needed. The features on hematoxylin and eosin staining that are diagnostic of Hirschsprung’s disease are the absence of ganglion cells and the presence of hypertrophic nerves. SPSE 1

Answer 35

E The transition zone is a segment of the colon where there is an admixture of areas with ganglion cells and areas of aganglionosis. It is easier to see on a contrast enema in older children and is a helpful guide in planning for the pullthrough procedure. It is characterised by the presence of hypertrophic nerves (nerves larger than 40 µm) against a background of reduced number of ganglion cells (hypoganglionosis). The bowel should never be pulled through until normal ganglion cells and normal-sized nerves are present and it is advisable to go a few centimetres above where the intraoperative frozen section sample was obtained and reported to be normal. SPSE 1

Answer 36

D The most common type of Hirschsprung’s disease, seen in two- thirds of patients, is one in which the extent of aganglionosis includes the rectum and sigmoid colon. long-segment Hirschsprung’s disease, which occurs in 10% of patients, signifies that aganglionosis extends proximal to the splenic flexure. The entire colon is aganglionic in patients with total colonic aganglionosis, frequently including the terminal ileum. Total colonic aganglionosis (TCA) occurs in 10% of the patients with Hirschsprung’s disease. The severity of symptoms seen in patients does not necessarily correlate with the extent of aganglionosis; in fact, TCA patients often present late and have more subtle symptomatology, such as chronic distension and failure to thrive. SPSE 1

Answer 37

A Ganglion cells are absent in the rectum and, to a varying degree, the colon in Hirschsprung’s disease. Ganglion cells are missing from Auerbach’s plexus (the myenteric plexus is located between the circular and longitudinal layers of bowel wall), Henle’s plexus (in the deep submucosa) and also meissner’s plexus (in the superficial submucosa). In addition to the finding of aganglionosis, there is an increase in acetylcholinesterase in the aganglionic colon. This can be shown using acetylcholinesterase staining and can assist in the diagnosis of Hirschsprung’s disease. Nitric oxide has been postulated as a neurotransmitter that is responsible for the inhibitory action that is elicited by enteric nerves, and a lack of nitric oxide synthase has been demonstrated in the myenteric plexus of the aganglionic segment of bowel. SPSE 1

Answer 38

D The pathophysiology of enterocolitis has not been fully elucidated. However, in patients with Hirschsprung’s disease, the presence of stasis resulting from aganglionosis has been associated with overgrowth of unusual anaerobic bacteria including Clostridium difficile, which leads to secretory diarrhoea and hypovolaemia. In contrast, stasis in the absence of aganglionosis in patients with idiopathic constipation does not produce enterocolitis. Patients with Hirschsprung’s disease have an altered mucin composition in the intestine with almost undetectable levels of muC2, the major mucin component in the colon in humans. other immunologic defects include decline in the amounts and function of immunoglobulin A and T-lymphocytes. SPSE 1

Answer 39

B Enterocolitis can occur in patients with Hirschsprung’s disease, both preceding and after the pull-through. It occurs in 10%–40% of patients who have undergone a definitive pull-through procedure. The mechanism of enterocolitis is still unclear. Enterocolitis after a technically correct pull-through responds to an aggressive course of irrigations and metronidazole. If enterocolitis becomes recurrent after a pull-through procedure, further investigation for an anatomical cause (e.g. a constricting Soave’s cuff) or pathological cause (retained aganglionosis or transition zone pull-through) becomes necessary. oral metronidazole is very useful in the treatment of enterocolitis, especially when combined with irrigations. Enemas are not effective when compared with rectal irrigations in treating enterocolitis. The administration of an enema will exacerbate the distension in a patient with enterocolitis and aggravate the condition. The fluid must be washed out of the lumen of the bowel, which can be accomplished with irrigations, to break the cycle of stasis and bacterial overgrowth. SPSE 1

Answer 40

A The ideal treatment of Hirschsprung’s disease nowadays is a primary pullthrough, without protective colostomy. A diverting colostomy may be indicated as an emergency procedure in very ill patients or if intraoperative pathology is not available. A diverting colostomy has to be sited at an optimal location which depends on the level of aganglionosis. Without the availability of pathological correlation, in most patients the safest area is proximal to the sigmoid colon usually in the descending or transverse colon or an ileostomy. In a centre without a paediatric pathologist, diversion with a colostomy can be life-saving, with a reconstruction planned for a future date. If frozen section is available, an option is to perform a levelling colostomy. Then the colostomy can be pulled down at the time of the definitive repair. This deprives the patient of the protection of proximal diversion, but reduces the needed operations from three to two. A colostomy would be ineffective in the treatment of total colonic aganglionosis. An ileostomy is the preferred form of diversion. SPSE 1

Answer 41

D Swenson and Bill performed the first corrective surgery for Hirschsprung’s disease in 1948. The Swenson procedure involves dissection of the rectum, staying as close to the bowel wall as possible, and resection of the aganglionic as well as the dilated parts of the colon and the rectum. The coloanal anastomosis is done 1–2 cm above the dentate line. The dentate line should be protected in all forms of surgery for Hirschsprung’s disease because of the risk of faecal incontinence associated with destruction of the dentate line. In Soave’s original description, there was a transabdominal dissection through the seromuscular layer, starting 2 cm above the peritoneal reflection and this was carried down to 1–2 cm above the dentate line. The aganglionic rectum and colon were then resected and the colostomy out of the anal canal pulled through a muscular cuff. The protruding colon was left dangling outside and a coloanal anastomosis performed at a later date. Boley modified this approach by performing a primary coloanal anastomosis. The Duhamel procedure involves dissection through a presacral retrorectal space in an attempt to limit the risk of injury to pelvic nerves and urogenital structures with pull-through of ganglionic bowel, and anastomosing it to the aganglionic pouch. Martin described the use of the aganglionic portion of the colon to treat total colonic aganglionosis by creating a long channel of anastomosed ganglionic small bowel to aganglionic colon. Today, the most common approach is a transanal Soave-like technique, which sometimes can be completed without entering the abdomen at all. SPSE 1

Answer 42

E Idiopathic constipation is a poorly understood entity. A secondary psychological component is a consequence of delay in the proper management of idiopathic constipation particularly when encopresis (overflow soiling) occurs. Individuals who have the incapacity to empty their colon and soil their underwear daily can have serious psychological distress. In addition, the passage of large, hard pieces of stool may provoke pain, which will make the patient afraid to have bowel movements. The cause remains unknown; it is not thought to be due to a hyperactive internal anal sphincter, but rather related to an inherent dysmotility of the colon. The contrast enema in idiopathic constipation typically shows a megarectosigmoid colon, the opposite of that seen in Hirschsprung’s disease. Idiopathic constipation is not a fatal condition, unlike another rarer cause of constipation – intestinal pseudo-obstruction – which can have serious systemic complications. SPSE 1

Answer 43

B Enterocolitis is a symptom seen in patients with Hirschsprung’s disease but not those with idiopathic constipation. Even though stasis plays a role, there are other mechanisms which are poorly understood, that lead to enterocolitis in patients with Hirschsprung’s disease. Soiling is typical with idiopathic constipation (also called encopresis) and when it occurs without the patient’s awareness, it is an ominous sign of bad constipation. It is unusual in patients with Hirschsprung’s disease unless the anal canal or sphincters have been damaged during the pull-through. A rectal biopsy taken 1–2 cm above the dentate line for histology is the gold standard in the diagnosis of Hirschsprung’s disease. If the biopsy is taken right at the dentate line, there may be a false positive result because of the natural zone of aganglionosis in the anal canal at the level of, and just above, the dentate line. A transitional zone of hypoganglionosis and hypertrophic nerves is present in Hirschsprung’s disease but is not a feature of idiopathic constipation. Fissures occur in idiopathic constipation and can lead to a vicious cycle of symptoms. As the fissures attempt to heal, constipation and passage of hard stools reopen the fissures. SPSE 1

Answer 44

E The boy has features consistent with idiopathic constipation. Hirschsprung’s disease is highly unlikely because the patient stooled normally at birth, soils every day and has a normal physical examination at 8 years of age despite not having had surgery. The radiographic appearance in idiopathic constipation is a megarectosigmoid; the colon is normal proximally, which is exactly the opposite of what is found in Hirschsprung’s disease, in which the distal bowel is contracted. SPSE 1

Answer 45

A Chronic intestinal pseudo-obstruction is called different names by different authors. It is a highly fatal form of functional intestinal obstruction sometimes requiring intestinal transplantation. The histological appearance of colonic biopsy ranges from a normal appearance to specific abnormalities that are described as muscle fibrosis, vacuolar degeneration, disorganisation of myofilaments, or an arrest in the maturation of the myenteric plexus. Ganglion cells are present and nerve trunks are normal in size. In addition to idiopathic causes, intestinal pseudo-obstruction has been associated with Down’s syndrome, neurofibromatosis, multiple endocrine neoplasia 2B, Russell–Silver’s syndrome, Duchenne’s muscular dystrophy, viral gastroenteritis and prematurity. Secondary causes include Chagas’s disease, a parasitic infection caused by Trypanosoma cruzi that affects the myenteric plexus. Drug-induced pseudo-obstruction can be encountered in newborns with prenatal transplacental drug exposure or with prolonged ingestion of narcotics. SPSE 1

Answer 46

E Intestinal neuronal dysplasia has been considered a cause of constipation in children but its histology is inconsistent and it is unclear if it is truly a distinct clinical entity. It has been described by different authors to have features such as hypertrophy of ganglion cells, normal ganglion cells, immature ganglia and hypoganglionosis, hyperplasia of the submucous and myenteric plexuses with formation of giant ganglia, hypoplasia or aplasia of sympathetic innervations of the myenteric plexus, and increased acetylcholinesterase positive nerve fibres around submucosal vessels and in the lamina propria. In postoperative Hirschsprung’s patients who are experiencing obstructive symptoms, their problems may instead represent transition-zone bowel. SPSE 1

Answer 47

The classic manifestations of HAEC include abdominal distention, fever, and diarrhea. However, there is a broad clinical spectrum with which children present, and other signs or symptoms may include vomiting, rectal bleeding, lethargy, loose stools, and obstipation. Of note, these symptoms are non-specific and this likely contributes to the highly variable incidence of HAEC reported in the literature. Mild cases, manifesting with only fever, mild distension, and diarrhea, present just like viral gastroenteritis, which is very common in young children. Given the difficulty in making a definitive diagnosis, combined with the high morbidity associated with a delayed or missed diagnosis, most pediatric surgeons err on the side of assigning the diagnosis of HAEC and presumptively treating suspected cases. In general, assuming the child has HAEC and initiating treatment is preferable to delaying the diagnosis and having the child present later with more advanced disease. In an attempt to address the difficulty in establishing the diagnosis of HAEC, a group of 27 gastroenterologists and surgeons participated in a Delphi process, starting with 38 features (history, patient characteristics, physical exam signs, laboratory findings, radiology findings, pathology findings) and iteratively refining this list to 16 items to develop a HAEC score. The resulting tool, although useful for standardizing outcome measures in research studies, is cumbersome for routine use, has not been validated for clinical application, and has not been widely adopted in the clinical setting. More recently, another group described a “clinical grade” for HAEC for use in a prospective trial. This system grades the degree of diarrhea, abdominal distention and systemic manifestations into mild, moderate and severe in order to assign an overall clinical grade. Following a staging system similar to that described by Bell for necrotizing enterocolitis (NEC), and incorporating elements of published HAEC grading systems and clinical experience, we have categorized the clinical suspicion and severity of HAEC into three grades based on history, physical examination, and imaging studies [Figure 1]. The goal of this approach is to create a standardized, clinically relevant, and easy to use system that can be universally adopted to allow a consistent approach to the diagnosis and treatment of HAEC. In general, presence of higher grade findings should prompt providers to err toward assigning the higher grade and initiating the corresponding treatment. Guideline for the diagnosis and grading of HAEC from grade I (possible HAEC) through grade III (severe HAEC) based on clinical history, physical examination, and radiographic findings. This figure is not intended as a scoring system, but rather a decision-support tool to ensure that all of the relevant history, examination and radiographic findings are considered. In general, presence of higher grade findings should prompt providers to assign the higher grade. (HAEC: Hirschsprung-associated enterocolitis, DRE: digital rectal examination). PubMed Central

Answer 48

Since the cause of HAEC is generally unknown, treatment remains empiric and directed toward alleviating acute symptoms as well as managing the factors that may contribute to pathogenesis. Treatment is based on the severity of the clinical presentation, as detailed in Figure 2. In cases classified as Grade I (possible HAEC), outpatient management can typically be employed. Treatment in these cases should include oral metronidazole and oral hydration with Pedialyte or other electrolyte-rich solution. Rectal irrigations to wash retained stool out of the colon should be considered in children who have abdominal distension or who are not evacuating fully. They may also be used as a trial to see if irrigation leads to symptomatic improvement. Close monitoring is necessary in case symptoms progress to a higher grade of disease. In more severe cases, Grade II (Definite HAEC), inpatient admission is often necessary. These children are managed with either clear liquids or nothing by mouth, intravenous fluids, and nasogastric decompression if there is significant abdominal distension. Rectal irrigations are very effective, helping to resolve fecal stasis. Metronidazole (oral or parenteral) is used to treat anaerobes, including Clostridium difficile, which has been associated with HAEC. In addition to metronidazole, broad spectrum intravenous antibiotic coverage using either the combination of ampicillin and gentamicin, or piperacillin/tazobactam, or aztreonam (in the case of penicillin allergy) should be considered. Children with findings consistent with Grade III (severe) HAEC, particularly with shock, may require admission to an intensive care unit. Bowel rest, intravenous fluid resuscitation, rectal irrigations, and broad-spectrum antibiotics (including metronidazole) are required. Patients who fail to improve may benefit from proximal enteric diversion. Rarely, pneumoperitoneum can occur, which would prompt immediate surgical intervention. PubMed Central

Answer 49

Children with recurrent HAEC should undergo additional evaluation to determine whether a cause can be identified. In these cases, it is important to evaluate for an anatomic or pathologic cause of obstruction. Anatomic problems include anastomotic stricture, a twisted or kinked anastomosis, megarectum, a Duhamel spur or kink, or a tight Soave cuff. Causes of functional obstruction, such as a transition zone pull-through or retained aganglionosis, should also be considered. Physical examination is typically performed under anesthesia and should include careful assessment for a stricture, presence and function of the anal sphincters, size of the rectal pouch (if present), and presence of a palpable Soave cuff. A contrast enema using a water-soluble agent can identify any mechanical causes of obstruction. Because of risk of perforation, contrast enemas should not be performed during acute HAEC episodes. Additional evaluation includes rectal biopsy to exclude aganglionosis or transition zone pull-through. Review of pathology slides from the original surgery should exclude transition zone pull-through. If the workup reveals an anatomic etiology for obstructive symptoms and recurrent HAEC, surgical management directed at correcting the defect should be performed. If there is no anatomic or pathologic cause identified, non-relaxation of the internal anal sphincter may be the cause of stasis with obstructive symptoms and recurrent HAEC in some patients, and can be confirmed by anorectal manometry. Injection of Clostridium botulinum toxin (Botox, Allergan, Plc) into the intersphincteric groove has been shown to decrease hospital admissions in children with recurrent symptomatology. PubMed Central

Answer 50

Occasionally a premature infant will develop distal intestinal obstruction, and the possibility of Hirschsprung disease will be raised on the basis of clinical and radiologic parameters. Early rectal biopsy in these children is not recommended for two reasons: (1) The pathologist may have difficulty recognizing ganglion cells due to their immaturity, and (2) it may be difficult to obtain enough tissue without increasing the risk of complications in a small premature infant. It is best in this situation to decompress the rectum using stimulations and/or irrigations and wait until the child is closer to term before doing the rectal biopsy. Although some surgeons believe that Hirschsprung disease is not seen in premature infants, this condition has been well-documented in a number of series. Coran

Answer 51

Long-segment Hirschsprung disease is usually defined as a transition zone that is proximal to the midtransverse colon. The most common is total colonic aganglionosis, which usually also includes some of the distal ileum. In rare cases most of or the entire small bowel is aganglionic. Long-segment disease is more likely to be associated with a positive family history and is more likely to be diagnosed prenatally. Contrast enema typically shows a shortened, relatively narrow colon (“question mark colon”), and there may also be a transition zone in the small bowel. The rectal biopsy shows absence of ganglion cells, but in many cases there are no hypertrophic nerves or abnormalities of acetylcholinesterase staining. Coran

Answer 52

Early resuscitation and management is similar to that described for standard Hirschsprung disease. Sequential colonic biopsies are done looking for ganglion cells on frozen section. These can be done through a standard laparotomy, laparoscopically, or through an umbilical incision, which in a newborn can be used to access all parts of the colon. Traditionally, many surgeons started with an appendectomy, assuming that lack of ganglion cells in the appendix would be diagnostic of total colonic disease. However, this may result in a false-positive diagnosis of total colonic Hirschsprung disease because there may be a paucity of ganglion cells in the appendix in children with shorter segment disease. Once the level of aganglionosis has been identified, most surgeons create a stoma, wait for permanent sections, and do a definitive reconstructive procedure at a later time. Although primary pull-through without ileostomy for total colonic disease has been reported, this approach requires a high degree of confidence in the pathologist because it requires doing a total colectomy on the basis of frozen sections alone. In addition, many surgeons believe that the results of pull-through surgery are better once the stool has thickened, which usually occurs in the first few months of life. Three types of operations are available for reconstruction in children with long-segment Hirschsprung disease: straight pull-through, colon patch, and J-pouch construction. Straight pull-through procedures involve bringing the normally innervated ileum to just above the anal sphincter, using any one of the standard techniques (Swenson, Duhamel, or Soave). Colon patch procedures involve a side-to-side anastomosis between normally innervated small bowel and aganglionic colon, using the small bowel for motility and the colon as a reservoir for storage of stool and absorption of water. The Martin procedure consists of a Duhamel reconstruction that extends proximally to involve the entire left colon. Kimura, using the rationale that the right colon is better at water absorption than the left colon, advocated a staged procedure, in which the right colon is anastomosed side-to-side to the ileum. The “ileo-colon” is then disconnected from the right colonic blood supply after several months and anastomosed above the anal sphincter. The J-pouch procedure is done commonly for children and adults with ulcerative colitis and familial polyposis syndrome, and some pediatric surgeons have reported the use of this operation for children with long-segment Hirschsprung disease. There are no prospective or well-controlled series reporting long-term results of surgery for long-segment Hirschsprung disease. Although the colon patch procedures theoretically result in decreased stool output due to better water absorption, the aganglionic colon gradually tends to dilate and many of these patients develop severe enterocolitis, which requires removal of the patch or a permanent stoma. Children undergoing straight pull-through tend to experience gradually decreasing stool frequency over time, with an acceptable quality of life. Coran

Answer 53

Rarely, almost the entire intestinal tract of a patient is aganglionic, usually leaving 10 to 40 cm of normally innervated jejunum. In most of these cases, there is not enough functional small bowel to support enteral nutrition and intestinal failure results. These children require total parenteral nutrition from birth, a situation that has been associated with a high risk of mortality from liver failure. The surgical approach at the time of the first laparotomy is to determine the extent of aganglionosis on the basis of frozen sections and to bring out a stoma at the most distal point that has normally innervated bowel. Some surgeons prefer to bring out a more distal stoma, but this approach may increase the risk of chronic intestinal obstruction and bacterial overgrowth. A central venous catheter should be inserted for parenteral nutrition, and a gastrostomy should be considered for continuous “trophic” feeding of breast milk or elemental formula. The management of these children is similar to the management of any child with intestinal failure. Strict attention to prevention of sepsis, treatment of bacterial overgrowth, use of trophic feeds, and prevention of TPN-related cholestasis are all extremely important. Recent experience with omega-3 lipids has resulted in encouraging trends toward prevention and treatment of this problem. A number of surgical options are available for children with near-total aganglionosis. For children who develop significant proximal dilatation of the normally innervated bowel, tapering, imbrication, or bowel-lengthening procedures such as the Bianchi or serial transverse enteroplasty (STEP) procedure may be used. Zeigler has popularized a technique known as “myectomy-myotomy,” in which a length of aganglionic small bowel distal to the transition zone undergoes myectomy. Although a few successful cases using this technique have been reported, most surgeons have not found it to be successful and have noted high rates of postoperative complications. For children with ongoing liver failure, small bowel or combined small bowel-liver transplantation may offer the only chance for survival. A recent report from Paris documented extremely good results in 12 patients, many of whom underwent successful pull-through surgery following their intestinal transplant. Coran

Answer 54

Dilating Your Child’s New Anus You will start by dilating your child’s new anus two times each day – one time in the morning and one time in the evening. Put your child on their back with the knees pulled up towards the chest. Lubricate the dilator. Put the dilator in the anus and keep in place for 30 seconds. Remove it and put it in again for 30 seconds. It is best to not dilate your child right after they eat a meal. Changing the Size of the Dilator Every week, you will increase the size of the dilator, using the next larger size. Continue to dilate your child’s anus two times a day until you get to the goal size set by the doctor. Tips about Dilatations The dilatations may cause some discomfort for your child as you get closer to the last 2-3 sizes. You may feel that you want to stop dilating your child’s anus every day because of the slight discomfort, but it is very important to keep dilating two times a day. For best comfort, be sure to lubricate the dilator well. Lubricate and insert a smaller dilator, just before you insert the right size dilator. Position your child without movement. If the dilation plan is not followed right, there is risk of scarring during the healing process. This can narrow the anus. If this happens, your child may need to have more surgery to correct the problem. For Children with a Colostomy If your child had a colostomy before this surgery, the colostomy may be closed when the goal size of the anus is reached. After the colostomy is closed, you will still need to dilate your child’s anus until the dilator goes in easily with no discomfort. This will likely be about 3-4 weeks after you get to the last size dilator. Cincinnati Children’s

Answer 55

Once you find that the dilator goes in easy two times a day and does not cause discomfort, you may start to taper (reduce) how often you dilate your child’s anus. While you taper, you will still use the goal size dilator. Month 1: One time a day for a month. Month 2: One time every other day for a month. Month 3: One time every third day for a month. Month 4: Two times a week for a month. Month 5: One time a week for a month. Month 6-8: One time a month for three months. If the dilatation gets harder, causes discomfort, or is bloody at any time during the above schedule, go back to dilating two times a day. When you can easily put in the dilator without discomfort, start the taper schedule again from the beginning (one time a day for a month). Cincinnati Children’s

Answer 56

Most children undergoing a laparoscopic or transanal pullthrough for standard Hirschsprung disease can be fed immediately, and most can be discharged within 24 to 48 hours. The anastomosis should be calibrated with an appropriately sized dilator or finger 1 to 2 weeks after the procedure. Although many surgeons instruct the parents to dilate the anastomosis on a daily basis, others have found it to be unnecessary in most cases and instead perform weekly calibration for a period of 4 to 6 weeks. It is important for the parents to protect the buttocks with a barrier cream because at least 50% of children will have frequent stools and perineal skin breakdown postoperatively. Fortunately, this problem tends to resolve over time. As with any operation, children undergoing a pull-through may develop a wound infection or intra-abdominal bleeding. In addition, anastomotic complications such as leak or stricture may occur. Intestinal perforation can occur at a proximal biopsy site due to back pressure from anal sphincter spasm or due to unrecognized cautery injury. Bowel obstruction can result from intra-abdominal adhesions, a twist in the pullthrough bowel, or a muscular cuff that has rolled down and constricted the pull-through bowel. In rare cases, rectovesical or rectovaginal fistulas have developed after pull-through surgery. Close monitoring for and early treatment of these complications is imperative. In addition, children with Hirschsprung disease can develop enterocolitis, even in the early postoperative period. The family and the primary care physician should be educated about the signs and symptoms of enterocolitis, and the family must be told to bring the child to the hospital if there are any signs suggestive of this problem because children can become very sick and even die from enterocolitis. Coran

Answer 57

There are a range of obstructive symptoms that can be seen after a pull-through. Abdominal distension, bloating, vomiting, or ongoing severe constipation may be present immediately after surgery or may develop later after an initial period of normal bowel function. There are five major reasons for persistent obstructive symptoms following a pull-through: mechanical obstruction, recurrent or acquired aganglionosis, disordered motility in the proximal colon or small bowel, internal sphincter achalasia, or functional megacolon caused by stool-holding behavior. The clinician will have much greater success in managing these difficult patients if an organized approach to this problem is taken. One proposed algorithm is shown in Figure 101-9. 1) Mechanical Obstruction The most common cause of mechanical obstruction after a pull-through is a stricture, which usually occurs after a Swenson or Soave procedure. Patients undergoing a Duhamel procedure may have a retained “spur” consisting of the anterior aganglionic bowel, which may fill with stool and obstruct the pulled-through bowel. In other cases, there may be obstruction secondary to a twist in the pulled-through bowel, or narrowing due to a long muscular cuff in children who have had a Soave procedure. Obstruction can be identified using a combination of digital rectal examination and a barium enema. Initial management of anastomotic stricture consists of repeated dilatation using a finger, dilator, or radially dilating balloon. Some authors have advocated innovative techniques for recalcitrant strictures including antegrade dilatation over a string using Tucker dilators and the use of intralesional steroid. In some cases the stricture cannot be successfully dilated, and revision of the pull-through is necessary. This is best done using the Duhamel technique, although other operations have also been advocated. Duhamel spurs can be resected from above or managed by extending the staple line from below, with or without laparoscopic visualization. Twisted pullthroughs and narrow muscular cuffs usually require surgical intervention, typically a repeat pull-through. In some cases, a muscular cuff can be divided laparoscopically without having to re-do the entire pull-through. 2) Persistent or Acquired Aganglionosis This rare problem may be due to pathologist error, a transition zone pull-through, or ganglion cell loss after a pull-through. Repeat rectal biopsy, above the previous anastomosis (it must be posterior in the case of an initial Duhamel procedure), should be done to determine whether there are normal ganglion cells present in all patients with persistent obstructive symptoms after surgery. The pathology from the original operation should be reviewed to ensure that there was normal innervation at the proximal margin, and in some cases further sections should be done circumferentially from the resection margin because the transition zone is often asymmetrical in children with Hirschsprung disease. The best treatment for persistent or acquired aganglionosis in most cases is a repeat pull-through, which can be done using either a Soave or Duhamel approach. 3) Motility Disorder Children with Hirschsprung disease often have associated motility disorders including an increased incidence of gastroesophageal reflux and delayed gastric emptying, small bowel dysmotility, and disordered colonic motility. Some cases are more focal, usually involving the left colon. In some cases the disordered motility may be associated with histological abnormalities such as intestinal neuronal dysplasia (discussed in greater detail later). In children who have been shown not to have a mechanical obstruction and who have normal ganglion cells on rectal biopsy, investigations for motility disorders should be undertaken. This can include a radiologic shape study, radionuclide colon transit study, colonic manometry, and laparoscopic biopsies looking for evidence of intestinal neuronal dysplasia. If a focal abnormality is found, consideration should be given to resection and repeat pull-through using normal bowel. If the abnormality is diffuse, the appropriate treatment is bowel management and the use of prokinetic agents. Some children with particularly dysmotile colon will benefit from placement of a cecostomy for antegrade colonic enemas. 4) Internal Sphincter Achalasia This term refers to the lack of a normal RAIR that is present in all children with Hirschsprung disease (as described earlier in “Diagnosis”). It is unclear why only some children develop obstructive symptoms from this nonrelaxation, while others function normally in the postoperative period. It is also unclear why most children eventually “grow out” of this problem over time, usually by the age of 5 years. Internal sphincter achalasia is a diagnosis of exclusion, which is made after ruling out mechanical obstruction, aganglionosis, and dysmotility. The diagnosis can be confirmed by demonstrating a clinical response to intrasphincteric botulinum toxin. However, the response to botulinum toxin is not related to the absolute value of the internal anal sphincter pressure (i.e., patients with a higher resting pressure are not necessarily more likely to benefit from botulinum toxin). The standard treatment of internal sphincter achalasia has been internal sphincterotomy or myectomy, but because this problem tends to resolve on its own in most children and there is concern about sphincter-cutting operations exacerbating future soiling issues, we prefer to use “chemical sphincterotomy” with intrasphincteric botulinum toxin. In many cases repeated injection of botulinum toxin or applications of nitroglycerine paste or topical nifedipine are necessary while waiting for resolution of the problem. 5) Functional Megacolon Functional megacolon is the result of stool-holding behavior, a common cause of constipation that some authors claim affects up to half of normal children at some time during their first few years of life. This condition is probably even more common in children with Hirschsprung disease because of their predisposition to constipation, which leads to hard painful stools, withholding behavior, and a resulting vicious cycle. The treatment for this problem is a bowel management regimen consisting of laxatives, enemas, and behavior modification including support for the child and family. In some severe cases of obstructive symptoms, the child may be best served by use of a cecostomy and administration of antegrade enemas, or even by the creation of a proximal stoma. In many cases the cecostomy or stoma can ultimately be reversed when the child reaches adolescence. Coran

Answer 58

There are three broad causes of soiling after a pull-through: abnormal sphincter function, abnormal sensation, or “pseudo-incontinence” related to abnormal rectal function or obstipation. Abnormal sphincter function may be due to sphincter injury during the pull-through or to a previous myectomy or sphincterotomy and can usually be identified using anorectal manometry. Two forms of abnormal sensation exist. The first is lack of sensation of a full rectum, which is also identifiable using anorectal manometry by expanding a balloon in the rectum and asking the child to state when he can feel it. The other type of sensation that may be abnormal is the ability to detect the difference between gas and stool, which is dependent on intact transitional epithelium in the anal canal. This sensation may be impaired if the anastomosis is done too low and the transitional epithelium is damaged. This problem is usually evident on simple physical examination. Neither sphincter weakness nor abnormal sensation is amenable to a surgical solution, and most of these children are best managed using a bowel routine that may include a constipating diet, rectal enemas, or antegrade enemas through a cecostomy. Biofeedback training has been advocated, especially for those children with sphincter weakness. In some cases the child is best served by a colostomy. If both the sphincter and sensation are intact, the most common cause of soiling after a pull-through is “pseudoincontinence.” Some patients have severe obstipation with a massively distended rectum and develop overflow of liquid stool around the fecal mass. Others simply leak small amounts of stool through the day, creating “skid marks” in the underwear on a constant basis. Other children suffer from hyperperistalsis of the pulled-through bowel, which results in inability of the anal sphincter to achieve control despite normal sphincter function. Successful management depends on a clear understanding of the underlying basis for the soiling, which requires a clear history and physical examination, as well as investigations such as abdominal radiograph, barium enema, anorectal manometry, and in some cases colonic manometry. Children with severe constipation will benefit from laxative therapy. However, if the sphincter or sensation, or both, are inadequate, passive laxatives such as lactulose or PEG 3300 will make the problem worse and the child should instead be treated with stimulant laxatives such as senna or enemas. On the other hand, children with stool-holding behavior who have a normal sphincter and sensation will often experience exacerbation of the behavioral problem by rectal enemas or any other kind of anal manipulation. Children without constipation who have hyperperistalsis of the pulled-through bowel or abnormal sphincter function or sensation will benefit from a constipating diet and medications such as loperamide. Children with slow transit constipation or stool-holding behavior, on the other hand, will benefit from a high-fiber diet and passive laxative therapy. The treatment of soiling must be based on a clear understanding of the child’s underlying problem. Coran

Answer 59

Enterocolitis may be present both before and after surgical correction of the disease, and it can be severe or life threatening. HAEC is more common in children diagnosed at a younger age, those with longer segment disease, and those with trisomy 21. The clinical features of HAEC are generally agreed on and include fever, abdominal distention, diarrhea, elevated white blood cell count, and evidence of intestinal edema on abdominal radiograph. Because there is overlap between HAEC and other conditions such as obstructive symptoms and gastroenteritis, there has been confusion in the literature as to the exact definition and the true incidence of the condition. A recently developed HAEC score may be useful in the future in both the clinical setting and in research into this area (Table 101-4). The treatment of postoperative HAEC involves nasogastric drainage, intravenous fluids, broad-spectrum antibiotics, and decompression of the rectum and colon using rectal stimulation or irrigations. The risk of HAEC can be minimized by using preventive measures such as routine irrigations or chronic administration of metronidazole or probiotic agents, particularly in those who are thought to be at higher risk for this complication on the basis of clinical or histologic grounds. Because enterocolitis is the most common cause of death in children with Hirschsprung disease and can occur postoperatively even in children who did not have it preoperatively, it is extremely important that the surgeon educate the family about the risk of this complication and urge early return to the hospital if the child should develop any concerning symptoms. Coran

Answer 60

Intestinal neuronal dysplasia (IND) was first described by Meier-Ruge in 1971 as a malformation of enteric plexus. The first association between IND and HD was reported by my colleagues and me in a 5-year-old Arab boy who had rectosigmoid aganglionosis and IND of descending and transverse colon. In 1983 Fadda and colleagues classified IND into two clinically and histologically distinguished subtypes. Type A, which occurs in less than 5% of cases, is characterized by congenital aplasia or hypoplasia of the sympathetic innervation and presents acutely in the neonatal period with episodes of intestinal obstruction, diarrhea, and bloody stools. Type B is clinically indistinguishable from HD, is characterized by a malformation of the parasympathetic submucous and myenteric plexuses, and accounts for more than 95% of cases of IND. IND occurring in association with HD is of type B. Since its original description, little has been written about IND type A. IND has become synonymous with IND type B. Many investigators have raised doubts about the existence of IND as a distinct histopathologic entity. It has been suggested that the pathologic changes seen in IND may be part of normal development or may be a secondary phenomenon induced by congenital obstruction and inflammatory disease. On the other hand, the literature contains several familial cases of IND suggesting that genetic factors may be involved in this condition. Martuccielo and colleagues observed three families with multiple IND cases, and Moore and colleagues and Kobayashi and colleagues reported IND in monozygotic twins. The strongest evidence that IND is a real entity stems from the animal models. Hox11L1 is a homeobox gene involved in peripheral nervous system development and is reported to play a role in the proliferation or differentiation of neural crest cell lines. Two different Hox11L1 knockout mouse models have been generated. In both cases, homozygous mutant mice were viable but developed megacolon at the age of 3 to 5 weeks. Histologic and immunohistochemical analysis showed hyperplasia of myenteric ganglia, a phenotype similar to that observed in human IND type B. However, the mutation screening of this gene in 48 patients with IND did not show any sequence variant, either causative missense mutation or neutral substitution. In 2002 Von Boyen and colleagues 15 reported abnormalities of the enteric nervous system in heterozygous EDNRBdeficient rats resembling IND in humans. They showed that a heterozygous 301-base-pair deletion of the EDNRB gene led to abnormalities of the enteric nervous system. Malformations of the enteric nervous system observed in + /sl rats included hyperganglionosis, giant ganglia, and hypertrophied nerve fibers in the submucous plexus resembling the histopathologic features of IND type B in humans. These findings support the concept that IND may be linked to a genetic defect. However, no mutations of the EDNRB gene were detected in a small series of IND patients. INCIDENCE Intestinal neuronal dysplasia is the most commonly encountered variant of HD. The incidence of isolated IND has varied from 0.3% to 40% of all suction rectal biopsies in different centers. The incidence varies considerably among different countries. IND immediately proximal to a segment of aganglionosis is not uncommon and often presents as persistent obstructive symptoms after a pull-through operation for HD. Some investigators have reported that 25% to 35% of patients with HD have associated IND. However, others have rarely encountered IND in association with HD. The uncertainty regarding the incidence of IND has resulted from the considerable confusion regarding the essential diagnostic criteria. The diagnostic difficulty is centered on a wide variability encountered in the literature, not only in terms of age of the patient, the type of specimen examined, and the stains performed but also in the diagnostic criteria used. CLINICAL PRESENTATION The characteristic clinical pattern of IND can be found in infants younger than 1 year old with a history of constipation and abdominal distention, thus mimicking HD. Montedonico and colleagues classified IND according to the severity of histochemical changes in rectal biopsies. The criteria used for the diagnosis of severe IND included hyperplasia of submucous plexus, giant ganglia, ectopic ganglia, and increased acetylcholinesterase (AChE) activity in the lamina propria or around submucosal blood vessels. Any biopsy that showed giant ganglia of the submucous plexus with only one of the other criteria was considered mild. Montedonico and colleagues reported that the patients with severe IND begin their symptoms at an earlier age than those with mild IND (5.2 +/- 112 months vs. 17.5 +/- 23 months). The incidence of associated anomalies in IND has been reported to be between 25% and 30%. The common associated anomalies include anorectal malformations, intestinal malrotation, MMIHS, congenital short bowel, hypertrophic pyloric stenosis, necrotizing enterocolitis, and Down syndrome. Coran

Answer 61

DIAGNOSTIC CRITERIA Since the first description in 1971, most controversy surrounding IND has been regarding which histologic diagnostic criteria are required for definitive diagnosis. The presently recognized diagnostic criteria, previously reported by our group and supported by others, are hyperganglionosis and giant ganglia, in addition to the presence of at least one of the following on suction rectal biopsy: ectopic ganglia in the lamina propria and increased AChE-positive nerve fibers around submucosal blood vessels and in the lamina propria. However, Lumb and Moore believe that giant ganglia can be a normal feature in normal bowel, having identified them in segments of adult bowel removed during surgery for colorectal carcinoma. To overcome the confusion in diagnostic criteria, Borchard and colleagues produced guidelines for identifying IND in mucosal rectal biopsies. These comprised two obligatory criteria (hyperplasia of the submucous plexus and an increase in AChE-positive nerve fibers around submucosal blood vessels) and two additional criteria (neuronal heterotopia and increased AChE activity in the lamina propria). In our experience, hyperganglionosis and giant ganglia are the most important features for the diagnosis of IND in suction rectal biopsies, except in the newborn, when hyperganglionosis is a normal finding. DIAGNOSIS Suction rectal biopsy is the principal method for the diagnosis of disorders of intestinal innervation. It is necessary to include a sufficient amount of submucosa in the suction biopsy specimens. Traditionally, hematoxylin and eosin and AChE histochemical staining (Figs. 102-1 and 102-2) in suction rectal biopsy specimens have provided the basis for the diagnostic evaluation of IND. However, there has been discussion about whether AChE histochemistry is sufficient for the accurate diagnosis of IND and other additional staining techniques have been proposed. Meier-Ruge and colleagues suggest lactate dehydrogenase histochemistry. In my laboratory, neuronal markers currently being used are reduced nicotinamide-adenine dinucleotide phosphate (NADPH) diaphorase histochemistry and immunohistochemistry using antibodies raised against neural cell adhesion molecule, protein gene product 9.5 (PGP9.5), S-100, peripherin, and synaptophysin. Ganglion-cell counting can be difficult. Standard immunohistochemical techniques, using antibodies raised against neuron-specific enolase or PGP9.5, which are commonly used to display the enteric nervous system, are less suitable for cell counting because they stain not only the cell bodies but also the axonal processes. Cuprolinic blue staining has been proposed as the method that stains the largest number of ganglion cells. Furthermore, this method stains only the cell bodies and not the axons, which makes it relatively easy to distinguish the individual cells. Barium enema in IND does not show any specific radiologic features other than rectosigmoid distention. Similarly, anorectal manometry may show the rectosphincteric reflex to be present, absent, or atypical. CORRELATION BETWEEN HISTOLOGIC FINDINGS AND CLINICAL SYMPTOMS Several investigators have raised doubts about the existence of IND as a distinct histopathologic entity. One reason for this has been the weak correlation found between the severity of clinical symptoms and the histologic findings. It has been suggested that the histologic findings of IND can be a part of normal development or secondary to prolonged constipation. Recently, Montedonico and colleagues correlated specific clinical, radiologic, and manometric findings with the severity of histopathologic findings in 44 patients with IND treated at their institution over 20 years. They classified IND according to the severity of histochemical alteration into two groups: mild IND and severe IND. The criteria used for the diagnosis of severe IND included hyperplasia of the submucous plexus, giant ganglia with more than seven ganglion cells, increased AChE activity in the lamina propria or surrounding submucosal blood vessels, and heterotopic neuronal cells in the lamina propria. Any biopsy specimen that showed giant ganglia of the submucous plexus with only one of the other elements was considered mild IND. According to their results, the characteristic clinical pattern of severe IND can be found in infants younger than 1 year old with a history of constipation and abdominal distention, thus mimicking HD, with absence of internal sphincter relaxation in anorectal manometry but who have a normal barium enema. The median age at presentation of severe IND was 5 months, and similar results have been reported in other series. These authors found a correlation between the histologic severity of IND and the clinical symptoms, suggesting that IND is a distinct entity. Although many cases of IND are clinically indistinguishable from HD, barium enema findings in IND are often equivocal or show slight to moderate rectosigmoid distention but lack the typical narrow segment of aganglionosis. Coran

Answer 62

MANAGEMENT Current treatment of IND type B is in the first instance conservative, consisting of laxatives and enemas. In the majority of patients the clinical problem resolves or is manageable in this way because maturation of nerve cells is often observed in IND. If bowel symptoms persist after at least 6 months of treatment, internal sphincter myectomy should be considered. Resection and a pull-through operation are rarely indicated in IND. The indication for pull-through should not be determined on the basis of histopathologic findings alone; rather, the decision must be based on the individual patient’s clinical symptoms. OUTCOME Gillick and colleagues 24 reported results of treatment in 33 patients with IND observed for periods ranging from 1 to 8 years (mean 2.4 years). Twenty-one (64%) patients had a good response to conservative management and currently have normal bowel habits. Twelve patients (36%) underwent internal sphincter myectomy after failed conservative management. Seven of these patients now have normal bowel habits. Two patients were able to stay clean with regular enemas. Three patients who continued to have persistent constipation after myectomy and underwent resection of redundant and dilated sigmoid colon now had normal bowel habits. Coran

Answer 63

Isolated hypoganglionosis (IH) has been classified as a “hypogenetic type” of intestinal innervation disorders. Clinically, IH resembles classical HD: Patients present with severe constipation or pseudo-obstruction. Due to the fact that IH is one of the rarest subtypes of intestinal innervation disorders, accounting for only 5% of all cases, the number of reported cases in the literature is limited. Dingemann and Puri recently reviewed 92 patients with IH reported in the English literature between 1978 and 2008 and critically analyzed the current state of the epidemiologic, diagnostic, and therapeutic features of this rare neuronal intestinal disorder. EPIDEMIOLOGY In the reported review the overall male-to-female ratio of IH was 3:1. This is similar to the overall male-to-female ratio of HD, which is commonly considered to be 4:1. Although 29 (32%) patients were diagnosed in the newborn period, the median age at diagnosis of the reported patients with IH was 4.85 years. This is due to the fact that, in some patients, diagnosis was made as late as the age of 17 years. This differs significantly from HD. Although late diagnosis is also possible in HD, more than 90.6% of patients are diagnosed in the newborn period. This late diagnosis of IH might reflect the difficulties in diagnosing IH in rectal suction biopsies but also the rareness of the disease. CLINICAL PRESENTATION Even though the median age at diagnosis is significantly higher in patients with IH than in those with HD, the symptoms of IH resemble classical aganglionosis. The symptoms reported in all IH included intractable constipation, ileus, and enterocolitis. As in HD, enterocolitis of the newborn remains the most serious complication of IH, as 6 of the 7 reported IH related deaths were neonates with enterocolitis. HISTOPATHOLOGIC APPROACH The diagnosis of IH by means of rectal suction biopsy is difficult. As recommended by the interdisciplinary consensus conference, a full-thickness bowel is essential for the diagnosis of IH. Besides standard hematoxylin and eosin staining, histochemical evaluation of AChE was performed by 91% of the authors in the review by Dingemann and Puri to visualize the characteristic changes for IH such as low mucosal activity of AChE, deficiency of nerve cells in the myenteric plexuses, and hypertrophy of muscularis mucosae and circular muscle layers. Morphometric measurements in IH using AChE staining, as suggested by Meier-Ruge and colleagues, represent one of the cornerstones of diagnostic criteria for the disease. It has been shown that plexus area and nerve cell number are dramatically decreased, and the distance between ganglia is almost doubled. Several additional neuronal markers have been used to diagnose IH. Rolle and colleagues used NADPH diaphorase staining, which not only allows one to characterize the nitrergic innervation of the muscle but also differentiates mature fully developed ganglia from the immature ganglia in IH. Coran

Answer 64

According to literature, the treatment of hypoganglionosis is similar to HD involving resection of the affected segment and pull-through operation. In the review of 92 patients with IH reported by Dingemann and Puri, patients received resection of affected bowel and pull-through procedures of different types; 11 underwent ileostomy, colostomy, or jejunostomy alone; and 2 underwent sphincter myectomy. In 25 patients, the operative treatment was not clearly stated. The treatment of choice remains resection of the affected segment. The exact method used must always be tailored to the extent of affected bowel, the localization of the disease, and presumably it will also depend on the surgeon’s preference in this rare disease. OUTCOME AND COMPLICATIONS The overall mortality of the patients included in this review was 8%. Six of the seven patients who died were newborns suffering from severe enterocolitis. The other patient died due to total parenteral nutrition–associated complications during follow-up. During a postoperative follow-up of 7 months to 12 years, typical complications reported were similar to those in HD. Enterocolitis, chronic constipation, overflow encopresis, and the need for redo pull-through for residual disease were reported. Coran

Answer 65

The internal anal sphincter (IAS), a specialized smooth muscle continuation of the circular muscle layer of rectum, plays a significant role in the maintenance of anorectal continence and in the pathophysiology of incontinence and constipation. The IAS relaxes in response to rectal distension, a phenomenon called the rectosphincteric inhibitory reflex, which is mediated by intramural nerves descending from the rectum to the IAS. The IAS receives adrenergic, cholinergic, and nonadrenergic noncholinergic (NANC) innervations. Several investigators have reported that IAS relaxation is brought about by the activation of intramural NANC nerves. Nitric oxide (NO) is now recognized as a potent mediator of nonadrenergic noncholinergic inhibitory nerves, which regulate smooth muscle relaxation in the mammalian gastrointestinal tract including IAS. Internal anal sphincter achalasia (IASA) is a clinical condition with presentation similar to HD but with the presence of ganglion cells on suction rectal biopsy. The diagnosis of IASA is made on anorectal manometry, which shows the absence of rectosphincteric reflex on rectal balloon inflation. Previously, IASA has been referred to as ultrashort segment HD. The ultrashort segment HD, which is a rare condition, is characterized by an aganglionic segment of 1 to 3 cm long and normal acetylcholinesterase (AChE) activity in the lamina propria and increased AChE activity in the muscularis mucosae. Many patients who are considered to have ultrashort HD on abnormal anorectal manometric findings show presence of ganglion cells and normal acetylcholinesterase (AChE) activity in suction rectal biopsies. Many investigators have therefore suggested that the term IASA is more suitable because it reflects more accurately failure of relaxation of the internal sphincter, which is the causative factor in this condition. INCIDENCE The exact incidence of isolated internal anal sphincter achalasia is not known. De Caluwe and colleagues reported an incidence of 4.5% among 332 children who were investigated for severe chronic constipation. PATHOGENESIS The exact pathogenesis and pathophysiology of IASA is not fully understood. Altered intramuscular innervation has been reported in IASA, and this is believed to be responsible for the motility dysfunction seen in these patients. Hirakawa and colleagues reported absence of nitrergic innervation within the IAS muscle in patients with IASA and suggested that nitrergic nerve depletion may play an important role in the development of IASA. Because nitrergic nerves regulate smooth muscle relaxation, their deficiency or absence in IASA may be responsible for the spasm or increased tone in the IAS in these patients. Oue and Puri reported defective innervation of the neuromuscular junction (NMJ) of the IAS in patients with IASA. If the NMJ is abnormal, the neurotransmitter chemicals synthesizing neurons cannot be transmitted to muscle cells, thereby causing motility dysfunction. Altered distribution of c-kit positive interstitial cells of Cajal (ICCs) has been reported in the internal sphincter of patients with internal sphincter achalasia, which may further contribute to motility dysfunction in these patients. Piotrowska and colleagues reported deficiency or absence of ICCs in the IAS myectomy specimens obtained from patients with IASA at the time of internal sphincter myectomy. The functions of ICCs include the generation of electrical pacemaker activity, generation of slow waves, and neurotransmission between the enteric nervous system and smooth muscle cells. It has been proposed that ICCs in certain regions of the gut may not act as pacemakers, but as stretch receptors. The lack or deficient expression of NO and ICCs in the IASA may lead to defective generation of nitric oxidemediated pacemaker activity causing motility dysfunction. Coran

Answer 66

Patients with IASA have clinical presentation similar to HD. The vast majority of patients present with severe constipation with or without soiling. About one third of the patients give history of abdominal distension. Laxatives usually fail to improve constipation in patients with IASA. Definite diagnosis of IASA is based on anorectal manometry, which shows absence of rectosphincteric reflex on rectal balloon inflation and the presence of marked rhythmic activity of the internal anal sphincter, presence of ganglion cells and normal acetylcholinesterase activity in the suction rectal biopsy. Coran

Answer 67

Posterior internal sphincter myectomy has been recommended as the treatment of choice for patients with internal sphincter achalasia. The myectomy is performed posteriorly starting at the level of the pectinate line, and a 5- to 10-mm wide strip of smooth muscle is resected extending proximally for varying lengths ranging from 15 to 50 mm. De Caluwe and colleagues reported bowel function in 15 consecutive patients with IASA 2 to 6 years after posterior internal sphincter myectomy. At the time of follow-up, seven patients had regular bowel motions and were not on any laxatives. Six patients had normal bowel habits but were on small doses of laxatives. One patient was able to stay clean with a regular enema regimen. One patient required resection of dilated and redundant sigmoid colon and now has normal bowel habits with laxatives. Recently Heikkinen and colleagues reported long-term follow-up in 10 IASA patients, 7 to 16 years after internal sphincter myectomy. Three of the ten patients in their study needed laxatives at the time of follow-up, and one patient had required resection of the dilated and redundant rectosigmoid 2½ years after myectomy. The remaining six patients had one to two bowel motions daily without the help of laxatives. Four of their patients suffered from soiling-related social problems. Recently intrasphincteric injection of botulinum toxin has been used to treat patients with IASA. This is thought to work by interfering with the Ach release at the neuromuscular junction (NMJ) and thus inhibiting sympathetic stimulation to the IAS. Intrasphincteric injection is thought to produce a local and transient chemical denervation of the sphincter. This treatment modality has been found to be safe, but the effects are transient. The IAS is injected in four quadrants, 25 i.u. per quadrant at the level of the dentate line. Irani and colleagues injected Botox in 24 patients with IASA and found that the duration of response following Botox injection was variable, ranging from 1 month to longer than 1 year. Foroutan and colleagues 38 compared efficacy of intrasphincteric Botox injection and internal sphincter myectomy in patients with IASA and found that Botox injection was as effective as myectomy. Further studies with longer follow-up are necessary to determine the effectiveness of this treatment modality in the management of internal sphincter achalasia. Coran

Answer 68

MEGACYSTIS-MICROCOLON-INTESTINAL HYPOPERISTALSIS SYNDROME MMIHS is a rare congenital and generally fatal cause of functional intestinal obstruction in the newborn. This syndrome is characterized by abdominal distension caused by a distended nonobstructed urinary bladder, microcolon, and decreased or absent intestinal peristalsis. Usually incomplete intestinal rotation and shortened small bowel are associated. PATHOGENESIS MMIHS was first described in1976 by Berdon and colleagues and, to date, 182 cases have been reported in the literature. The etiology of this syndrome remains unclear. Several hypotheses have been proposed to explain the pathogenesis of MMIHS: genetic, neurogenic, myogenic, and hormonal origin. Histologic studies of the myenteric and submucosal plexuses of the bowel of MMIHS patients have found normal ganglion cells in the majority of the patients, decreased in some, hyperganglionosis, and giant ganglia in others. Recently, Piotrowska and colleagues 34 reported absence of interstitial cells of Cajal (ICCs) in the bowel and urinary bladder of patients with MMIHS. ICCs are pacemaker cells that assist active propagation of electrical events and neurotransmission, and their absence may result in hypoperistalsis and voiding dysfunction in MMIHS. Puri and colleagues showed, in 1983, vacuolar degenerative changes in the smooth muscle cells (SMCs) with abundant connective tissue between muscle cells in the bowel and bladder of patients with MMIHS and suggested that a degenerative disease of smooth muscle cells could be the cause of this syndrome. Several subsequent reports have confirmed evidence of intestinal myopathy in MMIHS. Other investigators have reported absence or marked reduction in a-smooth muscle actin and other contractile and cytoskeletal proteins in the smooth muscle layers of MMIHS bowel. Contractile and cytoskeletal proteins are important structural and functional components of SMCs and play a vital role in the interaction of the filaments in smooth muscle contraction. Coran

Answer 69

PRENATAL DIAGNOSIS Puri and Shinkai reviewed 182 cases of MMIHS reported in the literature. In 54 cases ultrasound findings associated with MMIHS were described. The most frequent finding was enlarged bladder (88%), with hydronephrosis seen in 31 patients (57%). Normal amniotic fluid volume was revealed in 32 cases (59%), increased volume occurred in 18 (33%), and volume decreased in 4 (7%). In three cases (5%) abdominal distention caused by dilated stomach was detected. Three cases of oligohydramnios during the second and early third trimesters were reported, probably related to the functional bladder obstruction. Serial obstetrical ultrasonography showed that the earliest finding in MMIHS is enlarged bladder, detectable from 16 weeks of gestational age. A later finding is hydronephrosis, caused by the functional obstruction of the bladder. Usually polyhydramnios develops late, appearing during the third trimester. CLINICAL PRESENTATION Of the 182 cases reported in the literature, sex of the patient was mentioned in 149 patients. Ninety-eight were females and 43 were males. In four cases, pregnancy was terminated after ultrasonography detected MMIHS, which was confirmed at autopsy in all cases. The duration of pregnancy was reported in 98 cases. Fifty-eight patients (59%) were born at term, 25 (25.5%) at 36 to 39 weeks of gestation, 12 (12%) at 32 to 35 weeks, and 3 (3%) at 31 weeks and less. Dystocia delivery caused by abdominal distention was reported in eight cases. In four cases Caesarean section was required, and in four cases the bladder was so distended that the baby could only be delivered vaginally after removal of 250, 500, 650, 500 mL of urine, respectively, from fetal bladder by paracentesis. The mean birth weight was normal (3 kg) for gestational age. The clinical symptoms of MMIHS are similar to other neonatal intestinal obstructions. Characterized by abdominal distention, bile-stained vomiting, and absent or decreased bowel sounds, abdominal distention was a constant and early finding. A consequence of the distended, nonobstructed urinary bladder was relieved by catheterization. Of 182 cases 61 had bilious vomiting, and failure to pass meconium was clearly reported in only 23 cases. The majority of patients were not able to void spontaneously. In the review by Puri and Shinkai, 19 sets of siblings affected with MMIHS were reported. Eighteen families had two affected siblings and one had three. Four sets of affected siblings occurred to consanguineous parents. In another case an affected child was born to a member of the family reported by Penman, and consanguinity was also present in these parents. In three further cases an elder sibling of the affected child died just after birth because of intestinal obstruction 30 or multiple abnormalities; in another case a sibling of the patient was affected by prune-belly syndrome. The occurrence of MMIHS in 19 sets of affected siblings and consanguinity in four sets of parents suggest an autosomal recessive pattern of inheritance. RADIOLOGIC FINDINGS In the vast majorities of the 182 cases, radiologic evaluation usually suggested the diagnosis of MMIHS. Plain abdominal films showed either dilated small bowel loops or a gasless abdomen with evident gastric bubble. An enlarged urinary bladder was present in all patients who had cystography or ultrasonography (Fig. 102-5). Intravenous urography or ultrasonography detected unilateral or bilateral hydronephrosis in 84 patients. Forty-four patients had an upper gastrointestinal series both before and after laparotomy: hypoperistalsis or aperistalsis in stomach, duodenum, and small bowel was a constantly detected symptom. In three cases reverse peristalsis from small bowel into the stomach was also observed. In two cases hypoperistalsis was associated with gastroesophageal reflux, and in one case the esophagus was aperistaltic. Barium enema showed microcolon in all 71 patients in whom this study was performed; in 39 cases malrotation was associated. Coran

Answer 70

Megacystis and microcolon were the two most frequent findings at surgery or autopsy and were present in all patients. In the review by Puri and Shinkai, short-bowel syndrome was found in 37 cases, dilated proximal small bowel in 19, segmental stenosis of the small bowel in 3, duodenal web in 1, and Meckel diverticulum in 1. Malrotation was found in a total of 81 cases. Although surgical management was not mentioned in several reports, 93 patients (70%) underwent one or more surgical procedures. A variety of interventions were performed: gastrostomy, jejunostomy, ileostomy, cecostomy, segmental resection of jejunum and ileum, lysis of adhesions, and internal sphincter myectomy. Surgical manipulation of the gastrointestinal tract has generally been unsuccessful, and in most patients total parenteral nutrition was required. In 37 patients vesicostomy was performed to decompress the urinary tract and to preserve renal function. HISTOLOGIC FINDINGS Histologic studies of the myenteric and submucous plexuses were reported in 93 out of 182 cases. In 72 the ganglion cells were normal in appearance and number, and in the remaining 21 cases the various neuronal abnormalities reported included hypoganglionosis, hyperganglionosis, and immature ganglia. The majority of reports do not mention the histologic findings in the muscle layers of bowel and bladder wall. Nevertheless, some authors found significant abnormalities in SMCs. In nine cases thinning of the longitudinal muscle was found on light microscopy. Electron microscopy showed vacuolar degeneration in the center of the smooth muscle of the bowel in 11 cases and of the bladder in 8 cases. Connective tissue proliferation was found in the bowel in nine cases and in the bladder in eight cases. In three more cases the bladder showed elastosis. In two patients electron microscopy revealed vacuolar degeneration of smooth cells in the muscle layers of the bowel and the bladder in addition to neuronal abnormalities. Other investigators have reported absence or marked reduction in a-smooth muscle actin and other contractile and cytoskeletal proteins in the smooth muscle layers of MMIHS bowel. OUTCOME The management of patients with MMIHS is frustrating. A number of prokinetic drugs and gastrointestinal hormones have been tried without success. Surgical manipulation of the gastrointestinal tract has generally been unsuccessful. The outcome of this condition is generally fatal: Only 23 of the 182 reported patients were alive, the oldest being 18 years old. Twenty-one of the 23 patients were being maintained by total or partial parenteral nutrition. The need for surgical intervention should be made carefully and individualized, in that most explorations have not been helpful and are probably not necessary. Coran

Answer 71

C Failure of migration of neural crest cells because there is deficiency of glycoprotein (e.g., fibronectin, laminin and hyaluronic acid), which guides the migration. Increase expression of class II antigen in mucosa and submucosa of patients with Hirschsprung’s disease, which demonstrates possibility of immunological response against neuroblast. Mutation at long arm of chromosome number 10, causes deficient nitrous oxide synthetase. Nitrous oxide is major inhibitory mediator. Its deficiency leads to spastic condition. Syed/MCQ

Answer 72

A In Hirschsprung’s disease, there is nascence of ganglionic cells. Ganglionic cells cause contraction and relaxation of smooth muscles. Relaxation is predominant in normal condition. Increased extrinsic innervation is seen in Hirschsprung’s disease. Hypertrophy of nerve bundle seen. Normally, cholinergic is excitatory and adrenergic is inhibitory, but in Hirschsprung’s disease, adrenergic also becomes excitatory, leading to spastic condition of ganglionic part. Syed/MCQ

Answer 73

E There is decreased recto-sigmoid index in Hirschsprung’s disease. Addition features of Hirschsprung’s disease in barium Enema are, post-evacuation radiograph, 24 hours or more shows incomplete evacuation of barium and saw tooth appearance in enterocolitis. Syed/MCQ

Answer 74

D Hypothyroidism is one of the differential diagnoses of Hirschsprung’s disease. Other differential diagnosis includes small intestinal stenosis, low imperforate anus, prematurity, meconium plug syndrome, sepsis, electrolyte imbalance, functional constipation and intestinal neuronal dysplasia. Syed/MCQ

Answer 75

D Martin’s modification is for total colonic aganglionosis. Syed/MCQ

Answer 76

E A, B, and C are complications of surgical procedures of Hirschsprung’s disease. Other complications of Hirschsprung’s disease are stenosis and post-operative intestinal obstruction, post-operative enterocolitis, fecaloma, anastomotic disruption, and enterocolic fistula. Syed/MCQ

Answer 77

A Biopsy should be taken 1–2 cm above the dentate line. Biopsy is taken from posterior wall. Rectal defect after taking biopsy should be closed by interrupted or running stitches. Stay suture helps in taking biopsy. Syed/MCQ

Answer 78

E A, B, and C all are true statements Syed/MCQ

Answer 79

A It is difficult to identify transitional zone in neonates. Syed/MCQ

Answer 80

C The specimen should be taken from posterior or lateral wall, not from anterior wall. Syed/MCQ

Answer 81

E Hypothyroidism causes constipation. Syed/MCQ

Answer 82

C 86 per cent of patients are full term, while 14 per cent are preterm. 81 percent are boys and 19 percent are girls. Age at the diagnosis is less than one month in 43 percent of cases, one month to one year in 37 percent of cases, more than one year in 20 percent of cases. As far as clinical features are concerned abdominal distension is seen in 59 percent of cases, failure to pass meconium in 42 percent of cases, bilious vomiting in 41 percent, enterocolitis in 7 percent, perforation 3 per cent and complete bowel obstruction in 3 percent of cases. Level of disease noted as recto-sigmoid in 79 percent of cases. Syed/MCQ

Answer 83

A Risk of future offspring is around 4 percent. Syed/MCQ

Answer 84

B 4–8 percent. Syed/MCQ

Answer 85

C Enterocolitis is the most common late complication. Presents with abdominal distension, pain, fever and explosive watery diarrhoea. The disease may be mild or fulminant gram negative sepsis or intestinal perforation. The enterocolitis may occur prior to colostomy or after properly done pull-through. Syed/MCQ

Answer 86

E All statements A, B, C and D are true.

Answer 87

A 10–30 percent percent of Hirschsprung’s disease is associated with meconium plug syndrome.