Lakshmana Das Narla, MD Elizabeth A.

Hingsbergen, MD

Case 22: Total Colonic Aganglionosis Long-Segment Hirschsprung Disease1

HISTORY
A 9-day-old term female neonate presented with bilious vomiting. A radiograph of the abdomen obtained with the patient supine (Fig 1), a spot lateral radiograph of the colon obtained with the patient in a left posterior oblique position after administration of an enema containing water-soluble contrast material (Fig 2), and a radiograph of the abdomen obtained with the patient supine 20 hours after the first radiograph was obtained (Fig 3) are shown. Initial rectal biopsy results showed no ganglion cells, which is consistent with Hirschsprung disease. At the time of surgery for ostomy placement, results of biopsy of the rectum, sigmoid colon, hepatic flexure, appendix, and terminal ileum showed no ganglion cells (Fig 4). Ganglion cells were demonstrated in the ileum 15 cm from the ileocecal valve. Appendectomy and loop ileostomy were performed. The findings of irregular muscular contractions in the region of the hepatic flexure, normal-caliber colon, and small-bowel dilatation suggested a diagnosis of total colonic aganglionosisa long-segment form of Hirschsprung disease.

IMAGING FINDINGS DISCUSSION

A radiograph of the abdomen obtained with the patient supine showed multiple dilated bowel loops throughout the abdomen (Fig 1). A spot lateral radiograph of the colon obtained with the patient in a left posterior oblique position after administration of an enema containing iohexol (Omnipaque 180 [osmolality 408 mOsm/kg water]; Nycomed Amersham, Princeton, NJ), which is slightly hyperosmolal, showed multiple filling defects throughout the colon (Fig 2). The overall caliber of the colon was normal, with slight decrease in caliber of the rectosigmoid. The patient passed large amounts of meconium immediately after the study and during the next 10-15 hours. A radiograph of the abdomen obtained with the patient supine 20 hours after the first radiograph was obtained showed residual contrast material throughout the normal-caliber colon (Fig 3). Irregularity of the wall at the hepatic flexure, which is consistent with muscular contractions, was noted on only this one radiograph. There were persistently dilated loops of small bowel in the upper abdomen. Any newborn with clinical findings and abdominal radiographs suggestive of low intestinal obstruction (failure to pass meconium, abdominal distention, bilious emesis, abdominal radiographs with multiple dilated loops of bowel) should be examined by means of a nonionic iso-osmolal water-soluble enema. The causes of low intestinal obstruction include imperforate anus; meconium plug syndrome; meconium ileus; Hirschsprung disease; small left colon syndrome; megacystis-microcolon-intestinal hypoperistalsis syndrome; and colonic, ileal, or distal jejunal atresia or stenoses. Since this patient was 9 days old, the diagnoses of imperforate anus and small-bowel atresia were not considered. Diagnosis of imperforate anus is made by means of physical examination, with diagnostic work-up performed to determine high or low type and any associated genitourinary anomalies. Contrast materialenhanced enema examination and clinical information are used to attempt to differentiate the remaining entities. Evaluation of the caliber of the colon is essential in attempting to elucidate the cause of low intestinal obstruction. A microcolon shows a very small caliber, generally less than 1 cm in diameter, owing to disuse of the colon from a more proximal obstruction. Microcolon is seen in patients with meconium ileus; distal jejunal, ileal, or proximal colonic atresia; and megacystis-microcolon-intestinal hypoperistalsis syndrome. It is seen in less than one-fourth of patients with total colonic Hirschsprung disease (1). Results of examination with contrast material that show a narrow descending colon with a marked change of caliber at the splenic flexure can be seen with syndromes of neonatal functional immaturity of the large bowel (small left colon syndrome and meconium plug syndrome) or in long-segment Hirschsprung disease. For diagnostic enema results in newborns, a relatively dilute ionic, water-soluble contrast material, such as iothalamate meglumine (Cysto-Conray [400 mOsm/kg water]; Mallinckrodt, St
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Index terms: Colon, aganglionosis, 75.145 Colon, stenosis or obstruction, 75.143 Diagnosis Please Infants, newborn, gastrointestinal tract, 75.145 Radiography, in infants and children, 75.1281, 75.1283 Radiology 2000; 215:391394
1

From the Department of Radiology, Medical College of Virginia of Virginia Commonwealth University, 401 N 12th St, Rm 3-415, Richmond, VA 23298. Received September 14, 1998; revision requested October 22; final revision received March 18, 1999; accepted April 8. Address correspondence to L.D.N. (e-mail: ldnarla@hsc.vcu.edu). RSNA, 2000

Figure 1. Radiograph of the abdomen obtained with the patient supine shows distention of bowel loops with elevated hemidiaphragms, which is consistent with low intestinal obstruction.

Figure 2. Spot lateral radiograph of the colon obtained with the patient in a left posterior oblique position after administration of an enema containing water-soluble contrast material demonstrates filling defects in the colon (meconium plugs) and decrease in the caliber of the rectosigmoid area. Note the absence of dilated colon proximal to the narrowed rectosigmoid.

Louis, Mo), or a low-osmolal, nonionic, water-soluble contrast material, such as iohexol (Omnipaque [411 mOsm/kg water]; Nycomed Amersham), can be used. In neonates, water-soluble contrast materials are preferable to barium because, although it is rare, perforation due to the obstruction may not be depicted at conventional radiography and because contrast material may spill into the peritoneal cavity. Infants with either functional immaturity of the colon or meconium ileus, especially the latter, benefit from enemas with water-soluble contrast material: Therapy thus begins immediately, with the diagnostic study. There has been greater success in reducing meconium ileus by using water-soluble contrast material for the initial diagnostic enema rather than barium. Passage of meconium after the enema does not preclude the diagnosis of Hirschsprung disease. In equivocal cases, or if persistent problems with passing stool occur, Hirschsprung disease should be considered, and rectal biopsy is indicated. Rectal biopsy is performed at the bedside, and a deep transrectal specimen to include myenteric plexus is obtained. Hirschsprung disease is a common cause of all neonatal bowel obstruction and accounts for one-third of all cases. The incidence of Hirschsprung disease is one per 5,000 livebirths per year and increases to 3.6% in families with one affected male member and to 8.0% with one affected female member (2). Hirschsprung disease occurs three or four times more often in boys than in girls and, for unknown reasons, is rare in premature infants. In the uncommon total colonic variant, the prevalence in boys and girls is nearly equal, with a strong hereditary tendency. Patients present in the neonatal period 80% of the time, with presenting symptoms including delay in passage of meconium, abdominal distention, constipation, and bilious vomiting (3). Twenty percent of patients have associated abnormalities,
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including Down syndrome (8%), cardiac defects (8%), genitourinary abnormalities (6%), and gastrointestinal anomalies (4%). Gastrointestinal anomalies can include colonic atresia, imperforate anus, and neurocristopathy. Neurocristopathies can occur singularly or in combination with neurocristopathic syndromes such as neuroblastoma; pheochromocytoma; neurofibromatosis; Waardenburg syndrome; multiple endocrine neoplasia, type 2; and congenital central hypoventilation syndrome, also known as Ondine curse (4). The histopathologic criterion for diagnosis of Hirschsprung disease is absence of the ganglion cells of the myenteric plexus; this results in a narrowed aganglionic segment with a dilated segment proximal to this distal obstruction. The myenteric ganglion cells arise from the neural crest and migrate cephalocaudally along the vagal trunks through the intestines. An early arrest in the migration between the 7th and 12th weeks of gestation leads to Hirschsprung disease and can affect a variable length of the colon and the small bowel (5,6). The transition zone from abnormal to normal ganglionic bowel is found in the rectosigmoid or sigmoid colon in 65% of patients, the descending colon in 14%, the rectum in 8%, and the more proximal large bowel in 10% (7). Aganglionosis affecting the small bowel is rare and occurs in approximately 3% of patients (7). Ultrashort Hirschsprung disease cannot be identified at contrast-enhanced enema examination, and it is defined by the presence of ganglion cells in rectal biopsy results, as well as failure of the internal sphincter to relax at rectal manometry (anorectal achalasia). Resolution of chronic constipation was noted in all patients after internal sphincter myomectomy (8).
Narla and Hingsbergen

Figure 4. Photomicrograph of a specimen from the hepatic flexure shows absence of ganglion cells in the myenteric plexus (arrows). (Hematoxylin-eosin stain; original magnification, 250.)

Figure 3. Radiograph of the abdomen obtained with the patient supine 20 hours after Figure 1 was obtained shows persistent dilatation of loops of small bowel (arrows) in the upper abdomen, with irregular contractions at the hepatic flexure (arrowheads).

Another histopathologic finding in Hirschsprung disease is increased number and size of nerve fibers within the lamina propria, muscularis mucosae, and subjacent submucosa at acetylcholinesterase staining. In one series of 168 patients with Hirschsprung disease treated during 19741992, enterocolitis occurred in 34% preoperatively and in 8% postoperatively. In 5%, it occurred pre- and postoperatively (9). With small-bowel involvement (10), overall mortality has been as high as 33%. A reduced turnover of mucins, as shown by incorporation of radioactive precursors, will give rise to a defective colonic mucous defensive barrier. The lower the turnover, the more likely a patient is to develop postoperative enterocolitis. It is therefore possible that organ culture with radioactive mucin precursors of the proximal ganglionated mucosa performed at the time of the pullthrough procedure has a predictive value in the development of postoperative enterocolitis (11). Enema is contraindicated in patients with signs of perforation on abdominal radiographs or signs of fulminant enterocolitis. Another well-documented complication of Hirschsprung disease, which occurs in 4% of patients, is perforation of the bowel (12). This most commonly involves the proximal colon (68%), the appendix (17%), or the distal small bowel (6%). This complication is most commonly associated (62%) with total aganglionosis and generally occurs by 4 months of age. At the time of perforation, the neonate may have no other symptoms relating to aganglionosis, and thus the true diagnosis may not be considered. Therefore, unexplained perforation of the colon, appendix, or small bowel is another indication for biopsy to exclude Hirschsprung disease (13).
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The child should not have any bowel preparation prior to contrast-enhanced enema examination, as it may interfere with demonstration of the transition zone. A rectal examination is also best avoided, although there is some evidence that it does not affect diagnostic accuracy. The enema examination is begun with the patient in the lateral position; a soft catheter should be taped in place; balloon inflation should not be used (7). The colon should be filled gradually to identify a transition zone, which is seen in approximately 80% of patients with Hirschsprung disease (2). Once the transition zone is delineated, the examination is stopped without filling the rest of the colon. Delayed radiographs may be helpful to evaluate evacuation of contrast material from the bowel; delayed radiographs may also demonstrate a transition zone not appreciated on the initial radiographs. Radiographic findings that can be seen at contrast-enhanced enema examination in Hirschsprung disease include a transition zone, a rectosigmoid caliber ratio less than 1, denervation hyperspasticity (narrowing) of the distal segment with a sawtooth configuration due to muscular contractions (14,15), microcolon, delayed or disordered evacuation of the contrast material from the colon, and bowel shortening. Work hypertrophy of the colon may be seen in children older than 3 months, as the proximal colon develops hypertrophy of the circular and longitudinal muscle fibers in response to the obstruction of the aganglionic segment. Meconium plugs coexist in 10%30% of cases (2,16). Frequently, a meconium plug is assumed to be the sole cause of a neonatal obstruction, and the diagnosis of concurrent Hirschsprung disease can be missed; these patients need close clinical follow-up and possibly delayed radiographs. Diverting colostomy is traditionally the initial treatment, with the site determined by means of the documentation of ganglion cells at the time of surgery. At a later date, a pullthrough procedure (Duhamel, Soave, or Swenson) is performed. Frequently now, instead of a two-step procedure, the primary pull-through procedure is performed during the newborn period. Laparoscopic pull-through procedures recently have been performed (17). The laparoscopic port releases the colonic attachments, ligates vessels, and allows caudal mobilization with removal of the aganglionic segment of the colon, which brings the normal bowel through the pelvic floor and
Total Colonic AganglionosisLong-Segment Hirschsprung Disease 393

anastomoses the bowel to the anorectal verge. Advantages of the laparoscopic approach include shorter hospital stay, fewer complications from disruption of skin integrity, and good results. Hirschsprung disease is a common and treatable cause of neonatal low-bowel obstruction; contrast-enhanced enema examination is the initial examination of choice. In addition to the typical presentations, persistent small-bowel dilatation or unexplained perforation of the distal small bowel, colon, or appendix warrants performing biopsy to exclude Hirschsprung disease.
References 1. Berdon WE, Baker DH, Santulli TV, Amoury RA, Blanc WA. Microcolon in newborn infants with intestinal obstruction: its correlation with the level and time of onset of obstruction. Radiology 1968; 90:878885. 2. Miller KE. The child with constipation. In: Hilton SW, Edwards DK, eds. Practical pediatric radiology. 2nd ed. Philadelphia, Pa: Saunders, 1994; 215238. 3. Berdon WE, Baker DH. Roentgenographic diagnosis of Hirschsprungs disease in infancy. AJR Am J Roentgenol 1965; 93:432446. 4. Roshkow JE, Haller JO, Berdon WE, Sane SM. Hirschsprungs disease, Ondines curse, and neuroblastoma: manifestations of neurocristopathy. Pediatr Radiol 1988; 19:4549. 5. Okamoto E, Takasi U. Embryogenesis of intramural ganglia of the gut and its relationship to Hirschsprungs disease. J Pediatr Surg 1967; 2:437443. 6. Berdon WE, Koontz P, Baker DH. The diagnosis of colonic and terminal ileal aganglionosis. AJR Am J Roentgenol 1964; 91:680 689.

7. 8. 9.

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17.

Stringer DA. Large bowel: functional disorders. In: Pediatric gastrointestinal imaging. Philadelphia, Pa: Decker, 1989; 363469. Neilson IR, Yazbeck S. Ultrashort Hirschsprungs disease: myth or reality. J Pediatr Surg 1990; 25:11351138. Elhalby EA, Coran AL, Blane CE, Hinschl RB, Teitelbaum DH. Enterocolitis associated with Hirschsprungs disease: a clinical histopathological correlative study. J Pediatr Surg 1995; 30:1023 1027. Suita S, Taguchi T, Kamimuna T, Yanai K. Total colonic aganglionosis with or without small bowel involvement: a changing profile. J Pediatr Surg 1997; 32:15371541. Aslam A, Spicer RD, Corfield AP. Turnover of radioactive mucin precursors in the colon of patients with Hirschsprungs disease correlates with the development of enterocolitis. J Pediatr Surg 1998; 33:103105. Newman B, Nussbaum A, Kirkpatrick JA Jr. Bowel perforation in Hirschsprungs disease. AJR Am J Roentgenol 1987; 148:1195 1197. Newman B, Nussbaum A, Kirkpatrick JA, Colodny A. Appendiceal perforation, pneumoperitoneum, and Hirschsprungs disease. J Pediatr Surg 1988; 23:854856. Hope JW, Bonns PF, Berg PK. Roentgenologic manifestations of Hirschsprungs disease in infancy. AJR Am J Roentgenol 1965; 96:217229. Rosenfield NS, Albow RC, Markowitz RI, et al. Hirschsprung disease: accuracy of the barium enema examination. Radiology 1984; 150:393400. Pochaczevsky R, Leonidas JC. Meconium plug syndrome, roentgenographic evaluation and differentiation from Hirschsprungs disease and other pathological states. AJR Am J Roentgenol 1974; 120:342352. Georgeson KE, Fuenfer MM, Hardin WD. Primary laparoscopic pull-through for Hirschsprungs disease in infants and children. J Pediatr Surg 1995; 30:10171021.

Our congratulations to the 46 individuals who submitted the most likely diagnosis (total colonic aganglionosislong-segment Hirschsprung disease) for Diagnosis Please, Case 22. Credit was given for Hirschsprung disease only if long-segment or total aganglionosis was mentioned. The names and locations of the individuals, as submitted, are as follows: Hisashi Abe, Osaka-city, Japan Roger Antonelli, MD, Dayton, Ohio Dean Baird, MD, Arlington, Va Ken Baliga, Rockford, Ill Richard A. Barth, MD, Stanford, Calif Doug Brown, MD, Durham, NC Michael P. Buetow, MD, Okemos, Mich Nancy Chandler, MD, Greenville, Miss John F. Cockburn, FRCR, Norfolk, UK Martin Cohen, MD, Westlake Village, Calif Julio Dabdab, Santa Marcelina SP, Brazil M. G. de Baets, MD, Lugano, Switzerland Keith D. Epperson, MD, Milwaukee, Wis Laura Z. Fenton, MD, Denver, Colo Teresa Adriana Garcia, MD, Buenos Aires, Argentina Douglas Gardner, MD, Windsor, Ontario, Canada Dietrich Gerhardt, Waterloo, Iowa Katsumi Hayakawa, MD, Kyoto, Japan Maureen Heldmann, MD, Shreveport, La Bret Henricks, Lakeland, Fla Douglas S. Katz, MD, Mineola, NY Eung-Yeop Kim, MD, Seoul, Korea Stephanos Lachanis, MD, Athens Greece Jong Beum Lee, MD, Seoul, Korea Joseph H. Lock, Jr, Mankato, Minn Douglas Moote, London, Ontario, Canada Michael Neuman, Wichita, Kan Julio Neves Junior, MD, Sao Paulo, Brazil James A. Newcomb, MD, Allentown, Pa Dr. Roberto E. Perez Gautrin, Sonora, Mexico Amir B. Perez Lanz, MD, Tabasco, Mexico Rubem Pochaczevsky, MD, Bronx, NY Anita Price, MD, Mineola, NY M. R. Ramakrishnan, MD, Big Stone Gap, Va Arturo Ramos-Pablos, Son., Mexico Cesar Rodrigo Trippia, Curitiba, Brazil Mourad Said, MD, Monastir, Tunisia Hanna Schulman, MD, Beer-Sheva, Israel Matt Shapiro, MD, Lowell, Mass Paolo Siotto, MD, Cagliari, Italy Juan Carlos Spina, MD, Buenos Aires, Argentina Douglas L. Teich, MD, Brookline, Mass Shendee Teng, MD, Woodbridge, NJ D. Dean Thornton, MD, Kirkwood, Mo Binh C. Truong, Austin, Tex Christopher Vittore, MD, Rockford, Ill

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