Meconium ileus due to extensive intestinal aganglionosis

Meconium Ileus due to Extensive Intestinal Aganglionosis Stringer,

By M.D.

R.J. Brereton, D.P. Drake, E.M. Kiely, M. Agrawal, P.D.E. Mouriquand, London, England; Cambridge, England; and Oxford, England

l Seven full-term infants with agenglionosis extending into the small bowel presented with clinical, radiological, and operative features of maconium ileus. Misdiagnosis resulted in inappropriate treatment. The correct diagnosis was eventually established by rectal suction biopsy, mostly after either recurrent intestinal obstruction or stoma1 dysfunction, and after cyetfc fibrosis had been excluded. For two patients, the results of rectal suction biopsies were initially misleading. Two infants died. Extensive intestinal aganglionosis should be considered a rare possibility in all infants with meconium ileus. In such cases, histological examination of the appendix may avoid this potential pitfall. Copyright Q 1994 by W. B. Saunders Company INDEX WORDS: Colonic aganglionosis, disease; meconium ileus.

total; Hirschsprung’s

T

OTAL COLONIC aganglionosis (TCA) accounts for approximately 8% of patients with Hirschsprung’s disease, 1-3but extensive small bowel involvement is much rarer. Whereas it usually causes signs of neonatal intestinal obstruction, it should be considered in the differential diagnosis of neonatal appendicitis, necrotizing enterocolitis, or intestinal perforation.Q8 More rarely, TCA may be associated with ileocolic atresia2,4-6 or small bowel v01vulus.~ Misdiagnosis as meconium ileus secondary to presumed cystic fibrosis has been mentioned in previous reports,1,3,5,7,9-12but this potential pitfall has been poorly documented. MATERIALS

AND METHODS

During the last 10 years, seven patients presenting with meconium ileus resulting from extensive intestinal aganglionosis were identified in four neonatal surgical units. The clinical, radiological, and pathological details were examihed. RESULTS

All patients presented within 3 days of birth, having passed no meconium and with signs of intestinal obstruction (Table 1). On plain abdominal radiographs there was evidence of bowel obstruction and Neuhauser’s sign, a mottled appearance resulting from small air bubbles within luminal meconium,i3 and three infants were judged to have complicated meconium ileus because of the presence of speckled calcification (Fig 1). Five patients had a contrast enema, but subsequent treatment with Gastrografin (Schering Health Care Ltd, Sussex, England) was avoided because of failure to opacify the proximal dilated bowel. Contrast studies did not show the classical radiological features of TCA,l4 and no atJournalofpediarric

Surgery, Vol 29, No 4 (April),1994: pp 501-503

and P.K.H. Tam

tempt was made to demonstrate prolonged retention of contrast material. During surgery it was noted that all patients had features typical of meconium ileus, ie, intestinal obstruction proximal to a microcolon and a collapsed terminal ileum containing inspissated pellets of meconium. In two patients there was an associated ileal volvulus and another had multiple ileal perforations. In only one case (patient 2) was the surgeon alerted intraoperatively to the possibility of Hirschsprung’s disease because the meconium appeared less tenacious than usual; TCA was confirmed by a postoperative rectal suction biopsy together with histological examination of the appendicectomy specimen. The diagnosis of TCA was delayed beyond the neonatal period in four patients. Results of postoperative rectal suction biopsies were misleading for two patients; in one of them, an aganglionic appendix was initially reported as histologically normal. Most patients failed to thrive after their first laparotomy and had evidence of stoma1 dysfunction or intestinal obstruction, which prompted further investigation by rectal biopsy. Markedly dilated but aganglionic small bowel was discovered in five patients. Two patients died, including one with complete intestinal aganglionosis (Bodfan Carter Ward syndrome)*5; two patients with proxima1 jejunostomies are dependent on long-term parenteral nutrition. The remaining three survivors were successfully treated by the Martin modification of the Duhamel procedure, I6 but one of them has had recurrent problems with intestinal obstruction and enterocolitis and recently had her ileostomy reestablished. DISCUSSION

The successful management of extensive intestinal aganglionosis depends on early recognition, prompt decompression of the obstructed bowel by formation

From the Department of Paediatric Surgery, The Hospitals for Sick Children and Guy’s Hospital, London, England; the Department of Paediam? Surgev, Addenbrooke S Hospital, Cambridge, England; and the Nufield Deparunent of Surgery, John Radcliffe Hospital, Oxford, England. Date accepted: May 24, 1993. Address reprint requests to M.D. Stringer MD, Department of Paediam’c Surgery, Clarendon Wing, The General Infirmary at Leeds, Belmont Grove, Leeds LS2 9NS, England. Copvright 0 1994 by KB. Saunders Company 0022-346?3/9412904-0007$03.00/0 501

502

STRINGER ET AL

Table 1. Clinical Details Gestation and Patient

Birth Weight

No./Sex

(kg)

l/M

Full-term, 2.9

Radiographic Presentation Neonatal

asphyxia,

ious vomiting

Operative

Findings bil-

d3

Findings

and Procedure

Distal bowel obstruction, speckled calcification

Meconium RIF

ileus and dilated

proximal jejunum:

mid small

bowel loop stoma

Clinical Outcome Poorly functioning

stoma; IAT and

sweat test normal; RSB equivocal result. Deteriorating

neurological

state; ventilator dependent. 5 wk. Autopsy:

complete

Died et

intestinal

aganglionosis 2/M

Full-term, 4.0

Bilious vomiting dl, distended abdomen

+

palpable bowel loops

Distal bowel obstruction;

Meconium

ileus with micro-

Postoperative

RSB = Hirschsprung’s.

barium enema: microcolon

colon and dilated proximal

Reoperation

and biopsies: dilated

end no reflux into dilated

ileum: enterotomy

aganglionic

proximal ileum + mid-

bowel

lavage; appendicectomy

and

small bowel transitional tomy, colectomy, tula. Duhamel

zone. Ileos-

and mucous fis-

(Martin) at 7 mo. Now

well at 6 yr, but has frequent stools. 3/M

Full-term,

3.7

Bilious vomiting meconium

and no

by d2. dis-

tended abdomen palpable

+

bowel loops

Meconium

Distal bowel obstruction;

ileus with micro-

barium enema: microcolon

colon and proximal

and no reflur into dilated

vulus: derotation,

bowel

otomy, and lavage

ileal volenter-

Postoperative

RSB = Hirschsprung’s.

Reoperatio”

and biopsies: transi-

tional zone in midileum. colectomy Duhamel

Subtotal

end proximal stoma. (Martin) procedure

et 6

mo. Now 3 yr and well. 4iF

Full-term,

3.6

Bilious vomiting abdominal

and

distension

on d2

Distal bowel obstruction;

con-

Meconium

ileus end multiple

Resected ileum erroneously

ileal perforations

with meco-

ganglionic.

no reflux proximal to

nium peritonitis;

ileal resec-

Persistent obstruction

midtransverse

tion and anastomosis

trast enema: microcolon

with

colon

reported

CF gene probe negative.

ileostomy.

needing loop

At 1 mo, stoma closure

end intestinal biopsies = hyperganglionosis of proximal

20 cm jejunum

and distal aganglionosis. pneumonia 5/M

Full-term, 4.5

Bilious vomiting

dl, vague

mess in RIF

Proximal bowel obstruction speckled calcification

Meconium

+

RIF

ileus with jejunoileal

Died of

at 3 mo.

Persistent obstruction

unresponsive

obstruction

and microcolon;

Gastrografin

enterotomy

and lavage

test normal. RSB = Hirschsprung’s. Laparotomy

to

enemas. IRT and sweat and biopsies: agangli-

onic beyond proximal 20 cm jejunum. Jelunostomy

and distal

bowel resection. Later, Elianchl bowel lengthening.

Remains on

TPN. 6/F

Full-term, 4.5

Polyhydramnios;

father

Proximal

bowel obstruction

had Hirschsprung’s:

faint calcification

bilious vomiting dl

enema: microcolon

Meconium

+

RIF: barium with no

ileus: jejunal enter-

otomy and la-age;

ileostomy

and mucous fistula

reflux into dilated bowel

IRT and gene probe negative for CF. At 6 wk. resection grossly dilated proximal ileum, and stoma closed RSB = Hirschsprung’s.

At 3rd lapa-

rotomy, aganglionosis

confirmed

beyond proximal 25 cm jejunum. Jejunostomy

and TPN. Later, agan-

glionic distal bowel resected. 7/F

Full-term,

2.7

Abdominal

distension.

Distal bowel obstruction;

Gas-

Meconium

ileus and distal ileal

Histology

= meconium

ileus + gangli-

bilious vomiting and

trografin enema: microcolon

volvuIus; ileal resection and

onic ileum. IRT and gene probe

no meconium

with no reflux into dilated

ileocolic lavage with primary

negative for CF. Recurrent bowel

bowel

anastomosis;

obstruction

on d2

tomy

appendicec-

and FlT. Laparotomy

at

3 mo: ileocecal resection and stoma. RSB reported es ‘normal.’ Reobstructed

after stoma closed at

8 mo. Review of histology Duhamel

= TCA.

(Martin) procedure

mo. Later, loop ileostomy obstruction,

and colectomy

at 18

for further for

severe enterocolitis. Abbreviations:

IRT. immunoreactive

trypsin: RSB, rectal suction biopsy; TPN, total parenteral

of a ganglionic stoma, detailed attention to fluid and nutritional balance, and appropriate definitive surgery. Diagnostic delay is common and a major cause of morbidity and mortality.3~5,7~11 Misdiagnosis as meconium ileus secondary to presumed cystic fibrosis contributes to this problem, as evidenced by inappropriate surgery in four of our patients. In selected reports of TCA, 3% to 25% of infants presented with meconium ileusiJJ~7~9Ji; five of the nine reported patients died, largely because of diagnostic delay and inappropriate treatment. A meconium ileus presenta-

nutrition;

RIF, right iliac fossa; CF. cystic fibrosis; FiT, failure to thrive.

tion is more common when there is extensive small bowel aganglionosis, which was the case in six of our patients. How often does meconium ileus result from Hirschsprung’s disease ? Our data suggest that this combination is present in no more than 5% of patients with meconium ileus. During the initial laparotomy, the chance of misdiagnosis can be reduced by removing the appendix for histopathology, to determine whether it is aganglionic.5 Anderson and Chandra challenged the pathologist’s dictum that the appendix is unreliable in

MECONIUM

ILEUS AND INTESTINAL

503

AGANGLIONOSIS

biopsy. A rectal biopsy should be performed in any infant with meconium ileus for whom investigations for cystic fibrosis are inconclusive. ACKNOWLEDGMENT The authors thank Dr Laurence Berman for the radiological information on patient 6. REFERENCES

Fig 1. Plain abdominal radiograph (patient 5) showing intestinal obstruction and speckled calcification in the right lower quadrant.

the diagnosis of TCA and convincingly demonstrated the absence of ganglion cells in all of their patients with total colonic involvement.” Any resected bowel or biopsies from enterotomy or stoma1 sites should be similarly examined. Nonetheless, histological difficulties may add to the clinical and radiological problems of diagnosis. In TCA, the abnormal proliferation of nerve fibers characteristic of aganglionic bowel in Hirschsprung’s disease may not be apparent through acetylcholinesterase staining of rectal suction biopsies,11J2J8 as was the case in two of our patients, neither does it occur proximal to the splenic flexure. After surgical treatment of meconium ileus, signs of recurrent intestinal obstruction or stoma1 dysfunction should indicate the possibility of extensive aganglionosis and should prompt investigation by rectal

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