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Total colonic aganglionosis initially diagnosed in an adolescent
GASTROENTEROLOGY
CASE
1984;87:1364-6
REPORTS
Total Colonic Aganglionosis Initially Diagnosed in an Adolescent MARC HOMA
P. LEFEBVRE, LUCIAN SAFAII, and RICHARD
L. LEAPE, J. GRAND
DOUGLAS
A. POHL,
Departments of Pathology, Pediatric Surgery, and Pediatrics (Division of Gastroenterology), University School of Medicine and New England Medical Center, Boston, Massachusetts
A la-yr-old girl was admitted for evaluation of a 5wk history of increasing abdominal pain. She also reported a history of constipation since birth requiring chronic laxative use. Occasional bouts of abdominal distention and vomiting resulted in dehydration necessitating hospitalization. Two previous laparotomies had identified an apparent obstructing angulation of the ascending colon. Rectal biopsy specimens obtained on this admission failed to reveal any ganglion cells. Sequential biopsy specimens of the entire colon obtained at laparotomy also failed to reveal any ganglion cells. Ganglion cells were found in the distal ileum. A total colectomy was performed. Three previously reported cases of total colonic aganglionosis initially diagnosed in older patients are reviewed. Similarities included nonspecific radiographic findings, a history of constipation since birth, and initial laparotomies revealing spurious causes of bowel obstruction. Total
colonic
aganglionosis
(TCA) accounts for 5%disease (1). Invariably these cases are diagnosed and treated within the first 3 mo of life. Death has been considered inevitable if surgical intervention is not instituted before this age (2,3). Only 3 cases of long-term survival with TCA have been previously reported: 2 cases first diagnosed in adolescence (4,~) and 1 case in adulthood (6). This report describes a fourth case of TCA with long-term survival initially diagnosed in an adolescent.
15% of all cases of Hirschsprung’s
Received February 6, 1984. Accepted June 25, 1984. Address requests for reprints to: Marc P. Lefebvre, M.D., Department of Pathology, New England Medical Center, 171 Harrison Avenue, Boston, Massachusetts 02111. The authors thank Dr. Julie Stiles for reviewing the radiographs, Mrs. Christine Hicks and Mrs. Darlene Casey for assistance in preparing the manuscript, Mr. Steve Halpern for photographic aid, and Dr. Eugene Foster for his helpful comments. 0 1984 by the American Gastroenterological Association 0016-5085/84/$3.00
Tufts
Case Report A 12-yr-old white girl was transferred to Tufts-New England Medical Center for evaluation of a 5-wk history of abdominal pain. The patient was born full term weighing 8 lb and 12 oz. Pregnancy was uncomplicated except for daily use of Bendectin (Merrell-National Laboratories, Cincinnati, Ohio) by her mother. Gastrointestinal problems began at birth with a s-day delay in passage of meconium and the production of small-caliber stool. At 4 wk of age she had an episode of abdominal distention associated with bloody diarrhea. A barium enema demonstrated an apparent intussusception at the level of the ileocecal valve. Laparotomy revealed a Meckel’s diverticulum which was resected; the ascending colon was described as “sharply angulated” and congenital bands were lysed to free up the ascending colon. No intussusception was found. No biopsy of the colon was performed. Postoperatively, during infancy, and throughout early childhood, bowel movements were dependent on the daily use of laxatives and glycerine suppositories. In addition to chronic constipation the patient experienced numerous episodes of abdominal distention and vomiting requiring enemas for relief. These episodes were more frequent during the sedentary winter months and occasionally resulted in dehydration requiring hospitalization. Throughout this time the patient’s development was normal. She walked at 12 mo and was toilet trained at 2 yr. No periods of growth failure were noted. She enjoyed school and was a good student. At age 9 the patient had an episode of abdominal distention and vomiting not relieved by enemas. A barium enema showed what was thought to be a stricture of the ascending colon. At laparotomy there was evidence of chronic obstruction of the terminal ileum and proximal colon, which was again thought to be due to angulation of the colon. A coloplasty of the angulated area was performed. No biopsy specimen of the colon was obtained. This procedure resulted in only mild improvement. Five weeks before admission, her abdominal symptoms
Abbreviations nosis.
used
in this paper:
TCA, total colonic
aganglio-
December 1984
became more intense. Solid foods especially produced severe abdominal pain. She was admitted to another hospital where radiographic examination revealed the colon to be moderately filled with stool. No other significant abnormalities were noted [Figure 1). After a rectal biopsy specimen demonstrated the absence of ganglion cells, she was transferred to our institution for further evaluation of possible Hirschsprung’s disease. On admission in December 1983, the patient weighed 49.4 kg and measured 154.5 cm in height. Blood pressure was 120/66, pulse 78, and respirations 12. Physical examination was normal except for abdominal scars. Her medications included two tablespoons of milk of magnesia and one teaspoon of mineral oil per day. Neurologic inventory was negative. No one in her family, including two siblings, had any gastrointestinal complaints. A flat plate of the abdomen revealed areas of small bowel distention in the right lower quadrant suggesting a localized inflammatory process. There was no fecal impaction. Laboratory tests were within normal limits. A lactose breath test was negative. Repeat rectal biopsy was negative for ganglion cells. Because of the long history of adequate control of her constipation, short segment Hirschsprung’s disease was suspected. At operation, the sigmoid colon appeared dilated and thickened, although frozen section biopsy specimen revealed no ganglion cells. Numerous biopsy specimens, taken the length of the colon, also revealed no ganglion cells. Ganglion cells, however, were present in the termi-
TOTAL COLONIC
I. Radiograph of barium enema showing moderate amount of stool in the distal colon. No other abnormalities are present.
1365
nal ileum. Total colectomy was performed with ileoanal endorectal pull-through and ileostomy. Pathologic examination identified a colectomy specimen measuring 134 cm in length with an attached 12.5-cm segment of distal ileum. Full-thickness sections of the entire colon were taken at 2-cm intervals. Ganglion cells were found in the ileum and in the cecum only to a point 2 cm distal to the ileocecal valve. After surgery the ileostomy functioned properly: she was discharged on the seventh postoperative day. The patient has had no symptoms since pull-through and ileostomy. Closure of the ileostomy is anticipated within several months.
Discussion Hirschsprung’s disease commonly involves a short segment of the rectum, producing constriction of the affected segment with proximal colonic dilation. On plain radiographic examination of the abdomen this latter phenomenon is appreciated as megacolon. Short segment disease is usually diagnosed in infancy, although numerous cases have not been (7). diagnosed until adulthood Total colonic aganglionosis, including cases with short ileal segment involvement, nearly always becomes clinically apparent in the first few weeks of life. Paradoxically the severity of the symptoms does not directly correlate with the length of the aganglionic segment (8). Plain abdominal roentgenograms usually show air-fluid levels in the distal small bowel, but contrast studies in many of these cases are usually nonspecific (9). Surgical therapy for TCA in the neonatal period
has been associated
Figure
AGANGLIONOSIS
with a mortality
rate of up to
76% (lo), although a recent analysis of 16 cases reported a mortality of 25% (11). Enterocolitis with concomitant sepsis and fluid and electrolyte losses is a major complication of TCA. Attacks of watery diarrhea and fever may even recur in patients who have had definitive surgical therapy (11). This case is unusual in that the patient was 12 yr old at the time of the initial diagnosis. Only three older survivors with TCA have been reported (4-6). The similarities between all four clinical histories are striking. All 4 patients had constipation from birth requiring daily laxatives and frequent enemas to produce bowel movements. Two of the three patients in the previously reported cases had undergone initial laparotomies for signs and symptoms suggestive of intestinal obstruction. Fecal impaction in 1 patient and a hypertrophied ileocecal valve in the other patient were deemed to be the obstructing lesions in these cases. In retrospect it is easy to appreciate that these plausible etiologies were merely secondary manifestations of the underlying autonomic disorder.
GASTROENTEROLOGY Vol. 87,
1366 LEFEBVRE ET AL.
Similarly, the patient in this report was considered cured at 1 mo of age when an unusual angulation of the ascending colon was discovered at laparotomy. To reduce this obstruction, congenital bands were lysed and the ascending colon was freed up. This kinking might have been related to a shortening of the bowel sometimes seen in TCA (9). Berdon, in the same report, also noted that barium studies in this disorder may be misinterpreted as an ileal intussusception. An identical error was made in our patient at the time of her first laparotomy. It is not widely appreciated that TCA accounts for up to 15% of all cases of Hirschsprung’s disease presenting in the neonatal period. As shown in this report, TCA should also be suspected in cases of intestinal obstruction in older patients, particularly when there is a history of constipation since birth and a previous laparotomy not resulting in complete amelioration of the abdominal symptoms. Numerous factors contribute to a delayed diagnosis both in the neonatal group and in the older population: radiographic findings are frequently nonspecific; the clinical presentation can be that of mild obstruction with fluctuating abdominal distention; and at laparotomy the bowel might appear relatively normal or provide some spurious cause of obstruction. Once the presence of aganglionosis has been ascertained, the level of denervation can be determined by sequential frozen-section biopsy specimens of the colon. These specimens must include Auerbach’s plexus which is found between the two layers of the muscularis externa. Frozen-section interpretation of biopsy specimens can be difficult. A particular problem is distinguishing between immature ganglion cells and supporting satellite cells. To aid in this differential diagnosis, a rapid (3-6 min) nonspecific cholinesterase (12) or lactate dehydrogenase (13) stain may be used. The most provocative question raised by these 4 cases of TCA is what accounts for their survival. Is it solely the result of the scrupulous use of laxatives and enemas? (From this perspective it is interesting to note that the mother of the child in this report was a pediatric nurse and was able to provide professional bowel care.) Or do these 4 cases represent a forme
No.6
fruste of an incompletely understood disease? Tsuto et al. (14) have recently demonstrated the absence of vasoactive intestinal polypeptide, a modulator of intestinal motility, in the aganglionic segment of rectosigmoid Hirschsprung’s disease. They suggest that this lack of vasoactive intestinal polypeptide might contribute to the colonic constriction typically seen in aganglionosis. Perhaps these 4 cases of TCA had intermediate amounts of vasoactive intestinal polypeptide, thus allowing for some degree of smooth muscle relaxation. We will be soon examining this case for the presence of vasoactive intestinal polypeptide as well as other intestinal polypeptides.
References 1.
Louw JH. Total colonic aganglionosis. Can J Surg 1978; 21:397-409. disease. 2. Bodian M, Carter CO, Ward BCH. Hirschsprung’s Lancet 1951;i:302-9. 3. Hoffert P, Zuber S, Salzman A, Spinelli V. Aganglionosis of the entire colon. Surgery 1959;46:810-8. 4. Gerald B. Aganglionosis of the colon and terminal ileumlong term survival. Am J Roentgen01 1965;95:230-4. 5. Stone WD, Thomas BM, Hendrix R, Schuster MM. Aganglionosis of the entire colon in an adolescent. Gastroenterology 1965;48:636-41. 6. Myers MB, Bradburn D, Vela R, Payzant Z, Karlin S. Total aganglionic colon in an adult-first reported case. Ann Surg 1966;163:97-102. 7. Reifferscheid P, Flach A. Congenital megacolon in adults. In: Holschneider AM, ed. Hirschsprung’s disease. Stuttgart: Hippokrates Verlag, 1982:115-24. disease. Chicago: Year Book 8. Ehrenpreis T. Hirschsprung’s Medical, 1970:57-8. 9. Berdon WE, Koontz P, Baker DH. The diagnosis of colonic and terminal ileal aganglionosis. Am J Roentgen01 1964; 91:680-g. 10. Walker AW, Kempson RL. Ternberg JL. Aganglionosis of the small intestine. Surgery 1966;60:449-57. 11. Caresky JM, Weber TR, Grosfeld JL. Total colonic aganglionosis-analysis of 16 cases. Am J Surg 1982;143:160-7. 12. Davis BJ. Ornstein L. High resolution enzyme localization with a new diazo reagent hexasonium pararosaniline. J Histothem Cytochem 1959;7:297-8. 13. Meier-Ruge W. Morphological diagnosis of Hirschsprung’s disease. In: Holschneider AM, ed. Hirschsprung’s disease. Stuttgart: Hippokrates Verlag. 1982:62-71. 14. Tsuto T, Okamura H, Fukui K, et al. An immunohistochemical investigation of vasoactive intestinal polypeptide in the colon of patients with Hirschsprung’s disease. Neurosci Lett 1982:34:57-62.
CASE
1984;87:1364-6
REPORTS
Total Colonic Aganglionosis Initially Diagnosed in an Adolescent MARC HOMA
P. LEFEBVRE, LUCIAN SAFAII, and RICHARD
L. LEAPE, J. GRAND
DOUGLAS
A. POHL,
Departments of Pathology, Pediatric Surgery, and Pediatrics (Division of Gastroenterology), University School of Medicine and New England Medical Center, Boston, Massachusetts
A la-yr-old girl was admitted for evaluation of a 5wk history of increasing abdominal pain. She also reported a history of constipation since birth requiring chronic laxative use. Occasional bouts of abdominal distention and vomiting resulted in dehydration necessitating hospitalization. Two previous laparotomies had identified an apparent obstructing angulation of the ascending colon. Rectal biopsy specimens obtained on this admission failed to reveal any ganglion cells. Sequential biopsy specimens of the entire colon obtained at laparotomy also failed to reveal any ganglion cells. Ganglion cells were found in the distal ileum. A total colectomy was performed. Three previously reported cases of total colonic aganglionosis initially diagnosed in older patients are reviewed. Similarities included nonspecific radiographic findings, a history of constipation since birth, and initial laparotomies revealing spurious causes of bowel obstruction. Total
colonic
aganglionosis
(TCA) accounts for 5%disease (1). Invariably these cases are diagnosed and treated within the first 3 mo of life. Death has been considered inevitable if surgical intervention is not instituted before this age (2,3). Only 3 cases of long-term survival with TCA have been previously reported: 2 cases first diagnosed in adolescence (4,~) and 1 case in adulthood (6). This report describes a fourth case of TCA with long-term survival initially diagnosed in an adolescent.
15% of all cases of Hirschsprung’s
Received February 6, 1984. Accepted June 25, 1984. Address requests for reprints to: Marc P. Lefebvre, M.D., Department of Pathology, New England Medical Center, 171 Harrison Avenue, Boston, Massachusetts 02111. The authors thank Dr. Julie Stiles for reviewing the radiographs, Mrs. Christine Hicks and Mrs. Darlene Casey for assistance in preparing the manuscript, Mr. Steve Halpern for photographic aid, and Dr. Eugene Foster for his helpful comments. 0 1984 by the American Gastroenterological Association 0016-5085/84/$3.00
Tufts
Case Report A 12-yr-old white girl was transferred to Tufts-New England Medical Center for evaluation of a 5-wk history of abdominal pain. The patient was born full term weighing 8 lb and 12 oz. Pregnancy was uncomplicated except for daily use of Bendectin (Merrell-National Laboratories, Cincinnati, Ohio) by her mother. Gastrointestinal problems began at birth with a s-day delay in passage of meconium and the production of small-caliber stool. At 4 wk of age she had an episode of abdominal distention associated with bloody diarrhea. A barium enema demonstrated an apparent intussusception at the level of the ileocecal valve. Laparotomy revealed a Meckel’s diverticulum which was resected; the ascending colon was described as “sharply angulated” and congenital bands were lysed to free up the ascending colon. No intussusception was found. No biopsy of the colon was performed. Postoperatively, during infancy, and throughout early childhood, bowel movements were dependent on the daily use of laxatives and glycerine suppositories. In addition to chronic constipation the patient experienced numerous episodes of abdominal distention and vomiting requiring enemas for relief. These episodes were more frequent during the sedentary winter months and occasionally resulted in dehydration requiring hospitalization. Throughout this time the patient’s development was normal. She walked at 12 mo and was toilet trained at 2 yr. No periods of growth failure were noted. She enjoyed school and was a good student. At age 9 the patient had an episode of abdominal distention and vomiting not relieved by enemas. A barium enema showed what was thought to be a stricture of the ascending colon. At laparotomy there was evidence of chronic obstruction of the terminal ileum and proximal colon, which was again thought to be due to angulation of the colon. A coloplasty of the angulated area was performed. No biopsy specimen of the colon was obtained. This procedure resulted in only mild improvement. Five weeks before admission, her abdominal symptoms
Abbreviations nosis.
used
in this paper:
TCA, total colonic
aganglio-
December 1984
became more intense. Solid foods especially produced severe abdominal pain. She was admitted to another hospital where radiographic examination revealed the colon to be moderately filled with stool. No other significant abnormalities were noted [Figure 1). After a rectal biopsy specimen demonstrated the absence of ganglion cells, she was transferred to our institution for further evaluation of possible Hirschsprung’s disease. On admission in December 1983, the patient weighed 49.4 kg and measured 154.5 cm in height. Blood pressure was 120/66, pulse 78, and respirations 12. Physical examination was normal except for abdominal scars. Her medications included two tablespoons of milk of magnesia and one teaspoon of mineral oil per day. Neurologic inventory was negative. No one in her family, including two siblings, had any gastrointestinal complaints. A flat plate of the abdomen revealed areas of small bowel distention in the right lower quadrant suggesting a localized inflammatory process. There was no fecal impaction. Laboratory tests were within normal limits. A lactose breath test was negative. Repeat rectal biopsy was negative for ganglion cells. Because of the long history of adequate control of her constipation, short segment Hirschsprung’s disease was suspected. At operation, the sigmoid colon appeared dilated and thickened, although frozen section biopsy specimen revealed no ganglion cells. Numerous biopsy specimens, taken the length of the colon, also revealed no ganglion cells. Ganglion cells, however, were present in the termi-
TOTAL COLONIC
I. Radiograph of barium enema showing moderate amount of stool in the distal colon. No other abnormalities are present.
1365
nal ileum. Total colectomy was performed with ileoanal endorectal pull-through and ileostomy. Pathologic examination identified a colectomy specimen measuring 134 cm in length with an attached 12.5-cm segment of distal ileum. Full-thickness sections of the entire colon were taken at 2-cm intervals. Ganglion cells were found in the ileum and in the cecum only to a point 2 cm distal to the ileocecal valve. After surgery the ileostomy functioned properly: she was discharged on the seventh postoperative day. The patient has had no symptoms since pull-through and ileostomy. Closure of the ileostomy is anticipated within several months.
Discussion Hirschsprung’s disease commonly involves a short segment of the rectum, producing constriction of the affected segment with proximal colonic dilation. On plain radiographic examination of the abdomen this latter phenomenon is appreciated as megacolon. Short segment disease is usually diagnosed in infancy, although numerous cases have not been (7). diagnosed until adulthood Total colonic aganglionosis, including cases with short ileal segment involvement, nearly always becomes clinically apparent in the first few weeks of life. Paradoxically the severity of the symptoms does not directly correlate with the length of the aganglionic segment (8). Plain abdominal roentgenograms usually show air-fluid levels in the distal small bowel, but contrast studies in many of these cases are usually nonspecific (9). Surgical therapy for TCA in the neonatal period
has been associated
Figure
AGANGLIONOSIS
with a mortality
rate of up to
76% (lo), although a recent analysis of 16 cases reported a mortality of 25% (11). Enterocolitis with concomitant sepsis and fluid and electrolyte losses is a major complication of TCA. Attacks of watery diarrhea and fever may even recur in patients who have had definitive surgical therapy (11). This case is unusual in that the patient was 12 yr old at the time of the initial diagnosis. Only three older survivors with TCA have been reported (4-6). The similarities between all four clinical histories are striking. All 4 patients had constipation from birth requiring daily laxatives and frequent enemas to produce bowel movements. Two of the three patients in the previously reported cases had undergone initial laparotomies for signs and symptoms suggestive of intestinal obstruction. Fecal impaction in 1 patient and a hypertrophied ileocecal valve in the other patient were deemed to be the obstructing lesions in these cases. In retrospect it is easy to appreciate that these plausible etiologies were merely secondary manifestations of the underlying autonomic disorder.
GASTROENTEROLOGY Vol. 87,
1366 LEFEBVRE ET AL.
Similarly, the patient in this report was considered cured at 1 mo of age when an unusual angulation of the ascending colon was discovered at laparotomy. To reduce this obstruction, congenital bands were lysed and the ascending colon was freed up. This kinking might have been related to a shortening of the bowel sometimes seen in TCA (9). Berdon, in the same report, also noted that barium studies in this disorder may be misinterpreted as an ileal intussusception. An identical error was made in our patient at the time of her first laparotomy. It is not widely appreciated that TCA accounts for up to 15% of all cases of Hirschsprung’s disease presenting in the neonatal period. As shown in this report, TCA should also be suspected in cases of intestinal obstruction in older patients, particularly when there is a history of constipation since birth and a previous laparotomy not resulting in complete amelioration of the abdominal symptoms. Numerous factors contribute to a delayed diagnosis both in the neonatal group and in the older population: radiographic findings are frequently nonspecific; the clinical presentation can be that of mild obstruction with fluctuating abdominal distention; and at laparotomy the bowel might appear relatively normal or provide some spurious cause of obstruction. Once the presence of aganglionosis has been ascertained, the level of denervation can be determined by sequential frozen-section biopsy specimens of the colon. These specimens must include Auerbach’s plexus which is found between the two layers of the muscularis externa. Frozen-section interpretation of biopsy specimens can be difficult. A particular problem is distinguishing between immature ganglion cells and supporting satellite cells. To aid in this differential diagnosis, a rapid (3-6 min) nonspecific cholinesterase (12) or lactate dehydrogenase (13) stain may be used. The most provocative question raised by these 4 cases of TCA is what accounts for their survival. Is it solely the result of the scrupulous use of laxatives and enemas? (From this perspective it is interesting to note that the mother of the child in this report was a pediatric nurse and was able to provide professional bowel care.) Or do these 4 cases represent a forme
No.6
fruste of an incompletely understood disease? Tsuto et al. (14) have recently demonstrated the absence of vasoactive intestinal polypeptide, a modulator of intestinal motility, in the aganglionic segment of rectosigmoid Hirschsprung’s disease. They suggest that this lack of vasoactive intestinal polypeptide might contribute to the colonic constriction typically seen in aganglionosis. Perhaps these 4 cases of TCA had intermediate amounts of vasoactive intestinal polypeptide, thus allowing for some degree of smooth muscle relaxation. We will be soon examining this case for the presence of vasoactive intestinal polypeptide as well as other intestinal polypeptides.
References 1.
Louw JH. Total colonic aganglionosis. Can J Surg 1978; 21:397-409. disease. 2. Bodian M, Carter CO, Ward BCH. Hirschsprung’s Lancet 1951;i:302-9. 3. Hoffert P, Zuber S, Salzman A, Spinelli V. Aganglionosis of the entire colon. Surgery 1959;46:810-8. 4. Gerald B. Aganglionosis of the colon and terminal ileumlong term survival. Am J Roentgen01 1965;95:230-4. 5. Stone WD, Thomas BM, Hendrix R, Schuster MM. Aganglionosis of the entire colon in an adolescent. Gastroenterology 1965;48:636-41. 6. Myers MB, Bradburn D, Vela R, Payzant Z, Karlin S. Total aganglionic colon in an adult-first reported case. Ann Surg 1966;163:97-102. 7. Reifferscheid P, Flach A. Congenital megacolon in adults. In: Holschneider AM, ed. Hirschsprung’s disease. Stuttgart: Hippokrates Verlag, 1982:115-24. disease. Chicago: Year Book 8. Ehrenpreis T. Hirschsprung’s Medical, 1970:57-8. 9. Berdon WE, Koontz P, Baker DH. The diagnosis of colonic and terminal ileal aganglionosis. Am J Roentgen01 1964; 91:680-g. 10. Walker AW, Kempson RL. Ternberg JL. Aganglionosis of the small intestine. Surgery 1966;60:449-57. 11. Caresky JM, Weber TR, Grosfeld JL. Total colonic aganglionosis-analysis of 16 cases. Am J Surg 1982;143:160-7. 12. Davis BJ. Ornstein L. High resolution enzyme localization with a new diazo reagent hexasonium pararosaniline. J Histothem Cytochem 1959;7:297-8. 13. Meier-Ruge W. Morphological diagnosis of Hirschsprung’s disease. In: Holschneider AM, ed. Hirschsprung’s disease. Stuttgart: Hippokrates Verlag. 1982:62-71. 14. Tsuto T, Okamura H, Fukui K, et al. An immunohistochemical investigation of vasoactive intestinal polypeptide in the colon of patients with Hirschsprung’s disease. Neurosci Lett 1982:34:57-62.