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Total aganglionosis of the colon: Recognition and management
Total Aganglionosis
of the Colon : Recognition
and
Management By LUIS R. SOLTERO-HARRLNCTON, RAUL GARCIA-RINALDI, AND LUKE w. ABLE OTAL MEGACOLON (aganglionosis of the entire colon) has been recognized with increasing frequency. It is, though not common, more unrecognized than extremely rare.l There have been only sporadic reports of successfully treated cases; the most acceptable method has been ileostomy, with ileoproctostomy at a later stage. The mortality is very high. Bodian, Carter, and Ward in 1951 reviewed 160 cases of Hirschsprung’s disease.2 Of theses, 8.8 per cent were atypical, 2 per cent were total. They collected 14 long segment variants, 13 died, most of them in the first month of life. Bodian reported one case of aganglionosis disease from the duodenojejunal junction to the anus. Potts had 2 similar cases .3 Zuelzer and Wilson reported 2 cases of total Hirschsprung’s disease (20 per cent of their series) .4 AlI succumbed in early infancy. Sandegard reported in 1953 the fust instance of total aganghonic colon treated successfully.G Swenson and Fisher in 1955 had 2 patients,6 and Swenson added more in 1959. The incidence of total Hirschsprung’s disease was 2.5 per cent. Dorman reported three successfully treated cases in 1967’ and Edehnan reported two more in 1960.* Five other cases have been reported by other authors since 1960.g-11 At Texas Children’s Hospital up to 1967 there have been 87 patients with typical aganglionic disease of the distal colon and 13 with Hirschsprung’s disease of the entire colon. Twelve of the 13 patients with total megacolon were operated upon. Seven recovered, 2 of whom succumbed to unrelated causes.
T
CASE REPORTS Case 1: M.H. (T.C.H. #10323), white male, age 6 days, was first admitted 6/6/54. He had vomited bile since birth. Abdominal distention had been progressive and stools scanty. Vomiting and distention subsided temporarily with gastric suction and enemas, hut reFrom the Department of Surgay, Hospital Del Maestro, Huto Rey, Puerto Rico. and the Texas Children’s Hospital, Houston, Texas. Lurs R. SOLTERO-HARRINGTON,M.D.: Chairman, Cardiovascular Unit, Presbyterian Hospital, San Juan, Puerto Rico; Consultant in Surgery, Presbyteriun Hospital, San Juan, P.R.; Chairman Pediatric and Cardiovusculur Surgery Section, Hospital aId Maestro, Hato Rey, P.R. RAYJL GARCIA-RINALDI, M.D.: Resident in Surgery, Baylor University College of Medicine, Department of Surgery, Houston., Texas. LUKE W. ABLE, M.D.: Associate Clinical Professor of Surgery, Baylor University College of Medicine, Houston, Texas; Surgeon in Chief, Texas Chi.&en’s Hospital, Texas Medical Center, Houston, Texas. 330
JOURNAL OF F'EDLURICSURGERY,VOL. 4, No. 3 (JUNE), 1969
TOTAL AGANGLIONOSIS
curred
OF THE COLON
331
24 hours
later. Barium enema revealed a normal colon with retention of barium At laparotomy, the ileum was enlarged and hypertrophied, except for the 6 cm. The colon appeared normal. Biopsy of the narrow segment of the ileum
over 24 hours.
terminal
revealed no ganglion cells. A tube ileostomy was performed with which he was discharged. Salt was added to his formula. He was readmitted at 2 years. There were no ganglia on biopsy of the colon and terminal ileum. An ileoproctostomy was done using 4-6 cm. of his distal rectum. The rest of the colon was left in situ. He was readmitted at 5 years of age when resection of the defunctionalized colon and terminal ileum was performed. The ileum proximal to his ileoproctostomy was enlarged to the size of normal colon. He was seen in 1967 at 13 years of age. He is normal in growth and development and has only one formed stool daily. Cme 2: J.R.A. (T.C.H. #3695), white male, age 23 days, was admitted 10/2/54. He had vomiting and frequent stools from 2 days on. He had failed to gain weight and had There was gas throughout the intestinal developed progressive abdominal distention. tract. The small bowel was dilated. Barium enema showed the abdominal colon to be larger than the pelvic colon. He was treated with flush enemas and intravenous supportive therapy. Hirschsprung’s disease of the colon was considered, but during preparation for surgery he convulsed, became comatose, and died the following day. At autopsy the ileum was distended down to 10 cm. above that ileocecal valve where it was small, but otherwise grossly normal. There were no ganglion cells in the colon or the terminal 20 cm. of the ileum. Case 3: D.H. (T.C.H. #9503), white female, age 8 weeks, was first admitted 12/14/55 for obstipation, abdominal distention, and intermittent vomiting since birth. She also had congenitally dislocated hips and visible intestinal loops. A colon study showed a colon of normal size without constriction, but containing a large amount of fecal material. At laparotomy, the proximal ileum was thick and dilated, and there was a gradual transition to the empty but normal-looking terminal ileum 4 inches from the ileocecal valve. The terminal ileum, cecum, and appendix were removed and continuity re-established by an ileo-ascending colostomy. There were no ganglion cells in the resected specimen. A focalumbilical fistula developed and a loop enterostomy was done under local anesthesia on bowel that was thought to be ileum just proximal to the ileocolostomy. She had tremendous loss of liquids from the enterostomy, but maintained balance by taking 3 to 4 L. of fluid by mouth daily, with added salt. Fourteen months later, at reoperation, this enterostomy proved to be a high jejunostomy. It was closed and an end-to-side ileorectostomy was done 6-8 cm. above the anus. The proximal end of the ascending colon was exteriorized. She was discharged on a normal diet and was readmitted at age 3?i years when a subtotal colectomy of the defunctionalized segment was performed. There were no ganglion cells. Six months later she was doing well, walking, gaining, and having 5-8 formed stools per day, but with bouts of abdominal distention requiring rectal tube decompression. One year later she developed recurrent respiratory infections and Pseudomonas enterocohtis, later septicemia which caused her death. Case 4: K.W. (T.C.H. #322X), white male, age 11 days, was admitted 4/26/57 for abdominal distention and intermittent vomiting since birth. Intestinal pattern and peristaltic waves were visible. A scout film showed dilated small bowel with air fluid levels. At laparotomy, the small bowel was collapsed in the terminal 10 cm. but dilated proximally. A loop ileostomy was performed at the dilated ileum. Biopsy confirmed that ganglion cells were present at this level. Explosive ileostomy drainage became profuse and at 4 weeks postoperatively he expired. Autopsy showed hemosiderosis of the spleen, acute Pseudomonas euterocolitis, and a complete absence of ganglion cells of the terminal ileum and colon. Case 5: R.M. (T.C.H. #39069), white male, age 5 weeks, was admitted 8/5/57 for intermittent vomiting since birth. He was debilitated and dehydrated. There were palpable 100~~of lmwA Barium enema showed a colon with normal size lumen. Twenty-four-hour film showed no appreciable evacuation of the barium from the colon,
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ET AL.
At laparotomy, the terminal 15 cm. of ileum was collapsed, but proximal to this the ileum was dilated and thick. A loop ileostomy was done in the dilated portion. Biopsy at opening the ileostomy showed ganglion cells in normal quantity. He was discharged the ninth postoperative day, eating well, gaining, and 0.5 Gm. of salt added to every 24 oz. of formula. At age 6 months he was readmitted for a fulminating episode of vomiting and diarrhea. He was severely hyponatremic and hypokalemic requiring vigorous intravenous replacement of continuing losses. Isotonic electrolyte solution containing NaCI, NaHCO,, and KC1 was also given by drip into his distal ileostomy loop. Weight loss was replaced with electrolyte solution. At 11 months an ileoproctostomy was performed using the abdominoperineal approach, leaving 4 cm. of the distal rectum. The proximal end of this rectum was brought out the left lower guadrant. His postoperative course was uneventful and he was discharged the eleventh day, having 3 to 5 stools daily. At 3 years the defunctionalized colon and terminal ileum was resected. He recovered uneventfully and at 10 years he was normal in growth and development, having only one stool per day. Case 6: T.L. (T.C.H. #42598), white male, age 19 months, was admitted g/29/57 with a history of intermittent abdominal distention and vomiting since birth. At 5 weeks an ileotransversostomy had been performed. He gained poorly and his abdominal distention recurred. A second laparotomy had been performed for “adhesions.” On admission he was undernourished, the abdomen was distended, and the bowel sounds hyperactive. A scout film showed many dilated loops of small bowel and a dilated colon. Barium enema demonstrated a large colon throughout. At laparotomy the colon was large, paper-thin, and atonic. Ganglion cells were very sparse throughout the whole specimen. An anterior subtotal colectomy and ileoproctostomy were done, leaving 6 cm. of rectum. His postoperative course was characterized by frequent stools requiring intravenous therapy for one week. For the next 2 months he required added salt to the diet. At 15 months he had normal growth and deveIopment. He takes a normal diet for age without added salt and has 5 to 8 formed stools daily. Case 7: F.B. (T.C.H. #18754), colored male, age 6 weeks, was admitted 10/2/57 with a history of intermittent bile vomiting and distention since birth. He was a malnourished, debilitated infant weighing 5 lbs, 10 oz. His abdomen was distended, peristaltic waves were visible, and there were palpable fecal masses. There was marked distention of the small and large bowel and barium enema showed a large amount of retained feces. The colon did not empty in 24 hours. At laparotomy, 10/5/57, the colon was distended, as well as the cecum and ileum, and all contained impacted feces. A cecostomy was performed. Cecostomy irrigations were started the next day. He improved for 4 days, but became septic and expired the following day. Autopsy revealed a perforation of the ascending colon and peritonitis. No ganglia present in the colon. Case 8: J.P. (T.C.H. #50283), white male, age 9 days, was admitted 2/l/58 with a history There were palpable loops of bowel and of bile vomiting and abdominal distention. visible peristaltic waves. Swallowed barium had normal passage through the upper small intestine, At 9 hours the barium appeared to be in the right colon, but at 72 hours most of the barium was in the ileum. At laparotomy the terminal 3 cm. of ileum were collapsed, but proximal to this was thick and distended. There was no mechanical block. Barium and milk curds were in the dilated loops. There were no ganglia in the sigmoid and distal ileum, but were present in the dilated portion of the ileum. A Mikulicz ileostomy was done in the dilated portion. He was discharged 17 days later with salt added to his regular formula and supplemental electrolyte fluids into the distal stoma of his ileostomy. He was readmitted at 2% months for anemia and failure to thrive, and was transfused twice in the first 24 hours. He vomited and aspirated; resuscitation efforts were temporarily successful, but he expired 6 hours later. At autopsy there was an intra-abdominal abscess
TOTAL AGANGLIONOSIS
at the site of the ileostomy and terminal
333
OF THE COLON
with partial obstruction
and proximal
dilatation.
The entire colon
ileum were aganglionic.
Case 9: S.K.H. (T.C.H. #136123), white female, admitted on 3/4/62 at the age 5 days with a history of abdominal distention since a few hours after birth. During these 5 days she had become very dehydrated. There was colon stasis as well as massive dilatation of the small bowel by x-ray. At operation, the small bowel was dilated, except the distal 5-6 cm. of ileum which was contracted as was the colon. Biopsies of the distal ileum and all the colon showed no ganglion cells. A double-barrelled ileostomy as well as resection of the distal 25 cm. of ileum were done. The patient was discharged on a formula with added electrolyte solution. Three months later an ileoproctostomy using the Duhamel technic was done after resection of the recta sigmoid. The distal descending colon was exteriorized in the left lower quadrant. She was discharged to have half strength saline and bicarbonate installations 2-3 times per day at home. This patient had a good response to surgery, having Four months later she died from fulminating gastroenteritis, cular accident.
4 semi-formed stools per day. dehydration, and a cerebrovas-
Case IO: N.D.K. (T.C.H. #145169), 3- week-old white male was admitted on 8/2/62 after a 2%week history of vomiting, obstipation, progressive abdominal distention, and dehydration. A peristaltic pattern was evident and bowel sounds normal. He was severely dehydrated and emaciated. Scout film showed distal small bowel obstruction; barium enema showed non-emptying of the colon. At operation there was a dilated ileum and hypertrophy and edema of the distal ileal segment. The colon appeared normal. There were no ganglion cells in the colon. Ileostomy was performed. The first 6 postoperative months were very satisfactory and the patient gained weight. On 3/16/64 he had partial resection of the sigmoid colon, a Ieft descending colostomy, as well as an ileoproctostomy. The patient did well except for 3 episodes of vomiting, abdominal pain, and inability to pass feces, but these responded to rectal tube. At 3 years we resected his colon and terminal ileum. Colostomy and ileostomy sites were closed. In December of 1967, the patient was well, having 2 formed stools per day. Case 11: L.A.N. (T.C.H. #156946). A 6?&month-old white female was admitted for severe abdominal distention, dehydration, and constipation. At 12 hours she had a partial resection of gangrenous small bowel. At 3 and 5 months she had 2 more laparotomies for intestinal obstruction. Abdominal films showed small bowel obstruction. After decompression and hydration ileostomy was performed. She had a cardiac arrest during the procedure with successful resuscitation, but died on the first postoperative day after a second cardiac arrest. At postmortem there was total colonic aganglionosis, malrotation of the bowel, and fibrinous peritonitis. Case II”: P.E.L. (T.C.H. # 17018). A 25-day-old infant was admitted on l/20/64 with vomiting, abdominal distention, and dehydration. The colon was small and contracted throughout its length by barium enema. There was small bowel distention and perforation of the cecum at operation. No ganglion cells were found but were present in the ileum. A cecostomy was performed. During the latter part of 1965, the patient had a total colectomy and an ileoproctostom> (Duhamel) done elsewhere. Initially, she had mild fecal incontinence which resolved. This patient was seen recently, is of normal development and activity and has only one formed stool per day. CUSS 13: L.E.B. (T.C.H. #232552). A 4%-month-old white male was admitted on 2/16/67 for treatment of total colonic aganglionosis. During the first week of life he had a double-barrelled ileostomy for absence of ganglion cells in the colon, discovered during abdominal exploration for abdominal distention, severe constipation and vomitings. His father had a colostomy for Hirschsprung’s disease.
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SOLTERO-HARRINGTON ET AL.
On 2/17/67 biopsies confirmed the diagnosis. An ileoproctostomy was performed and the double ileostomy excised. A left colostomy and ileostomy were installed for irrigations. The postoperative course was mild and on 4/13/67 he had total colectomy with closure of the colostomy and ileostomy. One day postoperative, the patient had a respiratory arrest, was found to be hypoglycemic and had a seizure. He responded to intravenous glucose (10 per cent) and did well. About 20 days postoperative, he showed signs of intestinal obstruction, temperature elevation, and oliguria. He was re-explored in an attempt to relieve intestinal obstruction and numerous adhesions were divided, but died the first postoperative day.
DISCXJSSION Nine of our 13 patients were males; one of these was a Negro. A maternal uncle of the first patient had died of Hirschsprung’s disease; the father had aganglionosis. No other defects of ectodermal origin have been noted in these thirteen patients. Among early symptoms, meconium stools were delayed and persisted longer than usual. These patients often vomited and were distended during their stay in the newborn nursery. The age at first admission varied between 12 hours and 6 weeks. They were hospitalized for progressive abdominal distention, intermittent vomiting, and failure to gain. Three patients had “obstructive diarrhea1 stools.” No patient improved on change of formula; all improved by discontinuing the feedings. All were in severe abdominal distress during the first months of life. None showed persistently significant febrile response; and elevated white blood count was common, Sandegard,5 Zuelzer,4 and Swenson6 found similar and emphasized that this is one of the emergencies of the newborn period. All these patients became debilitated and dehydrated. An intestinal pattern with visible peristalsis and palpable loops were present in 6 cases. The bowel sounds were variable, hypoactive sounds being more frequent in the most debilitated infants. Enemas produced some stools, but did not empty the colon. One patient had convulsions and died following enemas during the preoperative period, while another convulsed in the postoperative period. One patient died following a cerebrovascular accident. All of the 13 patients showed dilated loops of small bowel on x-rays. Three had both large and small bowel dilatation. Contrast colon studies were performed in 9 patients; the lumen was normal in 7 and dilated in 2. No transition zones were noted. There was no complete emptying of the colon in any case. Colon stasis was the outstanding x-ray finding. Upper gastrointestinal studies were done in 2 cases. The 6-7 hour films showed the small intestine to be within normal limits, but later followup showed that the contrast material remained in the ileum for a week. The symptoms, pattern, signs, and x-ray picture of partial ileal obstruction and colon stasis in a newborn is almost diagnostic of total colonic aganglionic disease. Rectal biopsy proves aganglionosis, but does not determine the extent.12 The appearance of the bowel at laparotomy is classical; the ileum is thick and dilated, filled with inspissated milk curd of barium; it tapers abruptly into an empty, normal looking terminal ileum and colon (Fig. 1). Handling of this bowel results in a loss of the definite line of demarcation.
TOTAL
AGANGLIONOSIS
Table l.--Summary Case No.
Age at Diagnosis
335
OF THE COLON
of 13 Patients with Total Aganglionosis of the Colon First Procedure
1
6 days
2 3
23 days 8 weeks
4 5
11 days 5 weeks
6
5 weeks
Ileotransversostomy
7 8 9
6 weeks 9 days 5 days
Cecostomy Mikulicz ileostomy Double-barrelled ileostomy
10
2% weeks
Ileostomy
11 12
12 mos. 25 days
Ileostomy Cecostomy
13
7 days
Tube
ileostomy
Died before surgery Ileo-ascending colastomy; tube colostomy Loop ileostomy Loop ileostomy
Double-barrelled ileostomy
Final Procedure
Ileoproctostomy subtotal colectomy None Ileoproctostomy ( anterior approach ) subtotal colectomy None IIeoproctostomy; abdominoperineal “pull through” Ileoproctostomy (anterior approaching subtotal colectomy None None Ileoproctostomy (Duhamel); resection of rectosigmoid colon Ileoproctostomy; total colectomy None Ileoproctostomy (Duhamel); total colectomy Ileoproctostomy; total colectomy
ReSUlt
Excellent Died Good; died of unrelated causes Died Excellent
Good
Died Died Good; died of unrelated causes Excellent Died Excellent Died
The air and feces are easily manipulated into the previously collapsed segment. Multiple biopsies above and below the transitional zone and search for intramural ganglion cells will establish the diagnosis and the extent of the aganglioSeveral other lesions may simulate the total aganglionosis. In the typical short-segment lesion, the symptoms are often milder and may even not appear until after the neonatal period. A rectal tube and irrigations may completely relieve the obstruction in patients with short-segment disease. A contrast enema will delineate the change of caliber in the distal colon, which becomes clearer as the disproportion increases with time. The meconium impaction of pancreatic fibrosis produces early vomiting, abdominal distention, and visible and palpable intestinal loops. The plain x-rays of the abdomen may be suggestive of either disease, but colon contrast studies in the meconium ileus show an used colon with good evacuation. Malrotation of the colon with volvulus may also simulate aganglionosis. Vomiting of bile is more prominent in malrotation, since the obstruction is higher. A contrast enema shows incomplete rotation or malrotation. Peritonitis in the newborn can sometimes be confused with aganglionic disease. The septic course, acuteness of the disease, and the picture of the ileus all heIp to make the diagnosis. A history of norma gastrointestinal function helps rule out aganglionosis. The “fetal distress syndrome” due to hypoxia, local or general, during fetal
336
SOLTERO-HARRINGTON
ET AL.
Fig. L-The small aganglionic terminal ileum and colon appear normal. The proximal ileum is hypertrophied and dilated. A more definite transition could be better observed before the bowel was handled.
development or at birth, may affect the gastrointestinal tract. This may be diagnosed as obstruction, but more often as colitis “above and beyond” the usual. Enteritis is common. These patients have variable degrees of obstruction by their nonfunctioning segment and perforation does occur. We had one such infant on whom we did an ileostomy as an emergency, but closed it later when biopsies showed normal ganglion cells. Two others had segmental resections for a perforated lesion in their mid-ileum. At first these were thought to be segmental aganglionic areas, but restudy demonstrated ganglion cells. Prolonged conservative treatment has resulted in death in every case reported in the literature and in our group. Before surgery is undertaken electrolyte and fluid deficiency is corrected and blood transfusion given when necessary. The primary operation should relieve the obstruction and establish the level of normal bowel. A decompressing ileostomy is preferable; ileotransverse colostomy or cecostomy does not relieve the obstruction. Biopsies of the colon and ileum are taken if the patient’s condition permits. We have given procaine, penicillin, and streptomycin, and if there is any contamination, a broad-spectrum antibiotic is also given. Cultures and sensitivity studies of the peritoneal fluid and the bowel contents are guides to these. Ileostomy losses are not severe unless there is enteritis or a partial obstruction at the site of the ileostomy. The addition of 0.5 Gm. of sodium chloride and 0.5 Gm. of sodium bicarbonate to each 24 oz. of formula corrects the ordinary
TOT.IL AGANGLIONOSIS
OF THE COLON
337
Fig. 2.-A plastic appliance is laid over cohesive ointment around the ileostomy to prevent skin excoriation. electrolyte losses by ileostomy. Some patients need hospitalization and massive, rapid, intravenous electrolyte therapy to keep up with these losses. The distal (aganglionic) bowel has normal absorption. Fluid and electrolyte replacement through this route is effective and economical; the mother can administer it at home. Excoriation of the skin around the ileostomy has not been a problem. The skin is washed twice daily and dried thoroughly. Cod liver oil, zinc oxide ointment is applied to the skin 4 inches out from the ileostomy. A plastic sheet with a central opening the size of the ileostomy is then applied so that none of the ileostomy drainage comes in contact with the skin (Fig. 2). A regular diaper may be folded over the ileostomy and held in place by another wrapped around the body. At the second stage, an ileoproctostomy is done by the abdominoperineal approach using the Swenson or the Duhamell” technic. The distal ileostomy or colostomy serves as a route for administration of fluids when oral intake is insufficient. Enteritis is always a threat to the young patient’s survival. By-passed colon and terminal ileum may be removed electively. All patients in our group have adequate sphincter control and produce formed stools. No special diets are needed and growth and development are normal. SUMMARY AND CONCLUSIONS The diagnosis and management of the common variety of Hirschsprung’s disease is not a small matter in a newborn, but total aganglionosis is an in-
SOLTERO-HARRINGTON ET AL.
338
finitely more serious and tedious problem frequently accompanied by fulminating complications. The diagnosis is likely when a high-grade partial ileal obstruction is accompanied by fecal impaction of the colon. Rectal biopsy establishes the diagnosis, but the extent of the aganglionosis is determined only at laparotomy with biopsies. A preliminary loop ileostomy is done in the ganglionic intestine. At a later stage an ileoproctostomy is performed in one or more stages. Bowel function and life expectancy are normal for survivors. SUMMARIO
IN
INTERLINGUA
Aganglionosis total de1 colon es un serie problema de therapia e therapeutica e resulta frequentemente in complicationes fulminante. Septe de 15 patientes superviveva, sed 2 de1 7 succumbeva plus tarde a morbos non relationate. Le prompte diagnose-suggestionate per obstruction de1 intestino tenue in le presentia de colonic impaction fecal-es essential pro le superviventia. Ileostomia es le procedimento primari, sed un varietate de possibilitates es disponibile pro le therapia definitive. Normal function intestinal seque ileoproctostomia. ACKNOWLEDGMENT We are grateful to Mr. Carlos E. Lopez, and preparing the material.
S.M.S.
for his assistance
in reviewing
the literature
REFERENCES 1. Gerald, B.: Aganglionosis of the colon and terminal ileum (long term survival). Amer. J. Roentgen. Rad. Ther. Nucl. Med. 95:230, 1965. 2. Bodian, M., Carter, C. O., and Ward, B. E. H.: Hirschsprung’s Disease. Lancet 260:302, 1951. 3. Potts, W. J.: Personal Communication, February 1959. 4. Zuelzer, W. W., and Wilson, J. L.: Functional intestinal obstruction as a congenital neurogenic basis in infancy. Amer. J. Dis. Child. 75340-64, 1948. 5. Sandegard, E.: Hirschsprung’s disease with ganglion cell aplasia of the colon and terminal ileum. Acta Chirurg. Stand. 106: 68, 1953. 6. Swenson, O., and Fisher, J. H.: Treatment of Hirschsprung’s disease with the entire colon involved in the aganglionic defect. A.M.A. Arch. Surg. 70:53%538, 1955.
7. Dorman, G.: Universal aganglionosis of the colon. Surgery 47:672, 1957. 8. Edelman, S., Strauss, L., Becker, J., and Arnheim, E.: Universal aganglionosis of the colon. Surgery 47:667, 1957. 9. Berdon, W., Koontz, P., and Baker, D.: The diagnosis of colonic and terminal ileal aganglionosis. Amer. J. Roentgen. 91: 680, 1964. 10. Desjardings, J,, and Simpson, J.: Neonatal Hirschsprung’s disease (treatment of complete aganglionosis of the colon by the Duhamel operation). Arch. Surg. 87: 1019, 1963. 11. Stone, W., Hendrix, T., and Schuster, M.: Aganglionosis of the entire colon in an adolescent. Gastroenterology 48:636, 1965. 12. Swenson, O., Fisher, J. H., and MacMahon, H. E.: Rectal biopsy as an aid in the diagnosis of Hirschsprung’s disease. New Eng. J. Med. 253:632, 1955.
of the Colon : Recognition
and
Management By LUIS R. SOLTERO-HARRLNCTON, RAUL GARCIA-RINALDI, AND LUKE w. ABLE OTAL MEGACOLON (aganglionosis of the entire colon) has been recognized with increasing frequency. It is, though not common, more unrecognized than extremely rare.l There have been only sporadic reports of successfully treated cases; the most acceptable method has been ileostomy, with ileoproctostomy at a later stage. The mortality is very high. Bodian, Carter, and Ward in 1951 reviewed 160 cases of Hirschsprung’s disease.2 Of theses, 8.8 per cent were atypical, 2 per cent were total. They collected 14 long segment variants, 13 died, most of them in the first month of life. Bodian reported one case of aganglionosis disease from the duodenojejunal junction to the anus. Potts had 2 similar cases .3 Zuelzer and Wilson reported 2 cases of total Hirschsprung’s disease (20 per cent of their series) .4 AlI succumbed in early infancy. Sandegard reported in 1953 the fust instance of total aganghonic colon treated successfully.G Swenson and Fisher in 1955 had 2 patients,6 and Swenson added more in 1959. The incidence of total Hirschsprung’s disease was 2.5 per cent. Dorman reported three successfully treated cases in 1967’ and Edehnan reported two more in 1960.* Five other cases have been reported by other authors since 1960.g-11 At Texas Children’s Hospital up to 1967 there have been 87 patients with typical aganglionic disease of the distal colon and 13 with Hirschsprung’s disease of the entire colon. Twelve of the 13 patients with total megacolon were operated upon. Seven recovered, 2 of whom succumbed to unrelated causes.
T
CASE REPORTS Case 1: M.H. (T.C.H. #10323), white male, age 6 days, was first admitted 6/6/54. He had vomited bile since birth. Abdominal distention had been progressive and stools scanty. Vomiting and distention subsided temporarily with gastric suction and enemas, hut reFrom the Department of Surgay, Hospital Del Maestro, Huto Rey, Puerto Rico. and the Texas Children’s Hospital, Houston, Texas. Lurs R. SOLTERO-HARRINGTON,M.D.: Chairman, Cardiovascular Unit, Presbyterian Hospital, San Juan, Puerto Rico; Consultant in Surgery, Presbyteriun Hospital, San Juan, P.R.; Chairman Pediatric and Cardiovusculur Surgery Section, Hospital aId Maestro, Hato Rey, P.R. RAYJL GARCIA-RINALDI, M.D.: Resident in Surgery, Baylor University College of Medicine, Department of Surgery, Houston., Texas. LUKE W. ABLE, M.D.: Associate Clinical Professor of Surgery, Baylor University College of Medicine, Houston, Texas; Surgeon in Chief, Texas Chi.&en’s Hospital, Texas Medical Center, Houston, Texas. 330
JOURNAL OF F'EDLURICSURGERY,VOL. 4, No. 3 (JUNE), 1969
TOTAL AGANGLIONOSIS
curred
OF THE COLON
331
24 hours
later. Barium enema revealed a normal colon with retention of barium At laparotomy, the ileum was enlarged and hypertrophied, except for the 6 cm. The colon appeared normal. Biopsy of the narrow segment of the ileum
over 24 hours.
terminal
revealed no ganglion cells. A tube ileostomy was performed with which he was discharged. Salt was added to his formula. He was readmitted at 2 years. There were no ganglia on biopsy of the colon and terminal ileum. An ileoproctostomy was done using 4-6 cm. of his distal rectum. The rest of the colon was left in situ. He was readmitted at 5 years of age when resection of the defunctionalized colon and terminal ileum was performed. The ileum proximal to his ileoproctostomy was enlarged to the size of normal colon. He was seen in 1967 at 13 years of age. He is normal in growth and development and has only one formed stool daily. Cme 2: J.R.A. (T.C.H. #3695), white male, age 23 days, was admitted 10/2/54. He had vomiting and frequent stools from 2 days on. He had failed to gain weight and had There was gas throughout the intestinal developed progressive abdominal distention. tract. The small bowel was dilated. Barium enema showed the abdominal colon to be larger than the pelvic colon. He was treated with flush enemas and intravenous supportive therapy. Hirschsprung’s disease of the colon was considered, but during preparation for surgery he convulsed, became comatose, and died the following day. At autopsy the ileum was distended down to 10 cm. above that ileocecal valve where it was small, but otherwise grossly normal. There were no ganglion cells in the colon or the terminal 20 cm. of the ileum. Case 3: D.H. (T.C.H. #9503), white female, age 8 weeks, was first admitted 12/14/55 for obstipation, abdominal distention, and intermittent vomiting since birth. She also had congenitally dislocated hips and visible intestinal loops. A colon study showed a colon of normal size without constriction, but containing a large amount of fecal material. At laparotomy, the proximal ileum was thick and dilated, and there was a gradual transition to the empty but normal-looking terminal ileum 4 inches from the ileocecal valve. The terminal ileum, cecum, and appendix were removed and continuity re-established by an ileo-ascending colostomy. There were no ganglion cells in the resected specimen. A focalumbilical fistula developed and a loop enterostomy was done under local anesthesia on bowel that was thought to be ileum just proximal to the ileocolostomy. She had tremendous loss of liquids from the enterostomy, but maintained balance by taking 3 to 4 L. of fluid by mouth daily, with added salt. Fourteen months later, at reoperation, this enterostomy proved to be a high jejunostomy. It was closed and an end-to-side ileorectostomy was done 6-8 cm. above the anus. The proximal end of the ascending colon was exteriorized. She was discharged on a normal diet and was readmitted at age 3?i years when a subtotal colectomy of the defunctionalized segment was performed. There were no ganglion cells. Six months later she was doing well, walking, gaining, and having 5-8 formed stools per day, but with bouts of abdominal distention requiring rectal tube decompression. One year later she developed recurrent respiratory infections and Pseudomonas enterocohtis, later septicemia which caused her death. Case 4: K.W. (T.C.H. #322X), white male, age 11 days, was admitted 4/26/57 for abdominal distention and intermittent vomiting since birth. Intestinal pattern and peristaltic waves were visible. A scout film showed dilated small bowel with air fluid levels. At laparotomy, the small bowel was collapsed in the terminal 10 cm. but dilated proximally. A loop ileostomy was performed at the dilated ileum. Biopsy confirmed that ganglion cells were present at this level. Explosive ileostomy drainage became profuse and at 4 weeks postoperatively he expired. Autopsy showed hemosiderosis of the spleen, acute Pseudomonas euterocolitis, and a complete absence of ganglion cells of the terminal ileum and colon. Case 5: R.M. (T.C.H. #39069), white male, age 5 weeks, was admitted 8/5/57 for intermittent vomiting since birth. He was debilitated and dehydrated. There were palpable 100~~of lmwA Barium enema showed a colon with normal size lumen. Twenty-four-hour film showed no appreciable evacuation of the barium from the colon,
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ET AL.
At laparotomy, the terminal 15 cm. of ileum was collapsed, but proximal to this the ileum was dilated and thick. A loop ileostomy was done in the dilated portion. Biopsy at opening the ileostomy showed ganglion cells in normal quantity. He was discharged the ninth postoperative day, eating well, gaining, and 0.5 Gm. of salt added to every 24 oz. of formula. At age 6 months he was readmitted for a fulminating episode of vomiting and diarrhea. He was severely hyponatremic and hypokalemic requiring vigorous intravenous replacement of continuing losses. Isotonic electrolyte solution containing NaCI, NaHCO,, and KC1 was also given by drip into his distal ileostomy loop. Weight loss was replaced with electrolyte solution. At 11 months an ileoproctostomy was performed using the abdominoperineal approach, leaving 4 cm. of the distal rectum. The proximal end of this rectum was brought out the left lower guadrant. His postoperative course was uneventful and he was discharged the eleventh day, having 3 to 5 stools daily. At 3 years the defunctionalized colon and terminal ileum was resected. He recovered uneventfully and at 10 years he was normal in growth and development, having only one stool per day. Case 6: T.L. (T.C.H. #42598), white male, age 19 months, was admitted g/29/57 with a history of intermittent abdominal distention and vomiting since birth. At 5 weeks an ileotransversostomy had been performed. He gained poorly and his abdominal distention recurred. A second laparotomy had been performed for “adhesions.” On admission he was undernourished, the abdomen was distended, and the bowel sounds hyperactive. A scout film showed many dilated loops of small bowel and a dilated colon. Barium enema demonstrated a large colon throughout. At laparotomy the colon was large, paper-thin, and atonic. Ganglion cells were very sparse throughout the whole specimen. An anterior subtotal colectomy and ileoproctostomy were done, leaving 6 cm. of rectum. His postoperative course was characterized by frequent stools requiring intravenous therapy for one week. For the next 2 months he required added salt to the diet. At 15 months he had normal growth and deveIopment. He takes a normal diet for age without added salt and has 5 to 8 formed stools daily. Case 7: F.B. (T.C.H. #18754), colored male, age 6 weeks, was admitted 10/2/57 with a history of intermittent bile vomiting and distention since birth. He was a malnourished, debilitated infant weighing 5 lbs, 10 oz. His abdomen was distended, peristaltic waves were visible, and there were palpable fecal masses. There was marked distention of the small and large bowel and barium enema showed a large amount of retained feces. The colon did not empty in 24 hours. At laparotomy, 10/5/57, the colon was distended, as well as the cecum and ileum, and all contained impacted feces. A cecostomy was performed. Cecostomy irrigations were started the next day. He improved for 4 days, but became septic and expired the following day. Autopsy revealed a perforation of the ascending colon and peritonitis. No ganglia present in the colon. Case 8: J.P. (T.C.H. #50283), white male, age 9 days, was admitted 2/l/58 with a history There were palpable loops of bowel and of bile vomiting and abdominal distention. visible peristaltic waves. Swallowed barium had normal passage through the upper small intestine, At 9 hours the barium appeared to be in the right colon, but at 72 hours most of the barium was in the ileum. At laparotomy the terminal 3 cm. of ileum were collapsed, but proximal to this was thick and distended. There was no mechanical block. Barium and milk curds were in the dilated loops. There were no ganglia in the sigmoid and distal ileum, but were present in the dilated portion of the ileum. A Mikulicz ileostomy was done in the dilated portion. He was discharged 17 days later with salt added to his regular formula and supplemental electrolyte fluids into the distal stoma of his ileostomy. He was readmitted at 2% months for anemia and failure to thrive, and was transfused twice in the first 24 hours. He vomited and aspirated; resuscitation efforts were temporarily successful, but he expired 6 hours later. At autopsy there was an intra-abdominal abscess
TOTAL AGANGLIONOSIS
at the site of the ileostomy and terminal
333
OF THE COLON
with partial obstruction
and proximal
dilatation.
The entire colon
ileum were aganglionic.
Case 9: S.K.H. (T.C.H. #136123), white female, admitted on 3/4/62 at the age 5 days with a history of abdominal distention since a few hours after birth. During these 5 days she had become very dehydrated. There was colon stasis as well as massive dilatation of the small bowel by x-ray. At operation, the small bowel was dilated, except the distal 5-6 cm. of ileum which was contracted as was the colon. Biopsies of the distal ileum and all the colon showed no ganglion cells. A double-barrelled ileostomy as well as resection of the distal 25 cm. of ileum were done. The patient was discharged on a formula with added electrolyte solution. Three months later an ileoproctostomy using the Duhamel technic was done after resection of the recta sigmoid. The distal descending colon was exteriorized in the left lower quadrant. She was discharged to have half strength saline and bicarbonate installations 2-3 times per day at home. This patient had a good response to surgery, having Four months later she died from fulminating gastroenteritis, cular accident.
4 semi-formed stools per day. dehydration, and a cerebrovas-
Case IO: N.D.K. (T.C.H. #145169), 3- week-old white male was admitted on 8/2/62 after a 2%week history of vomiting, obstipation, progressive abdominal distention, and dehydration. A peristaltic pattern was evident and bowel sounds normal. He was severely dehydrated and emaciated. Scout film showed distal small bowel obstruction; barium enema showed non-emptying of the colon. At operation there was a dilated ileum and hypertrophy and edema of the distal ileal segment. The colon appeared normal. There were no ganglion cells in the colon. Ileostomy was performed. The first 6 postoperative months were very satisfactory and the patient gained weight. On 3/16/64 he had partial resection of the sigmoid colon, a Ieft descending colostomy, as well as an ileoproctostomy. The patient did well except for 3 episodes of vomiting, abdominal pain, and inability to pass feces, but these responded to rectal tube. At 3 years we resected his colon and terminal ileum. Colostomy and ileostomy sites were closed. In December of 1967, the patient was well, having 2 formed stools per day. Case 11: L.A.N. (T.C.H. #156946). A 6?&month-old white female was admitted for severe abdominal distention, dehydration, and constipation. At 12 hours she had a partial resection of gangrenous small bowel. At 3 and 5 months she had 2 more laparotomies for intestinal obstruction. Abdominal films showed small bowel obstruction. After decompression and hydration ileostomy was performed. She had a cardiac arrest during the procedure with successful resuscitation, but died on the first postoperative day after a second cardiac arrest. At postmortem there was total colonic aganglionosis, malrotation of the bowel, and fibrinous peritonitis. Case II”: P.E.L. (T.C.H. # 17018). A 25-day-old infant was admitted on l/20/64 with vomiting, abdominal distention, and dehydration. The colon was small and contracted throughout its length by barium enema. There was small bowel distention and perforation of the cecum at operation. No ganglion cells were found but were present in the ileum. A cecostomy was performed. During the latter part of 1965, the patient had a total colectomy and an ileoproctostom> (Duhamel) done elsewhere. Initially, she had mild fecal incontinence which resolved. This patient was seen recently, is of normal development and activity and has only one formed stool per day. CUSS 13: L.E.B. (T.C.H. #232552). A 4%-month-old white male was admitted on 2/16/67 for treatment of total colonic aganglionosis. During the first week of life he had a double-barrelled ileostomy for absence of ganglion cells in the colon, discovered during abdominal exploration for abdominal distention, severe constipation and vomitings. His father had a colostomy for Hirschsprung’s disease.
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SOLTERO-HARRINGTON ET AL.
On 2/17/67 biopsies confirmed the diagnosis. An ileoproctostomy was performed and the double ileostomy excised. A left colostomy and ileostomy were installed for irrigations. The postoperative course was mild and on 4/13/67 he had total colectomy with closure of the colostomy and ileostomy. One day postoperative, the patient had a respiratory arrest, was found to be hypoglycemic and had a seizure. He responded to intravenous glucose (10 per cent) and did well. About 20 days postoperative, he showed signs of intestinal obstruction, temperature elevation, and oliguria. He was re-explored in an attempt to relieve intestinal obstruction and numerous adhesions were divided, but died the first postoperative day.
DISCXJSSION Nine of our 13 patients were males; one of these was a Negro. A maternal uncle of the first patient had died of Hirschsprung’s disease; the father had aganglionosis. No other defects of ectodermal origin have been noted in these thirteen patients. Among early symptoms, meconium stools were delayed and persisted longer than usual. These patients often vomited and were distended during their stay in the newborn nursery. The age at first admission varied between 12 hours and 6 weeks. They were hospitalized for progressive abdominal distention, intermittent vomiting, and failure to gain. Three patients had “obstructive diarrhea1 stools.” No patient improved on change of formula; all improved by discontinuing the feedings. All were in severe abdominal distress during the first months of life. None showed persistently significant febrile response; and elevated white blood count was common, Sandegard,5 Zuelzer,4 and Swenson6 found similar and emphasized that this is one of the emergencies of the newborn period. All these patients became debilitated and dehydrated. An intestinal pattern with visible peristalsis and palpable loops were present in 6 cases. The bowel sounds were variable, hypoactive sounds being more frequent in the most debilitated infants. Enemas produced some stools, but did not empty the colon. One patient had convulsions and died following enemas during the preoperative period, while another convulsed in the postoperative period. One patient died following a cerebrovascular accident. All of the 13 patients showed dilated loops of small bowel on x-rays. Three had both large and small bowel dilatation. Contrast colon studies were performed in 9 patients; the lumen was normal in 7 and dilated in 2. No transition zones were noted. There was no complete emptying of the colon in any case. Colon stasis was the outstanding x-ray finding. Upper gastrointestinal studies were done in 2 cases. The 6-7 hour films showed the small intestine to be within normal limits, but later followup showed that the contrast material remained in the ileum for a week. The symptoms, pattern, signs, and x-ray picture of partial ileal obstruction and colon stasis in a newborn is almost diagnostic of total colonic aganglionic disease. Rectal biopsy proves aganglionosis, but does not determine the extent.12 The appearance of the bowel at laparotomy is classical; the ileum is thick and dilated, filled with inspissated milk curd of barium; it tapers abruptly into an empty, normal looking terminal ileum and colon (Fig. 1). Handling of this bowel results in a loss of the definite line of demarcation.
TOTAL
AGANGLIONOSIS
Table l.--Summary Case No.
Age at Diagnosis
335
OF THE COLON
of 13 Patients with Total Aganglionosis of the Colon First Procedure
1
6 days
2 3
23 days 8 weeks
4 5
11 days 5 weeks
6
5 weeks
Ileotransversostomy
7 8 9
6 weeks 9 days 5 days
Cecostomy Mikulicz ileostomy Double-barrelled ileostomy
10
2% weeks
Ileostomy
11 12
12 mos. 25 days
Ileostomy Cecostomy
13
7 days
Tube
ileostomy
Died before surgery Ileo-ascending colastomy; tube colostomy Loop ileostomy Loop ileostomy
Double-barrelled ileostomy
Final Procedure
Ileoproctostomy subtotal colectomy None Ileoproctostomy ( anterior approach ) subtotal colectomy None IIeoproctostomy; abdominoperineal “pull through” Ileoproctostomy (anterior approaching subtotal colectomy None None Ileoproctostomy (Duhamel); resection of rectosigmoid colon Ileoproctostomy; total colectomy None Ileoproctostomy (Duhamel); total colectomy Ileoproctostomy; total colectomy
ReSUlt
Excellent Died Good; died of unrelated causes Died Excellent
Good
Died Died Good; died of unrelated causes Excellent Died Excellent Died
The air and feces are easily manipulated into the previously collapsed segment. Multiple biopsies above and below the transitional zone and search for intramural ganglion cells will establish the diagnosis and the extent of the aganglioSeveral other lesions may simulate the total aganglionosis. In the typical short-segment lesion, the symptoms are often milder and may even not appear until after the neonatal period. A rectal tube and irrigations may completely relieve the obstruction in patients with short-segment disease. A contrast enema will delineate the change of caliber in the distal colon, which becomes clearer as the disproportion increases with time. The meconium impaction of pancreatic fibrosis produces early vomiting, abdominal distention, and visible and palpable intestinal loops. The plain x-rays of the abdomen may be suggestive of either disease, but colon contrast studies in the meconium ileus show an used colon with good evacuation. Malrotation of the colon with volvulus may also simulate aganglionosis. Vomiting of bile is more prominent in malrotation, since the obstruction is higher. A contrast enema shows incomplete rotation or malrotation. Peritonitis in the newborn can sometimes be confused with aganglionic disease. The septic course, acuteness of the disease, and the picture of the ileus all heIp to make the diagnosis. A history of norma gastrointestinal function helps rule out aganglionosis. The “fetal distress syndrome” due to hypoxia, local or general, during fetal
336
SOLTERO-HARRINGTON
ET AL.
Fig. L-The small aganglionic terminal ileum and colon appear normal. The proximal ileum is hypertrophied and dilated. A more definite transition could be better observed before the bowel was handled.
development or at birth, may affect the gastrointestinal tract. This may be diagnosed as obstruction, but more often as colitis “above and beyond” the usual. Enteritis is common. These patients have variable degrees of obstruction by their nonfunctioning segment and perforation does occur. We had one such infant on whom we did an ileostomy as an emergency, but closed it later when biopsies showed normal ganglion cells. Two others had segmental resections for a perforated lesion in their mid-ileum. At first these were thought to be segmental aganglionic areas, but restudy demonstrated ganglion cells. Prolonged conservative treatment has resulted in death in every case reported in the literature and in our group. Before surgery is undertaken electrolyte and fluid deficiency is corrected and blood transfusion given when necessary. The primary operation should relieve the obstruction and establish the level of normal bowel. A decompressing ileostomy is preferable; ileotransverse colostomy or cecostomy does not relieve the obstruction. Biopsies of the colon and ileum are taken if the patient’s condition permits. We have given procaine, penicillin, and streptomycin, and if there is any contamination, a broad-spectrum antibiotic is also given. Cultures and sensitivity studies of the peritoneal fluid and the bowel contents are guides to these. Ileostomy losses are not severe unless there is enteritis or a partial obstruction at the site of the ileostomy. The addition of 0.5 Gm. of sodium chloride and 0.5 Gm. of sodium bicarbonate to each 24 oz. of formula corrects the ordinary
TOT.IL AGANGLIONOSIS
OF THE COLON
337
Fig. 2.-A plastic appliance is laid over cohesive ointment around the ileostomy to prevent skin excoriation. electrolyte losses by ileostomy. Some patients need hospitalization and massive, rapid, intravenous electrolyte therapy to keep up with these losses. The distal (aganglionic) bowel has normal absorption. Fluid and electrolyte replacement through this route is effective and economical; the mother can administer it at home. Excoriation of the skin around the ileostomy has not been a problem. The skin is washed twice daily and dried thoroughly. Cod liver oil, zinc oxide ointment is applied to the skin 4 inches out from the ileostomy. A plastic sheet with a central opening the size of the ileostomy is then applied so that none of the ileostomy drainage comes in contact with the skin (Fig. 2). A regular diaper may be folded over the ileostomy and held in place by another wrapped around the body. At the second stage, an ileoproctostomy is done by the abdominoperineal approach using the Swenson or the Duhamell” technic. The distal ileostomy or colostomy serves as a route for administration of fluids when oral intake is insufficient. Enteritis is always a threat to the young patient’s survival. By-passed colon and terminal ileum may be removed electively. All patients in our group have adequate sphincter control and produce formed stools. No special diets are needed and growth and development are normal. SUMMARY AND CONCLUSIONS The diagnosis and management of the common variety of Hirschsprung’s disease is not a small matter in a newborn, but total aganglionosis is an in-
SOLTERO-HARRINGTON ET AL.
338
finitely more serious and tedious problem frequently accompanied by fulminating complications. The diagnosis is likely when a high-grade partial ileal obstruction is accompanied by fecal impaction of the colon. Rectal biopsy establishes the diagnosis, but the extent of the aganglionosis is determined only at laparotomy with biopsies. A preliminary loop ileostomy is done in the ganglionic intestine. At a later stage an ileoproctostomy is performed in one or more stages. Bowel function and life expectancy are normal for survivors. SUMMARIO
IN
INTERLINGUA
Aganglionosis total de1 colon es un serie problema de therapia e therapeutica e resulta frequentemente in complicationes fulminante. Septe de 15 patientes superviveva, sed 2 de1 7 succumbeva plus tarde a morbos non relationate. Le prompte diagnose-suggestionate per obstruction de1 intestino tenue in le presentia de colonic impaction fecal-es essential pro le superviventia. Ileostomia es le procedimento primari, sed un varietate de possibilitates es disponibile pro le therapia definitive. Normal function intestinal seque ileoproctostomia. ACKNOWLEDGMENT We are grateful to Mr. Carlos E. Lopez, and preparing the material.
S.M.S.
for his assistance
in reviewing
the literature
REFERENCES 1. Gerald, B.: Aganglionosis of the colon and terminal ileum (long term survival). Amer. J. Roentgen. Rad. Ther. Nucl. Med. 95:230, 1965. 2. Bodian, M., Carter, C. O., and Ward, B. E. H.: Hirschsprung’s Disease. Lancet 260:302, 1951. 3. Potts, W. J.: Personal Communication, February 1959. 4. Zuelzer, W. W., and Wilson, J. L.: Functional intestinal obstruction as a congenital neurogenic basis in infancy. Amer. J. Dis. Child. 75340-64, 1948. 5. Sandegard, E.: Hirschsprung’s disease with ganglion cell aplasia of the colon and terminal ileum. Acta Chirurg. Stand. 106: 68, 1953. 6. Swenson, O., and Fisher, J. H.: Treatment of Hirschsprung’s disease with the entire colon involved in the aganglionic defect. A.M.A. Arch. Surg. 70:53%538, 1955.
7. Dorman, G.: Universal aganglionosis of the colon. Surgery 47:672, 1957. 8. Edelman, S., Strauss, L., Becker, J., and Arnheim, E.: Universal aganglionosis of the colon. Surgery 47:667, 1957. 9. Berdon, W., Koontz, P., and Baker, D.: The diagnosis of colonic and terminal ileal aganglionosis. Amer. J. Roentgen. 91: 680, 1964. 10. Desjardings, J,, and Simpson, J.: Neonatal Hirschsprung’s disease (treatment of complete aganglionosis of the colon by the Duhamel operation). Arch. Surg. 87: 1019, 1963. 11. Stone, W., Hendrix, T., and Schuster, M.: Aganglionosis of the entire colon in an adolescent. Gastroenterology 48:636, 1965. 12. Swenson, O., Fisher, J. H., and MacMahon, H. E.: Rectal biopsy as an aid in the diagnosis of Hirschsprung’s disease. New Eng. J. Med. 253:632, 1955.