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Experimental production of rectal stenosis and atresia in the rabbit
Experimental Production of Rectal S t e n o s i s and Atresia in the Rabbit By H. Hadan Stone and A. W . Wilkinson
Atlanta, Georgia, and London, England 9 Clinical reviews have suggested that there are different causes for the various types of anorectal atresia and stenosis, Such inferences have primarily been based upon t h e presence or absence of associated fistulas and other anogenital, urinary, and more remote congenital defects. Rectal stenosis and atresia of the middle a n d / o r upper third of the rectum w e r e produced in 27 of 38 rabbit feti subjected to partial to complete interruption of the blood supply to the rectosigmoid colon b e t w e e n the 24th asnd 26th day of gestation. Such experimental feti w e r e located in the right tube, while a sham laparotomy was performed during t h e same maternal operation on 26 feti located in the left tube. An additional undisturbed 28 feti w e r e available in both tubes to serve as controls. No other anomalies w e r e produced in any group. These findings suggest that local ischemia, occurring late during fetal life, may well he the mechanism responsible for the creation of rectal stenosis and atresia of t h e middle a n d / o r upper rectum.
identified and isolated. For feti in the experimental group (those in the right uterine tube), the sigmoid mesentery was divided; and the rectum was dissected free from its attachment to all adjacent structures well down into the depths of the pelvis. The fetal abdomen was then closed with a single continuous suture of 6-0 silk. The fetus was returned to its compartment in the uterine tube, and the uterus was repaired with a continuous suture of 3-0 silk. Feti of the sham group(those in the left uterine tube) were subjected to the same procedure, with the exception that the sigmoid mesentery was not divided and the rectum was not separated from its immediate attachments in the pelvis. Control animals were those remaining feti that had been left undisturbed in the uterine tubes. The maternal abdomen was then closed in two layers with 3-0 silk, both continuous with one for the peritoneum and midline fascia and the other as a subcuticular stitch. On the 30th or 31st day of gestation, the pregnant rabbits were sacrificed with an overdose of intraperitoneal pentobarbital. Careful necropsies were then performed on all the shams and experimental feti, as well as on one or two of the non-operated feti which then served as controls.
INDEX W O R D S : Rectal stenosis; rectal atresia.
F T H E S E V E R A L etiologic mechanisms proposed as an explanation for the development of anorectal atresia, each with its individual variations has been used to explain the occurrence of all forms of the anomaly. ~-3 Only in recent years has it been suggested that more than one cause might be responsible for the different types of anal atresia now recognized. 4'5 The studies of Louw and Barnard were the first to demonstrate that the majority of atresias of jejunum, ileum, and colon are probably the result of mesenteric vascular accidents during intrauterine life. 6 The possibility that similar local ischemia might be responsible for the high rectal atresias has also been mentioned. 5
O
RESULTS
O f t h e 3 2 p r e g n a n t r a b b i t s , feti c o u l d b e r e c o v e r e d f r o m o n l y 24. T h e r e w e r e a t o t a l o f 38 e x p e r i m e n t a l s , 2 6 s h a m s , a n d 28 c o n t r o l s . E x c l u s i v e o f 13 m a c e r a t e d feti, a n a b n o r m a l r e c t u m w a s f o u n d in o n l y o n e s p e c i m e n o u t o f a t o t a l o f 54 a n i m a l s in t h e c o m b i n e d c o n t r o l a n d s h a m g r o u p s ( T a b l e 1). I n t h i s o n e e x c e p t i o n , a f e t u s w i t h r e c t a l s t e n o s i s , a n e n e r g e t i c a t t e m p t to isolate the rectosigmoid had inadvertently c r e a t e d a t e a r in t h e m e s e n t e r y o f t h e s i g m o i d c o l o n a n d m a y t h e r e b y h a v e in a c t u a l i t y c o n verted this fetus into an experimental animal. O f t h e 38 feti in t h e e x p e r i m e n t a l g r o u p , a n o r m a l r e c t u m d e v e l o p e d in o n l y t h r e e a n i m a l s ( T a b l e 1). T h e r e w e r e 8 w i t h m a c e r a t e d a b d o m i -
METHODS
Thirty-two pregnant rabbits were anesthetized with intraperitoneal sodium pentobarbital (20-30 mg/kg of body weight) and were then subjected to laparotomy under sterile conditions on their 24th to 26th day of gestation. Without any attempt at preserving amniotic fluid, longitudinal incisions were made through the uterine wall over the rumps of one or two contained feti in each of the tubes. The lower half of the fetus was extracted, and an incision was made through the fetal abdominal wall in the right lower quadrant. Using applicator sticks moistened with saline, viscera were retracted superiorly so that the sigmoid colon could be
Journal of Pediatric Surgery, Vol. 18, No. 1 (February), 1983
From the Department of Surgery, Emory University School of Medicine, Atlanta, Georgia, and the Department of Paediatric Surgery, Institute of Child Health. University of London, London, England. Presented before the XXIX Annual Congress of the British Association of Paediatric Surgeons, Madrid, Spain, July 21-23, 1982. Address reprint requests to H, Harlan Stone, Department of Surgery, Emory University School of Medicine, 69 Butler St., Atlanta, Ga. 30303. 9 1983 by Grune & Stratton, Inc. 89
90
STONE AND WILKINSON
Table 1. Preliminary Results From Ischemia of the
Table 2. Status of the Rectum in Pelvic Masses
Fetal Rectum Status
Experimental
Normal rectum
Sham
Control
Normal rectum
3
18
22
Rectal atresia
5
--
--
Rectal stenosis Pelvic mass Macerated viscera Total
5 17
1* --
0
Apparent rectal atresia Apparent rectal stenosis Total
12 5 t7
---
8
7
6
38
26
28
*Probably the result of excessive mobilization of the rectosigmold colon.
nal viscera, 17 with a pelvic mass, and 5 with rectal stenosis. A n a d d [ t i o n a l f i v e had high rectal atresias, t h a t is, the r e c t u m was absent, b u t a well-formed anus e n d e d as a blind pouch j u s t at the level of the levator ani muscle, Dissection o f 17 pelvic masses in the experim e n t a l group revealed 12 a p p a r e n t high rectal atresias and 5 instances o f r e c t a l stenosis ( T a b l e 2). W i t h the a d d i t i o n of these findings f r o m dissection of the p d v i c mass, the e x p e r i m e n t a l p r o c e d u r e was noted to have p r o d u c e d a high
r e c t a l a t r e s i a and 17 and a rectal stenosis in 10 o f the animals. COMMENT
M o s t of the large clinical series have r e p o r t e d t h a t associated a n o m a l i e s and rectal fistulas a r e u n c o m m o n in congenital a n a l stenosis a n d the high rectal atresia. 4'7's This would indeed suggest a difference in the etiologic m e c h a n i s m s for the production o f such anomalies. T h e successful creation of rectal stenosis and the high rectal atresia in e x p e r i m e n t a l a n i m a l s a d d s further credence to this supposition. Fistulas a n d o t h e r associated a n o m a l i e s did not develop. Thus, the cause of a n a l stenosis a n d the high rectal a t r e s i a m a y well be based on an ischemic insult to the r e c t u m d u r i n g fetal life.
REFERENCES
1. Arey LB: Developmental Anatomy (ed 5). Philadelphia, W.B. Saunders, 1947, pp 225, 263 2. Bill AH Jr, Johnson RJ: Failure of migration of the rectal opening as a cause for most cases of imperforate anus. Surg Gynecol Obstet 106:643-651, 1958 3. Romualdi PA: A new heretical approach to pathogenesis of the malformation of anus and rectum. Riv Chir Pediatr 4:113-116, 1962 4. Kiesewetter WB, Turner CR, Sieber WK: Imperforate anus; review of a 16 year experience with 146 patients. Am J Surg 107:412--421, 1964
5. Santulli TV, Schullinger JN, Amoury RA: Malformations of the anus and rectum. Surg Clin North Am 45:12531271, 1965 6. Louw JH, Barnard CA: Congenital intestinal atresia; observations on its origin. Lancet 2:1065-1067, 1955 7. Cozzi F, Wilkinson AW: Congenital abnormalities of anus and rectum; mortality and function. Br Med J 1:144147, 1968 8. Moore TC, Lawrence EA: Congenital malformations of the rectum and anus; associated anomalies encountered in a series of 120 cases. Surg Gynecol Obstet 95:281-288, 1952
Atlanta, Georgia, and London, England 9 Clinical reviews have suggested that there are different causes for the various types of anorectal atresia and stenosis, Such inferences have primarily been based upon t h e presence or absence of associated fistulas and other anogenital, urinary, and more remote congenital defects. Rectal stenosis and atresia of the middle a n d / o r upper third of the rectum w e r e produced in 27 of 38 rabbit feti subjected to partial to complete interruption of the blood supply to the rectosigmoid colon b e t w e e n the 24th asnd 26th day of gestation. Such experimental feti w e r e located in the right tube, while a sham laparotomy was performed during t h e same maternal operation on 26 feti located in the left tube. An additional undisturbed 28 feti w e r e available in both tubes to serve as controls. No other anomalies w e r e produced in any group. These findings suggest that local ischemia, occurring late during fetal life, may well he the mechanism responsible for the creation of rectal stenosis and atresia of t h e middle a n d / o r upper rectum.
identified and isolated. For feti in the experimental group (those in the right uterine tube), the sigmoid mesentery was divided; and the rectum was dissected free from its attachment to all adjacent structures well down into the depths of the pelvis. The fetal abdomen was then closed with a single continuous suture of 6-0 silk. The fetus was returned to its compartment in the uterine tube, and the uterus was repaired with a continuous suture of 3-0 silk. Feti of the sham group(those in the left uterine tube) were subjected to the same procedure, with the exception that the sigmoid mesentery was not divided and the rectum was not separated from its immediate attachments in the pelvis. Control animals were those remaining feti that had been left undisturbed in the uterine tubes. The maternal abdomen was then closed in two layers with 3-0 silk, both continuous with one for the peritoneum and midline fascia and the other as a subcuticular stitch. On the 30th or 31st day of gestation, the pregnant rabbits were sacrificed with an overdose of intraperitoneal pentobarbital. Careful necropsies were then performed on all the shams and experimental feti, as well as on one or two of the non-operated feti which then served as controls.
INDEX W O R D S : Rectal stenosis; rectal atresia.
F T H E S E V E R A L etiologic mechanisms proposed as an explanation for the development of anorectal atresia, each with its individual variations has been used to explain the occurrence of all forms of the anomaly. ~-3 Only in recent years has it been suggested that more than one cause might be responsible for the different types of anal atresia now recognized. 4'5 The studies of Louw and Barnard were the first to demonstrate that the majority of atresias of jejunum, ileum, and colon are probably the result of mesenteric vascular accidents during intrauterine life. 6 The possibility that similar local ischemia might be responsible for the high rectal atresias has also been mentioned. 5
O
RESULTS
O f t h e 3 2 p r e g n a n t r a b b i t s , feti c o u l d b e r e c o v e r e d f r o m o n l y 24. T h e r e w e r e a t o t a l o f 38 e x p e r i m e n t a l s , 2 6 s h a m s , a n d 28 c o n t r o l s . E x c l u s i v e o f 13 m a c e r a t e d feti, a n a b n o r m a l r e c t u m w a s f o u n d in o n l y o n e s p e c i m e n o u t o f a t o t a l o f 54 a n i m a l s in t h e c o m b i n e d c o n t r o l a n d s h a m g r o u p s ( T a b l e 1). I n t h i s o n e e x c e p t i o n , a f e t u s w i t h r e c t a l s t e n o s i s , a n e n e r g e t i c a t t e m p t to isolate the rectosigmoid had inadvertently c r e a t e d a t e a r in t h e m e s e n t e r y o f t h e s i g m o i d c o l o n a n d m a y t h e r e b y h a v e in a c t u a l i t y c o n verted this fetus into an experimental animal. O f t h e 38 feti in t h e e x p e r i m e n t a l g r o u p , a n o r m a l r e c t u m d e v e l o p e d in o n l y t h r e e a n i m a l s ( T a b l e 1). T h e r e w e r e 8 w i t h m a c e r a t e d a b d o m i -
METHODS
Thirty-two pregnant rabbits were anesthetized with intraperitoneal sodium pentobarbital (20-30 mg/kg of body weight) and were then subjected to laparotomy under sterile conditions on their 24th to 26th day of gestation. Without any attempt at preserving amniotic fluid, longitudinal incisions were made through the uterine wall over the rumps of one or two contained feti in each of the tubes. The lower half of the fetus was extracted, and an incision was made through the fetal abdominal wall in the right lower quadrant. Using applicator sticks moistened with saline, viscera were retracted superiorly so that the sigmoid colon could be
Journal of Pediatric Surgery, Vol. 18, No. 1 (February), 1983
From the Department of Surgery, Emory University School of Medicine, Atlanta, Georgia, and the Department of Paediatric Surgery, Institute of Child Health. University of London, London, England. Presented before the XXIX Annual Congress of the British Association of Paediatric Surgeons, Madrid, Spain, July 21-23, 1982. Address reprint requests to H, Harlan Stone, Department of Surgery, Emory University School of Medicine, 69 Butler St., Atlanta, Ga. 30303. 9 1983 by Grune & Stratton, Inc. 89
90
STONE AND WILKINSON
Table 1. Preliminary Results From Ischemia of the
Table 2. Status of the Rectum in Pelvic Masses
Fetal Rectum Status
Experimental
Normal rectum
Sham
Control
Normal rectum
3
18
22
Rectal atresia
5
--
--
Rectal stenosis Pelvic mass Macerated viscera Total
5 17
1* --
0
Apparent rectal atresia Apparent rectal stenosis Total
12 5 t7
---
8
7
6
38
26
28
*Probably the result of excessive mobilization of the rectosigmold colon.
nal viscera, 17 with a pelvic mass, and 5 with rectal stenosis. A n a d d [ t i o n a l f i v e had high rectal atresias, t h a t is, the r e c t u m was absent, b u t a well-formed anus e n d e d as a blind pouch j u s t at the level of the levator ani muscle, Dissection o f 17 pelvic masses in the experim e n t a l group revealed 12 a p p a r e n t high rectal atresias and 5 instances o f r e c t a l stenosis ( T a b l e 2). W i t h the a d d i t i o n of these findings f r o m dissection of the p d v i c mass, the e x p e r i m e n t a l p r o c e d u r e was noted to have p r o d u c e d a high
r e c t a l a t r e s i a and 17 and a rectal stenosis in 10 o f the animals. COMMENT
M o s t of the large clinical series have r e p o r t e d t h a t associated a n o m a l i e s and rectal fistulas a r e u n c o m m o n in congenital a n a l stenosis a n d the high rectal atresia. 4'7's This would indeed suggest a difference in the etiologic m e c h a n i s m s for the production o f such anomalies. T h e successful creation of rectal stenosis and the high rectal atresia in e x p e r i m e n t a l a n i m a l s a d d s further credence to this supposition. Fistulas a n d o t h e r associated a n o m a l i e s did not develop. Thus, the cause of a n a l stenosis a n d the high rectal a t r e s i a m a y well be based on an ischemic insult to the r e c t u m d u r i n g fetal life.
REFERENCES
1. Arey LB: Developmental Anatomy (ed 5). Philadelphia, W.B. Saunders, 1947, pp 225, 263 2. Bill AH Jr, Johnson RJ: Failure of migration of the rectal opening as a cause for most cases of imperforate anus. Surg Gynecol Obstet 106:643-651, 1958 3. Romualdi PA: A new heretical approach to pathogenesis of the malformation of anus and rectum. Riv Chir Pediatr 4:113-116, 1962 4. Kiesewetter WB, Turner CR, Sieber WK: Imperforate anus; review of a 16 year experience with 146 patients. Am J Surg 107:412--421, 1964
5. Santulli TV, Schullinger JN, Amoury RA: Malformations of the anus and rectum. Surg Clin North Am 45:12531271, 1965 6. Louw JH, Barnard CA: Congenital intestinal atresia; observations on its origin. Lancet 2:1065-1067, 1955 7. Cozzi F, Wilkinson AW: Congenital abnormalities of anus and rectum; mortality and function. Br Med J 1:144147, 1968 8. Moore TC, Lawrence EA: Congenital malformations of the rectum and anus; associated anomalies encountered in a series of 120 cases. Surg Gynecol Obstet 95:281-288, 1952