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Is preserving the entire aganglionic colon reasonable in the surgicaltreatment of total colonic aganglionosis?
Is Preserving the Entire Aganglionic Colon Reasonable in the Surgical Treatment of Total Colonic Aganglionosis? By Seiichi G o t o and Jay L. Grosfeld Indianapolis, Indiana
9 Clinical reports describe an increased incidence of severe enterocolitis in infants w i t h t o t a l colonic aganglionosis (TCA) following the Martin extended Duhamel procedure using the entire aganglionic colon. This study evaluates the efficacy of this procedure in an experimental model of T C A in comparison w i t h an antimesenteric aganglionic colon patch in rats. TCA was produced by serosal application of 0.1% benzalkonium chloride in 18 SpragueDawley rats (250 g). Five additional rats served as operated controls. Ileoanal pull-through was performed in 18 T C A rats, in conjunction w i t h t h e M a r t i n extended Duhamel procedure using the entire colon in six rats, with an aganglionic colon patch in nine (using the right [3 rats], transverse [3 rats] and left [3 ratsJ colon), and w i t h o u t other procedures in three rats. Animals w e r e evaluated for survival, weight change, food intake, stool consistency and volume, barium enema, complete blood cell c o u n t (CBC}, t o t a l protein, and serum electrolytes at 4 and 12 weeks. Survival was 83% (5/6) rats w i t h t h e M a r t i n procedure, 100% in t h e nine rats w i t h various colon patches, zero in three rats with ileonal pull-through alone, and 1 0 0 % in controls. Rats w i t h the M a r t i n procedure gained 2.2 • 3.27% of preoperative weight, while controls gained 11.2 • 0.52% at 4 weeks. All other rats showed an early weight loss, A t 12 w e e k s , right and transverse colon patched rats had weight gain. Blood count and laboratory studies w e r e similar in each group. Barium enema showed rapid t r a n s i t in rats w i t h ileonal pull-through, and slower transit in rats w i t h colon patches or the Martin procedure. Rats w i t h colon patches had minimal dilatation at the patch site while massive bowel dilatation associated with severe abdominal distention and explosive diarrhea was observed in rats with the Martin procedure. These latter findings are similar to those observed by some authors in the clinical setting following the Martin operation, Although the Martin procedure may be a rational method of treatment in TCA, these data suggest that segmental right and transverse aganglionic colon patches are effective alternatives and may avoid the complications observed with the M a r t i n e x t e n d e d Duhamel operation. 9 1987 b y Grune & Stratton, Inc. INDEX WORDS: Hirschsprung's disease; total colonic aganglionosis; aganglionic patch enteroplasty; Martin modification of Duhamel procedure; enterocolitis of Hirschsprung's disease.
PPROXIMATELY 8% to 10% of infants with A Hirschsprung s disease have total colonic aganglionosis (TCA). These patients have a considerable morbidity and mortality especially in instances of aganglionosis extending to the mid or proximal small intestine./ 3 The use of an aganglionic colon patch with either left or right colon slows transit time and prevents water and sodium losses in both patients and experimental animals with TCA. 4g Since the patched area Journal of Pediatric Surgery, Vol 22, No 7 (July), 1987: pp 623-627
has both absorptive and propulsive activities, it seems reasonable to preserve these aganglionic colon segments in instances of TCA in order to improve bowel function. In babies with TCA, Martin 9 has advocated preserving the entire aganglionic colon with a sideto-side anastomosis to the normally innervated small intestine. The efficacy of this unique concept, however, has not yet been confirmed, because a suitable experimental model for Hirschsprung's disease has been lacking. Recently, we reported a method to produce a TCA model in the rat using topically applied benzalkonium chloride solution) ~ This study compares the efficacy of the Martin procedure with ileoanal pullthrough alone and pull-through plus an aganglionic patch enteroplasty in rats with experimental TCA. MATERIALS AND METHODS
Thirty-six male Sprague-Dawley rats weighing 250 to 300 g were used. Animals were housed individually in stainless steel cages and allowed laboratory chow and water ad libitum. After overnight fasting, midline laparotomy was performed under general anesthesia with intramuscular injection of ketamine (80 mg/kg). In 19 rats, TCA was produced by stage treatment using topical application 0.1% benzalkonium chloride solution (using the technique of Goto et al ~~and a side-to-side ileocolonic anastomosis was performed (Fig 1). The first stage produces aganglionosis of the anorectum and left half of the colon. After a seven-day interval, a side-to-side ileo-left half of the colon anastomosis was performed in an isoperistaltic direction with an inner layer of continuous 6-0 silk sutures and an outer layer of interrupted 6-0 silk sutures, with the ileocecal junction ligated. Then, seven days later, the right half of the colon was similarly treated by topical application of 0.1% benzalkonium chloride solution as the third step. After seven more days, a side-to-side ileo-right half of the colon anastomosis was performed to complete the anastomosis of the ileum to the entire aganglionic colon. During the course of developing TCA, 13 out of 19 rats died due to technical dilficulties. Nine died after the final step, three after the second step, and one after the third step. Finally, 4 weeks after completing the fourth step, ileoendorectal pull-through (IEP) with preservation of the entire aganglionic colon was performed in the six surviving rats (Fig 2). In order to compare this TCA model with other IEP groups with
From the Section of Pediatric Surgery, Department of Surgery, Indiana University Medical Center and the James Whitcomb Riley Hospital for Children, Indianapolis, IN. Presented at the 35th Annual Meeting of the Surgical Section of the American Academy of Pediatrics, Washington, DC, November 1-2, 1986. Address reprint requests to Jay L. Grosfeld, MD, Surgeonin-Chief J.W. Riley Hospital for Children, 702 Barnhill Dr (K21), Indianapolis, IN 46223. 9 1987 by Grune & Stratton, Inc. 0022-3468/87/2207-0011503.00/0 623
624
GOTO AND GROSFELD
remov cm pull - t h r o u g h
1 st Step
2 nd
Step
Fig 2.
Final step includes excision of cecum and IEP.
evaluated for weight gain as a long-term follow-up. All data were expressed as mean +SEM, and statistical evaluation of the data was performed by the Student's t-test. RESULTS
3rd
Step
4th
Step
Fig 1. Staged technique in the development of TCA induced by topical application of 0.1% benzalkonium chloride.
TCA, we used 12 additional rats; three underwent total colectomy and IEP pull-through alone and nine had an ileoanal endorectal pull-through plus a 3.0 cm antimesenteric aganglionic colon patch using right, transverse, and left colon (three in each group), prepared in a previously described manner, l~ Five sham operated rats (SH) that underwent transection of terminal ileum and reanastomosis acted as operated controls without IEP. All animals were fed laboratory chow and had free access to 10% High Nitrogen Vivonex (HNV); (Norwich Eaton Pharmaceuticals, Inc, Norwich, NY) from postoperative day 1 to 5 weeks. Thereafter, they were allowed only standard rat chow and water ad libitum. All rats were weighed daily at the same time early in the morning. At 4 weeks post-IEP, rats were evaluated for survival, body weight change, recovery rate (% of rats with restoration of initial body weight), daily food intake, stool consistency, perineal skin findings and intestinal transit time by barium marker, blood hemoglobin, serum electrolytes, and total protein. At 12 weeks, all animals were
Survival at 4 weeks was 83.3% (5/6) post-lEP with Martin's entire colon side-to-side anastomosis and 100% (5/5) in SH controls. The mean initial body weight before the final operation was 349.0 +_ 14.10 g in TCA rats with IEP plus Martin procedure and 352.4 +_ 4.68 g in SH controls. T C A rats with IEP plus Martin-type anastomosis showed a temporary early weight loss of about 10%, then an upward increase. SH rats showed a steady weight increase. The rates of weight increase were similar after seven days. Change in percent body weight at 4 weeks was +2.2 _+ 3.27% in IEP with the Martin procedure and + 11.2 __+0.52% in SH controls (P < .05). The number of days required for initial body weight to be restored were 4.6 _+ 3.11 in SH controls and 19.6 _+ 5.95 in rats with the Martin procedure (P < .01). Recovery rate at 4 weeks was 100% (5/5) in SH but was 40% (2/5) in IEP with the Martin anastomosis. None of the other groups (IEP alone or with patches) restored their baseline weight at 4 weeks. Data concerning abdominal findings, stool consistency, and development of perineal excoriation are summarized in Table 1. The differences in food intake were not significant. Stool volumes were also similar. However, rats with IEP plus the Martin procedure
Table 1. Summary of Clinical Findings
SH Martin Patch Right colon
Transverse colon Left colon IEP
Abdominal
Stool
Excoriated
Findings
Pattern
Perianal Skin
No distention Abdomen distention
Solid Liquid
None
No distention No distention No distention No distention
Mushy Mushy Liquid Liquid
Minimal Minimal Minimal to moderate Severe
Rats with the Martin procedure had abdominal distention, liquid stools, and moderate perianal skin excoriation.
Moderate
TOTAL COLONIC AGANGLIONOSIS
never developed a solid stool as seen in SH controls, but always had diarrhea. Barium enema in post-IEP rats with the Martin operation showed significant dilatation of the entire colon and distal ileum (Fig 3). Intestinal transit time from the stomach to the anus was similar (IEP with the Martin procedure: more than 8 hours, 30 minutes [n = 4], >6 hours [n = 1]; SH: more than 8 hours, 30 minutes [n = 4], >7 hours [n = 1]). All patched rats had a prolonged transit time when compared with rats following colectomy and IEP alone. IEP only had a mean transit time of 31/2 hours while right and transverse colon patched rats had transit time of greater than 81/2 hours similar to the Martin procedure animals. Rats with a left colon patch had a more rapid transit time (51/2 hours). All the rats with prolonged transit time (more than 8 hours, 30 minutes) completely evacuated barium within 24 hours. Blood hemoglobin, serum electrolytes, and total protein were within normal levels in all groups. Results of long-term follow-up are summarized in Table 2. Four of five rats with IEP and the Martin procedure (entire colon used for anastomosis) showed a significant weight gain at 12 weeks, while only one of three rats (33%) with IEP and a segmental aganglionic right colon or transverse colon patch, and 0% (0/3) with IEP and a left colon patch had a similar weight gain. All three rats that underwent IEP without any type of colon patch (Martin or segmental) all lost
Fig 3. Rats with IEP and the Martin procedure developed significant dilatation of the side-to-side anastomosis of the entire aganglionic colon to the pull-through ileum.
625
Table 2. Weight Gain or Loss 4 Weeks
12 Weeks
SH
+
+
Martin
+
+
Patch Right colon
--
+
Transverse colon
--
+
Left colon
--
--
--
All died
IEP
Rats with the Martin procedure showed weight gain at 4 and 12 weeks. Right and transverse colon patches showed early weight loss and some weight gain at 12 weeks. All IEP rats lost weight and died.
weight, had diarrhea, severe perianal excoriation, and died during the course of this study. Rats with IEP and the Martin procedure never had solid stools, had moderate perianal excoriation and, in addition, 60% (3/5) of rats showed severe abdominal distention (Fig 4A and B). Rats with segmental patches all survived, had mushy stools, minimal perianal excoriation, and no evidence of abdominal distention. DISCUSSION
The care of the infant with TCA remains a difficult management problem especially when the aganglionic process extends to the more proximal regions of the small intestine. Diagnosis may be difficult and fluid and electrolyte disturbances and nutrition have been significant problems resulting in a high morbidity and mortality (25% to 65%). 13 Infants with TCA usually require enhanced nutritional support using total parenteral nutrition or enteral nutrition with highly defined elemental diets. 8'11 These management problems were also noted in the experimental setting in our rat model. It is difficult to keep post-IEP rats on total parenteral nutrition for extended periods of time, limiting its applicability as a support source in attempting to evaluate long-term results (eg, > 12 weeks). In a recent unpublished pilot study, we have observed that an elemental diet used as a nutritional supplement results in an improved survival in the rat following total eolectomy and IEP. All the experimental animals in this present study were therefore managed with an elemental diet for the first 5 weeks, in addition to a solid diet using standard rat chow. After 5 weeks, all the animals received only water and rat chow ad libitum. The data from this study show that the Martin operation (using the entire aganglionic colon in a side-to-side anastomosis with the pull-through ileum) may be effective in the surgical treatment of TCA. The survival rate (83%) and transit time was acceptable, and the recovery rate for weight was 40% at 4 weeks and 100% at 12 weeks. Since rats with the Martin
626
GOTO AND GROSFELD
Fig 4. (A) Significant abdmonial distention w a s observed in rats with the Martin procedure (right) when compared with unresected controls (left) and other pull-through groups. (B) Gross appearance of the dilated bowel in a rat with the Martin procedure.
procedure gained weight somewhat better than the other groups in this study, preserving the entire aganglionic colon may be a useful adjunct. However, rats with IEP and Martin's procedure also showed severe abdominal distention, significant dilation of the entire side-to-side ileocolonic anastomosis, persistent diarrhea, and perianal excoriation. These observations may be due to inflammatory changes related to retention in the entire aganglionic colon resulting in a pattern quite similar to clinical instances of severe enterocolitis. Clinical reports regarding the efficacy of the Martin procedure in infants with TCA have raised concern because of a high incidence of debilitating enterocolitis complicat-
ing this operation. 3'~u2 The fact that segmental antimesenteric aganglionic intestinal patches (as advocated by Kimura, 4 Boley: Kottmeier et al, 6 and others 7,*'a~ may slow transit time at the patch site and are capable of fluid and electrolyte absorption in both the clinical and experimental 1~setting suggest that this technique may be an effective and attractive alternative procedure in babies with TCA. Previous data from our laboratory indicate that both sodium and water absorption does occur in rats with aganglionic colon patches, l~ The right colon is superior to both the transverse and left colon as a patch and should preferably be used in instances of TCA when possible if this technique is applied) '8'1~ This is the first successful experimental report of IEP with preservation of the entire aganglionic colon in the rat. These data indicate that Martin's concept of preserving the entire aganglionic colon may be rational for the surgical treatment of T C A from the point of view of survival, weight gain, and transit time. However, enterocolitis (characterized by abdominal distention, explosive diarrhea, and dilated bowel on abdominal x-ray) observed both in this experiment and the clinical setting (probably related to inflammation and/ or bacterial stasis in the long side-to-side ileocolonic anastomosis) remains a problem that requires further investigation. Although Heath et al u have demonstrated an increased transport of electrolytes in aganglionic colon of patients with Hirschsprung's disease, this preliminary report did not study nutrient, water, and electrolyte absorption, bacterial colonization, or histologic changes in the mucosa of the aganglionic segment. Although there were only a small number of animals used in each of these preliminary experiments, definite trends were observed. Further investigation of these adjunctive procedures are currently in progress and may shed additional light on the subject. These modifications of surgical treatment of infants with TCA (with extension of the aganglionic process to the proximal small bowel) have resulted in an improved survival. In addition, a recent report by Ziegler and associates ~4 suggests that myotomy-myectomy in proximal small bowel aganglionosis may also have a role in the correction of this condition and result in survival of patients previously considered hopeless cases. ACKNOWLEDGMENT
Full credit should be given to Drs Martin,9 Kimura,4 Kottmeier,6 Boley,5and Ziegler14for their innovativecontributionsin the management of this difficultclinical problem.
REFERENCES
h Martin LW: Surgical management of Hirschsprung's disease involvingthe small intestine. Arch Surg 97:183-189, 1968
2. WalkerA, KempsonR, TernbergJ: Aganglionosisof the small intestine. Surgery60:444-457, 1966
TOTAL COLONIC AGANGLIONOSlS
3. Careskey J, Weber TR, Grosfeld JL: Total colonic aganglionosis: Analysis of 16 cases. Am J Surg 143:160-168, 1982 4. Kimura K, Nishijima E, Muraji T, et al: A new surgical approach to extensive aganglionosis. J Pediatr Surg 16:840-843, 1981 5. Boley S J: A new operative approach to total aganglionosis of the colon. Surg Gynecol Obstet 159:481-484, 1984 6. Kottmeier PK, Jongco B, Velcek FT, et al: Absorptive function of the aganglionic ileum. J Pediatr Surg 16:275-278, 1981 7. Shandling B: Total colonic aganglionosis: A new operation. J Pediatr Surg 19:503-505, 1984 8. Grosfeld JL, Rescorla F J, West KW: Short bowel syndrome in infancy and childhood. Am J Surg 151:41-46, 1986 9. Martin LW: Total colonic aganglionosis; preservation and utilization of the entire colon. J Pediatr Surg 17:635-637, 1982
627
10. Goto S, Gunter M, Scherer LR, et al: Surgical treatment of total colonic aganglionosis: Efficacy of aganglionic patch enteroplasty in the rat. J Pediatr Surg 21:601-607, 1986 11. Vane DW, Grosfeld JL: Hirschsprung's disease: Experience with the Duhamel procedure in 195 cases. Pediatr Surg Int 1:95-99, 1986 12. Davies MRQ, Cywes S: Inadequate pouch emptying following Martin's pull-through procedure for intestinal aganglionosis. J Pediatr Surg 18:14-20, 1983 13. Heath AL, Spitz L, Mella PJ: The absorptive function of colonic aganglionic intestine: Are the Duhamel and Martin procedures rational? J Pediatr Surg 20:34-36, 1985 14. Ziegler M, Ross A, Bishop H: Total intestinal aganglionosis: A new technique for prolonged survival. Presented at the 17th Annual Meeting of the American Pediatric Surgical Association, Toronto, Canada, May 1986, J Pediatr Surg (in press)
9 Clinical reports describe an increased incidence of severe enterocolitis in infants w i t h t o t a l colonic aganglionosis (TCA) following the Martin extended Duhamel procedure using the entire aganglionic colon. This study evaluates the efficacy of this procedure in an experimental model of T C A in comparison w i t h an antimesenteric aganglionic colon patch in rats. TCA was produced by serosal application of 0.1% benzalkonium chloride in 18 SpragueDawley rats (250 g). Five additional rats served as operated controls. Ileoanal pull-through was performed in 18 T C A rats, in conjunction w i t h t h e M a r t i n extended Duhamel procedure using the entire colon in six rats, with an aganglionic colon patch in nine (using the right [3 rats], transverse [3 rats] and left [3 ratsJ colon), and w i t h o u t other procedures in three rats. Animals w e r e evaluated for survival, weight change, food intake, stool consistency and volume, barium enema, complete blood cell c o u n t (CBC}, t o t a l protein, and serum electrolytes at 4 and 12 weeks. Survival was 83% (5/6) rats w i t h t h e M a r t i n procedure, 100% in t h e nine rats w i t h various colon patches, zero in three rats with ileonal pull-through alone, and 1 0 0 % in controls. Rats w i t h the M a r t i n procedure gained 2.2 • 3.27% of preoperative weight, while controls gained 11.2 • 0.52% at 4 weeks. All other rats showed an early weight loss, A t 12 w e e k s , right and transverse colon patched rats had weight gain. Blood count and laboratory studies w e r e similar in each group. Barium enema showed rapid t r a n s i t in rats w i t h ileonal pull-through, and slower transit in rats w i t h colon patches or the Martin procedure. Rats w i t h colon patches had minimal dilatation at the patch site while massive bowel dilatation associated with severe abdominal distention and explosive diarrhea was observed in rats with the Martin procedure. These latter findings are similar to those observed by some authors in the clinical setting following the Martin operation, Although the Martin procedure may be a rational method of treatment in TCA, these data suggest that segmental right and transverse aganglionic colon patches are effective alternatives and may avoid the complications observed with the M a r t i n e x t e n d e d Duhamel operation. 9 1987 b y Grune & Stratton, Inc. INDEX WORDS: Hirschsprung's disease; total colonic aganglionosis; aganglionic patch enteroplasty; Martin modification of Duhamel procedure; enterocolitis of Hirschsprung's disease.
PPROXIMATELY 8% to 10% of infants with A Hirschsprung s disease have total colonic aganglionosis (TCA). These patients have a considerable morbidity and mortality especially in instances of aganglionosis extending to the mid or proximal small intestine./ 3 The use of an aganglionic colon patch with either left or right colon slows transit time and prevents water and sodium losses in both patients and experimental animals with TCA. 4g Since the patched area Journal of Pediatric Surgery, Vol 22, No 7 (July), 1987: pp 623-627
has both absorptive and propulsive activities, it seems reasonable to preserve these aganglionic colon segments in instances of TCA in order to improve bowel function. In babies with TCA, Martin 9 has advocated preserving the entire aganglionic colon with a sideto-side anastomosis to the normally innervated small intestine. The efficacy of this unique concept, however, has not yet been confirmed, because a suitable experimental model for Hirschsprung's disease has been lacking. Recently, we reported a method to produce a TCA model in the rat using topically applied benzalkonium chloride solution) ~ This study compares the efficacy of the Martin procedure with ileoanal pullthrough alone and pull-through plus an aganglionic patch enteroplasty in rats with experimental TCA. MATERIALS AND METHODS
Thirty-six male Sprague-Dawley rats weighing 250 to 300 g were used. Animals were housed individually in stainless steel cages and allowed laboratory chow and water ad libitum. After overnight fasting, midline laparotomy was performed under general anesthesia with intramuscular injection of ketamine (80 mg/kg). In 19 rats, TCA was produced by stage treatment using topical application 0.1% benzalkonium chloride solution (using the technique of Goto et al ~~and a side-to-side ileocolonic anastomosis was performed (Fig 1). The first stage produces aganglionosis of the anorectum and left half of the colon. After a seven-day interval, a side-to-side ileo-left half of the colon anastomosis was performed in an isoperistaltic direction with an inner layer of continuous 6-0 silk sutures and an outer layer of interrupted 6-0 silk sutures, with the ileocecal junction ligated. Then, seven days later, the right half of the colon was similarly treated by topical application of 0.1% benzalkonium chloride solution as the third step. After seven more days, a side-to-side ileo-right half of the colon anastomosis was performed to complete the anastomosis of the ileum to the entire aganglionic colon. During the course of developing TCA, 13 out of 19 rats died due to technical dilficulties. Nine died after the final step, three after the second step, and one after the third step. Finally, 4 weeks after completing the fourth step, ileoendorectal pull-through (IEP) with preservation of the entire aganglionic colon was performed in the six surviving rats (Fig 2). In order to compare this TCA model with other IEP groups with
From the Section of Pediatric Surgery, Department of Surgery, Indiana University Medical Center and the James Whitcomb Riley Hospital for Children, Indianapolis, IN. Presented at the 35th Annual Meeting of the Surgical Section of the American Academy of Pediatrics, Washington, DC, November 1-2, 1986. Address reprint requests to Jay L. Grosfeld, MD, Surgeonin-Chief J.W. Riley Hospital for Children, 702 Barnhill Dr (K21), Indianapolis, IN 46223. 9 1987 by Grune & Stratton, Inc. 0022-3468/87/2207-0011503.00/0 623
624
GOTO AND GROSFELD
remov cm pull - t h r o u g h
1 st Step
2 nd
Step
Fig 2.
Final step includes excision of cecum and IEP.
evaluated for weight gain as a long-term follow-up. All data were expressed as mean +SEM, and statistical evaluation of the data was performed by the Student's t-test. RESULTS
3rd
Step
4th
Step
Fig 1. Staged technique in the development of TCA induced by topical application of 0.1% benzalkonium chloride.
TCA, we used 12 additional rats; three underwent total colectomy and IEP pull-through alone and nine had an ileoanal endorectal pull-through plus a 3.0 cm antimesenteric aganglionic colon patch using right, transverse, and left colon (three in each group), prepared in a previously described manner, l~ Five sham operated rats (SH) that underwent transection of terminal ileum and reanastomosis acted as operated controls without IEP. All animals were fed laboratory chow and had free access to 10% High Nitrogen Vivonex (HNV); (Norwich Eaton Pharmaceuticals, Inc, Norwich, NY) from postoperative day 1 to 5 weeks. Thereafter, they were allowed only standard rat chow and water ad libitum. All rats were weighed daily at the same time early in the morning. At 4 weeks post-IEP, rats were evaluated for survival, body weight change, recovery rate (% of rats with restoration of initial body weight), daily food intake, stool consistency, perineal skin findings and intestinal transit time by barium marker, blood hemoglobin, serum electrolytes, and total protein. At 12 weeks, all animals were
Survival at 4 weeks was 83.3% (5/6) post-lEP with Martin's entire colon side-to-side anastomosis and 100% (5/5) in SH controls. The mean initial body weight before the final operation was 349.0 +_ 14.10 g in TCA rats with IEP plus Martin procedure and 352.4 +_ 4.68 g in SH controls. T C A rats with IEP plus Martin-type anastomosis showed a temporary early weight loss of about 10%, then an upward increase. SH rats showed a steady weight increase. The rates of weight increase were similar after seven days. Change in percent body weight at 4 weeks was +2.2 _+ 3.27% in IEP with the Martin procedure and + 11.2 __+0.52% in SH controls (P < .05). The number of days required for initial body weight to be restored were 4.6 _+ 3.11 in SH controls and 19.6 _+ 5.95 in rats with the Martin procedure (P < .01). Recovery rate at 4 weeks was 100% (5/5) in SH but was 40% (2/5) in IEP with the Martin anastomosis. None of the other groups (IEP alone or with patches) restored their baseline weight at 4 weeks. Data concerning abdominal findings, stool consistency, and development of perineal excoriation are summarized in Table 1. The differences in food intake were not significant. Stool volumes were also similar. However, rats with IEP plus the Martin procedure
Table 1. Summary of Clinical Findings
SH Martin Patch Right colon
Transverse colon Left colon IEP
Abdominal
Stool
Excoriated
Findings
Pattern
Perianal Skin
No distention Abdomen distention
Solid Liquid
None
No distention No distention No distention No distention
Mushy Mushy Liquid Liquid
Minimal Minimal Minimal to moderate Severe
Rats with the Martin procedure had abdominal distention, liquid stools, and moderate perianal skin excoriation.
Moderate
TOTAL COLONIC AGANGLIONOSIS
never developed a solid stool as seen in SH controls, but always had diarrhea. Barium enema in post-IEP rats with the Martin operation showed significant dilatation of the entire colon and distal ileum (Fig 3). Intestinal transit time from the stomach to the anus was similar (IEP with the Martin procedure: more than 8 hours, 30 minutes [n = 4], >6 hours [n = 1]; SH: more than 8 hours, 30 minutes [n = 4], >7 hours [n = 1]). All patched rats had a prolonged transit time when compared with rats following colectomy and IEP alone. IEP only had a mean transit time of 31/2 hours while right and transverse colon patched rats had transit time of greater than 81/2 hours similar to the Martin procedure animals. Rats with a left colon patch had a more rapid transit time (51/2 hours). All the rats with prolonged transit time (more than 8 hours, 30 minutes) completely evacuated barium within 24 hours. Blood hemoglobin, serum electrolytes, and total protein were within normal levels in all groups. Results of long-term follow-up are summarized in Table 2. Four of five rats with IEP and the Martin procedure (entire colon used for anastomosis) showed a significant weight gain at 12 weeks, while only one of three rats (33%) with IEP and a segmental aganglionic right colon or transverse colon patch, and 0% (0/3) with IEP and a left colon patch had a similar weight gain. All three rats that underwent IEP without any type of colon patch (Martin or segmental) all lost
Fig 3. Rats with IEP and the Martin procedure developed significant dilatation of the side-to-side anastomosis of the entire aganglionic colon to the pull-through ileum.
625
Table 2. Weight Gain or Loss 4 Weeks
12 Weeks
SH
+
+
Martin
+
+
Patch Right colon
--
+
Transverse colon
--
+
Left colon
--
--
--
All died
IEP
Rats with the Martin procedure showed weight gain at 4 and 12 weeks. Right and transverse colon patches showed early weight loss and some weight gain at 12 weeks. All IEP rats lost weight and died.
weight, had diarrhea, severe perianal excoriation, and died during the course of this study. Rats with IEP and the Martin procedure never had solid stools, had moderate perianal excoriation and, in addition, 60% (3/5) of rats showed severe abdominal distention (Fig 4A and B). Rats with segmental patches all survived, had mushy stools, minimal perianal excoriation, and no evidence of abdominal distention. DISCUSSION
The care of the infant with TCA remains a difficult management problem especially when the aganglionic process extends to the more proximal regions of the small intestine. Diagnosis may be difficult and fluid and electrolyte disturbances and nutrition have been significant problems resulting in a high morbidity and mortality (25% to 65%). 13 Infants with TCA usually require enhanced nutritional support using total parenteral nutrition or enteral nutrition with highly defined elemental diets. 8'11 These management problems were also noted in the experimental setting in our rat model. It is difficult to keep post-IEP rats on total parenteral nutrition for extended periods of time, limiting its applicability as a support source in attempting to evaluate long-term results (eg, > 12 weeks). In a recent unpublished pilot study, we have observed that an elemental diet used as a nutritional supplement results in an improved survival in the rat following total eolectomy and IEP. All the experimental animals in this present study were therefore managed with an elemental diet for the first 5 weeks, in addition to a solid diet using standard rat chow. After 5 weeks, all the animals received only water and rat chow ad libitum. The data from this study show that the Martin operation (using the entire aganglionic colon in a side-to-side anastomosis with the pull-through ileum) may be effective in the surgical treatment of TCA. The survival rate (83%) and transit time was acceptable, and the recovery rate for weight was 40% at 4 weeks and 100% at 12 weeks. Since rats with the Martin
626
GOTO AND GROSFELD
Fig 4. (A) Significant abdmonial distention w a s observed in rats with the Martin procedure (right) when compared with unresected controls (left) and other pull-through groups. (B) Gross appearance of the dilated bowel in a rat with the Martin procedure.
procedure gained weight somewhat better than the other groups in this study, preserving the entire aganglionic colon may be a useful adjunct. However, rats with IEP and Martin's procedure also showed severe abdominal distention, significant dilation of the entire side-to-side ileocolonic anastomosis, persistent diarrhea, and perianal excoriation. These observations may be due to inflammatory changes related to retention in the entire aganglionic colon resulting in a pattern quite similar to clinical instances of severe enterocolitis. Clinical reports regarding the efficacy of the Martin procedure in infants with TCA have raised concern because of a high incidence of debilitating enterocolitis complicat-
ing this operation. 3'~u2 The fact that segmental antimesenteric aganglionic intestinal patches (as advocated by Kimura, 4 Boley: Kottmeier et al, 6 and others 7,*'a~ may slow transit time at the patch site and are capable of fluid and electrolyte absorption in both the clinical and experimental 1~setting suggest that this technique may be an effective and attractive alternative procedure in babies with TCA. Previous data from our laboratory indicate that both sodium and water absorption does occur in rats with aganglionic colon patches, l~ The right colon is superior to both the transverse and left colon as a patch and should preferably be used in instances of TCA when possible if this technique is applied) '8'1~ This is the first successful experimental report of IEP with preservation of the entire aganglionic colon in the rat. These data indicate that Martin's concept of preserving the entire aganglionic colon may be rational for the surgical treatment of T C A from the point of view of survival, weight gain, and transit time. However, enterocolitis (characterized by abdominal distention, explosive diarrhea, and dilated bowel on abdominal x-ray) observed both in this experiment and the clinical setting (probably related to inflammation and/ or bacterial stasis in the long side-to-side ileocolonic anastomosis) remains a problem that requires further investigation. Although Heath et al u have demonstrated an increased transport of electrolytes in aganglionic colon of patients with Hirschsprung's disease, this preliminary report did not study nutrient, water, and electrolyte absorption, bacterial colonization, or histologic changes in the mucosa of the aganglionic segment. Although there were only a small number of animals used in each of these preliminary experiments, definite trends were observed. Further investigation of these adjunctive procedures are currently in progress and may shed additional light on the subject. These modifications of surgical treatment of infants with TCA (with extension of the aganglionic process to the proximal small bowel) have resulted in an improved survival. In addition, a recent report by Ziegler and associates ~4 suggests that myotomy-myectomy in proximal small bowel aganglionosis may also have a role in the correction of this condition and result in survival of patients previously considered hopeless cases. ACKNOWLEDGMENT
Full credit should be given to Drs Martin,9 Kimura,4 Kottmeier,6 Boley,5and Ziegler14for their innovativecontributionsin the management of this difficultclinical problem.
REFERENCES
h Martin LW: Surgical management of Hirschsprung's disease involvingthe small intestine. Arch Surg 97:183-189, 1968
2. WalkerA, KempsonR, TernbergJ: Aganglionosisof the small intestine. Surgery60:444-457, 1966
TOTAL COLONIC AGANGLIONOSlS
3. Careskey J, Weber TR, Grosfeld JL: Total colonic aganglionosis: Analysis of 16 cases. Am J Surg 143:160-168, 1982 4. Kimura K, Nishijima E, Muraji T, et al: A new surgical approach to extensive aganglionosis. J Pediatr Surg 16:840-843, 1981 5. Boley S J: A new operative approach to total aganglionosis of the colon. Surg Gynecol Obstet 159:481-484, 1984 6. Kottmeier PK, Jongco B, Velcek FT, et al: Absorptive function of the aganglionic ileum. J Pediatr Surg 16:275-278, 1981 7. Shandling B: Total colonic aganglionosis: A new operation. J Pediatr Surg 19:503-505, 1984 8. Grosfeld JL, Rescorla F J, West KW: Short bowel syndrome in infancy and childhood. Am J Surg 151:41-46, 1986 9. Martin LW: Total colonic aganglionosis; preservation and utilization of the entire colon. J Pediatr Surg 17:635-637, 1982
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10. Goto S, Gunter M, Scherer LR, et al: Surgical treatment of total colonic aganglionosis: Efficacy of aganglionic patch enteroplasty in the rat. J Pediatr Surg 21:601-607, 1986 11. Vane DW, Grosfeld JL: Hirschsprung's disease: Experience with the Duhamel procedure in 195 cases. Pediatr Surg Int 1:95-99, 1986 12. Davies MRQ, Cywes S: Inadequate pouch emptying following Martin's pull-through procedure for intestinal aganglionosis. J Pediatr Surg 18:14-20, 1983 13. Heath AL, Spitz L, Mella PJ: The absorptive function of colonic aganglionic intestine: Are the Duhamel and Martin procedures rational? J Pediatr Surg 20:34-36, 1985 14. Ziegler M, Ross A, Bishop H: Total intestinal aganglionosis: A new technique for prolonged survival. Presented at the 17th Annual Meeting of the American Pediatric Surgical Association, Toronto, Canada, May 1986, J Pediatr Surg (in press)