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Segmental small-intestinal transplantation: A comparison of jejunal and ileal grafts
Segmental small-intestinal transplantation: A comparison of jejunal and ileal grafts Tomoaki Taguchi, MD, PhD, and Sachiyo Suita, MD, PhD, FACS, Fukuoka, Japan
Strong immune responses, such as rejection and graft-versus-host disease, have been major obstacles to achieving a successful intestinal transplantation. Segmental small-intestinal transplantation is considered to result in a weaker response than total length grafting. Problems relating to organ harvesting from a living donor and spacial constraints of the recipient’s abdominal cavity are the other reasons why a segmental small intestinal transplantation is required. It is also important to select the most suitable part of the intestine to be used in transplantation; therefore, the jejunal and ileal grafts were comparatively reviewed from the aspects of native bowel characteristics, function, preservation, and immunological response. Immunologically, the jejunum is considered to have a slight advantage over the ileum. However, the control of rejection does not become inordinately more difficult for ileal grafts. Functionally, the ileum is considered to be better with regard to several parameters, such as greater absorptive capacities of fat, bile acids, and vitamins, and adaptation potential. Anatomically, an ileal graft is feasible for living-related transplantation. However, there is no conclusive factor for choosing the ileum as a suitable segmental graft. Further extensive studies are still needed to clarify various experimental as well as clinical aspects regarding intestinal transplantation. (Surgery 2002;131:S294-300). From the Department of Pediatric Surgery, Reproductive and Developmental Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
SMALL-INTESTINAL TRANSPLANTATION is the only radical surgical therapy for short-bowel syndrome. However, the small intestine contains a large amount of lymphoid tissue, and therefore a strong immune response remains an obstacle to achieving successful intestinal transplantation. Recent advances in immunosuppressants, such as cyclosporine, tacrolimus, mycophenolate mophetil, and monoclonal antibody to interleukin 2 receptor (daclizumab; Zenapax), now enable the small intestine to be clinically transplanted.1 However, the long-term survival rate is not as good as that for other solid organs. Actually, the overall 3-year graft survival has been reported to be less than 40% in the international registry.2 Because of the large antigeneic load in a small-intestinal graft, a segmental intestinal transplantation is considered to result in a weaker response than total length grafting. Problems relating to organ harvesting from a living donor and spacial constraints of the recipient’s abdominal cavity are the other reasons why a segmental small-intestinal Reprint requests: Tomoaki Taguchi, MD, PhD, Department of Pediatric Surgery, Reproductive and Developmental Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. Copyright © 2002 by Mosby, Inc. 0039-6060/2002/$35.00 + 0 11/0/119962 doi:10.1067/msy.2002.119962
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transplantation is required. In addition, it is also important to select the most suitable part of the intestine to be used in transplantation. It has been experimentally observed that a segmental graft is an effective surgical procedure for short-bowel syndrome in rats,3,4 dogs,5,6 and pigs.7,8 In clinical, living-related, segmental smallintestinal transplantation in Japan (Table I), ileal grafts measuring from 100 to 150 cm in length were used in all cases.9,10 The harvesting of the ileum is achieved with greater technical ease than that of the jejunum from a living-related donor. If we choose the jejunum for grafting, the size of vessels for anastomosis are very small, or a considerable length of donor small intestine must be resected to harvest an adequate size of vessels for anastomosis. In cadaveric transplantation the optimal site of a human intestinal segment appears to be the jejunoileum (ie, the middle portion of the small intestine).11 We herein comparatively review the use of jejunal and ileal grafts from the standpoint of native bowel characteristics, function, preservation, and immunologic response. NATIVE BOWEL CHARACTERISTICS The jejunum and ileum differ in several respects. Macroscopically, the jejunum has a larger
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Fig 1. Weight gain of normal, unoperated Lewis rats and of Lewis rats with either a total, segmental jejunal, or ileal allograft. Bars indicate SDs. There was no statistically significant difference among the groups.
Fig 2. Morphological change of intestinal mucosa after transplantation. Extensions of villus height and crypt depth were more prominent in ileal grafts than in jejunal grafts.
diameter and a thicker wall than the ileum. The circular folds of Kerckring are much more prominent in the jejunum, thus serving to increase the absorptive surface area. Microscopically, the intestinal villi are longer and broader in the jejunum than in the ileum, further increasing the jejunal surface area relative to the ileum. Overall, the surface area of the human intestine has been estimated at greater than 200 m2, with the jejunal surface area being twice that of the ileum. The normal human jejunum is presented with 10 L/d fluid, arising from the combination of dietary intake plus the products of salivary, gastric, pancreatic, biliary, and duodenal secretion. Approximately 5 L of this 10-L volume (50% of the presented volume) are absorbed by the jejunum, and 5 L/d pass into the
ileum. Ileal absorption totals 4 L/d (80% of the presented volume), with 1 L being delivered to the colon. Differences exist between the types of molecules typically absorbed by the normal jejunum and ileum as well. The jejunum is largely responsible for the absorption of nutrients, such as carbohydrates, amino acids, and fats, and ions, such as calcium and iron, whereas the ileum is responsible for the absorption of vitamin B12 and bile acids. Per unit of length, the jejunum absorbs much more of the nutrients than does the ileum. However, the jejunum lacks the ability to absorb vitamin B12 and bile acids, whereas the ileum cannot absorb lactose. As for water and electrolyte absorption, Anthone et al12 demonstrated distinct site-specific variations in basal and meal-stimulated intestinal water and elec-
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Fig 4. Chronologic changes in adenosine triphosphate during cold preservation of jejunal and ileal grafts. There were no significant differences in the adenosine triphosphate contents between jejunal and ileal grafts at any time of cold preservation up to 48 hours. ATP, Adenosine triphosphate.
Fig 3. Chronologic change of immediate-early gene after intestinal transplantation. The expression of c-Fos and cJun tended to be stronger and earlier in ileal grafts than in jejunal grafts.
trolyte absorption in dogs. The magnitude of ileal absorption exceeds the magnitude of jejunal absorption in both the basal and the meal-stimulated states. We demonstrated that the jejunal short-bowel rats (with 10 cm of jejunum remaining) showed a poor survival rate and anemia, whereas the ileal short-bowel rats (10 cm of ileum remained) showed a good survival and no evidence of anemia.13 Secondary anemia induced by a vitamin B12 deficiency may explain the death of jejunal shortbowel rats; in contrast, no animal died of anemia among the ileal short-bowel rats. It has often been stated that there are compensatory changes in the intestinal remnant after small-bowel resection and that the jejunum and ileum respond differently.14 Mucosa hypertrophy and enhanced glucose absorption were demonstrated in the intestinal remnant after extensive small-bowel resection in the rat.15 These compensatory changes developed in as short a period as 2 weeks after resection and were maximal at 1 month. These responses were found to a much greater extent in the ileal remnant after a proximal
resection than in the jejunum after a distal resection. Hanson et al16 revealed that the jejunal and ileal crypts responded nearly the same during the first 12 days after 70% intestinal resection, with their sizes increasing to about 150% of control values. However, although the jejunal villus cell counts increased to 125% of control values, the ileal villus cell counts increased to 180% of the control values. Ischemia-reperfusion injury and endotoxininduced bacterial translocation have been reported to be mediated by xanthine dehydrogenase and oxidase.17,18 The response of xanthine dehydrogenase and oxidase activity to endotoxin is higher in the ileum than in the jejunum, and therefore the ileum is considered to be more susceptible to endotoxin shock. Histologically, the ileal mucosa was severely damaged after the administration of endotoxin, whereas the jejunum showed only minimal changes.19 However, these experiments were performed in a neurovascularly intact bowel segment. Compared with the native bowel, a transplanted intestinal graft has the physiologic disadvantages of denervation, lymphatic disruption, venous drainage route, and temporary ischemic injury. FUNCTION Various comparisons of the jejunal and ileal graft have been performed, mainly following the rat small-intestinal transplantation model. Schraut et al3 replaced the entire small bowel with an intestinal allograft consisting of the entire
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Fig 5. Blood cytokine levels after allogeneic jejunal or ileal transplantation. *Statistically significant between jejunal and ileal transplantation. Bars indicate SDs. Adapted from unpublished data presented at the 17th Congress of Asian Association of Pediatric Surgeons, November 6-9, 2000, Fukuoka, Japan.
small bowel, the jejunum, or the ileum under immunosupression with cyclosporine (15 mg administered intramuscularly on alternate days). All recipients demonstrated normal global nutritional parameters (hematocrit and serum albumin) and gained weight at a rate comparable with that for age-matched control subjects (Fig 1). No nutritional deficiencies were clinically apparent. However, the levels of fat-soluble vitamins (A and E) significantly decreased in recipients of segmental grafts. Fecal fat was significantly elevated in all rats with grafts, but the increase was most pronounced in those with jejunal grafts. Therefore, fat absorption is considered to be better in an ileal graft than in a jejunal graft. Schlemminger et al20 compared 27 cm of the proximal, middle, or distal small-intestinal grafts in the rat. Fecal excretion of fat was not elevated in allografts of the middle and distal portion, but it was elevated in those of the proximal portion. Allogeneic transplantation was successful when the middle or distal portion was grafted. All recipients of proximal allografts showed a severe loss of body weight and died between days 8 and 10 after transplant, although postmortem examination revealed no signs of acute rejection. Kiyozaki et al21 compared 35 cm of jejunal and ileal isografts in the rat. The fecal fat excretion was higher, whereas the bile acid concentration in the bile juice was lower in the jejunal transplant. These 3 articles demonstrated that ileal transplantation is therefore more conducive to lipid absorption than jejunal transplantation.
Regarding the length of the graft, Kimura et al22 demonstrated that enterectomized rats receiving 20cm jejunal or ileal isografts gained weight progressively, and no significant difference was observed in the weight gain between rats receiving jejunal and ileal grafts. We investigated the long-term results of extremely short segmental jejunal or ileal syngeneic transplantations, and a 10-cm graft showed sufficient survival and weight gain.23 In addition, no significant differences were seen in the survival rate or weight gain between jejunal and ileal grafts. Nearly all the hematologic findings, serum nutritional parameters, and results of liver-function tests were normal for both jejunal and ileal transplantation. The only difference was that the serum total bile acid level was significantly higher in ileal transplants (17.8 ± 13.3 µmol/L in jejunal grafts and 73.8 ± 48.7 µmol/L in ileal grafts [P < .05] 50 weeks after transplantation). This may be explained by the presence of an active transport system for bile acid in the ileum and the systemic venous drainage of the graft. We also demonstrated the adaptive hyperplasia of villi and crypt histologically (Fig 2). These adaptive changes were more pronounced in the ileal graft. The ileal graft is thus considered to have a better morphological adaptability. We also showed that the expression of the immediate-early genes c-Fos and c-Jun are stronger and earlier in the ileum than that in the jejunum (Fig 3).24 These genes are linked to the proliferating process in the gastrointestinal tract, such as after massive small-bowel resection,25 after ischemiareperfusion injury, and in the healing of peptic
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Table I. Cases of living-related small-intestinal transplantation in Japan Recipient
Indication
Donor
Length of graft
1. Boy: 2 y, 6 mo 2. Girl: 4 y, 5 mo
Midgut volvulus Gastroschisis, intrauterine volvulus
31-y-old mother 31-y-old mother
Ileum, 100 cm Ileum, 120 cm
3. Boy: 3 y, 6 mo
Oomphalocele, intrauterine volvulus Microvillus inclusion disease Malrotation, volvulus, liver failure
28-y-old mother
Ileum, 140 cm
59-y-old grandmother 28-y-old mother
Ileum, 150 cm
4. Boy: 16 y 5. Boy: 8 mo
Ileum, 130 cm
Present state as of September 2001 is shown. Adapted from unpublished data presented at the 7th International Small bowel Transplant Symposium, September 12-15, 2001, Stockholm, Sweden.
Table II. Graft survival of segmental jejunal and ileal allotransplant Graft Jejunum (n = 6) Ileum (n = 8)
5d
10 d
15 d
20 d
25 d
30 d
100% 100%
100% 100%
100% 75%
67% 50%
33% 20%
33% 20%
There was no significant difference in survival between jejunal and ileal allografts with 0.5 mg/d tacrolimus administered intramuscularly.
ulcers, and are considered to precede the adaptive response. Therefore the ileum seems to have a stronger and earlier adaptive response than the jejunum in small-intestinal transplantation. PRESERVATION The small intestine has been reported to preserve good nerve and smooth-muscle function with cold University of Wisconsin (UW) solution for up to 24 hours in the rat.26 In the canine model the small intestine has also been reported to be preserved for 24 hours by means of simple cold storage.27 In clinical cadaveric transplantation the small intestine is considered to be preserved for up to 12 hours with UW solution.1 We compared the jejunal and ileal graft regarding the adenine nucleotide levels during cold storage and after reperfusion in the rat.28 There was no significant difference in the level of adenosine triphosphate, total adenine nucleotide, and energy charge during cold preservation for up to 48 hours in UW solution (Fig 4).29 In a reperfusion study the recovery levels of adenosine triphosphate 30 minutes after reperfusion were slightly higher in the jejunum than in the ileum; however, there were no statistically significant differences. As a result, no significant differences were observed between the jejunum and ileum regarding energy metabolism either during cold preservation or after reperfusion.
Takeyoshi et al30 preserved an autograft for 24 hours in cold lactated Ringer’s solution and subsequently transplanted it. Thereafter, they evaluated the electrophysiologic function using the potential differences, mucosa enzymes, and the histology of the jejunum and chronologically compared the findings.30 The electrophysiologic function and mucosa biochemical marker recovered within 3 days in the jejunum and within 7 to 14 days in the ileum. These findings suggested that the recovery of the ileum was slower than the recovery of the jejunum. However, the ileum finally recovered completely and showed a normal function 14 days after transplantation. IMMUNOLOGIC RESPONSE Anatomically, 2 types of Peyer patches (PPs) have been reported to exist: the ileal PP and the jejunal PP.31 The ileal PP is a large continuous PP that extends 100 to 200 cm along the terminal ileum, whereas jejunal PPs are found as 30 to 40 smaller lymphoid aggregates in the jejunum and proximal ileum. Lymphopoietic tissue predominates in the ileal PP, whereas lymphocyte traffic tissue predominates in jejunal PPs. As a result, lymphoid extravasation is substantially greater in jejunal PPs than in the ileal PP. In addition, T cells account for about 30% to 50% of jejunal PP cells but only 1% to 2% of ileal PP cells. Both types gain full lymphopoietic capacity in utero and reach
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Operative date May 1996 April 1998
Outcome
Institute Kyoto University Kyoto University
January 2000
Died of Carinii pneumonia at 1 y, 5 mo Graft was taken out at 1 y, 10 mo after transplantation because of chronic rejection. Cadaveric graft was retransplanted, and then the patient died of sepsis 7 months after retransplantation. Surviving for 1 y, 8 mo
March 2000
Surviving for 1 y, 6 mo
Osaka University
June 2001
Died of liver failure on postoperative day 17
Kyoto University
their maximum size by 2 to 3 months after birth. Thereafter, the ileal PP undergoes progressive involution and tends to regress. The jejunal PPs, by contrast, remain intact throughout life. Two types of PPs are considered to be functionally different. The ileal PP is equivalent to the avian bursa of Fabricius, whereas jejunal PPs are more committed to the mucosa immune system. Therefore jejunal PPs are considered to be related to the immunologic response after transplantation. From the standpoint of the distribution of jejunal PPs, no difference is seen in the density between the jejunum and the ileum. An immunologic response is not expected to be different between the jejunum and the ileum. A segmental intestinal transplantation is thus expected to have a lower immunologic reaction. Kimura et al32 confirmed that the frequency and severity of graft-versus-host disease (GVHD) correlated with the length of the transplanted intestine. When choosing the portion of the segmental graft in intestinal transplantation, the most immunologically beneficial method should be selected. Lossing et al33 showed that GVHD and signs of rejection occurred with the same frequency in both types of intestinal segments. It also has been reported that the onset of rejection and GVHD was not related to the segment of the transplanted small intestine. Other investigators have shown no significant difference in the posttransplant immunologic responses between jejunal and ileal grafts in the rat model.34,35 Stangel et al34 suggested that, in light of both GVHD and rejection, the selection of the portion of small intestine to be used for transplantation should be made based on the distinctive absorptive capacity rather than based on any immunologic difference. In another study Stangel
Kyoto University
et al36 reported that equal doses of cyclosporine did not prolong survival, nor did they alter the course of rejection in either jejunal or ileal grafts. In a dog model Benchimol et al6 noted no major difference between jejunal and ileal allografts with respect to GVHD or rejection. Considering all these studies, it appears that there was no significant difference in the immunologic response between jejunal and ileal grafts. Rejection clinically occurred in patchy form throughout the entire small intestine; however, the incidence was thought to be a little more frequent in the ileum than in the jejunum.1 In our experiment, after daily administration of 0.5 mg of tacrolimus administered intramuscularly, no significant differences were found in rat survival between the jejunal and ileal grafts (Table II).29 Histologically, however, the infiltration of lymphocytes in the proper muscle layer was a little more dominant in ileal grafts than in jejunal grafts 10 days after transplantation. Moreover, the blood levels of interleukin 2 and interleukin 1β were significantly higher in ileal transplantation than in jejunal transplantation (Fig 5).37 On the basis of both clinical reports and our experimental results, the jejunum might therefore be slightly preferable to the ileum. CONCLUSION Immunologically, the jejunum is considered to have a slight advantage over the ileum; however, the control of rejection does not become inordinately more difficult for ileal grafts. Functionally, the ileum is considered better with regard to several parameters. Anatomically, an ileal graft is feasible for living-related transplantation. Up to now, an ileal graft has been thought to be preferable over a jejunal graft because of its greater absorptive capac-
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ity and adaptation potential. Further extensive studies, however, are still called for to clarify various experimental, as well as clinical, aspects regarding intestinal transplantation. REFERENCES 1. Reyes J, Abu-Elmagd K. Intestinal and multivisceral transplantation. Presented at the 17th Congress of Asian Association of Pediatric Surgeons; 2000 Nov 6-9; Fukuoka, Japan. 2. International Transplant Registry. Available at: http://www.ihcs.on.ca/itr/. 3. Schraut WH, Lee KWK, Sitrin M. Recipient growth and nutritional status following transplantation of segmental smallbowel allografts. J Surg Res 1987;43:1-9. 4. Sonnino RE, Harmel RP. Technical aspects of intestinal transplantation in the rat. J Invest Surg 1988;1:55-64. 5. Wolvekamp MCJ, Heineman E, Marquet RL, Meijssen MAC, deBruin RWF, Molenaar JC. Segmental intestinal transplantation can be an adequate therapy for short bowel syndrome in growing dogs. J Pediatr Surg 1995;30:396-401. 6. Benchimol D, Pesce A, Delque-Bayer P, et al. Jejunal versus ileal segmental allografts in the dog: comparison of immunologic and functional results. Surgery 1992;112:918-27. 7. Kimura K, LaRosa CA, Blank MA, et al. Successful segmental intestinal transplantation in enterectomized pigs. Ann Surg 1990;211:158-64. 8. Nakao M, Taguchi T, Suit S, et al. Technical aspects of pig model in living-related small intestinal transplantation. Asian J Surg 2001;24:353-6. 9. Hasegawa T, Sasaki T, Shimizu Y, et al. Living-related small bowel transplantation for a 16-year-old patient with microvillus inclusion disease. Presented at 17th Congress of Asian Association of Pediatric Surgeons; 2000 Nov 6-9; Fukuoka, Japan. 10. Uemoto S, Tanaka K. Surgical techniques and results in living donor small bowel transplantation. Presented at the 7th International Small bowel Transplant Symposium; 2001, Sept 12-15; Stockholm, Sweden. 11. Schroeder P, Goulet O, Lear PA. Small-bowel transplantation: European experience. Lancet 1990;336:110-1. 12. Anthone GJ, Wang BH, Zinner MJ, Yeo CJ. Site-specific variations in basal and meal-stimulated intestinal absorption. J Surg Res 1992;52:454-8. 13. Taguchi T, Hirata Y, Hirose R, Yamada T, Suita S. Short segmental intestinal transplantation in rats—functional comparison of jejunal and ileal grafts. Transplant Proc 1992;24:107980. 14. Booth CC, Evans KT, Menzies T, Street DF. Intestinal hypertrophy following partial resection of the small bowel in the rat. Br J Surg 1959;46:403-10. 15. Dowling RH, Booth CC. Structural and functional changes following small intestinal resection in the rat. Clin Sci 1967;32:139-49. 16. Hanson WR, Osborne JW, Sharp JG. Compensation by the residual intestine after intestinal resection in the rat. II: Influence of postoperative time interval. Gastroenterology 1977;72:701-5. 17. Hirata Y, Ishii K, Taguchi T, Suita S, Takeshige K. Conversion of xanthine dehydrogenase to xanthine oxidase during ischemia of the rat small intestine and the effect of trifluoperazine on the conversion. J Pediatr Surg 1993;28:597-600. 18. Deitch EA, Specian RD, Berg RD. Endotoxin-induced bacterial translocation and mucosa permeability: role of xanthine oxidase, complement activation, and macrophage products. Crit Care Med 1991;19:785-91.
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19. Deitch EA, Taylor M, Grisham M, Ma L, Bridges W, Berg R. Endotoxin induces bacterial translocation and increases xanthine oxidase activity. J Trauma 1989;29:1679-83. 20. Schlemminger R, Lottermoser S, Gieseler RKH, et al. The adaptive response of the rat small intestine after resection and segmental transplantation during the early postoperative phase. Res Exp Med 1993;193:213-24. 21. Kiyozaki H, Kobayashi E, Toyama N, Miyata M. Segmental small bowel transplantation in the rat: comparison of lipid absorption between jejunal and ileal grafts. J Parent Ent Nutr 1996;20:67-70. 22. Kimura K, Money SR, Jaffe BM. Short-segment orthotopic intestinal isografts and allografts in enterectomized rats. Transplantation 1987;44:579-82. 23. Rahman MS, Taguchi T, Nakao M, Yamada T, Suita S. Longterm results of short segmental syngeneic small intestinal transplantation: Comparison of jejunal and ileal grafts. J Pediatr Surg 1996;31:908-11. 24. Taguchi T, Fujii Y, Nakao M, Ogita K, Shima Y, Suita S. Expression of immediate-early genes c-Fos and c-Jun in small intestinal transplantation. Transplant Proc 2000; 32:1279. 25. Ehrenfried JA, Townsend CM, Thompson JC, Evers BM. Increases in nup475 and c-jun are early molecular events that precede the adaptive hyperplastic response after small bowel resection. Ann Surg 1995;222:51-6. 26. Taguchi T, Zorychta E, Guttman FM. Evaluation of UW solution for preservation of small intestinal transplants in the rat. Transplantation 1992;53:1202-5. 27. Raju S, Fujiwara H, Lewin JR, Grogan JB. Twelve hour and twenty four hour preservation of small bowel allografts by simple hypothermia. Transplantation 1988;45:290-3. 28. Nakao M, Taguchi T, Yanai K, Yamada T, Suita S. Energy metabolism during cold ischemia and reperfusion in rat small intestinal transplantation: comparison of jejunal and ileal grafts. J Pediatr Surg 1997;32:1675-8. 29. Taguchi T, Nakao M, Yanai K, Rahman MS, Yamada T, Suita S. Comparison of jejunal and ileal grafts from the aspects of cold preservation and immunologic reaction. Transplant Proc 1998;30:2636-7. 30. Takeyoshi I, Zhang S, Nomoto M, et al. Mucosa damage and recovery of the intestine after prolonged preservation and transplantation in dogs. Transplantation 2001;71:1-7. 31. Reynolds JD, Kirk D. Two types of sheep Peyer’s patches: location along gut does not influence involution. Immunology 1989;66:308-11. 32. Kimura K, Money SR, Jaffe BM. The effects of cyclosporine on varying segments of small-bowel grafts in the rat. Surgery 1988;104:64-9. 33. Lossing A, Nordgren S, Cohen Z, et al. Histologic monitoring of rejection in small intestinal transplantation. Transplant Proc 1982;14:643-5. 34. Stangel MJ, Schraut WH, Moynihan HL, Lee T. Rejection of ileal versus jejunal allografts. Transplantation 1989;47:424-7. 35. DeBruin RWF, Heineman E, Meijssen MAC, Jeekel H, Marquet RL. Small bowel transplantation in rats. The effect of pretransplant donor-specific blood transfusions on various segments of small bowel grafts. Transplantation 1990;50:92830. 36. Stangel MJ, Schraut WH, Moynihan HL, Lee TK, Lee KKW. Effect of cyclosporin therapy in comtrolling the rejection of ileal versus jejunal allografts. Transplant Int 1990;3:149-55. 37. Yamada T, Ogita K, Nakao M, Taguchi T, Suita S. Comparison of jejunal and ileal transplantation -from the aspect of blood cytokine levels. Presented at the 17th Congress of Asian Association of Pediatric Surgeons; 2000 Nov 6-9; Fukuoka, Japan.
Strong immune responses, such as rejection and graft-versus-host disease, have been major obstacles to achieving a successful intestinal transplantation. Segmental small-intestinal transplantation is considered to result in a weaker response than total length grafting. Problems relating to organ harvesting from a living donor and spacial constraints of the recipient’s abdominal cavity are the other reasons why a segmental small intestinal transplantation is required. It is also important to select the most suitable part of the intestine to be used in transplantation; therefore, the jejunal and ileal grafts were comparatively reviewed from the aspects of native bowel characteristics, function, preservation, and immunological response. Immunologically, the jejunum is considered to have a slight advantage over the ileum. However, the control of rejection does not become inordinately more difficult for ileal grafts. Functionally, the ileum is considered to be better with regard to several parameters, such as greater absorptive capacities of fat, bile acids, and vitamins, and adaptation potential. Anatomically, an ileal graft is feasible for living-related transplantation. However, there is no conclusive factor for choosing the ileum as a suitable segmental graft. Further extensive studies are still needed to clarify various experimental as well as clinical aspects regarding intestinal transplantation. (Surgery 2002;131:S294-300). From the Department of Pediatric Surgery, Reproductive and Developmental Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
SMALL-INTESTINAL TRANSPLANTATION is the only radical surgical therapy for short-bowel syndrome. However, the small intestine contains a large amount of lymphoid tissue, and therefore a strong immune response remains an obstacle to achieving successful intestinal transplantation. Recent advances in immunosuppressants, such as cyclosporine, tacrolimus, mycophenolate mophetil, and monoclonal antibody to interleukin 2 receptor (daclizumab; Zenapax), now enable the small intestine to be clinically transplanted.1 However, the long-term survival rate is not as good as that for other solid organs. Actually, the overall 3-year graft survival has been reported to be less than 40% in the international registry.2 Because of the large antigeneic load in a small-intestinal graft, a segmental intestinal transplantation is considered to result in a weaker response than total length grafting. Problems relating to organ harvesting from a living donor and spacial constraints of the recipient’s abdominal cavity are the other reasons why a segmental small-intestinal Reprint requests: Tomoaki Taguchi, MD, PhD, Department of Pediatric Surgery, Reproductive and Developmental Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. Copyright © 2002 by Mosby, Inc. 0039-6060/2002/$35.00 + 0 11/0/119962 doi:10.1067/msy.2002.119962
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transplantation is required. In addition, it is also important to select the most suitable part of the intestine to be used in transplantation. It has been experimentally observed that a segmental graft is an effective surgical procedure for short-bowel syndrome in rats,3,4 dogs,5,6 and pigs.7,8 In clinical, living-related, segmental smallintestinal transplantation in Japan (Table I), ileal grafts measuring from 100 to 150 cm in length were used in all cases.9,10 The harvesting of the ileum is achieved with greater technical ease than that of the jejunum from a living-related donor. If we choose the jejunum for grafting, the size of vessels for anastomosis are very small, or a considerable length of donor small intestine must be resected to harvest an adequate size of vessels for anastomosis. In cadaveric transplantation the optimal site of a human intestinal segment appears to be the jejunoileum (ie, the middle portion of the small intestine).11 We herein comparatively review the use of jejunal and ileal grafts from the standpoint of native bowel characteristics, function, preservation, and immunologic response. NATIVE BOWEL CHARACTERISTICS The jejunum and ileum differ in several respects. Macroscopically, the jejunum has a larger
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Fig 1. Weight gain of normal, unoperated Lewis rats and of Lewis rats with either a total, segmental jejunal, or ileal allograft. Bars indicate SDs. There was no statistically significant difference among the groups.
Fig 2. Morphological change of intestinal mucosa after transplantation. Extensions of villus height and crypt depth were more prominent in ileal grafts than in jejunal grafts.
diameter and a thicker wall than the ileum. The circular folds of Kerckring are much more prominent in the jejunum, thus serving to increase the absorptive surface area. Microscopically, the intestinal villi are longer and broader in the jejunum than in the ileum, further increasing the jejunal surface area relative to the ileum. Overall, the surface area of the human intestine has been estimated at greater than 200 m2, with the jejunal surface area being twice that of the ileum. The normal human jejunum is presented with 10 L/d fluid, arising from the combination of dietary intake plus the products of salivary, gastric, pancreatic, biliary, and duodenal secretion. Approximately 5 L of this 10-L volume (50% of the presented volume) are absorbed by the jejunum, and 5 L/d pass into the
ileum. Ileal absorption totals 4 L/d (80% of the presented volume), with 1 L being delivered to the colon. Differences exist between the types of molecules typically absorbed by the normal jejunum and ileum as well. The jejunum is largely responsible for the absorption of nutrients, such as carbohydrates, amino acids, and fats, and ions, such as calcium and iron, whereas the ileum is responsible for the absorption of vitamin B12 and bile acids. Per unit of length, the jejunum absorbs much more of the nutrients than does the ileum. However, the jejunum lacks the ability to absorb vitamin B12 and bile acids, whereas the ileum cannot absorb lactose. As for water and electrolyte absorption, Anthone et al12 demonstrated distinct site-specific variations in basal and meal-stimulated intestinal water and elec-
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Fig 4. Chronologic changes in adenosine triphosphate during cold preservation of jejunal and ileal grafts. There were no significant differences in the adenosine triphosphate contents between jejunal and ileal grafts at any time of cold preservation up to 48 hours. ATP, Adenosine triphosphate.
Fig 3. Chronologic change of immediate-early gene after intestinal transplantation. The expression of c-Fos and cJun tended to be stronger and earlier in ileal grafts than in jejunal grafts.
trolyte absorption in dogs. The magnitude of ileal absorption exceeds the magnitude of jejunal absorption in both the basal and the meal-stimulated states. We demonstrated that the jejunal short-bowel rats (with 10 cm of jejunum remaining) showed a poor survival rate and anemia, whereas the ileal short-bowel rats (10 cm of ileum remained) showed a good survival and no evidence of anemia.13 Secondary anemia induced by a vitamin B12 deficiency may explain the death of jejunal shortbowel rats; in contrast, no animal died of anemia among the ileal short-bowel rats. It has often been stated that there are compensatory changes in the intestinal remnant after small-bowel resection and that the jejunum and ileum respond differently.14 Mucosa hypertrophy and enhanced glucose absorption were demonstrated in the intestinal remnant after extensive small-bowel resection in the rat.15 These compensatory changes developed in as short a period as 2 weeks after resection and were maximal at 1 month. These responses were found to a much greater extent in the ileal remnant after a proximal
resection than in the jejunum after a distal resection. Hanson et al16 revealed that the jejunal and ileal crypts responded nearly the same during the first 12 days after 70% intestinal resection, with their sizes increasing to about 150% of control values. However, although the jejunal villus cell counts increased to 125% of control values, the ileal villus cell counts increased to 180% of the control values. Ischemia-reperfusion injury and endotoxininduced bacterial translocation have been reported to be mediated by xanthine dehydrogenase and oxidase.17,18 The response of xanthine dehydrogenase and oxidase activity to endotoxin is higher in the ileum than in the jejunum, and therefore the ileum is considered to be more susceptible to endotoxin shock. Histologically, the ileal mucosa was severely damaged after the administration of endotoxin, whereas the jejunum showed only minimal changes.19 However, these experiments were performed in a neurovascularly intact bowel segment. Compared with the native bowel, a transplanted intestinal graft has the physiologic disadvantages of denervation, lymphatic disruption, venous drainage route, and temporary ischemic injury. FUNCTION Various comparisons of the jejunal and ileal graft have been performed, mainly following the rat small-intestinal transplantation model. Schraut et al3 replaced the entire small bowel with an intestinal allograft consisting of the entire
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Fig 5. Blood cytokine levels after allogeneic jejunal or ileal transplantation. *Statistically significant between jejunal and ileal transplantation. Bars indicate SDs. Adapted from unpublished data presented at the 17th Congress of Asian Association of Pediatric Surgeons, November 6-9, 2000, Fukuoka, Japan.
small bowel, the jejunum, or the ileum under immunosupression with cyclosporine (15 mg administered intramuscularly on alternate days). All recipients demonstrated normal global nutritional parameters (hematocrit and serum albumin) and gained weight at a rate comparable with that for age-matched control subjects (Fig 1). No nutritional deficiencies were clinically apparent. However, the levels of fat-soluble vitamins (A and E) significantly decreased in recipients of segmental grafts. Fecal fat was significantly elevated in all rats with grafts, but the increase was most pronounced in those with jejunal grafts. Therefore, fat absorption is considered to be better in an ileal graft than in a jejunal graft. Schlemminger et al20 compared 27 cm of the proximal, middle, or distal small-intestinal grafts in the rat. Fecal excretion of fat was not elevated in allografts of the middle and distal portion, but it was elevated in those of the proximal portion. Allogeneic transplantation was successful when the middle or distal portion was grafted. All recipients of proximal allografts showed a severe loss of body weight and died between days 8 and 10 after transplant, although postmortem examination revealed no signs of acute rejection. Kiyozaki et al21 compared 35 cm of jejunal and ileal isografts in the rat. The fecal fat excretion was higher, whereas the bile acid concentration in the bile juice was lower in the jejunal transplant. These 3 articles demonstrated that ileal transplantation is therefore more conducive to lipid absorption than jejunal transplantation.
Regarding the length of the graft, Kimura et al22 demonstrated that enterectomized rats receiving 20cm jejunal or ileal isografts gained weight progressively, and no significant difference was observed in the weight gain between rats receiving jejunal and ileal grafts. We investigated the long-term results of extremely short segmental jejunal or ileal syngeneic transplantations, and a 10-cm graft showed sufficient survival and weight gain.23 In addition, no significant differences were seen in the survival rate or weight gain between jejunal and ileal grafts. Nearly all the hematologic findings, serum nutritional parameters, and results of liver-function tests were normal for both jejunal and ileal transplantation. The only difference was that the serum total bile acid level was significantly higher in ileal transplants (17.8 ± 13.3 µmol/L in jejunal grafts and 73.8 ± 48.7 µmol/L in ileal grafts [P < .05] 50 weeks after transplantation). This may be explained by the presence of an active transport system for bile acid in the ileum and the systemic venous drainage of the graft. We also demonstrated the adaptive hyperplasia of villi and crypt histologically (Fig 2). These adaptive changes were more pronounced in the ileal graft. The ileal graft is thus considered to have a better morphological adaptability. We also showed that the expression of the immediate-early genes c-Fos and c-Jun are stronger and earlier in the ileum than that in the jejunum (Fig 3).24 These genes are linked to the proliferating process in the gastrointestinal tract, such as after massive small-bowel resection,25 after ischemiareperfusion injury, and in the healing of peptic
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Table I. Cases of living-related small-intestinal transplantation in Japan Recipient
Indication
Donor
Length of graft
1. Boy: 2 y, 6 mo 2. Girl: 4 y, 5 mo
Midgut volvulus Gastroschisis, intrauterine volvulus
31-y-old mother 31-y-old mother
Ileum, 100 cm Ileum, 120 cm
3. Boy: 3 y, 6 mo
Oomphalocele, intrauterine volvulus Microvillus inclusion disease Malrotation, volvulus, liver failure
28-y-old mother
Ileum, 140 cm
59-y-old grandmother 28-y-old mother
Ileum, 150 cm
4. Boy: 16 y 5. Boy: 8 mo
Ileum, 130 cm
Present state as of September 2001 is shown. Adapted from unpublished data presented at the 7th International Small bowel Transplant Symposium, September 12-15, 2001, Stockholm, Sweden.
Table II. Graft survival of segmental jejunal and ileal allotransplant Graft Jejunum (n = 6) Ileum (n = 8)
5d
10 d
15 d
20 d
25 d
30 d
100% 100%
100% 100%
100% 75%
67% 50%
33% 20%
33% 20%
There was no significant difference in survival between jejunal and ileal allografts with 0.5 mg/d tacrolimus administered intramuscularly.
ulcers, and are considered to precede the adaptive response. Therefore the ileum seems to have a stronger and earlier adaptive response than the jejunum in small-intestinal transplantation. PRESERVATION The small intestine has been reported to preserve good nerve and smooth-muscle function with cold University of Wisconsin (UW) solution for up to 24 hours in the rat.26 In the canine model the small intestine has also been reported to be preserved for 24 hours by means of simple cold storage.27 In clinical cadaveric transplantation the small intestine is considered to be preserved for up to 12 hours with UW solution.1 We compared the jejunal and ileal graft regarding the adenine nucleotide levels during cold storage and after reperfusion in the rat.28 There was no significant difference in the level of adenosine triphosphate, total adenine nucleotide, and energy charge during cold preservation for up to 48 hours in UW solution (Fig 4).29 In a reperfusion study the recovery levels of adenosine triphosphate 30 minutes after reperfusion were slightly higher in the jejunum than in the ileum; however, there were no statistically significant differences. As a result, no significant differences were observed between the jejunum and ileum regarding energy metabolism either during cold preservation or after reperfusion.
Takeyoshi et al30 preserved an autograft for 24 hours in cold lactated Ringer’s solution and subsequently transplanted it. Thereafter, they evaluated the electrophysiologic function using the potential differences, mucosa enzymes, and the histology of the jejunum and chronologically compared the findings.30 The electrophysiologic function and mucosa biochemical marker recovered within 3 days in the jejunum and within 7 to 14 days in the ileum. These findings suggested that the recovery of the ileum was slower than the recovery of the jejunum. However, the ileum finally recovered completely and showed a normal function 14 days after transplantation. IMMUNOLOGIC RESPONSE Anatomically, 2 types of Peyer patches (PPs) have been reported to exist: the ileal PP and the jejunal PP.31 The ileal PP is a large continuous PP that extends 100 to 200 cm along the terminal ileum, whereas jejunal PPs are found as 30 to 40 smaller lymphoid aggregates in the jejunum and proximal ileum. Lymphopoietic tissue predominates in the ileal PP, whereas lymphocyte traffic tissue predominates in jejunal PPs. As a result, lymphoid extravasation is substantially greater in jejunal PPs than in the ileal PP. In addition, T cells account for about 30% to 50% of jejunal PP cells but only 1% to 2% of ileal PP cells. Both types gain full lymphopoietic capacity in utero and reach
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Operative date May 1996 April 1998
Outcome
Institute Kyoto University Kyoto University
January 2000
Died of Carinii pneumonia at 1 y, 5 mo Graft was taken out at 1 y, 10 mo after transplantation because of chronic rejection. Cadaveric graft was retransplanted, and then the patient died of sepsis 7 months after retransplantation. Surviving for 1 y, 8 mo
March 2000
Surviving for 1 y, 6 mo
Osaka University
June 2001
Died of liver failure on postoperative day 17
Kyoto University
their maximum size by 2 to 3 months after birth. Thereafter, the ileal PP undergoes progressive involution and tends to regress. The jejunal PPs, by contrast, remain intact throughout life. Two types of PPs are considered to be functionally different. The ileal PP is equivalent to the avian bursa of Fabricius, whereas jejunal PPs are more committed to the mucosa immune system. Therefore jejunal PPs are considered to be related to the immunologic response after transplantation. From the standpoint of the distribution of jejunal PPs, no difference is seen in the density between the jejunum and the ileum. An immunologic response is not expected to be different between the jejunum and the ileum. A segmental intestinal transplantation is thus expected to have a lower immunologic reaction. Kimura et al32 confirmed that the frequency and severity of graft-versus-host disease (GVHD) correlated with the length of the transplanted intestine. When choosing the portion of the segmental graft in intestinal transplantation, the most immunologically beneficial method should be selected. Lossing et al33 showed that GVHD and signs of rejection occurred with the same frequency in both types of intestinal segments. It also has been reported that the onset of rejection and GVHD was not related to the segment of the transplanted small intestine. Other investigators have shown no significant difference in the posttransplant immunologic responses between jejunal and ileal grafts in the rat model.34,35 Stangel et al34 suggested that, in light of both GVHD and rejection, the selection of the portion of small intestine to be used for transplantation should be made based on the distinctive absorptive capacity rather than based on any immunologic difference. In another study Stangel
Kyoto University
et al36 reported that equal doses of cyclosporine did not prolong survival, nor did they alter the course of rejection in either jejunal or ileal grafts. In a dog model Benchimol et al6 noted no major difference between jejunal and ileal allografts with respect to GVHD or rejection. Considering all these studies, it appears that there was no significant difference in the immunologic response between jejunal and ileal grafts. Rejection clinically occurred in patchy form throughout the entire small intestine; however, the incidence was thought to be a little more frequent in the ileum than in the jejunum.1 In our experiment, after daily administration of 0.5 mg of tacrolimus administered intramuscularly, no significant differences were found in rat survival between the jejunal and ileal grafts (Table II).29 Histologically, however, the infiltration of lymphocytes in the proper muscle layer was a little more dominant in ileal grafts than in jejunal grafts 10 days after transplantation. Moreover, the blood levels of interleukin 2 and interleukin 1β were significantly higher in ileal transplantation than in jejunal transplantation (Fig 5).37 On the basis of both clinical reports and our experimental results, the jejunum might therefore be slightly preferable to the ileum. CONCLUSION Immunologically, the jejunum is considered to have a slight advantage over the ileum; however, the control of rejection does not become inordinately more difficult for ileal grafts. Functionally, the ileum is considered better with regard to several parameters. Anatomically, an ileal graft is feasible for living-related transplantation. Up to now, an ileal graft has been thought to be preferable over a jejunal graft because of its greater absorptive capac-
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ity and adaptation potential. Further extensive studies, however, are still called for to clarify various experimental, as well as clinical, aspects regarding intestinal transplantation. REFERENCES 1. Reyes J, Abu-Elmagd K. Intestinal and multivisceral transplantation. Presented at the 17th Congress of Asian Association of Pediatric Surgeons; 2000 Nov 6-9; Fukuoka, Japan. 2. International Transplant Registry. Available at: http://www.ihcs.on.ca/itr/. 3. Schraut WH, Lee KWK, Sitrin M. Recipient growth and nutritional status following transplantation of segmental smallbowel allografts. J Surg Res 1987;43:1-9. 4. Sonnino RE, Harmel RP. Technical aspects of intestinal transplantation in the rat. J Invest Surg 1988;1:55-64. 5. Wolvekamp MCJ, Heineman E, Marquet RL, Meijssen MAC, deBruin RWF, Molenaar JC. Segmental intestinal transplantation can be an adequate therapy for short bowel syndrome in growing dogs. J Pediatr Surg 1995;30:396-401. 6. Benchimol D, Pesce A, Delque-Bayer P, et al. Jejunal versus ileal segmental allografts in the dog: comparison of immunologic and functional results. Surgery 1992;112:918-27. 7. Kimura K, LaRosa CA, Blank MA, et al. Successful segmental intestinal transplantation in enterectomized pigs. Ann Surg 1990;211:158-64. 8. Nakao M, Taguchi T, Suit S, et al. Technical aspects of pig model in living-related small intestinal transplantation. Asian J Surg 2001;24:353-6. 9. Hasegawa T, Sasaki T, Shimizu Y, et al. Living-related small bowel transplantation for a 16-year-old patient with microvillus inclusion disease. Presented at 17th Congress of Asian Association of Pediatric Surgeons; 2000 Nov 6-9; Fukuoka, Japan. 10. Uemoto S, Tanaka K. Surgical techniques and results in living donor small bowel transplantation. Presented at the 7th International Small bowel Transplant Symposium; 2001, Sept 12-15; Stockholm, Sweden. 11. Schroeder P, Goulet O, Lear PA. Small-bowel transplantation: European experience. Lancet 1990;336:110-1. 12. Anthone GJ, Wang BH, Zinner MJ, Yeo CJ. Site-specific variations in basal and meal-stimulated intestinal absorption. J Surg Res 1992;52:454-8. 13. Taguchi T, Hirata Y, Hirose R, Yamada T, Suita S. Short segmental intestinal transplantation in rats—functional comparison of jejunal and ileal grafts. Transplant Proc 1992;24:107980. 14. Booth CC, Evans KT, Menzies T, Street DF. Intestinal hypertrophy following partial resection of the small bowel in the rat. Br J Surg 1959;46:403-10. 15. Dowling RH, Booth CC. Structural and functional changes following small intestinal resection in the rat. Clin Sci 1967;32:139-49. 16. Hanson WR, Osborne JW, Sharp JG. Compensation by the residual intestine after intestinal resection in the rat. II: Influence of postoperative time interval. Gastroenterology 1977;72:701-5. 17. Hirata Y, Ishii K, Taguchi T, Suita S, Takeshige K. Conversion of xanthine dehydrogenase to xanthine oxidase during ischemia of the rat small intestine and the effect of trifluoperazine on the conversion. J Pediatr Surg 1993;28:597-600. 18. Deitch EA, Specian RD, Berg RD. Endotoxin-induced bacterial translocation and mucosa permeability: role of xanthine oxidase, complement activation, and macrophage products. Crit Care Med 1991;19:785-91.
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19. Deitch EA, Taylor M, Grisham M, Ma L, Bridges W, Berg R. Endotoxin induces bacterial translocation and increases xanthine oxidase activity. J Trauma 1989;29:1679-83. 20. Schlemminger R, Lottermoser S, Gieseler RKH, et al. The adaptive response of the rat small intestine after resection and segmental transplantation during the early postoperative phase. Res Exp Med 1993;193:213-24. 21. Kiyozaki H, Kobayashi E, Toyama N, Miyata M. Segmental small bowel transplantation in the rat: comparison of lipid absorption between jejunal and ileal grafts. J Parent Ent Nutr 1996;20:67-70. 22. Kimura K, Money SR, Jaffe BM. Short-segment orthotopic intestinal isografts and allografts in enterectomized rats. Transplantation 1987;44:579-82. 23. Rahman MS, Taguchi T, Nakao M, Yamada T, Suita S. Longterm results of short segmental syngeneic small intestinal transplantation: Comparison of jejunal and ileal grafts. J Pediatr Surg 1996;31:908-11. 24. Taguchi T, Fujii Y, Nakao M, Ogita K, Shima Y, Suita S. Expression of immediate-early genes c-Fos and c-Jun in small intestinal transplantation. Transplant Proc 2000; 32:1279. 25. Ehrenfried JA, Townsend CM, Thompson JC, Evers BM. Increases in nup475 and c-jun are early molecular events that precede the adaptive hyperplastic response after small bowel resection. Ann Surg 1995;222:51-6. 26. Taguchi T, Zorychta E, Guttman FM. Evaluation of UW solution for preservation of small intestinal transplants in the rat. Transplantation 1992;53:1202-5. 27. Raju S, Fujiwara H, Lewin JR, Grogan JB. Twelve hour and twenty four hour preservation of small bowel allografts by simple hypothermia. Transplantation 1988;45:290-3. 28. Nakao M, Taguchi T, Yanai K, Yamada T, Suita S. Energy metabolism during cold ischemia and reperfusion in rat small intestinal transplantation: comparison of jejunal and ileal grafts. J Pediatr Surg 1997;32:1675-8. 29. Taguchi T, Nakao M, Yanai K, Rahman MS, Yamada T, Suita S. Comparison of jejunal and ileal grafts from the aspects of cold preservation and immunologic reaction. Transplant Proc 1998;30:2636-7. 30. Takeyoshi I, Zhang S, Nomoto M, et al. Mucosa damage and recovery of the intestine after prolonged preservation and transplantation in dogs. Transplantation 2001;71:1-7. 31. Reynolds JD, Kirk D. Two types of sheep Peyer’s patches: location along gut does not influence involution. Immunology 1989;66:308-11. 32. Kimura K, Money SR, Jaffe BM. The effects of cyclosporine on varying segments of small-bowel grafts in the rat. Surgery 1988;104:64-9. 33. Lossing A, Nordgren S, Cohen Z, et al. Histologic monitoring of rejection in small intestinal transplantation. Transplant Proc 1982;14:643-5. 34. Stangel MJ, Schraut WH, Moynihan HL, Lee T. Rejection of ileal versus jejunal allografts. Transplantation 1989;47:424-7. 35. DeBruin RWF, Heineman E, Meijssen MAC, Jeekel H, Marquet RL. Small bowel transplantation in rats. The effect of pretransplant donor-specific blood transfusions on various segments of small bowel grafts. Transplantation 1990;50:92830. 36. Stangel MJ, Schraut WH, Moynihan HL, Lee TK, Lee KKW. Effect of cyclosporin therapy in comtrolling the rejection of ileal versus jejunal allografts. Transplant Int 1990;3:149-55. 37. Yamada T, Ogita K, Nakao M, Taguchi T, Suita S. Comparison of jejunal and ileal transplantation -from the aspect of blood cytokine levels. Presented at the 17th Congress of Asian Association of Pediatric Surgeons; 2000 Nov 6-9; Fukuoka, Japan.