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Treatment of Short Gut Syndrome With Early Living Related Small Bowel Transplantation
Treatment of Short Gut Syndrome With Early Living Related Small Bowel Transplantation S.F. Wang, X.M. Che, J.C. Chen, S.Y. Lu, L. Fan, R. Wang, and G.W. Li ABSTRACT Aim. To investigate the results of treating short bowel syndrome with an early living related small bowel transplantation (SBT). Methods. A 17-year-old boy with a 20-cm-long residual intestine due to necrotic volvulus received an early living related SBT from his mother. Donor-specific blood transfusion was performed for 8 weeks before transplantation, each time for 50 mL every week. Cytomegalovirus status in both donor and recipient was negative. A 160-cm distal ileal segment was removed from the donor. The graft ilecolic artery and vein were anastomosed to the recipient’s infrarenal aorta and caval vein. The proximal end of the graft was anastomosed end-to-end to the residual recipient jejunum; the distal anastomosis, between the distal end of the graft and transverse colon. An ileostomy was also performed. Immunosuppression, infection prophylaxis, and antithrombotic and nutrition support were given postoperatively. Results. The donor had an uneventful recovery. No technical complications were observed. The recipient was alive and well at 31 weeks after the operation. No graft rejection or infection was observed. He was off TPN 8 weeks after the operation and took low-fat food. The D-xylose test in the recipient was almost normal. Conclusions. Early living related small intestine transplantation is a good treatment for short bowel syndrome.
A
AT PRESENT, with the progress of surgical techniques, effective immunosuppressive protocols, and improved perioperative management, small bowel transplantation (SBT) has shown a steady increase in graft and patient survival. SBT has now become an accepted therapy for intestinal failure such as short bowel syndrome. We report the case of a 17-year-old boy with ultra-short gut syndrome who was successfully treated with early living related small bowel transplantation. CASE REPORT The patient was referred with complaints of acute abdominal pain and underwent massive small intestine and ascending colon resection secondary to necrotic volvulus in November 2003. Only 20 cm of jejunum distal to the ligament of Treitz remained; there was no ileocecal valve. The boy was maintained on total parenteral nutrition (TPN) for a relatively short period (6 months) before transplantation. The donor was the recipient’s 41-year-old mother (157 cm, 53 kg). Blood type was identical (O to O). The donor and recipient were mismatched at three HLA loci: donor A 11,30; B 35,51; DR 11,14 versus recipient A 24,30; B 35,51; DR 11,15.
Selective superior mesenteric angiogram of the donor defined the size and position of the ileocolic vessels as the vascular pedicle for the ileal graft. Virologic studies for hepatitis B and C, cytomegalovirus (CMV), and Epstein-Barr virus in donor and recipient were negative. Weekly donor-specific blood transfusion (DSBT) of 50 mL was performed for 8 weeks before transplantation. The surgical techniques of graft procurement and transplantation were those described by Gruessner and Sharp.1 The distal 160 cm of the ileum was resected from the donor small intestine from a length of 480 cm, leaving the ileocecal valve and terminal ileum intact. Donor ileal continuity was reestablished with an end-to-end anastomosis. In the recipient, the graft artery was anastomosed to the infrarenal aorta and the graft vein to the infrarenal inferior From the Department of General Surgery, First Hospital (S.F.W., X.M.C., J.C.C., S.Y.L., L.F., R.W.) and Second Hospital (G.W.L.), Xi’an Jiaotong University, Xi’an, Shaanxi Province, China. Address reprint requests to Mr S.F. Wang, First Hospital, Xi’an, Jiaotong University, Department of General Surgery, 1 Jiang Kang Xi Road, Xi’an, Shaanxi Province, 710061, People’s Republic of China.
© 2005 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/05/$–see front matter doi:10.1016/j.transproceed.2005.10.092
Transplantation Proceedings, 37, 4461– 4463 (2005)
4461
4462 vena cava, both of them end-to-side. The proximal end of the graft was anastomosed end-to-end to the recipient residual small intestine using an EEA stapling device, which was also used for the anastomosis between the distal end of the ileal graft and the transverse colon. An ileostomy was made at the distal end of the graft to serve as a window for rejection surveillance. Posttransplant immunosuppression consisted of two doses daclizumab and maintenance with a combination of tacrolimus, mycophenolate mofetil (MMF), and prednisone. A short course of perioperative antibiotic prophylaxis with cefoperazone/sulbacta was used, while antiviral and antifungal prophylaxis was achieved using gancyclovir and fluconazole.
RESULTS
The donor had an uneventful recovery, with a hospital stay of 7 days. During follow-up at 1 month after the operation, she had occasional diarrhea that was easily controlled with symptomatic therapy, but at present diarrhea has not recurred. She maintained the same preoperative weight. Serial testing for D-xylose absorption and serum total protein as well as serum albumin demonstrated normal values. The recipient is currently alive with a follow-up of 31 weeks. Postoperative anastomotic leak, intraabdominal infection, or graft thrombosis were not observed. Tacrolimus trough levels were maintained at 20, 25, and 15 ng/mL during months 1, 2, and 3, respectively, and about 10 ng/mL thereafter. Graft bleeding from the stoma was observed at 22 days after operation. The trough level was increases to 30 ng/mL for 3 days for the purpose of controlling graft rejection, but it was not confirmed on pathological exam. So the trough level was again adjusted to the target level of 20 to 25 ng/mL for the remaining days of the first month. Graft surveillance was conducted at 2 days after operation. Endoscopic assessments and directed mucosal biopsies were performed through the stoma. Up to now, pathological analyses of biopsies and clinical features of the recipient indicated no graft rejection. Enteral nutrition, which began 2 days after transplant to maintain mucosal integrity and function, was increased slowly up to the calculated goal. TPN was slowly tapered and stopped at 8 weeks after the operation. Now the donor takes low-fat food; meanwhile, his weight has increased from 45 kg before transplantation to 50 kg. The D-xylose absorption test progressively improved to be close to normal values. The serum albumin level normalized. DISCUSSION
The intestine has been more difficult to transplant than other solid organs. In recent years new potent immunosuppressive drugs such as tacrolimus, MMF, and daclizumab are being used, so clinical outcomes of SBT have improved markedly. In some larger centers, the 1-year patient survival rate for intestinal transplants has been 84%.2 In addition, transplantation with a living donor has some advantages: a good HLA match, milder rejection, and shorter ischemic time, so living related SBT is a new option for patients with
WANG, CHE, CHEN ET AL
intestinal failure. Obviously, this case with 20-cm length of residual intestine cannot benefit from bowel rehabilitation. He had a higher chance to develop fatal complications during long-term TPN support. The cost of prolonged TPN is higher than that of SBT3; second, more than 55% of patients with short gut syndrome require a simultaneous liver transplant for TPN-induced liver failure at the time of referral (International Transplant Registry, 2001 data); third, longer-term TPN may cause a poor quality of life for the patient.4 Taking these factors into account and referring to previous experience,5 we have decided to treat the patient with early living related SBT after only 6 months after TPN support. At present, the operation for SBT is not standardized. Among approaches to venous drainage of the graft, for example, Hashimoto and Ohyanagi reported that systemic drainage is preferable from a technical feasibility viewpoint.6 We adapted this method in our first case. However, some articles support portal drainage from an immunological and metabolic point of view.7,8 Still others have held that there is no difference between these two methods of reconstruction, regarding bacterial translocation, immunological, and metabolic aspects.9 –11 Therefore, further studies will be necessary to determine whether there is difference between the two kinds of venous drainage. In addition to administration of tacrolimus, MMF, and daclizumab for postoperative management, we applied donor-specific blood transfusions preoperatively with the aim to induce immune tolerance. Regardless of rats or larger animals such as pigs, preoperative or intraoperative DSBT can induce immune tolerance and promote chimerism. A recent report indicated that clinical SBT may benefit from intraoperative DSBT.12 To analyze our recipient, no graft rejection has been observed up to now, according to clinical findings and pathological results of biopsies through the ileostomy, probably partially attributed to preoperative DSBT. The recipient received intensive care and management and showed no signs of pathogen infection. The initial success of this case shows that reasonable administration of immunosuppressive agents and appropriate use of antibacterial, antiviral, and antifungal drugs as well as earlier enternal feeding to maintain gut barrier function are key to infection prophylaxis. REFERENCES 1. Gruessner RW, Sharp HL: Living-related intestinal transplantation: first report of a standardized surgical technique. Transplantation 64:1605, 1997 2. Nishida S, Levi D, Kato T, et al: Ninety-five cases of intestinal transplantation at the university of Miami. Journal of Gastrointestinal Surgery 6:233, 2002 3. Wamer BW, Vanderhoof JA, Rdyes JD: What is new in the management of short gut syndrome in children. J Am Coll Surg 190:725, 2000 4. Holden C: Review of home paediatric parenteral nutrition on the UK. Br J Nurs 10:782, 2001 5. Cicalese L, Sileri P, Benedetti E, et al: Early living related segmental intestinal transplantation for trauma-induced ultra-short gut syndrome. Transplant Proc 34:914, 2002
SHORT GUT SYNDROME 6. Hashimoto N, Ohyanagi H: Metabolic effects of systemic venous drainage in small bowel transplantation. Transplant Proc 35:1567, 2003 7. Nymann T, Hathaway DK, Shokouh MH, et al: Incidence of kidney and pancreas rejection following portal enteric verus systemic-bladder pancreas-kidney transplantation. Transplant Proc 29:640, 1997 8. Todo S, Reyes J, Furukawa H, et al: Outcome analysis of 71 clinical intestinal transplantations. Ann Surg 222:270, 1995 9. Fryer JP, Kim S, Wells CL, et al: Bacterial translocation in a large-animal model of small bowel transplantation. Portal vs systemic
4463 venous drainage and effect of tacrolimus immunosurppression. Arch Surg 131:77, 1996 10. Hashimoto N, Ishii H, Kitada T, et al: Significance of venous drainage for small-bowel allografts. Hepatogastroenterology 39: 511, 1992 11. Shaffer D, Diflo T, Love W, et al: Metabolic effects of systemic versus portal venous drainage of orthotopic small bowel isografts. Transplant Proc 21:2872, 1989 12. Pirenne J, Koshiba T, Geboes K, et al: Complete freedom from rejection after intestinal transplantation using a new tolerance protocol combined with low immunosuppression. Transplantation 73:966, 2002
A
AT PRESENT, with the progress of surgical techniques, effective immunosuppressive protocols, and improved perioperative management, small bowel transplantation (SBT) has shown a steady increase in graft and patient survival. SBT has now become an accepted therapy for intestinal failure such as short bowel syndrome. We report the case of a 17-year-old boy with ultra-short gut syndrome who was successfully treated with early living related small bowel transplantation. CASE REPORT The patient was referred with complaints of acute abdominal pain and underwent massive small intestine and ascending colon resection secondary to necrotic volvulus in November 2003. Only 20 cm of jejunum distal to the ligament of Treitz remained; there was no ileocecal valve. The boy was maintained on total parenteral nutrition (TPN) for a relatively short period (6 months) before transplantation. The donor was the recipient’s 41-year-old mother (157 cm, 53 kg). Blood type was identical (O to O). The donor and recipient were mismatched at three HLA loci: donor A 11,30; B 35,51; DR 11,14 versus recipient A 24,30; B 35,51; DR 11,15.
Selective superior mesenteric angiogram of the donor defined the size and position of the ileocolic vessels as the vascular pedicle for the ileal graft. Virologic studies for hepatitis B and C, cytomegalovirus (CMV), and Epstein-Barr virus in donor and recipient were negative. Weekly donor-specific blood transfusion (DSBT) of 50 mL was performed for 8 weeks before transplantation. The surgical techniques of graft procurement and transplantation were those described by Gruessner and Sharp.1 The distal 160 cm of the ileum was resected from the donor small intestine from a length of 480 cm, leaving the ileocecal valve and terminal ileum intact. Donor ileal continuity was reestablished with an end-to-end anastomosis. In the recipient, the graft artery was anastomosed to the infrarenal aorta and the graft vein to the infrarenal inferior From the Department of General Surgery, First Hospital (S.F.W., X.M.C., J.C.C., S.Y.L., L.F., R.W.) and Second Hospital (G.W.L.), Xi’an Jiaotong University, Xi’an, Shaanxi Province, China. Address reprint requests to Mr S.F. Wang, First Hospital, Xi’an, Jiaotong University, Department of General Surgery, 1 Jiang Kang Xi Road, Xi’an, Shaanxi Province, 710061, People’s Republic of China.
© 2005 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/05/$–see front matter doi:10.1016/j.transproceed.2005.10.092
Transplantation Proceedings, 37, 4461– 4463 (2005)
4461
4462 vena cava, both of them end-to-side. The proximal end of the graft was anastomosed end-to-end to the recipient residual small intestine using an EEA stapling device, which was also used for the anastomosis between the distal end of the ileal graft and the transverse colon. An ileostomy was made at the distal end of the graft to serve as a window for rejection surveillance. Posttransplant immunosuppression consisted of two doses daclizumab and maintenance with a combination of tacrolimus, mycophenolate mofetil (MMF), and prednisone. A short course of perioperative antibiotic prophylaxis with cefoperazone/sulbacta was used, while antiviral and antifungal prophylaxis was achieved using gancyclovir and fluconazole.
RESULTS
The donor had an uneventful recovery, with a hospital stay of 7 days. During follow-up at 1 month after the operation, she had occasional diarrhea that was easily controlled with symptomatic therapy, but at present diarrhea has not recurred. She maintained the same preoperative weight. Serial testing for D-xylose absorption and serum total protein as well as serum albumin demonstrated normal values. The recipient is currently alive with a follow-up of 31 weeks. Postoperative anastomotic leak, intraabdominal infection, or graft thrombosis were not observed. Tacrolimus trough levels were maintained at 20, 25, and 15 ng/mL during months 1, 2, and 3, respectively, and about 10 ng/mL thereafter. Graft bleeding from the stoma was observed at 22 days after operation. The trough level was increases to 30 ng/mL for 3 days for the purpose of controlling graft rejection, but it was not confirmed on pathological exam. So the trough level was again adjusted to the target level of 20 to 25 ng/mL for the remaining days of the first month. Graft surveillance was conducted at 2 days after operation. Endoscopic assessments and directed mucosal biopsies were performed through the stoma. Up to now, pathological analyses of biopsies and clinical features of the recipient indicated no graft rejection. Enteral nutrition, which began 2 days after transplant to maintain mucosal integrity and function, was increased slowly up to the calculated goal. TPN was slowly tapered and stopped at 8 weeks after the operation. Now the donor takes low-fat food; meanwhile, his weight has increased from 45 kg before transplantation to 50 kg. The D-xylose absorption test progressively improved to be close to normal values. The serum albumin level normalized. DISCUSSION
The intestine has been more difficult to transplant than other solid organs. In recent years new potent immunosuppressive drugs such as tacrolimus, MMF, and daclizumab are being used, so clinical outcomes of SBT have improved markedly. In some larger centers, the 1-year patient survival rate for intestinal transplants has been 84%.2 In addition, transplantation with a living donor has some advantages: a good HLA match, milder rejection, and shorter ischemic time, so living related SBT is a new option for patients with
WANG, CHE, CHEN ET AL
intestinal failure. Obviously, this case with 20-cm length of residual intestine cannot benefit from bowel rehabilitation. He had a higher chance to develop fatal complications during long-term TPN support. The cost of prolonged TPN is higher than that of SBT3; second, more than 55% of patients with short gut syndrome require a simultaneous liver transplant for TPN-induced liver failure at the time of referral (International Transplant Registry, 2001 data); third, longer-term TPN may cause a poor quality of life for the patient.4 Taking these factors into account and referring to previous experience,5 we have decided to treat the patient with early living related SBT after only 6 months after TPN support. At present, the operation for SBT is not standardized. Among approaches to venous drainage of the graft, for example, Hashimoto and Ohyanagi reported that systemic drainage is preferable from a technical feasibility viewpoint.6 We adapted this method in our first case. However, some articles support portal drainage from an immunological and metabolic point of view.7,8 Still others have held that there is no difference between these two methods of reconstruction, regarding bacterial translocation, immunological, and metabolic aspects.9 –11 Therefore, further studies will be necessary to determine whether there is difference between the two kinds of venous drainage. In addition to administration of tacrolimus, MMF, and daclizumab for postoperative management, we applied donor-specific blood transfusions preoperatively with the aim to induce immune tolerance. Regardless of rats or larger animals such as pigs, preoperative or intraoperative DSBT can induce immune tolerance and promote chimerism. A recent report indicated that clinical SBT may benefit from intraoperative DSBT.12 To analyze our recipient, no graft rejection has been observed up to now, according to clinical findings and pathological results of biopsies through the ileostomy, probably partially attributed to preoperative DSBT. The recipient received intensive care and management and showed no signs of pathogen infection. The initial success of this case shows that reasonable administration of immunosuppressive agents and appropriate use of antibacterial, antiviral, and antifungal drugs as well as earlier enternal feeding to maintain gut barrier function are key to infection prophylaxis. REFERENCES 1. Gruessner RW, Sharp HL: Living-related intestinal transplantation: first report of a standardized surgical technique. Transplantation 64:1605, 1997 2. Nishida S, Levi D, Kato T, et al: Ninety-five cases of intestinal transplantation at the university of Miami. Journal of Gastrointestinal Surgery 6:233, 2002 3. Wamer BW, Vanderhoof JA, Rdyes JD: What is new in the management of short gut syndrome in children. J Am Coll Surg 190:725, 2000 4. Holden C: Review of home paediatric parenteral nutrition on the UK. Br J Nurs 10:782, 2001 5. Cicalese L, Sileri P, Benedetti E, et al: Early living related segmental intestinal transplantation for trauma-induced ultra-short gut syndrome. Transplant Proc 34:914, 2002
SHORT GUT SYNDROME 6. Hashimoto N, Ohyanagi H: Metabolic effects of systemic venous drainage in small bowel transplantation. Transplant Proc 35:1567, 2003 7. Nymann T, Hathaway DK, Shokouh MH, et al: Incidence of kidney and pancreas rejection following portal enteric verus systemic-bladder pancreas-kidney transplantation. Transplant Proc 29:640, 1997 8. Todo S, Reyes J, Furukawa H, et al: Outcome analysis of 71 clinical intestinal transplantations. Ann Surg 222:270, 1995 9. Fryer JP, Kim S, Wells CL, et al: Bacterial translocation in a large-animal model of small bowel transplantation. Portal vs systemic
4463 venous drainage and effect of tacrolimus immunosurppression. Arch Surg 131:77, 1996 10. Hashimoto N, Ishii H, Kitada T, et al: Significance of venous drainage for small-bowel allografts. Hepatogastroenterology 39: 511, 1992 11. Shaffer D, Diflo T, Love W, et al: Metabolic effects of systemic versus portal venous drainage of orthotopic small bowel isografts. Transplant Proc 21:2872, 1989 12. Pirenne J, Koshiba T, Geboes K, et al: Complete freedom from rejection after intestinal transplantation using a new tolerance protocol combined with low immunosuppression. Transplantation 73:966, 2002