- Email: [email protected]
Living Related Pancreas Transplantation Alone With Enteric Drainage in Japan: Case Report
WHOLE GLAND
Living Related Pancreas Transplantation Alone With Enteric Drainage in Japan: Case Report Y. Sato, H. Nakatsuka, S. Yamamoto, H. Oya, T. Kobayashi, T. Watanabe, H. Kokai, T. Kenmochi, and K. Hatakeyama ABSTRACT In this study, we report a living donor partial pancreas transplantation using intraportal donor-specific leukocyte transfusion (DSLT). The recipient was a 38-year-old woman who had type I diabetes mellitus for 17 years. Hypoglycemia occurred 2 or 3 times per week. Her hemoglobin A1c level was 9.0%, and she required 70 U of insulin almost every day. The donor was her 64-year-old father. The steroid-minimized immunosuppressive protocol included 1.5mg of thymoglobulin administered with a steroid bolus on days 0, 4, and 7 postoperatively. Steroids were never prescribed thereafter. Postoperative maintenance therapy included tacrolimus (FK506) and mycophenolate mofetil. In addition to these conventional approarches, we administered intraportal DSLT on days 0, 1, 4, and 7 after transplantation. The donor-specific leukocytes (40mL) had been separated from donor whole blood using an apheresis filter (Cellsorba EX; Asahi Kasei medical Co, Ltd, Tokyo, Japan). In the recipient operation, a segmental pancreas graft was transplanted into the right iliac cavity with enteric drainage with a pancreatic duct stent. Operation time was 6 hours. The postoperative course was uneventful. The patient was discharged on day 15 after transplantation. There was no acute rejection for six months after transplantation. The hemoglobin A1c level recovered to 5.1% with 6 U of insulin per day. At immunologic analysis, only interleukine-10 cytokine production was elevated at 7 days after transplantation. At flow cytometry cross-match analysis, the immunoglobulin M antibody decreased from day 7 after transplantation. We conclude that intraportal DSLT may be an effective adjunct to a steroid-free regimen.
From the Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Niigata, Japan. This study was supported in part by a Grant-in-Aid for Scientific Research (No. 17390461) from the Ministry of Education, Science, Sports, and Culture of Japan.
Address reprint requests to Yoshinobu Sato, MD, PhD, Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, 1-757 Asahimachi-dori, Niigata City, Niigata 951-8510, Japan. E-mail: [email protected]
© 2008 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/08/$–see front matter doi:10.1016/j.transproceed.2008.08.052
Transplantation Proceedings, 40, 2559 –2561 (2008)
2559
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SATO, NAKATSUKA, YAMAMOTO ET AL
Table 1. Cytokine Production after DSLT Via Portal Vein in Living Related Pancreas Transplantation Alone Postoperative Day Variable
Preoperation
1
4
7
14
40
IL-2, U/mL IL-4, U/mL IL-10, pg/mL IFN-␥, IU/mL TNF-␣, pg/mL
1.2 8.1 ⬍2 ⬍0.1 ⬍5
⬍0.8 6.6 ⬍2 ⬍0.1 ⬍5
⬍0.8 6.1 ⬍2 ⬍0.1 ⬍5
⬍0.8 4.4 158 ⬍0.1 ⬍5
1.0 5.2 5 ⬍0.1 15
⬍0.8 3.5 ⬍2 ⬍0.1 ⬍5
Only IL-10 cytokine production was elevated on day 7 after transplantation. DSLT, donor-specific luekocyte transplantation; IL, interleukin; IFN, interferon; TNF, tumor necrosis factor.
R
ecently, the number of cadaver donor pancreas transplantations has remarkably increased because of improved immunosuppression. However, only a few pancreas transplantations have been performed in Japan because of the shortage of cadaver donors. In this serious situation, since 2004, a few living related donor pancreas transplantations (LRPT) have been performed in patients with type I diabetes mellitus.1 The pancreatic duct drainage had been performed using a bladder anastomosis.1 In this study, we performed an enteric drainage with a steroid-minimization regimen together with intraporatal administration of donor-specific leukocytes. PATIENTS AND METHODS A 38-year-old woman with a 21-year history of type I diabetes mellitus underwent living related partial pancreatic transplantation on August 10, 2006. She had experienced hypoglycemic episodes several times per week. Preoperatively, her body weight was 66 kg, with body mass index of 25.9, and hemoglobin A1c level was 9.0%. She had only slight complications of diabetes. The donor was her 64-year-old father, whose preoperative revealed oral and intravenous glucose tolerance tests (75 g of glucose) normal results.
Immunosuppresion We performed intraportal infusion of donor-specific antigen, which enabled both a rapid reduction in immunosuppression and sought to achieve macrochimerism of donor type CD56-positive T cells in the grafted liver.2– 4 Induction of immunosuppression included both thymoglobulin, 1.5 mg/kg, on days 0, 4, and 7 and intraportal administration of donor leukocytes on days 0, 4, 7, and 10 after transplantation. At each time point, approximately 40 mL of donor-specific leukocytes was separated from donor whole blood using an apheresis filter (Cellsorba EX; Asahi Kasei medical Co, Ltd, Tokyo, Japan) which has been used as leukocytoapheresis therapy with a leukocyte removal filter for ulcerative colitis. The
Fig 1. Mixed lymphocyte reaction after living related pancreas transplantation alone.
leukocyte count was 1 to 5 ⫻ 108/L. Maintenance of immunosuppression was with tacrolimus (FK506) and mycophenolate mofetil. Interleukin (IL)–2, IL-4, and IL-10, and interferon-␥-related Th1 and Th2 cytokines were examined in the early period after transplantation. Mixed lymphocyte reactions were also analyzed after transplantation.
Operative Procedure The donor underwent distal pancreatectomy with splenectomy. The pancreas was cut to the left of the portal vein such that remnant pancreas was half of the whole pancreas at computed tomographic volumetry. The pancreatic duct was repaired by ligation transfixation suture. The pancreas was closed by fishmouth suturing with 6-0 polypropylene sutures. Operative time was 4 hours 17 minutes; intraoperative hemorrhage was 420 mL. In the recipient, a midline abdominal incision was made. First, the right iliac vein and splenic vein anastomoses were made using 6-0 prolene polypropylene sutures. Second, the right iliac artery to splenic arterial anastomosis was made using 7-0 polypropylene sutures. Third, the pancreatic duct reconstruction was performed using a mucosal-mucosal end-to-side Rouxen-Y anastomosis to the jejunum using 6-0 PDS sutures (Ethicon Inc, Pescataway, new Jersey) 80 cm from the ligament of Treitz.
RESULTS
The donor was discharged at 2 weeks after surgery without any complications. The recipient postoperative course was also uneventful. Immunosuppression was performed using a steroid-free regimen with thymoglobulin, tacrolimus, and mycophenolate mofetil, with intraportal infusion of donorspecific antigen.2 There was neither hemorrhage nor pancreatic leakage. The patient was discharged 15 days after the transplantation procedure. Immunologic analysis revealed activation of IL-10 of Th2-type cytokine on day 7 after transplantation (Table 1). Mixed lymphocyte reaction demonstrated donor-specific immunosuppression at 8 months after transplantation (Fig 1). The patient no longer had hypoglycemia. Her body weight decreased by 56 kg, and hemoglobin A1c level decreased to 5.1% at 6 months after the operation. There has been no rejection to date. DISCUSSION
This case in Japan used physiologic enteric drainage and a minimal steroid regimen in a patient who underwent LRPT. Enteric drainage has remarkably increased in use in cadaver pancreas transplantations. In living partial pancreas transplantation, enteric drainage is considered one option for physiologic reconstruction. In patients with type 1 diabetes
LIVING RELATE PANCREAS TRANSPLANTATION
mellitus, LRPT may be a useful therapy to prevent complications of diabetes. We have previously reported intraportal administration of donor-specific transfusion in living related donor liver transplantation. In this study, we demonstrated that intraportal administration of donor leukocytes may also be effective for redundant induction therapy for a steroid-free regimen in LRPT.5 REFERENCES 1. Kenmochi T, Asano T, Maruyama M, et al: Current and future status of simultaneous pancreas-kidney transplant from living donor. Nippon Geka Gakkai Zasshi 106:489, 2005
2561 2. Sato Y, Ichida T, Yamamoto S, et al: Analysis of microchimerism in peripheral blood by short tandem repeat sequences immediately after living related liver transplantation. Transplant Proc 35:412, 2003 3. Sato Y, Watanabe H, et al: Macrochimerism of donor type CD56⫹CD3⫹ T cells in donor specific transfusion via portal vein following living related donor liver. Hepatogastroenterol 50:2161, 2003 4. Sato Y, Ichida T, Watanabe H, et al: Repeating intraportal donor specific transfusion may induce tolerance following adult living related donor liver transplantation. Hepatogastroenterology 51:601, 2003 5. Tanchanco R, Krishnamurthi V, Winans C, et al: Beneficial outcomes of a steroid-free regimen with thymoglobulin induction in pancreas-kidney transplantation. Transplant Proc 40:1551, 2008
Living Related Pancreas Transplantation Alone With Enteric Drainage in Japan: Case Report Y. Sato, H. Nakatsuka, S. Yamamoto, H. Oya, T. Kobayashi, T. Watanabe, H. Kokai, T. Kenmochi, and K. Hatakeyama ABSTRACT In this study, we report a living donor partial pancreas transplantation using intraportal donor-specific leukocyte transfusion (DSLT). The recipient was a 38-year-old woman who had type I diabetes mellitus for 17 years. Hypoglycemia occurred 2 or 3 times per week. Her hemoglobin A1c level was 9.0%, and she required 70 U of insulin almost every day. The donor was her 64-year-old father. The steroid-minimized immunosuppressive protocol included 1.5mg of thymoglobulin administered with a steroid bolus on days 0, 4, and 7 postoperatively. Steroids were never prescribed thereafter. Postoperative maintenance therapy included tacrolimus (FK506) and mycophenolate mofetil. In addition to these conventional approarches, we administered intraportal DSLT on days 0, 1, 4, and 7 after transplantation. The donor-specific leukocytes (40mL) had been separated from donor whole blood using an apheresis filter (Cellsorba EX; Asahi Kasei medical Co, Ltd, Tokyo, Japan). In the recipient operation, a segmental pancreas graft was transplanted into the right iliac cavity with enteric drainage with a pancreatic duct stent. Operation time was 6 hours. The postoperative course was uneventful. The patient was discharged on day 15 after transplantation. There was no acute rejection for six months after transplantation. The hemoglobin A1c level recovered to 5.1% with 6 U of insulin per day. At immunologic analysis, only interleukine-10 cytokine production was elevated at 7 days after transplantation. At flow cytometry cross-match analysis, the immunoglobulin M antibody decreased from day 7 after transplantation. We conclude that intraportal DSLT may be an effective adjunct to a steroid-free regimen.
From the Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Niigata, Japan. This study was supported in part by a Grant-in-Aid for Scientific Research (No. 17390461) from the Ministry of Education, Science, Sports, and Culture of Japan.
Address reprint requests to Yoshinobu Sato, MD, PhD, Division of Digestive and General Surgery, Niigata University Graduate School of Medical and Dental Sciences, Niigata, 1-757 Asahimachi-dori, Niigata City, Niigata 951-8510, Japan. E-mail: [email protected]
© 2008 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/08/$–see front matter doi:10.1016/j.transproceed.2008.08.052
Transplantation Proceedings, 40, 2559 –2561 (2008)
2559
2560
SATO, NAKATSUKA, YAMAMOTO ET AL
Table 1. Cytokine Production after DSLT Via Portal Vein in Living Related Pancreas Transplantation Alone Postoperative Day Variable
Preoperation
1
4
7
14
40
IL-2, U/mL IL-4, U/mL IL-10, pg/mL IFN-␥, IU/mL TNF-␣, pg/mL
1.2 8.1 ⬍2 ⬍0.1 ⬍5
⬍0.8 6.6 ⬍2 ⬍0.1 ⬍5
⬍0.8 6.1 ⬍2 ⬍0.1 ⬍5
⬍0.8 4.4 158 ⬍0.1 ⬍5
1.0 5.2 5 ⬍0.1 15
⬍0.8 3.5 ⬍2 ⬍0.1 ⬍5
Only IL-10 cytokine production was elevated on day 7 after transplantation. DSLT, donor-specific luekocyte transplantation; IL, interleukin; IFN, interferon; TNF, tumor necrosis factor.
R
ecently, the number of cadaver donor pancreas transplantations has remarkably increased because of improved immunosuppression. However, only a few pancreas transplantations have been performed in Japan because of the shortage of cadaver donors. In this serious situation, since 2004, a few living related donor pancreas transplantations (LRPT) have been performed in patients with type I diabetes mellitus.1 The pancreatic duct drainage had been performed using a bladder anastomosis.1 In this study, we performed an enteric drainage with a steroid-minimization regimen together with intraporatal administration of donor-specific leukocytes. PATIENTS AND METHODS A 38-year-old woman with a 21-year history of type I diabetes mellitus underwent living related partial pancreatic transplantation on August 10, 2006. She had experienced hypoglycemic episodes several times per week. Preoperatively, her body weight was 66 kg, with body mass index of 25.9, and hemoglobin A1c level was 9.0%. She had only slight complications of diabetes. The donor was her 64-year-old father, whose preoperative revealed oral and intravenous glucose tolerance tests (75 g of glucose) normal results.
Immunosuppresion We performed intraportal infusion of donor-specific antigen, which enabled both a rapid reduction in immunosuppression and sought to achieve macrochimerism of donor type CD56-positive T cells in the grafted liver.2– 4 Induction of immunosuppression included both thymoglobulin, 1.5 mg/kg, on days 0, 4, and 7 and intraportal administration of donor leukocytes on days 0, 4, 7, and 10 after transplantation. At each time point, approximately 40 mL of donor-specific leukocytes was separated from donor whole blood using an apheresis filter (Cellsorba EX; Asahi Kasei medical Co, Ltd, Tokyo, Japan) which has been used as leukocytoapheresis therapy with a leukocyte removal filter for ulcerative colitis. The
Fig 1. Mixed lymphocyte reaction after living related pancreas transplantation alone.
leukocyte count was 1 to 5 ⫻ 108/L. Maintenance of immunosuppression was with tacrolimus (FK506) and mycophenolate mofetil. Interleukin (IL)–2, IL-4, and IL-10, and interferon-␥-related Th1 and Th2 cytokines were examined in the early period after transplantation. Mixed lymphocyte reactions were also analyzed after transplantation.
Operative Procedure The donor underwent distal pancreatectomy with splenectomy. The pancreas was cut to the left of the portal vein such that remnant pancreas was half of the whole pancreas at computed tomographic volumetry. The pancreatic duct was repaired by ligation transfixation suture. The pancreas was closed by fishmouth suturing with 6-0 polypropylene sutures. Operative time was 4 hours 17 minutes; intraoperative hemorrhage was 420 mL. In the recipient, a midline abdominal incision was made. First, the right iliac vein and splenic vein anastomoses were made using 6-0 prolene polypropylene sutures. Second, the right iliac artery to splenic arterial anastomosis was made using 7-0 polypropylene sutures. Third, the pancreatic duct reconstruction was performed using a mucosal-mucosal end-to-side Rouxen-Y anastomosis to the jejunum using 6-0 PDS sutures (Ethicon Inc, Pescataway, new Jersey) 80 cm from the ligament of Treitz.
RESULTS
The donor was discharged at 2 weeks after surgery without any complications. The recipient postoperative course was also uneventful. Immunosuppression was performed using a steroid-free regimen with thymoglobulin, tacrolimus, and mycophenolate mofetil, with intraportal infusion of donorspecific antigen.2 There was neither hemorrhage nor pancreatic leakage. The patient was discharged 15 days after the transplantation procedure. Immunologic analysis revealed activation of IL-10 of Th2-type cytokine on day 7 after transplantation (Table 1). Mixed lymphocyte reaction demonstrated donor-specific immunosuppression at 8 months after transplantation (Fig 1). The patient no longer had hypoglycemia. Her body weight decreased by 56 kg, and hemoglobin A1c level decreased to 5.1% at 6 months after the operation. There has been no rejection to date. DISCUSSION
This case in Japan used physiologic enteric drainage and a minimal steroid regimen in a patient who underwent LRPT. Enteric drainage has remarkably increased in use in cadaver pancreas transplantations. In living partial pancreas transplantation, enteric drainage is considered one option for physiologic reconstruction. In patients with type 1 diabetes
LIVING RELATE PANCREAS TRANSPLANTATION
mellitus, LRPT may be a useful therapy to prevent complications of diabetes. We have previously reported intraportal administration of donor-specific transfusion in living related donor liver transplantation. In this study, we demonstrated that intraportal administration of donor leukocytes may also be effective for redundant induction therapy for a steroid-free regimen in LRPT.5 REFERENCES 1. Kenmochi T, Asano T, Maruyama M, et al: Current and future status of simultaneous pancreas-kidney transplant from living donor. Nippon Geka Gakkai Zasshi 106:489, 2005
2561 2. Sato Y, Ichida T, Yamamoto S, et al: Analysis of microchimerism in peripheral blood by short tandem repeat sequences immediately after living related liver transplantation. Transplant Proc 35:412, 2003 3. Sato Y, Watanabe H, et al: Macrochimerism of donor type CD56⫹CD3⫹ T cells in donor specific transfusion via portal vein following living related donor liver. Hepatogastroenterol 50:2161, 2003 4. Sato Y, Ichida T, Watanabe H, et al: Repeating intraportal donor specific transfusion may induce tolerance following adult living related donor liver transplantation. Hepatogastroenterology 51:601, 2003 5. Tanchanco R, Krishnamurthi V, Winans C, et al: Beneficial outcomes of a steroid-free regimen with thymoglobulin induction in pancreas-kidney transplantation. Transplant Proc 40:1551, 2008