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Utilization of pediatric donors for pancreas transplantation
Utilization of Pediatric Donors for Pancreas Transplantation W.J. Van der Werf, J. Odorico, A.M. D’Alessandro, S. Knechtle, Y. Becker, B. Collins, J. Pirsch, R. Hoffman, and H.W. Sollinger
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OST transplant programs are reluctant to use pediatric donors for pancreas transplantation for fear of inadequate islet cell mass and increased risk of technical complications. Currently, the lower age or size limit for cadaveric pancreas donors is not well defined. In 1996, although there were 162 cadaveric organ donors between 6 and 10 years of age, only 20 pancreas allografts were procured for transplantation. With 1464 patients waiting for simultaneous pancreas and kidney transplants (SPK) and 324 patients waiting for pancreas only transplants at the end of 1996, there is clearly a need to use all available pancreas allografts. We have used donors between 4 and 10 years of age for SPK transplants since 1986. In this paper, we compare the immediate and long term results of our pediatric donor (4 to 10 years of age) and adult donor (11 to 40 years of age) SPK transplants.
PATIENTS AND METHODS From 1986 to 1997, 17 patients at the University of Wisconsin Hospital and Clinics received SPK transplants from pediatric cadaveric donors with a mean age of 8 (range 4 to 10) years, mean weight of 30 (18 to 50) kg, and mean donor to recipient weight ratio of 0.46 (.26 to .92). A comparison analysis was made with 374 SPK recipients who received grafts from “ideal” donors between 11 and 40 years of age. An additional 111 patients who received SPK transplants from donors greater than 40 years of age were excluded from this study. The pancreas grafts were harvested en bloc with the liver and preserved in University of Wisconsin (UW) solution.1 The kidneys were either stored on a pulsatile perfusion machine or cold stored with UW solution. All pancreas grafts were anastomosed to the iliac vessels utilizing a same donor iliac Y graft as previously described. The duodenal segment was drained to either the bladder or small bowel. One patient received a double en bloc kidney. All vascular anastomosis were performed with running 6-0 or 7-0 prolene. The ureter was reconstructed utilizing an extravesical Liche ureteroneocystostomy over a silastic stent. All patients received induction with OKT3, ALG, or ATG, and maintenance immunosuppression with azathioprine or mycophenylate mofetil, cyclosporine or FK 506, and prednisone.
Statistical Analysis Donor, recipient, and outcome variables were compared using the Wilcoxon rank sums test. Survival curves were obtained using the methods of Kaplan and Meier. Survival was compared using the log rank test. All analysis were performed using SAS statistical software (SAS Institute Inc., Cary, North Carolina). 0041-1345/99/$–see front matter PII S0041-1345(98)01578-4
RESULTS
A comparative analysis of donor, recipient, and clinical characteristics between the pediatric (4- to 10-year-old) and adult (11- to 40-year-old) pancreas donor groups demonstrated a significant (P , .01) difference in donor weight (30 vs 74 kg), recipient weight (60 vs 70 kg), donor to recipient weight ratio (0.51 vs 1.08), and recipient gender (76% vs 37% females). This reflects an attempt to select smaller recipients for the smaller pediatric pancreas donors. Other variables analysed were similar for both groups and include year of transplant (1993 vs 1992), and pancreas drainage technique (29% vs 21% enteric). In order to assess whether the choice of smaller, more female recipients may have influenced the graft or patient survival, a multivariate analysis was performed on SPK transplants from donors 4 to 40 years of age demonstrating no significant effect of donor weight, recipient weight, donor to recipient weight ratio, and recipient gender on renal graft, pancreas graft, or patient survival. Early renal and pancreas function was evaluated by serum creatinine and urinary amylase on day 1, day 7, and day of discharge, and fasting blood sugar on day of discharge. All 17 recipients of pediatric pancreas grafts were normoglycemic without insulin immediately posttransplant and had a mean discharge fasting blood sugar of 90 (range 66 to 117) mg/dL. Two patients required enteric conversion for urethritis and one patient underwent ileo-transverse colostomy diversion for a leak after primary enteric drainage. The urinary amylase was significantly higher for the adult donor group on days 1 and 7; however by the day of discharge the pediatric donor group was making an equivalent amount of urinary amylase. Early renal function as measured by serum creatinine was similar for the pediatric and adult groups on day 1 (4.1 vs 5.2), day 7 (1.4 vs 2.0), and day of discharge (1.4 vs 1.6). One patient in the pediatric group underwent ureteropyelostomy for ureteral stenosis.
From the Department of Surgery, University of Florida (W.V.d.W.), Gainesville, Floridaand Division of Organ Transplantation, Department of Surgery, University of Wisconsin (J.O., A.M.D., S.K., Y.B., B.C., J.P., R.H., H.W.S.), Madison, Wisconsin. Address reprint requests to Hans Sollinger, MD, PhD, University of Wisconsin Department of Surgery, 600 Highland Ave, Room H4/780, Madison, WI 53792-7375. © 1999 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010
610
Transplantation Proceedings, 31, 610–611 (1999)
PEDIATRIC DONORS
There were no vascular complications in the pediatric group. The pediatric donor and adult donor groups had similar 1-, 3-, and 5-year kidney (94, 94, 94 vs 90, 86, 81), pancreas (94, 94, 94 vs 89, 84, 79), and patient (100, 100, 100 vs 97, 94, 89) survival. There may be a trend to improved survival for the pediatric donor group; however it did not reach statistical significance. One patient in the pediatric donor group lost both the kidney and pancreas grafts to acute cellular rejection 3 months after transplant. The remaining 16 (94%) patients in the pediatric donor group have good kidney and pancreas graft function with a mean follow up of 4 (range 0.2 to 11) years.
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survival of both the kidney and pancreas. An attempt was made to match the pediatric donor SPKs with smaller recipients. The mean donor to recipient weight ratio was 0.51 with a range of 0.26 to 0.93. We conclude that excellent results can be achieved with pediatric donors for SPK transplantation by utilizing donors 5 years of age or older, and maintaining a donor to recipient weight ratio greater than 0.25. Maximum use of pediatric donors will potentially yield up to 142 additional pancreas allografts each year in the United States.
REFERENCES DISCUSSION
The use of pediatric donors for renal transplantation has been extensively studied and has been shown to result in good graft function even when transplanted as single kidneys from donors less than 5 years of age.2– 4 There are only a couple of studies, with few patients, which report the use of donors less than 10 years of age for pancreas transplantation.5,6 In this study we show that in a group of 17 patients receiving SPKs from donors 4 to 10 years of age, we achieved excellent early function as well as long-term graft
1. Odorico JS, Young CJ, Sollinger HW: Dig Surg 11:420, 1994 2. Ratner LE, Cigarroa FG, Bender JS, et al: J Am Coll Surg 185:437, 1997 3. Abouna GM, Kumar MSA, Chvala R, et al: Transplant Proc 27:2564, 1995 4. Bretan PN, Friese C, Goldstein RB, et al: Transplantation 63:233, 1997 5. Odorico JS, Heisey DM, Voss BJ, et al: Transplant Proc 30:276, 1998 6. Abouna GM, Kumar MSA, Miller JL, et al: Transplant Proc 25:2232, 1993
M
OST transplant programs are reluctant to use pediatric donors for pancreas transplantation for fear of inadequate islet cell mass and increased risk of technical complications. Currently, the lower age or size limit for cadaveric pancreas donors is not well defined. In 1996, although there were 162 cadaveric organ donors between 6 and 10 years of age, only 20 pancreas allografts were procured for transplantation. With 1464 patients waiting for simultaneous pancreas and kidney transplants (SPK) and 324 patients waiting for pancreas only transplants at the end of 1996, there is clearly a need to use all available pancreas allografts. We have used donors between 4 and 10 years of age for SPK transplants since 1986. In this paper, we compare the immediate and long term results of our pediatric donor (4 to 10 years of age) and adult donor (11 to 40 years of age) SPK transplants.
PATIENTS AND METHODS From 1986 to 1997, 17 patients at the University of Wisconsin Hospital and Clinics received SPK transplants from pediatric cadaveric donors with a mean age of 8 (range 4 to 10) years, mean weight of 30 (18 to 50) kg, and mean donor to recipient weight ratio of 0.46 (.26 to .92). A comparison analysis was made with 374 SPK recipients who received grafts from “ideal” donors between 11 and 40 years of age. An additional 111 patients who received SPK transplants from donors greater than 40 years of age were excluded from this study. The pancreas grafts were harvested en bloc with the liver and preserved in University of Wisconsin (UW) solution.1 The kidneys were either stored on a pulsatile perfusion machine or cold stored with UW solution. All pancreas grafts were anastomosed to the iliac vessels utilizing a same donor iliac Y graft as previously described. The duodenal segment was drained to either the bladder or small bowel. One patient received a double en bloc kidney. All vascular anastomosis were performed with running 6-0 or 7-0 prolene. The ureter was reconstructed utilizing an extravesical Liche ureteroneocystostomy over a silastic stent. All patients received induction with OKT3, ALG, or ATG, and maintenance immunosuppression with azathioprine or mycophenylate mofetil, cyclosporine or FK 506, and prednisone.
Statistical Analysis Donor, recipient, and outcome variables were compared using the Wilcoxon rank sums test. Survival curves were obtained using the methods of Kaplan and Meier. Survival was compared using the log rank test. All analysis were performed using SAS statistical software (SAS Institute Inc., Cary, North Carolina). 0041-1345/99/$–see front matter PII S0041-1345(98)01578-4
RESULTS
A comparative analysis of donor, recipient, and clinical characteristics between the pediatric (4- to 10-year-old) and adult (11- to 40-year-old) pancreas donor groups demonstrated a significant (P , .01) difference in donor weight (30 vs 74 kg), recipient weight (60 vs 70 kg), donor to recipient weight ratio (0.51 vs 1.08), and recipient gender (76% vs 37% females). This reflects an attempt to select smaller recipients for the smaller pediatric pancreas donors. Other variables analysed were similar for both groups and include year of transplant (1993 vs 1992), and pancreas drainage technique (29% vs 21% enteric). In order to assess whether the choice of smaller, more female recipients may have influenced the graft or patient survival, a multivariate analysis was performed on SPK transplants from donors 4 to 40 years of age demonstrating no significant effect of donor weight, recipient weight, donor to recipient weight ratio, and recipient gender on renal graft, pancreas graft, or patient survival. Early renal and pancreas function was evaluated by serum creatinine and urinary amylase on day 1, day 7, and day of discharge, and fasting blood sugar on day of discharge. All 17 recipients of pediatric pancreas grafts were normoglycemic without insulin immediately posttransplant and had a mean discharge fasting blood sugar of 90 (range 66 to 117) mg/dL. Two patients required enteric conversion for urethritis and one patient underwent ileo-transverse colostomy diversion for a leak after primary enteric drainage. The urinary amylase was significantly higher for the adult donor group on days 1 and 7; however by the day of discharge the pediatric donor group was making an equivalent amount of urinary amylase. Early renal function as measured by serum creatinine was similar for the pediatric and adult groups on day 1 (4.1 vs 5.2), day 7 (1.4 vs 2.0), and day of discharge (1.4 vs 1.6). One patient in the pediatric group underwent ureteropyelostomy for ureteral stenosis.
From the Department of Surgery, University of Florida (W.V.d.W.), Gainesville, Floridaand Division of Organ Transplantation, Department of Surgery, University of Wisconsin (J.O., A.M.D., S.K., Y.B., B.C., J.P., R.H., H.W.S.), Madison, Wisconsin. Address reprint requests to Hans Sollinger, MD, PhD, University of Wisconsin Department of Surgery, 600 Highland Ave, Room H4/780, Madison, WI 53792-7375. © 1999 by Elsevier Science Inc. 655 Avenue of the Americas, New York, NY 10010
610
Transplantation Proceedings, 31, 610–611 (1999)
PEDIATRIC DONORS
There were no vascular complications in the pediatric group. The pediatric donor and adult donor groups had similar 1-, 3-, and 5-year kidney (94, 94, 94 vs 90, 86, 81), pancreas (94, 94, 94 vs 89, 84, 79), and patient (100, 100, 100 vs 97, 94, 89) survival. There may be a trend to improved survival for the pediatric donor group; however it did not reach statistical significance. One patient in the pediatric donor group lost both the kidney and pancreas grafts to acute cellular rejection 3 months after transplant. The remaining 16 (94%) patients in the pediatric donor group have good kidney and pancreas graft function with a mean follow up of 4 (range 0.2 to 11) years.
611
survival of both the kidney and pancreas. An attempt was made to match the pediatric donor SPKs with smaller recipients. The mean donor to recipient weight ratio was 0.51 with a range of 0.26 to 0.93. We conclude that excellent results can be achieved with pediatric donors for SPK transplantation by utilizing donors 5 years of age or older, and maintaining a donor to recipient weight ratio greater than 0.25. Maximum use of pediatric donors will potentially yield up to 142 additional pancreas allografts each year in the United States.
REFERENCES DISCUSSION
The use of pediatric donors for renal transplantation has been extensively studied and has been shown to result in good graft function even when transplanted as single kidneys from donors less than 5 years of age.2– 4 There are only a couple of studies, with few patients, which report the use of donors less than 10 years of age for pancreas transplantation.5,6 In this study we show that in a group of 17 patients receiving SPKs from donors 4 to 10 years of age, we achieved excellent early function as well as long-term graft
1. Odorico JS, Young CJ, Sollinger HW: Dig Surg 11:420, 1994 2. Ratner LE, Cigarroa FG, Bender JS, et al: J Am Coll Surg 185:437, 1997 3. Abouna GM, Kumar MSA, Chvala R, et al: Transplant Proc 27:2564, 1995 4. Bretan PN, Friese C, Goldstein RB, et al: Transplantation 63:233, 1997 5. Odorico JS, Heisey DM, Voss BJ, et al: Transplant Proc 30:276, 1998 6. Abouna GM, Kumar MSA, Miller JL, et al: Transplant Proc 25:2232, 1993