Diabetes patients undergoing pancreas transplant from September of 2003 to May of 2020 were included in this study. Perioperative and follow-up data for each patient were prospectively collected and kept in a computer database. This study was approved by our institutional review board (IRB), Institutional Review Board, Taipei Veterans General Hospital, (IRB-TPEVGH No.: 2020-05-006CC). The study was carried out in accordance with our IRB guidelines and regulations. The informed consent was waived in this retrospective cohort study with anonymity of the data by our institutional review board. The official indications for pancreas transplant in Taiwan include the following: (1) T1DM with diabetic complications such as nephropathy, retinopathy, neuropathy, and cardio-cerebral vasculopathy; (2) T1DM with frequent life-threatening hypoglycemia or hyperglycemia; (3) T1DM with severe disability in school learning, working, and living; and (4) type 2 DM (T2DM) with kidney disease leading to ESRD under insulin control with insulin requirement of less than 1.5 units/kg/day. Based on the patient’s condition, pancreas transplants were classified into 4 subgroups at our institute: PBK, pancreas before kidney transplant; SPK, simultaneous pancreas-kidney transplant; PAK, pancreas after kidney transplant; PTA, pancreas transplant alone. According to the regulations of Taiwan Organ Registry and Sharing Center, the waiting lists for pancreas and kidney grafts are separate, and there are always more than 7,000 uremic patients waiting for a kidney graft, but only about 100 diabetic patients waiting for a pancreas graft (assessed on June 1, 2021 at https://www.torsc.org.tw/about/about_08.jsp). There is always more competition for kidney grafts from deceased donors in our country. A diabetic patient with ESRD might not have pancreas and kidney transplanted at the same time, and some patients who actually needed SPK would even accept pancreas transplant first, so called PBK, after the procedure is fully explained.
Clinical data and outcomes including early (before discharge) and late (after discharge) complications, surgical mortality, acute and chronic rejections, graft loss, fasting blood sugar, serum hemoglobin A1c (HbA1c), serum C-peptide, and pancreas graft survival were compared between each subgroup of pancreas transplant. In this study, surgical mortality was defined as postoperative death before discharge or within 90 days after operation. Any return to insulin use was counted as pancreas graft failure. Graft loss due to patient death with functioning graft was considered as censor, not event of interest, in graft survival analysis.
The primary endpoints were comparisons of pancreas transplant first in PBK group to other subgroups in terms of endocrine function, immunological, and graft survival outcomes. The secondary endpoints were comparisons of pancreas transplant first in PBK group to other subgroups in terms of surgical outcomes and patient survival.
Patients with a positive crossmatch against donor cells were excluded for pancreas transplant. The pancreas grafts were procured in a “‘no touch” technique en bloc with the duodenum. The spleen was routinely separated from the pancreas before aorta cross-clamping. Histidine-tryptophan-ketoglutarate solution was used for in situ perfusion, with 4,000 to 6,000 c.c. via aorta and 2,000 to 4,000 c.c. via inferior mesenteric vein. Back-table bench preparation included removal of the peripancreatic fat and arterial Y-graft reconstruction. The graft portal vein was anastomosed end-to-side to the recipient’s distal vena cava with head-up position of the pancreas graft. The superior mesenteric and splenic arteries reconstructed by donor iliac arterial Y-graft at the back-table was anastomosed to the recipient’s right common iliac or external iliac artery. Exocrine drainage was achieved by enteric drainage with a hand-sewn side-to-side duodenojejunostomy 30–50 cm beyond the flexure of Treitz ligament using roux-en-Y technique and retroperitoneal placement.
Immunosuppressive treatment was quadruple therapy for all recipients of pancreas transplantation without any specific protocol for each subgroup. Induction therapy included basiliximab (Simulect, Novartis Pharmaceuticals Corp., East Hanover, NJ), 20 mg given on postoperative days 0 to 4, or anti-thymocyte globulin (Thymoglobulin®; Genzyme, Cambridge, Mass., USA) for high risk of rejection such as positive panel-reactive antibody (PRA) and re-transplant, 1 mg/kg daily from postoperative days 1 to 7. Maintenance therapy mainly included administration of tacrolimus (Prograf; Astellas Pharma US, Inc., Deerfield, IL), enteric-coated mycophenolic acid (Myfortic; Novartis Pharmaceuticals Corp., East Hanover, NJ), and prednisolone. Prednisolone was tapered and gradually withdrawn 6 months after transplant. The target trough level for tacrolimus was 8–12 ng/mL during the first year and 6–8 ng/mL thereafter.
Statistical analyses were performed using Statistical Product and Service Solutions (SPSS) version 21.0 software (SPSS Inc., IBM, Armonk, NY, USA). All continuous data were presented as median and mean ± standard deviation (SD), and frequencies were presented when appropriate to the type of data. The mean values of the continuous variables were compared using a two-tailed Student’s t-test. Nonparametric statistical tests were used if the variables did not follow normal distribution. Categorical variables were presented as numbers and percentages. Categorical variables were compared using Pearson’s χ2 test or Fisher’s exact test contingency tables. Actuarial graft survival rates were estimated using the Kaplan-Meier method, excluding the primary graft failure and surgical mortality. The log-rank test was used to compare differences in the survival curves. For all analyses, P < 0.05 was considered to be statistically significant.