Andreas Wunsch

Long-term results of pancreas transplantation in patients older than 50 years

Aging of the population and improvements in diabetes therapy have led to an increased number of older pancreas transplant candidates. The aim of our retrospective study was to evaluate pancreas transplantation (PT) outcomes in patients ≥50 years, as limited data exist in these patients. We analyzed 398 consecutive pancreas transplant patients from June 1994 to June 2009 for different outcomes (patient/graft survival, rejection rate, and surgical complications) between the age groups ≥50 years (n = 69) and <50 years (n = 329). Donor and recipient characteristics were similar except for recipient age (54.0 vs. 38.8 years), BMI (24.6 vs. 22.9 kg/m2), and duration of diabetes mellitus (36.0 vs. 27.7 years). One‐, 5‐, and 10‐year patient and graft (kidney/pancreas) survival were not significantly different between the groups with patient survival rates reaching 84% and pancreas graft survival up to 67% after 10 years. Surgical complications such as relaparotomy rate (34% vs. 33%) or pancreas graft thrombosis (14% vs. 11%) as well as 1‐year rejection rates (35% vs. 31%) were not significantly different. PT in selected patients aged ≥50 years resulted in survival comparable with that of younger patients. In conclusion, advanced age should no longer be considered as an exclusion criterion for PT. However, good medical assessment and careful patient selection are necessary.

Incidence of pancreas graft thrombosis using low-molecular-weight heparin

Abstract:  Introduction:  Simultaneous pancreas–kidney transplantation is the current treatment of choice for patients with type I diabetes and end stage renal disease. Vascular graft thrombosis (VGT) after pancreas transplantation is the main cause of early graft loss.

Long-Term Results After Simultaneous Pancreas-Kidney Transplantation Using Donors Aged 45 Years or Older

UNLABELLED With the shortage of organ donors, there is a critical need to use all available pancreas grafts for transplantation. METHODS From June 1994 to December 2006 we performed 340 pancreas transplantations (317 simultaneous pancreas-kidney 5 pancreas only, 18 pancreas after kidney) including 69 (20%) transplantations from donors aged 45 years or older. Pancreas grafts from older donors were analyzed for graft and patient survival as well as surgical complications, compared with results from younger donors. RESULTS Recipient characteristics were comparable in both groups. The older donor group mean age was 47.8 years (+/-2.1) versus 27.9 years (+/-10.3) for the younger group. Cumulative patient survival was 96% versus 98% after 1, 82% versus 91% after 5 and 82% versus 88% after 10 years with 1-5- and 10-year kidney graft survivals of 82%, 72%, 57% versus 93%, 83%, 73%, respectively. Pancreas transplant survival after 1, 5, and 10 years were 69%, 60%, 45% in older and 88%, 76%, and 72% in younger donor cohorts. There were 14 (20%) cases of venous thrombosis in the older group and 25 (9%) in the younger group (P = .012). CONCLUSION Our results demonstrated that utilization of pancreas grafts from donors over 45 years resulted in acceptable outcomes after simultaneous pancreas-kidney transplant and could expand the donor pool. Among the older donor group, patient survival was slightly lower than the younger group, whereas pancreas graft function was significantly inferior (P < .01). Since venous thrombosis was the main reason for pancreas graft loss in older group, anticoagulation is essential.

Soluble total human leukocyte antigen class I and human leukocyte antigen–G molecules in kidney and kidney/pancreas transplantation

The expression of human leukocyte antigen (HLA)-G, a nonclassical HLA class I molecule, and its soluble forms (sHLA-G) are found to improve graft acceptance. In this study we investigated whether sHLA-G is the most biologically relevant molecule among all types of soluble HLA class I molecules for graft acceptance. We addressed this question in kidney-transplanted (n = 32) and kidney/pancreas-transplanted patients (n = 29). To this end we analyzed the levels of total soluble HLA class I (sHLA-I) in comparison to sHLA-G in 488 plasma samples procured before and serial after transplantation by specific enzyme-linked immunoabsorbent assay. Samples from 126 healthy individuals served as controls. Pretransplantation sHLA-I levels were significantly increased in patients (p < 0.001), whereas sHLA-G levels were in the range of those of healthy controls. Importantly, pretransplantation sHLA-I and sHLA-G levels did not differ between the two groups. Patients with biopsy-proven rejection (n = 15) revealed significantly lower sHLA-G levels before transplantation (mean +/- standard error of the mean, 12.9 +/- 1.8 vs. 20.1 +/- 1.9, p = 0.013) and after transplantation (p = 0.006, two-way analysis of variance) than patients without rejection (n = 46). In contrast, sHLA-I was slightly increased after but not before transplantation in patients with rejection (p < 0.05, two-way analysis of variance). Nonparametric determination analysis showed that pretransplantation levels of sHLA-G < 11.5 ng/ml (sensitivity, 60%; specificity, 80.4%) were related to rejection. Regarding antibody status, retransplantation, number of HLA mismatches, recipient age, and recipient body mass index, multivariate analysis showed that sHLA-G but not sHLA-I is an independent risk factor for graft rejection. Thus high levels of sHLA-G but not of sHLA-I seem to contribute to better graft acceptance after kidney or kidney/pancreas transplantation.

Preprocurement Pancreas Allocation Suitability Score Does Not Correlate With Long-Term Pancreas Graft Survival

BACKGROUND Within recent years, more marginal donors have been offered to Eurotransplant. To help identify suitable pancreas donors, the Eurotransplant Pancreas Advisory Committee introduced a donor score system (P-PASS). Little is known about the influence of P-PASS on long-term pancreas graft survival. METHODS From June 1994 to September 2009, we performed 405 pancreas transplantations. In a retrospective study we analyzed P-PASS in 318 cases. Pancreas grafts from donors with P-PASS < 17 (n = 146) analyzed for graft and patient survival as well as for surgical complications were compared with donors of a PASS > or = 17 (n = 172). The mean follow-up was 7.2 +/- 4.3 years. RESULTS Recipient characteristics were comparable in both groups. Mean P-PASS was 16.7 +/- 2.7 for both groups: 14.3 +/- 1.5 for P-PASS < 17 and 18.8 +/- 1.6 for P-PASS > or = 17. Pancreas graft survival rates for 1, 5, and 10 years were 85%, 77%, and 73% among P-PASS < 17 and 81%, 73%, and 64% among P-PASS > or = 17 groups (P = .12). There were 12 (8.2%) cases of venous thrombosis in the <17 group and 22 (12.7%) in the > or =17 group (P < .05). The relaparotomy rate was significant higher (38.7% vs 28.7%) and duration of hospital treatment longer (40.2 vs 32 days) in the P-PASS > or = 17 group (P < .05). There was no significant difference in patient or kidney graft survival between groups. CONCLUSIONS The data demonstrated that utilization of pancreas grafts from donors with a P-PASS > or = 17 resulted in good overall outcomes and could expand the organ donor pool. There was no correlation between P-PASS and long-term patient or graft outcome. Complications requiring relaparotomy were more frequent among patients after transplantation from donors with higher P-PASS.

125 Cases of duodenoduodenostomy in pancreas transplantation: a single-centre experience of an alternative enteric drainage.

Several exocrine drainage procedures have been successfully developed to perform pancreas transplantation (PT). Retroperitoneal graft placement allows exocrine drainage via direct duodenoduodenostomy (DD). This technique provides easy access for endoscopic surveillance and biopsy. A total of 241 PT procedures were performed in our centre between 2002 and 2012. DD was performed in 125 patients, and duodenojejunostomy (DJ) in 116 patients. We retrospectively compared our experience with these two types of enteric drainage, focusing on graft and patient survivals, as well as postoperative complications. With a mean follow‐up of 59 months, both groups demonstrated comparable patient and graft survivals. 14 (11%) of 125 cases in the DD group and 21 (18%) of 116 cases in the DJ group had pancreatic graft loss (P = 0.142). Graft thrombosis [5 (4%) vs. 18 (16%) P = 0.002], anastomotic insufficiency [2 (1.6%) vs. 8 (7%) P = 0.052] and relaparotomy [52 (41%) vs. 56 (48%) P = 0.29] occurred more frequently in the DJ group, whereas gastrointestinal bleeding [14 (11%) vs. 4 (3%) P = 0.026] occurred more often in the DD group. DD is a feasible and safe technique in PT, with no increase in enteric complications. It is equivalent to other established techniques and extends the feasibility of anastomotic sites, especially in recipients who have undergone a second transplantation.

En Bloc Retroperitoneal Pancreas-Kidney Transplantation With Duodenoduodenostomy Using Pediatric Organs

BACKGROUND Given the shortage of organ donors, there is a critical need to use all available pancreas grafts for transplantation. In the Eurotransplant region, only 26% of all offered pancreas grafts were transplanted during 2007. Pediatric donors are rarely used in pancreas transplantation. METHODS In this case report, we describe a retroperitoneal en bloc pancreas-kidney transplantation (SPK) with systemic venous anastomosis and duodenoduodenostomy using grafts from an 11-year-old child. The bloc was transplanted in a 42-year-old type I diabetic patient with end-stage renal disease. The proximal end of the aortic graft was closed. Arterial anastomosis was performed end-to-end between right internal iliac artery and the aortic graft because of severe atherosclerosis. Donor portal vein and donor renal vein were anastomosed separately end-to-side to recipient inferior vena cava. Exocrine drainage was carried out with a side-to-side duodenoduodenostomy. Both grafts were in the retroperitoneal position. RESULTS The pancreas graft functioned immediately, the kidney graft resumed function at 7 days posttransplantation. Graft function was excellent over a follow-up of 18 months. The patient had no episodes of acute rejection or graft dysfunction, no severe infections, and no additional morbidity from the modified technique of retroperitoneal pancreas transplantation using duodenoduodenostomy. CONCLUSIONS This case indicates that pediatric donors could be used more frequently in pancreas transplantation for adult recipients and could increase the organ donor pool. En bloc SPK is a feasible and safe technique. Further studies are required to confirm the benefits of a retroperitoneal SPK using duodenoduodenostomy.

Modified release tacrolimus in de novo immunosuppression after simultaneous pancreas-kidney transplantation--a first single-center experience.

BACKGROUND Modified release tacrolimus is a new, once-daily oral formulation of the established immunosuppressive agent tacrolimus. Little is known about de novo immunosuppression after simultaneous pancreas-kidney transplantation using modified release tacrolimus. METHODS To test the feasibility of modified release tacrolimus in simultaneous pancreas-kidney transplantation (SPK), we conducted a prospective study of 14 consecutive transplants using modified release tacrolimus (Advagraf, ADV), mycophenolate mofetil, and low-dose corticosteroids as the initial immunosuppressive regimen. Patient and graft survival, the rates of acute rejection, graft function as well as ADV dosages, and trough levels (C(min)) were investigated after a mean follow-up time of 11.0 +/- 3.1 months. RESULTS Overall patient, kidney, and pancreas graft survival were 100%, 100%, and 93%, respectively. One pancreas graft was lost owing to vascular graft thrombosis 2 days after transplantation. The incidence of rejection episodes at 11 months was 38%. ADV was well tolerated in the majority of patients. Only in 1 case tacrolimus (ADV) was stopped because of psychotic symptoms. In week 2 and 3 posttransplant, a significant adjustment in the ADV dosage was necessary to achieve sufficient tacrolimus trough levels. CONCLUSIONS The results of this case series report demonstrate that patients after SPK can be safely treated with modified release tacrolimus. Further studies are needed to investigate pharmacokinetic profiles of modified release tacrolimus after SPK.

Autotransplantation for the treatment of severe renal artery stenosis in a solitary kidney after repeated percutaneous transluminal angioplasty: a case report.

A 66-year-old female suffering from massive atherosclerosis with a long history of renal artery stenosis in the left solitary kidney was admitted to reevaluate an in-stent restenosis. Advanced peripheral arterial disease had formerly been treated by aortobifemoral bypass surgery and a highly eccentric infrarenal abdominal aortic stenosis of 70 - 80% had been treated by patch angioplasty. In this patient several percutaneous transluminal renal angioplasties after a former stent deployment had resulted in recurrent in-stent restenoses. The renal artery stenosis was reevaluated and a re-angioplasty attempt was unsuccessful due to technical failure. Blood pressure remained difficult to manage. Renal function decreased as a result of presumed acute renal failure. A further progression of the renal artery stenosis was found. Autotransplantation to the left iliac fossa was done, because aortorenal bypass was considered impossible. Renal function normalized and follow-up Doppler ultrasonography examinations revealed a newly developed ostial anastomotic stenosis of 60 - 70%. While medical therapy and percutaneous transluminal angioplasty with stent deployment are common treatment options, surgical interventions are reserved for cases of complex stenoses. Autotransplantation as a complex option in the treatment of renal artery stenosis seems to be an adequate alternative in patients with severe, generalized atherosclerosis after failure of interventional procedures and the impossibility of standard surgical techniques.

Complications after Pancreas Transplantation

Pancreas transplantation (PT) shows a higher rate of complications compared with other organ transplantations. Graft thrombosis and intraabdominal infections are the most common causes for relaparatomy. We analyzed the influence of complications on the organ function after PT. Methods 145 pancreas grafts were transplanted between 01/2010 and 12/2015 at our hospital with 132 simultaneous pancreas-kidney transplantations, 5 isolated pancreas transplantations and 8 pancreas after kidney transplantation. Out of this, 16 were retransplantations. A further analyzation was done for 132 of these transplants. Results Complications occurred in 72 of 132 patients (54,55%). Pancreatitis (n=53), pancreatic fistulas (n=33) and postoperative bleeding (n=24) were most commonly observed. A relaparatomy was required for every third patient, mainly because of infectious reasons as abscess and pancreatitis. 22 pancreas transplants and 14 kidney transplants lost their function shortly after transplant. Until 05/2017 68,18 % of the pancreas and 78,03 % of the kidney transplants are full functional. Complications had an significant influence on the organ function after PT (p=7.046e-05). Operative revision (p=0,0009), pancreatitis (p=0,0114), bleeding (p=0,0045) and graft thrombosis (p=0,0054) showed statistical significant influence on the pancreas graft function after transplantation. Rejection (p=0,1778), pancreatic fistulas (p = 0,0843) and CT-drainage (p=0,8088) demonstrated no further influence. Our data showed no correlation between the occurrence of complications and donor or recipient variables (e.g. BMI, age). Neither had the ischemia time nor the operation duration or the presence of positive germ wraps any significant influence. Conclusion Complication rates are still high in PT and affect the function of the pancreas graft significant. Strategies to reduce postoperative pancreatitis and infections need to be further investigated.