Richard Viebahn

Plasma cell-rich rejection processes in renal transplantation: morphology and prognostic relevance.

Background. Renal transplantation is the most effective therapy in end-stage renal disease. The prognosis of transplant survival is still determined by rejection. Morphologically, this involves interstitial rejection with potential development of vascular rejection (VR) and/or glomerular rejection processes, designated as transplant glomerulopathy (TGP). The cellular infiltrates are usually dominated by lymphocytes and macrophages in differing quantity, characterizing the severity of the rejection processes. Methods. In 14% of the renal transplant biopsies and explants in our investigation (n=399) plasma cells (PR) predominate in the cellular infiltrate. To determine whether the enrichment of PR has an impact on graft function or could even constitute an independent parameter for transplant survival, we analyzed 109 cases of transplanted patients matched for AR and CR and divided them into those rich and those nonrich in PR. Results. In the group rich in PR, PR comprised 30% of all infiltrates in comparison to 5% in the group non-rich in PR. VR and TGP appeared significantly more often in PR-rich rejections (P=0.0044). The group rich in PR had a significantly more adverse prognosis (P=0.0024), especially if PR enrichment was observed in the chronic rejection processes (P=0.0148). In the Cox proportional hazard model the occurrence of VR was the only independent factor. Conclusion. In itself, plasma-cell enrichment is not a prognostic marker, but it is an indicator of a more adverse outcome because it is often accompanied by the appearance or subsequent development of VR±TGP. The detection of PR-rich rejection processes should therefore encourage the clinician to intensify the immunosuppressive schedule.

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.

Blood‐based detection of RAS mutations to guide anti‐EGFR therapy in colorectal cancer patients: concordance of results from circulating tumor DNA and tissue‐based RAS testing

An accurate blood‐based RAS mutation assay to determine eligibility of metastatic colorectal cancer (mCRC) patients for anti‐EGFR therapy would benefit clinical practice by better informing decisions to administer treatment independent of tissue availability. The objective of this study was to determine the level of concordance between plasma and tissue RAS mutation status in patients with mCRC to gauge whether blood‐based RAS mutation testing is a viable alternative to standard‐of‐care RAS tumor testing. RAS testing was performed on plasma samples from newly diagnosed metastatic patients, or from recurrent mCRC patients using the highly sensitive digital PCR technology, BEAMing (beads, emulsions, amplification, and magnetics), and compared with DNA sequencing data of respective FFPE (formalin‐fixed paraffin‐embedded) tumor samples. Discordant tissue RAS results were re‐examined by BEAMing, if possible. The prevalence of RAS mutations detected in plasma (51%) vs. tumor (53%) was similar, in accord with the known prevalence of RAS mutations observed in mCRC patient populations. The positive agreement between plasma and tumor RAS results was 90.4% (47/52), the negative agreement was 93.5% (43/46), and the overall agreement (concordance) was 91.8% (90/98). The high concordance of plasma and tissue results demonstrates that blood‐based RAS mutation testing is a viable alternative to tissue‐based RAS testing.

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.

Pancreas removal by external teams

ZusammenfassungDie kombinierte Pankreas-Nieren-Transplantation (SPK) gilt als etabliertes Therapiekonzept für terminal oder präterminal niereninsuffiziente Typ-1-Diabetiker. Die Entnahmetechnik des Pankreas im Rahmen der Multiorganspende ist standardisiert. Dennoch kommt es gelegentlich zu einer Fehleinschätzung der Pankreasqualität durch Entnahmeteams, die nicht die anschließende Transplantation durchführen. Der Anteil der dadurch bei der Back-table-Präparation als „nichttransplantabel“ eingestuften Pankreata ist bisher nicht evaluiert worden.Zwischen 06/1994 und 12/2003 wurden in unserem Zentrum 271 Pankreastransplantationen durchgeführt. Im Rahmen der Back-table-Präparation wurden von 262 (89,7%) durch externe Teams entnommenen Pankreata 21 (8,0%) als „nichttransplantabel“ eingestuft. Kausal führend waren hier das Ausmaß der Organverfettung und die kritische Gefäßsituation. In 2 Fällen konnte aufgrund von Veränderungen des Nierentransplantates eine SPK nicht erfolgen. Mit 92% war die Quote der transplantablen Pankreata sehr hoch. Dies spiegelt den hohen Standard und die Qualität der Pankreasentnahme im Eurotransplant-Gebiet wider.AbstractCombined pancreas and kidney transplantation is an established procedure for terminal or preterminal, uremic, type 1 diabetics. The current procurement technique allows simultaneous recovery of liver and pancreas. One problem is the assessment of organ quality. It remains unclear how many pancreas organs must be withdrawn during back-table preparation.Between June 1994 and December 2003, 271 pancreas transplantations were performed at our transplant centre. Two hundred sixty-two (89.7%) pancreas grafts were harvested by teams which were not part of the transplant team. Twenty-one (8.0%) grafts were discharged for transplantation at the time of back-table preparation. Liposis of the graft and critical vessel situations were the main reasons for withdrawal. Two kidney grafts were not usable for transplantation, and 92% of the pancreas grafts were. This demonstrates the high standard of pancreas procurement in the Eurotransplant region.