Reviews

2011 Update on Pancreas Transplantation: Comprehensive Trend Analysis of 25,000 Cases Followed Up Over the Course of Twenty-Four Years at the International Pancreas Transplant Registry (IPTR)

Angelika C. Gruessner

Abstract

AIM: This study aimed to analyze the outcome of pancreas and pancreas-kidney transplantations based on the comprehensive follow-up data reported to the International Pancreas Transplant Registry (IPTR). METHODS: As of December 2010, more than 35,000 pancreas transplantations have been reported to the IPTR: more than 24,000 transplantations in the US and more than 12,000 outside the US. Cases with follow-up information until March 2011 were included in the analysis. RESULTS: Pancreas transplantations in diabetic patients were divided into 3 categories: those performed simultaneously with a kidney (SPK) (75%), those given after a previous kidney transplantation (PAK) (18%), and pancreas transplantation alone (PTA) (7%). The total number of pancreas transplantations steadily increased until 2004 but has since declined. The largest decrease was seen in PAK, which decreased by 50% from 2004 through 2010. Comparatively, the number of SPK decreased by 7% during this time. Era analysis of US transplantations between 1987 and 2010 showed changes in recipient and donor characteristics. Recipient age at transplantation increased significantly as well as transplantations in type 2 diabetes patients. The trend over time was towards tighter donor criteria. There was a concentration on younger donors, preferable trauma victims, with short preservation time. Surgical techniques for the drainage of the pancreatic duct changed over time, too. Now enteric drainage is the predominantly used technique in combination with systemic drainage of the venous effluent of the pancreas graft. Immunosuppressive protocols developed towards antibody induction therapy with tacrolimus and MMF as maintenance therapy. The rate of transplantations with steroid avoidance increased over time in all 3 categories. These changes have led to improved patient and graft survival. Patient survival now reaches over 95% at one year post-transplant and over 83% after 5 years. The best graft survival was found in SPK with 86% pancreas and 93% kidney graft function at one year. PAK pancreas graft function reached 80%, and PTA pancreas graft function reached 78% at one year. In all 3 categories, early technical graft loss rates decreased significantly to 8-9%. Likewise, the 1-year immunological graft loss rate also decreased: in SPK, the immunological 1-year graft loss rate was 1.8%, in PAK 3.7%, and in PTA 6.0%. CONCLUSIONS: Patient survival and graft function improved significantly over the course of 24 years of pancreas transplantation in all 3 categories. With further reduction in surgical complications and improvements in immunosuppressive protocols, pancreas transplantation offers excellent outcomes for patients with labile diabetes.

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Pancreas Transplantation: Lessons Learned From a Decade of Experience at Wake Forest Baptist Medical Center

Jeffrey Rogers¹, Alan C. Farney¹, Samer Al-Geizawi¹, Samy S. Iskandar², William Doares³, Michael D. Gautreaux¹, Lois Hart¹, Scott Kaczmorski³, Amber Reeves-Daniel⁴, Stephanie Winfrey¹, Mythili Ghanta⁴, Patricia L. Adams⁴, Robert J. Stratta¹

Abstract

This article reviews the outcome of pancreas transplantations in diabetic recipients according to risk factors, surgical techniques, and immunosuppression management that evolved over the course of a decade at Wake Forest Baptist Medical Center. A randomized trial of alemtuzumab versus rabbit anti-thymocyte globulin (rATG) induction in simultaneous kidney-pancreas transplantation (SKPT) at our institution demonstrated lower rates of acute rejection and infection in the alemtuzumab group. Consequently, alemtuzumab induction has been used exclusively in all pancreas transplantations since February 2009. Early steroid elimination has been feasible in the majority of patients. Extensive experience with surveillance pancreas biopsies in solitary pancreas transplantation (SPT) is described. Surveillance pancreas biopsy-directed immunosuppression has contributed to equivalent long-term pancreas graft survival rates in SKPT and SPT recipients at our center, in contrast to recent registry reports of persistently higher rates of immunologic pancreas graft loss in SPT. Furthermore, the impact of donor and recipient selection on outcomes is explored. Excellent results have been achieved with older (extended) donors and recipients, in recipients of organs from donation after cardiac death donors managed with extracorporeal support, and in African-American patients. Type 2 diabetics with detectable C-peptide levels have been transplanted successfully with outcomes comparable to those of insulinopenic diabetics. Our experiences are discussed in the light of findings reported in the literature.

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Current Perspectives on Laparoscopic Robot-Assisted Pancreas and Pancreas-Kidney Transplantation

Ugo Boggi¹, Stefano Signori¹, Fabio Vistoli¹, Gabriella Amorese², Giovanni Consani², Nelide De Lio¹, Vittorio Perrone¹, Chiara Croce¹, Piero Marchetti³, Diego Cantarovich⁴, Franco Mosca⁵

Abstract

Pancreas transplant recipients continue to suffer high surgical morbidity. Current robotic technology provides a unique opportunity to test whether laparoscopy can improve the post-operative course of pancreas transplantation (PT). Current knowledge on robotic pancreas and renal transplantation was reviewed to determine feasibility and safety of robotic PT. Information available from literature was included in this review, together with personal experience including three PT, and two renal allotransplants. As of April 2011, the relevant literature provides two case reports on robotic renal transplantation. The author’s experience consists of one further renal allotransplantation, two solitary PT, and one simultaneous pancreas-kidney transplantation. Information obtained at international conferences include several other renal allotransplants, but no additional PT. Preliminary data show that PT is feasible laparoscopically under robotic assistance, but raises concerns regarding the effects of increased warm ischemia time on graft viability. Indeed, during construction of vascular anastomoses, graft temperature progressively increases, since maintenance of a stable graft temperature is difficult to achieve laparoscopically. There is no proof that progressive graft warming produces actual damage to transplanted organs, unless exceedingly long. However, this important question is likely to elicit a vibrant discussion in the transplant community.

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The IKEM Pancreas and Islet Transplant Program as Part of Healthcare for Type 1 Diabetes Patients: Retrospective Analysis of Outcome from 1983 to 2010

Peter Girman, Frantisek Saudek

Abstract

Currently, 25-30 pancreas transplantations per year are carried out in type 1 diabetes (T1D) recipients residing in Czech Republic. Most of the recipients are transplanted together with kidney allografts, but pancreas is also transplanted alone in selected patients with brittle diabetes. Since 2005, the Institute for Clinical and Experimental Medicine (IKEM) islet transplant program was initiated as complementary therapeutic modality. The aim of this paper was to analyze the transplant program at our clinical center, and to examine the survival of recipients, and their pancreas, kidney, and islet grafts. Patient and graft survival rates were evaluated in the following three categories using Kaplan-Meier test: simultaneous pancreas and kidney transplantation (SPKTx), pancreas transplantation alone (PTA), and islet transplantation (ITx). Three hundred and ninety SPKTx, 34 PTA and 44 ITx were carried out between 1983 and 2010. One- and 5-year patient survival rates were 92 % and 81% in SPKTx, respectively. In SPKTx, the 1-year survival rate of pancreas grafts was 78%, and the 5-year rate was 66%. Kidney graft survival rates were 89% and 79%, respectively, after the same follow-up periods. In the PTA category, recipient survivals were 100% after 1 year, and 92% after 3 years. 70% and 65% of pancreatic grafts were working properly at 1 and 3-year follow-ups, respectively. To date, we have carried out 44 islet transplantations in 31 recipients. Islet function (C-peptide ≥ 0.2 ng/ml) was documented in 60% of recipients after 12 months. So far, only 3 patients remained free of exogenous insulin. While SPKTx is a well established treatment for uremic T1D patients, ITx represents an emerging complementary treatment modality. The latter is especially suitable for high-risk recipients, but routine clinical application is still hampered by the limited availability of usable organ transplants and viability of transplanted islets.

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Risks and Benefits of Transplantation in the Cure of Type 1 Diabetes: Whole Pancreas Versus Islet Transplantation. A Single Center Study

Paola Maffi, Marina Scavini, Carlo Socci, Lorenzo Piemonti, Rossana Caldara, Chiara Gremizzi, Raffaella Melzi, Rita Nano, Elena Orsenigo, Massimo Venturini, Carlo Staudacher, Alessandro Del Maschio, Antonio Secchi

Abstract

BACKGROUND: Pancreas and islet transplantation are the only available options to replace beta-cell function in patients with type 1 diabetes. Great variability in terms of rate of success for both approaches is reported in the literature and it is difficult to compare the respective risks and benefits. OBJECTIVES: The aim of this study was to analyze risks and benefits of pancreas transplantation alone (PTA) and islet transplantation alone (ITA) by making use of the long-term experience of a single center where both transplantations are performed. We focused on the risks and benefits of both procedures, with the objective of better defining indications and providing evidence to support the decision-making process. The outcomes of 33 PTA and 33 ITA were analyzed, and pancreas and islet function (i.e., insulin independence), perioperative events, and long-term adverse events were recorded. RESULTS: We observed a higher rate of insulin independence in PTA (75%) versus ITA (59%), with the longer insulin independence among PTA patients receiving tacrolimus. The occurrence of adverse events was higher for PTA patients in terms of hospitalization length and frequency, re-intervention for surgical and immunological acute complications, CMV reactivation, and other infections. CONCLUSIONS: In conclusion, these results support the practice of listing patients for PTA when the metabolic control and the progression of chronic complications require a rapid normalization of glucose levels, with the exception of patients with cardiovascular disease, because of the high surgical risks. ITA is indicated when replacement of beta-cell mass is needed in patients with a high surgical risk.

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Islet Transplantation and Encapsulation: An Update on Recent Developments

Vijayaganapathy Vaithilingam, Bernard E. Tuch

Abstract

Human islet transplantation can provide good glycemic control in diabetic recipients without exogenous insulin. However, a major factor limiting its application is the recipient's need to adhere to life-long immunosuppression, something that has serious side effects. Microencapsulating human islets is a strategy that should prevent rejection of the grafted tissue without the need for anti-rejection drugs. Despite promising studies in various animal models, the encapsulated human islets so far have not made an impact in the clinical setting. Many non-immunological and immunological factors such as biocompatibility, reduced immunoprotection, hypoxia, pericapsular fibrotic overgrowth, effects of the encapsulation process and post-transplant inflammation hamper the successful application of this promising technology. In this review, strategies are discussed to overcome the above-mentioned factors and to enhance the survival and function of encapsulated insulin-producing cells, whether in islets or surrogate β-cells. Studies at our center show that barium alginate microcapsules are biocompatible in rodents, but not in humans, raising concerns over the use of rodents to predict outcomes. Studies at our center also show that the encapsulation process had little or no effect on the cellular transcriptome of human islets and on their ability to function either in vitro or in vivo. New approaches incorporating further modifications to the microcapsule surface to prevent fibrotic overgrowth are vital, if encapsulated human islets or β-cell surrogates are to become a viable therapy option for type 1 diabetes in humans.

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