Vascularized Pancreas Transplantation Research Articles

P.133: Systemic Venous Versus Portal Venous Drainage in Simultaneous Pancreas-Kidney Transplantation: A Matched-pair Analysis

Purpose: Portal venous drainage of pancreatic transplant appears more physiologic compared to systemic venous drainage. However, present data does not support the superiority of one technique over the other. The study purpose was to evaluate outcomes in vascularized pancreas transplantation (PTx) with enteric exocrine drainage based on technique of venous delivery. Methods: We retrospectively analyzed 231 simultaneous pancreas-kidney transplants (SPKTs) performed at our center between 7/2003 – 7/2019 and identified 27 that were performed with systemic venous (iliac vein) and enteric exocrine (systemic-enteric [S-E]) drainage. These 27 patients were compared to 27 case controls with portal venous and enteric exocrine drainage matched for recipient age, gender, race, and date of transplant. Results: The 2 groups were well-matched.Indications for S-E drainage were central obesity/thickened mesentery (10), unfavorable vascular anatomy (11), or surgeon preference (6). The S-E drainage group was characterized byslightly more patients ≥ 80 kg (44% S-E versus 26% P-E), with C-peptide positive diabetes (30% S-E versus 18% P-E), and with diabetes onset at >20 years of age (41% S-E versus 26% P-E, all p=NS), suggesting a Type 2 diabetes phenotype. Although the incidence of early pancreas thrombosis (3.7% S-E versus 0% P-E), early relaparotomy (30% S-E versus 22% P-E), and mean initial length of hospital stay (11 days S-E versus 8 days P-E) were numerically higher in S-E versus P-E SPKTs, none of these differences were significant. With a mean follow-up of 5 years in both groups, respective one and 3-year patient survival (100% and 96% S-E vs 100% and 100% P-E), kidney graft survival (100% and 96% S-E vs 100% and 89% P-E), and pancreas graft survival (96% and 96% S-E vs 100% and 100% P-E) rates were comparable. Conclusions: The method of venous delivery of insulin following PTx does not appear to influence medium-term outcomes in SPKT with enteric exocrine drainage. K. Gurung2, R. Stratta2, A. Farney2, G. Orlando2, C. Jay2, A. Reeves-Daniel3, A. Mena-Gutierrez3, N. Sakhovskaya3, W. Doares4, S. Kaczmorski4, M. Magid4, J. Rogers2 .

Exocrine drainage in vascularized pancreas transplantation in the new millennium

The history of vascularized pancreas transplantation largely parallels developments in immunosuppression and technical refinements in transplant surgery. From the late-1980s to 1995, most pancreas transplants were whole organ pancreatic grafts with insulin delivery to the iliac vein and diversion of the pancreatic ductal secretions to the urinary bladder (systemic-bladder technique). The advent of bladder drainage revolutionized the safety and improved the success of pancreas transplantation. However, starting in 1995, a seismic change occurred from bladder to bowel exocrine drainage coincident with improvements in immunosuppression, preservation techniques, diagnostic monitoring, general medical care, and the success and frequency of enteric conversion. In the new millennium, pancreas transplants are performed predominantly as pancreatico-duodenal grafts with enteric diversion of the pancreatic ductal secretions coupled with iliac vein provision of insulin (systemic-enteric technique) although the systemic-bladder technique endures as a preferred alternative in selected cases. In the early 1990s, a novel technique of venous drainage into the superior mesenteric vein combined with bowel exocrine diversion (portal-enteric technique) was designed and subsequently refined over the next ≥ 20 years to re-create the natural physiology of the pancreas with first-pass hepatic processing of insulin. Enteric drainage usually refers to jejunal or ileal diversion of the exocrine secretions either with a primary enteric anastomosis or with an additional Roux limb. The portal-enteric technique has spawned a number of newer and revisited techniques of enteric exocrine drainage including duodenal or gastric diversion. Reports in the literature suggest no differences in pancreas transplant outcomes irrespective of type of either venous or exocrine diversion. The purpose of this review is to examine the literature on exocrine drainage in the new millennium (the purported "enteric drainage" era) with special attention to technical variations and nuances in vascularized pancreas transplantation that have been proposed and studied in this time period.

Pancreas transplantation: review.

ABSTRACTVascularized pancreas transplantation is the only treatment that establishes normal glucose levels and normalizes glycosylated hemoglobin levels in type 1 diabetic patients. The first vascularized pancreas transplant was performed by William Kelly and Richard Lillehei, to treat a type 1 diabetes patient, in December 1966. In Brazil, Edison Teixeira performed the first isolated segmental pancreas transplant in 1968. Until the 1980s, pancreas transplants were restricted to a few centers of the United States and Europe. The introduction of tacrolimus and mycophenolate mofetil in 1994, led to a significant outcome improvement and consequently, an increase in pancreas transplants in several countries. According to the International Pancreas Transplant Registry, until December 31st, 2010, more than 35 thousand pancreas transplants had been performed. The one-year survival of patients and pancreatic grafts exceeds 95 and 83%, respectively. The better survival of pancreatic (86%) and renal (93%) grafts in the first year after transplantation is in the simultaneous pancreas-kidney transplant group of patients. Immunological loss in the first year after transplant for simultaneous pancreas-kidney, pancreas after kidney, and pancreas alone are 1.8, 3.7, and 6%, respectively. Pancreas transplant has 10 to 20% surgical complications requiring laparotomy. Besides enhancing quality of life, pancreatic transplant increases survival of uremic diabetic patient as compared to uremic diabetic patients on dialysis or with kidney transplantation alone.

Human islet transplantation

that achieves insulin-independent, constant normoglycemic state and avoidance of hypoglycemic episodes is the replacement of a patient’s islet of Langerhans either by pancreas transplantation or by isolated islet transplantation. The cost of this benefit, however, is the need for immunosupressive treatment of the recipient with all its potential risks. Currently, only vascularized pancreas transplantation can re-establish long-term normoglycemia however this has been associate with significant morbidity and mortality. Approximately 25.000 patients worldwide underwent this procedure and it has been shown to improve quality of life and even reverse some secondary complications of diabetes.4 Simultaneous pancreas and kidney transplantation are presently considered the standard of care for selected patients with type I diabetes with end-stage renal failure.5 Diabetes is a major burden to healthcare economies despite the use of exogenous insulin injections. Type I diabetes mellitus is a chronic metabolic disorder that currently afflicts 5 million individuals in the world. It results from auto-immune mediated destruction of insulin secreting beta cells in islet of Langerhans of the pancreas.1 Long-term studies strongly suggest that tight control of blood glucose achieved by conventional or intensive insulin treatment, self blood glucose monitoring, and patient education can significantly prevent developing and retard the progression of chronic complications of this disease.2 On the other hand, the cost of this benefit was a threefold increase in the number of severe hypoglycemic episodes, a significant increase of body weight and dietary and other lifestyle restrictions affecting the quality of life.3 The only treatment for Type I diabetes mellitus Human islet transplantation

Organ Donation and Transplantation in the UK—The Last Decade

Over the decade between 2003 and 2012, the UK has seen major changes in how organ donation and transplantation is delivered. The number of deceased organ donors has increased from 709 (12.0 per million population [pmp]) to 1,164 (18.3 pmp); this increase has been predominantly a result of an increase in donors after circulatory death (DCD) (from 1.1 pmp to 7.9 pmp) while the numbers of donors after brain death (DBD) has remained broadly stable (around 10.5 pmp). The donor population has become older (from 14% 60 years or over to 35%) and heavier (from 14% with body mass index >=30 kg/m2 to 23%). Despite these changes in demographic factors, the number of organs retrieved from DBD donors has risen from a mean of 3.6 to 4.0 per donor and for DCD donors from 2.2 to 2.6. The number of transplants in adults in 2012 was 2,709 (967 DBD, 708 DCD, and 1,034 living) for kidney alone, 246 pancreas (including 172 kidney and pancreas), 792 (611 DBD, 142 DCD, 36 living, and 3 domino) for liver, 136 for heart only, and 179 (145 DBD and 34 DCD) for lung only. Median waiting times to transplant for adult patients were 1,167, 339, 141, 293, and 311 days, respectively. The proportion of adult non-urgent registrants in 2009 (2007 for kidneys) who were removed from the waiting list or died awaiting a graft within 1 year was 3% for kidneys, 6% for pancreas, 19% for liver, 27% for heart, and 24% for lung. Outcomes after solid organ transplants are improving; for adult patients grafted between 2003 and 2005, 5-year graft survival for kidney is 84% (DBD), 87% (DCD), and 92% (living donor), for simultaneous kidney and pancreas 72%, and for pancreas alone 50% (DBD). Five-year patient survival for liver is 77% (DBD) and 68% (DCD), heart 67%, and lung 52% (DBD). Although rates of organ donation and transplantation have increased in the UK, this has been almost solely because of a rise in DCD donation. Although donor age and weight is increasing, graft survival has generally improved. Despite a recent fall in the number of patients on the transplant waiting list, there remains a significant gap between the need for transplantation and the number of organs available from deceased and living donors. The implementation of a new strategy following the recommendations of the Organ Donation Task Force in 2008 has had a major impact in bringing together clinicians involved in both organ donation and transplantation, and these changes and clinical enthusiasm have been instrumental in achieving success. With an emphasis on the need to increase the family consent rate for organ donation, which has failed to show any improvement over the last 5 years, a new UK strategy for organ donation and transplantation, introduced in 2013, will further increase organ transplantation in the UK.

Pancreas transplantation with portal venous drainage with an emphasis on technical aspects

Advances in surgical techniques and clinical immunosuppression have led to improving results in vascularized pancreas transplantation. Most pancreas transplants are performed with enteric exocrine drainage and systemic venous delivery of insulin (systemic-enteric technique) although bladder drainage (systemic-bladder technique) remains a viable option. To improve the physiology of pancreas transplantation, an innovative technique of portal venous delivery of insulin and enteric drainage of the exocrine secretions (portal-enteric technique) was developed and refined over the past 27yr. However, the potential of portal-enteric pancreas transplantation has never been fully realized as it is currently performed in only 18% of simultaneous pancreas-kidney/sequential pancreas after kidney and 10% of pancreas-alone transplants with enteric drainage. A number of studies have demonstrated no major or consistent differences in outcomes for bladder-drained or enteric-drained pancreas transplants with either portal or systemic venous drainage although some studies suggest purported metabolic and immunologic advantages associated with portal venous delivery of insulin. The purpose of this study is to review the existing literature on portal-enteric pancreas transplantation with an emphasis on surgical aspects and technical modifications/nuances that have been introduced with time and experience.

Technical Aspects of Pancreas Transplantation with Portal Venous Drainage

Vascularized pancreas transplantation was initially developed as a means to re-establish endogenous insulin secretion responsive to normal feedback controls and has evolved over time to a form of auto-regulating total pancreatic endocrine replacement therapy that reliably achieves a euglycemic state and normal glucose homeostasis without the need for either exogenous insulin therapy or close glucose monitoring.

Pancreas transplantation for type 2 diabetes mellitus

This review will provide evidence that selected patients with type 2 diabetes mellitus (T2DM) may benefit from vascularized pancreas transplantation (PTX). Initial experience with simultaneous pancreas-kidney transplantation (SPKT) in patients with T2DM and end-stage renal disease (ESRD) suggested that augmentation of endogenous insulin production by PTX in patients with C-peptide-positive, insulin-requiring diabetes resulted in insulin independence, improved glucose counter-regulation, and enhanced quality of life. A number of single-center retrospective studies have documented equivalent outcomes in patients with either type 1 diabetes mellitus (T1DM) or T2DM undergoing predominantly SPKT, although clearly a selection bias exists for patients in the latter category. Selection criteria for SPKT in T2DM include patients less than 55-60 years of age with a BMI less than 30-32 kg/m², insulin-requiring for a minimum of 5 years with a total daily insulin requirement less than 1 u/kg/day, a fasting C-peptide level less than 10 ng/ml, absence of severe vascular disease or tobacco abuse, adequate cardiac function, and presence of 'complicated' diabetes. Data from the International Pancreas Transplant Registry show that up to 7% of SPKT recipients are classified as having T2DM and that outcomes in these patients are comparable to those undergoing SPKT and classified as having T1DM. Consequently, characterization of the 'type' of diabetes may be irrelevant and insulin-requiring diabetic patients with ESRD should be evaluated for PTX based exclusively on their predicted ability to tolerate the surgical procedure and requisite immunosuppression as well as comply with a stringent posttransplant follow-up regimen.

Donor Pancreata: Evolving Approaches to Organ Allocation for Whole Pancreas Versus Islet Transplantation

As islet transplantation increasingly enters the clinical arena, its coexistence with vascularized pancreas transplantation makes it necessary to reassess the questions of donor selection and allocation. In answering these questions, one must put in the balance the short-term morbidity of pancreas transplantation with the long-term attrition of islet grafts. The preferential allocation of pancreases from obese and older donors for islet isolation has been based on their association with worse pancreas transplant outcomes and better islet isolation results in islet yields. In this overview, we show that transplanted islet mass does not necessarily correlate with graft function and make the case that donor selection criteria for islet transplantation, and hence allocation rules, may need to be redefined.

Vitacyte Collagenase HA: A Novel Enzyme Blend for Efficient Human Islet Isolation

Islet transplantation has found its niche in diabetes treatment. It has contributed to a better quality of life and better glycemic control of patients with diabetes suffering from severe hypoglycemia that are not eligible for vascularized pancreas transplantation. Islet isolation is a technically challenging procedure. The different studies within this doctoral thesis aim to improve and standardize different steps in the isolation procedure. They are in particular looking to improve human pancreas preservation during cold storage, to optimize islet release from the exocrine tissue and to assess whether the isolated islet yield can be predicted from a biopsy. We found that pancreas preservation with pre-oxygenated perfluorodecalin (two-layer method) did not improve the ischemic tolerance of the human pancreas as compared to cold storage with the University of Wisconsin (UW) solution. Furthermore, in pancreas with long cold ischemia time (CIT) (>10 hours), Histidine-Tryptophan-Ketoglutarate (HTK) had a limited preservation capacity as compared with the UW solution with respect to isolation outcome. We also found that during enzymatic pancreas digestion, Vitacyte HA was able to provide a similar islet yield and quality as Serva NB1 with less collagenase activity and shorter digestion time. We further describe the first experience with a new GMP manufactured enzyme called Liberase MTF-S for successful human islet isolation. Finally, we found that the isolated islet yield could not be predicted from a biopsy taken from the head of the pancreas concerning solely morphological parameters of the islets tissue. The improvement of pancreas preservation will allow for marginal organs with prolonged cold ischemia time to expand the donor pool. Better knowledge of how the pancreatic extracellular matrix is digested by collagenase will lead to a fast and predictable islet release from the exocrine tissue. By standardizing the isolation procedure and improving organ selection we will increase the success rate in human islet isolation, thereby making islet transplantation available for more patients.

A novel technique for heterotopic vascularized pancreas transplantation in mice to assess ischemia reperfusion injury and graft pancreatitis

Although various suture techniques for murine pancreas transplantation have been described, severe limitations have limited their widespread use. We therefore designed a surgical model for cervical heterotopic pancreas transplantation using a cuff technique. C57BL6 mice were used as donor and recipient pairs. Recipients were rendered diabetic with streptozotocin and subsequently transplanted. The donor pancreas was isolated using a no-touch technique and then placed in the recipient's cervical region. Vascular anastomoses were completed by pulling the portal vein over the external jugular vein cuff and the donor aortic segment over the carotid cuff and fixed with an 8-0 ligature thereby facilitating a nonsuture technique. To test applicability of this model, graft microcirculation was evaluated by intravital microscopy after prolonged cold ischemia (16 h). The immediate success rate was >90%. Donor operation lasted 40 +/- 5 min; dissection of recipient vessels lasted 20 +/- 4 min. Revascularization time was 4 to 6 min, resulting in a total pancreas ischemia time of 33 +/- 6 min. No thromboembolic complications on the cuff side were observed. Preoperative glucose levels were 518 +/- 59 mg/dl and returned to normal by postoperative day 1 (88 +/- 13 mg/dl). Histology on postoperative days 10 and 30 showed almost normal islet cell and acinar architecture of all grafts. In groups with prolonged cold ischemia, graft microcirculation was significantly reduced and paralleled by increased inflammation, interstitial edema, hemorrhage, acinar vacuolization, and focal areas of necrosis compared with nonischemic controls. This new model may provide an excellent tool to further investigate the pathophysiology as well as novel therapeutic strategies of preservation, ischemia reperfusion injury, and graft pancreatitis.

Cell transplantation for diabetes.

For 30 years there has been experimental work aimed at transplanting islets for the treatment of diabetes with a view to curing the disease and preventing the secondary complications. Many technical difficulties were experienced, first in isolating the islets without damaging them, and second in finding a suitable place to inject them, but until recently the results of a vascularized pancreas transplant have been superior to islet transplantation. In 2000, the group in Edmonton, headed by Shapiro, published encouraging results using a different immunosuppression in transplanting patients earlier in the course of their disease than had been attempted previously. The results were excellent at a year and good at 2 years in patients with Type I diabetes, however there was the rather worrying attrition at five years. Nevertheless, the Edmonton observations were proof of concept and have intensified interest in treating diabetes and other diseases where a specific protein synthesis was required by cell transplantation and/or genetic engineering. The recent interest in embryonic stem cells extenuated these efforts and progress is being made in defining the difficulties, which are greater than most workers would have predicted. In this review, the subject is discussed explaining where progress needs to be made in order to provide treatment that would be of value to patients.

Surgical Nuances in Pancreas Transplantation

The modern surgical era of vascularized pancreas transplantation (PTX) began with the systemic-bladder drainage technique. According to International Pancreas Transplant Registry (IPTR) data, most PTX procedures are performed with systemic venous delivery of insulin and either bladder (systemic bladder) or enteric (systemic-enteric) drainage of the exocrine secretions. Since 1995 the number of PTX procedures performed with primary enteric drainage has increased dramatically, accounting for more than 70% of cases since 2001. Despite an evolution in exocrine drainage, the proportion of enteric drained PTXs with portal venous delivery of insulin (portal enteric drainage) has remained low, representing about 20% of cases. In recent IPTR analyses no differences were reported in short-term outcomes according to surgical technique. Coincident with more physiologic implantation techniques, the surgical complication rate has decreased to 10% to 20%. Experience with donor and recipient selection can reduce morbidity, inasmuch as risk factors for surgical complications include prolonged pre-transplantation peritoneal dialysis, donor or recipient BMI body mass index >28 kg/m 2, donor or recipient age older than 45 years, cerebrovascular cause of donor brain death, prolonged preservation, and prior abdominal surgery in the recipient. New techniques include simultaneous living donor kidney and deceased donor PTX, gastroduodenal artery revascularization, laparoscopic living donor nephrectomy and distal pancreatectomy, en bloc kidney and pancreas transplantation, P-E drainage with venting jejunostomy, retroperitoneal PTX with P-E drainage, and unusual vascular grafts. In the future the emphasis will shift from short-term surgical to long-term medical outcomes as the ultimate measure of success.

LONG-TERM PRESERVATION OF THE PIG PANCREAS BY THE ONE-LAYER METHOD FOR SUCCESSFUL ISLET ISOLATION

P33 Aims: The oxygenation of the human pancreas during cold storage was recently established for clinical islet transplantation by introduction of the two-layer method (TLM). Nevertheless, simplification of TLM would facilitate its application as a broadly used pancreas preservation method for subsequent islet transplantation. Preliminary data about vascularized pancreas transplantation in rats and dogs indicate that successful preservation by a one-layer method (OLM) omitting UW solution (UWS) as the second layer is also possible. The purpose of the present study was therefore to examine the efficiency of OLM for pig islet isolation after 7 hours of cold ischemia. Methods: After resection adult pig pancreata were intraductally flushed with 2 mL/g of cold UWS. Subsequently, pancreata were either continuously oxygenated during cold ischemia by the TLM (n=10) or OLM (n=8), or processed promptly (n=6). Immediately before digestion-filtration pancreata were intraductally distended with cold UWS supplemented with Collagenase NB 8 and Neutral Protease NB (SERVA). Isolated islets were isolated and purified as previously described. Quality control included determination of islet yield expressed as islet equivalents (IEQ), isolation index (IEQ/islet number), trypan-blue exclusion, glucose stimulation index during static incubation (20 vs 2.8 mM glucose), insulin and ATP content, and mitochondrial activity measured as formazan production at 490 nm and expressed as optical density (OD). Islet in vivo function was evaluated after transplantation into diabetic nude mice. Results: No significant differences were found regarding islet purity (>90%) and viability (>95%). Compared to freshly procured pancreata (429200±86700 IEQ) postpurification islet yield was significantly decreased (P<0.05) after prolonged cold storage by TLM (238000±26600 IEQ). In contrast, islet yield was significantly higher (P<0.05) in cold-stored organs using OLM (338600±42100 IEQ, NS vs fresh). Metabolic islet integrity was not different between unstored pancreata and organs preserved by OLM or TLM as indicated by the intracellular insulin content (710±130 vs 830±120 vs 750±70 μU/IEQ), formazan production (0.7±0.1 vs 0.6±0.1 vs 0.7±0.1 OD/1000 IEQ) and ATP content (390±70 vs 370±80 vs 410±170 pg/IEQ). In contrast, glucose stimulation index was significantly decreased in islets isolated after TLM-storage (1.8±0.2, P<0.05) but not after OLM-storage (2.3±0.6, NS) compared to freshly isolated islets (2.5±0.4). Transplantation into diabetic nude mice demonstrated islet graft function in all experimental groups. Conclusions: The present study demonstrates clearly that viable pig islets can be successfully isolated from long-term stored pig pancreata utilizing perfluorochemicals as a single layer for oxygenation of pancreatic tissue during cold storage. This methodological simplification of the TLM might be of relevance for broad application in clinical islet transplantation.

A prospective comparison of bladder versus enteric drainage in vascularized pancreas transplantation

In previous years, the number of pancreas transplants has increased significantly. Debate continues over the optimum technique for exocrine drainage. Enteric drainage (ED) has recently been increasingly popular owing to the long-term complications of bladder drainage (BD). We prospectively evaluated 40 consecutive pancreas transplant recipients undergoing either bladder ( n = 20) or enteric ( n = 20) drainage. After simultaneous kidney-pancreas transplantation 1-year patient, kidney, and pancreas graft survival rates were 95%, 95%, 85% for the BD group, and 90%, 85%, 85%, for the ED group. Surgical complications were not significantly different between the two groups. The incidence of acute rejection, major infections and cytomegalovirus disease were also similar. The length of the initial hospital stay was likewise comparable. However, the BD group was characterized by a slight increase in the number of urologic complications, metabolic acidosis, and dehydration. Our results suggest excellent patient and graft survival irrespective of the drainage technique.

A prospective comparison of bladder versus enteric drainage in vascularized pancreas transplantation

Although the number of pancreas transplants has increased significantly in previous years, debate continues concerning the optimum technique for exocrine pancreas drainage. Enteric drainage (ED) has recently been increasingly popular due to the long-term complications with bladder drainage (BD). We prospectively assigned 40 consecutive pancreas transplant recipients to either bladder ( n = 20) or enteric ( n = 20) drainage. Patient, kidney, and pancreas graft survival rates at 1 year after simultaneous kidney-pancreas transplantation were 95%, 95%, 85%, for BD group and 90%, 85%, 85% for ED group, respectively. Surgical complications were not significantly different between the two groups. The incidence of acute rejection, major infections, and CMV disease were similar between groups. The length of the initial hospital stay was likewise comparable. However, the BD group showed a slight increase in the number of urologic complications, metabolic acidosis, and dehydration. Based on the results of our study, patient and graft survivals were excellent irrespective of technique.

Prolonged Improvement of Total Pancreatic Allograft Function by Previous Intrathymic Bone Marrow Cell Injection in Rats

Donor-specific induction of tolerance was previously achieved in the diabetic rat by intrathymic injection of pancreatic islets. It allowed a secondary islet graft in any site without immunosuppression. Since total pancreatic graft in man is metabolically more proficient than islet graft, we attempted tolerance induction for total vascularized pancreas transplantation in diabetic BN recipient rats by an intrathymic bone marrow cell (BMC) injection from Lewis donor rats, associated to an antilymphocyte antibody (ALS) administration. Control groups consisted of isogenic grafts, allogenic grafts without tolerance induction and allogenic grafts with ALS alone. In all grafted groups, mean blood glucose and plasma insulin were normalised within 24 h. Graft rejection (clinically suggested by diabetes recurrence and later confirmed by histology) appeared at 18 ± 2 postoperative days in the absence of intrathymic BMC injection and at 36 ± 8 days in the group with BMC injection (p < 0.05). Intrathymic bone marrow graft was successful in delaying rejection in our study.

Pancreas after kidney transplantation.

After three decades of controversy surrounding the therapeutic validity of pancreas transplantation, the procedure has become accepted as the preferred treatment for patients with insulin-dependent diabetes mellitus (IDDM) and advanced diabetic nephropathy with end-stage renal disease (ESRD) and for

Pancreas transplantation: Contemporary surgical techniques

Since its inception more than 30 years ago, vascularized pancreas transplantation has undergone considerable progress. Given the unique complications associated with transplantation of this organ, modifications in surgical technique have been necessary to improve outcomes. As a result of these surgical advances and improvements in organ preservation and immunosuppression, contemporary graft survival rates approach 90% at 1 year. Despite this level of success, the technique of pancreas transplantation remains controversial. Future efforts to reduce morbidity and minimize immunosuppression will enable pancreas transplantation to remain an important therapeutic option for selected patients with type 1 diabetes mellitus.

Islet transplantation.

Recently, significant advances have been made in the number and purity of islets that can be retrieved from the human pancreas, thus enabling several centers to initiate or resume clinical trials of islet transplantation in type I diabetic patients. Although the success rate of islet transplantation is lower than that of pancreas transplantation in terms of achievement of insulin-independence, islet transplantation has significant potential advantages over vascularized pancreas transplantation: it is a simple and safe procedure; it has the potential to be performed on an outpatient basis; it offers access to cell banking after cryopreservation; it offers the potential advantages of pre-transplant reduction of immunogenicity; and it even offers the future feasibility of xenotransplantation. In this article, the current status of clinical trials and future perspectives of islet transplantation, including immunomodulation, immunotolerance, immunoisolation, and xenotransplantation, are reviewed.