Transplantation of organs from living donors helps to decrease the organ shortage and shortens waiting times. Living donor (LD) transplantation is also generally associated with better outcomes. Unfortunately, there has been no comprehensive analysis and comparison of all types of solid-organ transplantation from living donors since the inception of the United Network for Organ Sharing (UNOS).

Using the UNOS/Organ Procurement and Transplantation Network (OPTN) database, all LD transplants from October 1, 1987, to December 31, 2015, were studied with univariate and multivariate analyses.

A total of 140,090 organs were transplanted from LDs, accounting for 21% of all transplants in the United States. Over 95% were kidney; 4% were liver; and <1% intestine, lung, and pancreas LDs. Only LD kidney transplant patient and graft survival rates were significantly higher compared deceased donor transplants over the period of analysis. The best long-term LD transplant results were achieved in pediatric liver recipients. Significantly more women than men donated organs and significantly more men than women received solid-organ transplants. A regional disparity was observed for LD kidney as well as for LD liver transplants. Despite improvements in outcomes and increased use of nonbiologic donors, the number of LD transplants in the United States has declined. This decline was greater in children than adults and was noted for all types of organ transplants.

Further efforts are needed to educate the public, health professionals, and transplant candidates on the advantages of living vs deceased donor organ transplantation. Compared with other countries, LD transplantation has yet to reach its full potential in the United States.

Pancreas transplant has evolved significantly in recent years. It has now become a viable treatment option on type 1 diabetic patients with poorly controlled diabetes on conventional treatment, insulin intolerance, hypoglycaemia unawareness, brittle diabetes and/ or end-stage kidney disease. The purpose of this review is to provide an overview of pancreas transplant historical origins and current barriers to broader utilization of pancreata for transplant, with a focus on areas for future improvement to better pancreas transplant care. Donor pancreata remain underutilized; pancreatic allograft discard rates remain close to 30% in the United States. Donations after cardiac death (DCD) pancreata are seldom procured. Study groups from Europe and the United Kingdom showed that procurement professionalization and standardization of technique, as well as development of independent regional procurement teams might increase organ procurement efficiency, decrease discards and increase pancreatic allograft utilization. Pancreas transplant programs should consider exploring pancreas procurement opportunities on DCD and obese donors. Selected type 2 diabetics should be considered for pancreas transplant. Longer follow-up studies need to be performed in order to ascertain the long-term cardiovascular and quality of life benefits following pancreas transplant; the outcomes of which might eventually spearhead advocacy towards broader application of pancreas transplant among diabetics.

The potential to reverse diabetes has to be balanced against the morbidity of long-term immunosuppression associated with transplantation. For a patient with renal failure, the treatment of choice is often a simultaneous transplant of the pancreas and kidney or pancreas after kidney. For a patient with glycaemic instability, choices between a solid organ or islet transplant have to be weighed against benefits and risks of remaining on insulin. Results of simultaneous transplant of the pancreas and kidney transplantation are comparable to other solid-organ transplants, and there is evidence of improved quality of life and life expectancy. There is some evidence of benefit with respect to the progression of secondary diabetic complications in patients with functioning transplants for several years.

The purposes of this study were to study and compare clinical and functional outcomes after simultaneous deceased donor pancreas and kidney transplantation (SPK DD), simultaneous deceased donor pancreas and living donor kidney transplantation (SPK DL), and simultaneous living donor pancreas and kidney transplantation (SPK LL).

From January 1, 1996 to September 1, 2005, 8918 primary, simultaneous pancreas and kidney transplantation (SPK) procedures were reported to the International Pancreas Transplant Registry. Of these, 8764 (98.3%) were SPK DD, 115 (1.3%) were SPK DL, and 39 (0.4%) were SPK LL. We compared these 3 groups with regard to several endpoints including patient and pancreas and kidney graft survival rates.

The 1-year and 3-year patient survival rates for SPK DD were 95% and 90%, 97% and 95% for SPK DL, and 100% and 100% for SPK LL recipients, respectively (P ≥ .07). The 1-year and 3-year pancreas graft survival rates for SPK DD were 84% and 77%, 83% and 71% for SPK DL, and 90% and 84% for SPK LL recipients, respectively (P ≥ .16). The 1-year and 3-year kidney graft survival rates for SPK DD were 92% and 84%, 94% and 86% for SPK DL, and 100% and 89% for SPK LL recipients, respectively (P ≥ .37).

Patient survival rates and graft survival rates for pancreas and kidney were similar among the 3 groups evaluated in this study.

We recently reported that (11)C-methionine positron-emission tomography (PET) is clinically useful for the evaluation of the pancreatic function of the living donor. The objective of this study was to evaluate the postoperative insulin independence in 10 living donor (LD) and 10 brain-dead donor (BD) pancreas transplantations for 20 patients with type I diabetes mellitus by using (11)C-methionine PET. After 6 months, PET/computed tomography was performed 30 minutes after (11)C-methionine (370-740 MBq) injection. The uptake in the pancreas was expressed as the standardized uptake value (SUV). Patient survival rates were 100% at 5 years for LD transplantations and at 2 years for BD transplantations. Insulin independence was 60% for LD transplantations at 5 years and 75% for BD transplantations at 2 years. There were no major surgical complications such as vascular thrombosis, intra-abdominal abscess, and graft pancreatitis. The SUVs for LD and BD pancreas transplantations with insulin independence were 7.2 ± 1.8 and 10.4 ± 2.3, respectively. The SUVs for LD pancreas transplantations with insulin dependence and BD pancreas transplantations with graft failure were 3.6 ± 1.1 and 2.9 ± 1.0, respectively. At 5 years after transplantation, for the LD transplants, the insulin-independent rate was 100% for the graft recipients with an SUV higher than 5, and the median insulin independence duration of the graft recipients with an SUV less than 5 was 7 months (P < .01). The (11)C-methionine PET may be a potent modality to predict long-term insulin independence and the avoidance of pancreas graft failure.

Chronic kidney disease (CKD) has become a real epidemic around the world, mainly due to ageing and diabetic nephropathy. Although diabetic nephropathy due to type 1 diabetes mellitus (T1DM) has been studied more extensively, the vast majority of the diabetic CKD patients suffer from type 2 diabetes mellitus (T2DM). Renal transplantation has been established as a first line treatment for diabetic nephropathy unless there are major contraindications and provides not only a better quality of life, but also a significant survival advantage over dialysis. However, T2DM patients are less likely to be referred for renal transplantation as they are usually older, obese and present significant comorbidities. As pre-emptive renal transplantation presents a clear survival advantage over dialysis, all T2DM patients with CKD should be referred for early evaluation by a transplant center. The transplant center should have enough time in order to examine their eligibility focusing on special issues related with diabetic nephropathy and explore the best options for each patient. Living donor kidney transplantation should always be considered as the first line treatment. Otherwise, the patient should be listed for deceased donor kidney transplantation. Recent progress in transplantation medicine has improved the "transplant menu" for T2DM patients with diabetic nephropathy and there is an ongoing discussion about the place of simultaneous pancreas kidney (SPK) transplantation in well selected patients. The initial hesitations about the different pathophysiology of T2DM have been forgotten due to the almost similar short- and long-term results with T1DM patients. However, there is still a long way and a lot of ethical and logistical issues before establishing SPK transplantation as an ordinary treatment for T2DM patients. In addition recent advances in bariatric surgery may offer new options for severely obese T2DM patients with CKD. Nevertheless, the existing data for T2DM patients with advanced CKD are rather scarce and bariatric surgery should not be considered as a cure for diabetic nephropathy, but only as a bridge for renal transplantation.

Diabetes mellitus remains one of the leading causes of morbidity and mortality worldwide. According to the Centers for Disease Control and Prevention, approximately 23.6 million people in the United States are affected. Of these individuals, 5-10% have been diagnosed with type 1 diabetes mellitus (TIDM), an autoimmune disease. Although it often appears in childhood, T1DM may manifest at any age. The effects of T1DM can be devastating, as the disease often leads to significant secondary complications, morbidity, and decreased quality of life. Since the late 1960s, surgical treatment for diabetes mellitus has continued to evolve and has become a viable alternative to chronic insulin administration. In this review, the historical evolution, current status, graft efficacy, benefits, and complications of pancreas transplantation are explored.

Diabetes mellitus is generally treated with oral diabetic drugs and/or insulin. However, the morbidity and mortality associated with this condition increases over time, even in patients receiving intensive insulin treatment, and this is largely attributable to diabetic complications or the insulin therapy itself. Pancreas transplantation in humans was first conducted in 1966, since when there has been much debate regarding the legitimacy of this procedure. Technical refinements and the development of better immunosuppressants and better postoperative care have brought about marked improvements in patient and graft survival and a reduction in postoperative morbidity. Consequently, pancreas transplantation has become the curative treatment modality for diabetes, particularly for type I diabetes. An overview of pancreas transplantation is provided herein, covering the history of pancreas transplantation, indications for transplantation, cadaveric and living donors, surgical techniques, immunosuppressants, and outcome following pancreas transplantation. The impact of successful pancreas transplantation on the complications of diabetes will also be reviewed briefly.

As result of improved surgical techniques and newer immunosuppressive regimens contributing significantly to better graft survival, exocrine pancreas transplantation remains the standard treatment of choice for patients with diabetes mellitus complicated by end-stage renal disease. Histologic assessment continues to play an important role in the diagnosis of graft complications after pancreas transplantation, especially for evaluating allograft rejection where histopathology is still considered the gold standard. This review elaborates on the current types of pancreas transplants and focuses on the patterns of allograft injury that are encountered in posttransplantation pancreas biopsies along with the pertinent differential diagnoses. In addition to optimal histologic assessment, as in any other organ transplant setting, clinical information including indication and duration of transplant as well as other serologic work-up must be taken into consideration during clinical decision making for optimal graft outcome.

Since the introduction of pancreas transplantation more than 40 years ago, efforts to develop more minimally invasive techniques for endocrine replacement therapy have been in progress, yet this surgical procedure still remains the treatment of choice for diabetic patients with end-stage renal failure. Many improvements have been made in the surgical techniques and immunosuppressive regimens, both of which have contributed to an increasing number of indications for pancreas transplantation. This operation can be justified on the basis that patients replace daily injections of insulin with an improved quality of life but at the expense of a major surgical procedure and lifelong immunosuppression. The various indications, categories, and outcomes of patients having a pancreas transplant are discussed, particularly with reference to the effect on long-term diabetic complications.

With the proliferation and expanding applications of laparoscopic techniques, we determined the applicability of the laparoscopic approach to living pancreas donation. We performed the first laparoscopic donor distal pancreatectomy in 1999. We herein present our initial experience with five hand-assisted laparoscopic donor pancreatectomies. Three donors underwent distal pancreatectomy alone; two underwent a simultaneous left nephrectomy. The mean donor age was 48.4+/-8.7 years with a body mass index of 23.7 kg/m2. The donor and recipient survival rate was 100% at up to 3 years of follow-up. There were no episodes of pancreatitis, leaks, or pseudocysts. All donors returned to their preoperative state of health and to work. None of the donors have required oral anti-diabetic medications or insulin. We conclude that laparoscopic donor distal pancreatectomy is a safe and efficient procedure; hand-assisted laparoscopic distal pancreatectomy appears to be preferable, because of the added margin of safety from increased tactile feedback and ease of pancreatic dissection. The procedure can be accomplished with a single 6-cm periumbilical incision and only two 12-mm ports, resulting in excellent cosmesis and high donor satisfaction.

Pancreas transplantation continues to evolve as a strategy in the management of diabetes mellitus. The first combined pancreas-kidney transplant was reported in 1967, but pancreas transplant now represents a number of procedures, each with different indications, risks, benefits, and outcomes. This review will summarize these procedures, including their risks and outcomes in comparison to kidney transplantation alone, and how or if they affect the consequences of diabetes: hyperglycemia, hypoglycemia, and microvascular and macrovascular complications. In addition, the new risks introduced by immunosuppression will be reviewed, including infections, cancer, osteoporosis, reproductive function, and the impact of immunosuppression medications on blood pressure, lipids, and glucose tolerance. It is imperative that an endocrinologist remain involved in the care of the pancreas transplant recipient, even when glucose is normal, because of the myriad of issues encountered post transplant, including ongoing management of diabetic complications, prevention of bone loss, and screening for failure of the pancreas graft with reinstitution of treatment when indicated. Although long-term patient and graft survival have improved greatly after pancreas transplant, a multidisciplinary team is needed to maximize long-term quality, as well as quantity, of life for the pancreas transplant recipient.

In the face of a rising incidence of diabetes, pancreatic transplantation seems to be the only treatment capable of normalizing glycosylated hemoglobin and stabilizing or improving the complications of diabetes. To date, more than 19,000 pancreatic transplantations have been done worldwide. Surgical indications must take into account the constraints and risks specific to the diabetic illness, the risks of a complex surgical procedure, and the absolute necessity for long term immunosuppression. Combined kidney/pancreas transplantation is the most common procedure (90% of cases) and is the most effective treatment for renal insufficiency due to diabetes. Results have improved significantly over the last ten Years due to improvements in the surgical technique and to improvement of immunosuppressive regimens. Results are at least as good and perhaps better than those achieved in the transplantation of other solid organs; patient survival, renal graft survival, and pancreatic graft survival are respectively 95%, 92%, and 85% at one Year. Results of pancreatic transplantation alone have improved and now seem equal to those of combined organ transplantation. Transplantation seems to be cost-effective in the overall care of advanced diabetes, particularly in those patients on chronic dialysis or having degenerative complications.

Simultaneous pancreas and kidney transplantation (SPK) from cadaveric donors has become a widely accepted therapeutic option for insulin-dependent uremic patients. In 1996 the first SPK from a live donor was performed. This procedure offers the advantage of a better immunologic match, reduced cold ischemia injury, and decreased waiting time. As such, it is an attractive alternative treatment for diabetic patients with end-stage nephropathy with an available living donor.

We performed six SPKs from living-related donors. There were four men and two women among the recipients; median age was 34 (range, 29-39) years. All donors were recipients' siblings with excellent HLA matching. Donors underwent standardized metabolic workup, anti-insulin and anti-islet antibody assays, and computed tomography of the abdomen. Both donors and recipients were treated with octreotide for 5 days perioperatively. After transplantation, the patients were maintained on tacrolimus-based immunosuppression, with the exception of one recipient of SPK from an identical twin, who received cyclosporine monotherapy.

All the donors are doing well and have normal renal function and blood glucose levels. One-year patient, renal, and pancreatic graft survival rates were 100%, 100%, and 83%, respectively. Acute kidney rejection was documented in two patients, and both recovered completely after OKT3 therapy. No rejection of pancreatic graft has been documented. Except for one patient who lost the graft because of hemorrhagic pancreatitis, all recipients maintained serum glucose levels at less than 130 mg/dL without insulin therapy. No major surgical complications such as graft thrombosis, intra-abdominal infection, or abscess were reported.

Living donor SPK can represent a successful alternative to cadaveric donor SPK. The procedure can be performed safely in the donor and with low morbidity in the recipient.

To determine outcome in diabetic pancreas transplant recipients according to risk factors and the surgical techniques and immunosuppressive protocols that evolved during a 33-year period at a single institution.

Insulin-dependent diabetes mellitus is associated with a high incidence of management problems and secondary complications. Clinical pancreas transplantation began at the University of Minnesota in 1966, initially with a high failure rate, but outcome improved in parallel with other organ transplants. The authors retrospectively analyzed the factors associated with the increased success rate of pancreas transplants.

From December 16, 1966, to March 31, 2000, the authors performed 1,194 pancreas transplants (111 from living donors; 191 retransplants): 498 simultaneous pancreas-kidney (SPK) and 1 simultaneous pancreas-liver transplant; 404 pancreas after kidney (PAK) transplants; and 291 pancreas transplants alone (PTA). The analyses were divided into five eras: era 0, 1966 to 1973 (n = 14), historical; era 1, 1978 to 1986 (n = 148), transition to cyclosporine for immunosuppression, multiple duct management techniques, and only solitary (PAK and PTA) transplants; era 2, 1986 to 1994 (n = 461), all categories (SPK, PAK, and PTA), predominantly bladder drainage for graft duct management, and primarily triple therapy (cyclosporine, azathioprine, and prednisone) for maintenance immunosuppression; era 3, 1994 to 1998 (n = 286), tacrolimus and mycophenolate mofetil used; and era 4, 1998 to 2000 (n = 275), use of daclizumab for induction immunosuppression, primarily enteric drainage for SPK transplants, pretransplant immunosuppression in candidates awaiting PTA.

Patient and primary cadaver pancreas graft functional (insulin-independence) survival rates at 1 year by category and era were as follows: SPK, era 2 (n = 214) versus eras 3 and 4 combined (n = 212), 85% and 64% versus 92% and 79%, respectively; PAK, era 1 (n = 36) versus 2 (n = 61) versus 3 (n = 84) versus 4 (n = 92), 86% and 17%, 98% and 59%, 98% and 76%, and 98% and 81%, respectively; in PTA, era 1 (n = 36) versus 2 (n = 72) versus 3 (n = 30) versus 4 (n = 40), 77% and 31%, 99% and 50%, 90% and 67%, and 100% and 88%, respectively. In eras 3 and 4 combined for primary cadaver SPK transplants, pancreas graft survival rates were significantly higher with bladder drainage (n = 136) than enteric drainage (n = 70), 82% versus 74% at 1 year (P =.03). Increasing recipient age had an adverse effect on outcome only in SPK recipients. Vascular disease was common (in eras 3 and 4, 27% of SPK recipients had a pretransplant myocardial infarction and 40% had a coronary artery bypass); those with no vascular disease had significantly higher patient and graft survival rates in the SPK and PAK categories. Living donor segmental pancreas transplants were associated with higher technically successful graft survival rates in each era, predominately solitary (PAK and PTA) in eras 1 and 2 and SPK in eras 3 and 4. Diabetic secondary complications were ameliorated in some recipients, and quality of life studies showed significant gains after the transplant in all recipient categories.

Patient and graft survival rates have significantly improved over time as surgical techniques and immunosuppressive protocols have evolved. Eventually, islet transplants will replace pancreas transplants for suitable candidates, but currently pancreas transplants can be applied and should be an option at all stages of diabetes. Early transplants are preferable for labile diabetes, but even patients with advanced complications can benefit.

Pancreas transplantation is still the best option to achieve normoglycaemia and insulin independence in patients with type I diabetes. As a result of improvements in surgical techniques, immunosuppression and patient selection, one year survival rates of 95, 83, and 88% for patient, pancreas, and kidney survival, respectively, are reported for patients with simultaneous pancreas and kidney transplantation. The main goals for the future are to reduce postoperative morbidity, to identify the relevant indications for single pancreas transplantation, to adopt the best surgical technique for individual patients' needs (bladder versus enteric drainage with or without portal venous delivery of insulin), and to develop immunosuppressive strategies with low nephrotoxic and diabetogenic potential.

Simultaneous pancreas-kidney transplant from living donors has been recently proposed as an effective therapeutic option in selected uremic patients with type I diabetes. We report the first simultaneous pancreas-kidney transplant performed between identical twins. Posttransplant, the recipient has been maintained on low dose cyclosporine to avoid recurrent auto-immune insulitis. At the 1-year follow-up, both donor and recipient are well with normal renal function and excellent glucose control. Simultaneous pancreas-kidney transplant between identical twins can be performed successfully using cyclosporine to prevent recurrent auto-immune insulitis.

A review of 100 living-liver donors was performed to evaluate the perisurgical complications of the procedure and thus to help quantify the risks to the donor.

Despite the advantages of living-donor liver transplantation (LDLT), the procedure has received criticism for the risk it imposes on healthy persons. A paucity of data exists regarding the complications and relative safety of the procedure.

One hundred LDLTs performed between November 1989 and November 1996 were reviewed. Donor data were obtained by chart review, anesthesia records, and the computerized hospital data base. Patient variables were compared by Fisher's exact test and the Student's t test.

There were 57 women and 43 men with a median age of 29. Donors were divided into two groups: group A (first 50 donors), and group B (last 50 donors). There were 91 left lateral segments and 9 left lobes. There were no deaths. Fourteen major complications occurred in 13 patients; 9 occurred in group A and 5 in group B. Biliary complications consisted of five bile duct injuries (group A = 4, group B = 1) and two cut edge bile leaks. Complications were more common in left lobe resections (55%) than in left lateral segment grafts (10%). Minor complications occurred in 20% of patients. A significant reduction in overall complications (major and minor) was observed between the groups (group A, n = 24 [45%] vs. group B, n = 10 [20%]). In addition, surgical time and hospital stay were both significantly reduced.

Although the procedure is safe, many LDLT donors have a perisurgical complication. Surgical experience and technical modifications have resulted in a significant reduction in these complications, however. To minimize the risks for these healthy donors, LDLT should be performed at institutions with extensive experience.

In this first report of a clinical series of simultaneous pancreas-kidney transplants (SPKs) from live donors, the authors assess donor and recipient outcome as well as the spectrum of surgical and metabolic complications.

The rationale for live (vs. cadaveric) donation includes an immunologic advantage (better matching, decreased drugs, and fewer rejection episodes) and elimination of waiting time. Only sequential kidney and pancreas or pancreas transplants alone from live donors had been done until the authors' current series.

Between March 15, 1994, and March 15, 1997, the authors performed 20 SPKs from live donors (6 human leukocyte antigen-identical siblings, 14 mismatched relatives [5 parents, 7 siblings, 1 daughter, 1 aunt]). Of the 20 donors, 13 were women, and 7 were men; median age was 43 years (range, 30-58 years). All donors underwent standardized metabolic workup, including oral glucose tolerance tests, determination of hemoglobin A1 c levels, and tests to study insulin secretion and functional insulin secretory reserve. Of the 20 recipients, 12 were women, and 8 were men; median age was 34 years (range, 14-50 years). Management of exocrine pancreatic secretions was with bladder drainage in 17 and duct injection in 3 recipients. Median follow-up was 9 months (range, 1-36 months).

Currently, all 20 kidney grafts are functioning. Of the 20 pancreas grafts, 15 are functioning, 3 thrombosed, but 2 of those patients underwent immediate retransplantation from a cadaveric donor, and their grafts currently are functioning. Recipient complications included three anastomotic leaks and three intra-abdominal abscesses. Donor complications included four splenectomies, two peripancreatic fluid collections, one pseudocyst, and one intra-abdominal abscess; two donors underwent reoperation. Three donors had impaired glucose metabolism postdonation. Using tacrolimus and mycophenolate mofetil for mainstay immunosuppression, only 8 of 20 recipients experienced > or =1 rejection episode; only 1 pancreas graft was lost to rejection. Donor and recipient mortality was 0%.

Simultaneous pancreas-kidney transplants from live donors can be done with no mortality and good graft outcome. With stringent donor criteria, this approach could become another surgical alternative for endocrine replacement therapy in selected patients with uremic type I diabetes.