To describe the evolution of pancreas transplantation, including improved outcomes and factors associated with improved outcomes over the past 5 decades.

The world's first successful pancreas transplant was performed in December 1966 at the University of Minnesota. As new modalities for diabetes treatment mature, we must carefully assess the current state of pancreas transplantation to determine its ongoing role in patient care.

A single-center retrospective review of 2500 pancreas transplants was performed over >50 years in bivariate and multivariable models. Transplants were divided into 6 eras; outcomes are presented for the entire cohort and by era.

All measures of patient and graft survival improved progressively through the 6 transplant eras. The overall death-censored pancreas graft half-lives were >35 years for simultaneous pancreas and kidney (SPK), 7.1 years for pancreas after kidney (PAK), and 3.3 years for pancreas transplants alone (PTA). The 10-year death-censored pancreas graft survival rate in the most recent era was 86.9% for SPK recipients, 58.2% for PAK recipients, and 47.6% for PTA. Overall, graft loss was most influenced by patient survival in SPK transplants, whereas graft loss in PAK and PTA recipients was more often due to graft failures. Predictors of improved pancreas graft survival were primary transplants, bladder drainage of exocrine secretions, younger donor age, and shorter preservation time.

Pancreas outcomes have significantly improved over time through sequential, but overlapping, advances in surgical technique, immunosuppressive protocols, reduced preservation time, and the more recent reduction of immune-mediated graft loss.

Simultaneous pancreas-kidney transplantation is an effective treatment option for end-stage renal disease with diabetes mellitus. Successful simultaneous pancreas-kidney transplantation allows achieving euglycemia, stabilizing existing microvascular complications and slowing their progression, improving the patient's quality of life, lipid and calcium-phosphorus metabolism, reducing the risks of cardiovascular events. Therefore, in view of the patient's severe general condition due to prolonged intoxication, hyperglycemia and other complications of chronic kidney disease, the earliest possible surgical treatment with minimization of the patient's stay on dialysis therapy is crucial to improve the outcome of transplantation.

There are nearly 150 living donors in the United States who donated more than one solid organ. Using our divisional database, we found 20 individuals who donated a liver and a kidney at different times. We performed a retrospective chart review of these donors, studying their motivating factors, complications and outcomes. The donors included 11 (55%) males and nine females. Thirteen (65%) donated the kidney before the liver. Fourteen (70%) were nondirected donors at the first donation, and four of the six directed donors in the first donation became nondirected in the second donation. Seventeen (85%) were nondirected at the second donation. Common reasons for donating the second time were a good experience with the first donation and knowing that one can donate again. Outcomes and the incidence of early complications were not significantly different after the 2nd versus the 1st donation. All donors recovered and currently are doing well. Our results show a significant number of dual organ donors are nondirected and motivated by their strong desire to help. A positive experience with the 1st donation often was the driving factor for the 2nd. A history of previous organ donation did not negatively impact the 2nd donation.

The insulin promoter is regulated by ubiquitous as well as pancreatic β-cell-specific transcription factors. In the insulin promoter, GG2-GG1/A2-C1 (bases - 149 to - 116 in the human insulin promoter) play important roles in regulating β-cell-specific expression of the insulin gene. However, these events were identified through in vitro studies, and we are unaware of comparable in vivo studies. In this study, we evaluated the activity of GG2-GG1/A2 elements in the insulin promoter region in vivo. We generated homozygous mice with mutations in the GG2-GG1/A2 elements in each of the Ins1 and Ins2 promoters by CRISPR-Cas9 technology. The mice with homozygous mutations in the GG2-GG1/A2 elements in both Ins1 and Ins2 were diabetic. These data suggest that the GG2-GG1/A2 element in mice is important for Ins transcription in vivo.

Diabetes mellitus is etiologically classified into type 1, type 2 and other types of diabetes. Despite distinct etiologies and pathogenesis of these subtypes, many studies have suggested the presence of shared susceptibilities and underlying mechanisms in β-cell failure among different types of diabetes. Understanding these susceptibilities and mechanisms can help in the development of therapeutic strategies regardless of the diabetes subtype. In this review, we discuss recent evidence indicating the shared genetic susceptibilities and common molecular mechanisms between type 1, type 2 and other types of diabetes, and highlight the future prospects as well.

Pancreas transplantation significantly improves the quality of life for people with type 1 diabetes, primarily by eliminating the need for insulin and frequent blood glucose measurements. Despite the growing numbers of solid organ transplantations worldwide, number of pancreas transplantations in the developing countries` remain significantly low. This difference of pancreas transplantation practices was striking among the participating countries at the 1st International Transplant Network Meeting which was held in Turkey on 2018. In this meeting more than 40 countries were represented. Most of these counties were developing countries located in Africa, Middle East or Asia. The aim of this article is to identify the challenges and limiting factors for pancreas transplantations in these developing countries, by exploring the Turkish example. The challenges faced by the developing countries are broadly classified in four categories; wait-listing, donor pool, team work and follow up. Under these categorical titles, issues are further discussed in detail, giving examples from Turkish practice of pancreas transplantation. Additionally, several solutions to these challenges have been proposed- some of which have already been undertaken by the Turkish Ministry of Health. With the insight and methods presented in this article, pancreas transplantation should be made possible for the potential recipients in the developing countries.

The donation of multiple allografts from a single living donor is a rare practice, and the patient characteristics and outcomes associated with these procedures are not well described.

Using the Scientific Registry of Transplant Recipients, we identified 101 living multiorgan donors and their 133 recipients.

The 49 sequential (donations during separate procedures) multiorgan donors provided grafts to 81 recipients: 21 kidney-then-liver, 15 liver-then-kidney, 5 lung-then-kidney, 3 liver-then-intestine, 3 kidney-then-pancreas, 1 lung-then-liver, and 1 pancreas-then-kidney. Of these donors, 38% donated 2 grafts to the same recipient and 15% donated 2 grafts as non-directed donors. Compared to recipients from first-time, single organ living donors, recipients from second-time living donors had similar graft and patient survival. The 52 simultaneous (multiple donations during one procedure) multiorgan donors provided 2 grafts to 1 recipient each: 48 kidney-pancreas and 4 liver-intestine. Donors had median of 13.4 years (interquartile range, 8.3-18.5 years) of follow-up. There was one reported death of a sequential donor (2.5 years after second donation). Few postdonation complications were reported over a median of 116 days (interquartile range, 0-295 days) of follow-up; however, routine living donor follow-up data were sparse. Recipients of kidneys from second-time living donors had similar graft (P = 0.2) and patient survival (P = 0.4) when compared with recipients from first-time living donors. Similarly, recipients of livers from second-time living donors had similar graft survival (P = 0.9) and patient survival (P = 0.7) when compared with recipients from first-time living donors.

Careful documentation of outcomes is needed to ensure ethical practices in selection, informed consent, and postdonation care of this unique donor community.

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.

Minimally invasive surgery is standard procedure for many operations. Further refinements include the introduction of robotic surgery which is still an emerging field especially in laparoscopic surgery. Since the successful introduction of the da Vinci Robotic Surgical System, the robotic approach in organ transplantation has become of great interest in both the live donor organ retrieval and the recipient operation. Robotic surgery for kidney, liver, and pancreas transplantation is feasible. Over 700 donor nephrectomies and 100 kidney transplantations have been performed already, and robotic surgery is standard in a small number of pioneer centers; however, larger series and most importantly randomized controlled trials for the highest evidence are needed. Longer warm ischemia time and higher costs limit these procedures at the moment.

The first total pancreatectomy and islet autotransplantation (TP-IAT) was performed for chronic pancreatitis in 1977 with the goal to ameliorate the pain and simultaneously preserve islet function. We reviewed the recent medical literature regarding indications, patient suitability, current outcomes, and challenges in TP-IAT.

Current indications for TP-IAT include intractable pain secondary to chronic pancreatitis (CP) or acute recurrent pancreatitis (ARP) with failed medical and endoscopic/surgical management. Independent studies have shown that TP-IAT is associated with elimination or significant improvement in pain control and partial or full islet graft function in the majority of patients. In single-center cost analyses, TP-IAT has been suggested to be more cost-effective than medical management of chronic pancreatitis. While initially introduced as a surgical option for adults with long-standing chronic pancreatitis, TP-IAT is now often utilized in children with chronic pancreatitis and in children and adults with intractable acute recurrent pancreatitis. The surgical procedure has evolved over time with some centers offering minimally invasive operative options, although the open approach remains the standard. Despite many advances in TP-IAT, there is a need for further research and development in disease diagnosis, patient selection, optimization of surgical technique, islet isolation and quality assessment, postoperative patient management, and establishment of uniform metrics for data collection and multicenter studies. TP-IAT is an option for patients with otherwise intractable acute recurrent or chronic pancreatitis which presents potential for pain relief and improved quality of life, often with partial or complete diabetes remission.

Transplant patients face challenging medical journeys, with many detours to the intensive care unit. Before and after transplantation, they have significant psychological and cognitive comorbidities, which decrease their quality of life and potentially compromise their medical outcomes. Critical care staff are essential in these journeys. Being cognizant of relevant psychosocial and mental health aspects of transplant patients' experiences can help critical care personnel take comprehensive care of these patients. This knowledge can empower them to understand their patients' psychological journeys, recognize patients' mental health needs, provide initial interventions, and recognize need for expert consultations.

Minimally invasive surgical approaches in transplantation are gaining increasing interest, and many centers are reporting their, mainly laparoscopic, experiences. Robotic surgery (RS) has some hypothetical advantages over traditional laparoscopy and has been successfully applied, although infrequently to organ transplantation. Our goal was to review and critique the publications reporting RS use in organ transplantation. Most of the RS experience has been with living renal donor organ procurement and, to a lesser extent, with RS procedures in the transplant recipient. The available literature suggests that RS appears to be a safe surgical alternative to standard open procedures. RS in living liver donor surgery remains limited, and more experience is required before commenting on RS-related outcomes RS in pancreatic transplantation is exceedingly rare. The enhanced precision and ergonomics of RS may expand its applicability to liver living donation and pancreas transplantation at some point in the future.