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ASAIO Journal (American Society For... Apr 2021Type 1 diabetes mellitus is a common and highly morbid disease for which there is no cure. Treatment primarily involves exogenous insulin administration, and, under... (Review)
Review
Type 1 diabetes mellitus is a common and highly morbid disease for which there is no cure. Treatment primarily involves exogenous insulin administration, and, under specific circumstances, islet or pancreas transplantation. However, insulin replacement alone fails to replicate the endocrine function of the pancreas and does not provide durable euglycemia. In addition, transplantation requires lifelong use of immunosuppressive medications, which has deleterious side effects, is expensive, and is inappropriate for use in adolescents. A bioartificial pancreas that provides total endocrine pancreatic function without immunosuppression is a potential therapy for treatment of type 1 diabetes. Numerous models are in development and take different approaches to cell source, encapsulation method, and device implantation location. We review current therapies for type 1 diabetes mellitus, the requirements for a bioartificial pancreas, and quantitatively compare device function.
Topics: Animals; Diabetes Mellitus, Type 1; Humans; Pancreas, Artificial
PubMed: 32826394
DOI: 10.1097/MAT.0000000000001252 -
World Journal of Transplantation Dec 2020In pancreas transplantation, complications can arise at each step of the process, from the initial selection of donors and recipients through the surgical technique... (Review)
Review
In pancreas transplantation, complications can arise at each step of the process, from the initial selection of donors and recipients through the surgical technique itself and the post-operative period, when lifelong immunosuppression is required. In the early steps, careful retrieval and preservation of the pancreas are crucial for the viability of the organ and ultimate success of the transplant. The pancreas is a low-flow gland, making it highly sensitive to transplantation conditions and presenting risk of pancreatitis due to periods of ischemia. The two groups of donors - after brain death (DBD) or after cardiac arrest (DCD) - require different strategies of retrieval and preservation to avoid or reduce the risk of complications developing during and after the transplantation. For DBD donor transplantation, multiorgan retrieval and cold preservation is the conventional technique. Asystole donor (DCD) transplantation, in contrast, can benefit from the newest technologies, such as hypothermic and especially normothermic preservation machines (referred to as NECMO), to optimize organ preservation. The latter has led to an increase in the pool of donors by facilitating recuperation of organs for transplantation that would have been discarded otherwise.
PubMed: 33437671
DOI: 10.5500/wjt.v10.i12.381 -
World Journal of Transplantation Dec 2020The aim of this minireview is to compare various pancreas transplantation exocrine drainage techniques , bladder enteric. Both techniques have different difficulties... (Review)
Review
The aim of this minireview is to compare various pancreas transplantation exocrine drainage techniques , bladder enteric. Both techniques have different difficulties and complications. Numerous comparisons have been made in the literature between exocrine drainage techniques throughout the history of pancreas transplantation, detailing complications and their impact on graft and patient survival. Specific emphasis has been made on the early postoperative management of these complications and the related surgical infections and their consequences. In light of the results, a number of bladder-drained pancreas grafts required conversion to enteric drainage. As a result of technical improvements, outcomes of the varied enteric exocrine drainage techniques (duodenojejunostomy, duodenoduodenostomy or gastric drainage) have also been discussed , assessing specific risks benefits. Pancreatic exocrine secretions can be drained to the urinary or intestinal tracts. Until the late 1990s the bladder drainage technique was used in the majority of transplant centers due to ease of monitoring urine amylase and lipase levels for evaluation of possible rejection. Moreover, bladder drainage was associated at that time with fewer surgical complications, which in contrast to enteric drainage, could be managed with conservative therapies. Nowadays, the most commonly used technique for proper driving of exocrine pancreatic secretions is enteric drainage due to the high rate of urological and metabolic complications associated with bladder drainage. Of note, 10% to 40% of bladder-drained pancreata eventually required enteric conversion at no detriment to overall graft survival. Various surgical techniques were originally described using the small bowel for enteric anastomosis with Roux-en-Y loop or a direct side-to-side anastomosis. Despite the improvements in surgery, enteric drainage complication rates ranging from 2%-20% have been reported. Treatment depends on the presence of any associated complications and the condition of the patient. Intra-abdominal infection represents a potentially very serious problem. Up to 30% of deep wound infections are associated with an anastomotic leak. They can lead not only to high rates of graft loss, but also to substantial mortality. New modifications of established techniques are being developed, such as gastric or duodenal exocrine drainage. Duodenoduodenostomy is an interesting option, in which the pancreas is placed behind the right colon and is oriented cephalad. The main concern of this technique is the challenge of repairing the native duodenum when allograft pancreatectomy is necessary. Identification and prevention of technical failure remains the main objective for pancreas transplantation surgeons. In conclusion, despite numerous techniques to minimize exocrine pancreatic drainage complications , leakage and infection, no universal technique has been standardized. A prospective study/registry analysis may resolve this.
PubMed: 33437672
DOI: 10.5500/wjt.v10.i12.392 -
Cell Transplantation 2021Allocation of donated organs for transplantation is a complex process that considers numerous factors such as donor, organ and candidate characteristics and practical...
Allocation of donated organs for transplantation is a complex process that considers numerous factors such as donor, organ and candidate characteristics and practical issues such as geography. Whole pancreas and isolated islet transplantation are lifesaving for certain individuals with diabetes. Herein, we suggest a revised allocation schema that matches donor characteristics with candidate medical condition while allowing for geographic considerations. It is hoped that adoption of this schema will shorten allocation time, decrease organ waste and optimize the parity between organ donor characteristics and candidate state of health.
Topics: Humans; Islets of Langerhans Transplantation; Middle Aged; Pancreas Transplantation
PubMed: 34757859
DOI: 10.1177/09636897211057130 -
Radiologia Brasileira 2021Pancreas transplantation is a well-established treatment for patients with complicated diabetes mellitus and advanced renal failure. The most common procedure is...
Pancreas transplantation is a well-established treatment for patients with complicated diabetes mellitus and advanced renal failure. The most common procedure is simultaneous pancreas-kidney transplantation, in which the pancreas graft is positioned in the right pelvic region and the kidney graft is positioned in the left iliac fossa. Various imaging methods are used for the post-transplantation evaluation of the graft parenchyma and vascular anatomy, as well as for the identification of possible complications. As the number of cases increases, it is fundamental that radiologists understand the surgical procedure and the postoperative anatomy, as well as to recognize the possible postoperative complications and their imaging aspects, with the aim of providing the best guidance in the postoperative management of transplant recipients.
PubMed: 34393296
DOI: 10.1590/0100-3984.2020.0108 -
American Journal of Transplantation :... Feb 2021The overall number of pancreas transplants decreased slightly, from 1027 in 2018 to 1015, in 2019, up from a nadir of 947 in 2015. However, the number of simultaneous...
The overall number of pancreas transplants decreased slightly, from 1027 in 2018 to 1015, in 2019, up from a nadir of 947 in 2015. However, the number of simultaneous pancreas-kidney transplants (SPKs) increased in 2019, with a corresponding drop in pancreas-after-kidney transplants (PAKs) and pancreas transplants alone (PTAs). New waitlist registrations increased to 1772 in 2019, from 1606 in 2018. This was predominately driven by SPK listings, and those with type 2 diabetes. Waiting time for SPK decreased by 2 months, to a median of 12 months in 2019, but PTA recipient mean waiting time remained substantially higher, at 24 months, in 2018. Both short- and long-term outcomes, including patient survival, kidney graft survival, and acute rejection-free graft survival, have shown consistent improvement over the last decade. Pancreas graft survival data with the uniform definition of allograft failure is being collected by the Organ Procurement and Transplant Network (OPTN) and will be included in a future report.
Topics: Diabetes Mellitus, Type 2; Graft Survival; Humans; Pancreas; Pancreas Transplantation; Tissue and Organ Procurement
PubMed: 33595197
DOI: 10.1111/ajt.16496 -
Journal of Clinical Medicine May 2023Whole-organ pancreas and islets transplantations are two therapeutic options to treat type 1 diabetic patients resistant to optimised medical treatment in whom severe... (Review)
Review
Whole-organ pancreas and islets transplantations are two therapeutic options to treat type 1 diabetic patients resistant to optimised medical treatment in whom severe complications develop. Selection of the best option for β-cell replacement depends on several factors such as kidney function, patient comorbidities, and treatment goals. For a patient with end-stage kidney disease, the treatment of choice is often a simultaneous transplant of the pancreas and kidney (SPK). However, it remains a major surgical procedure in patients with multiple comorbidities and therefore it is important to select those who will benefit from it. Additionally, in view of the organ shortage, new strategies to improve outcomes and reduce immune reactions have been developed, including dynamic organ perfusion technologies, pancreas bioengineering, and stem cell therapies. The purpose of this article is to review the indications, surgical techniques, outcomes, and future directions of whole-organ pancreas and islets transplantations.
PubMed: 37176684
DOI: 10.3390/jcm12093245 -
Presse Medicale (Paris, France : 1983) Dec 2022Type 1 diabetes is a disease resulting from autoimmune destruction of the insulin-producing beta cells in the pancreas. When type 1 diabetes develops into severe... (Review)
Review
Type 1 diabetes is a disease resulting from autoimmune destruction of the insulin-producing beta cells in the pancreas. When type 1 diabetes develops into severe secondary complications, in particular end-stage nephropathy, or life-threatening severe hypoglycemia, the best therapeutic approach is pancreas transplantation, or more recently transplantation of the pancreatic islets of Langerhans. Islet transplantation is a cell therapy procedure, that is minimally invasive and has a low morbidity, but does not display the same rate of functional success as the more invasive pancreas transplantation because of suboptimal engraftment and survival. Another issue is that pancreas or islet transplantation (collectively known as beta cell replacement therapy) is limited by the shortage of organ donors and by the need for lifelong immunosuppression to prevent immune rejection and recurrence of autoimmunity. A bioartificial pancreas is a construct made of functional, insulin-producing tissue, embedded in an anti-inflammatory, immunomodulatory microenvironment and encapsulated in a perm-selective membrane allowing glucose sensing and insulin release, but isolating from attacks by cells of the immune system. A successful bioartificial pancreas would address the issues of engraftment, survival and rejection. Inclusion of unlimited sources of insulin-producing cells, such as xenogeneic porcine islets or stem cell-derived beta cells would further solve the problem of organ shortage. This article reviews the current status of clinical islet transplantation, the strategies aiming at developing a bioartificial pancreas, the clinical trials conducted in the field and the perspectives for further progress.
Topics: Animals; Swine; Diabetes Mellitus, Type 1; Pancreas; Islets of Langerhans Transplantation; Pancreas Transplantation; Insulin; Islets of Langerhans
PubMed: 36202182
DOI: 10.1016/j.lpm.2022.104139 -
Diabetology & Metabolic Syndrome Jul 2023Type 1 diabetes mellitus (T1D) is a condition resulting from autoimmune destruction of pancreatic β cells, leading patients to require lifelong insulin therapy, which,...
BACKGROUND
Type 1 diabetes mellitus (T1D) is a condition resulting from autoimmune destruction of pancreatic β cells, leading patients to require lifelong insulin therapy, which, most often, does not avoid the most common complications of this disease. Transplantation of isolated pancreatic islets from heart-beating organ donors is a promising alternative treatment for T1D, however, this approach is severely limited by the shortage of pancreata maintained under adequate conditions.
METHODS
In order to analyze whether and how this problem could be overcome, we undertook a retrospective study from January 2007 to January 2010, evaluating the profile of brain-dead human pancreas donors offered to our Cell and Molecular Therapy NUCEL Center ( www.usp.br/nucel ) and the basis for organ refusal.
RESULTS
During this time period, 558 pancreata were offered by the São Paulo State Transplantation Central, 512 of which were refused and 46 were accepted for islet isolation and transplantation. Due to the elevated number of refused organs, we decided to analyze the main reasons for refusal in order to evaluate the possibility of improving the organ acceptance rate. The data indicate that hyperglycemia, technical issues, age, positive serology and hyperamylasemia are the top five main causes for declination of a pancreas offer.
CONCLUSIONS
This study underlines the main reasons to decline a pancreas offer in Sao Paulo-Brazil and provides some guidance to ameliorate the rate of eligible pancreas donors, aiming at improving the islet isolation and transplantation outcome.
TRIAL REGISTRATION
Protocol CAPPesq number 0742/02/CONEP 9230.
PubMed: 37391848
DOI: 10.1186/s13098-023-01089-8 -
Frontiers in Immunology 2023Focal segmental glomerulosclerosis (FSGS) is a common glomerular disorder that manifests clinically with the nephrotic syndrome and has a propensity to recur following... (Review)
Review
Focal segmental glomerulosclerosis (FSGS) is a common glomerular disorder that manifests clinically with the nephrotic syndrome and has a propensity to recur following kidney transplantation. The pathophysiology and therapies available to treat FSGS currently remain elusive. Since the podocyte appears to be the target of apparent circulating factor(s) that lead to recurrence of proteinuria following kidney transplantation, this article is focused on the podocyte. In the context of kidney transplantation, the performance of pre- and post-reperfusion biopsies, and the establishment of podocyte liquid biopsies/assays allow for the development of clinically relevant studies of podocyte biology. This has given insight into new pathways, involving novel targets in innate and adaptive immunity, such as SMPDL3b, cGAS-STING, and B7-1. Elegant experimental studies suggest that the successful clinical use of rituximab and abatacept, two immunomodulating agents, in our case series, may be due to direct effects on the podocyte, in addition to, or perhaps distinct from their immunosuppressive functions. Thus, tissue biomarker-directed therapy may provide a rational approach to validate the mechanism of disease and allow for the development of new therapeutics for FSGS. This report highlights recent progress in the field and emphasizes the importance of kidney transplantation and recurrent FSGS (rFSGS) as a platform for the study of primary FSGS.
Topics: Humans; Podocytes; Glomerulosclerosis, Focal Segmental; Kidney Glomerulus; Nephrotic Syndrome; Adaptive Immunity
PubMed: 37564655
DOI: 10.3389/fimmu.2023.1201619