Clinical pancreas and islet transplantation. Part 2: pancreas transplantation at the University of Minnesota.
David E.R. SutherlandFrederick C. GoetzPatricia L. ChinnBarbara A. ElickRichard L. SimmonsJohn S. Najarian
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Pancreas transplantation
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The only known cure for insulin-dependent diabetes mellitus is transplantation of functioning islet cells, either alone or via transplantation of the entire pancreas in sufficient mass to restore normal carbohydrate metabolism. Such therapy may also ameliorate or eliminate certain long-term consequences of diabetes. More than 3,000 patients have received pancreas transplants at 150 centers worldwide since 1966. Urinary drainage of pancreatic exocrine secretions has dramatically improved long-term survival, especially when a kidney was transplanted at the same time. Metabolic control then resumes normal function for up to six years, in some cases preventing or reversing long-term complications of diabetes. While nephropathy and neuropathy can be prevented and even somewhat reversed, retinopathy and neuropathy resist improvement. The large number of islets that must be harvested makes islet cell transplantation difficult to achieve, although the process has been accomplished in humans with limited success.
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Islet and pancreas transplantation may compete for a limited number of organs. We analyzed records from the national Swiss transplant registry during a 4-year period to investigate the proportion of donors that are suitable for islet and pancreas transplantation. Suitability for pancreas transplantation was mainly defined as: age 10-45 years; weight
Pancreas transplantation
Islet cell transplantation
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Pancreas transplantation
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Pancreas transplantation and islet of Langerhans transplantation are potential solutions to treat patients with type 1 diabetes. However, pancreas grafts are scarce and there is a shortage of donor pancreata relative to the number of patients needing a transplant. The aim of this thesis was to further optimize pancreas graft survival in pancreas transplantation and to optimize islet isolation outcomes in islet of Langerhans transplantation, leading to better use of available organs.
The focus in pancreas transplantation should be on optimizing recipients to improve graft survival and on improving quality of pancreata procured by centers not performing pancreas transplantation (for example, by training procurement surgeons to optimize pancreas procurement, thereby increasing the number of transplantable organs.
In islets transplantation, it is recommended that the reporting of donor, pancreas and isolation factors should become more standardized, which would enable us to determine more accurately which factors are important predictors for islet isolation outcome. Furthermore, if more biomedical factors (e.g. the presence of hyperemic islets) would be reported in addition to the other factors, we would be able to assess the independent effect of these biomedical factors for islet isolation outcome and eventually the effect on islet transplantation in the clinical setting.
Pancreas transplantation
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The concept of pancreatic β-cell mass is fundamental to the understanding of normal metabolism, the pathogenesis of diabetes, and the transplantation of β-cell tissue. The amount of β-cell tissue present in the pancreas is a major determinant of the quantity of insulin that can be secreted, and its mass will vary according to the size of the individual and the degree of insulin resistance present. Not all insulin-producing cells are the same, and the dimensions of this heterogeneity remain to be defined. Pancreatic β-cell mass is markedly reduced in insulin-dependent diabetes mellitus and moderately reduced in non-insulin-dependent diabetes mellitus. In both forms of diabetes, there are qualitative and quantitative abnormalities of insulin secretion that cannot be explained entirely by changes in β-cell mass. The amount of β-cell tissue needed for successful transplantation has only been partially defined. Segmental (∼50% of the pancreas) transplantation can normalize plasma glucose levels in humans. Difficulty obtaining sufficient amounts of β-cell tissue is expected to remain a barrier to successful islet transplantation for the immediate future. More should be learned about the function and fate of grafted islet cells.
Islet cell transplantation
BETA (programming language)
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Pancreas transplantation
Alloxan
Insulin dependent diabetes
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There are three possible indications for pancreas transplantation** 1. to correct the diabetic state; 2. to cure or ameliorate the complications of diabetes or to delay or diminish their deterioration; 3. to prevent the complications. The diabetes we are considering here is type 1 or insulin‐dependent diabetes, a disorder in which there is more or less complete insulin deficiency. No one has suggested pancreas transplantation for type 2, non‐insulin dependent diabetes. This article questions the rationale of pancreas transplantation. It maintains that the value of the procedure has not been established.
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Up to now we registered all over the world 485 transplantations of the pancreas. The partial donation of organs of relatives was performed in forty cases. On August 1st 1984 297 patients (70%) survived after a transplantation of the pancreas; of them 131 had a functioning transplant (30%). 54 transplanted organs (13%) had a good function for longer than 1 year. The most frequent complications were the thrombosis of the transplant, the pancreatitis, the fistulae of the pancreas and the rejection. Of 166 human allogenic islet transplantations at present none is functioning. Early rejections were the causes for the short function times. There were no cases of death by an islet transplantation. The present research concentrates to new methods of the islet isolation from the human pancreas and the immunological influence on the isolated islets.
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Pancreas transplantation
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Non-traditional methods of treatment of diabetes and its complications are discussed, including transplantation of the pancreas and the pancreatic islet-cell cultures, application of the artificial endocrine pancreas device and insulin-dosing apparatus, hemosorption, hemodialysis, and kidney transplantation. The pancreas transplantation is the procedure allowing to completely withhold exogenous insulin injections but which should be performed in specialized transplantation centres due to its complexity. Demonstrated is the long-term positive effect of the pancreatic islet-cell culture transplantation on the course and late complications of diabetes. The specific features and prospects of automated insulin administration by electromechanical devices in diabetes management are discussed. Noted is the positive effect of hemosorption on different diabetes manifestations, which is most pronounced in insulin-resistant cases associated with high anti-insulin antibody titres. The described methodologies require further improvement and may be used both as independent procedures and as valuable aids in traditional management of diabetes.
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