Pancreas transplantation. Lancet

Department of Hepatopancreatobiliary and Transplantation Surgery, Freeman Hospital, Newcastle upon Tyne, Tyne and Wear, UK.
The Lancet (Impact Factor: 45.22). 06/2009; 373(9677):1808-17. DOI: 10.1016/S0140-6736(09)60609-7
Source: PubMed


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.

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Available from: James A Shaw, Sep 29, 2015
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    • "At present, islet transplantation is considered to be one of the most effective therapies for the treatment of patients with severe diabetes123. However, the shortage of donor human pancreases limits such clinical therapy. "
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    ABSTRACT: Insulin-producing cells (IPCs) derived from human pluripotent stem cells (hPSCs) may be useful in cell therapy and drug discovery for diabetes. Here, we examined various growth factors and small molecules including those previously reported to develop a robust differentiation method for induction of mature IPCs from hPSCs. We established a protocol that induced PDX1-positive pancreatic progenitor cells at high efficiency, and further induced mature IPCs by treatment with forskolin, dexamethasone, Alk5 inhibitor II and nicotinamide in 3D culture. The cells that differentiated into INSULIN-positive and C-PEPTIDE-positive cells secreted insulin in response to glucose stimulation, indicating a functional IPC phenotype. We also found that this method was applicable to different types of hPSCs.
    Scientific Reports 03/2014; 4:4488. DOI:10.1038/srep04488 · 5.58 Impact Factor
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    • "Associated nephropathy can lead to dialysis with its own major risk factors for cardiovascular disease and a low quality of life. Simultaneous pancreas kidney transplantation (SPK) or pancreas transplantation after kidney (PAK) are the only curative treatment options for type 1 diabetic patients with impaired kidney function [1,2]. The aim of SPK is to optimize blood sugar control, prevent retinopathy progression and reduce other cardiovascular diseases, thereby restoring life quality and length [3-5]. "
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    ABSTRACT: Simultaneous pancreas kidney transplantation (SPK), pancreas transplantation alone (PTA) or pancreas transplantation after kidney (PAK) are the only curative treatment options for patients with type 1 (juvenile) diabetes mellitus with or without impaired renal function. Unfortunately, transplant waiting lists for this indication are increasing because the current organ acceptability criteria are restrictive; morbidity and mortality significantly increase with time on the waitlist. Currently, only pancreas organs from donors younger than 50 years of age and with a body mass index (BMI) less than 30 are allocated for transplantation in the Eurotransplant (ET) area. To address this issue we designed a study to increase the available donor pool for these patients. This study is a prospective, multicenter (20 German centers), single blinded, non-randomized, two armed trial comparing outcome after SPK, PTA or PAK between organs with the currently allowed donor criteria versus selected organs from donors with extended criteria. Extended donor criteria are defined as organs procured from donors with a BMI of 30 to 34 or a donor age between 50 and 60 years. Immunosuppression is generally standardized using induction therapy with Myfortic, tacrolimus and low dose steroids. In principle, all patients on the waitlist for primary SPK, PTA or PAK are eligible for the clinical trial when they consent to possibly receiving an extended donor criteria organ. Patients receiving an organ meeting the current standard criteria for pancreas allocation (control arm) are compared to those receiving extended criteria organ (study arm); patients are blinded for a follow-up period of one year. The combined primary endpoint is survival of the pancreas allograft and pancreas allograft function after three months, as an early relevant outcome parameter for pancreas transplantation. The EXPAND Study has been initiated to investigate the hypothesis that locally allocated extended criteria organs can be transplanted with similar results compared to the currently allowed standard ET organ allocation. If our study shows a favorable comparison to standard organ allocation criteria, the morbidity and mortality for patients waiting for transplantation could be reduced in the future.Trial registration: Trial registered at: NCT01384006.
    07/2013; 2(1):12. DOI:10.1186/2047-1440-2-12
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    • "For nephropathy, normoglycemia can stop the progression of diabetic glomerulopathy, but does not reverse it (36,37). Similarly, pancreas transplantation alone can limit further reduction in glomerular filtration rate (33), and SPK protects the graft kidney from developing diabetic nephropathy (38). "
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    ABSTRACT: Diabetic neuropathy is associated with increased morbidity and mortality. To date, limited data in subjects with impaired glucose tolerance and diabetes demonstrate nerve fiber repair after intervention. This may reflect a lack of efficacy of the interventions but may also reflect difficulty of the tests currently deployed to adequately assess nerve fiber repair, particularly in short-term studies. Corneal confocal microscopy (CCM) represents a novel noninvasive means to quantify nerve fiber damage and repair. Fifteen type 1 diabetic patients undergoing simultaneous pancreas-kidney transplantation (SPK) underwent detailed assessment of neurologic deficits, quantitative sensory testing (QST), electrophysiology, skin biopsy, corneal sensitivity, and CCM at baseline and at 6 and 12 months after successful SPK. At baseline, diabetic patients had a significant neuropathy compared with control subjects. After successful SPK there was no significant change in neurologic impairment, neurophysiology, QST, corneal sensitivity, and intraepidermal nerve fiber density (IENFD). However, CCM demonstrated significant improvements in corneal nerve fiber density, branch density, and length at 12 months. Normalization of glycemia after SPK shows no significant improvement in neuropathy assessed by the neurologic deficits, QST, electrophysiology, and IENFD. However, CCM shows a significant improvement in nerve morphology, providing a novel noninvasive means to establish early nerve repair, missed by currently advocated assessment techniques.
    Diabetes 01/2013; 62(1):254-60. DOI:10.2337/db12-0574 · 8.10 Impact Factor
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