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Current Diabetes Reports Jul 2019Pancreas transplantation enables complete patient independence from exogenous insulin administration and increases both patient survival and quality of life. Despite... (Review)
Review
PURPOSE OF REVIEW
Pancreas transplantation enables complete patient independence from exogenous insulin administration and increases both patient survival and quality of life. Despite this, there has been a decline in pancreas transplantation for the past 20 years, influenced by changing donor demographics with more high-risk extended criteria (ECD) and donation after cardiac death (DCD) donors. This review discusses whether the advent of machine perfusion (MP), if extended to the pancreas, can increase the pool of suitable donor organs.
RECENT FINDINGS
Hypothermic and normothermic MP, as forms of preservation deemed superior to cold storage for high-risk kidney and liver donor organs, have opened the avenue for translation of this work into the pancreas. Recent experimental models of porcine and human ex-vivo pancreatic MP are promising. Applications of MP to the pancreas however need refinement-focusing on perfusion protocols and viability assessment tools. Emerging research shows pancreatic MP can potentially offer superior preservation capacity, the ability to both resuscitate and manipulate organs, and assess functional and metabolic organ viability. The future of MP will lie in organ assessment and resuscitation after retrieval, where ultimately organs initially considered high risk and unsuitable for transplantation will be optimised and transformed, making them then available for clinical use, thus increasing the pool of suitably viable pancreata for transplantation.
Topics: Animals; Humans; Organ Preservation; Pancreas Transplantation; Perfusion; Quality of Life; Swine; Tissue Donors
PubMed: 31292740
DOI: 10.1007/s11892-019-1165-y -
Global Health & Medicine Dec 2020In Japan, the first pancreas transplantation was performed in 1984 from a brain-dead donor; subsequently, however, the concept of brain death became a social issue.... (Review)
Review
In Japan, the first pancreas transplantation was performed in 1984 from a brain-dead donor; subsequently, however, the concept of brain death became a social issue. Thereafter, the "Organ Transplant Act", which enables brain-dead transplantation, was enacted in 1997, and then revised in 2010 so that donation after brain death became possible only with the consent of the family. Under the recipient selection and registration system developed after the enactment of the "Organ Transplant Act", more than 400 pancreas transplants have been carried out at facilities certified for brain-dead pancreas transplantation in Japan. Of the 410 total cadaveric pancreas transplants performed by the end of 2019, the patient survival and pancreatic and kidney graft survival rates were considered to be comparable to those in the United States and Europe despite the high frequency of marginal donors. Minimally invasive allogenic islet transplantation came to be covered by national health insurance in 2020 following good outcomes of a recent trial. Furthermore, to overcome the serious donor shortage in Japan, development of xenogeneic islet transplantation and regenerative medicine using stem cells is in progress, with xenotransplantation using porcine islets appearing particularly promising.
PubMed: 33409415
DOI: 10.35772/ghm.2020.01069 -
Transplant International : Official... Jun 2019Organ preservation and re-conditioning using machine perfusion technologies continue to generate promising results in terms of viability assessment, organ utilization... (Review)
Review
Organ preservation and re-conditioning using machine perfusion technologies continue to generate promising results in terms of viability assessment, organ utilization and improved initial graft function. Here, we summarize the latest findings and study the results of ex-vivo/ex-situ hypothermic (HMP) and normothermic machine perfusion (NMP) in the area of abdominal organ transplantation (kidney, liver, pancreas and intestine). We also consider the potential role of normothermic regional perfusion (NRP) to re-condition donors after circulatory death organs before retrieval. The findings from clinical studies reported to date suggest that machine perfusion will offer real benefits when compared with conventional cold preservation. Several randomized trials are expected to report their findings within the next 2 years which may shed light on the relative merits of different perfusion methods and could indicate which perfusion parameters may be most useful to predict organ quality and viability. Further work is needed to identify composite endpoints that are relevant for transplanted organs that have undergone machine preservation. Multi-centre trials to compare and analyse the combinations of NRP followed by HMP and/or NMP, either directly after organ retrieval using transportable devices or when back-to-base, are needed. The potential applications of machine preservation technology beyond the field of solid organ transplantation are also considered.
Topics: Animals; Graft Survival; Humans; Intestines; Kidney; Kidney Transplantation; Liver; Liver Transplantation; Organ Preservation; Pancreas; Pancreas Transplantation; Perfusion; Tissue Donors
PubMed: 30980772
DOI: 10.1111/tri.13441 -
Seminars in Pediatric Surgery Jun 2022Pediatric patients constitute an important group within the general transplant population, given the opportunity to significantly extend their lives with successful...
Pediatric patients constitute an important group within the general transplant population, given the opportunity to significantly extend their lives with successful transplantation. Children have historically received special consideration under the various abdominal solid organ allocation algorithms, but matching patients with size and weight restrictions with appropriate donors remains an ongoing issue. Here, we describe the historical trends in pediatric organ allocation policies for liver, kidney, intestine, and pancreas transplantation. We also review recent changes to these allocation policies, with particular attention to recent amendments to geographical prioritization, with the dissolution of donor service areas and United Network for Organ Sharing (UNOS) regions and the subsequent creation of acuity circles.
Topics: Child; Humans; Liver Transplantation; Pancreas Transplantation; Tissue Donors; Waiting Lists
PubMed: 35725055
DOI: 10.1016/j.sempedsurg.2022.151180 -
The Cochrane Database of Systematic... Sep 2014Pancreas or kidney-pancreas transplantation improves survival and quality of life for people with type 1 diabetes mellitus and kidney failure. Immunosuppression after... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Pancreas or kidney-pancreas transplantation improves survival and quality of life for people with type 1 diabetes mellitus and kidney failure. Immunosuppression after transplantation is associated with complications. Steroids have adverse effects on cardiovascular risk factors such as hypertension, hyperglycaemia or hyperlipidaemia, increase risk of infection, obesity, cataracts, myopathy, bone metabolism alterations, dermatologic problems and cushingoid appearance. Whether avoiding steroids changes outcomes is unclear.
OBJECTIVES
We aimed to assess the safety and efficacy of steroid early withdrawal (treatment for less than 14 days after transplantation), late withdrawal (after 14 days after transplantation) or steroid avoidance in patients receiving a pancreas (including a vascularized organ) alone (PTA), simultaneous with a kidney (SPK) or after kidney transplantation (PAK).
SEARCH METHODS
We searched the Cochrane Renal Group's Specialised Register (to 18 June 2014) through contact with the Trials' Search Co-ordinator. We handsearched: reference lists of nephrology textbooks, relevant studies, recent publications and clinical practice guidelines; abstracts from international transplantation society scientific meetings; and sent emails and letters seeking information about unpublished or incomplete studies to known investigators.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) or cohort studies of steroid avoidance (including early withdrawal) versus steroid maintenance or versus late withdrawal in pancreas or pancreas with kidney transplant recipients. We defined steroid avoidance as complete avoidance of steroid immunosuppression, early steroid withdrawal as steroid treatment for less than 14 days after transplantation and late withdrawal as steroid withdrawal after 14 days after transplantation.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed the retrieved titles and abstracts, and where necessary the full text reports to determine which studies satisfied the inclusion criteria. Authors of included studies were contacted to obtain missing information. Statistical analyses were performed using random effects models and results expressed as risk ratio (RR) or mean difference (MD) with 95% confidence interval (CI). Cohort studies were not meta-analysed, but their findings summarised descriptively.
MAIN RESULTS
Three RCTs enrolling 144 participants met our inclusion criteria. Two compared steroid avoidance versus late steroid withdrawal and one compared late steroid withdrawal versus steroid maintenance. All studies included SPK and only one also included PTA. All studies had an overall moderate risk of bias and presented only short-term results (six to 12 months). Two studies (89 participants) compared steroid avoidance or early steroid withdrawal versus late steroid withdrawal. There was no clear evidence of an impact on mortality (2 studies, 89 participants: RR 1.64, 95% CI 0.21 to 12.75), risk of kidney loss censored for death (2 studies, 89 participants: RR 0.35, 95% CI 0.04 to 3.09), risk of pancreas loss censored for death (2 studies, 89 participants: RR 1.05, 95% CI 0.36 to 3.04), or acute kidney rejection (1 study, 49 participants: RR 2.08, 95% CI 0.20 to 21.50), however results were uncertain and consistent with no difference or important benefit or harm of steroid avoidance/early steroid withdrawal. The study that compared late steroid withdrawal versus steroid maintenance observed no deaths, no graft loss or acute kidney rejection at six months in either group and reported uncertain effects on acute pancreas rejection (RR 0.88, 95% CI 0.06 to 13.35). Of the possible adverse effects only infection was reported by one study. There were significantly more UTIs reported in the late withdrawal group compared to the steroid avoidance group (1 study, 25 patients: RR 0.41, 95% CI 0.26 to 0.66).We also identified 13 cohort studies and one RCT which randomised tacrolimus versus cyclosporin. These studies in general showed that steroid-sparing and withdrawal strategies had benefits in lowering HbAc1 and risk of infections (BK virus and CMV disease) and improved blood pressure control without increasing the risk of rejection. However, two studies found an increased incidence of acute pancreas rejection (HR 2.8, 95% CI 0.89 to 8.81, P = 0.066 in one study and 43.3% in the steroid withdrawal group versus 9.3% in the steroid maintenance, P < 0.05 at three years in the other) and one study found an increased incidence of acute kidney rejection (18.7% in the steroid withdrawal group versus 2.8% in the steroid maintenance, P < 0.05) at three years.
AUTHORS' CONCLUSIONS
There is currently insufficient evidence for the benefits and harms of steroid withdrawal in pancreas transplantation in the three RCTs (144 patients) identified. The results showed uncertain results for short-term risk of rejection, mortality, or graft survival in steroid-sparing strategies in a very small number of patients over a short period of follow-up. Overall the data was sparse, so no firm conclusions are possible. Moreover, the 13 observational studies findings generally concur with the evidence found in the RCTs.
Topics: Adult; Cohort Studies; Diabetes Mellitus, Type 1; Graft Rejection; Humans; Immunosuppression Therapy; Kidney Failure, Chronic; Kidney Transplantation; Living Donors; Middle Aged; Pancreas Transplantation; Randomized Controlled Trials as Topic; Steroids; Withholding Treatment
PubMed: 25220222
DOI: 10.1002/14651858.CD007669.pub2 -
World Journal of Transplantation Dec 2014Although the diagnosis of type 2 diabetes mellitus was once considered a contraindication to simultaneous pancreas-kidney transplantation, a growing body of evidence has... (Review)
Review
Although the diagnosis of type 2 diabetes mellitus was once considered a contraindication to simultaneous pancreas-kidney transplantation, a growing body of evidence has revealed that similar graft and patient survival can be achieved when compared to type 1 diabetes mellitus recipients. A cautious strategy regarding candidate selection may limit appropriate candidates from additional benefits in terms of quality of life and potential amelioration of secondary side effects of the disease process. Although our current understanding of the disease has changed, uniform listing characteristics to better define and study this population have limited available data and must be established.
PubMed: 25540731
DOI: 10.5500/wjt.v4.i4.216 -
Experimental and Clinical... Jun 2018Graft-versus-host disease after solid-organ transplant is exceedingly rare. Although the precise pathogenetic mechanisms are unknown, a progressive increase in donor... (Review)
Review
OBJECTIVES
Graft-versus-host disease after solid-organ transplant is exceedingly rare. Although the precise pathogenetic mechanisms are unknown, a progressive increase in donor chimerism is a requirement for its development. The incidence of mixed donor chimerism and its timeline after simultaneous pancreas-kidney transplant is unknown.
MATERIALS AND METHODS
After encountering 2 cases of graft-versus-host disease after simultaneous pancreas-kidney transplant at our institution over a period of < 2 years, a collaborative pilot study was conducted by the bone marrow transplant, nephrology, and abdominal transplant surgery teams. We enrolled all consecutive patients undergoing sex-mismatched simultaneous pancreas-kidney transplant over 1 year and longitudinally monitored donor chimerism using fluorescence in situ hybridization for sex chromosomes.
RESULTS
We found no evidence for chimerism in our 7 patients. In a comprehensive literature review, we found a total of 25 previously reported cases of graft-versus-host disease after kidney, pancreas, and simultaneous pancreas-kidney transplants. The median onset of graft-versus-host disease was approximately 5 weeks after transplant, with a median of about 2 weeks of delay between first presentation and diagnosis. Skin, gut, and bone marrow were almost equally affected at initial presentation, and fever of unknown origin occurred in more than half of patients. The median survival measured from the first manifestation of graft-versus-host disease was only 48 days.
CONCLUSIONS
Within the limitations related to small sample size, our results argue against an unusually high risk of graft-versus-host disease after simultaneous pancreas-kidney transplant. Collaboration between solid-organ and stem cell transplant investigators can be fruitful and can improve our understanding of the complications that are shared between the 2 fields.
Topics: Adult; Female; Graft Survival; Graft vs Host Disease; Humans; In Situ Hybridization, Fluorescence; Kidney Transplantation; Male; Middle Aged; Pancreas Transplantation; Pilot Projects; Sex Chromosomes; Time Factors; Transplantation Chimera; Treatment Outcome
PubMed: 28661312
DOI: 10.6002/ect.2016.0299 -
Current Diabetes Reports Nov 2019Beta-cell replacement is the best therapeutic option for patients with type 1 diabetes. Because of donor scarcity, more extended criteria donors are used for... (Review)
Review
PURPOSE OF REVIEW
Beta-cell replacement is the best therapeutic option for patients with type 1 diabetes. Because of donor scarcity, more extended criteria donors are used for transplantation. Donation after circulatory death donors (DCD) are not commonly used for pancreas transplantation, because of the supposed higher risk of complications. This review gives an overview on the pathophysiology, risk factors, and outcome in DCD transplantation and discusses different preservation methods.
RECENT FINDINGS
Studies on outcomes of DCD pancreata show similar results compared with those of donation after brain death (DBD), when accumulation of other risk factors is avoided. Hypothermic machine perfusion is shown to be a safe method to improve graft viability in experimental settings. DCD should not be the sole reason to decline a pancreas for transplantation. Adequate donor selection and improved preservation techniques can lead to enhanced pancreas utilization and outcome.
Topics: Death; Diabetes Mellitus, Type 1; Donor Selection; Graft Survival; Humans; Organ Preservation; Pancreas Transplantation; Retrospective Studies; Risk Factors; Tissue Donors; Treatment Outcome
PubMed: 31741132
DOI: 10.1007/s11892-019-1238-y -
Transplant International : Official... Apr 2021With a later onset of diabetes complications and thus increasing age of transplant candidates, many centers have extended upper age limits for pancreas transplantation....
With a later onset of diabetes complications and thus increasing age of transplant candidates, many centers have extended upper age limits for pancreas transplantation. This study investigates the effect of recipient and donor age on outcomes after pancreas transplantation.We retrospectively analyzed 565 pancreas transplants performed at two Eurotransplant centers. The cohort was split at a recipient and donor age of 50 and 40 years, respectively. Median recipient age in old patients (≥50 years; 27.2%) was 54 years and 40 years in young patients (<50 years). Compared to young recipients, old recipients had an inferior patient survival rate (≥50: 5yr, 82.8%; 10yr, 65.6%; <50: 5yr, 93.3%; 10yr, 82.0%; P < 0.0001). Old recipients demonstrated comparable death-censored pancreas (≥50: 1yr, 80.6%; 5yr, 70.2%; <50: 1yr, 87.3%; 5yr, 77.8%; P = 0.35) and kidney graft survival (≥50: 1yr, 97.4%; 5yr, 90.6%; <50: 1yr, 97.8%; 5yr, 90.2%; P = 0.53) compared to young recipients. Besides a lower rate of kidney rejection, similar relative risks for postoperative complications were detected in old and young patients. This study shows that despite an increased mortality in old recipients, excellent graft survival can be achieved similar to that of young patients. Age alone should not exclude patients from receiving a pancreas transplant.
Topics: Graft Rejection; Graft Survival; Humans; Kidney Transplantation; Middle Aged; Pancreas Transplantation; Retrospective Studies; Tissue Donors; Treatment Outcome
PubMed: 33570795
DOI: 10.1111/tri.13845 -
Transplant International : Official... 2022Ethnic disparities in the outcomes after simultaneous pancreas kidney (SPK) transplantation still exist. The influence of ethnicity on the outcomes of pancreas...
Ethnic disparities in the outcomes after simultaneous pancreas kidney (SPK) transplantation still exist. The influence of ethnicity on the outcomes of pancreas transplantation in the UK has not been reported and hence we aimed to investigate our cohort. A retrospective analysis of all pancreas transplant recipients ( = 171; Caucasians = 118/Black Asian Ethnic Minorities, BAME = 53) from 2006 to 2020 was done. The median follow-up was 80 months. Patient & pancreas graft survival, rejection rate, steroid free maintenance rate, HbA1c, weight gain, and the incidence of secondary diabetic complications post-transplant were compared between the groups. < 0.003 was considered significant (corrected for multiple hypothesis testing). Immunosuppression consisted of alemtuzumab induction and steroid free maintenance with tacrolimus and mycophenolate mofetil. Pancreas graft & patient survival were equivalent in both the groups. BAME recipients had a higher prevalence of type-2 diabetes mellitus pre-transplant (BAME = 30.19% vs. Caucasians = 0.85%, < 0.0001), and waited for a similar time to transplantation once waitlisted, although pre-emptive SPK transplantation rate was higher for Caucasian recipients (Caucasians = 78.5% vs. BAME = 0.85%, < 0.0001). Despite equivalent rejections & steroid usage, BAME recipients gained more weight (BAME = 7.7% vs. Caucasians = 1.8%, = 0.001), but had similar HbA1c (functioning grafts) at 3-,12-, 36-, and 60-months post-transplant.
Topics: Ethnicity; Glycated Hemoglobin; Graft Rejection; Humans; Immunosuppressive Agents; Kidney Transplantation; Pancreas Transplantation; Retrospective Studies; Steroids; United Kingdom
PubMed: 35781938
DOI: 10.3389/ti.2022.10490