Pancreas transplantation

Pancreas transplantation is now standard of care for selected patients with diabetes and end-stage renal failure or life-threatening diabetic complications. The morbidity and mortality of pancreas transplantation is higher than other transplant types, and for this reason selection criteria for both donors and recipients are more stringent. Meticulous organ retrieval technique and back-table preparation, and a standard implantation technique using enteric drainage are central to good outcomes. Modern immunosuppression has reduced acute rejection rates and lowered the need for long-term corticosteroids. Results have improved over time and recipients of a simultaneous kidney–pancreas transplant can now expect 5-year transplant survival of around 75%. The addition of a pancreas to a kidney transplant for suitable recipients has clear benefits in both length and quality of life, and there is increasing evidence that pancreatic transplantation can reduce or halt the progression of diabetic nephropathy, neuropathy, retinopathy and cardiovascular disease. In patients with normal renal function, pancreatic islet transplantation offers an alternative with reduced peri-procedural morbidity and mortality, at the expense of lower rates of long-term insulin independence.     

Pancreas transplantation

Pancreas transplantation is now standard of care for selected patients with diabetes and end-stage renal failure or life-threatening diabetic complications. The morbidity and mortality of pancreas transplantation is higher than other transplant types, and for this reason selection criteria for both donors and recipients are more stringent. Meticulous organ retrieval technique and back-table preparation, and a standard implantation technique using enteric drainage are central to good outcomes. Modern immunosuppression has reduced acute rejection rates and lowered the need for long-term corticosteroids. Results have improved over time and recipients of a simultaneous kidney-pancreas transplant can now expect 5-year transplant survival of over 75%. The addition of a pancreas to a kidney transplant for suitable recipients has clear benefits in both length and quality of life, and there is increasing evidence that pancreatic transplantation can reduce or halt the progression of diabetic nephropathy, neuropathy, retinopathy and cardiovascular disease. In patients with normal renal function, pancreatic islet transplantation offers an alternative with reduced peri-procedural morbidity and mortality, at the expense of lower rates of long-term insulin independence.     

Pancreas transplantation

Pancreas transplantation is now the standard of care for selected patients with diabetes and end-stage renal failure, with clear benefits in duration and quality of life. The indication for transplantation in patients with other severe diabetic complications are less clearly defined and the benefits less certain. The criteria for donor selection are more rigorous than for kidney and liver transplantation; selection of suitable organs and surgical retrieval technique are critical to success as the transplanted pancreas is vulnerable to preservation injury and post-transplant pancreatitis. Modern immunosuppressive strategies have reduced rejection rates and lowered the need for steroids; this has enabled surgical developments, particularly the enteric drainage of exocrine secretions, which have further reduced postoperative complications. As well as data relating to greater life expectancy, there is increasing evidence of stabilisation or long-term improvement in retinal, cardiovascular and neurological complications of diabetes. In patients with normal renal function, pancreatic islet transplantation may provide similar benefits without the morbidity of whole organ transplantation; this may be offered to patients suffering from life-threatening episodes of hypoglycaemic unawareness.     

Pancreas transplantation alone in children: a case report

Abstract: Pancreas transplantation (PT) is a relatively uncommon therapy for non‐uremic type 1 diabetes, as the severity of diabetes must warrant the risk of immunosuppression. In pediatric diabetic patients, who are less likely to display uremia because of the duration of diabetes, there is very little experience with pancreas transplantation alone (PTA). This report describes a 13‐yr‐old male PTA recipient. This patient was initially diagnosed with type 1 diabetes mellitus at the age of four yr. Following a multidisciplinary evaluation, PTA was found to be indicated based on a history of severe labile diabetes and hypoglycemic unawareness resulting in frequent episodes of hypoglycemia and hospital admissions. Because of the failure of medical management of the patient’s diabetes, a whole organ bladder and systemic drained PTA was performed. Immunosuppression included thymoglobulin, tacrolimus, mycophenolate mofetil, and steroids. Early outcome was uneventful and patient was discharged 12 d after surgery normoglycemic and insulin‐free. An episode of acute rejection (Maryland grade II) 20‐d post‐transplant was successfully treated with corticosteroids. A second and more severe episode of rejection (Maryland grade IV) occurred 13 months post‐transplant, requiring treatment with thymoglobulin and conversion from steroid to sirolimus. On tacrolimus, sirolimus, and mycophenolic acid, he remains euglycemic and insulin‐free 38 months after PTA. His quality‐of‐life is judged to be superior to his insulin dependent state prior to transplantation. According to the medical literature, this is the youngest patient ever to undergo PTA.     

Pancreas transplantation after bariatric surgery

Obese transplant candidates are at increased risk for perioperative and postoperative complications. In many transplant programs, morbid obesity is considered to be an exclusion criterion for transplantation. The only potential option that would grant these patients access to transplant is weight loss. Non-operative weight loss strategies such as behavioral modifications, exercise, diet, or medication have only very limited success in achieving long-term weight loss. In contrast, bariatric surgery was shown to achieve not only more excessive weight loss, but more importantly, this weight loss can be sustained for longer periods of time. Therefore, bariatric surgery presents an attractive option for weight loss for morbidly obese transplant candidates. We report our experience with four patients who underwent bariatric surgery prior to successful pancreas transplantation. Even though gastric bypass and laparoscopic adjustable gastric band present as equivalent alternatives for weight reduction, we believe that in the population of morbidly obese diabetic patients who are possible candidates for pancreas transplantation, laparoscopic adjustable gastric band placement is the more suitable procedure.     

Pancreas transplantation in crossmatch-positive recipients

BACKGROUND: Prolonged cold preservation time can unfavorably affect outcome in pancreas transplantation. To reduce this ischemic time, cadaver pancreas grafts, in selected cases, are sometimes transplanted before crossmatch results are known. We report our experience with pancreas transplants in recipients with either current or historically positive T- or B-cell crossmatches. METHODS: Crossmatch-positive pancreas transplants were identified using a computerized database. T-cell crossmatches were performed using an antihuman-globulin-augmented complement-dependent cytotoxicity (CDC) test; B-cell crossmatches were performed using an extended incubation CDC test. All patients received anti-T-cell induction therapy and either cyclosporine (1987-1993) or tacrolimus-based (1994-2001) immunosuppression. More recent recipients (2000-2001) also received intravenous gamma globulin and postoperative plasmapheresis. RESULTS: Between October 1, 1987 and March 31, 2001, of a total of 1076 pancreas transplants performed, 59 (5.48%) were crossmatch-positive. Of these, 8 had a current T-cell-positive crossmatch and 15 had a current B-cell-positive crossmatch. One recipient was both current B- and T-positive, and the rest were past B- and/or T-cell positive. One-year pancreas graft survival for current T- and B-cell crossmatch-positive transplants was 63% and 67%, respectively. T- or B-cell crossmatch-negative transplants had a 1-yr survival of 70%. In the T-cell crossmatch-positive group, four grafts are still functioning (follow-up range, 2-12 yr), one patient died with a functioning graft at 4 months, and four grafts failed (one each from pancreatitis, infection, primary nonfunction, and vascular thrombosis). No grafts were lost to rejection. In the B-cell crossmatch-positive group, six grafts are still functioning (follow-up range, 2-11 yr) and nine have failed (four from chronic rejection, three from vascular thromboses, and two from pancreatitis). Crossmatch-positive cases were significantly more likely to be retransplants (70.8%) than crossmatch-negative cases (14.8%, p < 0.0001). In a multivariate analysis, crossmatch positivity did not affect pancreas graft outcome, whereas retransplants had a significant impact on outcome (relative risk 1.84, p < 0.0001). CONCLUSIONS: (: i) Pancreas transplants performed in the setting of a positive current crossmatch may have long-term function. (ii) With current immunosuppressive protocols, graft loss from hyperacute and acute rejection may be prevented in current crossmatch-positive pancreas transplants. Chronic rejection was only seen in B-cell crossmatch-positive cases. (iii) High rates of technical graft loss in crossmatch-positive cases may reflect a high frequency of retransplants in this group.     

Islet transplantation

Recently, significant advances have been made in the number and purity of islets that can be retrieved from the human pancreas, thus enabling several centers to initiate or resume clinical trials of islet transplantation in type I diabetic patients. Although the success rate of islet transplantation is lower than that of pancreas transplantation in terms of achievement of insulin-independence, islet transplantation has significant potential advantages over vascularized pancreas transplantation: it is a simple and safe procedure; it has the potential to be performed on an outpatient basis; it offers access to cell banking after cryopreservation; it offers the potential advantages of pre-transplant reduction of im-munogenecity; and it even offers the future feasibility of xenotransplantation. In this article, the current status of clinical trials and future perspectives of islet transplantation, including immunomodulation, immunotolerance, immunoisolation, and xenotransplantation, are reviewed. Received for publication on Feb. 24, 1999; accepted on March 28, 1999     

Are Criteria for Islet and Pancreas Donors Sufficiently Different to Minimize Competition?

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 相似文献   

Current practices of donor pancreas allocation in the UK: future implications for pancreas and islet transplantation*

Recent refinements in technique mean islet cell transplantation offers the chance of a cure to an increasing patient cohort with diabetes. Such developments put pressure upon the scarce resource of donor organs, with potential competition between the modalities of cellular and solid organ transplantation. This questionnaire based study examines current patterns of donor pancreas procurement and use. Reasons for non procurement are studied together with the attitudes of transplant professionals to pancreas allocation. The minority of potentially useful pancreata are currently made available to either whole pancreas or islet transplant programs. Whilst professionals appreciate the role of each modality, there is a need to define criteria for pancreas allocation to avoid under use of donor organs.     

Islet transplantation as safe and efficacious method to restore glycemic control and to avoid severe hypoglycemia after donor organ failure in pancreas transplantation

The aim of this study was to assess safety and efficacy of islet transplantation after initial pancreas transplantation with subsequent organ failure. Patients undergoing islet transplantation at our institution after pancreas organ failure were compared to a control group of patients with pancreas graft failure, but without islet transplantation and to a group receiving pancreas retransplantation. Ten patients underwent islet transplantation after initial pancreas transplantation failed and were followed for a median of 51 months. The primary end point of HbA1c <7.0% and freedom of severe hypoglycemia was met by nine of 10 patients after follow‐up after islet transplantation and in all three patients in the pancreas retransplantation group, but by none of the patients in the group without retransplantation (n = 7). Insulin requirement was reduced by 50% after islet transplantation. Kidney function (eGFR) declined with a rate of ‐1.0 mL ± 1.2 mL/min/1.73 m² per year during follow‐up after islet transplantation, which tended to be slower than in the group without retransplantation (P = .07). Islet transplantation after deceased donor pancreas transplant failure is a method that can safely improve glycemic control and reduce the incidence of severe hypoglycemia and thus establish similar glycemic control as after initial pancreas transplantation, despite the need of additional exogenous insulin.     

Perfusion preservation of cadaver rat pancreas: II. Culture after perfusion and successful transplantation

We designed a new process for culturing pancreatic islets and applied this method to cultures of rat pancreatic islets which had degenerated during preservation by the perfusion-method for 6 hours under the condition of hypothermia and oxygenation. The objective was to determine the extent of the original function. Transplantation of these sotreated islets was also attempted. When pancreatic islets isolated from the ancreas after 6-hour-perfusion were cultured, morphological restoration was apparent within the first 3–4 days. Insulin contents of the culture media renewed every 3 days, ranged from 851 to 1,134 μU/ml/two islets during culture period of 21 days. In the glucose-loading test, insulin secretion of the islets was the same as that of islets in the control experiments. Transplantation of these islets into the portal vein of streptozotocin-induced diabetic rats resulted in a good recovery from the diabetic state.     

Extreme Subcutaneous, Intramuscular and Inhaled Insulin Resistance Treated by Pancreas Transplantation Alone

Diabetes mellitus with resistance to insulin administered subcutaneously or intramuscularly (DRIASM) is a rare syndrome and is usually treated with continuous intravenous insulin infusion. We present here two cases of DRIASM in 16 and 18 years female patients that were submitted to pancreas transplantation alone (PTA). Both were diagnosed with type 1 diabetes as young children and had labile glycemic control with recurrent episodes of diabetic ketoacidosis. They had prolonged periods of hospitalization and complications related to their central venous access. Exocrine and endocrine drainages were in the bladder and systemic, respectively. Both presented immediate graft function. In patient 1, enteric conversion was necessary due to reflux pancreatitis. Patient 2 developed mild postoperative hyperglycemia in spite of having normal pancreas allograft biopsy and that was attributed to her immunosuppressive regimen. Patient 1 died 9 months after PTA from septic shock related to pneumonia. In 8 months of follow-up, Patient 2 presented optimal glycemic control without the use of antidiabetic agents. In conclusion, PTA may be an alternative treatment for DRIASM patients.     

Minimization and withdrawal of steroids in pancreas and islet transplantation

For reducing the corticosteroid (CS)-related side-effects, especially cardiovascular events, CS-sparing protocols have become increasingly common in pancreas transplantation (PT). Lympho-depleting induction antibodies, such as rabbit anti-thymocyte globulin (rATG) or alemtuzumab, have been widely used in successful trials. The results of various CS-sparing protocols combining calcineurin inhibitors (CNI) and mycophenolate or sirolimus, have been mixed for rejection and survival rates. Most of the studies were uncontrolled trials of low-risk patients, therefore the grade of evidence is limited. Large-scale prospective studies with long-term follow up are necessary to assess risks and benefits of CS-sparing regimens in PT before recommending such strategies as standard practice. Islet allo-transplantation for patients with brittle type 1 diabetes mellitus, less invasive and safer procedure than PT, has been attempted since late 1980s, but diabetogenic immunosuppressants at maintenance, mainly CS and high-dose CNI, prevented satisfactory results (10% insulin-independence at 1-year post-transplant). Since 2000, CS-free and CNI-reducing protocols, including more potent induction [daclizumab, OKT3gamma1(ala-ala) anti-CD3 antibody, rATG] and maintenance (sirolimus, mycophenolate) agents, have significantly improved short-term outcomes whereas long-term are still inadequate (from 80% to 20% insulin-independence from 1- to 5-year post-transplant). Main limitations are allo- and autoimmunity, immunosuppression-related islet and systemic toxicity and transplant site unsuitability, which tolerogenic protocols and biotechnological solutions may solve.     

Islet alloautotransplantation: Allogeneic pancreas transplantation followed by transplant pancreatectomy and islet transplantation

Simultaneous pancreas–kidney (SPK) transplantation is an important treatment option for patients with type 1 diabetes (T1D) and end‐stage renal disease (ESRD). Due to complications, in up to 10% of patients, allograft pancreatectomy is necessary shortly after transplantation. Usually the donor pancreas is discarded. Here, we report on a novel procedure to rescue endocrine tissue after allograft pancreatectomy. A 39‐year‐old woman with T1D and ESRD who had undergone SPK transplantation required emergency allograft pancreatectomy due to bleeding at the vascular anastomosis. Islets were isolated from the removed pancreas allograft, and almost 480 000 islet equivalents were infused into the portal vein. The patient recovered fully. After 3 months, near‐normal mixed meal test (fasting glucose 7.0 mmol/L, 2‐hour glucose 7.5 mmol/L, maximal stimulated C‐peptide 3.25 nmol/L, without insulin use in the preceding 36 hours) was achieved. Glycated hemoglobin while taking a low dose of long‐acting insulin was 32.7 mmol/mol hemoglobin (5.3%). When a donor pancreas is lost after transplantation, rescue β cell therapy by islet alloautotransplantation enables optimal use of scarce donor pancreata to optimize glycemic control without additional HLA alloantigen exposure.     

Pancreas After Islet Transplantation: A First Report of the International Pancreas Transplant Registry

Pancreas after islet (PAI) transplantation is a treatment option for patients seeking insulin independence through a whole‐organ transplant after a failed cellular transplant. This report from the International Pancreas Transplant Registry (IPTR) and the United Network for Organ Sharing (UNOS) studied PAI transplant outcomes over a 10‐year time period. Forty recipients of a failed alloislet transplant subsequently underwent pancreas transplant alone (50%), pancreas after previous kidney transplant (22.5%), or simultaneous pancreas and kidney (SPK) transplant (27.5%). Graft and patient survival rates were not statistically significantly different compared with matched primary pancreas transplants. Regardless of the recipient category, overall 1‐ and 5‐year PAI patient survival rates for all 40 cases were 97% and 83%, respectively; graft survival rates were 84% and 65%, respectively. A failed previous islet transplant had no negative impact on kidney graft survival in the SPK category: It was the same as for primary SPK transplants. According to this IPTR/UNOS analysis, a PAI transplant is a safe procedure with low recipient mortality, high graft‐function rates in both the short and long term and excellent kidney graft outcomes. Patients with a failed islet transplant should know about this alternative in their quest for insulin independence through transplantation.     

Pancreas transplantation

Over the last 5 years, there has been a resumed interest in treating diabetes by transplantation, particularly islet transplantation. However, despite advances being reported in Canada and the US, replication in the UK has been much more difficult. At present there is still only one treatment that can consistently reverse insulin independence in the long-term and that is whole pancreas transplantation. Long-term normoglycaemia has beneficial effects on preventing and ameliorating the secondary complications of diabetes and will be discussed.     

Preservation of the donor pancreas for whole pancreas and islet transplantation

Ridgway D, Manas D, Shaw J, White S. Preservation of the donor pancreas for whole pancreas and islet transplantation.
Clin Transplant 2010: 24: 1–19. © 2009 John Wiley & Sons A/S.
Abstract:  Whole pancreas and islet cell transplantation are both reliant upon the procurement and preservation of a high quality donor pancreas for a successful outcome. In the climate of a reducing donor pool it is imperative that donor optimization, meticulous surgical retrieval and evidence based methods of preservation are practiced to ensure optimal graft quality. Moreover expanded criteria donors and novel methods of pancreas preservation have the potential to expand the number of usable grafts and increase the availability of these transplant modalities to suitable patients with diabetes. This article provides a review of the current literature surrounding donor management, surgical technique and the various technologies of organ preservation applicable to the donor pancreas.     

Pancreas transplantation with portal venous drainage with an emphasis on technical aspects

Advances in surgical techniques and clinical immunosuppression have led to improving results in vascularized pancreas transplantation. Most pancreas transplants are performed with enteric exocrine drainage and systemic venous delivery of insulin (systemic‐enteric technique) although bladder drainage (systemic‐bladder technique) remains a viable option. To improve the physiology of pancreas transplantation, an innovative technique of portal venous delivery of insulin and enteric drainage of the exocrine secretions (portal‐enteric technique) was developed and refined over the past 27 yr. However, the potential of portal‐enteric pancreas transplantation has never been fully realized as it is currently performed in only 18% of simultaneous pancreas‐kidney/sequential pancreas after kidney and 10% of pancreas‐alone transplants with enteric drainage. A number of studies have demonstrated no major or consistent differences in outcomes for bladder‐drained or enteric‐drained pancreas transplants with either portal or systemic venous drainage although some studies suggest purported metabolic and immunologic advantages associated with portal venous delivery of insulin. The purpose of this study is to review the existing literature on portal‐enteric pancreas transplantation with an emphasis on surgical aspects and technical modifications/nuances that have been introduced with time and experience.