Function of pancreas allografts more than 1 year following transplantation

At the University of Iowa, Iowa City, 75 pancreas transplant procedures were performed for type I diabetes mellitus from March 1984 to September 1988. Forty-seven of these transplants were performed simultaneously with kidney transplants from the same donor; 23 followed previous kidney transplants, and 5 were preuremic pancreas-only transplants. The 1-year patient survival rate is 85% and pancreas graft survival rate is 54%. The simultaneous kidney and pancrease group had a 1-year patient survival rate of 82%, a pancreas graft survival rate of 59%, and a renal graft survival rate of 73%. Thirty-one of 70 kidney and pancreas recipients had a functioning pancreas 1 year post transplantation and 26 of 31 currently have a functioning pancreas and are insulin free. Patient symptoms of neuropathy and gastroenteropathy are improved with long-term graft function. Some patients may develop type II diabetes post transplantation with impaired glucose tolerance despite high insulin production by the graft. Pancreas transplantation is the only therapy that achieves a euglycemic state as indicated by glycosylated hemoglobin and glucose tolerance testing. Centers must continue to follow up patients on a long-term basis to determine the final effects on the secondary complications of diabetes.     

Ipsilateral placement of simultaneous pancreas and kidney allografts

The current standard technique for simultaneous kidney pancreas transplantation usually involves transplanting the pancreas to the right and the kidney to the left iliac system. Here we describe a previously unreported technique where both organs are transplanted to the right iliac system through a single midline incision. Forty-nine patients underwent simultaneous ipsilateral pancreas and kidney transplantation. All pancreas grafts were drained enterically. Overall patient, pancreas, and kidney survival were 96% (47/49), 92% (45/49), and 94% (46/49) respectively. The 45 patients with functioning grafts are insulin free and off of dialysis. Mean serum creatinine at 1, 3, 6, and 12 months was 1.7+/-1.3, 1.2+/-0.3, 1.3+/-0.3, and 1.3+/-0.4 mg/dL, respectively. The placement of the pancreas and kidney transplants on the same side is safe and does not compromise patient or graft survival. This approach preserves the left iliac system for future retransplantation if necessary.     

Where are we with pancreas transplantation?

The question still remains: What is best for the patient? It appears that whole organ or segmental pancreas transplantation can be carried out, giving anywhere from a 46% to an 84% 1-year pancreas survival rate. At the moment there is no clear-cut evidence that patient survival--at least in the short term--is any better after a combined pancreas-kidney graft than after a kidney graft alone, and there are more complications from the combined procedure. It appears once again that patient survival is a function of control of ketoacidosis and its complications--whether by a pancreas graft or by better insulin delivery. Nevertheless, several things have been learned: (1) Patients who receive a pancreas-kidney graft simultaneously have the best pancreas 1-year survival. (2) A pancreatic graft without a simultaneous kidney graft does poorly. (3) A pancreas graft carried out after a kidney graft will not do as well. (4) A kidney transplanted to a diabetic patient may become nephropathic unless supported by a pancreatic graft. (5) Retinopathy is not improved by pancreatic transplantation. (6) Neuropathy is improved or stabilized by pancreatic transplantation. (7) Nephropathy is improved by pancreatic grafting. (8) There is no clear-cut difference in pancreatic graft survival, whether segmental or whole organ grafts are used. (9) Bladder-drained grafts appear to have slightly better survival at 1 year than enteric-drained or polymer-injected grafts. (10) Human islet cell homotransplantation is not yet an accomplished fact. As Barker has pointed out, the potential benefits of pancreatic grafting are for those who are prone to complications and who do not have irreversible diabetic complications. Predicting those in whom significant complications will develop is not easy, and a large percentage of the grafts done to date have been done for patients with end stage renal disease. It has been suggested that transplants are best used for those with early renal disease and for those with pre-proliferative retinopathy and for those that are metabolically difficult to handle with insulin and for those at high risk for complications with diabetes: namely, those with high levels of inactive renin that are associated with microvascular complications and high levels of insulin-like growth factor. These complications seem to be associated with accelerated progression of retinopathy. Diabetic children whose disease is associated with major neurovascular disease and children with impaired counter regulatory mechanisms may also be candidates for grafting.(ABSTRACT TRUNCATED AT 400 WORDS)     

Complication rate of pancreas retransplantation after simultaneous pancreas-kidney transplantation compared with pancreas after kidney transplantation

Simultaneous pancreas kidney transplantation is currently the state of the art therapy for patients with type 1 diabetes mellitus and diabetic nephropathy. Up to 30% of patients loose the pancreas with a kidney graft that continues to function. Under those conditions, isolated pancreas retransplantation can be indicated. We compared the outcome of these patients with the outcome of patients undergoing primary pancreas after kidney transplantation. From 1998 to 2005, we performed 205 pancreas transplantations. Three patients were considered for isolated pancreas retransplantation; to date, two have received a new organ. One was retransplanted twice. In two cases, the reasons for the initial graft loss in the retransplantation group were pancreatitis with hemorrhagic bleeding and in the third case severe rejection. After retransplantation two of three patients lost their graft owing to bleeding and venous thrombosis. One of three organs was successfully transplanted and the patient does not require insulin. During the same time, three pancreas after kidney transplantations were performed; all are doing well und are free of insulin. The study despite the small number of cases shows a high complication rate after pancreas retransplantation. Nevertheless, pancreatic retransplantation should be considered in selected patients.     

Bezoar-related pancreatitis in enterically drained pancreas transplant

Simultaneous kidney and pancreas transplantation is currently the treatment of choice for type 1 diabetes mellitus with end-stage renal disease. As a result of improvements in surgical techniques and the efficacy of immunosuppression, patient and graft survival rates have improved dramatically over the last two decades. Despite this, it remains a challenging surgical procedure with many potential complications and occasional controversies. Causes of pancreatitis after pancreas transplantation with enteric drainage are not well documented in the literature. We report a case of allograft pancreatitis from pancreatic duct outflow obstruction due to formation of a bezoar in a diverticulized transplant duodeno-jejunal anastomosis. To the best of our knowledge, this is the first case of allograft pancreatitis reported in the literature occurring from bezoar formation.     

Combined pancreas and kidney transplantation improves survival in patients with end-stage diabetic nephropathy

The purpose of this study was to find out whether prolonged normoglycemia, as achieved by a successful pancreas transplantation, can improve survival in patients with insulin-dependent diabetes mellitus. A retrospective analysis of actual 10-yr patient survival rates was done for all renal graft recipients who were given transplants more than 10 yr ago but within the cyclosporin era (i.e. 1981-1988). The actual 10-yr patient survival rate in non-diabetic renal graft recipients was 72%, In recipients of pancreas and kidney grafts and with prolonged function of the pancreas graft, the survival rate was 60%, whereas in patients subjected to simultaneous pancreas and kidney transplantation, but where the pancreatic grafts failed within 2 yr, the survival rate was 33%. In diabetic recipients of kidney transplants alone, the survival rate was 37%. The patient survival rate was substantially higher in non-diabetic patients and patients with functioning pancreas grafts compared with diabetic patients with kidney transplants alone or with failed pancreas grafts. We speculate that the decrease in mortality was due to the beneficial effect of long-term normoglycemia on diabetic late complications.     

Current status and future of pancreas transplantation

The results of pancreas transplantation have improved in the ciclosporin A era. Success rates are now similar to those in other types of organ transplantation, and the number of cases has increased concomitantly. As of December 1997, 10,283 pancreas transplantation procedures had been reported to the International Pancreas Transplant Registry. Since 1995, over 1,000 have been reported annually, 75% of which have been performed in the USA. The majority (88%) of those carried out in the USA consist of simultaneous pancreas and kidney (SPK) transplantations, followed by pancreas transplantation after kidney transplantation (10%) and pancreas transplantation alone (PTA) (2%). From 1994 to 1997, the overall one-year patient survival rate was 94%. The graft survival rate for SPK was the highest, with one- and three-year graft survival rates of 82% and nearly 80%, respectively. The administration of FK506 and mycophenolate mofetil has improved the results in patients undergoing pancreas transplantation. Althought the technical failure rate has decreased, graft thrombosis remains the most frequent cause of technical failure (5.5% for SPK with exocrine bladder drainage and 11% for SPK with enteric drainage). The standard surgical procedure has included pancreas-exocrine bladder drainage, but the current trend is to perform physiological enteric drainage. It has been reported that the portal venous and enteric exocrine drainage methods are safe, with outcomes similar to those of the standard technique. It appears that these will become the standard methods in the near future. The primary objective of improved quality of life is achieved in patients with functioning pancreas grafts, and transplantation results in modest reductions in secondary diabetes mellitus complications. However, it must still be confirmed whether the long-term quality-of-life benefits outweigh the potential risks. The secondary objective of pancreas transplantation is to prevent complications of diabetes mellitus. It is necessary to develop methods for the early detection of rejection, which will lead to significant improvements in the results of PTA. Although 15 pancreas transplantation surgeries have been carried out in Japan, they ceased after 1994. Currently, social debate to determine the rules governing such procedures is ongoing.     

The effect of center volume on pancreas transplant outcomes

BACKGROUND: Caseload often correlates with improved outcomes for several surgical procedures, including solid organ transplantation. Given the unique nature of pancreas transplantation and large variation in transplant center volumes, this study aims to determine whether center volume affects patient and graft survival after pancreas transplantation. METHODS: Registry data on all forms of whole organ pancreas transplants performed between 1995 and 2000 were obtained from the United Network for Organ Sharing. Patient and graft survival rates were followed until 2002. Center volume then was categorized as: low (< 10/year), medium (10-20/year), high (21-50/year), and very high (< 50/year). Cox proportional hazard regression models were developed to evaluate factors affecting pancreas transplant outcomes. RESULTS: Very-high-volume centers were more likely to do pancreas after kidney transplant, pancreas transplant alone, pancreas with kidney transplant, and repeat transplants, while other centers more frequently performed simultaneous pancreas-kidney transplants (P < .001). Very-high-volume centers were more likely to transplant older recipients and less likely to transplant minority or Medicaid patients. Low-volume centers tended to accept pancreatic allografts from younger donors and had the longest waiting times. In models adjusting for differences in patient population, there were no differences in patient survival. However, low-volume centers had a slightly increased risk of graft loss compared to other centers. Early graft loss was similar among all centers, but medium-volume centers were at increased risk for late graft loss. CONCLUSIONS: Low center volume is not associated with increased mortality after pancreas transplantation. Other factors appear to be more important than center volume in determining pancreas transplant outcomes.     

Morbidity of pancreas transplantation during cadaveric renal transplantation.

Simultaneous transplantation of the pancreas is an option for diabetic patients undergoing kidney transplantation to attempt to halt progression of diabetic complications, but the additional risk imposed by the procedure is unclear. Our aim was to determine the morbidity attributable to pancreas transplantation during simultaneous pancreas and kidney transplantation. We compared the first posttransplant year of 18 consecutive recipients of combined pancreas and kidney transplantation to 18 consecutive recipients of kidney transplantation alone. All patients received cadaver donor allografts between 1986 and 1989, and had type I diabetes mellitus with chronic renal failure. There were no differences in patient survival (94% both groups) or satisfactory renal allograft function (89% pancreas/kidney group, 83% kidney group) up to 18 months after transplantation. Eighty-eight percent of pancreas allografts were functioning satisfactorily at 18 months. There was a mean (+/- SD) of 1.5 +/- 1.0 acute rejection episodes per patient for the pancreas/kidney group compared to 0.8 +/- 6 for the kidney-only group (P less than 0.02). Cytomegalovirus infection and wound complications were each encountered more often after pancreas/kidney transplantation than kidney transplantation alone, and together with rejection accounted for a difference in days of hospitalization during the first year (71 +/- 34 vs. 27 +/- 13, P less than 0.001). We conclude that simultaneous pancreas transplantation during cadaver donor kidney transplantation accounted for more frequent rejection episodes, CMV infections, and wound complications. These complications resulted in more hospitalization for patients undergoing simultaneous pancreas/kidney transplantation than kidney transplantation alone.     

Clinical pancreas transplantation. Complete review of eight years experience

In the eight years since the initiation of pancreas transplantation at our center, 36 patients have received either segmental or whole pancreas grafts. Seventeen patients had segmental pancreas allografts, with eight of these receiving simultaneous kidney allografts from the same donor. Nineteen patients received whole pancreas and kidney allografts. Thirty five of the pancreases were preserved using hypothermic storage for up to 43 hours and 45 minutes, using either albumin-augmented crystalloid or hyperosmolar colloid preservation solution. The one-year actuarial graft survival was 12 per cent for segmental pancreas transplants and 42 per cent for whole pancreas grafts. The use of cyclosporine after whole pancreas transplantation as well as improved surgical techniques for exocrine drainage contributed to the improvement in graft survival in the whole pancreas graft group.     

Effect of the surgical technique on long-term outcome of pancreas transplantation

To date there is no general consensus as to the best surgical technique for pancreas transplantation. Patients with a pancreas transplant functioning for 3 years or more were retrospectively investigated to compare three surgical techniques: segmental graft with duct obstruction (DO), whole graft with bladder drainage (BD), and whole graft with enteric drainage (ED). Several parameters were studied: patient and graft survival, rejection, long-term surgical and medical complications, and endocrine function. The best results in terms of graft survival and quality of metabolic control were obtained in the group that underwent whole graft transplantation with ED. At 3 years, overall pancreas graft survival was 65 % for ED, 60 % for BD, and 47 % for DO. This surgical method has become the preferred technique in our unit. Received: 9 October 1997 Received after revision: 29 January 1998 Accepted: 30 March 1998     

A comparative study of pancreas transplantation between type 1 and 2 diabetes mellitus

BackgroundPancreas transplantation remains the best long-term treatment option to achieve physiological euglycemia and insulin independence in patients with labile diabetes mellitus (DM). It is widely accepted as an optimal procedure for type 1 DM (T1DM), but its application in type 2 DM (T2DM) is not unanimously acknowledged.MethodsIn total, 146 diabetes patients undergoing pancreas transplantation were included in this study. Clinical data and outcomes were compared between the T1DM and T2DM groups.ResultsMajority (93%) of the pancreas transplantations in T2DM were for uremic recipients. Complications occurred in 106 (73%) patients, including 70 (48%) with early complications before discharge and 79 (54%) with late complications during follow-up period. Overall, rejection of pancreas graft occurred in 37 (25%) patients. Total rejection rate in T2DM recipients was significantly lower than that in T1DM. The short- and long-term outcomes for endocrine function in terms of fasting blood sugar and hemoglobin A1c levels and graft survival rates are comparable between the T2DM and T1DM groups.ConclusionsT2DM is not inferior to T1DM after pancreas transplantation in terms of surgical risks, immunological and endocrine outcomes, and graft survival rates. Therefore, pancreas transplantation could be an effective option to treat selected uremic T2DM patients without significant insulin resistance.     

Outcomes after simultaneous kidney‐pancreas versus pancreas after kidney transplantation in the current era

Simultaneous pancreas and kidney (SPK) and pancreas after kidney (PAK) transplant are both potential options for diabetic ESRD patients. Historically, PAK pancreas graft outcomes were felt to be inferior to SPK pancreas graft outcomes. Little is known about outcomes in the modern era of transplantation. We analyzed our SPK and PAK recipients transplanted between 01/2000 and 12/2016. There were a total of 635 pancreas and kidney transplant recipients during the study period, 611 SPK and 24 PAK. Twelve of the PAK patients received a living donor kidney. There were no significant differences between the two groups in kidney or pancreas graft rejection at 1 year. Similarly, 1‐year graft survival for both organs was not different. At last follow‐up, uncensored and death‐censored graft survival was not statistically different for kidney or pancreas grafts. In addition, in Cox regression analysis SPK and PAK were associated with similar graft survival. Although the majority of pancreas transplants are in the form of SPK, PAK is an acceptable alternative. Simultaneous pancreas and kidney avoids donor risks associated with live donation, so may be preferable in regions with short wait times, but PAK with a living donor kidney may be the best alternative in regions with long SPK wait times.     

Evolution of pancreas transplant surgery

Background: Type 1 diabetes mellitus is a chronic condition often leading to disabling complications including retinopathy, neuropathy and cardiovascular disease which can be modified by intensive treatment with insulin. Such treatment, however, is associated with a restrictive lifestyle and risk of hypoglycaemic morbidity and mortality. Methods: This review examines the role of pancreas transplantation in patients with Type 1 diabetes mellitus. Results: Pancreas transplantation is currently the only proven option to achieve long‐term insulin independence, resulting in an improvement or stabilization of those diabetic related complications. The hazards of pancreas transplantation as a major operation are well known. Balancing the risks of a surgical procedure, with the benefits of restoring normoglycaemia remains an important task for the pancreas transplant surgeon. Pancreas transplantation is not an emergency operation to treat poorly managed and non‐compliant patients with debilitating complications. It is a highly specialized procedure which has evolved both in terms of the surgical technique, patient selection and assessment. Conclusion: Pancreas transplantation has emerged as the single most effective way to achieve normal glucose homeostasis in patients with Type 1 diabetes mellitus.     

Outcome of simultaneous kidney pancreas transplantation: a single center analysis

The aim of this study was to evaluate the outcome of simultaneous kidney pancreas transplantation (SKPT) by various surgical techniques. The 161 patients submitted to SKPT underwent the following: 36 pancreas with duct occlusion (from 1985 to 1989), 75 with whole pancreas with bladder diversion (from 1990 to 1998), and 50 whole pancreas with enteric diversion (40 with systemic and 10 with portal drainage) (from 1999 to September 2002). A positive effect on patient survival was evident using enteric diversion versus the duct occlusion group (P = .005), and versus the bladder diversion group (.035), and on pancreas graft survival in the enteric diversion versus the duct occlusion group (P < .028). These improvements may be due to refined donor and patient selection criteria, surgical technique, and immunosuppression.     

Combined kidney and pancreas transplantation. A safe and effective treatment for diabetic nephropathy

Seventeen patients with type I diabetes and diabetic nephropathy underwent combined kidney and pancreas transplantation. Mean age was 32 +/- 6 years and average duration of diabetes was 21 +/- 6 years. Transplantation was performed through bilateral iliac fossa incisions, and graft duodenocystostomy was used to achieve exocrine pancreas drainage. The actuarial patient and kidney survival rate was 92% and the pancreas survival rate, 88% (follow-up of 3 to 28 months). One patient with functioning grafts died at 10 months owing to a cardiac arrhythmia and one pancreas was "lost" to early thrombosis. Major morbidity was due to pancreas wound infection (53%) that required reoperation, but all patients have had subsequent healing of their wounds. Rehabilitation with return to meaningful activity has been accomplished by 15 patients. This experience demonstrates that combined kidney and pancreas transplantation can be performed safely and successfully.     

The time interval between kidney and pancreas transplantation and the clinical outcomes of pancreas after kidney transplantation

Pancreas after kidney (PAK) transplantation is one of the accepted pancreas transplant modalities. We studied the impact of time interval between kidney and pancreas transplantation on the outcomes of PAK transplantation. Using OPTN/SRTR data, we included 1853 PAK transplants performed between 1996 and 2005 with follow-up until November 1, 2008. Kaplan-Meier survival and multivariate Cox regression analyses were performed using the time interval between kidney and pancreas transplantation either as a categorical (less than one yr, between one and less than three yr, and greater than or equal to three yr) or as a continuous variable (months) to assess kidney graft and patient survival. Patients who received a pancreas transplant three yr or later after kidney transplantation had higher risk of death-censored kidney graft loss (HR 1.56, 95% CI 1.04, 2.32, p = 0.03). Each month beyond three yr between kidney and pancreas transplantation incurred 1% higher risk of subsequent death-censored kidney graft loss (HR 1.01, 95% CI 1.001, 1.02, p = 0.03). In conclusion, time interval between pancreas and kidney transplantation is an independent risk factor of kidney graft loss following pancreas transplantation. Shortening the time interval between pancreas and kidney transplantation to less than three yr may reduce the risk of kidney graft loss in qualified PAK transplant candidates.     

Simultaneous cadaver pancreas living-donor kidney transplantation: a new approach for the type 1 diabetic uremic patient

OBJECTIVE: To review the authors' experience with a new approach for type I diabetic uremic patients: simultaneous cadaver-donor pancreas and living-donor kidney transplant (SPLK). SUMMARY BACKGROUND DATA: Simultaneous cadaver kidney and pancreas transplantation (SPK) and living-donor kidney transplantation alone followed by a solitary cadaver-donor pancreas transplant (PAK) have been the transplant options for type I diabetic uremic patients. SPK pancreas graft survival has historically exceeded that of solitary pancreas transplantation. Recent improvement in solitary pancreas transplant survival rates has narrowed the advantage seen with SPK. PAK, however, requires sequential transplant operations. In contrast to PAK and SPK, SPLK is a single operation that offers the potential benefits of living kidney donation: shorter waiting time, expansion of the organ donor pool, and improved short-term and long-term renal graft function. METHODS: Between May 1998 and September 1999, the authors performed 30 SPLK procedures, coordinating the cadaver pancreas transplant with simultaneous transplantation of a laparoscopically removed living-donor kidney. Of the 30 SPLKs, 28 (93%) were portally and enterically drained. During the same period, the authors also performed 19 primary SPK and 17 primary PAK transplants. RESULTS: One-year pancreas, kidney, and patient survival rates were 88%, 95%, and 95% for SPLK recipients. One-year pancreas graft survival rates in SPK and PAK recipients were 84% and 71%. Of 30 SPLK transplants, 29 (97%) had immediate renal graft function, whereas 79% of SPK kidneys had immediate function. Reoperative rates, early readmission to the hospital, and initial length of stay were similar between SPLK and SPK recipients. SPLK recipients had a shorter wait time for transplantation. CONCLUSIONS: Early pancreas, kidney, and patient survival rates after SPLK are similar to those for SPK. Waiting time was significantly shortened. SPLK recipients had lower rates of delayed renal graft function than SPK recipients. Combining cadaver pancreas transplantation with living-donor kidney transplantation does not harm renal graft outcome. Given the advantages of living-donor kidney transplant, SPLK should be considered for all uremic type I diabetic patients with living donors.     

Simultaneous pancreas-kidney transplantation: portal versus systemic venous drainage of the pancreas allografts

Simultaneous pancreas-kidney (SPK) transplantation is considered a valid therapeutic option for patient with type I diabetes mellitus and end-stage diabetic nephropathy. This study was performed to determine whether the technique of pancreas venous drainage affects patient survival as well as graft survival and function. From October 1996 to April 1999 34 uremic patients with type I diabetes mellitus were randomly assigned to two groups: the first group (SV group=17) received SPK transplantation with systemic venous drainage, and the second group (PV group=17) received pancreas allograft with portal drainage. A Roux-en-Y loop was performed in all the patients. Patient follow-up included clinical course and metabolic studies. At 1 yr, patient survival rates were 88.2% in the SV group and 94.1% in the PV group while graft survival rate was 76.4% in both groups. Several surgical complications were attributed to the enteric drainage without any graft failure in both groups. One venous thrombosis occurred in each group. No significant differences have been evidenced in kidney and pancreas function. The preliminary results of this randomized trial did not evidence any significant differences between portal and systemic venous drainage of pancreas allograft.     

Everolimus with low‐dose tacrolimus in simultaneous pancreas and kidney transplantation

The efficacy and safety of everolimus (EVR) in simultaneous pancreas and kidney transplantation (SPKT) is unclear. We retrospectively evaluated 25 consecutive SPKT recipients at our center from November 2011 to March 2013. All patients received dual induction (Thymoglobulin/basiliximab) and low‐dose tacrolimus plus corticosteroids. Nine patients who received EVR were compared with 14 patients who received enteric‐coated mycophenolate sodium (EC‐MPS); two patients who received sirolimus were excluded from the analysis. With a median follow‐up of 14 months, the pancreas graft survival rate was 100% in both groups, and the kidney graft survival rate was 100% and 93% in EVR and EC‐MPS patients, respectively. One EC‐MPS patient lost her kidney graft from proteinuric kidney disease. Another EC‐MPS patient received treatment for clinically diagnosed pancreas and kidney graft rejection. No rejection was observed in EVR patients. Serum creatinine and HbA1c levels were similar between the groups. There was no significant difference of surgical or medical complications. In conclusion, EVR seems to provide comparable short‐term outcome to EC‐MPS when combined with low‐dose tacrolimus/steroids and dual induction therapy. A larger study with a longer follow‐up is required to further assess this combination.