Pancreas preservation with University of Wisconsin and Celsior solutions

BACKGROUND: Although the use of Celsior has been recently described for heart, lung, liver, and kidney transplantation, no data are available on its use for clinical pancreas preservation. METHODS: We herein describe the results of 112 pancreas transplants preserved with either University of Wisconsin (UW; (n = 56) or Celsior (n = 56) solution at two Italian transplant centers. The groups were comparable with regard to all donor and recipient characteristics. RESULTS: Mean cold and warm ischemia times were 10.1 +/- 2.2 hours and 37.2 +/- 8.2 minutes for UW compared to 10.8 +/- 2.4 hours and 38.3 +/- 6.7 minutes for Celsior (P = NS). Delayed endocrine pancreas function was recorded in two UW-preserved grafts (3.6%). Actuarial 1-year patient survival was 94.6% for UW as compared with 100% for Celsior (P = NS). Equivalent graft survival figures were 91.0% for UW as compared with 96.4% for Celsior (P = NS). CONCLUSIONS: Within the range of cold ischemia times reported in this study, UW and Celsior solutions have similar safety profiles for pancreas transplantation.     

Comparison of histidine-tryptophan-ketoglutarate solution and University of Wisconsin solution for organ preservation in clinical pancreas transplantation

BACKGROUND: University of Wisconsin (UW) solution is currently the standard preservation solution used for abdominal organ transplantation. This study assesses the efficacy of histidine-tryptophan-ketoglutarate (HTK) compared with UW in pancreas transplantation. METHODS: Between October 2002 and August 2003, 20 pancreas transplants were performed. Patients were divided into two groups: UW (n=10) and HTK (n=10). Donor and recipient demographics were similar in both groups. The mean cold ischemia time for both groups was 11 +/-3 hr. RESULTS: There was an anticipated difference between total preservative volumes used (HTK: 4.5 +/- 1.2 L vs. UW: 3.4 +/-0.8 L; P =0.03). Patient and graft survivals to date were 100% in both groups. Serum fasting blood glucose, peak amylase, and serial amylase levels remained comparable at all intervals posttransplantation. CONCLUSIONS: Within this range of cold ischemia time, UW and HTK demonstrate similar efficacy in pancreas preservation.     

Kidney transplantation from elderly donors: a prospective randomized study comparing celsior and UW solutions

AIM: The aim of present study was to assess the effect of Celsior as compared with University of Wisconsin (UW) solution on immediate and long-term function of kidney transplants harvested from elderly donors. METHODS: A prospective multicenter randomized study was designed to evaluate the efficacy of Celsior versus UW solution for the clinical preservation of the kidney. Fifty renal transplants were performed from donors over 60 years old. Twenty-five kidneys were stored in Celsior and 25 in UW solution. The groups were comparable with regard to donor and recipient characteristics. Renal function outcomes were compared by evaluating delayed graft function rates, daily urinary output, as well as the evolution of mean serum creatinine at 1, 3, 5, 7, and 15 days. RESULTS: The warm ischemia time was 42.4 +/- 11 minutes among Celsior vs 46.9 +/- 17.9 minutes in the UW cohort (P = NS). The cold ischemia time was 18 +/- 4.5 hours in Celsior and 19 +/- 6.5 hours in UW (P = NS). Delayed graft function occurred in 48% of the Celsior group and in 52% of the UW group (P = NS). Mean serum creatinine levels and mean daily urinary output were also similar. One- and 5-year graft survivals of kidneys preserved with Celsior were 91.8% and 79.3% compared with 96% and 87.4% for UW without any significant statistical difference. CONCLUSIONS: Our data show that the preservation of kidneys from elderly donors in Celsior solution is equivalent to that of UW solution.     

Efficacy and safety of Celsior preservation fluid in liver transplantation: one-year follow up of a prospective, multicenter, non-randomized study

The purpose of this prospective, nine-center, non-randomized study was to assess the efficacy and safety of Celsior preservation fluid in liver transplantation using unselected donors. As data comparing allograft outcomes following liver transplantation using Celsior and University of Wisconsin (UW) preservation fluids are limited, we also compared our cohort with matched controls selected from the European Liver Transplant Registry (ELTR) who received total liver grafts preserved with UW solution during the same period. One hundred and forty patients who received livers preserved with Celsior were included. The primary endpoint, graft loss at one-yr post-transplantation, was observed in 24 patients (17.1%) which was not significantly different from the 20.0% pre-defined threshold rate (95% confidence interval [CI] 10.9, 23.4; p=0.398). Predictive factors for graft loss on univariate analysis were moderate-to-severe steatosis on the donor graft (5/22 patients with graft loss vs. 8/107 patients without, p=0.046) and duration of warm ischemia (1.4±1.1 h in patients with graft loss vs. 0.9±0.5 h in patients without, p=0.034). Hepatic artery thrombosis and stenosis occurred in seven (5.0%) and six (4.3%) patients, respectively. The comparison of our patients to 420 ELTR controls showed that one-yr graft survival rates (Celsior: 82.9%, 95% CI 75.8, 88.2; UW: 78.6%, 95% CI 74.4, 82.2) and Kaplan-Meier one-yr graft survival distributions (p=0.285) were similar. Within the cold ischemia time achieved in our study, liver preservation with Celsior appeared efficient and safe. Comparison with ELTR patients suggested that liver allograft survival was similar using Celsior or UW solution for preservation of unselected donor grafts.     

University of Wisconsin solution versus Celsior solution in clinical pancreas transplantation

INTRODUCTION: This study compared the safety and efficacy of University of Wisconsin solution (UW) and Celsior solution (C) in pancreas transplantation (PTx). METHODS: A retrospective review of 154 PTx performed over a 61-month period included 77 grafts preserved with UW and 77 with C. The two groups were comparable for both donor and recipient characteristics. RESULTS: After a mean cold ischemia time of 624 minutes (range 360 to 945 minutes) for UW versus 672 minutes (range 415 to 1005 minutes) for C (P = NS), no primary endocrine nonfunction occurred. Delayed endocrine function was diagnosed in two grafts in the UW group (2.6%) versus none in the C group (P = NS). After a minimum follow-up of 4 months (mean 26.5 +/- 15.2 months), 22 recipients (UW = 11 vs C = 11; P = NS) required relaparotomy. Overall, 18 pancreata were lost due to either patient death with functioning graft (UW = 4 vs C = 1; P = NS) or graft loss due to other reasons (UW = 8 vs C = 5; P = NS). Actuarial 1- and 5-year patient survival rates were 93.5% and 86.8% for UW compared with 98.7% and 98.7% for C (P = .04). Actuarial graft survival rates at the same times were 88.3% and 75.0% for UW compared with 90.4% and 90.4% for C (P = NS). CONCLUSIONS: Within the range of cold ischemia times reported in this study, UW and C show similar safety and efficacy profiles for PTx.     

Follow-up experience using histidine-tryptophan ketoglutarate solution in clinical pancreas transplantation

In May 2003, at Indiana University, the standard cold preservation solution University of Wisconsin (UW) solution was replaced by histidine-tryptophan ketogluatarate (HTK) solution. Earlier, we presented our initial experience with HTK in pancreas preservation with an analysis of the first 10 pancreas transplants. Here we report updated results with HTK in pancreas transplantation over the past 18 months. Between May 2003 and March 2005, a total of 87 pancreas transplants were performed with 78 of these organs utilizing HTK. Seventy five patients received 78 organ transplants. Surgical procedures performed were: simultaneous kidney pancreas transplantation (n = 50, 64%), pancreas after kidney transplantation (n = 19, 24%), solitary pancreas transplantation (n = 9, 12%). Donor and recipient data were collected with primary outcomes as primary nonfunction and 30-day graft and patient survivals, and compared to the UW cohort from our original report. Donor and recipient demographics were similar. Mean follow-up time is 12 +/- 6 months. The mean cold ischemia time was 9 +/- 3 hours. There were no cases of primary graft nonfunction. Thirty-day and 1-year patient survivals were 99% and 93%. The 30-day and 1-year graft survivals were 96% and 93%. There were five grafts lost, including three within the first month (two venous and one arterial thrombosis). There was one case of chronic rejection and one noncompliance. All other patients were insulin-independent by discharge. Serum fasting blood glucose and serial amylase remained comparable at all intervals posttransplantation. Within this range of cold ischemia time, HTK appears to provide effective pancreas preservation.     

Comparison of histidine-tryptophan ketoglutarate and University of Wisconsin solutions as primary preservation in renal allografts undergoing pulsatile perfusion

INTRODUCTION: University of Wisconsin (UW) solution is the standard preservation solution for organ transplantation. Histidine-tryptophan ketogluatarate (HTK) solution has been used increasingly for kidney, pancreas, and liver transplantation. This study compared HTK and UW used during kidney procurement with subsequent pulsatile perfusion. METHODS: Between January and October 2003, 91 deceased renal and simultaneous kidney pancreas transplants were performed (UW, n = 41, and HTK, n = 50). There were no differences with regard to donor and recipient demographics or cold ischemia. RESULTS: Delayed graft function occurred in 3 (7%) of UW and 4 (8%) of HTK-preserved kidneys (P = NS). There were no significant differences between patient or graft survival. There was an anticipated difference between total preservative volumes used (HTK: 4.1 +/- 1.0 vs UW: 3.0 +/- 0.5; P < .005). CONCLUSION: UW and HTK appear to have similar efficacy in kidney preservation with pulsatile perfusion. HTK preservation solution can be used safely in conjunction with pulsatile preservation for cold storage of renal allografts.     

Pancreas preservation with the University of Wisconsin versus Celsior solutions

INTRODUCTION: The use of Celsior solution for organ preservation has not been thoroughly studied in pancreas transplantation. The aim of this study was to compare University of Wisconsin and Celsior solutions for preservation of pancreas grafts. PATIENTS AND METHODS: From March 1995 to December 2005, 72 patients with type 1 diabetes underwent pancreas transplantation. There were 42 men and 30 women, with a mean age at transplantation of 38.1 +/- 7.5 years (range: 27 to 55 years), and a mean duration of diabetes of 22.5 +/- 6.6 years. Recipients were classified into two groups according to the preservation solution: (A) Celsior (n = 28, 38.9%) and (B) Wisconsin (n = 44, 61.1%). RESULTS: The donor and recipient characteristics were similar in both groups. There were five cases of venous thrombosis in the Wisconsin group and two in the Celsior group (P = NS). The venous drainage technique in the former group was portocaval in 19 patients and portoiliac in 25; in the Celsior group, portocaval in 23 patients and portoiliac in five (P = .001). Enteric drainage was used in 19 patients from the Celsior group and 17 patients from the Wisconsin group (P = .01). Actuarial 2-year graft survival was 74.6% in the Wisconsin group and 77.4% in the Celsior group (P = NS). CONCLUSIONS: No differences were observed in venous thrombosis between the two groups. The lower rate of venous thrombosis with the portocaval technique was related to the type of venous drainage rather than the type of preservation solution. Celsior solution may be considered as good as Wisconsin solution for pancreas transplantation.     

Organ preservation with histidine-tryptophan ketogluatarate solution in clinical pancreas transplantation: an update of the indiana university experience

In May 2003, University of Wisconsin (UW) solution was replaced with Histidine-Tryptophan Ketoglutarate (HTK) solution as the preservation fluid for abdominal organ procurements in our center. Herein we have reported our updated results with HTK in pancreas transplantation. Between May 2003 and October 2006, 152 pancreas transplantations were performed in which 146 used HTK. The procedures were as follows: simultaneous kidney pancreas transplantation (n = 85; 55%), pancreas after kidney transplantation (n = 41; 30%), and solitary pancreas transplantation (n = 20; 15%). Donor and recipient data were collected with primary outcomes as primary nonfunction (PNF), and 30-day and 1-year graft and patient survival. Patient demographics are as follows: age (36 +/- 12 years), gender (males, 89: females, 57), race (white, 135; African American, 11). Mean flush volume was 3.8 +/- 1 L. The mean cold ischemia time was 8 +/- 3 hours. Mean warm ischemia time was 48 +/- 23 minutes. There were no cases of PNF in this cohort. Thirty-day and 1-year patient survival rates were 99% and 95%, respectively. The 30-day and 1-year graft survivals rates were 95% and 93%, respectively. There were 10 grafts lost with 7 vascular complications (6 venous and 1 arterial thrombosis). There were 2 cases of chronic rejection and 1 graft lost to noncompliance. These statistics compare favorably with International Pancreas Transplant Registry reported 1-year survival for pancreas allografts. All other patients were insulin independent by discharge. Serum fasting blood glucose and serial amylase remained comparable at all intervals posttransplantation to those of a historical UW cohort. Within this range of cold ischemia times, HTK appears to provide effective pancreas preservation.     

Kidney preservation in pigs with University of Wisconsin and Celsior solution

BACKGROUND: Although University of Wisconsin (UW) solution continues to be the most commonly used for intra-abdominal organs a new solution, Celsior, already utilized for heart and lungs, has been proposed for kidney and liver preservation. The aim of this research was to assess the effect of Celsior compared to UW on the immediate graft function of pig autotransplanted kidneys. METHODS: We used an autotransplantation pig model to avoid immunological interferences. After harvesting the graft was immediately bench perfused through the renal artery with 200 cc of solution and preserved for 24, 32 and 48 hrs. After cold ischemia grafts were autotransplanted on cava vein and aorta and a ureteral-ureteral anastomosis was performed. Contralateral nephrectomy was carried out at the end of this procedure. Each experimental group was composed of 5 animals. All animals were sacrificed after 1 week. RESULTS: All animals with 24 hr and 32 hr preserved grafts survived up to sacrifice; kidney function was recovered in all animals of 24 hr groups and in most of the animals of 32 hr preserved grafts (4/5) without any differences between the 2 solutions. In Celsior and UW 48 hr groups only 5 animals survived (3 and 2, respectively) and in all these animals kidney function was not totally recovered. CONCLUSIONS: Our data show that preservation of kidneys with the Celsior solution in the experimental setting is equivalent to UW solution.     

Comparison of UW solution and Euro-Collins solutions for cold preservation of human liver grafts

University of Wisconsin solution, a new organ preservation medium, is reported to extend the period of cold storage. In order to evaluate the efficacy of UW solution in human liver preservation we compared 58 donor liver grafts preserved in Euro-Collins (EC) solution. All livers were harvested in a similar manner. Donor and recipient characteristics in the two groups were comparable. The mean preservation time of the UW solution was 11.5 +/- 4.2 hr (range 3-20 hr), significantly longer than the EC mean preservation time of 4.9 +/- 1.6 hr (2-9.6 hr) (P = 0.0001). Evaluation of mean postoperative liver function tests and coagulation factors on days 1-7 showed no statistical difference between the two groups. There was one primary graft nonfunction in the EC group and none with the UW organs. Hepatic artery thrombosis was similar in each group. The incidence of early retransplantation was similar. Three-month graft survival was 81% in the UW group vs. 73% in the EC group. Patient survival at three months was 87% with the UW organs and 84% with the EC organs. We conclude that cold storage of liver grafts in the UW solution has allowed for significantly longer preservation, permitting transplantation to be performed under semielective conditions and procurement of organs from much further distances. Grafts stored in UW solution perform as well as those stored in Euro-Collins, with no significant difference in liver function abnormalities postoperatively.     

A comparison of cold storage solutions for pancreas preservation prior to islet isolation

BACKGROUND: Several solutions are used to preserve the pancreas prior to islet isolation. This study sought to assess whether the type of solution had an impact on the isolation outcome. METHODS: We reviewed data from 125 islet isolation procedures performed from January 2002 to January 2005. Pancreata were preserved in University of Wisconsin (UW) (n = 101), Celsior (CS) (n = 19), or IGL-1 (n = 5) solutions. Islet isolation results and transplantation rates were compared between groups. RESULTS: UW, CS, and IGL-1 groups were similar according to donor's age, weight, and body mass index. Weight of undigested pancreas was 20 +/- 13.1, 21.4 +/- 15.7, and 17.4 +/- 8.7 g for UW, CS, and IGL-1, respectively (P > .2). Final total number of IEQ was 267,000 +/- 132,000, 277,000 +/- 155,000, and 311,000 +/- 163,000, respectively (P > .4). Success rate (defined as >250,000 IEQ) was 55.5%, 52.9%, and 60% for UW, Celsior, and IGL-1 (P > .9); the transplantation rate was 42.2% for UW, 36.8% for Celsior, and 80% for IGL-1 preservation (P > .2). CONCLUSIONS: In this preliminary study, UW, Celsior, and IGL-1 solutions demonstrated similar islet isolation results. The new IGL-1 solution appears promising.     

Successful 96-Hr cold-storage preservation of canine pancreas with UW solution containing the thromboxane A2 synthesis inhibitor OKY046.

Prostanoids, such as prostacyclin (PGI) and thromboxane A2 (TxA), have been recently suggested to play an important role in preservation-induced injury of pancreas grafts. We have previously shown that the TxA synthesis inhibitor OKY046 prevents a decrease of both the PGI/TxA ratio and blood flow in pancreas grafts after 24-hr preservation with Euro-Collins solution. In our present study, we analyzed whether OKY046 added to University of Wisconsin (UW) solution could extend successful cold-storage preservation of segmental canine pancreas grafts, compared with UW alone. We divided 30 dogs into four preservation groups: Group 1, UW solution for 72 hr (n = 7); Group 2, UW solution for 96 hr (n = 8); Group 3, UW solution plus OKY046 (10(-4) M) for 72 hr (n = 7); and Group 4, UW solution plus OKY046 (10(-4) M) for 96 hr (n = 8). After the cold storage period, segmental pancreas auto-transplantation with immediate completion pancreatectomy was done. Preservation was deemed successful if serum glucose less than 150 mg/dl was maintained for at least 5 days. Intravenous glucose tolerance tests and biopsies were done in those dogs with functioning grafts 14 days post-transplant. Successful preservation rates were as follows: Group 1, 57.1%; Group 2, 12.5%; Group 3, 100%; and Group 4, 75%. The mean K values (+/- standard error) were: Group 1, 1.54 +/- 0.13; Group 2, 0.59; Group 3, 1.54 +/- 0.14; and Group 4, 1.59 +/- 0.24 (not statistically different).(ABSTRACT TRUNCATED AT 250 WORDS)     

Two-layer method (UW solution/perfluorochemical plus O2) for lung preservation in rat lung transplantation

A new preservation method using perfluorochemicals (PFC) with oxygen administered continuously was developed for lung preservation and compared with traditional cold preservation methods for rat lung transplantation. Male Sprague-Dawley rats underwent orthotopic left lung transplantations of grafts preserved in lactiated Ringers solution (LR), University of Wisconsin solution (UW), Celsior solution, or a two-layer (PFC plus O2) solution for 6 hours. One hour after reperfusion, the right pulmonary artery and bronchus were clamped and 5 minutes later we recorded peak airway pressure and PaO2 level. The isograft was excised for measurement of myeloperoxidase activity, wet-to-dry ratio, and histologic examination to evaluate isograft function. The mean peak airway pressure was 29.80+/-6.72 mm H2O in the LR group, 28.80+/-5.76 mm H2O in the UW group, 33.60+/-5.17 mm H2O in the Celsior group, and 32.40+/-2.60 in the two-layer group. The mean PaO2 level was 99.78+/-76.09 mm Hg in the LR group, 87.84+/-33.58 mm Hg in the UW group, 104.50+/-72.93 mm Hg in the Celsior group, and 62.08+/-31.34 mm Hg in PFC and UW solution plus O2 group (two layers). The mean net myeloperoxidase activity OD level was 0.110+/-0.104 in the LR group, 0.392+/-0.328 in the UW group, 0.351+/-0.620 in the Celsior group, and 0.532+/-0.616 in the two-layer group. The mean wet-to-dry ratio was 7.47+/-1.60 in the LR group, 6.56+/-0.62 in the UW group, 7.54+/-2.19 in the Celsior group, and 5.32+/-2.20 in the two-layer group. The differences between groups in these parameters were not significant. Upon histologic examination, more inflammatory cell aggregates were seen in the two-layer group, less in the LR and the Celsior groups. The function of the lung graft after 6 hours of storage was not better using this two-layer method for preservation than traditional preservation methods in rat lung transplantation. Histologic examination revealed more inflammatory cell aggregates in the lung graft preserved using a two-layer method.     

Advantages of Celsior solution in graft preservation from non-heart-beating donors in a canine liver transplantation model.

BACKGROUND: The optimal method for preserving livers from non-heart-beating donors (NHBD) is still unknown. We compared the Celsior solution, a new extracellular-type, low-potassium, low-viscosity preservation solution, with the University of Wisconsin (UW) solution in a canine orthotopic liver transplantation from NHBD. MATERIALS AND METHODS: Fourteen adult mongrel dogs, weighing 9 to 17 kg, were divided into two groups: the Celsior or the UW group (n = 7 each). The thoracic descending aorta and supradiaphragmatic inferior vena cava were cross-clamped for 20 min to induce warm ischemia as a NHBD model. The liver was flushed with the respective cold preservation solution and then stored at 4 degrees C for 4 h. The grafts were transplanted using the piggy-back technique under portal decompression by leaving the native right lobe as a temporary shunt. RESULTS: The duration of liver flushing out (min) was shorter (P < 0.05), and the serum glutamic oxaloacetic transaminase, glutamic pyruvic transaminase, lactate dehydrogenase, lactate, and alpha-glutathione S-transferase concentrations 2 and 6 h after reperfusion of the graft (RPF) were lower (P < 0.05) in the Celsior group than in the UW group. Hepatic tissue blood flow (HTBF) did not deteriorate as much (P < 0.05) in the Celsior group. The serum endothelin-1 level was lower (P < 0.05) in the Celsior group 2 h after RPF. Histopathology of liver specimens revealed portal congestion and hepatocyte necrosis with neutrophil infiltration in the UW group, while these findings were mild in the Celsior group. CONCLUSIONS: The Celsior solution improves vascular endothelial injury in livers from NHBDs and may have advantages in graft flush and preservation of grafts from NHBDs.     

Efficacy of renal preservation: comparative study of Celsior and University of Wisconsin solutions

OBJECTIVE: We sought to compare the efficacy of Celsior and University of Wisconsin (UW) solutions on the perfusion and cold storage of renal grafts for human transplantation. PATIENTS AND METHODS: Retrospective analyses of 313 kidney transplants were performed between 2002 and 2005; group A (n = 160), UW solution and group B (n = 153), Celsior solution were used in the preservation of the organs. The mean donor age was lower in group B (group A = 42.67 years vs group B = 38.96 years; P < .05), living donors were more frequent in the UW group (group A = 10% vs group B = 0.9%; P < .001). Multiorgan procurement procedures were more common in the Celsior group (group A = 75% vs group B = 81.7%; P < .001). Recipients with no associated comorbidities were more frequent in the UW group (group A = 50% vs group B = 36%; P < .001). Recipient mean age, cold ischemia time, and HLA matches were comparable. RESULTS: Delayed graft function (group A = 22.7% vs group B = 20.6%), acute rejections (group A = 21.4% vs group B = 18.4%), and serum creatinine at 6 months (group A = 1.75 vs group B = 1.67 mg/dL), 1 year (group A = 1.47 vs group B = 1.74 mg/dL), and 2 years (group A = 1.43 vs group B = 1.58 mg/dL) showed no differences (P = NS). Graft (group A = 82.23% vs group B = 84.11%) and patient (group A = 93% vs group B = 93.69%) survivals at 3 years were similar (P = NS). There were no differences in the causes of graft loss. CONCLUSION: The efficacy of UW and Celsior solutions is equivalent in the cold storage and renal preservation for transplantation.     

Comparison of Celsior and UW solution in experimental pancreas preservation

BACKGROUND: The University of Wisconsin solution (UW) is the gold standard for pancreas preservation. Celsior (CEL) was formulated specifically for heart preservation. Recently, experimental and clinical experience has been reported on the application of CEL to abdominal organs. In this animal study, pancreas preservation with CEL was compared with that in UW solution. PATIENTS AND MATERIALS: Heterotopic, allogeneic pancreaticoduodenal transplantation was performed in female G?ttingen Minipigs (n = 12 donors, n = 12 recipients). The grafts were flushed and stored for 6 h at 4 degrees C in UW or CEL. The recipients were randomized into two groups receiving either UW (n = 6)- or CEL (n = 6)-preserved grafts with a follow-up of 5 days. Blood flow (laser Doppler), partial oxygen tension, histological changes, endothelin-1 (plasma, immunohistochemistry), lipase, amylase, trypsinogen activation peptide, and C-reactive protein (CRP) were measured. RESULTS: Partial oxygen tension was lower in the CEL group (P < 0.05). However, blood flow did not differ between UW- and CEL-preserved organs. The histomorphologic analysis of the pancreatic grafts revealed significantly less edema in the UW-preserved organs. Serum levels of amylase, lipase, CRP, and TAP taken from the central venous blood were comparable in the two groups, except for higher amylase values 36 h after reperfusion in the CEL group compared to the UW group (P < 0.05). Likewise, TAP taken from the portal venous effluent of the graft was found to be higher in the CEL group than in UW (P < 0.05). Endothelin-1 serum levels rose significantly during reperfusion without differences between the two groups. ET-1 immunohistochemistry revealed increased local ET-1 during reperfusion in all grafts. However, the ET-1 immunostaining in the CEL group was more pronounced than that in the UW group (P < 0.05). CONCLUSIONS: Our results suggest that CEL solution is not as effective in preventing pancreatic ischemia/reperfusion damage as the standard UW solution in experimental pancreas transplantation. Increased ET-1 immunostaining and reduced p(ti)O(2) in the CEL group indicate increased microcirculatory damage in the CEL group.     

Clinical application of the two-layer (University of Wisconsin solution/perfluorochemical plus O2) method of pancreas preservation before transplantation

BACKGROUND: The two-layer method [University of Wisconson solution (UW)/perfluorochemical plus O2] for pancreas preservation has been demonstrated to be superior to simple UW storage alone in the canine model. For the first time, we applied the two-layer method to clinical whole-pancreas transplantation. METHODS: Pancreases were placed in the two-layer method in 10 cases and UW alone in 44 cases before transplant. The mean cold ischemic time was 16.5 hr in the two-layer group versus 18.1 hr in the UW group (P=NS). We compared the condition of graft at the time of reperfusion, and then 3 months posttransplant graft function and complications. RESULTS: At the time of reperfusion, no grafts in the two-layer group were edematous, compared with 10(23.3%) of 43 in the UW group (P=0.18). Seven (70%) of 10 grafts in the two-layer group obtained the best overall quality score, compared with 24(57.1%) of 42 in the UW group (P=0.72). Nine (90%) of 10 recipients in the two-layer group became insulin-independent during hospitalization, compared with 31(70.5%) of 44 in the UW group (P=0.26). Time to insulin independence was no different between the two groups. No pancreas grafts preserved by the two-layer method suffered acute rejection. Conclusions. The two-layer preservation method is feasible in human clinical transplantation. It was at least equivalent and may be superior to UW alone in both morphologic and functional assessment of the transplanted pancreas.     

Human islet transplantation from pancreases with prolonged cold ischemia using additional preservation by the two-layer (UW solution/perfluorochemical) cold-storage method

BACKGROUND: A two-layer (University of Wisconsin solution/perfluorochemical [UW/PFC]) cold-storage method delivers sufficient oxygen to the pancreas during preservation and restores the ischemically damaged pancreas. In this study, we determined whether the additional preservation by the two-layer method could improve islet recovery from human pancreases with prolonged cold storage in UW. METHODS: Human pancreases were procured from cadaveric organ donors and preserved by the two-layer method (UW/PFC) for 2.9+/-0.7 hours (mean+/-SEM) at 4 degrees C after 11.8+/-1.5 hours of cold storage in UW (UW/PFC group, n=7), or by cold UW alone for 11.3+/-0.3 hours (UW group, n=14). The selected pancreases met the criteria of having at least 10 hours of cold storage in UW. All were processed by using a standard protocol of Liberase perfusion with Pefabloc by way of the duct, gentle mechanical dissociation, and Ficoll gradient purification. Transplanted islets were selected with the criteria of the Edmonton protocol (>5,000 islet equivalents [IE]/kg recipient body weight). RESULTS: The islet recovery was significantly increased in the UW/PFC group compared with the UW group (349.2+/-44.1 x 10 and 214.0+/-31.0 x 10 IE, respectively; <0.05). This resulted in islet yields of 4.6+/-1.0 x 10 IE/g of pancreas in the UW/PFC group compared with 2.0+/-0.3 x 10 IE/g of pancreas in the UW group ( <0.05). Five of 7 cases (71%) in the UW/PFC group and 5 of 14 cases (36%) in the UW group were transplanted. The islet grafts in the UW/PFC group improved the ability of glycemic control and decreased exogenous insulin administration in all recipients. CONCLUSIONS: Improvements in methods to preserve and recover ischemically damaged human pancreases before islet isolation and transplant could be extremely beneficial to the field of clinical islet transplantation. This preliminary study shows that additional short preservation by the two-layer (UW/PFC) cold-storage method can significantly improve islet recovery and increase opportunities of islet transplantation from human pancreases after prolonged cold ischemia.     

Influence of preservation solution on human islet isolation outcome

BACKGROUND: The influence of the preservation solution used for in situ perfusion of the donor and pancreas storage on islet isolation has received little attention. METHODS: In this prospective controlled trial, we compared the outcome of human islet isolation from pancreata perfused with University of Wisconsin (UW) solution or Celsior, an alternative colloid-free extracellular solution. RESULTS: At the 1-year interim analysis, the viability and insulin secretion of islets isolated from donors perfused with UW (n=19) or Celsior (n=5) were identical. However, total islet recovery (IEQ) and isolation yield (IEQ/g) were 1.8-fold and 2.1-fold inferior in the Celsior group (P<0.05 vs. UW). Overall, 13 (68%) of islet preparations were effectively transplanted from the UW group vs. none from the Celsior group (P=0.01). The clinical study was discontinued and the causes of these differences were further explored in the pig (n=14). In contrast to UW, Celsior induced cell swelling and pancreas edema after only four hours of cold storage. These abnormalities were delayed when the donor was perfused with Solution de Conservation d'Organes et de Tissus (SCOT), an extracellular solution containing polyethylene glycol. CONCLUSIONS: Our results suggest that colloid-free preservation solutions might be suboptimal for pancreas perfusion and cold storage prior to islet isolation and transplantation. Because pancreata are now frequently recovered for islet transplantation, preliminary experimental and clinical data about islet isolation should be obtained prior to the routine implementation of new preservation solutions for abdominal perfusion during multiorgan recovery.