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.     

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.     

Celsior Versus University of Wisconsin Preserving Solutions for Liver Transplantation: Postreperfusion Syndrome and Outcome of a 5-Year Prospective Randomized Controlled Study

Background

Celsior solution (CS) is a high-sodium, low-potassium, low-viscosity extracellular solution that has been used for liver graft preservation in recent years, although experience with it is still limited. We performed an open-label randomized active-controlled trial comparing CS with the University of Wisconsin solution (UW) for liver transplantation (LT), with a follow-up period of 5?years.

Methods

Adult transplant recipients (n?=?102) were prospectively randomized to receive either CS (n?=?51) or UW (n?=?51). The two groups were comparable with respect to donor and recipient characteristics. The primary outcome measure was the incidence of postreperfusion syndrome (PRS). Secondary outcome measures included primary nonfunction (PNF) or primary dysfunction (PDF), liver retransplantation, and graft and patient survival. Other secondary outcome measures were days in the intensive care unit (ICU) and the rates of acute rejection, chronic rejection, infectious complications, postoperative reoperations, and vascular and biliary complications.

Results

In all, 14 posttransplant variables revealed no significant differences between the groups. There were no cases of PNF or PDF. The incidence of PRS was 5.9% in the CS group and 21.6% in the UW group (P?=?0.041). After reperfusion, CS revealed greater control of serum potassium (P?=?0.015), magnesium levels (P?=?0.005), and plasma glucose (P?=?0.042) than UW. Respective patient survivals at 3, 12, and 60?months were 95.7, 87.2, and 82.0% for the CS group and 95.7, 83.3, and 66.6% for the UW group (P?=?0.123).

Conclusions

While retaining the same degree of safety and effectiveness as UW for LT, CS may yield postliver graft reperfusion benefits, as shown in this study by a significant reduction in the incidence of PRS and greater metabolic control.     

Pancreas preservation with University of Wisconsin and Celsior solutions: a single-center, prospective, randomized pilot study

BACKGROUND: Celsior is an extracellular-type, low-viscosity, preservation solution already used for heart, lung, liver, and kidney transplantation. We report the results of a single-center, prospective, randomized pilot study specifically designed to compare the safety profile of Celsior solution with University of Wisconsin (UW) solution in clinical pancreas transplantation. METHODS: A total of 105 consecutive procurements were randomized to graft preservation with UW (n=53) solution or Celsior (n=52) solution. The groups were comparable with regard to all donor and recipient characteristics. RESULTS: Five grafts were discarded and 100 grafts (50 UW vs. 50 Celsior) were transplanted. Mean cold and warm ischemia times were 11.0 +/- 2.1 hr and 37.2 +/- 6.0 min for UW compared with 10.8 +/- 1.8 hr and 38.1 +/- 5.9 min for Celsior (P =not significant). Delayed endocrine pancreas function was recorded in one graft preserved with UW solution. Eleven recipients (UW 12% vs. Celsior 10%, P =not significant) required a relaparotomy. The mean serum levels of glucose, amylase, and lipase remained comparable between the study arms at equivalent intervals after transplantation. One recipient died with functioning grafts in each study arm; two further grafts were lost to arterial thrombosis (Celsior) and chronic rejection (UW), respectively. Actuarial 1-year patient and graft survival rates overlapped in the two study arms (98% and 96%, respectively). CONCLUSIONS: Within the range of cold ischemia time reported in this study, UW and Celsior solutions have similar safety profiles for pancreas preservation.     

Outcomes in Pancreas Transplantation With Exocrine Drainage Through a Duodenoduodenostomy Versus Duodenojejunostomy

Until recently, pancreas transplantation has mostly been performed with exocrine drainage via duodenojejunostomy (DJ). Since 2012, DJ was substituted with duodenoduodenostomy (DD) in our hospital, allowing endoscopic access for biopsies. This study assessed safety profiles with DD versus DJ procedures and clinical outcomes with the DD technique in pancreas transplantation. DD patients (n = 117; 62 simultaneous pancreas–kidney [SPK_DD] and 55 pancreas transplantation alone [PTA_DD] with median follow‐up 2.2 years) were compared with DJ patients (n = 179; 167 SPK_DJ and 12 PTA_DJ) transplanted in the period 1998–2012 (pre‐DD era). Postoperative bleeding and pancreas graft vein thrombosis requiring relaparotomy occurred in 17% and 9% of DD patients versus 10% (p = 0.077) and 6% (p = 0.21) in DJ patients, respectively. Pancreas graft rejection rates were still higher in PTA_DD patients versus SPK_DD patients (p = 0.003). Hazard ratio (HR) for graft loss was 2.25 (95% CI 1.00, 5.05; p = 0.049) in PTA_DD versus SPK_DD recipients. In conclusion, compared with the DJ procedure, the DD procedure did not reduce postoperative surgical complications requiring relaparatomy or improve clinical outcomes after pancreas transplantation despite serial pancreatic biopsies for rejection surveillance. It remains to be seen whether better rejection monitoring in DD patients translates into improved long‐term pancreas graft survival.     

Liver Transplantation Using University of Wisconsin or Celsior Preserving Solutions in the Portal Vein and Euro-Collins in the Aorta

Introduction

Orthotopic liver transplantation (OLT) is today the gold standard treatment of the end-stage liver disease. Different solutions are used for graft preservation. Our objective was to compare the results of cadaveric donor OLT, preserved with the University of Wisconsin (UW) or Celsior solutions in the portal vein and Euro-Collins in the aorta.

Methods

We evaluated retrospectively 72 OLT recipients, including 36 with UW solution (group UW) and 36 with Celsior (group CS). Donors were perfused in situ with 1000 mL UW or Celsior in the portal vein of and 3000 mL of Euro-Collins in the aortia and on the back table managed with 500 mL UW or Celsior in the portal vein, 250 mL in the hepatic artery, and 250 mL in the biliary duct. We evaluated the following variables: donor characteristics, recipient features, intraoperative details, reperfusion injury, and steatosis via a biopsy after reperfusion. We noted grafts with primary nonfunction (PNF), initial poor function (IPF), rejection episodes, biliary duct complications, hepatic artery complications, re-OLT, and recipient death in the first year after OLT.

Results

The average age was 33.6 years in the UW group versus 41 years in the CS group (P = .048). There was a longer duration of surgery in the UW group (P = .001). The other recipient characteristics, ischemia-reperfusion injury, steatosis, PNF, IPF, rejection, re-OLT, and recipient survival were not different. Stenosis of the biliary duct occured in 3 (8.3%) cases in the UW group and 8 (22.2%) in the CS (P = .19) with hepatic artery thrombosis in 4 (11.1%) CS versus none in the UW group (P = .11).

Conclusion

Cadaveric donor OLT showed similar results with organs preserved with UW or Celsior in the portal vein and Euro-Collins in the aorta.     

Re-operation in Pancreas Transplantation

BackgroundSurgical complications in pancreas transplantation are associated with increased morbidity and graft loss. The purpose of our study was to determine the frequency of re-operation in early and late postoperative of pancreas transplantation and its impact in relation to graft survival, patient survival, and hospital mortality.MethodsWe conducted a retrospective study of 238 pancreas transplants performed from 2001 to 2011. We analyzed surgical complications that led to the early and late re-operations by type of transplantation and its relation to pancreas graft survival, patient survival, and hospital mortality.ResultsWe studied 61 re-operated patients (25.63%), 58 patients with early re-operation and 3 with late re-operation. The median of re-operations per patient was 1.48 (range, 1 to 5). Seventy-five surgical complications required 90 re-operations. The causes of early re-operations were bleeding (8.8%), pancreas graft thrombosis (6.3%), pancreatitis (2.9%), bowel obstruction (2.1%), leaks (2.1%), and evisceration (1.7%). The hospital mortality rate was 0.43%. Pancreas graft survival at 1 and 5 years is higher in the group of non–re-operated than in the re-operated group (98% vs 74% and 93% vs 57%; P = .0001). Patient survival at 1 year is slightly higher in the non–re-operated group, but with no significant differences (99% vs 97%), and at 5 years the patient survival in the non–re-operated group is higher than in the re-operated group (98% vs 91%; P = .011).ConclusionsSurgical complications required re-operations that were associated with higher morbidity and lower pancreas graft and patient survival.     

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.     

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.     

Wisconsin and Celsior solutions in renal preservation: a comparative preliminary study

The aim of this study was to evaluate the efficacy of the Celsior (C) solution for flushing and cold storage of cadaveric renal allografts. Among 177 cadaveric renal allografts harvested and transplanted in our unit, 138 were preserved with the University of Wisconsin (W) solution and 39 with the C solution. The mean age of the recipients was 48.1 +/- 13.5 years, including 107 men and 70 women. The immunosuppressive regimens were tacrolimus-based (n = 118) or cyclosporine-based (n = 59). Grafts perfused with W solution were obtained from older donors than those perfused with C solution (42.3 +/- 16.9 vs 38.1 +/- 12.5 years; P = .017) and had been transplanted to older recipients (49.5 +/- 14.4 vs 43.3 +/- 13.0 years; P = .017). The prevalence of delayed graft function (DGF) was similar in the 2 groups (39.1% in the W group vs 23.7% in the C group; P = .097), as well as the incidence of primary nonfunction grafts (5.8% vs 2.7%; P = .427). The serum creatinine value at 1 month was significantly higher among grafts preserved with W versus solution (1.9 +/- 0.9 vs 1.5 +/- 0.5 mg/dL; P = .000) as well as at 12 months (1.63 +/- 0.5 vs 1.35 +/- 0.4 mg/dL; P = .003). There were no differences in graft survival at 12 months (97% C group vs 88% W group; P = .069). Our results showed that C solution was equivalent to W solution with respect to DGF and primary function of kidneys. The differences in renal function may have been due to differences in donor and recipient ages.     

Laparoscopic Biopsies in Pancreas Transplantation

As there is no precise laboratory test or imaging study for detection of pancreas allograft rejection, there is increasing interest in obtaining pancreas tissue for diagnosis. Pancreas allograft biopsies are most commonly performed percutaneously, transcystoscopically, or endoscopically, yet pancreas transplant surgeons often lack the skills to perform these types of biopsies. We have performed 160 laparoscopic pancreas biopsies in 95 patients. There were 146 simultaneous kidney–pancreas biopsies and 14 pancreas‐only biopsies due to pancreas alone, kidney loss, or extraperitoneal kidney. Biopsies were performed for graft dysfunction (89) or per protocol (71). In 13 cases, an additional laparoscopic procedure was performed at the same operation. The pancreas diagnostic tissue yield was 91.2%; however, the pancreas could not be visualized in eight cases (5%) and in 6 cases the tissue sample was nondiagnostic (3.8%). The kidney tissue yield was 98.6%. There were four patients with intraoperative complications requiring laparotomy (2.5%) with two additional postoperative complications. Half of all these complications were kidney related. There were no episodes of pancreatic enzyme leak and there were no graft losses related to the procedure. We conclude that laparoscopic kidney and pancreas allograft biopsies can be safely performed with very high tissue yields.     

Ductal Injection of University of Wisconsin Solution Prior to Pancreas Preservation Prevents Oxidative Cell Damage

Introduction

Several studies have been carried out investigating different preservation methods and preservation solutions for the pancreata of various species. Attention has to be drawn to the extreme vulnerability of porcine pancreata (PP) to oxidative stress due to the lack of endogenous antioxidants. This study sought to evaluate the influence of cannulation and infusion of different volumes of University of Wisconsin (UW) solution immediately after organ retrieval on PP organ quality.

Methods

PP from 24 slaughterhouse pigs were harvested with immediate cannulation of the pancreatic duct for infusion of 10 mL, 20 mL, 50 mL, or 100 mL UW solution. The organs were stored in cold UW solution. Control organs were only stored in UW. After 6 hours of cold ischemia, tissue and supernate samples were analyzed for markers of oxidative cell damage, adenosine triphosphate (ATP) levels, and occurrence of apoptosis.

Results

The fewest apoptotic cells were detected in the PP infused with 50 mL UW via the pancreatic duct (PP 50) as compared with all other groups. Oxidative cell damage was lowest and ATP levels were highest in the PP 50 group.

Discussion

Because PP 50 showed significantly better results when compared with all other groups, we suggest that infusion of 50 mL UW via the pancreatic duct immediately after organ retrieval may be useful to minimize oxidative cell damage and cell death in PP.     

Balancing Waitlist Dropout in Pancreas Transplantation

BackgroundThe time a patient spends on the waiting list for a Simultaneous Pancreas-Kidney (SPK) transplant depends on several donor and recipient-specific factors. The average wait-list time for SPK in the United States has been about 1 to 3 years, significantly shorter than the average wait time for kidney-only transplantation. A single-center retrospective analysis of SPK waitlisted candidates was performed to determine the implication of wait-list time on dropout from the wait-list due to death or poor health.MethodsWe analyzed all deceased donor Simultaneous Pancreas-Kidney wait-listed candidates between Jan 1994 and June 2021. Waitlisted candidates who got transplanted (TG) were compared to those who dropped out from the wait list due to death or poor health (DPHG).ResultsIn the study period, 297 candidates were waitlisted for SPK transplants. Eight candidates were removed, as transplantation was not needed due to improvement in health while on the waiting list. Fourteen wait-listed candidates transferred to another center were also excluded from the study group. Two hundred and thirty wait-listed candidates were transplanted (TG). Forty-five patients were delisted due to death or poor health (DPHG). The mean body mass index of candidates in TG and DPHG were 25.1 and 24.9, respectively. The mean age at dropout in DPHG was 40.7, similar to the mean age at transplant in TG (39.4). The mean age of diabetes onset was slightly lower in TG (17.4) compared to 20.02 in DPHG. The mean days spent by the candidates on the waitlist in DPHG were significantly higher than those in TG (821 days vs 252 days). Eight of the 45 patients (17.7%) in DPHG had 1 or more organ transplants before listing compared to 1 of 230 patients (0.43%) in TG. Despite low wait times for SPK transplants, increased wait times can account for a dropout from the waitlist due to death or poor health. Centers should exercise caution in wait listing SPK candidates with prior organ transplants.     

Occult Donor Malignancy in Pancreas Transplantation

Tumor of the pancreas allograft is extremely rare. We report a case of an occult donor malignant undifferentiated tumor arising in a pancreas allograft. A 42-year-old female with Type 1 diabetes received a macroscopically normal pancreas allograft. The donor was a 22-year-old male who died of spontaneous intracerebral hemorrhage. She underwent transplant pancreatectomy, the histology of the pancreas allograft demonstrated a tumor measuring 5 mm in diameter, and a diagnosis of malignant undifferentiated tumor was made. In a different transplant center, the recipient of the left kidney transplant from the same donor had a nephrectomy, and the recipient of the liver transplant died of metastatic disease. Microscopic examination of the liver and kidney allografts subsequently revealed histological features identical to the pancreas tumor. Tumor transmission in transplantation may occur from an organ that contains metastatic cells or, less commonly, from the transmission of an unrecognized or occult primary tumor. A report from the United Network for Organs Sharing transplant data 1997–2002 is illustrated and discussed. This case illustrates the difficulties associated with identifying donors with occult primary tumor or metastases.     

Greater Hemodynamic Instability With Histidine-Tryptophan-Ketoglutarate Solution Than University of Wisconsin Solution During the Reperfusion Period in Living Donor Liver Transplantation

Objective

University of Wisconsin (UW) and histidine-tryptophan-ketoglutarate (HTK) solutions are the 2 most commonly used liver preservation solutions. The aim of this study was to compare cardiovascular stability, acid-base status, and potassium concentrations between patients who received grafts preserved in either UW or HTK solution in orthotopic liver transplantation (OLT).

Patients and Methods

In this retrospective study, 87 patients who underwent living donor OLT were divided into 2 groups: UW (n = 28) and HTK (n = 59). Group HTK was subdivided into group NF-HTK (n = 31; nonflushed before reperfusion) and group F-HTK (n = 28; flushed before reperfusion). We determined mean arterial pressure (MAP) and heart rate every minute for 5 minutes after reperfusion and the maximum change in these values and incidence of postreperfusion syndrome (PRS). Body temperature, cardiovascular and acid-base parameters, as well as potassium concentrations were compared at 5 minutes before and 5 and 30 minutes after reperfusion.

Results

The maximum decreases in MAP within 5 minutes after reperfusion were significantly greater in both the NF-HTK and the F-HTK groups. The rate of PRS was significantly greater in the NF-HTK compared with the UW group. Flushing with HTK solution decreased the rate of PRS; there was no significant difference between the F-HTK and UW groups. All serial changes in body temperature, cardiovascular and acid-base parameters, as well as potassium concentrations were similar among the 3 groups.

Conclusions

The incidence of PRS was greater using HTK compared with UW solution during the reperfusion period. Therefore, careful hemodynamic management is advised when using HTK solution.     

Luminal preservation of rat small intestine with University of Wisconsin or Celsior solution

AIMS: Luminal administration of a preservation solution that prevents mucosal injury may decrease posttransplant complications. However, luminal administration of University of Wisconsin solution (UW) is controversial. In this study, we examined the potential of Celsior as a luminal small bowel preservation solution in comparison to UW or UW enriched with glutamine. METHODS: Small bowels of six normal WagRij rats were excised and divided into six equal segments. Each segment was luminally flushed with 10 mL ice-cold UW, UW with glutamine (20 g/L) or Celsior, and stored for 0, 2.5, and 24 hours at 4 degrees C. LDH, glucose, and lactate concentrations were determined in the preservation solutions. Histologic changes were determined using the Park score. RESULTS: Lactate dehydrogenase (LDH) was increased in all solutions after 2.5- and after 24-hour preservation. However, LDH was lower in Celsior than UW and UW with glutamine. Furthermore, higher glucose and lactate levels were found after 2.5- and 24-hour preservation in UW and UW with glutamine compared to Celsior. Histologically, jejunal segments were more susceptible to preservation than ileal segments, irrespective of the preservation solution used. Mucosal injury was evident after 2.5 hours (Park Scale 0-3) and increased significantly after 24 hours (park scale 3-6). CONCLUSIONS: Based on the lower glucose, lactate, and LDH levels in small intestines stored in Celsior, this study suggests that Celsior is a better luminal preservation solution than UW. Unfortunately, histological evaluations still show severe mucosal injury, indicating that there is a need for better luminal preservation solutions or for concomittant intravascular delivery of a preservation solution.     

Pancreas Transplantation After Liver Transplantation: A Case Report

Our aim was to describe the clinical indications, surgical technique, and clinical outcomes of a pancreas transplantation, performed 4 years after liver transplantation, as treatment for new-onset, uncontrolled diabetes mellitus in a 53-year-old man. Liver transplantation was performed for end-stage liver disease secondary to hepatitis B virus infection and hepatocellular carcinoma. The patient had no history of diabetes prior to the liver transplantation. The decision to proceed with a pancreas transplantation was made when the patient's blood sugar levels could not be normalized despite insulin doses >100 IU/d. A modified cadaveric transplantation technique was used, with the recipient's inferior vena cava dissected for anastomosis with the portal vein of the graft, using a diamond-shaped patch procedure. Moreover, the right common iliac artery was anastomosed with a Y-graft in the pancreas graft, and the duodenum remnant of the graft was anastomosed to the recipient's duodenum using a side-to-side procedure. The 6-month postoperative follow-up included repeated endoscopic biopsy of the graft duodenum, with no evidence of thrombosis or rejection of the graft, with glucose level within normal limits without requirement for diabetic drugs. To our knowledge, this is the first reported case of pancreas transplantation after liver transplantation.