First World Consensus Conference on pancreas transplantation: Part II - recommendations.

The First World Consensus Conference on Pancreas Transplantation provided 49 jury deliberations regarding the impact of pancreas transplantation on the treatment of diabetic patients, and 110 experts' recommendations for the practice of pancreas transplantation. The main message from this consensus conference is that both simultaneous pancreas-kidney transplantation (SPK) and pancreas transplantation alone can improve long-term patient survival, and all types of pancreas transplantation dramatically improve the quality of life of recipients. Pancreas transplantation may also improve the course of chronic complications of diabetes, depending on their severity. Therefore, the advantages of pancreas transplantation appear to clearly surpass potential disadvantages. Pancreas after kidney transplantation increases the risk of mortality only in the early period after transplantation, but is associated with improved life expectancy thereafter. Additionally, preemptive SPK, when compared to SPK performed in patients undergoing dialysis, appears to be associated with improved outcomes. Time on dialysis has negative prognostic implications in SPK recipients. Increased long-term survival, improvement in the course of diabetic complications, and amelioration of quality of life justify preferential allocation of kidney grafts to SPK recipients. Audience discussions and live voting are available online at the following URL address: http://mediaeventi.unipi.it/category/1st-world-consensus-conference-of-pancreas-transplantation/246.

Successful treatment of enteroatmospheric fistulas in combination with negative pressure wound therapy: Experience on 3 cases and literature review.

Enteroatmospheric fistulas (EAF) are rare but challenging and morbid complications of abdominal surgery and require time- as well as resource-consuming management. Furthermore, they severely affect patients' quality of life. Several treatment modalities for EAF management are described in the literature. We describe 3 consecutive cases of EAF treatment by employing negative pressure wound therapy (NPWT) along with either a special silicone fistula adapter or a Silo-Vac-like system in another case to isolate the fistula from the remaining abdominal wound. Spontaneous fistula closure was achieved in 2 of the 3 cases, and surgical resection of the small bowel segment harbouring EAF opening was possible in a third case after wound conditioning. The rate of fistula closure was 100% (n = 3/3). Compartmentalisation of the contaminated area using NPWT accelerated healing of the open abdominal wound remarkably. In summary, we present a useful tool for the challenging management of EAF and review the literature on different treatment options of EAF available today.

Technical and Clinical Outcome of Low-Milliampere CT Fluoroscopy-Guided Percutaneous Drainage Placement in Abdominal Fluid Collections after Liver Transplantation: A 16-Year Retrospective Analysis of 50 Consecutive Patients.

PURPOSE: Evaluation of the effectiveness of CT-guided drainage (CTD) placement in managing symptomatic postoperative fluid collections in liver transplant patients. The assessment included technical success, clinical outcomes, and the occurrence of complications during the peri-interventional period. METHODS: Analysis spanned the years 2005 to 2020 and involved 91 drain placement sessions in 50 patients using percutaneous transabdominal or transhepatic access. Criteria for technical success (TS) included (a) achieving adequate drainage of the fluid collection and (b) the absence of peri-interventional complications necessitating minor or prolonged hospitalization. Clinical success (CS) was characterized by (a) a reduction or normalization of inflammatory blood parameters within 30 days after CTD placement and (b) the absence of a need for surgical revision within 60 days after the intervention. Inflammatory markers in terms of C-reactive protein (CRP), leukocyte count and interleukin-6, were evaluated. The dose length product (DLP) for various intervention steps was calculated. RESULTS: The TS rate was 93.4%. CS rates were 64.3% for CRP, 77.8% for leukocytes, and 54.5% for interleukin-6. Median time until successful decrease was 5.0 days for CRP and 3.0 days for leukocytes and interleukin-6. Surgical revision was not necessary in 94.0% of the cases. During the second half of the observation period, there was a trend (p = 0.328) towards a lower DLP for the entire intervention procedure (median: years 2013 to 2020: 623.0 mGy·cm vs. years 2005 to 2012: 811.5 mGy·cm). DLP for the CT fluoroscopy component was significantly (p = 0.001) lower in the later period (median: years 2013 to 2020: 31.0 mGy·cm vs. years 2005 to 2012: 80.5 mGy·cm). CONCLUSIONS: The TS rate of CT-guided drainage (CTD) placement was notably high. The CS rate ranged from fair to good. The reduction in radiation exposure over time can be attributed to advancements in CT technology and the growing expertise of interventional radiologists.

Antibiotic Bowel Decontamination in Gastrointestinal Surgery-A Single-Center 20 Years' Experience.

Objective: Anastomotic leakage, surgical site infections, and other infectious complications are still common complications in gastrointestinal surgery. The concept of perioperative antibiotic bowel decontamination demonstrates beneficial effects in single randomized controlled trials (RCTs), but data from routine clinical use are still sparse. Our aim was to analyze the data from the routine clinical use of perioperative antibiotic bowel decontamination in gastrointestinal surgery. Methods: Based on 20 years' experience, we performed a retrospective analysis of all cases in oncologic gastrointestinal surgery with the use of antibiotic bowel decontamination in gastric, sigmoid, and rectal cancer. Clinical data and perioperative outcomes were analyzed, especially regarding anastomotic leakage, surgical site infections, and other infectious complications. Results: A total of n = 477 cases of gastrointestinal surgery in gastric cancer (n = 80), sigmoid cancer (n = 168), and rectal cancer (n = 229) using a perioperative regimen of antibiotic bowel decontamination could be included in this analysis. Overall, anastomotic leakage occurred in 4.4% (2.5% gastric cancer, 3.0% sigmoid cancer, 6.1% rectal cancer) and surgical site infections in 9.6% (6.3% gastric cancer, 9.5% sigmoid cancer, 10.9% rectal cancer). The incidence of all infectious complications was 13.6% (12.5% gastric cancer, 11.3% sigmoid cancer, 15.7% rectal cancer). Mortality was low, with an overall rate of 1.1% (1.3% gastric cancer, 1.8% sigmoid cancer, 0.4% rectal cancer). Antibiotic decontamination was completed in 98.5%. No adverse effects of antibiotic bowel decontamination could be observed. Conclusion: Overall, in this large cohort, we can report low rates of surgery-related serious morbidity and mortality when perioperative antibiotic bowel decontamination is performed. The rates are lower than other clinical reports. In our clinical experience, the use of perioperative antibiotic bowel decontamination appears to improve patient safety and surgical outcomes during gastrointestinal oncologic procedures in a routine clinical setting.

International Survey of Clinical Monitoring Practices in Pancreas and Islet Transplantation.

BACKGROUND: The long-term outcomes of both pancreas and islet allotransplantation have been compromised by difficulties in the detection of early graft dysfunction at a time when a clinical intervention can prevent further deterioration and preserve allograft function. The lack of standardized strategies for monitoring pancreas and islet allograft function prompted an international survey established by an International Pancreas and Islet Transplant Association/European Pancreas and Islet Transplant Association working group. METHODS: A global survey was administered to 24 pancreas and 18 islet programs using Redcap. The survey addressed protocolized and for-cause immunologic and metabolic monitoring strategies following pancreas and islet allotransplantation. All invited programs completed the survey. RESULTS: The survey identified that in both pancreas and islet allograft programs, protocolized clinical monitoring practices included assessing body weight, fasting glucose/C-peptide, hemoglobin A1c, and donor-specific antibody. Protocolized monitoring in islet transplant programs relied on the addition of mixed meal tolerance test, continuous glucose monitoring, and autoantibody titers. In the setting of either suspicion for rejection or serially increasing hemoglobin A1c/fasting glucose levels postpancreas transplant, Doppler ultrasound, computed tomography, autoantibody titers, and pancreas graft biopsy were identified as adjunctive strategies to protocolized monitoring studies. No additional assays were identified in the setting of serially increasing hemoglobin A1c levels postislet transplantation. CONCLUSIONS: This international survey identifies common immunologic and metabolic monitoring strategies utilized for protocol and for cause following pancreas and islet transplantation. In the absence of any formal studies to assess the efficacy of immunologic and metabolic testing to detect early allograft dysfunction, it can serve as a guidance document for developing monitoring algorithms following beta-cell replacement.

Antithrombin therapy in pancreas retransplantation and pancreas-after-kidney/pancreas-transplantation-alone patients.

Antithrombin (AT) is a coagulatory inhibitor with pleiotropic activities. AT reduces ischemia/reperfusion injury and has been successfully used in patients with simultaneous pancreas kidney transplantation. This study retrospectively analyzes prophylactic high-dose AT application in patients with solitary pancreas transplantation traditionally related to suboptimal results. In our center, 31 patients received solitary pancreas transplantation between 7/1994 and 7/2005 (pancreas retransplantation, PAK/PTA). The perioperative treatment protocol was modified in 5/2002 now including application of 3000 IU. AT was given intravenously before pancreatic reperfusion (AT, n = 18). Patients receiving standard therapy served as controls (n = 13). Daily blood sampling was performed during five postoperative days. Standard coagulatory parameters and number of transfused red blood cell units were not altered by AT. In AT patients serum amylase (p < 0.01) and lipase (p < 0.01) on postoperative days 1, 2 and 3 were significantly reduced. Our actual perioperative management protocol including high dose AT application in human solitary pancreas transplantation reduced postoperative liberation of pancreatic enzymes in this pilot study. Prophylactic AT application should deserve further clinical testing in a randomized controlled trial.

Enteric conversion after pancreatic transplantation: resolution of symptoms and long-term results.

PURPOSE: Bladder drainage (BD) of pancreatic transplants is associated with a unique set of complications. We intended to analyze the incidence, indications, complications and long-term results of enteric conversion procedures (EC). METHODS: Using a prospective database, 32 EC patients out of 433 simultaneous pancreas-kidney-transplant (SPK) recipients were identified. Graft and patient survival rates were compared with those after primary enteric drainage (ED). RESULTS: The mean SPK-EC interval was 5.0 yr, and the mean patient follow-up was 13.8 yr. Indications for EC were genitourinary symptoms (62.5%), duodenal complications (15.6%), graft pancreatitis (12.5%), pyelonephritis (6.3%), and metabolic acidosis (3.1%). All patients reported significant long-term resolution of symptoms. Surgical complications, reoperations, early graft loss, and 30-d mortality occurred in 31.3%, 25.0%, 6.3%, and 3.1% of cases, respectively. Pancreatic graft and patient survival rates at 1, 5, and 10 yr after SPK were comparable between EC patients and ED patients at the same institution. CONCLUSION: For the treatment of symptoms associated with BD, EC results in excellent long-term graft function and significant resolution of symptoms even years after SPK. Postoperative morbidity after EC including early reoperation and graft loss, however, has to be considered.

Molecular evidence of nosocomial Pneumocystis jirovecii transmission among 16 patients after kidney transplantation.

In recent years, clusters of Pneumocystis jirovecii (formerly Pneumocystis carinii) pneumonia (PCP) among immunocompromised individuals have been reported. Mostly, the source of infections was suspected to be within the clinical settings when transplant recipients and PCP patients shared hospital facilities. We report on a cluster of 16 renal transplant recipients positive for P. jirovecii. None of them received anti-Pneumocystis prophylaxis prior to P. jirovecii detection. Epidemiological studies revealed that 15 of them had received kidney transplants at a German university hospital and attended the same inpatient and outpatient clinic from January through September 2006. Multilocus sequence typing (MLST) was performed on the following genes: ITS1, beta-tub, 26S, and mt26S. P. jirovecii DNA was available from 14 patients and showed identical MLST types among these renal transplant recipients. Surprisingly, one patient who was treated at a different nephrological center and reported no personal contact with patients from the renal transplantation cluster harbored an identical P. jirovecii MLST type. Three HIV-positive patients and one bone-marrow-transplanted hematologic malignancy patient--treated at different medical centers--were used as controls, and different MLST types were revealed. Interestingly, in three of the four previously described regions, new alleles were detected, and one new polymorphism was observed in the mt26S region. The epidemiological data and the genotyping results strongly suggest a nosocomial patient-to-patient transmission of P. jirovecii as the predominant transmission route. Therefore, strict segregation and isolation of P. jirovecii-positive/suspected patients in clinical settings seems warranted.

Extended Pancreas Donor Program-The EXPAND Study: A Prospective Multicenter Trial Testing the Use of Pancreas Donors Older Than 50 Years.

BACKGROUND: Pancreas transplantation is the only curative treatment option for patients with juvenile diabetes. Organ shortage and restrictive allocation criteria are the main reasons for increasing waitlists, leading to severe morbidity and mortality. We designed a study to increase the donor pool with extended donor criteria (EDC) organs (donor age, 50-60 years; body mass index, 30-34 kg/m). METHODS: Utilization of EDC organs required the implementation of a new allocation system within Eurotransplant. The study was a prospective, multicenter, 2-armed trial. The primary endpoint was pancreas function after 3 months. Rejection episodes, kidney function, and waitlist time were secondary endpoints. Patients receiving an EDC organ were study group patients; recipients of standard organs were control group patients. Follow-up was 1 year. RESULTS: Seventy-nine patients were included in 12 German centers, 18 received EDC organs and 61 received standard organs. Recipient demographics were similar. Mean EDC donor age was 51.4 ± 5 years versus 31.7 ± 12 in the control group. Insulin-free graft survival was 83.3% for EDC and 67.2% for standard organs (P = 0.245) after 3 months. One-year pancreas survival was 83.3% and 83.5% in the EDC versus standard group. One-year kidney allograft survival was approximately 94% in both groups. Rejection episodes and morbidity were similar. CONCLUSIONS: The Extended Pancreas Donor Program (EXPAND) shows in a prospective trial that selected EDC organs of donors older than 50 years can be used with outcomes similar to standard-criteria organs, therefore showing potential to reduce organ shortage and waiting times. This study substantiates the full implementation of EDC organs in a pancreas allocation system.

Pulmonary function in patients with type 1 diabetes before and after simultaneous pancreas and kidney transplantation.

INTRODUCTION: Pulmonary function is impaired in type 1 diabetes mellitus and is associated with the quality of metabolic control. Correction of chronic hyperglycemia by pancreas transplantation may ameliorate pulmonary function. METHODS: Lung volume and diffusing capacity were measured in 75 uremic patients with type 1 diabetes and a long diabetes duration waiting for a simultaneous kidney and pancreas transplantation (SPK). In addition 85 patients after SPK and 20 patients after kidney transplantation alone (KA) were investigated. In a subgroup of 30 patients, data before and after SPK were available for prospective analysis. RESULTS: Reduced lung volume and diffusing capacity were found in type 1 diabetic patients before transplantation. Nearly all parameters of pulmonary function improved after SPK and KA. A significant change was found for forced expiratory volume at 1 sec (FEV1) and FEV1/forced vital capacity (FVC) (Tiffenau index). A significant amelioration of diffusing capacity was only found in the SPK group but not in the KA group. The prospective investigation revealed significant improvements of pulmonary function after SPK: FEV1 (P=0.001), FVC, (P=0,006), Tiffenau index (P=0.03), and Hb-corrected diffusing capacity (carbon monoxide transfer factor, TCO), P=0.03; transfer coefficient (KCO=TCO corrected for alveolar volume), P=0.01. CONCLUSION: Simultaneous pancreas and kidney transplantation is able to attain long-term normoglycemia and to improve pulmonary function in uremic type 1 diabetic patients.

Metabolic follow-up after long-term pancreas graft survival.

DESIGN: Successful pancreas transplantation results in insulin independence and normoglycemia. This prospective study was performed to investigate long-term metabolic changes after pancreas transplantation. METHODS: Thirty-eight type 1 diabetic patients after simultaneous pancreas/kidney transplantation (SPK) with a pancreas graft survival for at least 10 years were studied in a prospective manner. HbA(1c) and glucose levels before and during an oral glucose tolerance test (OGTT) were analyzed from 3 months to 10 years after SPK. In addition, insulin secretion and glucagon response were measured. RESULTS: Fasting glucose increased slightly and continuously from 3 months to 10 years (from 78 +/- 3 to 91 +/- 2 mg/dl). Even HbA(1c) levels showed a mild but significant increase from 3 months to 10 years after SPK. Glucose tolerance deteriorated markedly 10 years after SPK. Insulin secretion during OGTT remained stable for 10 years. Parameters of insulin resistance and sensitivity did not change significantly but glucagon secretion increased significantly during the course after SPK. Late after SPK, glucagon levels were higher in patients with an impaired or diabetic glucose tolerance. CONCLUSIONS: Pancreas transplantation is able to restore endogenous insulin secretion for 10 years or more. Especially, late after SPK, a deterioration of glycemic control was detected, even if glucose values were within the normal range. During prospective long-term follow-up, an increase of glucagon secretion but no decrease of insulin secretion was detected.

Center Volume Is Associated With Outcome After Pancreas Transplantation Within the Eurotransplant Region.

BACKGROUND: Outcome after surgery depends on several factors, among these, the annual volume-outcome relationship. This might also be the case in a highly complex field as pancreas transplantation. No study has investigated this relationship in a European setting. METHODS: All consecutive pancreas transplantations from January 2008 until December 2013 were included. Donor-, recipient-, and transplant-related factors were analyzed for their association with patient and graft survivals. Centers were classified in equally sized groups as being low volume (<5 transplantations on average each year in the 5 preceding years), medium volume (5-13/year), or high volume (≥13/year). RESULTS: In the study period, 1276 pancreas transplantations were included. Unadjusted 1-year patient survival was associated with center volume and was best in high volume centers, compared with medium and low volume: 96.5%, 94% and 92.3%, respectively (P = 0.017). Pancreas donor risk index (PDRI) was highest in high volume centers: 1.38 versus 1.21 in medium and 1.25 in low volume centers (P < 0.001). Pancreas graft survival at 1 year did not differ significantly between volume categories: 86%, 83.2%, and 81.6%, respectively (P = 0.114). After multivariate Cox-regression analysis, higher PDRI (hazard ratio [HR], 1.60; P < 0.001), retransplantation (HR, 1.91; P = 0.002), and higher recipient body mass index (HR, 1.04; P = 0.024) were risk factors for pancreas graft failure. High center volume was protective for graft failure (HR, 0.70; P = 0.037) compared with low center volume. CONCLUSION: Patient and graft survival after pancreas transplantation are superior in higher volume centers. High volume centers have good results, even though they transplant organs with the highest PDRI.

Extended pancreas donor program - the EXPAND study rationale and study protocol.

BACKGROUND: Simultaneous pancreas kidney transplantation (SPK), pancreas transplantation alone (PTA) or pancreas transplantation after kidney (PAK) are the only curative treatment options for patients with type 1 (juvenile) diabetes mellitus with or without impaired renal function. Unfortunately, transplant waiting lists for this indication are increasing because the current organ acceptability criteria are restrictive; morbidity and mortality significantly increase with time on the waitlist. Currently, only pancreas organs from donors younger than 50 years of age and with a body mass index (BMI) less than 30 are allocated for transplantation in the Eurotransplant (ET) area. To address this issue we designed a study to increase the available donor pool for these patients. METHODS/DESIGN: This study is a prospective, multicenter (20 German centers), single blinded, non-randomized, two armed trial comparing outcome after SPK, PTA or PAK between organs with the currently allowed donor criteria versus selected organs from donors with extended criteria. Extended donor criteria are defined as organs procured from donors with a BMI of 30 to 34 or a donor age between 50 and 60 years. Immunosuppression is generally standardized using induction therapy with Myfortic, tacrolimus and low dose steroids. In principle, all patients on the waitlist for primary SPK, PTA or PAK are eligible for the clinical trial when they consent to possibly receiving an extended donor criteria organ. Patients receiving an organ meeting the current standard criteria for pancreas allocation (control arm) are compared to those receiving extended criteria organ (study arm); patients are blinded for a follow-up period of one year. The combined primary endpoint is survival of the pancreas allograft and pancreas allograft function after three months, as an early relevant outcome parameter for pancreas transplantation. DISCUSSION: The EXPAND Study has been initiated to investigate the hypothesis that locally allocated extended criteria organs can be transplanted with similar results compared to the currently allowed standard ET organ allocation. If our study shows a favorable comparison to standard organ allocation criteria, the morbidity and mortality for patients waiting for transplantation could be reduced in the future. TRIAL REGISTRATION: Trial registered at: NCT01384006.

Early renal failure after domino liver transplantation using organs from donors with primary hyperoxaluria type 1.

BACKGROUND: Organ shortage is responsible for high mortality rates of patients awaiting liver transplantation (LT). Domino transplantation has had reported success in patients with metabolic disorders. Primary hyperoxaluria type 1 (PH1) is a rare metabolic disorder. There are a few case reports that suggest that PH1 livers originating from donors that have undergone combined liver-kidney transplantation can be successfully used for domino transplantation. METHODS: In the last decade, five patients received a domino liver transplant from patients with PH1 in the EUROTRANSPLANT region. In this study, we report the clinical course and outcome of these five patients who were received a domino graft transplant. RESULTS: All patients, with the exception of one, suffered from multifocal hepatocellular carcinoma and underwent domino LT from patients undergoing combined liver-kidney transplantation for PH1. Within the first 4 weeks, all the domino recipients developed dialysis-dependent kidney failure despite good liver function. Four of the five patients died. The only survivor underwent retransplantation due to hepatic artery thrombosis. Twenty months after transplantation, this patient is doing well and has had no recurrence of hepatocellular carcinoma. CONCLUSION: Domino LT using donors with PH1 results in early renal failure and cannot be recommended for transplantation unless preventive strategies have been identified.

Calcineurin-inhibitor avoidance in elderly renal allograft recipients using ATG and basiliximab combined with mycophenolate mofetil.

In old recipients of renal allografts from old donors, benefits of calcineurin-inhibitors (CNI) are curtailed by nephrotoxicity. Intending to improve the outcome of these recipients, we analyzed a CNI-free immunosuppressive regimen consisting of anti-thymocyte globulin (ATG), basiliximab, mycophenolate mofetil (MMF) and steroids. Kidney allograft recipients with low immunological risk (panel reactive antibodies <30%) were eligible for this study. Immunosuppression induction included ATG (4 mg/kg, day 0), basiliximab (20 mg, day 0 + 4) and steroids, followed by MMF (TL 2-6 microg/ml) and steroid maintenance treatment. Patient and graft survival rates respectively were 89.3% and 85.4% (12 months), and 86.6% and 76.8% (24 months). Delayed graft function occurred in 44.6%. S-creatinine at 12 months was 1.85 +/- 0.94 mg/dl. Thirty patients (53.6%) showed biopsy-proven rejections (6x Banff 3, 13x Banff 4I and 16x Banff 4II), 77% of which were steroid-sensitive, 23% required antibody treatment. After 12 months, 83% of the patients had an MMF-based immunosuppression, 43% were CNI-free. Cytomegalovirus (CMV) infections occurred in 28, tissue-invasive disease in three patients. Despite acceptable renal graft survival and function in some of patients with marginal organs, high incidences of rejections and CMV infections suggest the feasibility of CNI-avoidance using an MMF-based protocol only in carefully selected patients.

Single-shot antithrombin in human pancreas-kidney transplantation: reduction of reperfusion pancreatitis and prevention of graft thrombosis.

Reperfusion pancreatitis and graft thrombosis often induce early graft loss in simultaneous pancreas-kidney (SPK) transplantation. Antithrombin (AT) is a coagulatory inhibitor with pleiotropic activities that reduces experimental ischemia/reperfusion injury. This study retrospectively analyses prophylactic high-dose AT application in patients with first SPK. In an university transplantation center, 53 consecutive patients with SPK were studied without randomization. In one group, 3000 IU of AT was given intravenously before pancreatic reperfusion (AT, n = 24). Patients receiving standard therapy including postoperative AT supplementation (controls, n = 29) served as controls. Daily blood sampling was performed as a part of the clinical routine during four postoperative days. There were no differences in demographic and laboratory parameters [donor/recipient age, ischemia time, perfusion solution, body weight, mismatches] between both groups. Baseline creatinine values were lower in the control group versus AT group (P < 0.05). Coagulatory parameters and bleeding incidence were not influenced by AT, while incidence of graft thrombosis was reduced (control: 7/29; AT: 4/24; relative reduction of risk: -33%; P < 0.05). Single-shot AT application during SPK modulated serum lipase activity on postoperative days 2 and 3, and minimized risk for graft thromboses without increasing perioperative bleeding. This new concept should deserve testing in a prospective clinical trial.

Rejection after simultaneous pancreas-kidney transplantation.

BACKGROUND: Simultaneous pancreas-kidney (SPK) transplantation is an accepted therapy for type 1 diabetic patients with end-stage renal disease. This study analyses the occurrence of rejection episodes in patients undergoing SPK. METHODS: The study population was obtained from 205 patients enrolled in the Euro-SPK 001 study and randomized to receive tacrolimus- (n = 103) or cyclosporin microemulsion (ME)-based (n = 102) immunosuppressive therapy. All patients received concomitant antibody induction therapy, mycophenolate mofetil and short-term corticosteroids. RESULTS: After 3 years of follow-up, rejection episodes occurred in 41 patients receiving tacrolimus and in 51 patients receiving cyclosporin-ME. The majority of first rejection episodes in both groups occurred during the first 6 months (93 and 90%, respectively) and in most cases were treated with corticosteroids alone (88 vs 90%). Actuarial rejection-free kidney and/or pancreas graft survival was similar for tacrolimus (54%) and cyclosporin-ME (44%). Human leukocyte antigen (HLA) compatibility (P = 0.003) and graft vessel extension (P = 0.000001) had a significant influence on rejection-free graft survival. Also, rejection influenced pancreas graft survival (P = 0.01), and pancreas graft loss due to rejection influenced patient survival (P = 0.02). In the intent-to-treat analysis of early rejection, significantly fewer tacrolimus- than cyclosporin-ME-treated patients had (i) more than one rejection episode (11 out of 40 vs 24 out of 47; P = 0.03); (ii) first moderate to severe rejection (one out of 40 vs 12 out of 47; P = 0.004); and (iii) refractory rejection (two out of 40 vs 10 out of 47; P = 0.03). Pancreas survival was lower in late rejectors (53%) than non-rejectors (86%; P = 0.002). Also, serum creatinine was highest in late rejectors. CONCLUSION: Tacrolimus-based immunosuppressive therapy demonstrates significant advantages over cyclosporin-ME in terms of the severity of acute rejection in SPK transplant patients.