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BACKGROUND The main concern with live donor liver transplantation (LDLT) is the risk to the donor. Given the potential risk of liver insufficiency, most centers will only accept candidates with future liver remnants (FLR) >30%. We aimed to compare postoperative outcomes of donors who underwent LDLT with FLR ≤30% and >30%. METHODS Adults who underwent right hepatectomy for LDLT between 2000 and 2018 were analyzed. Remnant liver volumes were estimated using hepatic volumetry. To adjust for between-group differences, donors with FLR ≤30% and >30% were matched 1:2 based on baseline characteristics. Postoperative complications including liver dysfunction were compared between the groups. RESULTS A total of 604 live donors were identified, 28 (4.6%) of whom had a FLR ≤30%. Twenty-eight cases were successfully matched with 56 controls; the matched cohorts were mostly similar in terms of donor and graft characteristics. The calculated median FLR was 29.8 (range, 28.0-30.0) and 35.2 (range, 30.1-68.1) in each respective group. Median follow-up was 36.5 mo (interquartile range, 11.8-66.1). Postoperative outcomes were similar between groups. No difference was observed in overall complication rates (FLR ≤30%: 32.1% versus FLR >30%: 28.6%; odds ratio [OR], 1.22; 95% confidence interval [CI], 0.46-3.27) or major complication rates (FLR ≤30%: 14.3% versus FLR >30%: 14.3%; OR, 1.17; 95% CI, 0.33-4.10). Posthepatectomy liver failure was rare, and no difference was observed (FLR ≤30%: 3.6% versus FLR >30%: 3.6%; OR, 1.09; 95% CI, 0.11-11.1). CONCLUSION A calculated FLR between 28% and 30% on its own should not represent a formal contraindication for live donation.

Diabetes mellitus (DM) is said to adversely affect transplant outcomes. The aim of this study was to investigate the impact of pre-existing and new-onset DM on liver transplantation (LT) recipients.A single-center retrospective analysis of prospectively collected data of LT recipients (1990-2015) was undertaken.Of the 2209 patients, 13% (n = 298) had Pre-DM, 16% (n = 362) developed post-transplant diabetes mellitus (PTDM), 5% (n = 118) developed transient hyperglycemia (t-HG) post-LT, and 65% (n = 1431) never developed DM (no DM). Baseline clinical characteristics of patients with PTDM were similar to that of patients with Pre-DM. Incidence of PTDM peaked during the first year (87%) and plateaued thereafter. On multivariate analysis (Bonferroni-corrected), nonalcoholic fatty liver disease and the use of tacrolimus and sirolimus were independently associated with PTDM development. Both Pre-DM and PTDM patients had satisfactory and comparable glycemic control throughout the follow-up period. Those who developed t-HG seem to have a unique characteristic compared with others. Overall, 9%, 5%, and 8% of patients developed end-stage renal disease (ESRD), major cardiovascular event (mCVE), and de novo cancer, respectively. Both Pre-DM and PTDM did not adversely affect patient survival, retransplantation, or de novo cancer. The risks of ESRD and mCVE were significantly higher in patients with Pre-DM followed by PTDM and no DM.In this largest nonregistry study, patients with Pre-DM and PTDM share similar baseline clinical characteristics. Pre-DM increases the risk of ESRD and mCVE; however, patient survival was comparable to those with PTDM and without diabetes. Understanding the impact of PTDM would need prolonged follow-up.

BACKGROUND There is a lack of information about survival after dropout from the liver transplant waiting list. Therefore, we aimed to assess the overall survival, and risk factors for death, after waiting list dropout due to hepatocellular carcinoma (HCC) progression. METHODS We assessed patients who dropped out of the liver transplant waiting list between 2000 and 2016 in a single, large academic North American center. Patients were divided into 3 groups according to the types of HCC progression: locally advanced disease (LAD), extrahepatic disease (EHD), and macrovascular invasion (MVI). The primary outcome was overall survival. Survival was assessed by the Kaplan-Meier method. Predictors of death after dropout were assessed by multivariable Cox regression. RESULTS During the study period, 172 patients dropped out due to HCC progression. Of those, 37 (21.5%), 74 (43%), and 61 (35.5%) dropped out due to LAD, EHD, and MVI, respectively. Median survival according to cause of dropout (LAD, EHD, or MVI) was 1.0, 4.4, or 3.3 months, respectively (P = 0.01). Model for End-stage Liver Disease (MELD) score (hazard ratio [HR], 1.04; 95% confidence interval [CI], 1.01-1.08), alcoholic liver disease (HR, 1.66; 95% CI, 1.02-2.71), and α-fetoprotein >1000 ng/mL (HR, 1.86; 95% CI, 1.22-2.84) were predictors of mortality after dropout. Dropout due to EHD (HR, 0.61; 95% CI, 0.38-0.98) and undergoing treatment after dropout were protective factors (HR, 0.32; 95% CI, 0.21-0.48) for death. CONCLUSIONS Patient prognosis after dropout is dismal. However, a subgroup of patients may have longer survival. The present study identifies the patterns of waitlist dropout in patients with HCC and provides evidence for the effectiveness of treatment strategies offered to HCC patients after dropout.

Passenger lymphocyte syndrome (PLS) is a less known etiology of acute onset anemia following ABO-compatible (ABO-c) liver transplantation (LT). Available literature on PLS after pediatric LT is limited. Therefore, we evaluated the prevalence, clinical course, and risk factors of PLS in children following ABO-c LT.A single-center retrospective review of all children who underwent LT between 2000 and 2017 was performed. PLS was defined as a drop-in hemoglobin20 g/L within 30 days of LT, with positive direct antiglobulin test and 1 laboratory test confirming hemolysis. Chi square and student t tests compared variables between subjects with and without PLS.Amongst 333 pediatric LT performed, 51 children received an ABO-c graft. PLS was diagnosed in 7 (14%) subjects at a median of 10 days after LT. There were no significant differences in patient demographics, graft type, or immunosuppression between those who did and did not develop PLS. Recipient blood group A+ receiving a donor O+ graft was a risk factor for PLS (P = 0.015). All PLS subjects recovered with blood transfusions (median 2), and no additional interventions. Three subjects initially received recipient (instead of donor) blood group red cells.We report a 14% prevalence of PLS following pediatric ABO-c LT. Recipient blood group A+ receiving a donor O+ graft is a risk factor for PLS. Recognition of PLS as a cause of early acute anemia in pediatric ABO-c LT enables timely transfusion with donor (rather than recipient) blood group red cells.

The outcome after living donor liver transplantation (LDLT) using grafts with multiple bile ducts (BDs) remains unclear. We analyzed 510 patients who received an adult-to-adult right lobe LDLT between 2000 and 2015 and compared outcome parameters of those receiving grafts with 2 BDs (n = 169) with patients receiving grafts with 1 BD (n = 320). Additionally, patients receiving a graft with 3 BDs (n = 21) were analyzed. Demographic variables and disease severity were similar between the groups. Roux-en-Y reconstruction was significantly more common in the 2 BD group (77% versus 38%; P < 0.001) compared with the 1 BD group. No difference was found in biliary complication rates within 1 year after LDLT (1 BD versus 2 BD groups, 18% versus 21%, respectively; P = 0.46). In the 2 BD group, 82/169 (48.5%) patients were reconstructed with 2 anastomoses. The number of anastomoses did not negatively impact biliary complication rates. Recipients' major complication rate (Clavien ≥ 3b) was similar between both groups (1 BD versus 2 BD groups, 21% versus 24%, respectively; P = 0.36). Furthermore, no difference could be found between the 1 BD, the 2 BD, and the 3 BD groups in the frequency of developing biliary complications within 1 year (18%, 21%, 14%, respectively; P = 0.64), BD strictures (15%, 15%, 5%, respectively; P = 0.42), or BD leaks (10%, 11%, 10%, respectively; P = 0.98). In addition, the 1-year (90% versus 91%), 5-year (82% versus 77%), and 10-year (70% versus 66%) graft survival rates as well as the 1-year (92% versus 93%), 5-year (84% versus 80%), and 10-year (75% versus 76%) patient survival rates were comparable between the 1 BD and the 2 BD groups (P = 0.41 and P = 0.54, respectively). In conclusion, this study demonstrates that selected living donor grafts with 2 BDs can be used safely without negatively impacting biliary complication rates and graft or patient survival rates.

Portal vein thrombosis (PVT) is a severe complication after liver transplantation that can result in increased morbidity and mortality. Few data are available regarding risk factors, classification, and treatment of PVT after living donor liver transplantation (LDLT). Between January 2004 and November 2014, 421 adult-to-adult LDLTs were performed at our institution, and they were included in the analysis. Perioperative characteristics and outcomes from patients with no-PVT (n = 393) were compared with those with de novo PVT (total portal vein thrombosis [t-PVT]; n = 28). Ten patients had early portal vein thrombosis (e-PVT) occurring within 1 month, and 18 patients had late portal vein thrombosis (l-PVT) appearing later than 1 month after LDLT. Analysis of perioperative variables determined that splenectomy was associated with t-PVT (hazard ratio [HR], 3.55; P = 0.01), e-PVT (HR, 4.96; P = 0.04), and l-PVT (HR, 3.84; P = 0.03). In contrast, donor age was only found as a risk factor for l-PVT (HR, 1.05; P = 0.01). Salvage rate for treatment in e-PVT and l-PVT was 100% and 50%, respectively, without having an early event of rethrombosis. Mortality within 30 days did not show a significant difference between groups (no-PVT, 2% versus e-PVT, 10%; P = 0.15). No significant differences were found regarding 1-year (89% versus 92%), 5-year (79% versus 82%), and 10-year (69% versus 79%) graft survival between the t-PVT and no-PVT groups, respectively (P = 0.24). The 1-year (89% versus 96%), 5-year (82% versus 86%), and 10-year (79% versus 83%) patient survival was similar for the patients in the no-PVT and t-PVT groups, respectively (P = 0.70). No cases of graft loss occurred as a direct consequence of PVT. In conclusion, the early diagnosis and management of PVT after LDLT can lead to acceptable early and longterm results without affecting patient and graft survival.

Because of the shortfall between the number of patients listed for liver transplantation (LT) and the available grafts, strategies to expand the donor pool have been developed. Donation after circulatory death (DCD) and living donor (LD) grafts are not universally used because of the concerns of graft failure, biliary complications, and donor risks. In order to overcome the barriers for the implementation of using all 3 types of grafts, we compared outcomes after LT of DCD, LD, and donation after brain death (DBD) grafts. Patients who received a LD, DCD, or DBD liver graft at the University of Toronto were included. Between January 2009 through April 2017, 1054 patients received a LT at our center. Of these, 77 patients received a DCD graft (DCD group); 271 received a LD graft (LD group); and 706 received a DBD graft (DBD group). Overall biliary complications were higher in the LD group (11.8%) compared with the DCD group (5.2%) and the DBD group (4.8%; P < 0.001). The 1‐, 3‐, and 5‐year graft survival rates were similar between the groups with 88.3%, 83.2%, and 69.2% in the DCD group versus 92.6%, 85.4%, and 84.7% in the LD group versus 90.2%, 84.2%, and 79.9% in the DBD group (P = 0.24). Furthermore, the 1‐, 3‐, and 5‐year patient survival was comparable, with 92.2%, 85.4%, and 71.6% in the DCD group versus 95.2%, 88.8%, and 88.8% in the LD group versus 93.1%, 87.5%, and 83% in the DBD group (P = 0.14). Multivariate Cox regression analysis revealed that the type of graft did not impact graft survival. In conclusion, DCD, LD, and DBD grafts have similar longterm graft survival rates. Increasing the use of LD and DCD grafts may improve access to LT without affecting graft survival rates. Liver Transplantation 24 779–789 2018 AASLD.

The purpose of this study is to determine whether magnetic resonance (MR)-proton density fat fraction (PDFF) estimate of negligible hepatic fat percentage (

This multicentric study of 17 high-volume centers presents 12 benchmark values for liver transplantation. Those values, mostly targeting markers of morbidity, were gathered from 2024 "low risk" cases, and may serve as reference to assess outcome of single or any groups of patients.To propose benchmark outcome values in liver transplantation, serving as reference for assessing individual patients or any other patient groups.Best achievable results in liver transplantation, that is, benchmarks, are unknown. Consequently, outcome comparisons within or across centers over time remain speculative.Out of 7492 liver transplantation performed in 17 international centers from 3 continents, we identified 2024 low risk adult cases with a laboratory model for end-stage liver disease score ≤20 points, a balance of risk score ≤9, and receiving a primary graft by donation after brain death. We chose clinically relevant endpoints covering intra- and postoperative course, with a focus on complications graded by severity including the complication comprehensive index (CCI). Respective benchmarks were derived from the median value in each center, and the 75 percentile was considered the benchmark cutoff.Benchmark cases represented 8% to 49% of cases per center. One-year patient-survival was 91.6% with 3.5% retransplantations. Eighty-two percent of patients developed at least 1 complication during 1-year follow-up. Biliary complications occurred in one-fifth of the patients up to 6 months after surgery. Benchmark cutoffs were ≤4 days for ICU stay, ≤18 days for hospital stay, ≤59% for patients with severe complications (≥ Grade III) and ≤42.1 for 1-year CCI. Comparisons with the next higher risk group (model for end stage liver disease 21-30) disclosed an increase in morbidity but within benchmark cutoffs for most, but not all indicators, while in patients receiving a second graft from 1 center (n = 50) outcome values were all outside of benchmark values.Despite excellent 1-year survival, morbidity in benchmark cases remains high with half of patients developing severe complications during 1-year follow-up. Benchmark cutoffs targeting morbidity parameters offer a valid tool to assess higher risk groups.

Normothermic ex vivo liver perfusion (NEVLP) improves graft preservation by avoiding cold ischemia injury. We investigated whether the protective effects of NEVLP can be further improved by applying strategies targeted on reducing the activation of proinflammatory cytokines during perfusion. Livers retrieved under heart-beating conditions were perfused for 4 hours. Following the preservation period, a pig liver transplantation was performed. In group 1 (n = 5), anti-inflammatory strategies (alprostadil, n-acetylcysteine, carbon monoxide, sevoflurane, and subnormothermic temperature [33°C]) were applied. This was compared with a perfused control group (group 2) where livers (n = 5) were perfused at 37°C without anti-inflammatory agents, similar to the setup used in current European clinical trials, and to a control group preserved with static cold storage (group 3). During 3-day follow-up, markers of reperfusion injury, bile duct injury, and liver function were examined. Aspartate aminotransferase (AST) levels during perfusion were significantly lower in the study versus control group at 1 hour (52 ± 6 versus 162 ± 86 U/L; P = 0.01), 2 hours (43 ± 5 versus 191 ± 111 U/L; P = 0.008), and 3 hours (24 ± 16 versus 218 ± 121 U/L; P = 0.009). During perfusion, group 1 versus group 2 had reduced interleukin (IL) 6, tumor necrosis factor α, and galactosidase levels and increased IL10 levels. After transplantation, group 1 had lower AST peak levels compared with group 2 and group 3 (1400 ± 653 versus 2097 ± 1071 versus 1747 ± 842 U/L; P = 0.47) without reaching significance. Bilirubin levels were significantly lower in group 1 versus group 2 at day 1 (3.6 ± 1.5 versus 6.60 ± 1.5 μmol/L; P = 0.02) and 3 (2 ± 1.1 versus 9.7 ± 7.6 μmol/L; P = 0.01). A trend toward decreased hyaluronic acid, as a marker of improved endothelial cell function, was observed at 1, 3, and 5 hours after reperfusion in group 1 versus group 2. Only 1 early death occurred in each group (80% survival). In conclusion, addition of anti-inflammatory strategies further improves warm perfused preservation. Liver Transplantation 22 1573-1583 2016 AASLD.

Objective: To compare the outcome of adult live donor liver transplantation (LDLT) with grafts from older versus younger donors. Introduction: Using older donor grafts for adult LDLT may help expand the donor pool. However, the risks of LDLT with older donors remain controversial, and many centers are reluctant to use live donors aged 45 years or older for adult LDLT. Methods: Outcomes of patients receiving a LDLT graft from donors aged 50 years or older (n = 91) were compared with those receiving a live donor graft from donors younger than 50 years (n = 378). Results: Incidences of biliary (LDLT

The review discusses issues pertinent to fostering professional and public interest in living donor liver transplantation. We discuss practices that we have adopted at our center, issues that have arisen and provide suggestions to expand live donor transplantation.To bridge the gap between the current supply and demand of deceased donor organs, the transplant program in Toronto established the busiest live donor liver transplant program in the western world. To date, we have performed 664 live liver donor procedures with no donor deaths and excellent recipient and donor outcomes. To foster and grow live donation, we established a strong culture supporting live donation; hired a full-time, dedicated team of individuals to support the live donor program; obtained financial support for donors through a partnership agreement with the Trillium Gift of Life Network; developed linkages with the media, community service groups and the general public; generated patient education materials; and established a website.With the present and future trends of deceased donation worldwide, we anticipate that live liver donation will remain an important option to fully meet the needs of patients requiring liver transplantation for the foreseeable future.

We developed a novel technique of subnormothermic ex vivo liver perfusion (SNEVLP) for the storage of liver grafts before transplantation. To test the safety of SNEVLP for the nonextended criteria grafts (standard grafts), we compared it to a control group with minimal cold static storage (CS) time. Heart-beating pig liver retrieval was performed. Grafts were either stored in cold unmodified University of Wisconsin solution (CS-1), in cold University of Wisconsin solution with ex vivo perfusion additives (CS-2), or preserved with a sequence of 3 hours CS and 3 hours SNEVLP (33°C), followed by orthotopic liver transplantation. Liver function tests and histology were investigated. Aspartate aminotransferase (AST) levels during SNEVLP remained stable (54.3 ± 12.6 U/L at 1 hour to 47.0 ± 31.9 U/L at 3 hours). Posttransplantation, SNEVLP versus CS-1 livers had decreased AST levels (peak at day 1, 1081.9 ± 788.5 versus 1546.7 ± 509.3 U/L; P = 0.14; at day 2, 316.7 ± 188.1 versus 948.2 ± 740.9 U/L; P = 0.04) and alkaline phosphatase levels (peak at day 1, 150.4 ± 19.3 versus 203.7 ± 33.6 U/L; P = 0.003). Bilirubin levels were constantly within the physiological range in the SNEVLP group, whereas the CS-1 group presented a large standard deviation, including pathologically increased values. Hyaluronic acid as a marker of endothelial cell (EC) function was markedly improved by SNEVLP during the early posttransplant phase (5 hours posttransplant, 1172.75 ± 598.5 versus 5540.5 ± 2755.4 ng/mL). Peak international normalized ratio was similar between SNEVLP and CS-1 groups after transplantation. Immunohistochemistry for cleaved caspase 3 demonstrated more apoptotic sinusoidal cells in the CS-1 group when compared to SNEVLP grafts 2 hours after reperfusion (19.4 ± 19.5 versus 133.2 ± 48.8 cells/high-power field; P = 0.002). Adding normothermic CS-2 had no impact on liver injury or function after transplantation when compared to CS-1. In conclusion, SNEVLP is safe to use for standard donor grafts and is associated with improved EC and bile duct injury even in grafts with minimal CS time.

Because of a persistent discrepancy between the demand for liver transplantation (LT) and the supply of deceased donor organs, there is an interest in increasing living donation rates at centers trained in this method of transplantation. We examined a large socioeconomically heterogeneous cohort of patients listed for LT to identify recipient factors associated with living donation. We retrospectively reviewed 491 consecutive patients who were listed for LT at our center over a 24-month period. Demographic, medical, and socioeconomic data were extracted from electronic records and compared between those who had a potential living donor (LD) volunteer for assessment and those who did not; 245 patients (50%) had at least 1 potential LD volunteer for assessment. Multivariate logistic regression analysis identified that patients with a LD were more likely to have Child-Pugh C disease (odds ratio [OR], 2.44; P = 0.02), and less likely to be older (OR, 0.96; P = 0.002), single (OR, 0.34; P = 0.006), divorced (OR, 0.53; P = 0.03), immigrants (OR, 0.38; P = 0.049), or from the lowest income quintile (OR, 0.44; P = 0.02). In conclusion, this analysis has identified several factors associated with access to living donation. More research is warranted to define and overcome barriers to living donor liver transplantation through targeted interventions in underrepresented populations. Liver Transpl 21:897-903, 2015. © 2015 AASLD.

Data regarding transplantation outcomes in ventilated intensive care unit (ICU)–dependent patients with end-stage liver disease (ESLD) are conflicting. This single-center cohort study investigated the outcomes of patients with ESLD who were intubated with mechanical support before liver transplantation (LT). The ICU plus intubation group consisted of 42 patients with decompensated cirrhosis and mechanical ventilation before transplantation. LT was considered for intubated ICU patients if the fraction of inspired oxygen was ≤40% with a positive end-expiratory pressure ≤ 10, low pressor requirements, and the absence of an active infection. Intubated ICU patients were compared to 80 patients requiring ICU admission before transplantation without intubation and to 126 matched non–ICU-bound patients. Patients requiring ICU care with intubation and ICU care alone had more severe postoperative complications than non–ICU-bound patients. Intubation before transplantation was associated with more postoperative pneumonias (15% in intubated ICU transplant candidates, 5% in ICU-bound but not intubated patients, and 3% in control group patients; P = 0.02). Parameters of reperfusion injury and renal function on postoperative day (POD) 2 and POD 7 were similar in all groups. Bilirubin levels were higher in the ICU plus intubation group at POD 2 and POD 7 after transplantation but were normalized in all groups within 3 months. The ICU plus intubation group versus the ICU-only group and the non-ICU group had decreased 1-, 3-, and 5-year graft survival (81% versus 84% versus 92%, 76% versus 78% versus 87%, and 71% versus 77% versus 84%, respectively; P = 0.19), but statistical significance was not reached. A Glasgow coma scale score of 7 before transplantation was associated with high postoperative mortality in ICU-bound patients requiring intubation (38% versus 23%; P = 0.01). In conclusion, ICU admission and mechanical ventilation should not be considered contraindications for LT. With careful patient selection, acceptable long-term outcomes can be achieved despite increased postoperative complications. Liver Transpl 21:761–767, 2015. © 2015 AASLD.

Living donor liver resections are associated with significant postoperative pain. Epidural analgesia is the gold standard for postoperative pain management, although it is often refused or contraindicated. Surgically placed abdominal wall catheters (AWCs) are a novel pain modality that can potentially provide pain relief for those patients who are unable to receive an epidural. A retrospective review was performed at a single center. Patients were categorized according to their postoperative pain modality: intravenous (IV) patient-controlled analgesia (PCA), AWCs with IV PCA, or patient-controlled epidural analgesia (PCEA). Pain scores, opioid consumption, and outcomes were compared for the first 3 postoperative days. Propensity score matches (PSMs) were performed to adjust for covariates and to confirm the primary analysis. The AWC group had significantly lower mean morphine-equivalent consumption on postoperative day 3 [18.1 mg, standard error (SE) = 3.1 versus 28.2 mg, SE = 3.0; P = 0.02] and mean cumulative morphine-equivalent consumption (97.2 mg, SE = 7.2 versus 121.0 mg, SE = 9.1; P = 0.04) in comparison with the IV PCA group; the difference in cumulative-morphine equivalent remained significant in the PSMs. AWC pain scores were higher than those in the PCEA group and were similar to the those in the IV PCA group. The AWC group had a lower incidence of pruritus and a shorter hospital stay in comparison with the PCEA group and had a lower incidence of sedation in comparison with both groups. Time to ambulation, nausea, and vomiting were comparable among all 3 groups. The PSMs confirmed all results except for a decrease in the length of stay in comparison with PCEA. AWCs may be an alternative to epidural analgesia after living donor liver resections. Randomized trials are needed to verify the benefits of AWCs, including the safety and adverse effects. Liver Transpl 21:478–486, 2015. © 2015 AASLD.

Liver transplantation (LT) with donation after circulatory death (DCD) donors has been associated with a high rate of ischemic-type biliary strictures (ITBSs) and inferior graft survival. To investigate the impact of an intraoperative tissue plasminogen activator (tPA) on outcomes following DCD LT, we conducted a retrospective analysis of DCD LT at the Toronto General Hospital (TGH) and the Ochsner Medical Center (OMC). Between 2009 and 2013, 85 DCD LTs were performed with an intraoperative tPA injection (n=30 at TGH, n=55 at OMC), and they were compared with 33 DCD LTs without a tPA. Donor and recipient characteristics were similar in the 2 groups. There was no significant difference in the intraoperative packed red blood cell transfusion requirement (3.2 +/- 3.4 versus 3.1 +/- 2.3 U, P=0.74). Overall, biliary strictures occurred less commonly in the tPA-treated group (16.5% versus 33.3%, P=0.07) with a much lower rate of diffuse intrahepatic strictures (3.5% versus 21.2%, P=0.005). After 1 and 3 years, the tPA group versus the non-tPA group had superior patient survival (97.6% versus 87.0% and 92.7% versus 79.7%, P=0.016) and graft survival (96.4% versus 69.7% and 90.2% versus 63.6%, P

An ischemic-type biliary stricture (ITBS) is a common feature after liver transplantation using donation after cardiac death (DCD) grafts. We compared sequential subnormothermic ex vivo liver perfusion (SNEVLP; 33°C) with cold storage (CS) for the prevention of ITBS in DCD liver grafts in pig liver transplantation (n = 5 for each group). Liver grafts were stored for 10 hours at 4°C (CS) or preserved with combined 7-hour CS and 3-hour SNEVLP. Parameters of hepatocyte [aspartate aminotransferase (AST), international normalized ratio (INR), factor V, and caspase 3 immunohistochemistry], endothelial cell (EC; CD31 immunohistochemistry and hyaluronic acid), and biliary injury and function [alkaline phosphatase (ALP), total bilirubin, and bile lactate dehydrogenase (LDH)] were determined. Long-term survival (7 days) after transplantation was similar between the SNEVLP and CS groups (60% versus 40%, P = 0.13). No difference was observed between SNEVLP- and CS-treated animals with respect to the peak of serum INR, factor V, or AST levels within 24 hours. CD31 staining 8 hours after transplantation demonstrated intact EC lining in SNEVLP-treated livers (7.3 × 10−4 ± 2.6 × 10−4 cells/μm2) but not in CS-treated livers (3.7 × 10−4 ± 1.3 × 10−4 cells/μm2, P = 0.03). Posttransplant SNEVLP animals had decreased serum ALP and serum bilirubin levels in comparison with CS animals. In addition, LDH in bile fluid was lower in SNEVLP pigs versus CS pigs (14 ± 10 versus 60 ± 18 μmol/L, P = 0.02). Bile duct histology revealed severe bile duct necrosis in 3 of 5 animals in the CS group but none in the SNEVLP group (P = 0.03). Sequential SNEVLP preservation of DCD grafts reduces bile duct and EC injury after liver transplantation. Liver Transpl 20:1296-1305, 2014. © 2014 AASLD.

Despite its prominence as a concern among potential surgical candidates, there is little information in the literature regarding the short- and long-term pain experience after living liver donation. We undertook a prospective study to examine (1) the nature and incidence of acute and chronic pain after living donor hepatectomy and (2) the factors associated with an increased or decreased risk of adverse pain outcomes. Before donation, a comprehensive assessment of potential predictors of acute and chronic pain outcomes was conducted; this included donors' pain expectations, psychosocial factors, medical histories, and demographic factors. Detailed data regarding pain outcomes were collected postoperatively (days 1 and 2) and again during 6- and 12-month follow-up telephone interviews. Sixty-five adults (32 females and 33 males) scheduled for donor hepatectomy participated. Substantial proportions of the donors reported a moderate-to-severe level of pain intensity (≥4 on a 0-10 scale) at rest and after movement on day 1 (42% and 74%, respectively) and day 2 (33% and 32%, respectively). Persistent postsurgical pain was reported by 31% of the donors at the 6-month follow-up and by 27% of the donors at the 12-month follow-up. Generally, this pain was mild, and pain-related life interference was minimal. Female sex, a younger age, and several predonation measures of pain-related anxiety were associated with a significantly greater risk of developing persistent postsurgical pain. In conclusion, this study has identified a subset of patients who experience persistent pain after living liver donation. Additional prospective research using larger samples of liver donors is needed to replicate this work, to obtain a more detailed account of the acute and long-term pain experience, and to determine whether targeted interventions can minimize the frequency and severity of chronic pain.

Living liver donation is a successful treatment for patients with end-stage liver disease. Most adults are provided with a right lobe graft to ensure a generous recipient liver volume. Some centers are re-exploring the use of smaller left lobe grafts to potentially reduce the donor risk. However, the evidence showing that the donor risk is lower with left lobe donation is inconsistent, and most previous studies have been limited by potential learning curve effects, small sample sizes, or poorly matched comparison groups. To address these deficiencies, we conducted a case-control study. Forty-five consecutive patients who underwent left hepatectomy (LH; n = 4) or left lateral segmentectomy (LLS; n = 41) were compared with matched controls who underwent right hepatectomy (RH) or extended right hepatectomy (ERH). The overall complication rates of the 3 groups were similar (31%-37%). There were no grade 4 or 5 complications. There were more grade 3 complications for the RH patients (13.3%) and the ERH patients (15.6%) versus the LH/LLS patients (2.2%). The extent of the liver resection significantly correlated with the peak international normalized ratio (INR), the days to INR normalization, and the peak bilirubin level. A univariate analysis demonstrated that hepatectomy, the spared volume percentage, and the peak bilirubin level were strongly associated with grade 3 complications. A higher peak bilirubin level, which correlated with a lower residual liver volume, was associated with grade 3 complications in a multivariate analysis (P = 0.005). RH and grade 3 complications were associated with an increased length of stay (>7 days) in a multivariate analysis. In conclusion, this analysis demonstrates a significant correlation between the residual liver volume and liver dysfunction, serious adverse postoperative events, and longer hospital stays. Donor safety should be the first priority of all living liver donor programs. We propose that the surgical procedure removing the smallest amount of the liver required to provide adequate recipient graft function should become the standard of care for living liver donation.

Despite the increase in surgical volumes of live liver donation, there has been very little documentation of the postoperative pain experience. The primary aim of this study was to examine the difference in acute postoperative pain intensity and adverse effects between patients who received intravenous patient-controlled analgesia (IV PCA) or patient-controlled epidural analgesia (PCEA) for pain control after live liver donation surgery. A retrospective chart review was performed of 226 consecutive patients who underwent right living donor hepatic surgery at the Toronto General Hospital, Toronto, Canada. Patients who received as their primary postoperative analgesic modality IV PCA (n = 158) were compared to patients who received PCEA (n = 68). Demographic profiles for the 2 groups were similar with respect to age, sex, and body mass index at the time of surgery. For the first 3 postoperative days, pain intensity was significantly lower in patients who received epidural analgesia (P 4) was reported more frequently in the IV PCA group (P < 0.05) along with increased sedation (P < 0.05). Pruritus was reported more frequently in the PCEA group of patients compared to the IV PCA group (P < 0.05). Significant between-group differences were not found for the incidence of postoperative vomiting, the time at which patients began fluid intake, the time to initial ambulation, or the length of hospital stay. In conclusion, epidural analgesia provides better postoperative pain relief, less sedation, but more pruritus than IV PCA after live liver donation.

Liberal acceptance criteria are used when offering liver transplantation (LTx) for treatment of hepatocellular carcinoma (HCC) at our center. This provides a unique opportunity to assess outcomes in a large North American series of patients with advanced tumors.We hypothesized that acceptable survival rates can be achieved with LTx for any size or number of HCC provided that (a) imaging studies ruled out vascular invasion; (b) the HCC was confined to the liver; and (c) the HCC was not poorly differentiated on biopsy.Survival, based on pretransplant imaging staging, was compared between 189 Milan Criteria (M) and 105 beyond Milan Criteria (M+) HCC patients who received an LTx between 1996 and 2008.Imaging understaged 30% of the M group and over staged 23% of the M+ group. There was no difference in the 5-year overall survival in the M (72%) and M+ (70%) groups or 5-year disease-free survival in the M (70%) and M+ (66%) groups. The introduction of a protocol for a biopsy to exclude patients with poorly differentiated tumors and use of aggressive bridging therapy improved overall survival in the M+ group (P = 0.034). Serum alpha-fetoprotein more than 400 at LTx was associated with poorer disease-free survival (hazard ratio: 2.3; P = 0.031).Cross-sectional imaging did not reliably stage patients with HCC for LTx. A protocol using a biopsy to exclude poorly differentiated tumors and aggressive bridging therapy achieved excellent survival rates with LTx for otherwise incurable advanced HCC, irrespective of tumor size and number.

Background. Little is known about donors' perception and psychologic impact of the physical changes that occur after (open) living donor hepatectomy. The aim of this study was to examine the body image and scar satisfaction after donor hepatectomy and to measure the relationship to postdonation quality of life. Methods. Questionnaires measuring body image, cosmesis, and health-related quality of life were administered to 142 adults who underwent right lobe living donor hepatectomy between 2000 and 2007. Results. Liver donors reported a significantly lower body image and lower cosmetic satisfaction with their scar when compared with published data on donors who underwent open nephrectomy. Donors' predonation health concerns and the perception that the recipient was engaging in risky behavior posttransplant were associated with lower postdonation body image scores. In addition, younger age and non-white ethnicity were associated with lower cosmetic scores after donation. Donors with a lower perception of body image and cosmesis reported lower physical and mental health, based on scores on the 36-item Short-Form Health Survey health-related quality of life index, and significantly greater interference in both spousal relationships and their sex life. Younger donors and donors with perioperative complications were also more likely to report decreased confidence after donation. Conclusion. There are unique risk factors that predict a decreased perception of body image and cosmesis postdonation that may be useful in the donor evaluation process. Donors identified to be at risk for the development of a low perception of body image and cosmesis may require close follow-up and additional psychiatric services during the donation process.

In 2002, the New York State Committee on Quality Improvement in Living Liver Donation prohibited live liver donation for potential recipients with Model for End-stage Liver Disease (MELD) scores greater than 25. Despite the paucity of evidence to support this recommendation, many centers in North America remain reluctant to offer living donor (LD) to patients with moderate to high MELD scores.We analyzed 271 consecutive adult-to-adult right lobe LD liver transplants performed at our institution between 2002 and 2008 to study the relationship, between recipient MELD scores and the outcome of LD liver transplantation. The recipients were categorized according to their MELD score into a low (Low:25)and high (Hi:or=25) MELD group. We compared short-term donor morbidity, graft loss within 30 days, length of hospital stay, biochemical markers of hepatocyte injury and graft function, and 90 day posttransplant complications including infection, rejection, bleeding, and renal failure. Long-term posttransplant outcome was measured by graft and patient survival after 1-, 3-, and 5-years.Donor and recipient characteristics were similar between groups. Donor outcomes were similar in both groups. Peak recipient aspartat aminotransferase, alanine aminotransferase, and length of hospital stay were similar between both groups. The proportional decrease in postoperative INR and creatinine within the first week was greater in the high versus low MELD score group. High MELD score recipients had more frequent postoperative pneumonia (Low: 2.2% vs. Hi: 14%, P = 0.003), while no differences were observed in rates of biliary complications, rejection, renal failure, or overall infections. Recipients with a MELD25 versusor=25 had a similar 1-year (Low: 92% vs. Hi: 83%), 3-year (Low: 86% vs. Hi: 80%), and 5-year (Low: 78% vs. Hi: 80%) graft survival after LD liver transplantation (P = 0.51).LD liver transplantation can provide excellent graft function and survival rates in high MELD score recipients. Thus, when deceased donor organs are scare, a high MELD score alone should not be an absolute contraindication to living liver donation.

Many centers require a minimal graft to body weight ratio (GBWR) ≥ 0.8 as an arbitrary threshold to proceed with right-lobe living donor liver transplantation (RL-LDLT), and there is often hesitancy about transplanting lower volume living donor (LD) liver grafts into sicker patients. The data supporting this dogma, based on the early experience with RL-LDLT at Asian centers, are weak. To determine the effect of LD liver volume in the modern era, we investigated the impact of GBWR on the outcome of RL-LDLT with a GBWR as low as 0.6 at the University of Toronto. Between April 2000 and September 2008, 271 adult-to-adult RL-LDLT procedures and 614 deceased donor liver transplants were performed. Twenty-two living donor liver transplantation (LDLT) cases with a GBWR of 0.59 to 0.79 (group A) were compared with 249 LDLT cases with a GBWR ≥ 0.8 (group B) and with 66 full-graft deceased donor liver transplants (group C), who were matched 3:1 according to donor and recipient age, Model for End-Stage Liver Disease score, and presence of hepatitis C and hepatocellular carcinoma with the low-GBWR group. Portal vein shunts were not used. Markers of reperfusion injury [aspartate aminotransferase (AST) and alanine aminotransferase (ALT)], graft function (international normalized ratio and bilirubin), complications graded by the Clavien score, and graft and patient survival were compared. As expected, LD recipients had a significantly shorter cold ischemia time (94 ± 43 minutes for A, 96 ± 57 minutes for B, and 453 ± 152 minutes for C, P = 0.0001). However, the peak AST, peak ALT, absolute decrease in the international normalized ratio, day 7 bilirubin level, postoperative creatinine clearance, complication rate graded by the Clavien score, and median hospital stay were similar in all groups. The rate of biliary complications was higher with LD grafts than deceased donor grafts (19% for A versus 10% for B and 0% for C, P = 0.2). Patient survival was similar in all groups at 1, 3, and 5 years (91% for A versus 89% for B and 93% for C at 1 year, 87% for A versus 81% for B and 89% for C at 3 years, and 83% for A versus 81% for B and 87% for C at 5 years, P = 0.63). A Cox proportional regression analysis revealed only hepatitis C virus as a risk factor for poorer graft survival and not GBWR as a continuous or categorical variable. In conclusion, we found no evidence of inferior outcomes with smaller size grafts versus larger size LD grafts or full-size deceased donor grafts. Further studies are warranted to examine the factors affecting the function of smaller grafts for living liver donation and thereby define the safe lower limits for transplantation. Liver Transpl 15:1776–1782, 2009. © 2009 AASLD.

The ability to inform prospective donors of the psychosocial risks of living liver donation is currently limited by the scant empirical literature. The present study was designed to examine donor perceptions of the impact of donation on financial, vocational, and interpersonal life domains and identify demographic and clinical factors related to longer recovery times and greater life interference. A total of 143 donors completed a retrospective questionnaire that included a standardized measure of life interference [Illness Intrusiveness Rating Scale (IIRS)] and additional questions regarding the perceived impact of donation. Donor IIRS scores suggested that donors experience a relatively low level of life interference due to donation [1.60 ± 0.72, with a possible range of 1 (“not very much” interference) to 7 (“very much” interference)]. However, approximately 1 in 5 donors reported that donating was a significant financial burden. Logistic regression analysis revealed that donors with a psychiatric diagnosis at or prior to donation took longer to return to their self-reported predonation level of functioning (odds ratio = 3.78, P = 0.016). Medical complications were unrelated to self-reported recovery time. Multiple regression analysis revealed 4 independent predictors of greater life interference: less time since donation (b = 0.11, P < 0.001), income lower than CAD$100,000 (b = 0.28, P = 0.038), predonation concerns about the donation process (b = 0.24, P = 0.008), and the perception that the recipient is not caring for the new liver (b = 0.12, P = 0.031). In conclusion, life interference due to living liver donation appears to be relatively low. Donors should be made aware of risk factors for greater life disruptions post-surgery and of the potential financial burden of donation. Liver Transpl 15:1435–1442, 2009. © 2009 AASLD.

We studied the role of donor and recipient age in transplantation/ischemia-reperfusion injury (TIRI) and short- and long-term graft and patient survival. Eight hundred twenty-two patients underwent deceased donor liver transplantation, with 197 donors being ≥60 years old. We evaluated markers of reperfusion injury, graft function, and clinical outcomes as well as short- and long-term graft and patient survival. Increased donor age was associated with more severe TIRI and decreased 3- and 5-year graft survival (73% versus 85% and 72% versus 81%, P < 0.001) and patient survival (77% versus 88% and 77% versus 82%, P < 0.003). Hepatitis C virus (HCV) infection and recipient age were the only independent risk factors for graft and patient survival in patients receiving an older graft. In the HCV(+) cohort (297 patients), patients ≥ 50 years old who were transplanted with an older graft versus a younger graft had significantly decreased 3- and 5-year graft survival (68% versus 83% and 64% versus 83%, P < 0.009). In contrast, HCV(+) patients < 50 years old had similar 3- and 5-year graft survival if transplanted with either a young graft or an old graft (81% versus 82% and 81% versus 82%, P = 0.9). In conclusion, recipient age and HCV status affect the graft and patient survival of older livers. Combining older grafts with older recipients should be avoided, particularly in HCV(+) patients, whereas the effects of donor age can be minimized in younger recipients. Liver Transpl 15:1288–1295, 2009. © 2009 AASLD.

Hepatitis C recurs universally after liver transplantation (LT). Whether its progression differs after live donor liver transplantation (LDLT) and deceased donor liver transplantation (DDLT) is still debated. We retrospectively analyzed 201 consecutive LTs performed at our institution for hepatitis C–related end-stage liver disease between April 2000 and December 2005 (46 LDLTs and 155 DDLTs). Patients were followed with protocol biopsies for medians of 29 (LDLT) and 39 months (DDLT; P = 0.7). Although overall graft and patient survival did not differ, the mean fibrosis stage (Metavir) was significantly higher at 12 to 48 months post-LT (all P 45 years carried a relative risk of 8.17 (confidence interval = 2.6–25.5, P = 0.001) for reaching fibrosis stage 3 or 4 at 2 years post-LT. In conclusion, donor age, rather than the transplant approach, determines the progression of recurrent hepatitis C after LT. LDLT, allowing for the selection of younger donors, may particularly benefit hepatitis C patients. Liver Transpl 14:1778–1786, 2008. © 2008 AASLD.

Criteria for the selection of candidates for liver transplantation in the presence of hepatocellular carcinoma (HCC) should accurately predict posttransplant recurrence while not excluding excessive numbers of patients from candidacy. Existing criteria are challenged by the limited accuracy of radiological assessment. The total tumor volume (TTV) was calculated by the addition of the volume of each individual tumor. A preliminary analysis was carried out on HCC patient data from the Alberta Liver Transplant Program (52 patients) and then validated on the populations of the Universities of Toronto and Colorado programs (154 and 82 patients). A TTV cutoff of 115 cm(3) was chosen on the basis of the risk of recurrence with use of a receiver operating characteristic curve. Radiology correlated more closely to pathology with TTV than with Milan and University of California at San Francisco (UCSF) criteria (91% versus 69% and 75% of patients, P < 0.0001). Although more patients met qualifying criteria for transplant with TTV (28%-53% more than Milan and 16%-26% more than UCSF), no deterioration of outcome was demonstrated in an analysis of patients within TTV ≤ 115 cm(3) in comparison with those meeting Milan or UCSF classifications at all institutions. Patients with TTV > 115 cm(3) experienced more recurrences and lower patient survival in the Alberta and Colorado series (P < 0.05). When TTV with a cutoff of 115 cm(3) is used for candidate selection, the accuracy of pretransplant radiological assessment is enhanced, with posttransplant outcomes not different from those achieved with Milan and UCSF classifications despite a more inclusive patient population.

Objective: Identify an optimal approach to the timing of intestinal transplantation for children dependent on total parenteral nutrition (PN). Background Data: Children with short bowel syndrome are frequently dependent on PN for growth and development. Intestinal transplantation is often considered after PN-related complications occur, but optimal timing of transplantation is controversial. Methods: A Markov analytic model was used to determine life expectancy (LY) and quality-adjusted life years on a theoretical cohort of 4-year-old subjects for two treatment strategies: (1) standard care consisting of PN and referral to transplantation according to accepted guidelines and (2) early listing for isolated small intestine transplantation. Results: Early listing for intestinal transplantation was associated with 0.27 additional life years (13.16 vs. 12.89) and 0.76 additional quality-adjusted life years (10.51 vs. 9.75) as compared with current standard care. The unadjusted analysis was sensitive to the development of PN-associated liver disease, at a threshold of approximately 11% per year, and its related probability of dying at a threshold of 80% 2-year mortality. Early listing for transplantation was the dominant strategy until the probability of late bowel rejection reached 35% per year. Conclusions: Children with short bowel syndrome dependent on PN should be considered for intestinal transplantation earlier than what is current practice.

Background Patients with hepatic and pulmonary metastases from colorectal cancer (CRC) may benefit from aggressive surgical therapy. We examined the longterm outcomes of patients who underwent both lung and liver resections for colorectal metastases over a 10-year period. Study design Four hundred twenty-three hepatectomies were performed for metastatic CRC between 1992 and 2002 at two university-affiliated hospitals. Patients who underwent both lung and liver resections for metastatic CRC were studied. Demographic, perioperative, and survival data were evaluated by retrospective chart review. Disease-free survival (DFS) and overall survival (OS) were evaluated by Kaplan-Meier analysis and survival curves were compared using the log-rank test. Results Thirty-nine patients underwent both lung and liver resections for metastatic CRC. Eleven patients (28%) underwent staged liver and lung metastasectomy from synchronously identified metastases. Twenty-eight patients (72%) underwent sequential metastasectomy because of recurrent disease. The median disease-free and overall survivals after initial metastasectomy were 19.8 and 87months, respectively. Serial metastasectomy was common in this patient population. The mean number of metastasectomies performed was 2.6 per patient (range 1 to 4). There was no difference in overall survival for patients with synchronous versus metachronous presentation of liver and lung metastases (p=0.45). The site of first recurrence after initial metastasectomy was, most commonly, the lung (n=19, 49%), followed by the liver (n=8, 21%). Nineteen patients (49%) underwent subsequent resections for recurrences. Seven patients (18%) underwent 2 or more liver resections for recurrent disease, and 12 (31%) underwent multiple lung resections. Conclusions An aggressive multidisciplinary surgical approach should be undertaken for recurrent CRC metastases. In selected patients, serial metastasectomy for recurrent metastatic disease is safe and results in excellent longterm survival after CRC resection.

Early recurrence (ER) (1 year) after liver resection is one of the most important factors that impact the prognosis of patients with hepatocellular carcinoma (HCC). We sought to determine factors associated with ER of HCC and examine the outcomes thereafter.From March 2001 to June 2003, 56 patients underwent hepatic resection for HCC at University of Toronto and were prospectively followed with median followup of 24 months. Patients with ER were compared with those who remained disease free for more than 1 year. Patient characteristics, tumor stage, and operative procedures were evaluated for their prognostic significance by univariate and multivariable analysis. Time to recurrence and time to death were analyzed using Kaplan-Meier survival curves and compared using log-rank analysis.The initial procedure in all patients was surgical hepatectomy. ER occurred in 21 patients (38%), 31 (55%) remained disease free for more than 1 year, and 4 (7%) were omitted from evaluation because of early (30 days) death. Median survival after initial hepatic resection for those with ER was 27 months, and 2-year survival was 54%. There were no deaths in the group that remained disease free for more than 1 year (100% 2-year survival, p0.05). By multivariate analysis, vascular invasion and positive microscopic margins were significant predictors when all 4 variables were considered in the model (p0.05). After ER, 11 of 21 patients (52%) underwent additional therapy with significant improvement in median survival (33 months) compared with those not eligible for conventional therapy (18 months, p = 0.05).ER after liver resection for HCC is the leading cause of death during the first 2 years after potentially curative resection. ER will develop in approximately 75% of patients with either vascular invasion or positive margins. For patients with these predictive factors additional treatment might be advised.

Massive blood transfusion (MBT) remains a serious and common occurrence in liver transplantation surgery. This retrospective cohort study was undertaken to identify preoperative predictors of MBT and to develop a risk index for MBT in liver transplantation. Data were retrospectively collected on all liver transplantations carried out at a single institution between January 1998 and March 2004. Multivariable logistic regression analysis was used to identify independent predictor variables of MBT, defined as/=6 units of red blood cell concentrate (RBC) in the first 24 hours of surgery. The model was internally validated by bootstrapping. Of the 460 liver transplant recipients, 193 (42%) received/=6 units of RBC within 24 hours of surgery. Unadjusted analyses identified 12 preoperative predictors of MBT: age, height, gender, repeat transplantation, etiology of liver failure, and preoperative laboratory values (hemoglobin concentration, platelet count, international normalized ratio for prothrombin activity [INR], albumin, total bilirubin, and creatinine). In multivariable logistic regression, 7 independent predictors of MBT were identified: age (40 years), hemoglobin concentration (/=10.0 g/dL), INR (1.2-1.99, and2.0), platelet count (/=70 x 10(9)/L), creatinine (/=110 micromol/L for female subjects and/=120 micromol/L for male subjects), albumin (28 g/L), and repeat transplantation. The area under the receiver-operating characteristic curve (ROC) for the model was 0.82. By using the regression beta coefficients to derive weights for each of these predictors, a risk index was developed that assigned each patient a score between 0 and 8. The ROC for this risk index was 0.79. MBT in liver transplantation surgery can be accurately predicted by 7 readily available preoperative predictors.

Background Whether peritoneal dialysis is a risk factor for the development of intra-abdominal infection (IAI) after simultaneous pancreas kidney (SPK) transplantation is controversial. Methods We investigated the incidence of IAI, and patient and pancreas graft survival rates of 120 patients that received SPK between November 1995 and August 2003. All patients were dialysis-dependent prior to transplantation; mean duration of peritoneal dialysis (PD; n=52) and hemodialysis (HD; n=68) was 20+/-15 months and 23+/-16 months, respectively. Results IAI developed in five PD and six HD patients (P=0.88). The time of diagnosis of IAI and the spectrum of organisms cultured were similar in the two groups of patients. Age, duration of dialysis, and method of exocrine drainage did not have a significantly impact on infection rate. Patient and pancreas graft survival rates were 92.3% and 88.4% in the PD group and 95.5% and 92% HD group (p=ns) after a mean follow-up of 42+/-27 months and 39+/-27 months, respectively. Overall patient and pancreas graft survival was not significantly affected by IAI. Conclusions PD does not adversely affect IAI rate and is a safe mode of dialysis for patients awaiting SPK transplantation.

Objective: To determine if an aggressive surgical approach, with an increase in R0 resections, has resulted in improved survival for patients with gallbladder cancer. Summary Background Data: Many physicians express a relatively nihilistic approach to the treatment of gallbladder cancer; consensus among surgeons regarding the indications for a radical surgical approach has not been reached. Methods: A retrospective review of all patients with gallbladder cancer admitted during the past 12 years was conducted. Ninety-nine patients were identified. Cases treated during the 12-year period 1990 to 2002 were divided into 2 time-period (TP) cohorts, those treated in the first 6 years (TP1, N 35) and those treated in the last 6 years (TP2, N 64). Results: Disease stratification by stage and other demographic features were similar in the 2 time periods. An operation with curative intent was performed on 38 patients. Nine (26%) R0 resections were performed in TP1 and 24 (38%) in TP2. The number of liver resections, as well as the frequency of extrahepatic biliary resections, was greater in TP2 (P 0.04). In both time periods, an R0 resection was associated with improved survival (P 0.02 TP1, P 0.0001 TP2). Overall survival of all patients in TP2 was significantly greater than in TP1 (P 0.03), with a median survival of 9 months in TP1 and 17 months in TP2. The median 5-year survival in TP1 was 7%, and 35% in TP2. The surgical mortality rate for the entire cohort was 2%, with a 49% morbidity rate. Conclusions: A margin-negative, R0 resection leads to improved survival in patients with gallbladder cancer.

BACKGROUND The present study was undertaken to determine whether intravenous administration of GAS914, a polymeric form of alphaGal, would minimize porcine kidney xenograft rejection in baboons. Human decay accelerating factor renal xenografts were transplanted into 16 baboon recipients. METHODS Baseline immunosuppression for all groups included cyclosporine A, cyclophosphamide, SDZ-RAD, and methylprednisolone. Group 1 received only baseline immunosuppression; group 2 animals received low-dose GAS914 with baseline immunosuppression; group 3 animals received high dose GAS914 with high-dose baseline immunosuppression; and animals from group 4 received high-dose GAS914 and low-dose baseline immunosuppression. RESULTS None of the animals in this study developed hyperacute rejection. Intravenous administration of GAS914 significantly reduced xenoreactive antibodies as measured by antiporcine hemolytic assays and anti-Gal (immunoglobulin [Ig] G and IgM) antibody assays. Rejection was less severe in the GAS914-treated group. Only 25% (3 of 12) of GAS914-treated animals were killed as a result of rejection, whereas 75% (three of four) of non-GAS914-treated animals were killed because of terminal rejection (P

Background. Survival in pig-to-baboon kidney xenotransplantation is currently limited by acute humoral xenograft rejection (AHXR). We hypothesized that the administration of rabbit antithymocyte serum (RATS) would delay or prevent AHXR as compared with a cyclophosphamide (CyP)-based immunosuppressiv

Background. We evaluated patient characteristics of live donor liver transplant (LDLT) recipients undergoing a fast-track protocol without intensive care unit (ICU) admission versus LDLT patients receiving posttransplant ICU care. Methods. Of the 153 LDLT recipients, 46 patients were included in our fast-track protocol without ICU admission. Both, fast-tracked patients and ICU-admitted patients were compared regarding donor and patient characteristics, perioperative characteristics, and postoperative outcomes and complications. In a subgroup analysis, we compared fast-tracked patients with patients who were admitted in the ICU for less than 24 hours. Results. Fast-tracked versus ICU patients had a lower model for end-stage liver disease score (13 ± 4 vs 18 ± 7; P < 0.0001), lower preoperative bilirubin levels (51 ± 50 μmol/L vs 119.4 ± 137.3 μmol/L; P < 0.001), required fewer units of packed red blood cells (1.7 ± 1.78 vs 4.4 ± 4; P < 0.0001), and less fresh-frozen plasma (2.7 ± 2 vs 5.8 ± 5; P < 0.0001) during transplantation. Regarding postoperative outcomes, fast-tracked patients presented fewer bacterial infections within 30 days (6.5% [3] vs 29% [28]; P = 0.002), no episodes of pneumonia (0% vs 11.3% [11]; P = 0.02), and less biliary complications within the first year (6% [3] vs 26% [25]; P = 0.001). Also, fast-tracked patients had a shorter posttransplant hospital stay (10.8 ± 5 vs 21.3 ± 29; P = 0.002). In the subgroup analysis, fast-tracked vs ICU patients admitted for less than 24 hours had lower requirements of packed red blood cells (1.7 ± 1.78 vs 3.9 ± 4; P = 0.001) and fresh-frozen plasma (2.7 ± 2 vs 5.8 ± 4.5; P = 0.0001). Conclusions. Fast-track of selected patients after LDLT is safe and feasible. An objective score to perioperatively select LDLT recipients amenable to fast track is yet to be determined.

Posttransplant lymphoproliferative disease (PTLD) is associated with immunosuppression and lymphotrophic viral infections. Hepatitis C virus (HCV) has been identified as a risk factor for non-Hodgkin's lymphoma, but no association between HCV and PTLD has been shown. To investigate this possibility, we identified patients with HCV who received their first orthotopic liver transplant at our unit between January 1, 1992, and December 31, 1996, and compared them with contemporary liver transplant recipients without HCV for incidence and risk factors for PTLD and survival. Fifty-seven patients with HCV and 127 patients without HCV were compared. There was no age difference (52 v 53 years; P = .85), but there were more men in the HCV group (man-woman ratio, 2.1:1 v 0.9:1; P = .006). No difference was observed in the follow-up period, graft survival, rejection episodes, or use of different immunosuppressive regimes ( P > .05 for all). Four patients with HCV (7%) developed PTLD compared with 1 patient without HCV (0.8%; P = .02). The relative odds for developing PTLD in patients with HCV were 9.5. All patients who developed PTLD were administered OKT3 induction therapy. These data suggest that PTLD may be more prevalent in patients undergoing liver transplantation for HCV-related liver disease who also receive OKT3, and that HCV infection may be a risk factor for developing PTLD. (Liver Transpl 2000;6:570-574.)

Background. Clinical intestinal transplantation has been plagued by frequent and severe graft rejection. It has been proposed that the major histocompatibility complex (MHC) antigens might play a critical role in this process owing to their extensive expression on enterocytes and mucosa-associated immune cells. Methods. The present study examined the role of MHC antigens in intestinal graft rejection using MHC class I-deficient and MHC class II-deficient donors. Results. Grafts with normal MHC expression were rejected by 9 days, whereas survival was prolonged to 14 days in the MHC class II-deficient grafts (P=NS) and to 20 days in the MHC I-deficient grafts (P

With advances in microsurgery and molecular biology, the mouse model for organ transplantation has become increasingly popular. However, knowledge about these models is limited, as only a small number of centers have experience with murine models. In this study, we compared the rejection pattern after liver, kidney, heart, and small bowel transplantation in the three different mouse strain combinations: (1) C57BL/6 (H2b)-->BALB/c (H2d), (2) BALB/c (H2d)-->CBA (H2k), and (3) C57BL/6-->C3H/HeN (H2k). Our study demonstrated that mouse allograft survival varies depending on the organ graft and on the donor-recipient strain combinations. The majority of liver allografts were spontaneously accepted despite complete MHC disparity. A mixed pattern of acute rejection and acceptance occurred in kidney recipients depending on the donor-recipient strain combination. All the heart grafts developed rejection and all the intestinal grafts were rapidly rejected with no spontaneous acceptance. The criteria for rejection, the potential applications, and the limitations of each model are discussed. The models described in this article provide a number of useful choices for organ transplantation research.

In a recent series of 44 liver transplants we identified both extrapontine myelinolysis (EPM) - characteristic of cyclosporine neurotoxicity - and central pontine myelinolysis (CPM) in 5 recipients posttransplant. An additional 2 recipients had EPM only posttransplant. MRIs performed in 4 asymptomatic recipients were normal. Large perioperative shifts in serum sodium, hypomagnesemia, and high cyclosporine levels may play a role in the development of these lesions, although the evidence from this study is inconclusive. In addition to supportive care, dilantin was started in patients who had seizures; aggressive magnesium replacement was initiated for hypomagnesemia, and cyclosporine levels were reduced in all patients. All patients demonstrated a slow steady recovery and all but 2 are at home at the time of writing. CPM may be more prevalent than previously appreciated following liver transplantation, although its prognosis may not be as dismal.

The objective of this study was to study the factors affecting employment after liver transplantation. The employment status and health status of 203 adult liver transplant recipients was assessed retrospectively in a survey comprising an employment questionnaire, the Sickness Impact Profile (SID), and the Medical Outcomes Survey (MOS). The patient population consisted of all surviving adult patients who had undergone liver transplantation between 1982 and 1992 at our institution and who had survived a minimum of 9 months. Fifty-seven percent of the recipients were employed and 43% of the recipients were unemployed. Eighteen percent of the recipients considered themselves not well enough to work. Other reasons cited for not working in the unemployed patients were early retirement (8%), return to school (3%), family reasons (3%), no work available (3%), and chose not to work (3%). Patient age, duration of disability before transplantation, and type of job before transplantation significantly affected posttransplantation employment status. Health status measurements predicting employment were ambulation, home management, physical functioning, and pain. Older recipients and those who were continuously out of the workforce for several years before transplantation were the least likely to return to gainful employment after liver transplantation. These findings have implications for assessing the success of liver transplantation and the implementation of strategies to fully rehabilitate patients after liver grafting.

In addition to its role in absorbing nutrients, the intestinal mucosa provides an important barrier against toxins and bacteria in the bowel lumen. The present study evaluated gut barrier function following orthotopic (in continuity) intestinal grafting in rats. Graft histology, intestinal permeability, and bacterial translocation to the grafted mesenteric lymph nodes, the host's liver, and the host's spleen were assessed on the 3rd, 5th, and 7th postoperative days. The study group received no immunosuppression after allotransplantation. The two control groups included rats with isografts and rats with cyclosporine-treated allografts. On the 7th POD, the study animals had moderate transmural inflammation due to rejection, with normal histology in the isografts and CsA-treated allografts; increased intestinal permeability, measured by urinary excretion of oral 51Cr-EDTA (P less than 0.01); and increased number of bacteria in the MLN and spleen (P less than 0.05). The number of bacteria in the MLN and spleen of the study group positively correlated with the changes in intestinal permeability (P less than 0.05). Rejection of the orthotopic intestinal graft leads to increased intestinal permeability and bacterial translocation from the lumen of the graft to the host's reticuloendothelial system. Measures to improve gut barrier function and antibiotic therapy during rejection episodes may help reduce the incidence of septic complications after intestinal grafting.