Biliary complications (BCs) still remain the Achilles heel of liver transplantation (LT) with an overall incidence of 10% to 35% in pediatric series. We hypothesized that (1) the use of alternative techniques (reduced size, split, and living donor grafts) in pediatric LT may contribute to an increased incidence of BCs, and (2) surgery as a first treatment option for anastomotic BCs could allow a definitive cure for the majority of these patients. Four hundred twenty-nine primary pediatric LT procedures, including 88, 91, 47, and 203 whole, reduced size, split, and living donor grafts, respectively, that were performed between July 1993 and November 2010 were retrospectively reviewed. Demographic and surgical variables were analyzed, and their respective impact on BCs was studied with univariate and multivariate analyses. The modalities of BC management were also reviewed. The 1- and 5-year patient survival rates were 94% and 90%, 89% and 85%, 94% and 89%, and 98% and 94% for whole, reduced size, split, and living donor liver grafts, respectively. The overall incidence of BCs was 23% (n = 98). Sixty were anastomotic complications [47 strictures (78%) and 13 fistulas (22%)]. The graft type was not found to be an independent risk factor for the development of BCs. According to a multivariate analysis, only hepatic artery thrombosis and acute rejection increased the risk of anastomotic BCs (P < 0.001 and P = 0.003, respectively). Anastomotic BCs were managed primarily with surgical repair in 59 of 60 cases with a primary patency rate of 80% (n = 47). These results suggest that (1) most of the BCs were anastomotic complications not influenced by the type of graft, and (2) the surgical management of anastomotic BCs may constitute the first and best therapeutic option. Liver Transpl 20:893–903, 2014. © 2014 AASLD.

With oxygenation proposed as a resuscitative measure during hypothermic models of preservation, the aim of this study was to evaluate the optimal start time of oxygenation during continuous hypothermic machine perfusion (HMP). In this porcine ischemia‐reperfusion autotransplant model, the left kidney of a ±40 kg pig was exposed to 30 minutes of warm ischemia prior to 22 hours of HMP and autotransplantation. Kidneys were randomized to receive 2 hours of oxygenation during HMP either at the start (n=6), or end of the perfusion (n=5) and outcomes were compared to standard, non‐oxygenated HMP (n=6) and continuous oxygenated HMP (n=8). The brief initial and continuous oxygenated HMP groups were associated with superior graft recovery compared to either standard, non‐oxygenated HMP or kidneys oxygenated at the end of HMP. This correlated with significant metabolic differences in perfusate (e.g. lactate, succinate, flavin mononucleotide) and tissues (e.g. succinate, ATP, HIF‐1α, Nrf2) suggesting superior mitochondrial preservation with initial oxygenation. Brief initial O₂ uploading during HMP at procurement site might be an easy and effective preservation strategy to maintain aerobic metabolism, protect mitochondria and achieve an improved early renal graft function compared with standard HMP or oxygen supply shortly at the end of HMP preservation.

The aims of this study were to determine the most optimal timing to start machine perfusion during kidney preservation to improve early graft function and evaluate the impact of temperature and oxygen supply during machine perfusion in a porcine ischemia‐reperfusion autotransplant model. The left kidney of a ±40 kg female landrace pig was exposed to 30 minutes of warm ischemia by vascular clamping and randomized to one of 6 study groups: 1) 22hr static cold storage (SCS)(n=6), 2) 22hr hypothermic machine perfusion (HMP)(n=6), 3) 22hr oxygenated HMP(n=7), 4) 20hr HMP + 2hr normothermic perfusion (NP)(n=6), 5) 20hr SCS + 2hr oxygenated HMP(n=7), and 6) 20hr SCS + 2hr NP(n=6). Graft recovery measured by serum creatinine was significantly faster in continuous HMP preservation strategies compared to SCS alone and to all end ischemic strategies. The active oxygenated 22hr HMP group demonstrated a significantly faster recovery from early graft function compared to the 22hr non‐active oxygenated HMP group. Active oxygenation was also found to be an important modulator of a faster increase in renal flow during HMP preservation. Continuous oxygenated HMP applied from time of kidney procurement until transplantation might be the best preservation strategy to improve early graft function.

The use of high-risk renal grafts for transplantation requires optimization of pretransplant preservation and assessment strategies to improve clinical outcomes as well as to decrease organ discard rate. With oxygenation proposed as a resuscitative measure during hypothermic machine preservation, this review provides a critical overview of the fundamentals of active oxygenation during hypothermic machine perfusion, as well as the current preclinical and clinical evidence and suggests different strategies for clinical implementation.

The use of high-risk renal grafts for transplantation requires the optimization of pretransplant assessment and preservation reconditioning strategies to decrease the organ discard rate and to improve short- and long-term clinical outcomes. Active oxygenation is increasingly recognized to play a central role in dynamic preservation strategies, independent of preservation temperature, to recondition mitochondria and to restore the cellular energy profile. The oxygen-related decrease in mitochondrial succinate accumulation ameliorates the harmful effects of ischemia-reperfusion injury. The differences between normothermic and hypothermic machine perfusion with regard to organ assessment, preservation, and reconditioning, as well as the logistic and economic implications, are factors to take into consideration for implementation at a local level. Therefore, these different techniques should be considered complementary to the perfusion strategy selected depending on functional intention and resource availability. This review provides an overview of the current clinical evidence of normothermic and oxygenated hypothermic machine perfusion, either as a continuous or end-ischemic preservation strategy, and future perspectives.