Outcomes of left split graft transplantation in Europe: report from the European Liver Transplant Registry

Split liver transplantation (SLT) has been widely adopted across Europe, resulting in remarkable reduction in the paediatric waiting-list mortality. Left split graft (LSG) is commonly used for paediatric recipients; however, deceased donor criteria selection are not universal. The aim of this study was to analyse the LSG outcome from the European Liver Transplant Registry and to identify risk factors for graft failure. Data from 1500 children transplanted in 2006-2014 with LSG from deceased donors were retrospectively analysed. Overall, graft losses were 343(22.9%) after 5 years from transplantation, 240(70.0%) occurred within the first 3 months. Estimated patient survival was 89.1% at 3 months and 82.9% at 5 years from SLT. Re-transplantation rate was 11.5%. At multivariable analysis, significant risk factors for graft failure at 3 months included the following: urgent SLT (HR = 1.73, P = 0.0012), recipient body weight ≤6 kg (HR = 1.91, P = 0.0029), donor age >50 years (HR = 1.87, P = 0.0039), and cold ischaemic time (CIT) [HR = 1.07 per hour, P = 0.0227]. LSG has good outcomes and SLT is excellent option for paediatric recipients in the current organ shortage era. We identified practical guidelines for LSG donor and recipient selection criteria: donor age may be safely extended up to 50 years in the absence of additional risk factors; thus, children <6 kg and urgent transplantation need CIT <6 h and appropriate graft/recipient size-matching to achieve good outcomes

Study protocol for a multicenter randomized controlled trial to compare the efficacy of end-ischemic dual hypothermic oxygenated machine perfusion with static cold storage in preventing non-anastomotic biliary strictures after transplantation of liver grafts donated after circulatory death: DHOPE-DCD trial

Background: The major concern in liver transplantation of grafts from donation after circulatory death (DCD) donors remains the high incidence of non-anastomotic biliary strictures (NAS). Machine perfusion has been proposed as an alternative strategy for organ preservation which reduces ischemia-reperfusion injury (IRI). Experimental studies have shown that dual hypothermic oxygenated machine perfusion (DHOPE) is associated with less IRI, improved hepatocellular function, and better preserved mitochondrial and endothelial function compared to conventional static cold storage (SCS). Moreover, DHOPE was safely applied with promising results in a recently performed phase-1 study. The aim of the current study is to determine the efficacy of DHOPE in reducing the incidence of NAS after DCD liver transplantation. Methods: This is an international multicenter randomized controlled trial. Adult patients (≥18 yrs. old) undergoing transplantation of a DCD donor liver (Maastricht category III) will be randomized between the intervention and control group. In the intervention group, livers will be subjected to two hours of end-ischemic DHOPE after SCS and before implantation. In the control group, livers will be subjected to care as usual with conventional SCS only. Primary outcome is the incidence of symptomatic NAS diagnosed by a blinded adjudication committee. In all patients, magnetic resonance cholangiography will be obtained at six months after transplantation. Discussion: DHOPE is associated with reduced IRI of the bile ducts. Whether reduced IRI of the bile ducts leads to lower incidence of NAS after DCD liver transplantation can only be examined in a randomized controlled trial. Trial registration: The trial was registered in Clinicaltrials.gov in September 2015 with the identifier NCT02584283

Systematic review with meta-analysis of the epidemiological evidence relating smoking to COPD, chronic bronchitis and emphysema

<p>Abstract</p> <p>Background</p> <p>Smoking is a known cause of the outcomes COPD, chronic bronchitis (CB) and emphysema, but no previous systematic review exists. We summarize evidence for various smoking indices.</p> <p>Methods</p> <p>Based on MEDLINE searches and other sources we obtained papers published to 2006 describing epidemiological studies relating incidence or prevalence of these outcomes to smoking. Studies in children or adolescents, or in populations at high respiratory disease risk or with co-existing diseases were excluded. Study-specific data were extracted on design, exposures and outcomes considered, and confounder adjustment. For each outcome RRs/ORs and 95% CIs were extracted for ever, current and ex smoking and various dose response indices, and meta-analyses and meta-regressions conducted to determine how relationships were modified by various study and RR characteristics.</p> <p>Results</p> <p>Of 218 studies identified, 133 provide data for COPD, 101 for CB and 28 for emphysema. RR estimates are markedly heterogeneous. Based on random-effects meta-analyses of most-adjusted RR/ORs, estimates are elevated for ever smoking (COPD 2.89, CI 2.63-3.17, n = 129 RRs; CB 2.69, 2.50-2.90, n = 114; emphysema 4.51, 3.38-6.02, n = 28), current smoking (COPD 3.51, 3.08-3.99; CB 3.41, 3.13-3.72; emphysema 4.87, 2.83-8.41) and ex smoking (COPD 2.35, 2.11-2.63; CB 1.63, 1.50-1.78; emphysema 3.52, 2.51-4.94). For COPD, RRs are higher for males, for studies conducted in North America, for cigarette smoking rather than any product smoking, and where the unexposed base is never smoking any product, and are markedly lower when asthma is included in the COPD definition. Variations by sex, continent, smoking product and unexposed group are in the same direction for CB, but less clearly demonstrated. For all outcomes RRs are higher when based on mortality, and for COPD are markedly lower when based on lung function. For all outcomes, risk increases with amount smoked and pack-years. Limited data show risk decreases with increasing starting age for COPD and CB and with increasing quitting duration for COPD. No clear relationship is seen with duration of smoking.</p> <p>Conclusions</p> <p>The results confirm and quantify the causal relationships with smoking.</p

Lack of a correlation between portal vein flow and pressure: toward a shared interpretation of hemodynamic stress governing inflow modulation in liver transplantation

The portal vein flow (PVF), portal vein pressure (PVP), and hepatic venous pressure gradient (HVPG) were prospectively assessed to explore their relationships and to better define hyperflow and portal hypertension (PHT) during liver transplantation (LT). Eighty-one LT procedures were analyzed. No correlation between PVF and PVP was observed. Increases in the central venous pressure (CVP) were transmitted to the PVP (58%, range 25%-91%, P = 0.001). Severe PHT (HVPG >= 15 mm Hg) showed a significant reciprocal association with high PVF (P = 0.023) and lower graft survival (P = 0.04). According to this initial experience, an HVPG value >= 15 mm Hg is a promising tool for the evaluation of hemodynamic stress potentially influencing outcomes. An algorithm for graft inflow modulation based on flows, gradients, and systemic hemodynamics is provided. In conclusion, the evaluation of PHT severity with PVP could be delusive because of the influence of CVP. PVF and PVP do not correlate and should not be used individually to assess hyperflow and PHT during LT

Liver venous deprivation versus associating liver partition and portal vein ligation for staged hepatectomy for colo-rectal liver metastases: a comparison of early and late kinetic growth rates, and perioperative and oncological outcomes

Background: Different techniques have been developed to optimize the Future Liver Remnant (FLR). Associated liver partition and portal vein ligation for staged hepatectomy (ALPPS) and liver venous deprivation (LVD) have shown the higher hypertrophy rates, but their place in clinical practice is still debated. Methods: Thirty-two consecutive ALPPS and LVD procedures for CRLM performed between December 2015 and December 2019 were included. This retrospective study evaluated kinetic growth rates (KGR) as primary outcome, and perioperative and oncological outcomes as secondary endpoints. Results: A total of 17 patients underwent LVD before surgery, whereas 15 underwent ALPPS. On early evaluation (7 vs 9 days, respectively), KGR did not differ between ALPPS and LVD cohort (0.8% per day vs 0.3% per day, p = 0.70; 23 cc/day vs 26 cc/day, p = 0.31). Late evaluation (21 vs 9 days) showed a KGR significantly decreased in the LVD group (0.6% per day vs 0.2% per day, p = 0.21; 20 cc/day vs 10 cc/day p = 0.02). Mean FLR-V increase was comparable in the two groups (60% vs 49%, p 0.32). Successful resection rate was 100% and 94% in LVD and ALPPS group, respectively. The hospital stay (p < 0.0001) and severe complications rate (p = 0.05) were lower after LVD. One and 3-years overall survival (OS) were 72,7% and 27,4% in the ALPSS group, versus 81,3% and 54,7% in LVD group (p = 0.10). The Median DFS was comparable between both techniques (6.1 months and 5.9 respectively, p = 0.66). Conclusions: LVD and ALPPS shows similar KGR during the early period following preparation as well as similar survival outcomes. Hospital stay and severe complications are lower after LVD

Prospective evaluation of intraoperative hemodynamics in liver transplantation with whole, partial and DCD grafts.

The interaction of systemic hemodynamics with hepatic flows at the time of liver transplantation (LT) has not been studied in a prospective uniform way for different types of grafts. We prospectively evaluated intraoperative hemodynamics of 103 whole and partial LT. Liver graft hemodynamics were measured using the ultrasound transit time method to obtain portal (PVF) and arterial (HAF) hepatic flow. Measurements were recorded on the native liver, the portocaval shunt, following reperfusion and after biliary anastomosis. After LT HAF and PVF do not immediately return to normal values. Increased PVF was observed after graft implantation. Living donor LT showed the highest compliance to portal hyperperfusion. The amount of liver perfusion seemed to be related to the quality of the graft. A positive correlation for HAF, PVF and total hepatic blood flow with cardiac output was found (p = 0.001). Portal hypertension, macrosteatosis > 30%, warm ischemia time and cardiac output, independently influence the hepatic flows. These results highlight the role of systemic hemodynamic management in LT to optimize hepatic perfusion, particularly in LDLT and split LT, where the highest flows were registered

Prospective Evaluation of Intraoperative Hemodynamics in Liver Transplantation with Whole, Partial and DCD Grafts (vol 8, pg 1850, 2010)

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