BackgroundThe 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.MethodsThis 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.DiscussionDHOPE 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 registrationThe trial was registered in Clinicaltrials.gov in September 2015 with the identifier NCT02584283.

Purpose: Biodistribution of bispecific antibodies in patients is largely unknown. We therefore performed a feasibility study in 9 patients with advanced gastrointestinal adenocarcinomas to explore AMG 211 biodistribution (also known as MEDI-565), an approximately 55 kDa bispecific T-cell engager (BiTE Ò) directed against carcinoembryonic antigen (CEA) on tumor cells and cluster of differentiation 3 (CD3) on T-cells. Experimental Design: 89 Zr-labeled AMG 211 as tracer was administered alone or with cold AMG 211, for PET imaging before and/or during AMG 211 treatment. Results: Before AMG 211 treatment, the optimal imaging dose was 200-mg 89 Zr-AMG 211 þ 1,800-mg cold AMG 211. At 3 hours, the highest blood pool standardized uptake value (SUV) mean was 4.0, and tracer serum half-life was 3.3 hours. CD3-mediated uptake was clearly observed in CD3-rich lym-phoid tissues including spleen and bone marrow (SUV mean 3.2 and 1.8, respectively), and the SUV mean decreased more slowly than in other healthy tissues. 89 Zr-AMG 211 remained intact in plasma and was excreted predominantly via the kidneys in degraded forms. Of 43 visible tumor lesions, 37 were PET quantifiable, with a SUV max of 4.0 [interquartile range (IQR) 2.7-4.4] at 3 hours using the optimal imaging dose. The tracer uptake differed between tumor lesions 5-fold within and 9-fold between patients. During AMG 211 treatment, tracer was present in the blood pool, whereas tumor lesions were not visualized, possibly reflecting target saturation. Conclusions: This first-inhuman study shows high, specific 89 Zr-AMG 211 accumulation in CD3-rich lymphoid tissues, as well as a clear, inter-and intraindividual heterogeneous tumor uptake.

Currently, biomarkers that predict the efficacy of everolimus in metastatic renal cell carcinoma (mRCC) patients are lacking. Everolimus inhibits vascular endothelial growth factor A (VEGF-A) expression. We performed PET scans on mRCC patients with Zr-bevacizumab, a VEGF-A-binding antibody tracer. The aims were to determine a change in tumor tracer uptake after the start of everolimus and to explore whetherZr-bevacizumab PET can identify patients with early disease progression. Zr-bevacizumab PET was done before and 2 and 6 wk after the start of everolimus, 10 mg/d, in mRCC patients. Routine CT scans were performed at baseline and every 3 mo thereafter. Tumor tracer uptake was quantified using SUV The endpoints were a change in tumor tracer uptake and treatment response on CT after 3 mo. Thirteen patients participated. The median SUV of 94 tumor lesions was 7.3 (range, 1.6-59.5). Between patients, median tumor SUV varied up to 8-fold. After 2 wk, median SUV was 6.3 (1.7-62.3), corresponding to a mean decrease of 9.1% ( < 0.0001). Three patients discontinued everolimus early. At 6 wk, a mean decrease in SUV of 23.4% compared with baseline was found in 70 evaluable lesions of 10 patients, with a median SUV of 5.4 (1.1-49.4, < 0.0001). All 10 patients who continued treatment had stable disease at 3 mo. Everolimus decreasesZr-bevacizumab tumor uptake. Further studies are warranted to evaluate the predictive value of Zr-bevacizumab PET for everolimus antitumor efficacy.