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    Un nuovo sistema di perfusione parenchimale per la preservazione del graft epatico per trapianto: valutazione sperimentale sul piccolo e grande animale

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    Background In liver transplantation one of the most important promblem which has not a solution yet is the large discrepancy between supply and demand for liver transplantation. To expand the pool of organs we should find the way to utilize marginal livers like the Non-heart-beating-donors ones and the fatty grafts. The use of these livers is associated with high incidence of post-operative primary dysfunction caused by the damage due to the Cold Storage preservation in the context of the process of ischaemia- reperfusion in extreme hypothermia (4° C). The utilization of new methods in the conservation of hepatic grafts like Machine Perfusion becomes necessary, especially for its ability to reduce the damage of ischaemia-reperfusion in hypothermia. The great potentiality of this Machine in sane and marginal organ preservation and the number of works which took place about it, stimulated us to the deepen this argument. Purpose We decided to create a experimental model of Machine Perfusion for pigs and to test it with different temperatures to obtain the best condition of perfusion and graft preservation. We based our study on the various works that can be find in literature and on the research developed by the Università di Pavia on rats. Methods We used in our experiments 15 Landrace pig of the weight of 22 kilos each. We divided them in three groups of study. Group C: after hepatectomy the pig liver was preserved in Cold Storage (4° C) for 8 hours. Group N: after hepatectomy the pig liver was perfused in Normothermic Machine Perfusion (37°C) for 8 hours. Group I: the pig liver was perfused in Moderate Hypothermic Machine (20°C). After the preservation, all the 15 livers were tested with a rewarming (37°C) of 2 hours. During the two hours of the experiment we performed samples of blood and biopsies and we also valuated the indocianine green clearance. Results The results obtained by the histology, the functional test and biochemical levels of AST, ALT and LDH, in the moderate hypothermic perfusion prove the superiority of this machine . Conclusion It is concluded after these experiments the great ability of 20°C Machine Perfusion in pig's liver transplantation. We think that this method of preservation will be able to improve the pool of donors using NHBD livers and fatty livers. In future our research will deepen the problematic connected with the preservation of marginal organs, in particular of steatotic livers

    Tyrosine phosphorylation and liver regeneration: A glance at intracellular transducers.

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    Liver regeneration (LR) is a compensatory growth that occurs in response to resection or injury of the liver aimed at restoring the liver mass and maintaining body homeostasis. The activation of intracellular signaling pathways due to extracellular stimuli mainly reflects a highly coordinated spatial and temporal organization of phosphotyrosine-based signals generated by the concerted action of three basic functional modules, namely protein tyrosine kinases, protein tyrosine phosphatases, and the Src homology 2 (SH2) domain. In this review, we have selected a set of signaling proteins downstream of activated cytokine and growth factor receptors that highlight the multifaceted aspects of tyrosine phosphorylation with their impact on the course of LR. Besides being a process of remarkable biological interest, LR has recently emerged as a model for dissecting molecular mechanisms underlying diverse pathophysiological states, offering new perspectives in primarily, but not only, managing life-threatening liver diseases

    Frozen-Section Diagnosis in Donor Livers: Error Rate Estimation of Steatosis Degree

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    A high degree of macrovesicular steatosis is associated with a significant risk of graft dysfunction. Most centers, including ours, consider 60% the limit value for transplantability, while others have adopted 30% as a cutoff. Pretransplant frozen-section (PFS) evaluation is used for reliable quantification of steatosis. However, the accuracy of PFS analysis for the degree of steatosis has largely been debated due to its high grade of variability and subjectivity. The aim of our study was to evaluate the accuracy of PFS diagnosis compared with subsequent paraffin histology samples. We retrospectively analyzed PFS from 52 consecutive liver donors. All PFS were blindly reviewed by two pathologists. The results were graded according to two classifications: (A) lower or higher than 60% steatosis, or (B) mild (0%-30%), moderate (30%-60%), or severe (>60%) steatosis. The rate of error for A (two-grade classification score) was 1.9% with the erroneous discharge of a viable organ. The error rate for B (three-grade classification score) was 7.7% with four discrepancies. In three cases, the discrepancy was related to the mild to moderate cutoff value, leading to a clinical error rate of 5.8% (discharging organs with statosis >30%, when we used more strict criteria). Our study validated PFS analysis as a reliable technique when the maximum value for organ transplantation was 60% steatosis. There was a higher error rate when a cutoff value of 30% was used. This finding suggests the usefulness of another technique to support a more precise steatosis evaluation
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