Tesi etd-03132018-121208 |
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Tipo di tesi
Tesi di dottorato di ricerca
Autore
PEZZATI, DANIELE
URN
etd-03132018-121208
Titolo
Pilot, Open, Monocentric, Randomized, Prospective Trial for the Evaluation of the Efficacy of Normothermic Perfusion Machine for Organ Preservation in Liver Transplantation Using Brain Death Donors Older or Equal Than 70 Years
Settore scientifico disciplinare
MED/18
Corso di studi
FISIOPATOLOGIA CLINICA
Relatori
tutor Prof. Filipponi, Franco
tutor Prof. De Simone, Paolo
tutor Prof. De Simone, Paolo
Parole chiave
- liver transplantation
- NMP
Data inizio appello
30/03/2018
Consultabilità
Completa
Riassunto
Ex-situ normothermic machine perfusion (NMP) has the potential to minimize ischemia/reperfusion injury of liver grafts. Twenty primary, whole-size, adult, consenting liver transplants (LT) recipients of older grafts (≥70 years) were randomized 1:1 to NMP or to cold storage (CS). The study primary endpoints were: the posttransplant transaminase peak level; the 6-month graft and patient survival, and the cumulative incidence of ischemic-type biliary lesions. Liver and bile duct biopsies were collected at bench surgery, end of ex-situ NMP, and end of transplant surgery. Interleukin (IL) 6, 10 and TNF-α perfusate concentrations were tested during NMP.
Mean donor age was 80.9±4.5 and 80.9±8.9 for NMP and CS, respectively(p=0.64). Mean ex-situ time was 510±96 minutes for NMP (including a mean NMP time of 242±63) and 478±57 for CS (p=0.24). All grafts were successfully transplanted. Mean posttransplant AST peak was 1057±909 and 882±824 UI/L, for NMP and CS respectively (p=0.34). One hepatic artery thrombosis for NMP and one death for CS group were observed. In NMP, we observed high perfusate IL-6 and IL-10 levels and these were inversely correlated with TNF-α and lactate (p<0.001 (cos’è questo valore?). Electron microscopy showed decreased mitochondrial volume density and steatosis and increased volume density of autophagic vacuoles at the end of LT in NMP versus CS patients (p<0.001).
Use of NMP for older liver grafts is associated with histologic evidence of lower ischemia/reperfusion injury, although the clinical benefit remains to be demonstrated.
Mean donor age was 80.9±4.5 and 80.9±8.9 for NMP and CS, respectively(p=0.64). Mean ex-situ time was 510±96 minutes for NMP (including a mean NMP time of 242±63) and 478±57 for CS (p=0.24). All grafts were successfully transplanted. Mean posttransplant AST peak was 1057±909 and 882±824 UI/L, for NMP and CS respectively (p=0.34). One hepatic artery thrombosis for NMP and one death for CS group were observed. In NMP, we observed high perfusate IL-6 and IL-10 levels and these were inversely correlated with TNF-α and lactate (p<0.001 (cos’è questo valore?). Electron microscopy showed decreased mitochondrial volume density and steatosis and increased volume density of autophagic vacuoles at the end of LT in NMP versus CS patients (p<0.001).
Use of NMP for older liver grafts is associated with histologic evidence of lower ischemia/reperfusion injury, although the clinical benefit remains to be demonstrated.
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