With the aim to explore innovative tools for organ preservation, especially in marginal organs, we hereby describe a clinical trial of ex-vivo hypothermic oxygenated perfusion (HOPE) in the field of ...liver (LT) and kidney transplantation (KT) from Extended Criteria Donors (ECD) after brain death. A matched-case analysis of donor and recipient variables was developed: 10 HOPE-ECD livers and kidneys (HOPE-L and HOPE-K) were matched 1:3 with livers and kidneys preserved with static cold storage (SCS-L and SCS-K). HOPE and SCS groups resulted with similar basal characteristics, both for recipients and donors. Cumulative liver and kidney graft dysfunction were 10% (HOPE L-K) vs. 31.7%, in SCS group (p = 0.05). Primary non-function was 3.3% for SCS-L vs. 0% for HOPE-L. No primary non-function was reported in HOPE-K and SCS-K. Median peak aspartate aminotransferase within 7-days post-LT was significantly higher in SCS-L when compared to HOPE-L (637 vs.344 U/L, p = 0.007). Graft survival at 1-year post-transplant was 93.3% for SCS-L vs. 100% of HOPE-L and 90% for SCS-K vs. 100% of HOPE-K. Clinical outcomes support our hypothesis of machine perfusion being a safe and effective system to reduce ischemic preservation injuries in KT and in LT.
Left ventricular assist device (LVAD) support in donors may contribute in preserving proper haemodynamics and systemic perfusion during organ retrieval thus decreasing the risk of multiple organ ...injury. This is an option to expand the current organ supply. We report on intra-abdominal organs procurement strategy in a selected LVAD recipient who suffered a fatal cerebrovascular accident at the time of COVID-19 pandemic outbreak. The liver and kidneys grafts have been successfully transplanted.
The objective of the study is to evaluate 10 years of down-staging strategy for liver transplantation (LT) with a median follow-up of 5 years. Data on long-term results are poor and less information ...is available for hepatocellular carcinoma (HCC) non-responder patients or those ineligible for down-staging. The outcome of 308 HCC candidates and the long-term results of 231 LTs for HCC performed between 2003 and 2013 were analyzed. HCCs were divided according to tumor stage and response to therapy: 145 patients were T2 (metering Milan Criteria, MC), 43 were T3 successfully down-staged to T2 (Down-Achieved), 20 were T3 not fully down-staged to T2 (Down-not Achieved), and 23 patients were T3 not receiving down-staging treatments (No-Down). The average treatment effect (ATE) of LT for T3 tumors was estimated using the outcome of 535 T3 patients undergoing non-LT therapies, using inverse probability weighting regression adjustment. The 24-month drop-out rate during waiting time was significantly higher in the down-staging groups: 27.6% vs. 9.2%, p < 0.005. After LT, the tumor recurrence rate was significantly different: MC 7.6%, Down-Achieved 20.9%, Down-not Achieved 31.6%, and No-Down 30.4% (p < 0.001). The survival rates at 5 years were: 63% in Down-Achieved, 62% in Down-not Achieved, 63% in No-Down, and 77% in MC (p = n.s.). The only variable related to a better outcome was the effective down-staging to T2 at the histological evaluation of the explanted liver: recurrence rate = 7.8% vs. 26% (p < 0.001) and 5-year patient survival = 76% vs. 67% (p < 0.05). The ATE estimation showed that the mean survival of T3-LT candidates was significantly better than that of T3 patients ineligible for LT 83.3 vs 39.2 months (+44.6 months); p < 0.001. Long term outcome of T3 down-staged candidates was poorer than that of MC candidates, particularly for cases not achieving down-staging. However, their survival outcome was significantly better than that achieved with non-transplant therapies.
The poor availability of kidney for transplantation has led to a search for new strategies to increase the donor pool. The main option is the use of organs from extended criteria donors. We evaluated ...the effects of hypothermic oxygenated perfusion (HOPE) with and without extracellular vesicles (EV) derived from mesenchymal stromal cells on ischemic/reperfusion injury of marginal kidneys unsuitable for transplantation. For normothermic reperfusion (NR), we used artificial blood as a substitute for red blood cells. We evaluated the global renal ischemic dam-age score (GRS), analyzed the renal ultrastructure (RU), cytochrome c oxidase (COX) IV-1 (a mitochondrial distress marker), and caspase-3 renal expression, the tubular cell proliferation index, hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF) tissue levels, and effluent lactate and glucose levels. HOPE+EV kidneys had lower GRS and better RU, higher COX IV-1 expression and HGF and VEGF levels and lower caspase-3 expression than HOPE kidneys. During NR, HOPE+EV renal effluent had lower lactate release and higher glucose levels than HOPE renal effluent, suggesting that the gluconeogenesis system in HOPE+EV group was pre-served. In conclusion, EV delivery during HOPE can be considered a new organ preservation strategy for increasing the donor pool and improving transplant outcome.
Normothermic and hypothermic oxygenated perfusion for donation after circulatory death in kidney transplantation are becoming popular in Italy, with the purpose of reducing the risk of primary non ...function and delayed graft function due to the prolonged warm ischemia time. Potential complications related to these procedures are currently under investigation and are continuously emerging with the increasing experience. Post-operative infections - in particular graft arteritis - are a rare complication but determine high risk of mortality and of graft loss. The acute onset of the arterial complications makes it very difficult to find an effective treatment, and early diagnosis is crucial for saving both patient and graft. Prevention of such infections in this particular setting are advisable.
We present a patient with an acute arterial rupture after transplantation of a DCD graft treated in-vivo hypothermic oxygenated perfusion. The cause was a severe arteritis of the renal artery caused by Candida krusei and Pseudomonas aeruginosa. We discussed our treatment and we compared it to the other reported series.
Fungal infections in DCD transplant may be treacherous and strategies to prevent them should be advocated.
Organ shortage is one of the major limitations in the field of liver transplantation, which has led to the consideration of extended criteria donors as a way to expand the donor pool. The use of ...extended criteria donors in cases of high Model for End-Stage Liver Disease scores or urgent recipients could be complicated by increased postoperative mortality. Donors on left ventricular assist devices could be considered extended criteria donors because of the mechanical circulatory support itself and the potential of chronic liver damage due to right ventricular failure, but experiences in the literature are limited. Here, we report the first case of an urgent liver retransplant procured from a left ventricular assist device donor.
Cholesterol embolization (CE) is a rare and alarming post-transplant complication, responsible for primary non-function (PNF) or delayed graft function (DGF). Its incidence is expected to rise due to ...increasingly old donors and recipients and the extended criteria for donation. Therapy with statins and steroids has not been shown to be effective, while agonism of prostaglandin I
has been reported to be useful in systemic CE. We report two cases of acute post-transplant CE in which intravenous iloprost (0.05 mg/kg/day) was added to standard statin and steroid therapy. In the first instance, CE was due to embolization from the kidney artery resulting in embolization of the small vessels; after a long DGF and 15 days of iloprost therapy, renal function recovered. The second instance is a case of embolization from the iliac artery of the recipient, where CE manifested as a partial renal infarction. After 5 days of iloprost administration, creatinine levels improved. Iloprost acts on vasodilation and on different inflammatory pathways, improving the anti-inflammatory profile. Post-transplant CE is difficult to diagnose and, if not treated, can lead to loss of function. Iloprost added to standard therapy could be beneficial in accelerating renal function recovery immediately after transplant.
Hypothermic Oxygenated Perfusion (HOPE) of the liver can reduce the incidence of early allograft dysfunction (EAD) and failure in extended criteria donors (ECD) grafts, although data from prospective ...studies are very limited. In this monocentric, open‐label study, from December 2018 to January 2021, 110 patients undergoing transplantation of an ECD liver graft were randomized to receive a liver after HOPE or after static cold storage (SCS) alone. The primary endpoint was the incidence of EAD. The secondary endpoints included graft and patient survival, the EASE risk score, and the rate of graft or other graft‐related complications. Patients in the HOPE group had a significantly lower rate of EAD (13% vs. 35%, p = .007) and were more frequently allocated to the intermediate or higher risk group according to the EASE score (2% vs. 11%, p = .05). The survival analysis confirmed that patients in the HOPE group were associated with higher graft survival one year after LT (p = .03, log‐rank test). In addition, patients in the SCS group had a higher re‐admission and overall complication rate at six months, in particular cardio‐vascular adverse events (p = .04 and p = .03, respectively). HOPE of ECD grafts compared to the traditional SCS preservation method is associated with lower dysfunction rates and better graft survival.
A single‐center randomized study shows that hypothermic oxygenated perfusion is associated with lower graft dysfunction rates and better graft survival in extended criteria donor liver transplantation.
Liver stiffness measurement (LSM), assessed by transient elastography (Fibroscan), has been demonstrated to predict post-hepatectomy liver failure in patients who undergo hepatic resection for ...hepatocellular carcinoma (HCC). However, other complications are also likely to be related to the underlying grade of liver fibrosis. Herein, we aimed to identify predictors of postoperative complications and to build and develop a novel nomogram able to identify patients at risk of developing severe complications.
Data from patients who underwent hepatectomy for HCC between 2006 and 2016 at 2 referral centres were retrospectively reviewed. All surgical complications were recorded and scored using the comprehensive complication index (CCI), ranging from 0 (uneventful course) to 100 (death). A CCI ≥26.2 was used as a threshold to define severe complications.
During the study period, 471 patients underwent hepatic resection for HCC. Among them, 50 patients (10.6%) had a CCI ≥26.2. Age, model for end-stage liver disease (MELD) score and LSM values, together with serum albumin, were independent predictors of high CCI. The nomogram built on these variables was internally validated and showed good performance (optimism-corrected c-statistic = 0.751). A regression equation to predict the CCI was also established by multiple linear regression analysis: LSM (kPa) × 0.254 + age (years) × 0.118 + MELD score (pt.) × 1.050 − albumin (g/dl) × 2.395 − 3.639.
A novel nomogram, combining LSM values, age and liver function tests provided an excellent preoperative prediction of high CCI in patients with resectable HCC. This predictive model could be used as a reference for clinicians and surgeons to help them in clinical decision-making.
Liver stiffness measurement is increasingly being used to assess the degree of liver fibrosis in patients with cirrhosis and/or chronic hepatitis. Using Fibroscan, we developed a novel nomogram to predict severe complications following liver resection for hepatocellular carcinoma, according to the new comprehensive complication index. This tool could be used as a reference for clinicians and surgeons to help them in clinical decision-making.
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•Liver stiffness measurement (LSM) is emerging as the most promising non-invasive test to predict decompensation after resection.•Little is known about the predictive role of LSM on the occurrence of other complications after resection.•A novel nomogram based on LSM, liver function tests and age was built to predict severe postoperative complications.•This nomogram will serve as a reference for clinicians and surgeons to help them with pre-operative decision-making.
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