A multicentre outcome analysis to define global benchmarks for donation after circulatory death liver transplantation

BACKGROUND: To identify the best possible outcomes in liver transplantation from donation after circulatory death donors (DCD) and to propose outcome values, which serve as reference for individual liver recipients or patient groups. METHODS: Based on 2219 controlled DCD liver transplantations, collected from 17 centres in North America and Europe, we identified 1012 low-risk, primary, adult liver transplantations with a laboratory MELD of ≤20points, receiving a DCD liver with a total donor warm ischemia time of ≤30minutes and asystolic donor warm ischemia time of ≤15minutes. Clinically relevant outcomes were selected and complications were reported according to the Clavien-Dindo-Grading and the Comprehensive Complication Index (CCI). Corresponding benchmark cut-offs were based on median values of each centre, where the 75(th)-percentile was considered. RESULTS: Benchmark cases represented between 19.7% and 75% of DCD transplantations in participating centers. The one-year retransplant and mortality rate was 5.23% and 9.01%, respectively. Within the first year of follow-up, 51.1% of recipients developed at least one major complication (≥Clavien-Dindo-Grade-III). Benchmark cut-offs were ≤3days and ≤16days for ICU and hospital stay, ≤66% for severe recipient complications (≥Grade-III), ≤16.8% for ischemic cholangiopathy, and ≤38.9CCI points at one-year posttransplant. Comparisons with higher risk groups showed more complications and impaired graft survival, outside the benchmark cut-offs. Organ perfusion techniques reduced the complications to values below benchmark cut-offs, despite higher graft risk. CONCLUSIONS: Despite excellent 1-year survival, morbidity in benchmark cases remains high with more than half of recipients developing severe complications during 1-year follow-up. Benchmark cut-offs targeting morbidity parameters offer a valid tool to assess the protective value of new preservation technologies in higher risk groups, and provide a valid comparator cohort for future clinical trials. LAY SUMMARY: The best possible outcomes after liver transplantation of grafts donated after circulatory death (DCD) were defined using the concept of benchmarking. These were based on 2219 liver transplantations following controlled DCD donation in 17 centres worldwide. The following benchmark cut-offs for the most relevant outcome parameters were developed: ICU and hospital stay: ≤3 and ≤16 days; primary non function: ≤2.5%; renal replacement therapy: ≤9.6%; ischemic cholangiopathy: ≤16.8% and anastomotic strictures ≤28.4%. One-year graft loss and mortality were defined as ≤14.4% and 9.6%, respectively. Donor and recipient combinations with higher risk had significantly worse outcomes. The use of novel organ perfusion technology achieved similar, good results in this high-risk group with prolonged donor warm ischemia time, when compared to the benchmark cohort

Collective benefits of an urban transformation: Restoring the Navigli in Milan

The aim of this paper is to assess the collective benefits for the metropolitan city of Milan arising from the project to restore the Navigli, the ancient urban canals flowing underground for a large part. In this paper two of the most important impacts of this urban transformation, mostly of intangible nature, are considered. On the one hand, the improvement of urban and environmental quality has been estimated through the hedonic price methodology, considering expected price changes both in the residential as well as in the commercial real estate markets; on the other hand, a multiplier effect on infrastructure investment, generating an increase in final income, has been calculated using Input–Output Tables. Empirical results confirm the collective net advantage of the urban transformation

A new ex-situ machine perfusion device. A preliminary evaluation using a model of donors after circulatory death pig livers

We herein describe a new ex-situ machine perfusion device as a "technology spotlight" using a model of donors after circulatory death liver grafts procured from slaughterhouse pigs. Fourteen pig liver grafts were included. The device allowed stable perfusion in both hypothermic (n = 6) and normothermic (n = 8) conditions and no technical failure was observed. During perfusion, perfusate and bile samples were collected to assess liver metabolism and viability. An integrated adsorption device showed efficient removal of inflammatory cytokines during treatment. This preliminary experience represents the starting point for further investigations on the potential clinical benefits of cytokines and other inflammatory mediators adsorption during machine perfusion

Pancreatic ductal adenocarcinoma complete regression after preoperative chemotherapy: Surgical results in a small series

Background: Pancreatic ductal adenocarcinoma (PDAC) becomes a systemic disease from an early stage. Complete surgical resection remains the only validated and potentially curative treatment; disappointingly only 20% of patients present with a resectable tumour. Although a complete pathological regression (pCR) after the preoperative chemotherapy could intuitively lead to better outcomes and prolonged survival some reports highlighted significant rates of recurrence. Cases Presentation: We describe three cases of pCR following preoperative chemotherapy for PDAC. The first two cases received neoadjuvant mFOLFIRINOX and PAX-G scheme for borderline resectable PDAC. Recurrence appeared 9 and 12 months after surgery. Although both patients started adjuvant therapy straight after the diagnosis of recurrence, the disease rapidly progressed and led them to death 12 and 15 months after surgery. The third case was characterized by germline BRCA2 mutation. The patient presented with PDAC of the body, intrapancreatic biliary stenosis and suspected peritoneal metastasis. One year later, after first and second-line chemotherapy, she underwent explorative laparoscopy and total spleno-pancreatectomy without evidence of viable tumour cells in the surgical specimen. At six months she is recurrence-free. Conclusions: Very few reports describe a complete pathological response following preoperative chemotherapy in pancreatic cancer. We observed three cases in the last three years with disappointing oncological results. Further investigations are needed to predict PDAC prognosis in pCR after chemotherapy

A multicentric evaluation of pediatric lung transplantation in Italy

Background: Pediatric lung transplantation is performed in highly experienced centers due to the peculiar population characteristics. The literature is limited and not representative of individual countries' differences. The purpose of this study was to analyze the Italian experience. Methods: A multicentric retrospective analysis was performed on 110 pediatric patients (<18 years old) who underwent lung transplantation from 1992 to 2019 at 9 Italian centers. Heart-lung transplantations and lung retransplantations were excluded. Results: The population was composed of 44 male and 66 female patients, with a median age of 15 years. The most frequent indication was cystic fibrosis (83%). One quarter of patients were transplanted in an emergency setting. Median donors' Oto score and age were 1 and 15 years, respectively, with 43% of adult donors. In 17% of patients a graft reduction was performed. Postoperatively, the median duration of mechanical ventilation, intensive care unit, and in-hospital stay were 48 hours, 11 and 35 days, respectively. Thirty-day mortality was 6%, and 1-, 5-, and 10-year survival was 72%, 52%, and 33%, respectively. Risk factors for mortality were Oto score and recipients' body mass index. Conclusions: The outcomes of pediatric lung transplantation in Italy are comparable with current literature. Particular attention should be paid to the Oto score and recipient body mass index. Conversely, adult donors and graft reductions can be safely used to expand the donor pool

How to Preserve Liver Grafts From Circulatory Death With Long Warm Ischemia? A Retrospective Italian Cohort Study With Normothermic Regional Perfusion and Hypothermic Oxygenated Perfusion

Donation after circulatory death (DCD) in Italy, given its 20-min stand-off period, provides a unique bench-test for normothermic regional perfusion (NRP) and dual hypothermic oxygenated machine perfusion (D-HOPE)