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Lymph nodes (LNs)’ metastases have a well-known detrimental impact on the survival outcomes of patients suffering from pancreatic cancer of the body and tail. However, the extent of the lymphadenectomy for this tumor location is still debated. The aim of this study was to systematically review the current literature to explore the incidence and the prognostic impact of non-peripancreatic lymph nodes (PLNs) in patients suffering from pancreatic cancer of the body and tail. A systematic review was conducted according to PRISMA and MOOSE guidelines. The primary endpoint was to assess the impact of non-PLNs on overall survival (OS). As a secondary endpoint, the pooled frequencies of different non-PLN stations’ metastatic patterns according to tumor location were explored. Eight studies were included in data synthesis. An increased risk of death for patients with positive non-PLNs was detected (HR: 2.97; 95% CI: 1.81–4.91; p < 0.0001). Meta-analysis of proportions pointed out a 7.1% pooled proportion of nodal infiltration in stations 8–9. The pooled frequency for station 12 metastasis was 4.8%. LN stations 14–15 were involved in 11.4% of cases, whereas station 16 represented a site of metastasis in 11.5% of cases. Despite its potential beneficial effect on survival outcome, a systematic extended lymphadenectomy could not be recommended yet for patients suffering from PDAC of the body/tail.

In Italy, 20 minutes of continuous, flat-line electrocardiogram are required for declaration of death. In the setting of organ donation after cardiocirculatory death (DCD), prolonged warm ischemia time prompted introduction of abdominal normothermic regional perfusion (NRP) followed by post-procurement, ex-situ machine perfusion. This was a retrospective review of DCD liver transplantations performed at two centers using sequential NRP and ex-situ machine perfusion. From January 2018 to April 2019, 34 DCD donors were evaluated. Three (8.8%) were discarded before NRP, 11 (32.4%) based on NRP parameters (n=1, 3.0%), liver macroscopic appearance at procurement and/or biopsy results (n=9, 26.5%), or severe macroangiopathy at back table evaluation (N=1, 3.0%). Twenty grafts (58.8%) (12 uncontrolled DCD, 8 controlled DCD) were considered eligible for LT, procured and perfused ex-situ (9 normothermic and 11 dual hypothermic machine perfusion). Eighteen (52.9%; 11 uncontrolled) were eventually transplanted. Median (IQR) no-flow time was 32.5 (30-39) minutes, while median functional-warm ischemia time was 52.5 (47-74) minutes (controlled DCD) and median low-flow time 112 (105-129) minutes (uncontrolled DCD). There was no primary non-function, while post-reperfusion syndrome occurred in 8 (44%) recipients. Early allograft dysfunction happened in 5 (28%) patients, while acute kidney injury in 5 (28%). After a median follow up of 15.1 (9.5-22.3) months, one case of ischemic-type biliary lesion and one patient death were reported. DCD liver transplantation is feasible even with the 20-minute no-touch rule. Strict normothermic regional perfusion and ex-situ machine perfusion selection criteria are needed to optimize post-operative results.

Ex-situ machine perfusion (MP) techniques are increasingly used in clinical settings, especially on grafts derived from donors after cardiac death (DCD). However, comprehension of biological effects elicited during MP are largely unknown and a substantial number of animal studies are presently focused on this topic. The aim of the present study was to describe a model of DCD based on ex-situ perfusion of liver grafts derived from animals dedicated to food production. Procurement took place within a slaughterhouse facility. A clinically fashioned closed circuit normothermic MP (NMP) was built up. Autologous blood-enriched perfusion fluid was adopted. Perfusate and tissue samples were collected to asses NMP functionality. Grafts were classified as transplantable (LT-G) or not (n-LT) according to clinical criteria, while histopathological analysis was used to confirm graft viability. After cold storage, the liver grafts were connected to the NMP. During the rewarming phase, temperature and flows were progressively increased to reach target values. At the end of NMP, 4 grafts were classified as LT-G and 3 nLT-G. Histology confirmed absence of major damage in LT-G, while diffuse necrosis appeared in nLT-G. Interestingly, in nLT-G an early impairment of hepatocyte respiratory chain, leading to cell necrosis and graft non-viability, was documented for the first time. These parameters, together with indocyanine-green dye and citrate clearance could contribute to graft evaluation in clinical settings. In conclusion, this model provides a promising and reproducible method to replace dedicated experimental animals in DCD and MP research, in line with the 3Rs principles.