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Background: Organ transplantation using grafts from elderly donors entails a higher risk for severe ischemia‐reperfusion injury (IRI). Advanced IRI after liver transplantation (LT) seems to be associated with the development of acute kidney injury (AKI). We studied if end‐ischemic hypothermic oxygenated machine perfusion (HOPE) of liver grafts, aimed at mitigating liver IRI, impacts on the frequency and severity of AKI after LT. Methods: LTs performed at our center between January 2017 and December 2022 using organs from deceased brain‐dead donors aged 70 or older were reviewed. From November 2020 on, HOPE was performed routinely in this donor category. The frequency and severity of AKI (KDIGO criteria) within 48 hours of graft reperfusion and the model of early allograft function (MEAF) were compared between HOPE‐LTs (n = 30) and control LTs (n = 71). Results: AKI developed in 23/30 (77%) HOPE‐LTs and in 40/71 (56%) control LTs (p = n.s.), with no difference in severity and timing between groups. Renal replacement therapy was required in 3/30 (10%) HOPE‐LTs and 6/71 (8%) control LTs. In addition, transaminase leak during the first week (marker of IRI) and MEAF were similar between groups. These findings persisted after propensity matching. Histology showed more hepatocyte vacuolization and higher Suzuki score in HOPE‐LTs. Although this analysis could have been underpowered, no trends supporting the benefit of HOPE on liver and renal injury after LT were ever identified. Conclusions: In conclusion, HOPE in this group of older donors does not seem to improve either graft IRI, or the incidence of early AKI after LT. [ABSTRACT FROM AUTHOR]

Uveal melanoma is a malignant tumor of the eye that often metastasizes to the liver conferring poor prognosis. When comparing immune profiles in peripheral blood of untreated patients with uveal melanoma liver metastasis and healthy blood donors, it was observed that immune cells of uveal melanoma patients carried immunosuppressive features. Patient blood contained an increased content of CD14+HLA-DR−/low M-MDSCs and inflammatory CD16+ monocytes, while their dendritic cells expressed lower levels of activation markers. Melanoma patients also harbored an enhanced fraction of CD4+Foxp3+ regulatory T cells, while their effector T cells expressed lower levels of the activation marker HLA-DR. Biopsies from liver metastases were obtained from patients with uveal melanoma that subsequently underwent hyperthermic isolated hepatic perfusion (IHP) with melphalan. There were trends indicating a positive correlation between a high infiltration of CD8+ T cells in metastases and an activated immune cell profile in blood. High metastatic infiltration of CD8+ T cells and CD68+ macrophages, but not of immunosuppressive CD163+ macrophages, correlated to a longer overall survival in patients treated with IHP. Hence, while the immune system of patients with uveal melanoma shows signs of immunosuppression, the presence of activated immune cells may correlate to a longer survival, at least following IHP treatment. [ABSTRACT FROM AUTHOR]

Hyperthermic isolated limb perfusion (ILP) with high-dose melphalan is a treatment option for melanoma patients with metastasis confined to limbs (in-transit metastasis). The therapy entails a complete response (CR) rate of 50–70%. Cellular immunity is proposed to impact on the clinical efficacy of ILP, but the detailed aspects of ILP-induced immune activation remain to be explored. For this study, we explored the potential role of interferon-stimulated gene (ISG) products, including CXCL10, CCL2, PD-L2 and IFN-γ along with expression of their cognate receptors CXCR3, CCR4, CCR5 and PD-1 on lymphocytes, for the clinical efficacy of ILP. Patients with high serum levels of CXCL10, CCL2, PD-L2 and IFN-γ were more likely to achieve CR after ILP. Additionally, the expression of CXCR3, CCR4 and CCR5 on T cells and/or natural killer (NK) cells was enhanced by ILP. Peripheral blood mononuclear cells (PBMCs) secreted high levels of CXCL10, CCL2 and IFN-γ in response to co-culture with melphalan-exposed melanoma cells in vitro. Activated T cells migrated toward supernatants from these co-cultures. Furthermore, melphalan-exposed melanoma cells triggered upregulation of CXCR3, CCR4, CCR5 and PD-1 on co-cultured T cells and/or NK cells. Our results suggest that constituents released from melphalan-exposed melanoma cells stimulate the ISG axis with ensuing formation of chemokines and upregulation of chemokine receptor expression on anti-neoplastic immune cells, which may contribute in ILP-induced tumor regression. [ABSTRACT FROM AUTHOR]

Background: Sweden’s western region has successively introduced the use of validated non-invasive diagnostic algorithms and treatment allocation for hepatocellular cancer (HCC). The aim was to analyse whether between 2000 and 2011 these changes in strategy had an impact on survival. Methods: Data concerning diagnosis, survival and treatment for 687 individuals with HCC were retrieved from the regional cancer centre’s register and hospital charts. The 12-year period was divided into three four-year cohorts (A-B-C). Results: There was an increase in the crude incidence rate of HCC from 2.7 to 4.2 per 100 000 inhabitants (p < 0.0001) over the period studied. Imaging was increasingly used for diagnosis over the three time periods (1.4%, 7.9% and 29%;p < 0.0001). Alcohol abuse was the most common aetiology for underlying liver disease (42%). The median survival time for all HCC patients improved over time – period A: 3.8 months, period B: 5.1 months and period C: 7.0 months (p = 0.0007). The 209 patients without any underlying liver disease had a worse survival than the 377 with a reported underlying liver disease (p = 0.0001). Active palliative treatment (APT) increased from 17% to 35% during period C (p < 0.0001). For these patients, median survival increased from 8.8 months to 14.2 months. Best supportive care was used less over time. Discussion: Overall survival improved when more patients had APT, mainly trans arterial chemoembolisation (TACE). [ABSTRACT FROM PUBLISHER]