(1) Background: Post-reperfusion syndrome (PRS) and electrolyte shifts (ES) represent considerable challenges during liver transplantation (LT) being associated with significant morbidity. We aimed to investigate the impact of hypothermic oxygenated machine perfusion (HOPE) on PRS and ES in LT. (2) Methods: In this retrospective study, we compared intraoperative parameters of 100 LTs, with 50 HOPE preconditioned liver grafts and 50 grafts stored in static cold storage (SCS). During reperfusion phase, prospectively registered serum parameters and vasopressor administration were analyzed. (3) Results: Twelve percent of patients developed PRS in the HOPE cohort vs. 42% in the SCS group (p = 0.0013). Total vasopressor demand in the first hour after reperfusion was lower after HOPE pretreatment, with reduced usage of norepinephrine (−26%; p = 0.122) and significant reduction of epinephrine consumption (−52%; p = 0.018). Serum potassium concentration dropped by a mean of 14.1% in transplantations after HOPE, compared to a slight decrease of 1% (p < 0.001) after SCS. The overall incidence of early allograft dysfunction (EAD) was reduced by 44% in the HOPE group (p = 0.04). (4) Conclusions: Pre-transplant graft preconditioning with HOPE results in higher hemodynamic stability during reperfusion and lower incidence of PRS and EAD. HOPE has the potential to mitigate ES by preventing hyperpotassemic complications that need to be addressed in LT with HOPE-pre-treated grafts.

Background: Hypothermic oxygenated machine perfusion (HOPE) has emerged as a critical innovation in liver transplantation (LTx), offering significant protection against ischemia-reperfusion injury (IRI). This study focuses on quantifying and characterizing immune cells flushed out during HOPE to explore its effects on graft function and post-transplant outcomes. Materials and Methods: Fifty liver grafts underwent end-ischemic HOPE. Perfusate samples were collected at three time points: at the start of perfusion, after 10 min, and at the end of perfusion. The samples were analyzed to quantify and characterize immune cells, assessing the effectiveness of HOPE in reducing cellular debris and its impact on graft quality. Results: The primary perfusate contained significant concentrations of immune cells, mainly segmented neutrophils, lymphocytes, and monocytes. After 10 min of perfusion, outflow cell concentration decreased by over 95%, and by the end of perfusion, a more than 99% reduction was observed. Conclusions: HOPE effectively reduces immune cell concentrations in liver grafts, suggesting a mechanism for improved graft function and reduced post-transplant complications. These findings support the continued use and optimization of HOPE in LTx.

Background.: Liver transplantation (LT) remains the most effective treatment for patients with hepatocellular carcinoma (HCC), offering 5-y recurrence rates as low as 15%. Recent advances in organ preservation, particularly hypothermic oxygenated machine perfusion (HOPE), have demonstrated the ability to attenuate ischemia–reperfusion injury (IRI). However, whether HOPE can reduce HCC recurrence rates by mitigating IRI remains an open question. In this study, we aimed to compare oncological outcomes after LT for HCC with and without the use of HOPE. Methods.: We conducted a retrospective cohort study including 137 patients who underwent LT for HCC with grafts from donation after brain death. Risk factors for HCC recurrence were analyzed using Cox regression. To assess the impact of HOPE on oncological outcomes, propensity score matching was used to adjust for baseline differences. Results.: Cox regression identified Milan Criteria status as a significant predictor of HCC recurrence. Among the 32 patients in the HOPE group, no HCC recurrence was observed over a median follow-up of 2.11 y. In contrast, within the control group of 105 patients, 8 (7.6%) experienced recurrence within 2 y posttransplantation. Although this translated into a significant difference in time-to-recurrence after propensity score matching, recurrence-free survival and overall survival did not differ significantly. Conclusions.: Our findings suggest that HOPE treatment of donation after brain death liver grafts may reduce early HCC recurrence after LT. Although only nonsignificant trends were observed in recurrence-free survival and overall survival within the first 2 y posttransplant, these results underscore the potential of HOPE to influence oncological outcomes. Long-term follow-up, prospective randomized controlled trials, and basic research are warranted to further elucidate the role of HOPE and IRI.

A substantial number of viable donor livers are discarded due to the donor's underlying malignancy. Concurrently, patients with certain liver malignancies - such as unresectable colorectal cancer liver metastases (CRC-LM), unresectable intrahepatic or perihilar cholangiocarcinoma (iCCC/phCCC), or unresectable hepatocellular carcinoma (HCC) responding to immunotherapy - often face poor survival outcomes and are deemed ineligible for potentially curative liver transplantation. In this context, a rational risk-benefit analysis suggests that transplanting an organ with a theoretical risk of tumor transmission may be justifiable for these patients facing otherwise short-term fatal outcomes. The TRANSMIT study is a compassionate use exploratory study aimed at assessing the utility and safety of using donor organs from individuals with a current or past history of cancer for liver transplantation in patients with liver malignancies (CRC-LM, i/phCCC, HCC) who are not eligible for regular organ allocation. The study will evaluate the utilization rate of donor organs that would otherwise be discarded, overall survival, progression-free survival, and tumor transmission rates at one and three years, stratified by indication. Donor organs from individuals with a current or past history of cancer may represent a valuable and safe resource for expanding the limited donor pool, particularly for patients who lack access to standard organ allocation.

Aim: Postoperative adhesions cause medical and socio-economic problems. 4DryField PH (4DF) is a starch-based medical product/agent with approved anti-adhesive and haemostatic effects. However, the influence on anastomotic healing has not yet been evaluated. The purpose of this study was, therefore, to characterize the effects of intraoperatively applied 4DF on the incidence of anastomotic leakage (AL) after rectal surgery. Methods: In this retrospective, monocentric cohort study, 157 patients after rectal surgery and primary anastomosis were divided into two groups. One group received 4DF (n=57), the other was treated without 4DF application (n=100). The groups were followed up for confirmed ALs. Results: The rate of ALs (P=0.850) proved to be comparable. Other additional outcome parameters like postoperative hospital stay (P=0.801), wound infection rate (P=0.627), re-admission rate (P=1.000), re-operation rate (P=0.533) and the 30-day mortality (P=0.463) also showed no statistically significant differences. A multivariable regression model for the complete cohort could not identify 4DF application as prognostically relevant for the development of AL, whereas rectal cancer (OR=2.660 [1.184–5.974]; P=0.018), smoking (OR=3.555 [1.326–9.533]; P=0.012), an ASA (American Society of Anaesthesiologists) score ≥3 (OR=2.894 [1.300–6.442]; P=0.009) and male sex (OR=2.411 [1.040–5.591]; P=0.040) were determined as independent risk factors. Conclusion: The application of 4DF in proximity to the anastomotic region after rectal surgery did not increase the risk of AL and showed no impact on other investigated outcome parameters.

Background: Hepatic ischemia–reperfusion injury (IRI) remains a major challenge in liver transplantation (LTx) and hepatectomy. Previous studies identified a 12/15-lipoxygenase (12/15-LOX)-driven lipid peroxidation cascade promoting cell death, whereas glutathione peroxidase 4 (GPx4)-dependent metabolism acts antagonistically. This study investigated whether tacrolimus protects against hepatic IRI through this redox axis. Methods: Male C57BL/6 mice underwent 65% partial hepatic warm ischemia and reperfusion with or without tacrolimus preconditioning. Liver tissue and serum were analyzed by spectral photometry, Western blotting, TUNEL assay, and serum enzyme measurement. Results were statistically analyzed and compared with previously published results of 12/15-LOX inhibition by baicalein pretreatment and its carrier DMSO. Also, the combination of both tacrolimus and baicalein was investigated. Results: Tacrolimus increased the oxidative glutathione activity quotient (GSSG/GSH) by 75.1% (p = 0.0302), attenuated MAPK signaling, reduced SAPK/JNK by 84.6% (p = 0.0059), with ERK1/2 showing a downward trend, decreased Caspase-3 activation by 66.9% (p < 0.001) and PARP cleavage by 59.9% (p = 0.0330), and lowered TUNEL-positive cell death by 61.8% (p = 0.0015). Tacrolimus achieved hepatoprotection comparable to 12/15-LOX inhibition, but without hepatotoxicity, whereas combined treatment conferred no additional benefit yet bore toxic properties. Conclusions: Tacrolimus preconditioning mitigates hepatic IRI through a glutathione-linked redox–signaling–cell death axis and exerts cytoprotective effects beyond immunosuppression.