Background: The systemic inflammatory cascade triggered in donors after brain death enhances the ischemia-reperfusion injury after organ transplantation. Intravenous steroids are routinely used in the intensive care units for the donor preconditioning. Immunosuppressive medications could be potentially used for this purpose as well. Data regarding donor preconditioning with calcineurin inhibitors or inhibitors of mammalian target for Rapamycin is limited. The aim of this project is to investigate the effects of (oral) donor preconditioning with a calcineurin inhibitor (Cyclosporine) vs. an inhibitor of mammalian target for Rapamycin (Everolimus) compared to the conventional administration of steroid in the setting of donation after brain death in porcine renal transplantation. Methods: Six hours after the induction of brain death, German landrace donor pigs (33.2 ± 3.9 kg) were randomly preconditioned with either Cyclosporine (n = 9) or Everolimus (n = 9) administered via nasogastric tube with a repeated dose just before organ procurement. Control donors received intravenous Methylprednisolone (n = 8). Kidneys were procured, cold-stored in Histidine-Tryptophane-Ketoglutarate solution at 4 • C and transplanted in nephrectomized recipients after a mean cold ischemia time of 18 h. No post-transplant immunosuppression was given to avoid confounding bias. Blood samples were obtained at 4 h post reperfusion and daily until postoperative day 5 for complete blood count, blood urea nitrogen, creatinine, and electrolytes. Graft protocol biopsies were performed 4 h after reperfusion to assess early histological and immunohistochemical changes. Results: There was no difference in the hemodynamic parameters, hemoglobin/ hematocrit and electrolytes between the groups. Serum blood urea nitrogen and creatinine peaked on postoperative day 1 in all groups and went back to the Abbasi Dezfouli et al. Preconditioning in Pig Kidney Transplantation preoperative levels at the conclusion of the study on postoperative day 5. Histological assessment of the kidney grafts revealed no significant differences between the groups. TNF-α expression was significantly lower in the study groups compared with Methylprednisolone group (p = 0.01) Immunohistochemistry staining for cytochrome c showed no difference between the groups. Conclusion: Oral preconditioning with Cyclosporine or Everolimus is feasible in donation after brain death pig kidney transplantation and reduces the expression of TNF-α. Future studies are needed to further delineate the role of oral donor preconditioning against ischemia-reperfusion injury.

Lymphocele formation after kidney transplantation is a frequent complication which causes pain, secondary graft loss, rehospitalizations and reoperations. Therefore, prophylaxis of lymphocele formation is of utmost importance. To assess the effectiveness of peritoneal fenestration in renal transplantation to prevent lymphocele development. A systematic literature search was conducted combined with hand-searches on lymphocele prevention following renal transplantation using peritoneal fenestration. A qualitative and quantitative analysis of included trials was conducted. We identified three trials including 414 patients and 437 transplantations which studied peritoneal fenestration. Only one randomized controlled trial was identified. Critical appraisal uncovered a number of methodological flaws, predominantly in the nonrandomized studies. Most importantly endpoint definitions varied among trials, selection bias was high and interventions and follow-up were not standardized. Meta-analysis of the included trials showed a significant reduction of clinically symptomatic lymphoceles (OR: 0.23, 95% CI: 0.09-0.64, P = 0.005) and overall postoperative fluid collections (OR: 0.49, 95% CI: 0.28-0.88, P = 0.02) without a significant increase in other surgical complications. Although peritoneal fenestration is a promising technique to reduce lymphocele formation, only few studies have investigated this technique so far. Given the low methodological quality of included trials, more studies are necessary to evaluate the effectiveness and the risks and benefits of this technique.

Background Hepatocellular carcinoma (HCC) is the sixth most common form of cancer worldwide. Although surgical treatments have an acceptable cure rate, tumor recurrence is still a challenging issue. In this meta-analysis, we investigated whether statins prevent HCC recurrence following liver surgery. Methods PubMed, Web of Science, EMBASE and Cochrane Central were searched. The Outcome of interest was the HCC recurrence after hepatic surgery. Pooled estimates were represented as hazard ratios (HRs) and odds ratios (ORs) using a random-effects model. Summary effect measures are presented together with their corresponding 95% confidence intervals (CI). The certainty of evidence was evaluated using the Grades of Research, Assessment, Development and Evaluation (GRADE) approach. Results The literature search retrieved 1362 studies excluding duplicates. Nine retrospective studies including 44,219 patients (2243 in the statin group and 41,976 in the non-statin group) were included in the qualitative analysis. Patients who received statins had a lower rate of recurrence after liver surgery (HR: 0.53; 95% CI: 0.44–0.63; p < 0.001). Moreover, Statins decreased the recurrence 1 year after surgery (OR: 0.27; 95% CI: 0.16–0.47; P < 0.001), 3 years after surgery (OR: 0.22; 95% CI: 0.15–0.33; P < 0.001), and 5 years after surgery (OR: 0.28; 95% CI: 0.19–0.42; P < 0.001). The certainty of evidence for the outcomes was moderate. Conclusion Statins increase the disease-free survival of patients with HCC after liver surgery. These drugs seem to have chemoprevention effects that decrease the probability of HCC recurrence after liver transplantation or liver resection.

The disparity between the number of available donor livers and patients awaiting a liver transplant has led transplant centers to accept suboptimal livers. There has been no universally accepted tool to predict the posttransplant function of these organs to safely increase the donor pool, protect these livers against ischemia-reperfusion injury, or improve their quality before implantation. Ex situ liver machine preservation has emerged as a promising novel graft protective strategy in the field of liver transplantation, with remarkable ongoing research and evolving clinical trials within Europe and the United States. This technology has been shown to be safe and feasible in the clinical liver transplantation field, has shown to reduce liver ischemia-reperfusion injury, and has shown to decrease the graft discard rate compared with conventional static cold storage. This review focuses on the current status of ex situ machine preservation in clinical liver transplantation, describing the most important technical aspects with the emphasis on the findings of the most recent clinical studies.

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