During sepsis, a complex network of cytokine, immune, and endothelial cell interactions occur and disturbances in the microcirculation cause organ dysfunction or even failure leading to high mortality in those patients. In this respect, numerous experimental and clinical studies indicate sex-specific differences in infectious diseases and sepsis. Female gender has been demonstrated to be protective under such conditions, whereas male gender may be deleterious due to a diminished cell-mediated immune response and cardiovascular functions. Male sex hormones, i.e., androgens, have been shown to be suppressive on cell-mediated immune responses. In contrast, female sex hormones exhibit protective effects which may contribute to the natural advantages of females under septic conditions. Thus, the hormonal status has to be considered when treating septic patients. Therefore, potential therapies could be derived from this knowledge. In this respect, administration of female sex hormones (estrogens and their precursors) may exert beneficial effects. Alternatively, blockade of male sex hormone receptors could result in maintained immune responses under adverse circulatory conditions. Finally, administration of agents that influence enzymes synthesizing female sex hormones which attenuate the levels of pro-inflammatory agents might exert salutary effects in septic patients. Prospective patient studies are required for transferring those important experimental findings into the clinical arena.

The ALPPS approach induces a considerable hypertrophic response in HCC patients and allows resection of intermediate-stage HCC, albeit at the cost of a 31 % perioperative mortality rate. The use of ALPPS for HCC remains prohibitive for most patients and should be performed only for a highly selected patient population younger than 60 years with low-grade fibrosis.

This meta-analysis supports the use of EBRT for local tumor control in patients with resectable STSs. Based on a small number of non-randomized studies, a positive effect on OS may exist in the subgroup of retroperitoneal STSs.

SummaryThe role of intraoperative porto-caval shunts in orthotopic liver transplantation (OLT) is controversial. Aim of this study was to analyze the effects of an intraoperative, porto-caval catheter-shunt on graft function and survival following cava sparing OLT. Four hundred and forty-eight piggy back liver transplantations with or without a temporary spontaneous porto-caval shunt between 1997 and 2010 were analyzed (shunt n = 274 vs. no shunt n = 174). Lab MELD scores and donor risk indices (DRI) were calculated. Hepatic injury (ALT, AST), -function (bilirubin, prothrombin ratio), postreperfusion liver blood flow and graft survival were registered [mean follow-up: 50.5 (0-163.0) months]. The impact of a shunt on graft survival was determined using multivariate analysis. Usage of a porto-caval shunt was associated with reduced hepatic injury (ALT, AST), whereas graft function was not affected. The shunt group showed a significantly increased portal venous blood flow after reperfusion. Retransplantation rate was decreased (7.7% vs. 20.1%, P = 0.001) and long-term graft survival was significantly increased with a portocaval shunt (hazard ratio 2.1, P < 0.001). This effect was even more pronounced for marginal organs. Usage of intraoperative porto-caval catheter-shunts is beneficial in cava sparing OLT and is associated with reduced ischemia-reperfusion injury and improved organ survival in particular for recipients of marginal organs.

SummaryDe novo malignancies are a major cause of late death after liver transplantation. Aim of the present study was to determine whether use of cyclosporine versus tacrolimus affects long-term tumor incidence considering potential confounders. De novo malignancies in 609 liver transplant recipients at Munich Transplant Centre between 1985 and 2007 were registered. In 1996, the standard immunosuppressive regimen was changed from cyclosporine to tacrolimus. Different effects of those drugs on long-term tumor incidence were analyzed in multivariate analysis. During 3765 patient years of follow-up (median 4.78 years), 87 de novo malignancies occurred in 71 patients (mean age 47.5 AE 13.3 years, mean time after liver transplantation 5.7 AE 3.7 years). The cumulative incidence of de novo malignancies was 34.7% for all tumor entities after 15 years as compared to 8.9% for a nontransplanted population. The most frequent tumors observed were nonmelanoma skin cancers (44.83%). Moreover, post-transplant lymphoid disease, oropharyngeal cancer (n = 6, 6.9%), upper gastrointestinal tract cancer (n = 4, 4.6%), lung cancer (n = 4, 4.6%), gynecological malignancies (n = 4, 4.6%), and kidney cancer (n = 3, 3.45%) were detected. Multivariate analysis revealed recipient age [hazards ratio (HR) 1.06], male gender (HR 1.73), and tacrolimus-based immunosuppression (HR 2.06) as significant risk factors. Based on those results, a tacrolimus-based immunosuppression should be discussed especially in older male patients. Whether reducing tacrolimus target levels may reduce the risk for de novo malignancies has yet to be determined in prospective trials.

Intraoperative ICG clearance measurements allow real-time monitoring of intraoperative liver function during surgery. Trial clamping of arterial and portovenous inflow accurately predicts immediate post-resection liver function. The intraoperative measurement of liver function and simulation of post-resection liver function may help to avoid PHLF.

The continuing controversy about surgery for non-colorectal non-neuroendocrine liver metastases (NCRNNE) necessitates identifying risk factors of worsened outcomes to improve patient selection and survival. Prospectively collected data of 167 patients undergoing hepatectomy for NCRNNE were analyzed, and a comparison to a matched population of colorectal liver metastases (CLM) was performed. Overall survival (OS) (35 vs. 54 months; P = 0.008) and recurrence-free survival (RFS) (15 vs. 29 months; P = 0.004) of NCRNNE patients were significantly shorter compared to those with CLM. The best survival was found in the genitourinary (GU; OS, 45 months; RFS, 21 months) NCRNNE subgroup, whereas survival for gastrointestinal (GI) metastases was low (OS, 8 months; RFS, 7 months). Patients with renal cell carcinoma (RCC) showed excellent outcomes when compared to CLM (OS, 50 vs. 51 months; P = 0.901). Extrahepatic disease (EHD) was identified as independent prognostic factor for reducing both RFS (P = 0.040) and OS (P = 0.046). The number of liver lesions (P = 0.024), residual tumor (P = 0.025), and major complications (P = 0.048) independently diminished OS. The degree of survival advantage by surgery is determined by the primary tumor site, EHD, the number of metastases, and residual tumor. Thus-even more than in CLM-these oncological selection criteria must prevail. GU metastases, especially RCC, represent a favorable subgroup.

This meta-analysis found that temporary intraoperative porto-caval shunts in cava-sparing liver transplantation reduce blood loss as well as hepatic injury and enhance postoperative renal function without prolonging operative time. Randomized controlled trials investigating the use of temporary intraoperative porto-caval shunts are needed to confirm these findings.