Recent studies have shown that the tumor microenvironment plays an important role in cancer progression. Tumor-associated macrophages (TAMs), in particular, have been found to be associated with tumor progression. Macrophages have multiple biological roles, including antigen presentation, target cell cytotoxicity, removal of foreign bodies, tissue remodeling, regulation of inflammation, induction of immunity, thrombosis, and endocytosis. Recent immunological studies have identified two distinct states of polarized macrophage activation: the classically activated (M1) and the alternatively activated (M2) macrophage phenotypes. Bacterial moieties such as lipopolysaccharides and the Th1 cytokine interferon-γ polarize macrophages toward the M1 phenotype. The M2 polarization was discovered as a response to the Th2 cytokine interleukin-4. In general, M2 macrophages exert immunoregulatory activity, participate in polarized Th2 responses, and aid tumor progression. TAMs have recently been found to play an important role in hepatocellular carcinoma (HCC) progression. Based on the properties of TAMs, obtained from pathological examination of resected specimens, we have identified new therapeutic approaches, involving the targeting of TAMs with adjuvant therapy after hepatic resection for HCC. This review discusses the roles of TAM in HCC progression and the possibility of new therapies targeting TAMs.

PD-L1 status may be a good predictor of prognosis in HCC patients with high HLA class I expression. Novel therapies targeting the PD-L1/PD-1 pathway may improve the prognosis of patients with HCC.

The presence of tumor-infiltrating lymphocytes (TILs) in hepatocellular carcinoma (HCC) is relatively rare. The prognosis of patients with HCC and marked TILs is better than that of patients with HCC without TILs. TILs in HCC tissues are mainly T cells, and previous reports suggested that TILs might be important antitumor effector cells. TILs have been extensively analyzed, and subpopulations of CD3(+), CD4(+), and CD8(+) T cells are often present in HCC. Some studies have reported that the percentage of CD8(+) T cells, which might have cytotoxic activity, is decreased in tumors with TILs, as compared with noncancerous tissues. Although the antitumor effects of TILs seem to be impaired in HCCs, the underlying mechanism has remained unclear until quite recently. Pathological and in vitro studies have now shown that regulatory T cells play important roles in the deterioration of the antitumor effects of TILs. The aim of this review is to introduce recent pathological findings for TILs in HCC and to evaluate new therapeutic strategies in this field.

The Glasgow Prognostic Score (GPS), an inflammation-based score, has been used to predict the biologic behavior of malignant tumors. The aim of the current study was to elucidate a further significance of GPS in colorectal carcinoma. Correlation of GPS and modified GPS (mGPS), which are composed of combined score provided for serum elevation of C-reactive protein and hypoalbuminemia examined before surgical treatment, with clinicopathologic features was investigated in 272 patients with colorectal carcinoma. Survival of GPS 1 patients was significantly worse than that of GPS 0 patients (P= 0.009), and survival of GPS 2 patients was significantly worse than that of GPS 1 patients (P < 0.0001). Similarly, survival of mGPS 1 patients was significantly worse than that of mGPS 0 patients (P = 0.009), and survival of mGPS 2 patients was significantly worse than that of mGPS 1 patients (P = 0.0006). Multivariate analysis demonstrated that GPS (P < 0.0001) as well as tumor stage (P= 0.004) and venous invasion (P = 0.011) were factors independently associated with worse prognosis. Both GPS and mGPS could classify outcome of patients with a clear stratification, and could be applied as prognostic indicators in colorectal carcinoma.

Background:The mechanism whereby arachidonic acid (AA) activates the phagocyte oxidase Nox2 is not well understood, except for the AA-induced conformational change of p47 phox , a partner of the Nox2 activator p67 phox . Results: AA also triggers Rac-GTP formation and Nox2 interaction with the p67 phox ⅐Rac-GTP complex. Conclusion: AA regulates Nox2 assembly at multiple steps. Significance: p67 phox -Nox2 interaction is a novel regulatory step.

The aim of this study was to investigate the effects of preoperative oral supplementation with branched-chain amino acids (BCAAs) on postoperative bacteremia after living donor liver transplantation (LDLT) for chronic liver failure. Two hundred thirty-six patients who underwent adult-to-adult LDLT were evaluated in this retrospective study. The patients were divided into 2 groups: those who received oral supplementation with BCAAs before transplantation (the BCAA group; n ¼ 129) and those who did not (the non-BCAA group; n ¼ 107). Before the LDLT indication was determined, BCAA supplementation was prescribed by a hepatologist to preserve hepatic reserves. The clinical characteristics and the incidence of bacteremia were compared between the 2 groups. As for clinical characteristics, the Child-Pugh scores (P ¼ 0.0003) and the Model for End-Stage Liver Disease scores (P ¼ 0.0008) were significantly higher in the BCAA group versus the non-BCAA group. The incidence of bacteremia for Child-Pugh class C patients was significantly lower in the BCAA group (6/90 or 6.7%) versus the non-BCAA group (11/50 or 22.0%, P ¼ 0.0132). In a multivariate analysis, non-BCAA supplementation was an independent risk factor for bacteremia. In conclusion, preoperative BCAA supplementation might reduce the incidence of bacteremia after LDLT. Nevertheless, this is a preliminary report, and further studies, such as randomized, prospective studies, are necessary to clarify the beneficial effects of BCAA supplementation on postoperative bacteremia after liver transplantation.

The prevalence and clinical characteristics of bacterial pneumonia after living donor liver transplantation (LDLT) have not yet been elucidated. We performed a retrospective analysis of 346 LDLT recipients. Fifty patients (14.5%) experienced bacterial pneumonia after LDLT, and they had a higher short-term mortality rate (42.0%) than patients with other types of bacterial infections after LDLT. Gram-negative bacteria accounted for 84.0% of the causative pathogens. A multivariate analysis showed that preoperative diabetes (P < 0.01), United Network for Organ Sharing status 1 or 2A (P < 0.01), and an operative blood loss > 10 L (P ¼ 0.03) were significant risk factors for bacterial pneumonia after LDLT. Post-LDLT pneumonia was associated with the following post-LDLT events: the prolonged use of mechanical ventilation (!3 days), a prolonged stay in the intensive care unit (!7 days), the creation of a tracheostomy, primary graft dysfunction, the use of mycophenolate mofetil, and the need for renal replacement therapy. Among patients with bacterial pneumonia, the mortality rate was higher for patients with delayed-onset pneumonia, which occurred at least 10 days after transplantation (n ¼ 15), and it was significantly associated with graft dysfunction. A combination of broad-spectrum antibiotics and aminoglycosides provided cover for most gram-negative bacteria except Stenotrophomonas maltophilia, which was associated with a longer period of mechanical ventilation and was resistant to commonly used broad-spectrum antibiotics. Delayed-onset bacterial pneumonia is a serious type of bacterial infection after LDLT and is frequently associated with graft dysfunction. The multidrug resistance of S. maltophilia is an issue that needs to be addressed. Liver Transpl 18:1060-1068, 2012. V C 2012 AASLD.Received March 5, 2012; accepted May 27, 2012.Bacterial pneumonia is a major cause of severe hospital-acquired infections, and the severity of bacterial pneumonia is largely determined by the patient's underlying condition.1 Liver transplant recipients are at particularly high risk because of immunosuppression, massive blood loss and transfusions during surgery, systemic edema with fluid accumulation, and the prolonged period of mechanical ventilation.2-9 As a result, bacterial pneumonia is a major cause of morbidity and mortality for liver transplant recipients. [3][4][5][6][7][8] The types of causative bacteria and their propensity for hospital-acquired pneumonia have been studied in general intensive care unit patients and in patients

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