Expanded living-donor liver transplantation criteria for patients with hepatocellular carcinoma based on the Japanese nationwide survey: the 5-5-500 rule - a retrospective study.

Expansion of the liver transplantation indication criteria for patients with hepatocellular carcinoma (HCC) has long been debated. Here we propose new, expanded living-donor liver transplantation (LDLT) criteria for HCC patients based on a retrospective data analysis of the Japanese nationwide survey. A total of 965 HCC patients undergoing LDLT were included, 301 (31%) of whom were beyond the Milan criteria. Here, we applied the Greenwood formula to investigate new criteria enabling the maximal enrollment of candidates while securing a 5-year recurrence rate (95% upper confidence limit) below 10% by examining various combinations of tumor numbers and serum alpha-fetoprotein values, and maintaining the maximal nodule diameter at 5 cm. Finally, new expanded criteria for LDLT candidates with HCC, the 5-5-500 rule (nodule size ≤5 cm in diameter, nodule number ≤5, and alfa-fetoprotein value ≤500 ng/ml), were established as a new regulation with a 95% confidence interval of a 5-year recurrence rate of 7.3% (5.2-9.3) and a 19% increase in the number of eligible patients. In addition, the 5-5-500 rule could identify patients at high risk of recurrence, among those within and beyond the Milan criteria. In conclusion, the new criteria - the 5-5-500 rule - might provide rational expansion for LDLT candidates with HCC.

Critical role of an antiviral stress granule containing RIG-I and PKR in viral detection and innate immunity.

Retinoic acid inducible gene I (RIG-I)-like receptors (RLRs) function as cytoplasmic sensors for viral RNA to initiate antiviral responses including type I interferon (IFN) production. It has been unclear how RIG-I encounters and senses viral RNA. To address this issue, we examined intracellular localization of RIG-I in response to viral infection using newly generated anti-RIG-I antibody. Immunohistochemical analysis revealed that RLRs localized in virus-induced granules containing stress granule (SG) markers together with viral RNA and antiviral proteins. Because of similarity in morphology and components, we termed these aggregates antiviral stress granules (avSGs). Influenza A virus (IAV) deficient in non-structural protein 1 (NS1) efficiently generated avSGs as well as IFN, however IAV encoding NS1 produced little. Inhibition of avSGs formation by removal of either the SG component or double-stranded RNA (dsRNA)-dependent protein kinase (PKR) resulted in diminished IFN production and concomitant enhancement of viral replication. Furthermore, we observed that transfection of dsRNA resulted in IFN production in an avSGs-dependent manner. These results strongly suggest that the avSG is the locus for non-self RNA sensing and the orchestration of multiple proteins is critical in the triggering of antiviral responses.

Assessment of cerebral blood flow findings using 99mTc-ECD single-photon emission computed tomography in patients diagnosed with major depressive disorder.

BACKGROUND: Single-photon emission computed tomography (SPECT) is used as an ancillary diagnostic tool in clinical psychiatry. A variety of SPECT studies has been conducted on the findings and the factors that affect the findings, and there is a possibility that age has an effect on cerebral blood flow. We used SPECT to verify the cerebral blood flow findings of patients with major depressive disorder (MDD) considering the effect of age on the findings. METHODS: We conducted a retrospective survey of inpatients who fulfilled the DSM-IV diagnostic criteria for MDD and who had undergone imaging by technetium-99m ethyl cysteinate dimer ((99m)Tc-ECD) SPECT (N=98, 37 males). After excluding organic factors and comorbidities, we established a depression group (N=61, 24 males) and conducted an inter-group comparison with a normal control group by using SPM software considering the effect of age. RESULTS: The depression group showed the reduction of cerebral blood flow in the prefrontal area bilaterally, predominantly on the left, including the orbitofrontal cortex, anterior portion of the gyrus cinguli, and dorsolateral prefrontal area, in the left temporal lobe, and in the occipital lobe bilaterally, predominantly on the left. The findings were common to all age groups and that age-specific pattern was not detected. LIMITATIONS: The facts that this was a retrospective study and small sample size in each age group were limitations of this research. Although it also seems important to evaluate the impact of medication on cerebral blood flow and conduct an evaluation according to the subtype of depression, but we couldn't in this study. In the future it will be necessary to accumulate additional cases and conduct additional studies, including a prospective survey. CONCLUSION: The results of this study may suggest the existence of a common biological background in patients with MDD that is unaffected by age.

Omega-3 fatty acids exacerbate DSS-induced colitis through decreased adiponectin in colonic subepithelial myofibroblasts.

BACKGROUND: Although the immunoregulatory effects of omega-3 fatty acid and adiponectin have been postulated, their role in intestinal inflammation is controversial. The aim of this study was to determine whether dietary fat intake influences activity of colonic inflammation through modulating this system. METHODS: C57BL/6 mice received dextran sulfate sodium for induction of colitis. Mice were fed a control diet, omega-3 fat-rich diet, omega-6 fat-rich diet, or saturated fat-rich diet. Some mice were administered a peroxisome proliferator activated receptor-gamma; agonist, pioglitazone. Messenger RNA expression of adiponectin and its receptors were analyzed. Adiponectin expression in colonic mucosa of ulcerative colitis patients was also analyzed. RESULTS: The receptors for adiponectin were found to be ubiquitously expressed in epithelial cells, intraepithelial lymphocytes, lamina proprial mononuclear cells, and subepithelial myofibroblasts from colonic tissue, but adiponectin was only expressed in myofibroblasts. Induction of colitis significantly decreased the expression of adiponectin in colonic mucosa. The omega-3 fat diet group, but not the other fat diet groups, showed exacerbated colitis with a further decrease of adiponectin expression. Pioglitazone treatment ameliorated the level of decrease in adiponectin expression and improved colonic inflammation induced by the omega-3 fat-rich diet. In patients with ulcerative colitis, the expression level of adiponectin in colonic mucosa was also decreased compared with that in control mucosa. CONCLUSIONS: Adiponectin was found to be expressed in myofibroblasts. Adiponectin expression was significantly suppressed by induction of colitis, and aggravation of colitis after exposure to omega-3 fat may be due to a further decrease in the expression level of adiponectin.

Increased expression of galectin-3 in primary gastric cancer and the metastatic lymph nodes.

Galectin-3, a multifunctional beta-galactocide binding lectin possibly participates in a variety of biological events including cell proliferation, differentiation, and apoptosis. The implication of galectin-3 during malignancy progression has been suggested in several cancers, including colon, prostate, thyroid, and breast cancer, however, scarce data are available in gastric cancer. We examined the expression of galectin-3 in 86 primary gastric cancers and the 40 metastatic lymph nodes by immunohistochemistry to explore whether it is related to the malignant progression. Positive galectin-3 expression was observed in 84% of the gastric cancer cases. In enhanced cells of cancerous lesions, 48% showed stronger nuclear immunoreactivity than cytoplasmic one, whereas adjacent epithelial cells showed little or weak nuclear immunoreactivity. When galectin-3 expression in gastric carcinoma was compared with that in gastric tissues adjacent to the cancers, there was a significant difference. The degree of enhancement of immunoreactivity was different corresponding to various histopathological subtypes in cancer tissues. A significantly stronger expression of galectin-3 in cancer tissues was only observed in papillary and poorly differentiated adenocarcinoma. When galectin-3 expression and tumor progression (TNM staging) was compared, a significant correlation was observed in overall cases, and only in poorly differentiated adenocarcinoma the galectin-3 expression correlated with tumor progression among various subtypes. Galectin-3 expression was observed significantly stronger in metastatic lymph nodes than in the primary gastric cancers, and also in these cases among histological subtypes, only in poorly differentiated adenocarcinoma, the expression of galectin-3 in metastatic lymph nodes was stronger than the primary cancer. In conclusion galectin-3 might be a useful tumor marker for gastric cancers with respects to tumor progression and potentiality of lymph node metastasis especially in certain histological types of gastric cancer.