TACE-RFA was superior to RFA alone in improving survival for patients with HCC less than 7 cm.

Early metastasis is responsible for frequent relapse and high mortality of hepatocellular carcinoma (HCC), but its underlying mechanisms remain unclear. Epithelial-mesenchymal transition (EMT) has been considered a key event in metastasis. Based on histological examination of serial HCC sections and three-dimensional reconstruction, we found a novel and prevalent vascular pattern, vessels that encapsulated tumor clusters (VETC) and formed cobweb-like networks. The presence of VETC (VETC 1 ) predicted higher metastasis and recurrence rates of HCC. Using clinical samples and mouse xenograft models, we further showed that VETC was composed of functional vessels with blood perfusion and induced by tumor cells at the early stage of HCC. Subsequent investigations revealed that HCC cell-derived angiopoietin-2 was a prerequisite for VETC formation and that the VETC pattern was a critical factor promoting HCC metastasis as knockdown of angiopoietin-2 abolished this vascular pattern and consequently attenuated in vivo tumor metastasis. Interestingly, abrogation of EMT by knockdown of Snail or Slug significantly diminished in vivo metastasis of VETC -xenografts but did not affect that of VETC 1 ones, although silencing of Snail or Slug substantially reduced the in vitro migration of both VETC 1 and VETC -HCC cells. In contrast to human VETC -cases, EMT signatures were rarely observed in VETC 1 cases with metastatic potential. Further analysis revealed that VETC provided an efficient metastasis mode by facilitating the release of whole tumor clusters into the bloodstream. Conclusion: Our findings identify a novel metastasis mechanism that relies on vascular pattern but is independent of EMT, which may provide new targets for antimetastasis therapy and offer a basis for selecting patients who may benefit from certain molecularly targeted drugs. (HEPATOLOGY 2015;62:452-465) See Editorial on Page 343 T he current hypothesis of blood-borne metastasis holds that tumor cells must detach from the primary tumor, invade the extracellular matrix and vascular walls, survive in the circulation, extravasate from the vasculature, and grow at a new site.1,2 Accordingly, epithelial-mesenchymal transition (EMT) has been considered a key event for the epithelial tumor cells to lose cell-cell adhesion, acquire enhanced capacity for migration and invasion, and thereby dissociate from the

SUMMARY During B lymphocyte development, immunoglobulin heavy chain variable (VH), diversity (DH) and joining (JH) segments assemble to generate a diverse antigen receptor repertoire. Here we have marked the distal VH and DH-JH-Eμ regions with Tet-operator binding sites and traced their 3D-trajectories in pro-B cells transduced with a retrovirus encoding Tet-repressor-EGFP. We found that these elements displayed fractional Langevin motion (fLm) due to the viscoelastic hindrance from the surrounding network of proteins and chromatin fibers. Using fractional Langevin dynamics modeling, we found that, with high probability, DHJH elements reach a VH element within minutes. Spatial confinement emerged as the dominant parameter that determined the frequency of such encounters. We propose that the viscoelastic nature of the nuclear environment causes coding elements and regulatory elements to bounce back and forth in a spring-like fashion until specific genomic interactions are established and that spatial confinement of topological domains largely controls first-passage times for genomic interactions.

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Background-The residual Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery(SYNTAX) Score is an objective measure of the degree and complexity of residual stenosis after percutaneous coronary intervention (PCI). Methods and Results-In the randomized PCI cohort of the SYNTAX Trial (n=903), the baseline and residual SYNTAX Scores were calculated. Subjects with a residual SYNTAX Score of 0 were defined as having undergone complete revascularization (CR), and a residual SYNTAX Score >0 as incomplete revascularization (ICR). Five-year clinical outcomes were stratified by CR and ICR (tertiles of the residual SYNTAX Score: >0-4, >4-8, and >8). In the PCI cohort, the mean baseline and residual SYNTAX Scores were 28.4±11.5 and 4.5±6.9, respectively. The mean Δ SYNTAX Score (representative of the burden of disease removed by PCI) was 23.8±10.9. The residual SYNTAX Score was distributed as follows: CR, 0 (n=386, 42.7%); ICR, >0 to 4 (n=184, 20.4%), >4 to 8 (n=167, 18.5%), >8 (n=153, 16.9%). A progressively higher residual SYNTAX Score was shown to be a surrogate marker of increasing clinical comorbidity and anatomic complexity. Subjects with CR or residual SYNTAX Scores ≤8 had comparable 5-year mortality (CR, 8.5%; residual SYNTAX Score >0-4, 8.7%; >4-8, 11.4%; P=0.60). A residual SYNTAX Score >8 was associated with 35.3% all-cause mortality at 5-years (P<0.001). Stratified analyses in the predefined medical treated diabetic and left main subgroups yielded similar results. Conclusions-The

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Biochar as a carbon-rich coproduct of pyrolyzing biomass, its amendment has been advocated as a potential strategy to soil carbon (C) sequestration. Updated data derived from 50 papers with 395 paired observations were reviewed using meta-analysis procedures to examine responses of soil carbon dioxide (CO 2 ) fluxes, soil organic C (SOC), and soil microbial biomass C (MBC) contents to biochar amendment. When averaged across all studies, biochar amendment had no significant effect on soil CO 2 fluxes, but it significantly enhanced SOC content by 40% and MBC content by 18%. A positive response of soil CO 2 fluxes to biochar amendment was found in rice paddies, laboratory incubation studies, soils without vegetation, and unfertilized soils. Biochar amendment significantly increased soil MBC content in field studies, N-fertilized soils, and soils with vegetation. Enhancement of SOC content following biochar amendment was the greatest in rice paddies among different land-use types. Responses of soil CO 2 fluxes and MBC to biochar amendment varied with soil texture and pH. The use of biochar in combination with synthetic N fertilizer and waste compost fertilizer led to the greatest increases in soil CO 2 fluxes and MBC content, respectively. Both soil CO 2 fluxes and MBC responses to biochar amendment decreased with biochar application rate, pyrolysis temperature, or C/N ratio of biochar, while each increased SOC content enhancement. Among different biochar feedstock sources, positive responses of soil CO 2 fluxes and MBC were the highest for manure and crop residue feedstock sources, respectively. Soil CO 2 flux responses to biochar amendment decreased with pH of biochar, while biochars with pH of 8.1-9.0 had the greatest enhancement of SOC and MBC contents. Therefore, soil properties, land-use type, agricultural practice, and biochar characteristics should be taken into account to assess the practical potential of biochar for mitigating climate change.

BACKGROUND:The long‐term survival outcomes of hepatic resection (HR) compared with transcatheter arterial chemoembolization (TACE) for resectable hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) are unclear.MATERIALS AND METHODS:Between December 2002 and December 2007, 201 consecutive patients diagnosed with resectable HCC with PVTT received HR as an initial treatment in our center. These patients were compared with 402 case‐matched controls selected from a pool of 1798 patients (with a 1:2 ratio) who received TACE as an initial treatment during the study period. PVTT was classified to 4 types: PVTT involving the segmental branches of the portal vein or above (type I), PVTT extending to involve the right/left portal vein (type II), the main portal vein (type III), or the superior mesenteric vein (type IV).RESULTS:The 1‐, 3‐, and 5‐year overall survivals for the HR and TACE groups were 42.0%, 14.1%, and 11.1% and 37.8%, 7.3%, and 0.5%, respectively (P < .001). On subgroup analyses, the overall survivals for the HR group were better than the TACE group for type I PVTT, type II PVTT, single tumor, and tumor size >5 cm (P < .001, P = .002, P < .001, P < .001, respectively), but not for type III PVTT, type IV PVTT, multiple tumors, and tumor size <5 cm (P = .541, P = .371, P = .264, P = .338, P = .125, respectively). Multivariate analysis showed the type of PVTT and initial treatment allocation were significant prognostic factors for overall survival.CONCLUSIONS:Compared with TACE, HR provided survival benefits for patients with resectable HCC with PVTT, especially for those with a type I PVTT or a type II PVTT. Cancer 2012. © 2012 American Cancer Society.