The Molecular Pathogenesis and Clinical Implications of Hepatocellular Carcinoma

The prognosis of hepatocellular carcinoma (HCC) is affected by tumoral factors and liver functions; therefore it is often difficult to select the appropriate therapeutic methods for HCC. Recently, two global phase III trials showed that sorafenib, which is a tyrosine kinase inhibitor, improved the prognosis of patients with advanced HCC. As a new therapeutic strategy for HCC, sorafenib is expected to expand the indication for HCC in the future. However, it alone is insufficient for the molecular-targeted treatment of HCC because the signaling pathway exists not only in cancer cells but also in normal cells. Recently, cancer stem cells (CSCs) have attracted attention as a novel therapeutic target for HCC. There is now much evidence that stem cell properties such as self-renewal, unlimited proliferation, and differentiation are highly relevant to cancer recurrence and the drug resistance of HCC. In this review, we describe the molecular pathogenesis and the current state and future development of molecular- and CSC-therapeutic targeted agents for HCC, citing various reports

Prediction of postoperative liver failure and evaluation of modifi ed criteria for liver resection with computed volume analysis

Background/Aims: The exact resectable volume corresponding to liver function has never been elucidated for safe resection of a diseased liver. The aim of this study was to evaluate whether modifi ed criteria for safe liver resection could be used to predict postoperative liver failure/dysfunction.Methodology: Consecutive 86 patients who underwent liver resections were assessed. Clinical laboratory tests and liver volume were evaluated. The modifi ed criteria used to determine safe liver resection consisted of indocyanine green retention rate at 15 min (ICGR15), antithrombin III (ATIII), clearance index (HH15), and receptor index (LHL15). We compared clinical outcomes after liver resection using our modifi ed criteria and Makuuchi criteria. Results: There were 78 patients without liver failure and 8 with liver failure/dysfunction. ICGR15 (P < 0.001), ATIII (P = 0.036), operative time (P = 0.014), tumor type (P = 0.047), modifi ed criteria score (P = 0.037), lost liver volume (P = 0.006), and modifi ed criteria (P= 0.007) were signifi cantly different between the groups. Diagnostic probability of modifi ed criteria (P = 0.007) was better than the one of Makuuchi criteria (P = 0.271).Conclusions: Postoperative liver failure/dysfunction could be predicted using the modifi ed criteria. Furthermore, the criteria could be used to provide a putative liver volume for safe removal.departmental bulletin pape

Enhancement of superconducting properties in FeSe wires using a quenching technique

Enhancements of superconducting properties were observed in FeSe wires using a quenching technique. Zero resistivity was achieved at about 10 K in quenched wires, which is about 2 K higher than that of polycrystalline FeSe bulk. Furthermore, transport Jc of quenched wires showed three times higher than that of furnace-cooled wires. In contrast, the quenched polycrystalline FeSe bulks did not show the enhancement of Tc. The quenching technique is a greatly promising for fabricating FeSe wires with high Tc and high Jc, and quenched FeSe wires have high potential for superconducting wire applications

Short-and Midterm Outcomes of Laparoscopy Assisted Colectomy for Colon and Rectosigmoid Cancer

Background: Laparoscopy-assisted colectomy (LAC) has gained acceptance for the treatment of colon cancer. Objective: To evaluate the use and outcomes of LAC. Patients: Patients who underwent LAC (n = 176) for colon and rectosigmoid cancer (2001-2008). Results: There were 97 men (55.1%) and 79 women(44.9%), whose median age was 67.5 years (range, 33-99 years). The median operating time for patients who underwent LAC was 216 minutes (range, 70-440). The median blood loss was 60 ml (range 10-610 ml). Intra- and postoperative complicacomplications occurred in 3 (1.7%) and 16 patients (9.1%), respectively. The morbidity rate of patients was 0%. The overall survival rates for 3 years were 100.0%, 97.5%, 95.9%, 90.1% and 77.9% for stages 0,Ⅰ,Ⅱ,Ⅲa and Ⅲb, respectively. The relapse-free survival rates for 3 years were 100.0%, 100.0%, 90.1%, 65.7% and 62.3% for stages 0, Ⅰ,Ⅱ,Ⅲa and Ⅲb, respectively. Conclusion: This study confirmed the favorable short-and midterm operative results in patients who underwent LAC

Editorial: Conflicts

The Editorial Board reflects on the theme of 'conflict', as observed in the work published in this issue, and in the wider world

Surgical benefits of liver hanging maneuver for hepatectomy of huge liver tumor

In hepatic surgery, it is very important to control bleeding during liver resection. However, in hepatectomy for a huge liver tumor it is often difficult to reduce bleeding volume and maintain an excellent surgical view. The anterior pproach, which is hepatectomy done using the liver hanging maneuver, has beneficial effects reducing bleeding volume and preventing scattering of cancer cells from huge liver tumors. W e investigated the surgical benefits of the liver anging maneuver during hepatectomy for huge liver tumors in our department.

Role of PSCs in Regeneration of Remnant Pancreas after PX

Background and objectives Mechanism of regeneration of remnant pancreas after partial pancreatectomy (PX) is still unknown. In this study, effect of siRNA against the collagen specific chaperone, HSP47, which inhibits collagen secretion from activated pancreas stellate cells (aPSCs), and induces their apoptosis, on regeneration of remnant pancreas was determined. Methods Pancreatectomy was performed according to established methods. Proliferation of cells was assessed by BrdU incorporation. Immunostaining of HSP47 was employed to identify PSCs. Progenitor cells were identified by SOX9 staining. Acinar cells were immunostained for amylase. Co-culture of acinar cells with aPSCs were carried out in a double chamber with a cell culture insert. siRNA HSP47 encapsulated in vitamin A-coupled liposome (VA-lip siRNA HSP47) was delivered to aPSCs by iv injection. Results In remnant pancreas of 90% PX rat, new areas of foci were located separately from duodenal areas with normal pancreatic features. After PX, BrdU uptake of acinar cells and islet cells significantly increased, but was suppressed by treatment with VA-lip siRNA HSP47. BrdU uptake by acinar cells was augmented by co-culturing with aPSCs and the augmentation was nullified by siRNA HSP47. BrdU uptake by progenitor cells in foci area was slightly enhanced by the same treatment. New area which exhibited intermediate features between those of duodenal and area of foci, emerged after the treatment. Conclusion aPSCs play a crucial role in regeneration of remnant pancreas, proliferation of acinar and islet cells after PX through the activity of secreted collagen. Characterization of new area emerged by siRNA HSP47 treatment as to its origin is a future task

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)