Histological differentiation is a major pathological parameter associated with poor prognosis in patients with hepatocellular carcinoma (HCC) and the molecular signature underlying HCC differentiation may involve key proteins potentially affecting the malignant characters of HCC. To develop prognostic biomarkers for HCC, we examined the global protein expression profiles of 45 surgically resected tissues, including 27 HCCs with different degree of histological differentiation, 11 adjacent nontumor tissues, and seven normal liver tissues. Unsupervised classification grouped the 45 samples according to their histological classification based on the protein expression profiles created by laser microdissection and two-dimensional difference gel electrophoresis (2D-DIGE). Statistical analysis and mass spectrometry identified 26 proteins with differential expression, of which 14 were functionally linked to c-Myc, AP-1, HIF1A, hepatocyte nuclear factor 4 alpha, or the Ras superfamily (RhoA, CDC42, and Rac1). Among the proteins identified, we focused on APC-binding protein EB1 (EB1) because it was dominantly expressed in poorly differentiated HCCs, which generally correlate with the poor prognosis in patients with HCC. In addition, EB1 is controlled by c-Myc, RhoA, and CDC42, which have all been linked to HCC malignancy. Immunohistochemistry in a further 145 HCC cases revealed that EB1 significantly correlated with the degree of histological differentiation (P < 0.001), and univariate and multivariate analyses indicated that EB1 is an independent prognostic factor for recurrence (hazard ratio, 2.740; 95% confidence interval, 1.771-4.239; P < 0.001) and survival (hazard ratio, 2.256; 95% confidence interval, 1.337-3.807; P ‫؍‬ 0.002) of patients with HCC after curative surgery. Conclusion: Proteomic profiling revealed the molecular signature behind the progression of HCC, and the prognostic value of EB1 in HCC. (HEPATOLOGY 2008;48:1851-1863 H epatocellular carcinoma (HCC) is one of the most common and aggressive malignancies world-wide and is the third leading cause of cancer death. 1 HCC is a major health problem with high prevalence in Asia and Africa, 2,3 and recent studies indicated that the incidence of HCC has increased substantially in the United States and the United Kingdom over the last decades. 4,5

In this unprecedented COVID-19 pandemic, several key issues must be addressed to ensure safe treatment and prevent rapid spread of the virus and a consequential medical crisis. Careful evaluation of a patient's condition is crucial for deciding the triage plan, based on the status of the disease and comorbidities. As functionality of the medical care system is greatly affected by the environmental situation, the treatment may differ according to the medical and infectious disease circumstances of the institution. Importantly, all medical staff must prevent nosocomial COVID-19 by minimizing the effects of aerosol spread and developing diagnostic and surgical procedures. Polymerase chain reaction (PCR) screening for COVID-19 infection, particularly in asymptomatic patients, should be encouraged as these patients are prone to postoperative respiratory failure. In this article, the Japan Surgical Society addresses the general principles of surgical treatment in relation to COVID-19 infection and advocates preventive measures against viral transmission during this unimaginable COVID-19 pandemic.

Huge HCC (≥10 cm) is an independent risk factor due to a high risk for initial extra-hepatic recurrence. Future systemic adjuvant therapy is needed for these patients. J. Surg. Oncol. 2017;115:324-329. © 2016 Wiley Periodicals, Inc.

Background and Aim Combined hepatocellular–cholangiocarcinoma (CHC) is a primary liver cancer containing both hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) elements. Its reported clinicopathological features and prognoses have varied because of its low prevalence. This study aimed to clarify these aspects of CHC. Methods We enrolled 28 patients with CHC, 1050 with HCC, and 100 with ICC and compared the clinicopathological characteristics and prognosis of CHC with HCC and ICC. We also analyzed prognostic factors, recurrence patterns, and management in CHC patients. Results The incidences of hepatitis B virus and high α‐fetoprotein and protein induced by vitamin K absence or antagonists‐II levels were significantly higher among CHC compared with ICC patients. Multiple tumors were more frequent in CHC compared with the other groups, while vascular invasion and lymph node metastasis were more frequent in the CHC than the HCC group. The 5‐year overall survival and disease‐free survival rates for CHC were 25.1% and 22.6%, respectively. Overall survival was significantly lower than for HCC (P < 0.001) but not ICC (P = 0.152), while disease‐free survival was significantly lower than for HCC and ICC (P = 0.008 and P = 0.005, respectively). Multivariate analysis identified carcinoembryonic antigen levels and tumor size as independent predictors in patients with CHC. Conclusions The clinical features of CHC, including sex, hepatitis B virus infection, α‐fetoprotein, and protein induced by vitamin K absence or antagonists‐II levels, were similar to HCC, while its prognosis and pathological features, including vascular invasion and lymph node metastasis, were similar to ICC. Carcinoembryonic antigen levels and tumor size were independent prognostic factors in patients with CHC.

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SynopsisHepatectomy should be considered for hepatocellular carcinoma with bile duct tumor thrombus.3 Abstract Purpose: The purpose of this study was to evaluate the short-and long-term outcomes of hepatectomy for hepatocellular carcinoma (HCC) with bile duct tumor thrombus (BDTT), including cases with obstructive jaundice. Methods:We reviewed 42 HCC patients with BDTT, including 6 patients who needed preoperative biliary drainage due to obstructive jaundice and 732 HCC patients without BDTT. We analyzed the impact of BDTT on the surgical outcomes and assessed the outcomes of hepatectomy for patients presenting with obstructive jaundice.

Hepatocellular carcinoma (HCC) is a highly prevalent cancer with poor prognosis. The correlation between overexpression of fatty acid‐binding protein 5 (FABP5) and malignant potential of tumor growth and metastasis in several cancers has been previously reported. However, the correlation between FABP5 expression and HCC malignant behavior remains unknown. We compared FABP5 expression and patient characteristics in paired HCC and adjacent noncancerous liver tissues from 243 patients who underwent surgical resection of primary HCC. Cell proliferation, invasion, and migration assays were performed in HCC cell lines overexpressing FABP5 or downregulated for FABP5. Tumor growths were monitored in xenograft model, and liver and lung metastasis models were established. In the 243 HCC patients, FABP5‐positive staining (n = 139/243, 57.2%) was associated with poor prognosis and recurrence (P < 0.0001) and showed positive correlation with distant metastasis, tumor size and vascular invasion (P < 0.05). Cell proliferation, invasion, and migration in vitro were enhanced by upregulation of FABP5 and decreased by downregulation of FABP5 in HCC cell lines. Similar results in tumor formation and metastasis were obtained through in vivo analyses. PCR array results revealed upregulation of SNAI1 in FABP5‐overexpressing HepG2 cells. Western blot analysis showed significantly increased expression of E‐cadherin and ZO‐1 and decreased SNAI1 expression and nuclear translocation of β‐catenin by knockdown of FABP5. We revealed a significant role for FABP5 in HCC progression and metastasis through the induction of epithelial‐to‐mesenchymal transition. FABP5 may be a potential novel prognostic biomarker and new therapeutic target for HCC.

Background: The aims of this study were to investigate predictive factors for microscopic portal