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Somatic mutations in the telomerase reverse transcriptase (TERT) promoter are related to telomerase activation and frequently occur at two hot spots located at -124 and -146 bp relative to the start codon in various cancers. Here, we investigated the occurrence and implications of genetic alterations in the TERT promoter in hepatitis B viral hepatocellular carcinoma (B viral HCC). TERT promoter mutations, especially -124C>T, clearly enhanced transcriptional activity in HCC cell lines. In contrast, TERT mRNA expression was lower in B viral HCC patients with TERT promoter mutations than in those without. We identified prospero homeobox protein 1 (PROX1) as a novel transcriptional activator of TERT; this protein was shown to have particularly strong binding affinity for the mutant TERT promoter. However, stable expression of the hepatitis B virus X (HBx) protein inhibited PROX1-mediated TERT expression in vitro. Our data suggest that TERT promoter mutations can enhance the promoter activity in HCC cell lines expressing PROX1 but are not the predominant mechanism of TERT upregulation in B viral HCC patients, based on the inhibition of PROX1-dependent transcriptional activation by HBx.

BACKGROUND To date, there are few studies comparing the outcomes of robotic hepatectomy (RH) versus open hepatectomy (OH). We report the first systematic review and meta-analysis comparing the outcomes of RH versus OH. METHODS A systemic review was performed of all comparative studies of RH versus OH that reported the perioperative outcome(s) of interest. RESULTS Seven retrospective cohort studies were included. There was no significant difference in patients' baseline characteristics. RH was associated with a longer operation time (mean difference (MD) 61.47 min; 95% confidence interval (CI) (7.03, 115.91); P = 0.03), shorter hospital stay (MD -2.57 days; 95% CI (-3.31, -1.82); P < 0.001), lower costs, less overall (risk ratio (RR) 0.63; 95% CI (0.46, 0.86); P = 0.004), minor (RR 0.64; 95% CI (0.43, 0.95); P = 0.03) and major (RR 0.45; 95% CI (0.22, 0.94); P = 0.03) post-operative complications compared to OH. CONCLUSION RH had superior perioperative outcomes and was not cost prohibitive compared to OH, but had longer operation times.

Background This study was designed to compare perioperative and oncologic outcomes between minimally invasive liver resection (MILR) and conventional open liver resection (COLR) for hepatocellular carcinoma (HCC) using a propensity-score matched analysis. Methods Ninety-nine patients who received MILR were matched with 198 patients treated with COLR out of 928 patients with HCC who received curative liver resection from 2002 to 2012. A multivariable logistic model based on factors related to the patient, tumor, and surgical procedure was used to estimate a propensity score. Results The MILR group experienced significantly less intraoperative blood loss (mean: 389.55 vs 580.66 mL; P = 0.008), lower complication rates (13.1% vs 24.7%; P = 0.020), and a shorter length of hospital stay (mean: 8.40 vs 13.39 days; P < 0.001). The two groups did not differ significantly in disease-free (P = 0.701) or overall survival (P = 0.086). Conclusions MILR produced better perioperative and comparable oncologic outcomes than COLR for HCC. Copyright © 2015 John Wiley & Sons, Ltd.

Background Recurrence of hepatocellular carcinoma (HCC) after curative resection continues to be a major cause of death. This prospective study is designed to investigate whether histological subclassification of cirrhosis using the Laennec system could predict recurrence in patients with hepatitis B virus (HBV)-related HCC after curative resection. Methods Patients with HBV-related HCC who underwent curative resection and showed Laennec stage 3 to 4 were enrolled and the cases with stage 4 were subclassified histologically into three groups (stages 4A, 4B and 4C) according to the Laennec system. Between February 2006 and August 2009, 92 patients were recruited. Results Stage 3, 4A, 4B and 4C were identified in 24 (26.1%), 15 (16.3%), 43 (46.7%) and 10 (10.9%) patients respectively. The cumulative incidence rates of recurrence at 1, 2 and 3 years were 24.2%, 40.5% and 55.1% respectively. On multivariate analysis, serum albumin [hazard ratio (HR), 0.528; 95% confidence interval (CI), 0.312–0.891; P = 0.017] and Edmondson–Steiner grade III–IV (HR, 3.456; 95% CI, 1.123–10.517; P = 0.031) were significantly correlated with early recurrence (

Introduction Hypersplenism with thrombocytopenia is a common complication of cirrhosis with portal hypertension. We evaluated the role of splenectomy in patients with hepatocellular carcinoma (HCC) in terms of the improvement of biochemical indices and liver volume. Methods Nineteen patients with HCC underwent liver resection and splenectomy from January 2000 to December 2009. Thirty-nine patients who underwent liver resection during the same period were enrolled as case-matched controls. We performed a retrospective review of prospectively collected data. We analysed the results of biochemical tests, disease-free survival and overall survival and measured the liver volume before and at 90 days after operation. Results Preoperative white blood cell counts (P = 0.001), platelet counts (P = 0.021), total bilirubin (P ≤ 0.001) and prothrombin time by international normalized ratio (P = 0.043) were significantly different. However, these results had converged to similar levels 90 days after the operation. The degree of increment in liver volume were similar (P = 0.763). In splenectomy group, portal vein thrombosis developed in eight patients and all patients except one recovered using only conservative treatments. There was an operative mortality because of liver failure by thrombosis. Conclusions Although splenectomy may induce thrombosis, liver failure and subsequent mortality, splenectomy may improve liver function and expand the indication of liver resection if postoperative management is conducted conservatively.

Alpha-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP) are widely used complementary tumor markers for hepatocellular carcinoma (HCC). In this study, we investigated whether preoperative AFP and DCP levels predict recurrence after curative resection in patients with hepatitis B virus (HBV)-related HCC. Records for 267 patients who were diagnosed with HBV-related HCC and who underwent curative resection for HCC were retrospectively reviewed. Patients were divided into two preoperative groups: pre-op I (AFP ≥ 20 ng/dL and DCP ≥ 40 mAU/mL) and pre-op II (AFP ≥ 20 ng/dL and DCP

Background and Aim: Liver stiffness (LS) measurement can distinguish individuals with potential liver disease (LD) from the general population. However, if LS is sex-sensitive, prevalence of LD may be incorrectly estimated when the same reference LS value is applied irrespective of sex. Here, we evaluated whether normal ranges of LS differ between healthy men and women. Methods: LS was measured in a cohort of healthy living liver and kidney donors, none of whom suffered from diabetes mellitus, hypertension, hepatitis B or C virus infection, heart or liver dysfunction, or metabolic syndrome. Patients with abnormal laboratory findings related to potential LD (platelet count 40 IU/L; alanine aminotransferase [ALT] > 40 IU/L; albumin 1.2 mg/dL; gamma-glutamyl transpeptidase > 54 IU/L; alkaline phosphatase > 115 IU/L) were excluded. Results: Among 242 patients analyzed, the mean age was 34.1 for men (n = 121) and 40.5 years for women (n = 121) (P

Background and Aim: Although several studies have investigated the normal range of liver elasticity using acoustic radiation force impulse (ARFI) elastography in healthy volunteers, they could not strictly exclude the morphological and functional liver abnormalities. The aim of this study was to identify the normal range of ARFI velocity by recruiting healthy living liver and kidney donors who passed the full laboratory tests and imaging studies. Methods: The study prospectively enrolled 108 healthy living liver (n = 42) and kidney donors (n = 66) who were admitted for transplantation between July 2010 to April 2011. None of the subjects had abnormal liver function test and imaging findings including conventional ultrasonography, computed tomography or magnetic resonance imaging. Results: The mean age of the study population (58 men and 50 women) was 35.5 years, and the mean ARFI velocity was 1.07 ± 0.11 m/s (range: 0.79–1.27). ARFI velocity was not significantly different between subjects with body mass index (BMI)

Background and Aim: Despite improvements of treatment in hepatocellular carcinoma (HCC), the recurrence rate after curative hepatic resection still remains remarkably high. An immediate recurrence of HCC after surgery is frustrating. We tried to clarify risks of immediate postoperative recurrence of HCC; that is, within 4 months after curative hepatic resection. Methods: A total of 167 patients with HCC underwent hepatic resection; 60 had immediate postoperative recurrences (IPR group), and 107 had disease-free survival for more than 5 years (DFS group). Variables were compared between the two groups. Results: Univariate analysis showed the following variables were significant risk factors for immediate postoperative recurrence of HCC: male sex, elevated serum aspartate aminotransferase level, greater amount of blood loss, longer operation time, worse tumor differentiation, higher tumor node metastasis stage, and presence of any of the following: intrahepatic metastasis, tumor-rupture, portal venous invasion, or microvascular invasion. In multivariate analysis, only portal venous invasion was a significant risk factor (odds ratio = 3.2, P = 0.03, standard error = 0.5, Logistic regression analysis). Conclusions: Portal venous invasion may be the most significant risk factor for immediate postoperative recurrence of HCC. However, accurate assessment of this risk factor may require histological examination, limiting its utility as a preoperative predictor. Further research is necessary to definitively identify preoperative predictors.

Background: Hepatic resection for hepatocellular carcinoma (HCC) is not currently recommended for patients with clinically significant portal hypertension (PHT); however, recent studies have shown similar post-operative outcomes between patients with and without clinically significant PHT. Aim: To clarify the post-operative prognostic relevance of clinically significant PHT in Child–Pugh A cirrhotic patients. Methods: A total of 100 Child–Pugh A cirrhotic patients who underwent curative resection of HCC were eligible for this analysis. Patients were divided into two groups: PHT group (n=47) and non-PHT group (n=53). Results: Clinicopathological variables showed no significant differences except for prothrombine time. Liver-related complications were significantly higher in the PHT group (P=0.015), and the 5-year overall survival rate was significantly higher in the non-PHT group (78.7 vs. 37.9%, P

Background and Aim: Previous studies have reported different risk factors for early and late intrahepatic recurrence after resection of hepatocellular carcinoma (HCC). However, the prognostic significance of the risk factors for early and late recurrence has not been clarified. Methods: A total of 190 Hepatitis B surface antigen-positive patients who received curative resection for HCC were reviewed. We investigated prognostic factors for disease-free and overall survival after resection, and further analyzed the relationship between significant prognostic factors and risk factors for early (≤14 months) and late (>14 months) intrahepatic recurrence. Results: The 5-year disease-free and overall survival rates were 43.9% and 71.5%, respectively. In multivariate analysis, adverse prognostic factors for disease-free survival were presence of serum HBeAg, perioperative transfusion, and the presence of portal vein invasion (PVI) and/or intrahepatic metastasis (IM). Multivariate analysis revealed that overall survival was associated with ICG R15, serum albumin, Edmondson–Steiner grade, and the presence of PVI and/or IM. Independent risk factors for early intrahepatic recurrence were perioperative transfusion and PVI and/or IM, whereas positivity for HBeAg was the only risk factor for late recurrence. In addition, post-recurrence survival in patients with late intrahepatic recurrence was completely comparable to that of patients who never experienced recurrence. Conclusions: The presence of serum HBeAg, the risk factor for late intrahepatic recurrence did not affect overall survival after resection because late recurrence was relatively well controlled by current available treatments. To further improve long-term surgical outcomes, effective treatment and preventive methods for early intrahepatic recurrence should be investigated.