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Background: Microhepatocellular carcinoma with a gross bile duct tumor thrombus is extremely rare, making the correct preoperative diagnosis difficult. Case presentation: A 78-year-old man was referred to our department for close examination of a liver tumor that was incidentally detected using ultrasonography. Blood tests revealed normal levels of tumor markers. Abdominal ultrasonography showed a 2-cm-sized hyperechoic mass with indistinct borders and hypoechoic margins at the origin of the right hepatic duct. Dynamic computed tomography showed a tumor with arterial phase predominance, a heterogeneous contrast effect, and prolonged enhancement. Cystic structures were observed in the tumors. In addition, localized dilatation of the caudate lobe bile duct was observed near the tumor. Cholangiography showed that the common bile duct, right and left hepatic ducts, and secondary branches did not have dilatation or stenosis. Biopsies of the bile duct revealed no malignancy. Under suspicion of intrahepatic intraductal papillary neoplasm of the bile duct, right hemi-hepatectomy was performed. The extrahepatic bile duct was preserved, because no tumor was found at the margin of the right hepatic duct during intraoperative frozen diagnosis. Macroscopically, the lesion was an 18 × 15 mm tumor occupying a dilated intrahepatic bile duct near the right hepatic duct, with a soft, fine papillary tumor. Based on morphology and immunostaining, tumor matched with moderately differentiated hepatocellular carcinoma. In addition, a 2 mm-sized hepatocellular carcinoma was observed in the liver parenchyma near the bile duct, where the tumor was located. Conclusions: Based on these findings, the patient was diagnosed with small hepatocellular carcinoma with a gross bile duct tumor thrombus. The cystic part seen on the preoperative images was considered as a gap between the bile duct and the tumor thrombus. The patient recovered well with no signs of recurrence 20 months after surgery. [ABSTRACT FROM AUTHOR]

Background/Purpose: No effective postoperative adjuvant therapies have been established for patients with hepatocellular carcinoma (HCC). The aim of this study was to investigate the effect of oral administration of branched‐chain amino acids (BCAA) on the recurrence‐free survival (RFS) after hepatic resection in HCC patients. Methods: In this randomized clinical trial, HCC patients undergoing curative resections were randomly assigned in a 1:1 ratio to the BCAA group or surgery‐alone group. The BCAA group received BCAA (Livact®) for up to 4 years. The primary endpoint was RFS. The secondary endpoint was overall survival (OS). Multivariate analysis was performed to detect the clinical characteristics significantly associated with RFS. Results: Between January 2010 and October 2014, 156 patients (75 in BCAA group and 81 in surgery‐alone group) were enrolled in the study. Of these, two patients were excluded from the efficacy analysis. Comparison of the survival curves by the log rank test demonstrated no significant difference in the RFS (P =.579) or OS (P =.268) between the BCAA and the control group. Multivariate analysis revealed that the RFS was significantly associated with age and number of tumors. A beneficial effect of BCAA on the RFS was found in patients younger than 72 years old with a HbA1c level of < 6.4%. Conclusions: Oral BCAA supplementation could not reduce the risk of recurrence after hepatic resection in HCC patients; however, the results suggested that BCAA supplementation may be beneficial for selected patients who were younger and had mildly impaired glucose tolerance. [ABSTRACT FROM AUTHOR]

Purpose: Although alpha-fetoprotein (AFP) is a useful prognostic marker in patients with hepatocellular carcinoma (HCC), a recent study has shown that the preoperative neutrophil-to-lymphocyte ratio (NLR) is also associated with the postoperative survival in such patients. Objective: To investigate the significance of the NLR in patients with primary HCC (p-HCC) showing a normal preoperative AFP. Methods: Among 478 p-HCC patients undergoing curative surgery, 112 who had a normal AFP (< 8 ng/ml) were enrolled. The patients were divided into two groups: group A, who did not have an elevated NLR (≤ 3.2); and group B, who had an elevated NLR (> 3.2). Uni- and multivariate analyses were performed to compare clinical features with the overall survival (OS). Results: A multivariate analysis of the clinical features showed that the NLR (> 3.2/≤ 3.2) (hazard ratio 2.366; 95% CI 1.069–5.235; P = 0.034) was closely associated with the OS, along with the age (> 65/≤ 65 years) (P = 0.033). Group B had a significantly lower survival ratio than group A in terms of not only the OS (P = 0.013), but also the cancer-specific survival (P = 0.002) and relapse-free survival (P = 0.039). Conclusions: An elevated NLR (> 3.2) is predictive of a poor survival in patients with primary HCC (p-HCC) showing normal AFP levels. [ABSTRACT FROM AUTHOR]

Background and Aim: Although the Cancer of the Liver Italian Program (CLIP) score is useful for prognostication of patients with hepatocellular carcinoma (HCC), a previous study has reported that the CLIP score was unable to stratify the postoperative outcomes of HCC patients in whom the score was low (0‐1). Recent studies have reported that the preoperative lymphocyte‐to‐monocyte ratio (LMR) is useful for prognostication of patients with various cancer. Methods: We reviewed 329 HCC patients with a low CLIP score (0‐1) undergoing curative resection. This study had the approval of the Institutional Review Board (28068). Multivariate analyses were carried out to detect clinical factors correlating with overall survival (OS). Kaplan‐Meier analysis and the log‐rank test were used for comparison of OS. Results: Multivariate analysis showed that LMR (<4.35/≥4.35) was significantly associated with OS (hazard ratio [HR], 2.022; 95% CI, 1.141‐3.583; P = 0.016) as well as portal vein invasion (HR, 2.410; 95%CI, 1.258‐4.618; P = 0.008). Kaplan‐Meier analysis and the log‐rank test showed a significant difference in OS and relapse‐free survival between patients with high LMR and those with low LMR. Conclusion: Preoperative LMR is useful for stratifying the prognosis of HCC patients with a low CLIP score (0‐1) undergoing curative resection. [ABSTRACT FROM AUTHOR]

Background: Frequent alterations are observed in glucose metabolism in hepatocellular carcinoma (HCC). Activation of various enzymes, including ones involved in the pentose phosphate pathway, by NF‐E2‐related factor 2 (NRF2), controls redox homeostasis in HCC. However, the mechanisms mediating NRF2 activation remain unclear. Here, we aimed to investigate the correlation between NRF2, Kelch‐like ECH‐associated protein 1 (KEAP1) syntheses and p62 phosphorylation in HCC. Methods: Biospecimens were collected from 30 patients with HCC. Protein samples were prepared through subcellular localization. Protein synthesis and phosphorylation were measured by sodium dodecyl sulfate polyacrylamide gel electrophoresis and immunoblotting. Statistical correlations among immunoblotting data and clinical features were analyzed using SPSS. Results: Compared to non‐tumor counterpart, phosphorylated p62 was accumulated in HCC (12/30; 40% of patients). Nuclear localization of NRF2 was frequently augmented in HCC (19/30; 63.3%). Statistically, p62 phosphorylation was associated with augmented activation of NRF2 (P = 0.001). Accumulation of p62 per se was moderately associated with NRF2 activation (P = 0.132). Loss of KEAP1 protein, on the other hand, poorly correlated with NRF2 activation (P = 1.000). Conclusion: In Japanese HCC, NRF2 activation is associated with phosphorylation of p62, but not with KEAP1 status. Highlight NRF2 is constitutively activated in various cancers. Shimizu and colleagues found that phosphorylation of p62, a selective autophagy substrate, is associated with NRF2 activation in HCC, providing important insights into the molecular basis of NRF2 activation, and highlighting a role of selective autophagy in the glucose metabolism in HCC. [ABSTRACT FROM AUTHOR]

Background/Aims: Postoperative large amount of ascites (PLA) is a postoperative complication in patients undergoing liver resection (LR) for hepatocellular carcinoma (HCC) and can lead to poor prognosis. The purpose of this study is to investigate predictor and prognosis of patients with PLA. Methods: Four hundred HCC patients undergoing LR were divided into 2 groups: Group A, patients without PLA; Group B, patients with PLA. Statistical analysis was performed to assess the clinical features associated with PLA and to compare the survival between Groups A and B. Results: Multivariate analysis revealed that body mass index ( ≤ 22 kg/m 2 ), albumin ( ≤ 3.5 g/dl), hyaluronic acid (HA; >200 ng/ml), bleeding (>620 ml) and total intraoperative in-out balance (>5.0 ml/kg/h) were associated with PLA. HA (>200 ng/ml) was the most useful predictor of PLA, because the area under the receiver operating characteristic curve of HA was the highest among these 5 features. The relapse-free, cancer-specific and overall survival rates were poorer in Group B than in Group A. Conclusion: The serum HA level (>200 ng/ml) is a useful predic tor of PLA in HCC patients undergoing LR. As PLA leads to poor prognosis, the surgical method for HCC patients with an elevated serum HA level should be carefully considered. [ABSTRACT FROM AUTHOR]

Telomerase reverse transcriptase (TERT) is reportedly expressed in various types of cancer. However, to the best of our knowledge, the significance of subcellular expression of TERT in hepatocellular carcinoma (HCC) has not been evaluated in detail. The present study evaluated TERT expression in resected HCC tumor tissues using immunohistochemistry. TERT expression was assessed in both the cytoplasm and the nucleus of HCC cells. The associations between TERT expression and clinical characteristics, including expression levels of DNA-dependent protein kinase catalytic unit (DNA-PKcs) and 8-hydroxyganosine (8-OHdG), were investigated. Among the 135 HCCs, TERT expression was positive only in the cytoplasm in 86 tumors (63.7%), was positive only in the nucleus in 3 tumors (2.2%), was positive in both the cytoplasm and the nucleus in 5 tumors (3.7%) and was negative in 41 tumors (30.4%). Similar results were confirmed using another antibody for TERT. Cytoplasmic TERT expression was markedly associated with hepatitis B surface antigen, poor tumor differentiation, and expression levels of DNA-PKcs and 8-OHdG. However, TERT expression in the cytoplasm or in the nucleus was not significantly associated with the overall or recurrence-free survival periods. In conclusion, TERT was mainly expressed in the cytoplasm of HCC tissues. Cytoplasmic TERT expression was closely associated with hepatitis B virus-related HCC and DNA-PKcs expression, as well as oxidative stress. [ABSTRACT FROM AUTHOR]

Background: The tumor location is the most simple clinical factor and important in liver surgery to make surgical procedure. However, no previous study has investigated the prognostic differences and clinical features of hepatocellular carcinoma showing specific laterality. This study is the first report to focus on the laterality and aimed to lead to more simple and useful predictive factor rather than recent complicated predictive models. Methods: Patients who underwent liver resection for the first time for single tumors located within each lobe between 2000 and 2018 were enrolled. We divided them into two groups based on tumor location: a right-sided group and a left-sided group. Univariable and multivariable analyses were performed to assess survival differences in relation to several other factors. Results: There were 595 eligible patients; the 5-year survival rates and disease-free survival rates were 49.5% and 19.1% in the left-sided group and 55.6% and 24.5% in the right-sided group, respectively (p = 0.026). Statistical analyses revealed that the following preoperative prognostic factors were independently significant (p < 0.05) in the left-sided group: indocyanine green retention rate at 15 min, alpha fetoprotein, protein induced by vitamin K absence or antagonists-II level, and larger tumor size. Conclusion: The left-sided group had a poorer prognosis than the right-sided group. A left-sided tumor location is a significant preoperative factor predictive of poor outcome in patients with hepatocellular carcinoma. [ABSTRACT FROM AUTHOR]

Serum hyaluronic acid (HA) levels are increased in patients with solid tumors, and may predict outcomes. However, as HA levels also correlate with the degree of liver fibrosis, the prognostic significance of serum HA levels in patients with hepatocellular carcinoma (HCC) is unclear. A total of 656 consecutive patients who underwent hepatic resection for HCC were divided into two groups by serum HA level (high HA [≥200 ng/mL], n = 248; low HA [<200 ng/mL], n = 408). Clinicopathological characteristics and postoperative survival were compared between groups. Moreover, 1:1 propensity score matching analysis was applied to adjust characteristics between groups. Both the 5-year overall and relapse-free survival rates (OSR and RFSR) in the low HA group were significantly better than those in the high HA group (59.8% vs. 38.6%, respectively, p < 0.001 and 24.5% vs. 13.1%, respectively, p < 0.001). After propensity score matching, two comparable groups of 124 patients each were obtained. However, both the 5-year OSR and RFSR in the low HA group remained significantly better than those in the high HA group (57.4% vs. 38.3%, respectively, p = 0.006 and 22.5% vs. 14.7%, respectively, p = 0.003). High preoperative HA level predicts poor postoperative survival of patients with HCC. undergoing hepatic resection. [ABSTRACT FROM AUTHOR]