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Objective: To assess the added value of arterial enhancement fraction (AEF) color maps for the differentiation of small metastases from hepatic benign lesions. Subjects and Methods: We retrospectively analyzed 46 patients with colorectal cancer who underwent multiphasic liver CT imaging and had low-attenuating liver lesions smaller than 3 cm (123 total lesions; metastasis: benign = 32:91). AEF color maps of the liver were created from multiphasic liver CT images using dedicated software. Two radiologists independently reviewed multiphasic CT image sets alone and in combination with image sets with AEF color maps using a five-point scale. The additional diagnostic value of the color maps was assessed by means of receiver-operating characteristic (ROC) analysis. Results: The area under the ROC curve (Az) increased when multiphasic CT images were combined with AEF color map analysis as compared with evaluation based only on multiphasic CT images (from 0.698 to 0.897 for reader 1, and from 0.825 to 0.945 for reader 2; P < 0.001 and 0.002, respectively). The increase Az was especially significant for lesions less than 1 cm (from 0.702 to 0.888 for reader 1, and from 0.768 to 0.958 for reader 2; P = 0.001 and P = 0.001, respectively). The mean AEF of tumor-adjacent parenchyma (35.07 ± 27.2) was significantly higher than that of tumor-free liver parenchyma (27.3 ± 20.6) (P = 0.04). Conclusions: AEF color mapping can improve the diagnostic performance for small hepatic metastases from colorectal cancer and may allow for the elimination of additional examinations. [ABSTRACT FROM AUTHOR]

As a result of recent developments in imaging modalities and wide spread routine medical checkups and screening, more incidental liver lesions are found frequently on US these days. When incidental liver lesions are found on US, physicians have to make a decision whether to just follow up or to undergo additional imaging studies for lesion characterization. In order to choose the next appropriate imaging modality, the diagnostic accuracy of each imaging study needs to be considered. Therefore, we tried to compare the accuracy of contrast-enhanced multidetector CT (MDCT) and Gd-EOB-DTPA-enhanced MRI for characterization of incidental liver masses. We included 127 incidentally found focal liver lesions (94 benign and 33 malignant) from 80 patients (M∶F = 45∶35) without primary extrahepatic malignancy or chronic liver disease. Two radiologists independently reviewed Gd-EOB-DTPA-enhanced MRI and MDCT. The proportion of confident interpretations for differentiation of benign and malignant lesions and for the specific diagnosis of diseases were compared. The proportion of confident interpretations for the differentiation of benign and malignant lesions was significantly higher with EOB-MRI(94.5%–97.6%) than with MDCT (74.0%–92.9%). In terms of specific diagnosis, sensitivity and accuracy were significantly higher with EOB-MRI than with MDCT for the diagnosis of focal nodular hyperplasia (FNH) and focal eosinophilic infiltration. The diagnoses of the remaining diseases were comparable between EOB-MRI and MDCT. Hence, our results suggested that Gd-EOB-MRI may provide a higher proportion of confident interpretations than MDCT, especially for the diagnosis of incidentally found FNH and focal eosinophilic infiltration. [ABSTRACT FROM AUTHOR]

B Introduction: b We validated the prognostic power of ADV score (alpha-fetoprotein- des- -carboxyprothrombin (DCP)-tumor volume score: (AFP (ng/ml) x DCP [PIVKA-II] (mAu/mL) x tumor volume (mL): expressed in log SB 10 sb ) for predicting risk of hepatocellular carcinoma (HCC) recurrence after hepatic resection (HR). 5-year patient survival rate was around 90% in ADV score of 2log, 85% in ADV score of 4log, 75% in ADV score of 6log, 60% in ADV score of 8log and 50% in ADV score of >8log (p<0.001). B Conclusion: b Our results using a high-volume HCC cohort confirmed that ADV score is an integrated surrogate prognostic biomarker which can be reasonably applicable to the patients undergoing HR for HCC. [Extracted from the article]

The article offers information on a 68-year-old man who was incidentally found to have cystic liver lesion. It states that the tomography revealed a thick-walled cystic lesion with internal septation and the diagnosis shows the presence of mucinous cystic neoplasm and hydatid cyst disease. It adds that the diagnosis after a 1 year of follow-up shows that the person has hepatic neuroendocrine carcinoma.

Background & aims: Contrast‐enhanced ultrasound (CEUS) Liver Imaging Reporting and Data System (LI‐RADS) is a comprehensive system for standardizing CEUS at high risk for hepatocellular carcinoma (HCC). We performed a meta‐analysis to determine the diagnostic performance of the CEUS LR‐5 for HCC and the pooled proportions of HCCs in each CEUS LI‐RADS category. Methods: We searched multiple databases for studies reporting the diagnostic accuracy of the CEUS LI‐RADS. Random‐effects model was used to determine summary estimates of the diagnostic performance of CEUS LR‐5 and the pooled proportions of HCCs in each CEUS LI‐RADS category. Risk of bias and concerns regarding applicability were evaluated with the Quality Assessment of Diagnostic Accuracy Studies‐2 tool. Results: Eleven studies were included in the final analysis, which consisted of 5535 observations with 3983 HCCs. The pooled per‐observation sensitivity and specificity of the CEUS LR‐5 for diagnosing HCC were 69% (95% confidence interval [CI], 64%–73%) and 92% (95% CI, 83%–96%) respectively. The pooled proportions of HCCs were 0% (95% CI, 0‐0%) for LR‐1, 1% (95% CI, 0%–4%) for CEUS LR‐2, 26% (95% CI, 14%–39%) for CEUS LR‐3, 77% (95% CI, 68%–86%) for CEUS LR‐4, 97% (95% CI, 95%–98%) for CEUS LR‐5, 57% (95% CI, 44%–69%) for CEUS LR‐M and 100% (95% CI, 93%–100%) for CEUS LR‐5V or TIV. Conclusions: The CEUS LR‐5 category showed moderate sensitivity and high specificity for diagnosing HCC. The proportion of HCCs was higher in the higher CEUS LI‐RADS categories. [ABSTRACT FROM AUTHOR]

Background: Combined hepatocellular carcinoma and cholangiocarcinoma (cHC) has wide histological diversity. We intended to investigate the prognostic influence of tumor types of cHC. Methods: We analyzed the clinical and pathological features of cHC along 2010 WHO classification. Study group was 100 cHC patients who underwent primary resection. Control group comprised 200 propensity score-matched patients with intrahepatic cholangiocarcinoma (ICC). Results: In cHC group, tumor diameter was 4.4 ± 2.8 cm and 95 patients had single tumor. They were classified as classical type in 46 and subtypes with stem cell (SC) features in 54. Subtypes with SC features included typical in 16, intermediate cell in 22, and cholangiolocellular in 16. Their 1- and 3-year tumor recurrence rates were 31.7 and 59.8%; and 1- and 3-year patient survival rates were 92.5 and 77.3%, respectively. Tumor recurrence ( p = 0.008) and patient survival ( p = 0.005) rates were different according to tumor types. Further stratification by subtypes with SC features resulted in prognostic stratification in tumor recurrence ( p = 0.045) and patient survival ( p = 0.042). However, tumor stage was the only independent risk factor for tumor recurrence and patient survival. Comparing with ICC control group, cHC group showed no significant difference in rates of tumor recurrence ( p = 0.523), but better survival outcomes ( p = 0.008). Median post-recurrence patient survival period was 20 months in cHC patients and 6 months in ICC patients ( p = 0.001). Conclusions: Our results indicated that there would be close relationship between the post-resection prognosis and histological types according to the 2010 WHO classification, but these histological types did not become an independent prognostic factor. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is a fast growing tumor associated with a high tendency for vascular invasion and distant metastasis. Recently, we reported that fucoidan displays inhibitory effect on proliferation and invasion of HCC cells. In this study, we investigated the anti-metastatic effect of fucoidan on HCC cells and the key signal that modulates metastasis. The anti-metastatic effect of fucoidan was evaluated in vitro using an invasion assay with human HCC cells (Huh-7, SNU-761, and SNU-3085) under both normoxic (20% O 2 and 5% CO 2 , at 37 °C) and hypoxic (1% O 2, 5% CO 2 , and 94% N 2, at 37 °C) conditions. Complementary DNA (cDNA) microarray analysis was performed to find the molecule which is significantly suppressed by fucoidan. In vivo study using a distant metastasis model by injecting SNU-761 cells into spleen via portal vein was performed to confirm the inhibitory effect by small interfering RNA (siRNA) transfection. Immunoblot analyses were used to investigate the signaling pathway. Fucoidan significantly suppressed the invasion of human HCC cells (Huh-7, SNU-761, and SNU-3085). Using cDNA microarray analysis, we found the molecule, ID-1, which was significantly suppressed by fucoidan treatment. Downregulation of ID-1 by siRNA significantly decreased invasion of HCC cells, both in vitro and in vivo (both P < 0.05) in a NDRG-1/CAP43-dependent manner. In immunoblot assay, downregulation of ID-1 by siRNA decreased the expressions of epithelial-mesenchymal transition markers including CK19, vimentin, MMP2, and fibronectin. Immunofluorescence study also revealed that actin rearrangement was inhibited when ID-1 was down-regulated in HCC cells. Interestingly, in SNU-761 cells, the ID-1 expressions under hypoxic conditions were lower as compared to those under normoxic conditions. Under hypoxic conditions, HIF-1α up-regulated NDRG-1/CAP43, while HIF-2α down-regulated ID-1, which might be a compensatory phenomenon against hypoxia-induced HCC invasion. In conclusion, NDRG-1/CAP43-dependent down-regulation of ID-1 suppressed HCC invasion both in vitro and in vivo , which was modulated by fucoidan treatment. Moreover, the compensatory down-regulation of ID-1 against hypoxia-induced HCC invasion was observed. ID-1 is a novel therapeutic target for the treatment of metastatic HCC. [ABSTRACT FROM AUTHOR]

Background: Crosstalk between tumor cells and their microenvironment plays a crucial role in the progression of hepatocellular carcinoma (HCC). Hypoxia, a common feature of advanced HCC, has been shown to modulate the evolution of the tumor microenvironment. In this study, we investigated the effect of hypoxia on tumor-stroma crosstalk in HCC.Methods: Human HCC cell lines (Huh-BAT, SNU-475) were cocultured with an activated human hepatic stellate cell line (HSCs; LX-2) under either normoxic or hypoxic conditions. Cell growth was evaluated with the MTS assay. Apoptotic signaling cascades were assessed by immunoblot analysis. Expression of CD31 and phosphorylated (p-) Akt in HCC tissues was detected by immunohistochemistry.Results: Coculturing HCC cells with HSCs under hypoxic conditions enhanced their proliferation, migration, and resistance to bile acid (BA)-induced apoptosis compared to coculturing under normoxic conditions. Under hypoxia, of various HSC-derived growth factors, PDGF-BB was the most up-regulated, leading to the activation of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway in HCC cells. Immunohistochemical study also revealed that p-Akt was highly expressed in hypoxic, hypovascular HCC as compared to hypervascular HCC. Neutralizing antisera to PDGF-BB or a PI3K inhibitor attenuated the proliferation of HCC cells cocultured with HSCs, and sensitized HCC cells to BA-induced apoptosis, especially under hypoxic conditions.Conclusions: In conclusion, hypoxic HSC-derived PDGF-BB stimulates the proliferation of HCC cells through activation of the PI3K/Akt pathway, while the inhibition of PDGF-BB or PI3K/Akt pathways enhances apoptotic cell death. Targeting tumor-stroma crosstalk might be a novel therapy in the management of human HCCs. [ABSTRACT FROM AUTHOR]

Purpose: We evaluated the prognostic value of pretreatment F-fluorodeoxyglucose positron emission tomography with computed tomography (FDG PET/CT) in patients with Barcelona Clinic Liver Cancer (BCLC) stage 0 or A hepatocellular carcinoma (HCC) who had received curative treatment or transarterial chemoembolization (TACE). Methods: Between 2009 and 2010, 317 patients diagnosed with HCC at seven hospitals were enrolled. Among these, 195 patients underwent curative treatments including resection, liver transplantation, and radiofrequency ablation. TACE was performed in 122 patients. The tumor-to-normal liver standardized uptake value ratio (TLR) of the primary tumor was measured using pretreatment FDG PET/CT. The prognostic significance of TLR and other clinical variables was assessed using Cox regression models. Differences in the overall survival (OS) associated with TLR or other significant clinical factors were examined using the Kaplan-Meier method. Results: Over a median follow-up period of 46 months, 77 patients died from cancer. In the curative cohort, higher TLR (≥2) was significantly associated with death (hazard ratio [HR] = 2.68; 95 % CI, 1.16-6.15; P = 0.020) in multivariable analysis. Patients with a higher TLR had significantly worse OS than patients with a lower TLR (5-year overall survival, 61 % vs. 79.4 %; P = 0.006). In the TACE cohort, the Model for End-Stage Liver Disease (MELD) score (≥8) was a significant independent prognostic factor for OS (HR = 3.34; 95 % CI, 1.49-7.48; P = 0.003), whereas TLR was not associated with OS. The Kaplan-Meier curves showed significantly poorer OS in patients with higher MELD scores (≥8) than in those with lower MELD scores (5-year survival rate, 33.1 % vs. 79.6 %; P < 0.001). Conclusions: Pretreatment TLR measured using FDG PET/CT was an independent prognostic factor for OS in patients with BCLC stage 0 or A HCC undergoing curative treatment. In contrast, underlying liver function appeared to be important in predicting the prognosis of patients undergoing TACE. [ABSTRACT FROM AUTHOR]

Background & Aims Advanced liver fibrosis is associated with recurrence after curative resection of hepatocellular carcinoma ( HCC). This study aimed to investigate whether noninvasive fibrosis indices could predict intrahepatic recurrence and death after curative resection of HCC. Methods Patients who underwent curative resection for hepatitis B virus ( HBV)-related HCC between 2006 and 2010 at a single tertiary hospital were included. This study analysed the association of noninvasive fibrosis indices with recurrence and overall survival. Results A total of 303 patients were included. During a median follow-up period of 56.0 (interquartile range, 42.0-70.0) months, 151 (49.8%) patients experienced HCC recurrence and 54 (17.8%) died. Based on multivariate analysis, Forns index [hazard ratio ( HR), 1.238; 95% confidence interval ( CI), 1.097-1.398; P = 0.001] was independently associated with tumour recurrence after adjustment for anti- HBe positivity, histological cirrhosis, tumour size and number. Patients with Forns index <6.9 had a significantly longer recurrence-free survival rate than patients with Forns index ≥6.9 ( P < 0.001 by log-rank test). Forns index ( HR, 1.246; 95% CI, 1.034-1.501; P = 0.02) could also predict overall survival after adjustment for tumour size and number. Forns index detected cirrhosis with an AUROC of 0.700 (95% CI, 0.641-0.758). Aspartate aminotransferase-to-platelet ratio index, cirrhosis discriminant score, FIB-4 index, P2/ MS and Lok index detected cirrhosis comparably to Forns index, but were not associated with tumour recurrence or death. Conclusions Our data suggest that Forns index could be a useful predictor of recurrence and overall survival after curative resection of HBV-related HCC. [ABSTRACT FROM AUTHOR]

Backgrounds & Aims The aim of this study is to evaluate the prognostic significances of not only the initial and the best response during repeated transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC), but if eligible, also the time point of achieving treatment responses. Methods Three hundred and fourteen treatment-naïve patients with well-preserved liver function undergoing TACE were recruited. Treatment responses were assessed using modified Response Evaluation Criteria in Solid Tumors. Overall survival (OS) was analyzed using Kaplan–Meier methods, and Cox regression analysis was performed for multivariate analysis. Results After adjusting other variables, objective response (complete response [CR] and partial response [PR]) as the initial response (adjusted hazard ratio [HR] 0.410) and the best response (adjusted HR 0.335) had independent prognostic significances for OS, respectively (both p <0.001). Objective responders as the initial response had the longest OS, followed by patients who subsequently achieved objective response after at least two sessions and those who did not achieve objective response during treatment course eventually (52.6, 27.0, and 10.8 months, respectively; log-rank test, p <0.001). Likewise, patients with CR as the initial response had the longest OS, followed by those who subsequently achieved CR after at least two sessions and those who achieved PR as the best response (70.2, 40.6, and 23.0 months, respectively; log-rank test, p <0.001). Large (>5 cm) and multiple (⩾4) tumors were independently associated with failure to achieve CR after the initial TACE (both p <0.05). Conclusion Both the initial and the best response predicts OS effectively. However, achievement of treatment response at an early time point is still the most robust predictor for favorable outcomes. [ABSTRACT FROM AUTHOR]

Background/Aims: Sorafenib is a standard treatment for advanced hepatocellular carcinoma (HCC) (Barcelona Clinic Liver Cancer [BCLC] stage C). However, transarterial chemoembolization (TACE) has also been widely used as a treatment for patients with advanced HCC, even if they have extrahepatic metastases (EHM). The aim of this study was to determine the efficacy of TACE for advanced HCC patients with EHM upon initial diagnosis, as compared with those patients without EHM. Methods: This cohort study involved consecutive patients who underwent TACE as an initial treatment for advanced HCC. One hundred seventy-seven patients with EHM (the EHM group) and 205 with portal vein invasion without EHM (the non-EHM group) were included. A survival analysis was performed to compare overall survival between the two groups. Results: The mean age was 54.5±9.9 years, and median follow-up duration was 13.1 months (range, 0.5–111.0). Overall survival was significantly shorter in the EHM group than the non-EHM group (median, 8.3 vs. 19.1 months; P<0.001). A multivariate analysis showed that the presence of EHM was an independent poor prognostic factor for shorter overall survival (adjusted hazard ratio, 1.74; 95% confidence interval, 1.39–2.17; P<0.001) after adjustment for Child-Pugh classification, intrahepatic tumor T classification, tumor response to TACE, and serum alpha-fetoprotein level. Patients administered TACE and systemic therapy demonstrated a better survival rate than those administered TACE alone in both the EHM (median, 13.5 vs. 7.2 months) and non-EHM groups (median, 27.9 vs. 18.2 months) (both, P<0.05). Conclusions: The prognosis of advanced HCC patients with EHM is significantly worse than those without EHM administered repeated TACE treatments, even if their tumor stage was similar to BCLC stage C. These results suggest that EHM presence means aggressive tumor biology and that BCLC stage C might be subclassified according to EHM presence. [ABSTRACT FROM AUTHOR]

Objective: To compare the accuracy of multidetector computed tomography (MDCT) and gadoxetic acid-enhanced magnetic resonance imaging (MRI) for the detection of intrahepatic tumor recurrence after curative resection of hepatocellular carcinoma (HCC). Materials and methods: Fifty-six patients who underwent MDCT and gadoxetic acid-enhanced MRI for postoperative surveillance after resection of HCC were retrospectively analyzed; 26 patients had a recurrence (36 lesions) and 30 patients did not. Recurrent HCCs were confirmed by histological examinations in two, typical dynamic imaging findings on CT and/or MRI in 28, and by demonstration of growth or tumor staining on angiography on six. Two reviewers graded the confidence for the presence of recurrence on CT and MRI, using a five-point scale. The jackknife free-response receiver operating characteristic method was used to compare diagnostic performance. The accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated. Results: For 36 recurrent lesions, the figure of merit was significantly higher for MRI than MDCT for detecting recurrence for both reviewers ( p < 0.005 for both reviewers). In lesion-by-lesion analysis, the sensitivity was significantly higher on MRI (100% for reviewer 1 and 97% for reviewer 2) than on MDCT (44.4% and 66.6%) for both reviewers ( p < 0.005 for both reviewers). Also in patient-by-patient analysis, sensitivity was significantly higher on MRI (100% and 96.1%) than on MDCT (57.6% and 76.9%) for both reviewers ( p < 0.05 for both reviewers). Conclusion: Gadoxetic acid-enhanced MRI is superior to MDCT for detecting intrahepatic recurrence after curative resection of HCC. [ABSTRACT FROM AUTHOR]

Insulin like-growth factor-1 (IGF-1) reflects hepatic synthetic function and plays a major role in the development and progression of various cancers. In the present study, we investigated whether baseline serum IGF-1 levels predict time-to-progression (TTP) and overall survival (OS) in hepatocellular carcinoma (HCC) patients treated with transarterial chemoembolization (TACE). A total of 155 consecutive treatment-naive patients with HCC who had undergone TACE as initial treatment were included from a prospective cohort. Baseline serum IGF-1 levels were analyzed with regard to their associations with disease progression and survival. During a median follow-up period of 41.8 months, patients with low IGF-1 levels showed significantly shorter TTP (median, 6.0 months; 95% confidence interval [CI], 4.5–7.6) than patients with high IGF-1 levels (median, 16.5 months; 95% CI, 4.9–28.1; p = 0.003). In the multivariate analysis, BCLC stage, serum vascular endothelial growth factorlevels, and IGF-1 levels were independent risk factors for disease progression. The hazard ratio (HR) of progression for each 10 ng/mL decrease in IGF-1 level was 1.072 (95% CI, 1.029–1.117; p = 0.001). Furthermore, together with tumor size, stage, and treatment response, IGF-1 levels were an independent predictor of poorer survival (for each 10 ng/mL decrease in IGF-1 level; HR, 1.057; 95% CI, 1.001–1.115; p = 0.045). In conclusion, low baseline IGF-1 levels independently correlated with shorter TTP and poorer OS in patients with HCC who underwent TACE. [ABSTRACT FROM AUTHOR]

Background: Polymorphisms near the IL28B gene have been proposed to be strongly associated with treatment response and the rate of spontaneous clearance of hepatitis C virus infection, and treatment response of hepatitis B virus (HBV) infection. In this study, we aimed to determine whether these polymorphisms could affect natural courses of HBV in-fection. Methods:Genetic variations were identified through direct DNA sequencing using TaqMan assay in 1,439 patients with past or present HBV infection. Subjects included 404 spontaneously recovered patients, 313 chronic hepatitis B (CHB) patients, 305 liver cirrhosis (LC) patients and 417 hepa-tocellular carcinoma (HCC) patients. Three polymorphisms near the IL28B gene, rs8099917T>G, rs12979860C>T and rs12980275A>G, were identified. Associations between these polymorphisms and HBV clearance, hepatitis B e antigen (HBeAg) clearance as well as HCC occurrence among pa-tients were analyzed using logistic regression analyses ad-justed forage and gender. Results: There were no significant associations between these polymorphisms and the HBV clearance both in CHB and LC groups. Similarly, these poly-morphisms showed no significant associations with HBeAg clearance and the occurrence of HCC either. Discussion: No significant association was identified between polymor-phisms near the IL28B gene and the natural courses of chron-ic HBV infection, including the HBV clearance and HCC occur-rence [ABSTRACT FROM AUTHOR]

Objectives: To investigate the effectiveness of qualitative diffusion-weighted imaging (DWI), subtraction of unenhanced from arterial phase images, and hepatobiliary phase (HBP) images in estimating the histopathological grade of hepatocellular carcinoma (HCC). Methods: We retrospectively reviewed gadoxetic acid-enhanced magnetic resonance images of 175 patients with 201 surgically resected HCCs. The signal intensity and its relationship with histopathological grade were assessed for each sequence and a combination of sequences. Results: There was a tendency towards higher grades in tumours showing restricted diffusion on DWI ( P < 0.001) or arterial enhancement on subtraction imaging ( P <0.001), but not hepatocyte-defect on HBP images ( P = 0.33). When lesions were divided into three groups based on combined findings on DWI and subtraction imaging, a linear trend was observed between group and grade ( P < 0.001). The positive predictive value (PPV) of the combination of no restricted diffusion and no arterial enhancement in predicting well-differentiated HCC was 100%, higher than the PPV of individual findings on DWI (74%) or subtraction imaging (81%). Conclusions: DWI and subtraction imaging are helpful for predicting the histopathological grade of HCC, especially when the two sequences are considered together. Key Points: • Predicting the histopathological grade of hepatocellular carcinoma (HCC) preoperatively is important. • Diffusion-weighted imaging (DWI) and subtraction imaging are recently developed MR techniques. • Retrospective study showed DWI and subtraction imaging helps predict HCC grades. • Management of patients with HCC becomes more appropriate. [ABSTRACT FROM AUTHOR]

Background: Micro RNAs-371-372-373 (miRNAs-371-373), originating from the same pri-miRNA transcript, are reported to be upregulated in hepatocellular carcinoma (HCC) and to be related to the regulation of hepatitis B virus (HBV) infection. Our study investigated whether pri-miRNAs-371-373 polymorphisms are associated with the risk of HCC occurrence and HBV clearance. Methods: Genetic variations were identified through direct DNA sequencing using TaqMan assay. Three sequence variants of pri-miRNAs-371-373 were identified. Genetic associations of those with HCC occurrence and HBV clearance among patients with HBV infection were analyzed using logistic regression analyses with adjustment for age and gender (n = 1439). Results: For the occurrence of HCC, polymorphism rs3859501C.A acted as a protective factor both in chronic carriers (OR = 0.75, P = 0.005 in a codominant model; OR = 0.71, P = 0.02 in a dominant model; OR = 0.66, P = 0.03 in recessive model) and liver cirrhosis patients (OR = 0.69, P = 0.001 in a codominant model; OR = 0.60, P = 0.003 in a dominant model; OR = 0.63, P = 0.03 in a recessive model). The pri-miRNAs-371-373_ht2 [C-A-C] also showed a protective effect on HCC occurrence both in the chronic carrier and liver cirrhosis groups (p<0.05 in both). However, there was no significant association between primiRNAs- 371-373 polymorphisms and HBV clearance. Conclusions: In conclusion, among chronic carriers and liver cirrhosis patients, the A allele of rs3859501 and the haplotype pri-miRNAs-371-373_ht2 were more protective to HCC than other genotypes and haplotypes. Further studies into the roles of rs3859501 and pri-miRNAs-371-373_ht2 haplotype in hepatocarcinogenesis are needed. [ABSTRACT FROM AUTHOR]

Abstract: Background: To evaluate hepatocellular carcinoma (HCC) that developed in patients with no evidence of a tumor during a prior ultrasound (US) performed within 1 year of the diagnosis. Methods: We retrospectively analyzed data for 100 consecutive patients with liver cirrhosis who had undergone US within 1 year prior to HCC diagnosis and who showed no liver lesions on the previous US. Size and T stage of HCC were assessed as well as whether patients met surgical criteria for liver transplantation as HCC treatment [Milan or University of California at San Francisco (UCSF) criteria]. Results: The mean interval between the negative and diagnostic scans was 5 months, 13 days. HCC presented as a single nodule in 69 patients (size, 0.8–8.0cm), as two or more nodules in 18 patients, and as the diffuse form of HCC in 13 patients. HCC presented as a small tumor (<3cm) in 48 patients. T stages were: T1 in 26 patients, T2 in 45, T3 in 18, and T4 in 11. The Milan criteria were met in 79 patients. Eighty-five patients fulfilled the UCSF. Conclusion: Patients may present with advanced HCC, even if sonographic findings were negative within 1 year prior to diagnosis. [Copyright &y& Elsevier]

Objective: To assess whether reticular hypointensity on hepatobiliary phase images of gadoxetic acid-enhanced magnetic resonance imaging (EOB-MRI) is a diagnostic finding of sinusoidal obstruction syndrome (SOS) in patients with hepatic metastases who have undergone chemotherapy. Methods: We retrospectively analysed EOB-MRI of 42 patients who had undergone chemotherapy before hepatic resection of colorectal hepatic metastases. Two radiologists, who were unaware of whether or not the patients had SOS, reviewed the hepatobiliary phase images to determine the presence of hypointense reticulation in the liver using a 5-point scale. The sensitivity, specificity and area under the receiver operating characteristics curve (A) were calculated for each reviewer. Results: The sensitivity, specificity and A for the diagnosis of SOS were 75%, 100% and 0.957 for reader 1 and 75%, 96.2% and 0.936 for reader 2, respectively. In one patient who received a false-positive diagnosis by one reader, there was sinusoidal fibrosis on histological examination, but not diagnostic for SOS. False-negative diagnosis occurred in four patients for both readers; histology of these patients showed minimal and localised sinusoidal congestion and fibrosis. Conclusions: Reticular hypointensity on hepatobiliary phase images of EOB-MRI is highly specific for the diagnosis of SOS in patients with treated colorectal hepatic metastases. Key Points: • Gadoxetic acid enhanced magnetic resonance imaging (EOB-MRI) can identify the sinusoidal obstruction syndrome (SOS) • The diagnosis can be achieved with high specificity and good interobserver agreement. • SOS typically demonstrates diffuse hypointensity on hepatobiliary phase images on EOB-MRI. • EOB-MRI may be falsely negative in patients with minimal degree of SOS. [ABSTRACT FROM AUTHOR]

Abstract: Hypoxia induces survival signals in hepatocellular carcinoma (HCC). We attempted to find a hypoxia-induced signal that could be used for modulating HCC cell death. Cellular retinoic acid binding protein-II (CRABP-II) expression was significantly increased in hypoxic HCC cells. Treatment with retinoic acid (RA), a ligand for CRABP-II, induced HCC cell apoptosis more effectively in hypoxia than in normoxia, whereas hypoxia-induced CRABP-II expression attenuated RA-induced apoptosis. Inhibition of CRABP-II enhanced RA-induced apoptosis and sensitized RA-resistant HCC cells to RA cytotoxicity by attenuating p42/44 MAPK and Akt activation. Therefore, RA/CRABP-II signal modulation is therapeutically implicated in infiltrative HCCs exposed to hypoxia. [Copyright &y& Elsevier]

The prognosis of untreated hepatocellular carcinoma (HCC) is usually grave, although there have been a few case reports of spontaneous regression. Tumor recurrence after spontaneous regression has been rarely reported, and there have been no previous reports of recurrent hepatocellular carcinoma after spontaneous regression. Two cases of hepatocellular carcinoma that spontaneously regressed and subsequently recurred are presented. The patients' tumors spontaneously regressed, as reflected by the radiologically evidenced reduction in tumor size and markedly decreased alpha-fetoprotein levels. Subsequent tumor recurrences after regression were evidenced by radiologic findings of newly growing nodules and appreciably increased alpha-fetoprotein levels. To the authors' knowledge, these two patients represent the first reported cases of hepatocellular carcinoma recurrence after spontaneous regression. In both of these patients, new hepatocellular carcinomas recurred at different sites before the spontaneous regression of the original HCCs was complete. Although the precise causes of the regression and the subsequent recurrence remain to be further investigated, this phenomenon suggests that multicentric hepatocarcinogenicity and intratumoral events in each hepatocellular carcinoma nodule may be involved. [ABSTRACT FROM AUTHOR]