Liver Cancer
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Primary liver cancer is a disease in which the cells of liver become cancerous (malignant). Primary liver cancer is different from cancer that has spread from another place in the body to the liver. The liver is found in the upper right side of the abdomen. It is an an important organ which is involved in digesting food and converting it to energy and it also filters and stores blood. Liver cancer is relatively rare, known risk factors for liver cancer are prior hepatitis B or C infections or cirrhosis of the liver. There are two main types of liver cancer in adults: hepatocellular carcinoma and cholangiocarcinoma. Hepatoblastoma is another type of liver cancer which mostly occurs in children. Some types of liver cancer produce abnormaly high levels of alpha-fetoprotein (AFP) which can aid diagnosis.

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Menu: Liver Cancer

Information for Patients and the Public
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Latest Research Publications
Childhood Liver Cancer

Information Patients and the Public (12 links)

Information for Health Professionals / Researchers (13 links)

Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Chung H, Chapman WC
Liver transplantation for metastatic neuroendocrine tumors.
Adv Surg. 2014; 48:235-52 [PubMed] Related Publications
The ideal management of NET must be addressed on a case-by-case basis, with consideration given to patient factors, disease burden, and clinical tumor activity. Outcome improvement for LT in the setting of metastatic disease requires better characterization of the biological behavior of NETs and further identification of factors to be included in the selection criteria. Box 3 summarizes the many areas that have been, and are currently, undergoing investigation. LT as an attempt for cure rather than palliation is a justified treatment option for well-selected patients with metastatic neuroendocrine tumors of the pancreas and GI system. Optimization of pretransplantation staging and patient management algorithms, patient selection, and posttransplant management options are areas that need to be better defined. Further investigations for defining reproducible prognostic factors, consistent histopathologic evaluation, and uniform preoperative staging and site-specific data are needed. With the advancement of newer treatment modalities, it is necessary to define the role of LT along with the optimal perioperative management of existing and recurrent disease.

Related: Gastrointestinal System Cancers Cancer of the Pancreas Pancreatic Cancer

Franssen B, Alshebeeb K, Tabrizian P, et al.
Differences in surgical outcomes between hepatitis B- and hepatitis C-related hepatocellular carcinoma: a retrospective analysis of a single North American center.
Ann Surg. 2014; 260(4):650-6; discussion 656-8 [PubMed] Related Publications
OBJECTIVE: Compare surgical outcomes for hepatitis B virus (HBV)-hepatocellular carcinoma (HCC) versus hepatitis C virus (HCV)-hepatocellular carcinoma (HCC).
BACKGROUND: HCC is the second leading cause of death from cancer worldwide and is associated with hepatitis virus infection in 80% of cases.
METHODS: Between 1997 and 2011, 1008 patients with hepatitis B (HBV, n = 431) or hepatitis C (HCV, n = 577) underwent resection (n = 567) or transplantation (n = 441). Resection was indicated for Child's A patients with single HCC; transplantation was indicated for patients within Milan criteria. Univariate and multivariate analyses were performed as well as survival and recurrence analysis using log-rank test.
RESULTS: Based on uniform application of these criteria, resection: transplantation ratio was 3.6 for patients with HBV and 0.67 for patients with HCV. Resection: Patients with HBV had larger tumors and higher α-fetoprotein but less satellites and macrovascular invasion; 68% of HBV versus 89% of HCV were cirrhotic. Survival was better (P < 0.001) and recurrence was lower (P = 0.009) for HBV. Independent predictors of death included HCV (P = 0.024), transfusion (P = 0.013), and HCC of greater than 5 cm (P = 0.013). Limiting analysis to patients with cirrhosis, survival with HBV remained superior (P = 0.020) but recurrence did not. Transplantation: Tumors were similar in HBV and HCV. Survival was better (P = 0.002) for HBV; recurrence was similar. Independent predictors of death were HCV (P < 0.001), poor differentiation (P = 0.049), vascular invasion (P = 0.002), and outside Milan (P = 0.032). Limiting analysis to patients within Milan, HBV survival remained better for both resection (P = 0.030) and transplantation (P = 0.002).
CONCLUSIONS: Survival after both resection and transplantation for HCC was better in HBV- than in HCV-related HCC whereas recurrence was also lower for HBV-HCC in the resection group, these differences are influenced by both liver and tumor factors.

Xu Q, Hanna G, Grimm J, et al.
Quantifying rigid and nonrigid motion of liver tumors during stereotactic body radiation therapy.
Int J Radiat Oncol Biol Phys. 2014; 90(1):94-101 [PubMed] Related Publications
PURPOSE: To quantify rigid and nonrigid motion of liver tumors using reconstructed 3-dimensional (3D) fiducials from stereo imaging during CyberKnife-based stereotactic body radiation therapy (SBRT).
METHODS AND MATERIALS: Twenty-three liver patients treated with 3 fractions of SBRT were used in this study. After 2 orthogonal kilovoltage images were taken during treatment, the 3D locations of the fiducials were generated by the CyberKnife system and validated using geometric derivations. A total of 4824 pairs of kilovoltage images from start to end of treatment were analyzed. For rigid motion, the rotational angles and translational shifts were reported by aligning 3D fiducial groups from different image pairs, using least-squares fitting. For nonrigid motion, we quantified interfractional tumor volume variations by using the proportional volume derived from the fiducials, which correlates to the sum of interfiducial distances. The individual fiducial displacements were also reported (1) after rigid corrections and (2) without angle corrections.
RESULTS: The proportional volume derived by the fiducials demonstrated a volume-increasing trend in the second (101.9% ± 3.6%) and third (101.0 ± 5.9%) fractions among most patients, possibly due to radiation-induced edema. For all patients, the translational shifts in left-right, anteroposterior, and superoinferior directions were 2.1 ± 2.3 mm, 2.9 ± 2.8 mm, and 6.4 ± 5.5 mm, respectively. The greatest translational shifts occurred in the superoinferior direction, likely due to respiratory motion from the diaphragm. The rotational angles in roll, pitch, and yaw were 1.2° ± 1.8°, 1.8° ± 2.4°, and 1.7° ± 2.1°, respectively. The 3D individual fiducial displacements with rigid corrections were 0.2 ± 0.2 mm and increased to 0.5 ± 0.4 mm without rotational corrections.
CONCLUSIONS: Accurate 3D locations of internal fiducials can be reconstructed from stereo imaging during treatment. As an effective surrogate to tumor motion, fiducials provide a close estimation of both rigid and nonrigid motion of liver tumors. The reported displacements could be further utilized for tumor margin definition and motion management in conventional linear accelerator-based liver SBRT.

Noyes AM, Lonial K, Siegel RD
Tumor lysis syndrome in a nonsmall cell lung cancer.
Conn Med. 2014; 78(7):421-3 [PubMed] Related Publications
Tumor lysis syndrome (TLS) is an oncologic emergency caused by intense tumor cell destruction resulting in profound electrolyte abnormalities. It is generally recognized as a consequence of cytotoxic therapy in particularly chemotherapy-sensitive tumors such as hematologic cancers. Despite having been primarily recognized in hematologic malignancies, TLS has been reported in solid tumors as well. We present a case of a 72-year-old female who developed TLS after receiving etoposide and carboplatin for a poorly-differentiated carcinoma with areas of small-cell differentiation metastatic to her liver. She had previously undergone a thoracotomy and resection for a poorly differentiated squamous cell cancer of the lung.

Related: Carboplatin Non-Small Cell Lung Cancer Etoposide Lung Cancer

Wu Z, Guo K, Sun H, et al.
Caution for diagnosis and surgical treatment of recurrent cholangitis: lessons from 5 cases of bile duct tumor thrombus without a detectable intrahepatic tumor.
Medicine (Baltimore). 2014; 93(11):e80 [PubMed] Related Publications
The hepatocellular carcinoma (HCC) patients with bile duct tumor thrombus (BDTT) usually have no specific clinical symptoms at early stages. HCC with BDTT was usually misdiagnosed when the intrahepatic tumor was small, even undetectable. In this study, 5 cases of HCC with BDTT misdiagnosed as choledocholithiasis and cholangitis in the local hospital are described. We analyzed retrospectively and summarized our experiences of these 5 HCC patients with BDTT misdiagnosed in the local hospital during the past 5 years. The diagnosis, treatment, and outcome of the patients are discussed. Three patients underwent hepatectomy with thrombectomy and T-tube drainage. One patient underwent hepatectomy with the resection of the common bile duct and hepatojejunostomy, and palliative surgery was performed in 1 patient with portal vein tumor thrombus and intrahepatic metastasis. The patients were followed for 6-22 months; 4 patients died of tumor recurrence and metastasis or hepatic failure, despite 3 of these patients having received transhepatic arterial chemotherapy and embolization or radiofrequency ablation therapy. Early and accurate diagnosis of HCC with BDTT is very important. When patients have a history of abnormal recurrent cholangitis, HCC with BDTT should be highly suspected. Intraductal ultrasonography (US), intraoperative US, and histopathological examination are very valuable for the diagnosis. The prognosis of HCC patients with BDTT is dismal. Identification of this type of patient is clinically important, because surgical treatment may be beneficial.

Related: Extra-Hepatic Bile duct cancer (cholangiocarcinoma)

Choi JY, Lee JM, Sirlin CB
CT and MR imaging diagnosis and staging of hepatocellular carcinoma: part I. Development, growth, and spread: key pathologic and imaging aspects.
Radiology. 2014; 272(3):635-54 [PubMed] Related Publications
Computed tomography (CT) and magnetic resonance (MR) imaging play critical roles in the diagnosis and staging of hepatocellular carcinoma (HCC). The first article of this two-part review discusses key concepts of HCC development, growth, and spread, emphasizing those features with imaging correlates and hence most relevant to radiologists; state-of-the-art CT and MR imaging technique with extracellular and hepatobiliary contrast agents; and the imaging appearance of precursor nodules that eventually may transform into overt HCC.

Chou CT, Chen RC, Lin WC, et al.
Prediction of microvascular invasion of hepatocellular carcinoma: preoperative CT and histopathologic correlation.
AJR Am J Roentgenol. 2014; 203(3):W253-9 [PubMed] Related Publications
OBJECTIVE: The objective of our study was to prospectively investigate whether nonsmooth margins detected on multiphasic CT images correlate with the presence and location of microvascular invasion (MVI) in hepatocellular carcinoma (HCC).
SUBJECTS AND METHODS: A total of 102 patients with preoperative CT findings of solitary HCC were prospectively enrolled. Tumor size, tumor capsule, tumor margins, and peritumoral enhancement on preoperative CT images were assessed. Histopathologic results including the following were also recorded: tumor differentiation; liver fibrosis score; presence or absence of MVI; and, if present, the location of MVI. Correlation between tumor margin on preoperative CT images and histopathologic location of MVI was determined.
RESULTS: Pathologic examination revealed MVI in 60 of the 102 HCC specimens. Although the results of the univariate analysis showed that tumor size, higher Edmondson-Steiner grade, and nonsmooth tumor margins were associated with MVI, multivariate analysis revealed that only nonsmooth margins correlated with the presence of MVI in HCC (p < 0.001). Of the 60 HCC specimens with histopathologic evidence of MVI, 40 exhibited focal nonsmooth margins. In addition, the locations of the nonsmooth margins and MVI were similar in 36 of the 40 specimens.
CONCLUSION: Nonsmooth tumor margins correlated with the histopathologic presence and location of MVI. Therefore, nonsmooth margins detected on multiphasic CT may be predictive of MVI in HCC.

Related: Angiogenesis and Cancer

Shuman WP, Green DE, Busey JM, et al.
Dual-energy liver CT: effect of monochromatic imaging on lesion detection, conspicuity, and contrast-to-noise ratio of hypervascular lesions on late arterial phase.
AJR Am J Roentgenol. 2014; 203(3):601-6 [PubMed] Related Publications
OBJECTIVE: The purpose of this study was to evaluate the effect of use of dual-energy CT monochromatic imaging in the late hepatic arterial phase on hyperenhancing focal lesion detection and lesion conspicuity.
SUBJECTS AND METHODS: This prospective study included 72 patients imaged with a single-source dual-energy CT scanner. Late arterial phase imaging was performed with dual energies of 140 and 80 kVp, and the portal venous and delayed phases were performed with a single energy of 120 kVp. Two deidentified image sets were created: set A consisted of 77-keV images only, and set B consisted of 40-, 50-, 70-, and 77-keV images and iodine-based contrast material decomposition images. Two independent reviewers identified hypervascular lesions and subjectively scored lesion conspicuity. Contrast-to-noise ratios were calculated, and radiation dose (volume CT dose index) was recorded.
RESULTS: The 128 lesions identified had a mean size of 1.7 ± 1.4 cm. There was no difference in lesion detection between the two reviewers or the two image sets. The contrast-to-noise ratio at 50 keV was 72% greater than that at 77 keV (p < 0.0001). Subjective conspicuity was statistically greatest at 50 keV (p < 0.0001). There was no statistical difference in mean volume CT dose index between the dual-energy (12.8 mGy) and the two single-energy (14.4 and 14.2 mGy) phases.
CONCLUSION: Viewing dual-energy CT images may result in the greatest subjective lesion conspicuity and measured contrast-to-noise ratio at 50 keV with equal detection of hyperenhancing liver lesions compared with viewing 77-keV images alone. In addition, the radiation doses of dual-energy CT may be similar to those of single-energy CT.

Related: Angiogenesis and Cancer

Choi CK
Anesthetic considerations and management of a patient with unsuspected carcinoid crisis during hepatic tumor resection.
Middle East J Anaesthesiol. 2014; 22(5):515-8 [PubMed] Related Publications
Anesthetic management for massive blood loss in liver surgery concomitant with hemodynamic instability secondary to carcinoid crisis can be challenging in the perioperative setting. Hypotension, diarrhea, facial flushing, bronchospasm, and tricuspid and pulmonic valvular diseases are the common manifestations of carcinoid syndrome. This report illustrates the importance of early recognition and treatment for signs and symptoms of carcinoid syndrome not only in the preoperative setting but also in the intraoperative phase to prevent undue cardiovascular collapse.

Marrero JA, Ahn J, Rajender Reddy K,
ACG clinical guideline: the diagnosis and management of focal liver lesions.
Am J Gastroenterol. 2014; 109(9):1328-47; quiz 1348 [PubMed] Related Publications
Focal liver lesions (FLL) have been a common reason for consultation faced by gastroenterologists and hepatologists. The increasing and widespread use of imaging studies has led to an increase in detection of incidental FLL. It is important to consider not only malignant liver lesions, but also benign solid and cystic liver lesions such as hemangioma, focal nodular hyperplasia, hepatocellular adenoma, and hepatic cysts, in the differential diagnosis. In this ACG practice guideline, the authors provide an evidence-based approach to the diagnosis and management of FLL.

Related: Extra-Hepatic Bile duct cancer (cholangiocarcinoma)

Hayashi S, Tanaka H, Hoshi H
External beam radiotherapy for painful bone metastases from hepatocellular carcinoma: multiple fractions compared with an 8-Gy single fraction.
Nagoya J Med Sci. 2014; 76(1-2):91-9 [PubMed] Related Publications
External beam radiotherapy (EBRT) for hepatocellular carcinoma (HCC) bone metastases has not been popular in palliative therapy, and optimum dose schedules have not been decided because of limited published reports. We here evaluated the palliative effect of EBRT for HCC bone metastases and compared the dose-response relationship between multiple fractions (MFs) and an 8-Gy single fraction (SF). Twenty-eight patients (42 sites) with painful bone metastases who received EBRT and were analyzed retrospectively. Eight patients (12 sites) received SF. Of the remaining 20 patients (30 sites), 10 received MFs at moderate doses (20-30 Gy; 17 sites) and 10 received MFs at high doses (36-52 Gy; 13 sites). Overall response was achieved at 83% (35) of all sites; 75% (9) and 87% (26) for the SF and MF patients (88%, moderate dose; 85%, high dose), respectively. No significant differences in overall response were observed between each fraction schedule. Response duration was significantly longer for the high-dose MF patients than for the SF patients and moderate-dose MF patients (P < 0.05). SF was as effective as MF radiotherapy in terms of pain relief, but high-dose MF delivery relieved pain for a significantly longer duration.

Raoof M, Zhu C, Cisneros BT, et al.
Hyperthermia inhibits recombination repair of gemcitabine-stalled replication forks.
J Natl Cancer Inst. 2014; 106(8) [PubMed] Article available free on PMC after 01/08/2015 Related Publications
BACKGROUND: Gemcitabine is a potent nucleoside analogue against solid tumors, but development of drug resistance is a substantial problem. Removal of gemcitabine incorporated into DNA by repair mechanisms may contribute to resistance in chemo-refractory solid tumors. Human hepatocellular carcinoma (HCC) is usually very chemoresistant to gemcitabine.
METHODS: We treated HCC in vitro and in vivo (orthotopic murine model with human Hep3B or HepG2 xenografts, 7-10 CB17SCID mice per group) with gemcitabine. The role of homologous recombination repair proteins in repairing stalled replication forks was evaluated with hyperthermia exposure and cell-cycle analysis. The Student t-test was used for two-sample comparisons. Multiple group data were analyzed using one-way analysis of variance. All statistical tests were two-sided.
RESULTS: We demonstrated that Mre11-mediated homologous recombination repair of gemcitabine-stalled replication forks is crucial to survival of HCC cells. Furthermore, we demonstrated inhibition of Mre11 by an exonuclease inhibitor or concomitant hyperthermia. In orthotopic murine models of chemoresistant HCC, the Hep3B tumor mass with radiofrequency plus gemcitabine treatment (mean ± SD, 180±91mg) was statistically significantly smaller compared with gemcitabine alone (661±419mg, P = .0063).
CONCLUSIONS: This study provides mechanistic understanding of homologous recombination inhibiting-strategies, such as noninvasive radiofrequency field-induced hyperthermia, to overcome resistance to gemcitabine in refractory human solid tumors.

Related: Gemcitabine

Huang CH, Lujambio A, Zuber J, et al.
CDK9-mediated transcription elongation is required for MYC addiction in hepatocellular carcinoma.
Genes Dev. 2014; 28(16):1800-14 [PubMed] Article available free on PMC after 15/02/2015 Related Publications
One-year survival rates for newly diagnosed hepatocellular carcinoma (HCC) are <50%, and unresectable HCC carries a dismal prognosis owing to its aggressiveness and the undruggable nature of its main genetic drivers. By screening a custom library of shRNAs directed toward known drug targets in a genetically defined Myc-driven HCC model, we identified cyclin-dependent kinase 9 (Cdk9) as required for disease maintenance. Pharmacological or shRNA-mediated CDK9 inhibition led to robust anti-tumor effects that correlated with MYC expression levels and depended on the role that both CDK9 and MYC exert in transcription elongation. Our results establish CDK9 inhibition as a therapeutic strategy for MYC-overexpressing liver tumors and highlight the relevance of transcription elongation in the addiction of cancer cells to MYC.

Mano Y, Aishima S, Kubo Y, et al.
Correlation between biological marker expression and fluorine-18 fluorodeoxyglucose uptake in hepatocellular carcinoma.
Am J Clin Pathol. 2014; 142(3):391-7 [PubMed] Related Publications
OBJECTIVES: This study investigated the association between several biological markers and fluorine-18 fluorodeoxyglucose (FDG) uptake in patients with hepatocellular carcinoma.
METHODS: Forty-two patients with hepatocellular carcinoma who underwent FDG positron emission tomography were included in the study. Tumor sections were immunohistochemically stained for phosphorylated signal transducer and activator of transcription 3 (pSTAT3), hypoxia-inducible factor 1α (HIF1α), glucose transporter 1 (GLUT1), GLUT2, GLUT3, and GLUT4.
RESULTS: The high standardized uptake value (SUV) group showed larger tumor size, more frequent vascular invasion, and poorer differentiation compared with the low SUV group. The high SUV group also showed significantly higher immunohistochemical expression of pSTAT3, HIF1α, and GLUT1. The GLUT1 high-expression group showed higher α-fetoprotein (a tumor marker) and poorer differentiation than did the GLUT1 low-expression group.
CONCLUSIONS: Our study indicates that FDG uptake is associated with the expression of pSTAT3, HIF1α, and GLUT1 in hepatocellular carcinoma. The expression of these proteins shows a correlation with poor differentiation and vascular invasion.

Related: SLC2A1 HIF1A

Liszka L
Ductal adenocarcinoma of the pancreas usually retained SMAD4 and p53 protein status as well as expression of epithelial-to-mesenchymal transition markers and cell cycle regulators at the stage of liver metastasis.
Pol J Pathol. 2014; 65(2):100-12 [PubMed] Related Publications
There are limited data on the biology of metastatic pancreatic ductal adenocarcinoma (PDAC). The aim of the present study was to compare the expression of immunohistochemical markers that may be involved in the development of metastatic disease in primary PDAC and in synchronous liver metastatic tissues. Thirty-two stains (corresponding to proteins encoded by 31 genes: SMAD4, TP53, ACTA2, CDH1, CDKN1A, CLDN1, CLDN4, CLDN7, CTNNB1, EGFR, ERBB2, FN1, KRT19, MAPK1/MAPK3, MAPK14, MKI67, MMP2, MMP9, MUC1 (3 antibodies), MUC5AC, MUC6, MTOR, MYC, NES, PTGS2, RPS6, RPS6KB1, TGFB1, TGFBR1, VIM) were evaluated using tissue microarray of 26 pairs of primary PDACs and their liver metastases. There were no significant differences in expression levels of examined proteins between primary and secondary lesions. In particular, metastatic PDAC retained the primary tumour's SMAD4 protein status in all and p53 protein status in all but one case. This surprising homogeneity also involved expression levels of markers of epithelial-to-mesenchymal transition as well as cell cycle regulators studied. In conclusion, the biological profiles of primary PDACs and their liver metastases seemed to be similar. Molecular alterations of PDAC related to a set of immunohistochemical markers examined in the present study were already present at the stage of localized disease.

Related: Cancer of the Pancreas Pancreatic Cancer MADH4 TP53

Ishikawa M, Nakayama K, Rahman MT, et al.
Therapy-related myelodysplastic syndrome and acute myeloid leukemia following chemotherapy (paclitaxel and carboplatin) and radiation therapy in ovarian cancer: a case report.
Eur J Gynaecol Oncol. 2014; 35(4):443-8 [PubMed] Related Publications
In recent years, the incidence of therapy-related myelodysplastic syndrome (t-MDS) and therapy-related acute myeloid leukemia (t-AML) that occur during chemotherapy for ovarian cancer has increased. While alkylating agents and topoisomerase II inhibitors are particularly mutagenic and have strong leukemogenic potential, paclitaxel and combination chemotherapy/radiation therapy also appear to induce t-MDS. The present authors report a case of t-MDS that developed during chemotherapy and radiation therapy for ovarian cancer. The patient was a 75-year-old woman who received six courses of cyclophosphamide/doxorubicin/cisplatin (CAP) therapy after initial surgery for Stage IIIc grade ovarian cancer in 1995. Beginning in February 2005, the patient experienced multiple recurrences due to sternal metastasis. Chemotherapy, including paclitaxel and carboplatin (TC), was administered intermittently and was combined with radiation therapy to a sternal metastatic lesion. Pancytopenia was observed in December 2008, and she was diagnosed with t-MDS (WHO subtype, refractory cytopenias with multilineage dysplasia [RCMD]): the time from first chemotherapy to t-MDS onset was 106 months. Without evidence of blast crisis, the recurrent lesions continued to grow and caused multiple cerebral infarctions, from which she eventually died. The cumulative doses of paclitaxel and carboplatin administered to this patient were 1,968 mg and 6,480 mg, respectively.

Related: Carboplatin Acute Myeloid Leukemia (AML) Ovarian Cancer Paclitaxel

Nguyen LH, Robinton DA, Seligson MT, et al.
Lin28b is sufficient to drive liver cancer and necessary for its maintenance in murine models.
Cancer Cell. 2014; 26(2):248-61 [PubMed] Article available free on PMC after 11/08/2015 Related Publications
Lin28a/b are RNA-binding proteins that influence stem cell maintenance, metabolism, and oncogenesis. Poorly differentiated, aggressive cancers often overexpress Lin28, but its role in tumor initiation or maintenance has not been definitively addressed. We report that LIN28B overexpression is sufficient to initiate hepatoblastoma and hepatocellular carcinoma in murine models. We also detected Lin28b overexpression in MYC-driven hepatoblastomas, and liver-specific deletion of Lin28a/b reduced tumor burden, extended latency, and prolonged survival. Both intravenous siRNA against Lin28b and conditional Lin28b deletion reduced tumor burden and prolonged survival. Igf2bp proteins are upregulated, and Igf2bp3 is required in the context of LIN28B overexpression to promote growth. Therefore, multiple murine models demonstrate that Lin28b is both sufficient to initiate liver cancer and necessary for its maintenance.

Liu J, Xie B, Chen S, et al.
Association study of two inflammation-related polymorphisms with susceptibility to hepatocellular carcinoma: a meta-analysis.
BMC Med Genet. 2014; 15:92 [PubMed] Related Publications
BACKGROUND: Inflammation is a response of body tissues to injury or irritation. Small RNAs, such as miR-146a and miR-499, participate in various processes of tumorigenesis. A recent study indicates that inflammation and abnormal immune responses may promote malignant progression in cancer development, indicating that inflammation-related polymorphisms such as miR-146a rs2910164 and miR-499 rs3746444 are crucial. However, studies on the association of these two polymorphisms with hepatocellular carcinoma (HCC) are inconclusive and inconsistent. We aimed at accessing the combined result of reported studies and make a more precise estimate of the relationship.
METHODS: Meta-analysis was performed on the associations between the miR-146a rs2910164 C > G and miR-499 rs3746444 T > C polymorphisms and hepatocellular carcinoma, using: allele contrast, dominant, and recessive models. A total of 12 studies(8 on miR-146a rs2910164 and 4 on miR-499 rs3746444) with three populations (Chinese, Korean, Turkish) were included in this study.
RESULTS: Results show that both allele frequency and genotype distributions of miR-146a rs2910164 polymorphism are significantly associated with susceptibility to HCC (G versus C: OR = 1.153, 95% CI 1.083-1.228, P < 0.001; GC versus CC: OR = 1.165, 95% CI 1.054-1.286, P = 0.003; GG versus CC: OR = 1.361, 95% CI 1.192-1.553, P < 0.001; GG/GC versus CC: OR = 1.213, 95% CI 1.104-1.333, P < 0.001; GG versus GC/CC: OR = 1.210, 95% CI 1.080-1.356, P < 0.001). Our data suggest that people with G allele have a higher susceptibility to HCC as compared to those with C allele. However, meta-analysis failed to detect associations between miR-499 rs3746444 and HCC risk under each genetic model tested. Subgroup analysis showed that Chinese population with CC genotype are more vulnerable to HCC (OR = 2.171, 95% CI = 1.149-4.104, P = 0.017) than those with TT genotype.
CONCLUSIONS: We conclude that rs2910164 in miR-146a may confer susceptibility to HCC, especially in the Chinese population. No significant association was found between miR-499 rs3746444 and HCC, but subgroup study showed that subjects with CC genotype are more vulnerable to HCC than TT genotype in the Chinese population.

Lerebours A, Stentiford GD, Lyons BP, et al.
Genetic alterations and cancer formation in a European flatfish at sites of different contaminant burdens.
Environ Sci Technol. 2014; 48(17):10448-55 [PubMed] Related Publications
Fish diseases are an indicator for marine ecosystem health since they provide a biological end-point of historical exposure to stressors. Liver cancer has been used to monitor the effects of exposure to anthropogenic pollution in flatfish for many years. The prevalence of liver cancer can exceed 20%. Despite the high prevalence and the opportunity of using flatfish to study environmentally induced cancer, the genetic and environmental factors driving tumor prevalence across sites are poorly understood. This study aims to define the link between genetic deterioration, liver disease progression, and anthropogenic contaminant exposures in the flatfish dab (Limanda limanda). We assessed genetic changes in a conserved cancer gene, Retinoblastoma (Rb), in association with histological diagnosis of normal, pretumor, and tumor pathologies in the livers of 165 fish from six sites in the North Sea and English Channel. The highest concentrations of metals (especially cadmium) and organic chemicals correlated with the presence of tumor pathology and with defined genetic profiles of the Rb gene, from these sites. Different Rb genetic profiles were found in liver tissue near each tumor phenotype, giving insight into the mechanistic molecular-level cause of the liver pathologies. Different Rb profiles were also found at sampling sites of differing contaminant burdens. Additionally, profiles indicated that histological "normal" fish from Dogger sampling locations possessed Rb profiles associated with pretumor disease. This study highlights an association between Rb and specific contaminants (especially cadmium) in the molecular etiology of dab liver tumorigenesis.

Related: RB1

Ma L, Pan Q, Sun F, et al.
Cluster of differentiation 166 (CD166) regulates cluster of differentiation (CD44) via NF-κB in liver cancer cell line Bel-7402.
Biochem Biophys Res Commun. 2014; 451(2):334-8 [PubMed] Related Publications
Cluster of differentiation 166 (CD166) is critical for liver cancer cell survival. Our previously study demonstrated that CD166 exerts its anti-apoptotic role through interaction with YAP in liver cancer. However, the interaction between CD166 and other cell surface molecules remains unclear in liver cancer cells. In the current study, we found that both mRNA and protein of CD44 expression was significantly inhibited by knocking-down CD166. Moreover, CD166 affected-CD44 expression is dependent of transcription via blocking NF-κB pathway. On the contrary, CD44 promoted up-regulation of CD166 mRNA and protein. And it may be through E3 ubiquitin ligases COP1 and UBC3 to regulate CD166 protein degradation. Collectively, these results suggest that CD166 and CD44 play important roles in liver cancer development. Therefore, CD166 may develop as a potential therapeutic molecule target for the treatment of liver cancer.

Related: Apoptosis Signal Transduction

Tang HC, Chung KH
Quetiapine-induced neutropenia in a bipolar patient with hepatocellular carcinoma.
Int J Psychiatry Med. 2014; 47(3):255-61 [PubMed] Related Publications
OBJECTIVE: Quetiapine is a dibenzothiazepine derivative, similar to clozapine, which has the highest risk of causing blood dyscrasias, especially neutropenia. There are some case reports about this side effect of quetiapine, but possible risk factors are seldom discussed and identified. A case of a patient with hepatocellular carcinoma that developed neutropenia after treatment with quetiapine is described here.
CASE REPORT: A 62-year-old Taiwanese widow with bipolar disorder was diagnosed with hepatocellular carcinoma at age 60. She developed leucopenia after being treated with quetiapine. After quetiapine was discontinued, her white blood cell count returned to normal.
CONCLUSIONS: Although neutropenia is not a common side effect of quetiapine, physicians should be cautious about its presentation and associated risk factors. Hepatic dysfunction may be one of the possible risk factors, and concomitant fever may be a diagnostic marker for adverse reaction to quetiapine.

Lu JT, He W, Song SS, Wei W
Paeoniflorin inhibited the tumor invasion and metastasis in human hepatocellular carcinoma cells.
Bratisl Lek Listy. 2014; 115(7):427-33 [PubMed] Related Publications
OBJECTIVE: Evidence suggests that paeoniflorin may be involved in anticancer activities. Here, we have investigated the effects of paeoniflorin and correlative mechanisms on anti-invasion and anti-metastasis in human hepatocellular carcinoma (HCC) cell lines.
MATERIALS AND METHODS: In the current study, we have applied 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) assay to determine the proliferative effect of HepG2 and Bel-7402, two human hepatoma cell lines, and we have established a boyden chamber assay, a wound healing assay and cell adhesion assay to detect and quantify the invasion, metastasis and adhesion of both HepG2 and Bel-7402. In addition, we have analyzed the protein expression of matrix metalloproteinas (MMP)-9, E-cadherin (E-cad) and extracellular signal-regulated kinase (ERK) in both cell lines through western blot analysis.
RESULTS: Paeoniflorin (6. 25-200 µM) had inhibitory effect on the growth of HepG2 and Bel-7402 cell lines, and reduced significantly invasion, metastasis and adhesion of HCC cell lines. In addition, paeoniflorin decreased the expression of MMP-9 and ERK in HepG2 and Bel-7402 cells, and increased expression of E-cad in both cell lines.
CONCLUSIONS: Paeoniflorin is effective anti-metastatic and anti-invasive agent for suppressing HCC invasion and metastasis (Fig. 5, Ref. 30).

Related: MMP9: matrix metallopeptidase 9 Melphalan

Dhingra S, Fiel MI
Update on the new classification of hepatic adenomas: clinical, molecular, and pathologic characteristics.
Arch Pathol Lab Med. 2014; 138(8):1090-7 [PubMed] Related Publications
CONTEXT: Hepatic adenoma is an uncommon, benign, hepatic neoplasm that typically occurs in women of child-bearing age, often with a history of long-term use of oral contraceptive drugs. This is usually detected as an incidental mass lesion in a noncirrhotic liver during imaging studies. Pathologic evaluation by needle core biopsy remains the gold standard for diagnosis. Molecular studies have revealed that hepatic adenomas involve unique molecular pathways that are distinct from hepatocellular carcinoma. Based on these studies, a French collaborative group has recently proposed a molecular-pathologic classification for hepatic adenomas. In addition, advances in molecular studies have led to reclassification of the "telangiectatic variant of focal nodular hyperplasia" as "hepatic adenoma, inflammatory subtype."
OBJECTIVE: To review the proposed, new classification of hepatic adenoma and the changes in diagnostic workup in light of the above-mentioned developments.
DATA SOURCES: Review of published literature and illustrations from clinical case material.
CONCLUSIONS: Definitive diagnosis of liver mass lesion on needle core biopsies has a decisive role in clinical management. With the advent of the new classification of hepatic adenomas and its prognostic implications, it is vital for pathologists to be aware of the morphologic features seen in different subtypes and the available diagnostic tools, such as immunohistochemistry, to help identify the correct subtype.

Related: TCF1

De Kock I, Mortelé KJ, Smet B, et al.
Hepatic adenomatosis: MR imaging features.
JBR-BTR. 2014 Mar-Apr; 97(2):105-8 [PubMed] Related Publications
Hepatocellular adenomas are rare benign liver neoplasms that commonly occur in women with a history of oral contraceptives intake for more than 2 years. Hepatic adenomatosis is characterized by the presence of multiple adenomas, arbitrarily > than 10, involving both lobes of the liver, without any history of steroid therapy or glycogen storage disease. Although the adenomas in liver adenomatosis are histologically similar to other adenomas, liver adenomatosis appears to be a separate clinical entity. Adenomas in hepatic adenomatosis may be of the inflammatory, hepatocyte nuclear factor 1alpha-mutated, or beta-catenin-mutated subtype, and accordingly show variable imaging appearances. Hepatic adenomatosis carries the risk of impaired liver function, hemorrhage and malignant degeneration. We report a case with the inflammatory subtype of hepatic adenomatosis in a 39-year-old woman with liver steatosis. The magnetic resonance imaging features using extracellular gadolinium chelates and hepatocyte-targeted contrast agents are described.

Barbier L, Torrents J, Hardwigsen J
Hepatic angiomyolipoma: what management?
Acta Chir Belg. 2014 Mar-Apr; 114(2):139-42 [PubMed] Related Publications
An 80-year-old woman was referred for the surgical treatment of a 110-mm right hepatic tumor. The biopsy revealed an adenoma, and a right hepatectomy was performed. Histopathology indicated a major fat component with epitheliod cells, immunoreactivity for HMB45, Melan A, and smooth muscle actin, describing a hepatic epithelioid angiomyolipoma (AML). The AML belongs to the group of tumors with a Perivascular Epithelioid Cell differentiation. Its diagnosis is based on imaging and biopsy, and therefore might be difficult. Hepatic AML are mainly benign tumors; however, some tend to behave in a malignant manner. In case of histological proof, close clinical and radiological monitoring can be proposed if its size is less than 5 cm and no pejorative histological features are found. Nevertheless, follow-up is still required if resection is performed in search of recurrence or metastatic spread.

Sebagh M, Allard MA, Cunha AS, et al.
A proposed new method for assessing the pathological response to chemotherapy in resected colorectal liver metastases.
Br J Cancer. 2014; 111(3):470-6 [PubMed] Article available free on PMC after 29/07/2015 Related Publications
BACKGROUND: Pathological response (PR) to preoperative chemotherapy for colorectal liver metastases (CLM) is recognised as a prognostic factor of outcome. However, the optimal system to assess this parameter is still debated. This study focuses on current methods and proposes a possibly better method for assessing PR.
METHODS: Among 223 patients resected for CLM between 2004 and 2011, after more than three cycles of chemotherapy, the percentage of tumour cells, necrosis and fibrosis, and the tumour regression grade were assessed for each of 802 nodules. Pathological response was evaluated according to validated methods and their combinations. A new method combined the percentage of tumour cells and the size of all nodules as follows: , where n is each separate nodule, % is the percentage of remaining tumour cells within nodule n (%) and s is the size of nodule n (cm).The prognostic value of each method was calculated.
RESULTS: After a median follow-up of 47 months (3-106), the cumulative 5-year overall survival rate after liver resection was 59%. The proposed method categorised as follows: 0 residual tumour; 0.1-6-cm residual tumour; >6-cm residual tumour, and necrosis rate >50% stratified prognosis (P=0.0027; P=0.02), while the other methods did not. At multivariate analysis, our method remained an independent predictor of outcome (P=0.001).
CONCLUSIONS: Combining the percentage of tumour cells multiplied by the size of each separate tumour seems to be a better method for assessing PR. External validation is required.

Related: Colorectal (Bowel) Cancer Bevacizumab (Avastin) Cetuximab (Erbitux)

Chiu M, Tardito S, Pillozzi S, et al.
Glutamine depletion by crisantaspase hinders the growth of human hepatocellular carcinoma xenografts.
Br J Cancer. 2014; 111(6):1159-67 [PubMed] Related Publications
BACKGROUND: A subset of human hepatocellular carcinomas (HCC) exhibit mutations of β-catenin gene CTNNB1 and overexpress Glutamine synthetase (GS). The CTNNB1-mutated HCC cell line HepG2 is sensitive to glutamine starvation induced in vitro with the antileukemic drug Crisantaspase and the GS inhibitor methionine-L-sulfoximine (MSO).
METHODS: Immunodeficient mice with subcutaneous xenografts of the CTNNB1-mutated HCC cell lines HepG2 and HC-AFW1 were treated with Crisantaspase and/or MSO, and tumour growth was monitored. At the end of treatment, tumour weight and histology were assessed. Serum and tissue amino acids were determined by HPLC. Gene and protein expression were estimated with RT-PCR and western blot and GS activity with a colorimetric method. mTOR activity was evaluated from the phosphorylation of p70S6K1.
RESULTS: Crisantaspase and MSO depleted serum glutamine, lowered glutamine in liver and tumour tissue, and inhibited liver GS activity. HepG2 tumour growth was significantly reduced by either Crisantaspase or MSO, and completely suppressed by the combined treatment. The combined treatment was also effective against xenografts of the HC-AFW1 cell line, which is Crisantaspase resistant in vitro.
CONCLUSIONS: The combination of Crisantaspase and MSO reduces glutamine supply to CTNNB1-mutated HCC xenografts and hinders their growth.

Related: Crisantaspase MKI67

El-Serag HB, Kramer J, Duan Z, Kanwal F
Racial differences in the progression to cirrhosis and hepatocellular carcinoma in HCV-infected veterans.
Am J Gastroenterol. 2014; 109(9):1427-35 [PubMed] Related Publications
OBJECTIVES: The race of patients infected with hepatitis C virus (HCV) in the United States may be associated with the risk for cirrhosis and hepatocellular carcinoma (HCC). However, previous studies are too small to provide convincing data regarding the effect of race on cirrhosis and HCC risk after accounting for demographic, clinical, and virological factors.
METHODS: We used the Veterans Administration (VA) HCV Clinical Case Registry to identify patients with confirmed viremia between 2000 and 2009 and with at least 1 year of follow-up in the VA. We identified cirrhosis and HCC cases through early 2010. Cox proportional hazard regression models were performed to examine the effect of race on the risk for cirrhosis and HCC while adjusting for patients' age, gender, period of service (World War I/II, Vietnam era, post-Vietnam era), HIV coinfection, HBV coinfection, alcohol abuse, diabetes, body mass index, and antiviral treatment receipt and response.
RESULTS: There were 149,407 patients with active HCV viremia. Of them, 56.3% were non-Hispanic White (NHW), 36.1% were African American (AA), 6.0% were Hispanic, and 1.6% belonged to other racial groups. After an average follow-up of 5.2 years, 13,099 patients were seen to have a recorded diagnosis of cirrhosis and 3,551 had HCC. Hispanics had the highest annual incidence rates of cirrhosis and HCC (28.8 and 7.8%, respectively), whereas AAs had the lowest rates (13.3% and 3.9%, respectively) compared with NHWs (21.6 and 4.7%, respectively). There were differences among NHW, AA, and Hispanic patients in the rates of HIV infection (2.1, 2.5, and 6.0%, respectively), HCV genotype 1 (50.0, 50.6, and 64.2%, respectively), obesity (28.0, 25.4, and 30.9%, respectively), diabetes (8.7, 16.1, and 16.1%, respectively), and absence of antiviral treatment (81.1, 89.6, and 82.1%, respectively). However, adjusting for differences in demographic and clinical factors did not change the magnitude or direction of the race effect. Compared with NHWs, Hispanic patients had a higher risk of having cirrhosis recorded (adjusted hazard ratio (HR)=1.28, 95% confidence interval (CI)=1.21-1.37) and HCC (1.61, 95% CI=1.44-1.80). In contrast, AAs had a lower risk of cirrhosis (HR=0.58, 95% CI=0.55-0.60) and HCC (0.77, 95% CI=0.71-0.83) compared with NHWs.
CONCLUSIONS: Hispanics with HCV are at a significantly higher risk, whereas AAs are at a considerably lower risk of developing cirrhosis and HCC than are NHWs. These associations persisted even after adjusting for a range of factors including HCV genotype, HCV treatment, diabetes, and body mass index.

Related: USA

Teerasamit W, Saiviroonporn P, Pongpaibul A, Korpraphong P
Benefit of double contrast MRI in diagnosis of hepatocellular carcinoma in patients with chronic liver diseases.
J Med Assoc Thai. 2014; 97(5):540-7 [PubMed] Related Publications
OBJECTIVE: To assess the benefit on diagnosis of hepatocellular carcinoma (HCC) in patients with chronic liver disease or cirrhosis with double contrast MR imaging compared to the routine gadolinium-based MR imaging.
MATERIAL AND METHOD: Seventy-one consecutive patients with cirrhosis or chronic hepatitis underwent multiphase, gadolinium-enhanced liver MRI examination and sequentially superparamagnetic iron oxide (SPIO)-enhanced images. The presence signal intensities of lesions on non-contrast sequences, dynamic gadolinium-enhanced images and delayed 10-min post-SPIO T2*-weighted images were recorded.
RESULTS: Among 27 patients, 15 HCCs from 12 patients were diagnosed by surgical (n = 7) and non-surgical (n = 8) proofs. The overall sensitivity, specificity, positive predictive value, and negative predictive value of double contrast-enhanced images in 12 patients were 83.3% (95% CI: 58.5, 96.2), 33.3% (95% CI: 5.4, 88.4), 88.2% (95% CI: 63.5, 98.2), and 25% (95% CI: 4.1, 79.6) and these of gadolinium-enhanced images were 72.2% (95% CI: 46.5, 90.2), 33.3% (95% CI: 5.4, 88.4), 86.6% (95% CI: 59.5, 97.9), and 16.6% (95% CI: 2.7, 63.9), respectively. There were two benign hepatic nodules (1 adenoma, 1 dysplastic nodule) suspected as HCCs on MR images and two surgically proven-HCCs, invisible on gadolinium-enhanced images, detected as defect on only delayed 10-min post-SPIO T2*-weighted images.
CONCLUSION: SPIO-enhanced images in double contrast-enhanced MR imaging had an additional value on HCC detection, compared to gadolinium-enhanced MR imaging, in patients with chronic liver disease or cirrhosis.

Ly CL, Wong LL
Ethnicity as a predictive factor for hepatocellular carcinoma screening among patients in Hawaii.
Ethn Dis. 2014; 24(3):376-81 [PubMed] Related Publications
OBJECTIVES: Although hepatocellular carcinoma (HCC) surveillance is associated with mortality reduction, it continues to be underutilized. The failure to conduct screening tests is a significant factor in the late diagnosis of hepatocellular carcinoma when curative interventions may not be feasible. Reasons for these low surveillance rates are unclear and need to be elucidated.
DESIGN, SETTING, PATIENTS: This retrospective study reviewed 616 cases of HCC from a hepatobiliary surgery office in Hawaii for age, sex, ethnicity, birthplace, residence, education, employment, insurance, and obesity to determine their influence on HCC screening.
RESULTS: Of the 616 cases, only 132 patients (21.4%) had undergone screening. Although the majority of patients were male, those who were screened were more likely to be female (P = .0082). However, multivariate analysis found ethnicity to be the sole determinant of screening (P < .0005). Koreans were more likely than Whites to have had screening, whereas Japanese, Pacific Islanders, and Filipinos were less likely. Age > 60 years, sex, American birthplace, urban residence, high school completion, employment status, insurance, and BMI > 35 kg/m2 were not predictors of screening.
CONCLUSIONS: Of the sociodemographic factors, ethnicity was important in predicting screening. Further research is needed to understand the reasons for these ethnic differences and to develop targeted interventions to improve hepatocellular carcinoma surveillance utilization rates.

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