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.
Liver cancer explained - symptoms, diagnosis and treatment
Macmillan Cancer Support Video: Liver surgeon Aamir Khan explains primary liver cancer, including possible causes such as alcohol and obesity, symptoms, what tests might be done to diagnose liver cancer, and possible treatments such as surgery, chemotherapy or liver transplant.
PubMed Central search for free-access publications about Liver Cancer MeSH term: Liver Neoplasms US National Library of Medicine PubMed has over 22 million citations for biomedical literature from MEDLINE, life science journals, and online books. Constantly updated.
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Audigier C, Mansi T, Delingette H, et al. Lattice Boltzmann method for fast patient-specific simulation of liver tumor ablation from CT images. Med Image Comput Comput Assist Interv. 2013; 16(Pt 3):323-30 [PubMed] Related Publications
Radio-frequency ablation (RFA), the most widely used minimally invasive ablative therapy of liver cancer, is challenged by a lack of patient-specific planning. In particular, the presence of blood vessels and time-varying thermal diffusivity makes the prediction of the extent of the ablated tissue difficult. This may result in incomplete treatments and increased risk of recurrence. We propose a new model of the physical mechanisms involved in RFA of abdominal tumors based on Lattice Boltzmann Method to predict the extent of ablation given the probe location and the biological parameters. Our method relies on patient images, from which level set representations of liver geometry, tumor shape and vessels are extracted. Then a computational model of heat diffusion, cellular necrosis and blood flow through vessels and liver is solved to estimate the extent of ablated tissue. After quantitative verifications against an analytical solution, we apply our framework to 5 patients datasets which include pre- and post-operative CT images, yielding promising correlation between predicted and actual ablation extent (mean point to mesh errors of 8.7 mm). Implemented on graphics processing units, our method may enable RFA planning in clinical settings as it leads to near real-time computation: 1 minute of ablation is simulated in 1.14 minutes, which is almost 60x faster than standard finite element method.
Kadoury S, Abi-Jaoudeh N, Valdes PA Higher-order CRF tumor segmentation with discriminant manifold potentials. Med Image Comput Comput Assist Interv. 2013; 16(Pt 1):719-26 [PubMed] Related Publications
The delineation of tumor boundaries in medical images is an essential task for the early detection, diagnosis and follow-up of cancer. However accurate segmentation remains challenging due to presence of noise, inhomogeneity and high appearance variability of malignant tissue. In this paper, we propose an automatic segmentation approach using fully-connected higher-order conditional random fields (HOCRF) where potentials are computed within a discriminant Grassmannian manifold. First, the framework learns within-class and between-class similarity distributions from a training set of images to discover the optimal manifold discrimination between normal and pathological tissues. Second, the conditional optimization scheme computes non-local pairwise as well as pattern-based higher-order potentials from the manifold subspace to recognize regions with similar labelings and incorporate global consistency in the inference process. Our HOCRF framework is applied in the context of metastatic liver tumor segmentation in CT images. Compared to state of the art methods, our method achieves better performance on a group of 30 liver tumors and can deal with highly pathological cases.
Tay ShY, Lao WT, Chen ChL, Chan WP Contrast-enhanced ct and angiographic findings in hepatic perivascular epithelioid cell tumor. JBR-BTR. 2013 Sep-Oct; 96(5):308-10 [PubMed] Related Publications
We report a case of hepatic perivascular epithelioid cell tumor (PEComa) in a woman who was not a carrier of viral hepatitis and had a normal alpha-fetoprotein (AFP) level. CT scan showed a well-enhanced mass in the arterial-phase followed by early washout in the portal venous-phase in the lateral segment of the liver. Angiography revealed a hypervascular tumor in the liver with rapid washout of the contrast. If a hepatic tumor is found in a female patient with normal AFP level who is not a carrier of hepatitis and is free of alcoholic liver cirrhosis, tissue biopsy should precede treatment to avoid misdiagnosis of liver PEComa as hepatocellular carcinoma.
Taseva A, Tasev V, Bulanov D, et al. Diagnosis of liver hemangioma. Khirurgiia (Sofiia). 2013; (3):8-13 [PubMed] Related Publications
BACKGROUND: Benign liver tumors are now being diagnosed frequently with the advent of the greater use of imaging investigations. The most common lesion is the liver hemangioma 0.4-7.3%, with an incidence rate at autopsy ranging from 3% to 20%. MATERIAL AND METHODS: One hundred and one patients underwent operative treatment in the Department of General and Liver-pancreatic Surgery, UH "Alexandrovska" Sofia from 1995 to April 2013. There were 74 (73.3%) females and 27 (26.7%) males. Mean age was 50.7 years (range 25 to 77). Seventy-four patients (73.3%) had a solitary tumor. Methods for diagnosis included history of the disease, routine haematological and liver function tests, ultrasonography, CT, MRI or a combination of more than one technique. RESULTS: The diagnostic sensitivity of the imaging procedures was U/S 96.9%, CT scanning 98.3% and MRI 100% .The diagnostic specificity--U/S 60.3%, CT scanning 55.0%, MRI 85.7%. CONCLUSION: Hepatic hemangioma is diagnosed in most patients using non-invasive studies such as US, CT and MRI or a combination of them.
Lok T, Chen L, Lin F, Wang HL Immunohistochemical distinction between intrahepatic cholangiocarcinoma and pancreatic ductal adenocarcinoma. Hum Pathol. 2014; 45(2):394-400 [PubMed] Related Publications
Distinction between primary intrahepatic cholangiocarcinoma (ICC) and metastatic pancreatic ductal adenocarcinoma (PDA) on a liver biopsy is essentially impossible histologically but has important clinical implications. In this study, 41 ICCs and 60 PDAs were immunohistochemically evaluated for the expression of S100P, pVHL, IMP3, maspin, MUC5AC, and CK17 proteins. The results showed pVHL expression in 29 (71%) ICCs but in only 3 (5%) PDAs. S100P, MUC5AC, and CK17 were frequently expressed in PDAs, seen in 57 (95%), 40 (67%), and 36 (60%) cases, respectively. In contrast, only 11 (27%), 5 (12%), and 5 (12%) ICC cases expressed these proteins. IMP3 was expressed in 37 (90%) ICC and 54 (90%) PDA cases with equal frequency. All 60 (100%) PDA and 30 (73%) ICC cases showed positive maspin immunoreactivity. A S100P-/pVHL+/MUC5AC-/CK17- staining pattern was essentially indicative of ICC, whereas the S100P+/pVHL-/MUC5AC+/CK17+ and S100P+/pVHL-/MUC5AC-/CK17+ staining patterns were suggestive of PDA. These observations demonstrate that S100P, pVHL, MUC5AC, and CK17 are a useful immunohistochemical panel that may help distinguish primary ICC from metastatic PDA.
Gang Z, Ya-Lin K, Dong-Qing W, et al. Combining cortactin and CTTN detection with clinicopathologic features increases effectiveness of survival predictions for patients with resectable hepatocellular carcinoma. Clin Lab. 2013; 59(11-12):1343-52 [PubMed] Related Publications
BACKGROUND: Cortactin is an important regulator involved in invasion and migration of tumor cells. Although the relationship between cortactin and tumor invasion has been reported, it lacks follow-up evidence to support the forecasting role of cortactin for HCC prognosis. The aim of this study was to determine whether cortactin detection combined with clinicopathologic features predicts the prognosis efficaciously. METHODS: 91 resectable HCCs were grouped according to clinicopathologic characteristics, and immunohistochemical (IHC) cortactin tumor tissue expression was evaluated. Cortactin gene (CTTN) mRNA of 77 HCCs, as well as that of 20 normal liver tissues, was examined by real-time PCR. Kaplan-Meier method was used for survival analysis. RESULTS: It was found that cortactin expression was associated with liver capsule integrity, cancer embolus in portal vein or distant neoplasm metastasis, and with TNM stage. (p < 0.01) Moreover, CTTN mRNA expression level was higher in high invasiveness group. But no statistical significance was found between low invasiveness and normal control groups. Combining cortactin and CTTN mRNA detection with clinicopathologic features improved the predictive power. High expression of both cortactin and CTTN indicated poor survival time of 12 +/- 3.67 months and low expression indicated longer median survival time of 65 +/- 6.62 months. CONCLUSIONS: These results demonstrate for the first time that cortactin overexpression indicates highly invasive potentialities and poor prognoses with HCCs. Further, the results also suggest that this new accurate evaluating method may be more useful to survival prediction and, therefore, the clinical decision making for resectable
Dou L, Meng WS, Su BD, et al. Step-by-step vascular control for extracapsular resection of complex giant liver hemangioma involving the inferior vena cava. Am Surg. 2014; 80(1):15-20 [PubMed] Related Publications
Massive hemorrhage remains an important clinical problem in extracapsular resection of giant liver hemangiomas (GLHs), especially for those involving the proximal hepatic veins and/or inferior vena cava. Between July 2004 and March 2012, 87 patients with a complex GLH scheduled for surgical treatment were included in this study. All patients were underwent vascular preparation (Step 1), advanced hepatic artery clamping (Step 2), and stepwise vascular occlusion (Step 3). Intraoperative blood loss, blood transfusion volume, degree of ischemia-reperfusion injury, and postoperative complications were recorded. No patients required urgent vascular preparation to manage intraoperative bleeding. In total, 87, 64, and 21 patients had portal triad (PT), infrahepatic inferior vena cava (IVC), and suprahepatic IVC preparation; and 17, 43, and 11 patients had PT, PT and suprahepatic IVC, and all three (PT, infra-, and suprahepatic IVC) occlusions. The PT, infrahepatic IVC, and SIVC occlusion times were 12.1 ± 3.7 minutes, 7.9 ± 2.4 minutes, and 3.2 ± 1.4 minutes, respectively. Mean blood loss was 291.9 ± 124.5 mL, and only four patients received blood transfusions. No patients had life-threatening complications or died (Clavien-Dindo Grade 4, 5). Compared with paralleled studies, this technique has an advantage to decrease the blood loss in less liver ischemia time. For complex GLH resections, the described step-by-step vascular control technique was efficacious and feasible for controlling intraoperative bleeding.
Machado MV, Diehl AM Liver renewal: detecting misrepair and optimizing regeneration. Mayo Clin Proc. 2014; 89(1):120-30 [PubMed] Related Publications
UNLABELLED: Cirrhosis and liver cancer, the main causes of liver-related morbidity and mortality, result from defective repair of liver injury. This article summarizes rapidly evolving knowledge about liver myofibroblasts and progenitors, the 2 key cell types that interact to orchestrate effective repair, because deregulation of these cells is likely to be central to the pathogenesis of both cirrhosis and liver cancer. We focus on cirrhosis pathogenesis because cirrhosis is the main risk factor for primary liver cancer. Emerging evidence suggests that the defective repair process has certain characteristics that might be exploited for biomarker development. Recent findings in preclinical models also indicate that the newly identified cellular and molecular targets are amenable to therapeutic manipulation. Thus, recent advances in our understanding about key cell types and fundamental mechanisms that regulate liver regeneration have opened new avenues to improve the outcomes of liver injury. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01899859.
Frilling A, Modlin IM, Kidd M, et al. Recommendations for management of patients with neuroendocrine liver metastases. Lancet Oncol. 2014; 15(1):e8-21 [PubMed] Related Publications
Many management strategies exist for neuroendocrine liver metastases. These strategies range from surgery to ablation with various interventional radiology procedures, and include both regional and systemic therapy with diverse biological, cytotoxic, or targeted agents. A paucity of biological, molecular, and genomic information and an absence of data from rigorous trials limit the validity of many publications detailing management. This Review represents the views from an international conference, for which 15 expert working groups prepared evidence-based assessments addressing specific questions, and from which an independent jury derived final recommendations. The aim of the conference was to review the existing approaches to neuroendocrine liver metastases, assess the evidence on which management decisions were based, develop internationally acceptable recommendations for clinical practice (when evidence was available), and make recommendations for clinical and research endeavours. This report represents the final clinical statements and proposals for future research.
Park HJ, Kim SH, Jang KM, et al. Added value of diffusion-weighted MRI for evaluating viable tumor of hepatocellular carcinomas treated with radiotherapy in patients with chronic liver disease. AJR Am J Roentgenol. 2014; 202(1):92-101 [PubMed] Related Publications
OBJECTIVE: The purpose of this article is to evaluate the added value of diffusion-weighted imaging (DWI) to the diagnostic performance of conventional MRI in diagnosing viable hepatocellular carcinoma (HCC) tumors treated with radiotherapy in patients with chronic liver disease. MATERIALS AND METHODS: Twenty-nine patients with viable tumor and 35 patients without viable tumor were enrolled. We assessed the signal intensity of viable tumor compared with irradiated liver on MRI and DWI. Signal intensity ratios and apparent diffusion coefficient (ADC) ratios of viable tumor to nonirradiated liver were also assessed on DWI with ADC maps. Two observers reviewed conventional MRI and combined MRI and DWI and rated them using a 5-point scale. Diagnostic performance was evaluated using a receiver operating characteristic (ROC) curve. RESULTS: Viable tumors showed hyperintensity on T2-weighted and arterial phase images (16/29 [55.2%]) and hypointensity on portal (22/29 [75.9%]), 3-minute late (19/29 [65.5%]), and hepatobiliary phase (23/29 [79.3%]) images. Twenty-seven (93.1%) viable tumors showed hyperintensity on DWI and hypointensity on ADC maps. Mean signal intensity ratios and ADC ratios of viable tumor on DWI with ADC maps were significantly higher and lower than those of irradiated liver. Diagnostic performance (area under the ROC curve) improved significantly after adding DWI, and interobserver agreement was moderate for conventional MRI (κ = 0.450) and good after adding DWI (κ = 0.748). CONCLUSION: Adding DWI to conventional MRI can improve the detection of viable HCC tumors treated with radiotherapy compared to conventional MRI alone.
Kim HJ, Yu ES, Byun JH, et al. CT differentiation of mucin-producing cystic neoplasms of the liver from solitary bile duct cysts. AJR Am J Roentgenol. 2014; 202(1):83-91 [PubMed] Related Publications
OBJECTIVE: The purpose of this study was to identify the CT features required for differentiating mucin-producing cystic neoplasms of the liver (mucinous cystic neoplasms and cyst-forming intraductal papillary neoplasms of the bile duct) from solitary bile duct cysts. MATERIALS AND METHODS: CT images of pathologically confirmed mucinous cystic neoplasms (n = 15), cyst-forming intraductal papillary neoplasms of the bile duct (n = 16), and solitary bile duct cysts (n = 31) were reviewed. Analysis of the CT findings included shape, presence of septa, location of septa (peripheral vs central), thickness of septa (thin vs thick), mosaic pattern, mural nodules, intracystic debris, calcification, upstream bile duct dilatation, downstream bile duct dilatation, and communication between a cystic lesion and the bile duct. The maximum size of a cystic lesion and the maximum size of the largest mural nodule were measured. RESULTS: The presence of septa, central septa, mural nodules, upstream bile duct dilatation, and downstream bile duct dilatation were found to be significant CT findings for differentiating mucinous cystic neoplasms and cyst-forming intraductal papillary neoplasms of the bile duct from solitary bile duct cysts (p < 0.05 for each finding). When two of these five criteria were used in combination, the sensitivity and specificity for diagnosing mucin-producing cystic neoplasms and cyst-forming intraductal papillary neoplasms of the bile duct were 87% (27 of 31) and 87% (27 of 31), respectively. When two of these five criteria were used in combination, the sensitivity and specificity for diagnosing mucinous cystic neoplasms and cyst-forming intraductal papillary neoplasms of the bile duct were 87% (27 of 31) and 87% (27 of 31), respectively [corrected]. CONCLUSION: With the use of specific CT criteria, mucin-producing cystic neoplasms of the liver can be differentiated from solitary bile duct cysts with a high degree of accuracy.
Jin XT, Song L, Zhao JY, et al. Dichlorodiphenyltrichloroethane exposure induces the growth of hepatocellular carcinoma via Wnt/β-catenin pathway. Toxicol Lett. 2014; 225(1):158-66 [PubMed] Related Publications
Dichlorodiphenyltrichloroethane (DDT) is a persistent organic pollutant, involved in the progression of many cancers, including liver cancer. However, the underlying mechanism(s) of DDT, especially how low doses DDT cause liver cancer, is poorly understood. In this study, we evaluated the impact of p,p'-DDT on the growth of hepatocellular carcinoma using both in vitro and in vivo models. The present data indicated that the proliferation of HepG2 cells was strikingly promoted after exposed to p,p'-DDT for 4 days. In addition, reactive oxygen species (ROS) content was significantly elevated, accompanied with inhibitions of γ-glutamylcysteine synthetase (γ-GCS) and superoxide dismutase (SOD) activities. Interestingly, the levels of β-catenin and its downstream target genes (c-Myc and CyclinD1) were significantly up-regulated, and co-treatment of NAC, the ROS inhibitor, inhibited these over-expressed proteins. Moreover, the p,p'-DDT-stimulated proliferation of HepG2 cells could be reversed after NAC or β-catenin siRNA co-treatment. Likewise, p,p'-DDT treatment increased the growth of tumor in nude mice, stimulated oxidative stress and Wnt/β-catenin pathway. Our study indicates that low doses p,p'-DDT exposure promote the growth of hepatocellular carcinoma via Wnt/β-catenin pathway which is activated by oxidative stress. The finding suggests an association between low dose DDT exposure and liver cancer growth.
Foster R, Meyer J, Iyengar P, et al. Localization accuracy and immobilization effectiveness of a stereotactic body frame for a variety of treatment sites. Int J Radiat Oncol Biol Phys. 2013; 87(5):911-6 [PubMed] Related Publications
PURPOSE: The purpose of this study was to analyze the pretreatment setup errors and intrafraction motion using cone beam computed tomography (CBCT) for stereotactic body radiation therapy patients immobilized and localized with a stereotactic body frame for a variety of treatment sites. METHODS AND MATERIALS: Localization errors were recorded for patients receiving SBRT for 141 lung, 29 liver, 48 prostate, and 45 spine tumors representing 1005 total localization sessions. All patients were treated in a stereotactic body frame with a large custom-molded vacuum pillow. Patients were first localized to the frame using tattoos placed during simulation. Subsequently, the frame was aligned to the room lasers according to the stereotactic coordinates determined from the treatment plan. Every patient received a pretreatment and an intrafraction CBCT. Abdominal compression was used for all liver patients and for approximately 40% of the lung patients to reduce tumor motion due to respiration. RESULTS: The mean ± standard deviation pretreatment setup errors from all localizations were -2.44 ± 3.85, 1.31 ± 5.84, and 0.11 ± 3.76 mm in the anteroposterior, superoinferior, and lateral directions, respectively. The mean pretreatment localization results among all treatment sites were not significantly different (F test, P<.05). For all treatment sites, the mean ± standard deviation intrafraction shifts were 0.33 ± 1.34, 0.15 ± 1.45, and -0.02 ± 1.17 mm in the anteroposterior, superoinferior, and lateral directions, respectively. The mean unidimensional intrafraction shifts were statistically different for several of the comparisons (P<.05) as assessed by the Tukey-Kramer test. CONCLUSIONS: Despite the varied tumor locations, the pretreatment mean localization errors for all sites were found to be consistent among the treatment sites and not significantly different, indicating that the body frame is a suitable immobilization and localization device for a variety of tumor sites. Our pretreatment localization errors and intrafraction shifts compare favorably with those reported in other studies using different types of immobilization devices.
Park ES, Lee J, Kang SY, et al. A comparative study of telomerase activity and cytologic diagnosis in malignant ascites. Anal Quant Cytol Histol. 2013; 35(3):146-51 [PubMed] Related Publications
OBJECTIVE: To evaluate telomerase activity as an adjunct in the cytologic diagnosis of malignant ascites. STUDY DESIGN: Malignant ascites collected from 19 gastrointestinal or liver cancer patients with clinical or pathologic evidence of peritoneal metastasis were tested for routine cytology with a liquid-based preparation, and telomerase activity was measured by telomere-repeat amplification protocol (TRAP) and real-time quantitative TRAP (RTQ-TRAP) assays. For comparison, controls from peritoneal washings from 8 early gastric cancer patients were used. RESULTS: Cytological examination detected cancer cells in 8 patients (42%), and 3 cases (16%) were diagnosed as "atypia." With TRAP and RTQ-TRAP assays 16 (84%) and 15 (78%) cases, respectively, were positive for telomerase activity. The sensitivity of telomerase activity by TRAP, RTQ-TRAP assays, and cytology was 84%, 78%, and 58%, respectively. All cases with "atypia" by cytological examination were positive for both TRAP and RTQ-PCR assays. In all negative controls, cytology, TRAP and RTQ-TRAP assays were negative. CONCLUSION: Based on our findings telomerase activity is a more sensitive method than ascitic fluid cytology and therefore can be considered as a useful diagnostic adjunct to current standard diagnostic methods. However, further large cohort studies with clinical correlation are needed to confirm our findings.
Swadley MJ, Deliu M, Mosunjac MB, et al. Primary and secondary hepatic lymphomas diagnosed by image-guided fine-needle aspiration: a retrospective study of clinical and cytomorphologic findings. Am J Clin Pathol. 2014; 141(1):119-27 [PubMed] Related Publications
OBJECTIVES: To explore the diagnosis of hematolymphoid malignancies of the liver (hepatic lymphoma [HeL]) by image-guided fine-needle aspiration (FNA), which can often be difficult due to a low index of suspicion and nonspecific patient presentations, especially in the rare cases where the liver is the only site of disease (primary HeL [PHeL]). Understanding the clinical setting in which such lesions arise, as well as the cytomorphologic findings, may assist cytopathologists in making an accurate diagnosis and triaging samples for ancillary studies. METHODS: In this retrospective study of 32 patients with HeL, the largest such study to our knowledge, we review the clinical and diagnostic features of HeL. RESULTS: HeL and especially PHeL most commonly show a diffuse large B-cell lymphoma phenotype and have a poor prognosis (median survival of seven months). PHeL is strongly associated with human immunodeficiency virus infection (12/16 patients). CONCLUSIONS: Image-guided FNA with immediate evaluation is a reliable means to obtain diagnostic material and triage for ancillary tests.
Liu Y, Sogawa K, Sunaga M, et al. Increased concentrations of apo A-I and apo A-II fragments in the serum of patients with hepatocellular carcinoma by magnetic beads-assisted MALDI-TOF mass spectrometry. Am J Clin Pathol. 2014; 141(1):52-61 [PubMed] Related Publications
OBJECTIVES: Recent advances in sophisticated technologies in proteomics should provide promising ways to discover novel markers for hepatocellular carcinoma (HCC) in the early diagnosis. METHODS: Serum peptide and protein profiling was conducted by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Profiling was carried out in a training set of 16 patients with HCC and a testing set of 15 patients with cirrhosis without HCC. All the patients were hepatitis C virus positive. Candidate peaks were processed to partial purification, followed by protein identification by amino acid sequence analysis. Immunoprecipitation was conducted to confirm the protein identity. RESULTS: Partial purification and protein identification revealed that one peak that was up-regulated in HCC sera both in the training and the testing sets was a fragment of apolipoprotein A-I (apo A-I). Immunoprecipitation confirmed this result. CONCLUSIONS: MALDI-TOF MS analysis revealed that apo A-I is a potential novel serum marker of HCC. Combination of these pretreatments and the current magnet bead-assisted MALDI-TOF MS will further enhance the efficiency of biomarker discovery for HCC.
Xu M, Wang Y, Chen L, et al. Down-regulation of ribosomal protein S15A mRNA with a short hairpin RNA inhibits human hepatic cancer cell growth in vitro. Gene. 2014; 536(1):84-9 [PubMed] Related Publications
Ribosomal protein s15a (RPS15A) is a highly conserved protein that promotes mRNA/ribosome interactions early in translation. Recent evidence showed that RPS15A could stimulate growth in yeast, plant and human lung carcinoma. Here we report that RPS15A knockdown could inhibit hepatic cancer cell growth in vitro. When transduced with shRPS15A-containing lentivirus, we observed inhibited cell proliferation and impaired colony formation in both HepG2 and Bel7404 cells. Furthermore, cell cycle analysis showed that HepG2 cells were arrested at the G0/G1 phase when transduced with Lv-shRPS15A. In conclusion, our findings provide for the first time the biological effects of RPS15A in hepatic cancer cell growth. RPS15A may play a prominent role in heptocarcinogenesis and serve as a potential therapeutic target in hepatocellular carcinoma.
Gao S, Li A, Liu F, et al. NCOA5 haploinsufficiency results in glucose intolerance and subsequent hepatocellular carcinoma. Cancer Cell. 2013; 24(6):725-37 [PubMed] Article available free on PMC after 09/12/2014 Related Publications
Type 2 diabetes (T2D) and male gender are associated with hepatocellular carcinoma (HCC) development. We demonstrate that heterozygous deletion of the Ncoa5 gene causes spontaneous development of HCC exclusively in male mice. Tumor development is preceded by increased interleukin-6 (IL-6) expression, early-onset glucose intolerance, and progressive steatosis and dysplasia in livers. Blockading IL-6 overexpression averts glucose intolerance and partially deters HCC development. Moreover, reduced NCOA5 expression is associated with a fraction of human HCCs and HCCs with comorbid T2D. These findings suggest that NCOA5 is a haploinsufficient tumor suppressor and that NCOA5 deficiency increases susceptibility to both glucose intolerance and HCC, partially by increasing IL-6 expression. Thus, our findings open additional avenues for developing therapeutic approaches to combat these diseases.
Buchler T, Homolka J, Fencl P, et al. Nontuberculous mycobacterial infection after therapy with temsirolimus for metastatic renal cell carcinoma. Tumori. 2013 Jul-Aug; 99(4):e159-63 [PubMed] Related Publications
We describe the case of a patient with metastatic renal cell carcinoma (mRCC) who developed a nontuberculous mycobacteria (NTM)-related pulmonary nodule during therapy with the mammalian target of rapamycin (mTOR) inhibitor temsirolimus. After discontinuation of temsirolimus treatment, a small pulmonary nodule with increased glucose uptake was detected on a positron emission tomography (PET) scan. A lung resection carried out to confirm and treat the suspected solitary metastasis of RCC yielded the surprising finding of a caseating granuloma containing NTM. A single PET-positive nodule presents a significant differential diagnostic dilemma in the setting of mRCC treated with mTOR inhibitors. Although the treatment of mRCC with temsirolimus can lead to immunosuppression and opportunistic infections, there is no report to our knowledge on the occurrence of NTM infections in mRCC patients treated with mTOR inhibitors. These infections should be included in the differential diagnosis of lung nodules. Interestingly, there is strong preclinical evidence pointing to direct and indirect antimycobacterial activity of mTOR inhibitors. We therefore hypothesize that while the seeding of NTM can occur during temsirolimus therapy due to T-lymphocyte suppression, the infection may only become active after the discontinuation of mTOR inhibitor treatment.
Wu J, Zou H, Jiang JT, et al. Clinical application of serum alpha-fetoprotein-IgM complexes on the diagnosis of primary hepatocellular carcinoma in Kazakh and Han populations. Tumori. 2013 Jul-Aug; 99(4):535-9 [PubMed] Related Publications
AIMS AND BACKGROUND: We detected serum AFP-IgM levels in patients with primary hepatocellular carcinoma in Kazakh and Han populations to investigate the clinical significance of AFP-IgM in the diagnosis of hepatocellular carcinoma. METHODS AND STUDY DESIGN: Serum AFP-IgM levels were examined in 28 cases of hepatocellular carcinoma and 164 controls in the Kazakh population and in 85 cases of hepatocellular carcinoma and 187 controls in the Han population. AFP-IgM was detected with the ELISA assay. RESULTS: In general, serum AFP-IgM levels of hepatocellular carcinoma patients in the Han population and hepatocellular carcinoma patients in the Kazakh population were statistically higher than those of controls, but there was no statistical significance between hepatocellular carcinoma patients in the Han and hepatocellular carcinoma patients in the Kazakh population. CONCLUSIONS: AFP-IgM is an encouraging serological marker and may be useful in the diagnosis of hepatocellular carcinoma.
Okimoto K, Ogasawara S, Chiba T, et al. Efficacy of transcatheter arterial chemoembolization with miriplatin-lipiodol water-soluble contrast agent emulsion in patients with hepatocellular carcinoma. Anticancer Res. 2013; 33(12):5603-9 [PubMed] Related Publications
AIM: To evaluate the therapeutic efficacy of transcatheter arterial chemoembolization (TACE) using miriplatin emulsion in unresectable hepatocellular carcinoma (HCC). PATIENTS AND METHODS: The efficacy of TACE was evaluated by dynamic computed tomography or magnetic resonance imaging three months after TACE, according to the Response Evaluation Criteria in Cancer Study Group of Japan (RECICL). Adverse events were assessed using Common Terminology Criteria, version 4.0. RESULTS: Eighteen patients with 48 lesions received TACE with miriplatin-lipiodol (LPD) suspension (miriplatin suspension) and 53 patients with 114 HCC tumors received TACE with miriplatin-LPD water-soluble contrast agent emulsion (miriplatin emulsion). TACE with miriplatin emulsion enabled for administration of a higher dose of miriplatin compared to TACE with miriplatin suspension (p=0.016), although there were no significant differences in the frequency of adverse events between the two groups. The treatment effect per tumor was significantly higher in the emulsion group than in the suspension group (p=0.001). The time-to-progression per tumor was significantly shorter in the suspension group than in the emulsion group (p=0.001). CONCLUSION: TACE with miriplatin emulsion is more effective than that with miriplatin suspension.
Kumamoto T, Tanaka K, Matsuo K, et al. Adjuvant hepatic arterial infusion chemotherapy with 5-Fluorouracil and interferon after curative resection of hepatocellular carcinoma: a preliminary report. Anticancer Res. 2013; 33(12):5585-90 [PubMed] Related Publications
BACKGROUND AND AIM: Advanced hepatocellular carcinoma (HCC) with portal vein invasion or intrahepatic metastases has an unfavorable prognosis, even after curative hepatic resection. The aim of the present study was to evaluate the efficacy of adjuvant hepatic arterial infusion chemotherapy with 5-fluorouracil (5-FU) and systemic interferon (IFN). PATIENTS AND METHODS: Patients who were diagnosed as having HCC with portal vein invasion or intrahepatic metastases were included in the study (n=33). Out of these patients, 16 were treated with adjuvant therapy consisting of continuous arterial infusion of 5-FU and subcutaneous injection of IFN-α. Another 17 patients who underwent hepatic resection without adjuvant chemotherapy served as controls. RESULTS: The five-year cumulative survival rate was significantly higher in the adjuvant treatment group (71.1%) than in the control group (44.0%; p=0.023). The rate of patients with multiple (≥4) recurrent intrahepatic nodules was significantly lower in the adjuvant group (44.4%) than in the control group (100%; p=0.040). The development of intrahepatic recurrence within 12 months was significantly lower in the adjuvant group (33.3%) than in the control group (80.0%; p=0.040). CONCLUSION: Our data suggest that this adjuvant chemotherapy can improve postoperative prognosis by reducing intrahepatic recurrence.
Chamadol N, Somsap K, Laopaiboon V, Sukeepaisarnjaroen W Sonographic findings of hepatocellular carcinoma detected in ultrasound surveillance of cirrhotic patients. J Med Assoc Thai. 2013; 96(7):829-38 [PubMed] Related Publications
BACKGROUND: Hepatocellular carcinoma (HCC) is associated with high mortality. Patients with hepatitis B or C viral cirrhosis have an increased risk of developing HCC. Ultrasound is the most widely used screening method, and is recommended by many guidelines. OBJECTIVE: To study the sonographic findings ofHCC detected in ultrasound surveillance of cirrhotic patients. MATERIAL AND METHOD: Retrospective assessment of ultrasoundfindings of all nodules that were diagnosed HCC by either dynamic imaging (CTor MRI) or biopsy between October 2008 and July 2011. Nodules were classified based on echogenicity and other sonographic characteristics. RESULTS: Of 92 nodules, 42 (45.7%) were hyperechoic, 29 (31.5%) hypoechoic, 20 (21.7%) heterogeneous echoic and 1 (1.1%) isoechoic. Heteroechoic nodules were more common among nodules over 3.0 cm (p = 0.0037) while hypoechoic nodules tended to be the smaller ones. About half (48/92) of the nodules had a hypoechoic halo and occurred significantly more commonly among hyperechoic and heteroechoic nodules (p< 0. 001). Posterior enhancement was found in 54 nodules (58. 7%0), also more common in nodules >3.0 cm (p = 018). Lateral shadowing occurred in 40 nodules (43.5%). CONCLUSION: The sonographic findings of HCC nodules in the present studies varied, but the prevalence of hyperechoic nodules was higher than in most of other studies. The authors emphasize the necessity of performing dynamic imaging for any nodule detected in a cirrhotic liver in order to exclude their neoplastic nature, no matter what it may look like.
Frankel TL, D'Angelica MI Hepatic resection for colorectal metastases. J Surg Oncol. 2014; 109(1):2-7 [PubMed] Related Publications
The liver represents a common site for metastasis in colorectal cancer. Improvements in patient selection and surgical techniques has resulted in improved outcomes following hepatic metastasectomy with large series reporting 5- and 10-year overall survival rates of 40% and 20%, respectively. In recent years, criteria for resectability has expanded with the use of forced liver hypertrophy and staged resection. The role of perioperative chemotherapy remains controversial with a slight increase in survival and operative morbidity.
Bard-Chapeau EA, Nguyen AT, Rust AG, et al. Transposon mutagenesis identifies genes driving hepatocellular carcinoma in a chronic hepatitis B mouse model. Nat Genet. 2014; 46(1):24-32 [PubMed] Related Publications
The most common risk factor for developing hepatocellular carcinoma (HCC) is chronic infection with hepatitis B virus (HBV). To better understand the evolutionary forces driving HCC, we performed a near-saturating transposon mutagenesis screen in a mouse HBV model of HCC. This screen identified 21 candidate early stage drivers and a very large number (2,860) of candidate later stage drivers that were enriched for genes that are mutated, deregulated or functioning in signaling pathways important for human HCC, with a striking 1,199 genes being linked to cellular metabolic processes. Our study provides a comprehensive overview of the genetic landscape of HCC.
Shukla SD, Lim RW Epigenetic effects of ethanol on the liver and gastrointestinal system. Alcohol Res. 2013; 35(1):47-55 [PubMed] Article available free on PMC after 09/12/2014 Related Publications
The widening web of epigenetic regulatory mechanisms also encompasses ethanol-induced changes in the gastrointestinal (GI)-hepatic system. In the past few years, increasing evidence has firmly established that alcohol modifies several epigenetic parameters in the GI tract and liver. The major pathways affected include DNA methylation, different site-specific modifications in histone proteins, and microRNAs. Ethanol metabolism, cell-signaling cascades, and oxidative stress have been implicated in these responses. Furthermore, ethanol-induced fatty liver (i.e., steatohepatitis) and progression of liver cancer (i.e., hepatic carcinoma) may be consequences of the altered epigenetics. Modification of gene and/or protein expression via epigenetic changes also may contribute to the cross-talk among the GI tract and the liver as well as to systemic changes involving other organs. Thus, epigenetic effects of ethanol may have a central role in the various pathophysiological responses induced by ethanol in multiple organs and mediated via the liver-GI axis.
Wang H, Chen G, Wang H, Liu C RITA inhibits growth of human hepatocellular carcinoma through induction of apoptosis. Oncol Res. 2013; 20(10):437-45 [PubMed] Related Publications
RBP-J-interacting and tubulin-associated (RITA) is a novel RBP-J-interacting protein that downregulates Notch-mediated transcription. The current study focuses on the antitumor effect of RITA in human hepatocellular carcinoma (HCC) and aims to explore its molecular mechanism. Thirty paired HCC and adjacent non-tumoral liver samples were analyzed by real-time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). RITA overexpression was induced by transfection of a pcDNA3.1-Flag-RITA plasmid into HepG2 cells. RITA knockdown was achieved by siRNA transfection. mRNA and protein expression of target genes were quantified by qRT-PCR and Western blotting, respectively. Cell proliferation and apoptosis were measured using MTT assay and flow cytometry. Our results demonstrate that adjacent nontumoral liver samples exhibited increased RITA expression compared to HCC tissues (p < 0.05); RITA levels were associated with tumor differentiation status. Overexpression of RITA suppressed cell proliferation and promoted early apoptosis, while its silencing promoted cell growth dramatically (p < 0.05). RITA overexpression upregulated p53 and reduced cyclin E levels, whereas silencing of RITA had the opposite effect on p53 and cyclin E expression. Our in vitro results represent the first evidence that RITA might suppress tumor growth and induce apoptosis in HCCs, and may be a potent antitumoral agent for HCC treatment that deserves further exploration.
Li F, Guo Z, Wang H Influencing elements and treatment strategies associated with the relapse of hepatocellular carcinoma after surgery. Hepatogastroenterology. 2013 Jul-Aug; 60(125):1148-55 [PubMed] Related Publications
UNLABELLED: BACKGROUND/ AIMS: Long-term prognosis after surgical resection of Hepatocellular Carcinoma remains unsatisfactory, mainly because of the high postoperative incidence of recurrence and metastasis. An updated knowledge on the influencing factors of recurrence and treatment strategies of postoperative recurrence is important for clinicians in designing a strategy to optimize the chance of long-term survival in patients undergoing hepatic resection for HCC. METHODOLOGY: Using key words “Hepatocellular Carcinoma”, “liver cancer”, “resection”, “postoperative recurrence”, “treatment strategy”, “therapy”, “influencing factors”, “risk factors”, we performed a review of relevant English articles based on based on a Medline search before May 2012. RESULTS: Influencing factors include tumor size, venous invasion, satellite nodules, cirrhosis, alpha-foetoprotein, aspartate aminotransferase, alkaline phosphatase levels, hepatitis B virus and hepatitis C virus infection, Alpha-foetoprotein mRNA and some surgical factors. Treatment strategies include re-resection, transarterial chemoembolization, radiofrequency ablation, percutaneous ethanol injection, salvage liver transplantation, radioactive seed 125I implantation and other new treatment modalities of postoperative recurrent HCC are all used to prolong survival in patients with recurrence, and multimodality therapy of above mentioned therapies may offer additional beneﬁt. CONCLUSIONS: With advances in perioperative detection and therapeutic modalities, results of recurrence after resection of HCC will greatly improved.
Kan QC, Li DL, Yu ZJ Vector-mediated expression of interferon gamma inhibits replication of hepatitis B virus in vitro. Acta Virol. 2013; 57(4):421-8 [PubMed] Related Publications
Despite the existence of efficient vaccines against hepatitis B virus (HBV) infections, these still represent a serious threat to human health worldwide. Acute HBV infections often become chronic, marked by liver cirrhosis and hepatocellular carcinoma. Promising results with interferons alpha or gamma (IFN-α, γ) or nucleoside/nucleotide analogs in inhibiting HBV replication in vitro have led to therapeutic applications to chronic HBV patients, however, their results so far have not been satisfactory. The treatments were either not effective in all patients or had adverse effects. Certain progress was expected from expression of interferons targeted to liver by adenovirus vectors, however, this approach turned out to be limited by undesired expression of toxic viral genes and high production costs. Therefore, in this study, we attempted to inhibit HBV replication in HepG2.2.15 cells by human IFN-γ expressed through a non-viral vector, an eukaryotic plasmid. The results demonstrated that IFN-γ, targeted to HBV-replicating cells, significantly inhibited the virus growth without inducing apoptosis and indicated that local expression of this kind of cytokine may be a promising strategy of gene therapy.
Motavaf M, Safari S, Saffari Jourshari M, Alavian SM Hepatitis B virus-induced hepatocellular carcinoma: the role of the virus x protein. Acta Virol. 2013; 57(4):389-96 [PubMed] Related Publications
Hepatocellular carcinoma (HCC) is one of the most common malignant diseases and has the fourth highest mortality rate worldwide. Chronic hepatitis B virus (HBV) infection has been identified as a major risk factor in HCC. Currently available evidence support a critical role of hepatitis B virus x (HBx) gene and protein in the pathogenesis of HBV-induced HCC. HBx protein is a multifunctional regulator that modulates cellular signal transduction pathways, transcriptional regulations, cell cycle progress, DNA repair, apoptosis, and genetic stability by interacting with different host factors. This review describes the current state of knowledge about the biological roles of this protein in the development of HCC.