WorldWideScience

Sample records for hepatocellular carcinoma prognosis

  1. Noninvasive imaging of hepatocellular carcinoma: From diagnosis to prognosis

    Science.gov (United States)

    Jiang, Han-Yu; Chen, Jie; Xia, Chun-Chao; Cao, Li-Kun; Duan, Ting; Song, Bin

    2018-01-01

    Hepatocellular carcinoma (HCC) is the most common primary liver cancer and a major public health problem worldwide. Hepatocarcinogenesis is a complex multistep process at molecular, cellular, and histologic levels with key alterations that can be revealed by noninvasive imaging modalities. Therefore, imaging techniques play pivotal roles in the detection, characterization, staging, surveillance, and prognosis evaluation of HCC. Currently, ultrasound is the first-line imaging modality for screening and surveillance purposes. While based on conclusive enhancement patterns comprising arterial phase hyperenhancement and portal venous and/or delayed phase wash-out, contrast enhanced dynamic computed tomography and magnetic resonance imaging (MRI) are the diagnostic tools for HCC without requirements for histopathologic confirmation. Functional MRI techniques, including diffusion-weighted imaging, MRI with hepatobiliary contrast agents, perfusion imaging, and magnetic resonance elastography, show promise in providing further important information regarding tumor biological behaviors. In addition, evaluation of tumor imaging characteristics, including nodule size, margin, number, vascular invasion, and growth patterns, allows preoperative prediction of tumor microvascular invasion and patient prognosis. Therefore, the aim of this article is to review the current state-of-the-art and recent advances in the comprehensive noninvasive imaging evaluation of HCC. We also provide the basic key concepts of HCC development and an overview of the current practice guidelines. PMID:29904242

  2. Hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Farooqi, J.I.; Farooqi, R.J.

    2001-01-01

    Hepatocellular carcinoma (HCC) is a common cause of cancer mortality. Hepatitis B and C viruses, aflatoxin and alga toxin in the contaminated drinking water are the major etiological factors. Rapidly progressing medical imaging has resulted in the improved treatment results. Surgical resection has a major role for influencing prognosis of HCC. Local cancer therapies based on the advances in early diagnosis are progressing rapidly. Multimodality combination and sequential treatment has proved effective, unfortunately systemic chemotherapy for HCC remains disappointed. All of these have resulted in the improved prognosis of HCC. (author)

  3. Prognosis and therapy for ruptured hepatocellular carcinoma: Problems with staging and treatment strategy

    Energy Technology Data Exchange (ETDEWEB)

    Hiraoka, Atsushi, E-mail: hirage@m.ehime-u.ac.jp [Gastroenterology Center, Ehime Prefectural Central Hospital, Kasuga-cho 83, Matsuyama, Ehime 790-0024 (Japan); Kawamura, Tomoe; Aibiki, Toshihiko; Okudaira, Tomonari; Toshimori, Akiko; Yamago, Hiroka; Nakahara, Hiromasa; Suga, Yoshifumi; Azemoto, Nobuaki; Miyata, Hideki; Miyamoto, Yasunao; Ninomiya, Tomoyuki [Gastroenterology Center, Ehime Prefectural Central Hospital, Kasuga-cho 83, Matsuyama, Ehime 790-0024 (Japan); Murakami, Tadashi; Ishimaru, Yoshihiro [Department of Radiology, Ehime Prefectural Central Hospital (Japan); Kawasaki, Hideki [Department of Surgery, Ehime Prefectural Central Hospital (Japan); Hirooka, Masashi; Abe, Masanori; Matsuura, Bunzo; Hiasa, Yoichi [Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Ehime (Japan); Michitaka, Kojiro [Gastroenterology Center, Ehime Prefectural Central Hospital, Kasuga-cho 83, Matsuyama, Ehime 790-0024 (Japan)

    2015-03-15

    Highlights: •Although a patient with a ruptured HCC is generally considered to have a poor prognosis and treated as T4 in the 7th edition of the AJCC/UICC, some ruptured cases show a good clinical course. •There are no clear criteria established for treating a ruptured hepatocellular carcinoma (HCC) which is classified as T4 in TNM stage of UICC 7th. •This article describes that better prognosis can be expected with curative treatment in patients with a ruptured HCC, especially those with a single tumor, and without decompensated liver cirrhosis and PVTT/extrahepatic metastasis. T4 classification should not include all types of ruptured HCC. -- Abstract: Background: There are no clear criteria established for treating a ruptured hepatocellular carcinoma (HCC). To elucidate the clinical features of affected patients, we examined prognosis and therapy choices. Materials/methods: We enrolled 67 patients treated for a ruptured HCC (HCV 44, HBV 5, HBV + HCV 1, alcohol 2, others 15; naïve HCC 34, recurrent 33) from 2000 to 2013, and investigated their clinical background and prognosis. Results: Median survival time (MST) for all cases was 4 months. For patients who survived for more than 1 year after rupture, the percentages of Child-Pugh C and positive for portal vein tumor thrombosis (PVTT)/extrahepatic metastasis were less than for those who died within 1 year. Child-Pugh classification (A:B:C = 14:15:5 vs. 4:9:20, P < 0.001) was better, while the percentage of patients with multiple tumors was lower [19/34 (55.9%) vs. 29/33 (87.9%), respectively; P < 0.001] in the naïve group. The 1- and 3-year survival rates were better in the naïve as compared to the recurrent group (60.6% and 33.3% vs. 12.6% and 0%, respectively; P < 0.01). MST according to modified TNM stage (UICC 7th) calculated after exclusion of T4 factor of rupture, stage I was better than others (22.7 vs. (II) 2.2, (III) 1.2, and (IV) 0.7 months) (P = 0.010). Conclusion: In patients with a ruptured

  4. Circulating tumour DNA methylation markers for diagnosis and prognosis of hepatocellular carcinoma

    Science.gov (United States)

    Xu, Rui-Hua; Wei, Wei; Krawczyk, Michal; Wang, Wenqiu; Luo, Huiyan; Flagg, Ken; Yi, Shaohua; Shi, William; Quan, Qingli; Li, Kang; Zheng, Lianghong; Zhang, Heng; Caughey, Bennett A.; Zhao, Qi; Hou, Jiayi; Zhang, Runze; Xu, Yanxin; Cai, Huimin; Li, Gen; Hou, Rui; Zhong, Zheng; Lin, Danni; Fu, Xin; Zhu, Jie; Duan, Yaou; Yu, Meixing; Ying, Binwu; Zhang, Wengeng; Wang, Juan; Zhang, Edward; Zhang, Charlotte; Li, Oulan; Guo, Rongping; Carter, Hannah; Zhu, Jian-Kang; Hao, Xiaoke; Zhang, Kang

    2017-11-01

    An effective blood-based method for the diagnosis and prognosis of hepatocellular carcinoma (HCC) has not yet been developed. Circulating tumour DNA (ctDNA) carrying cancer-specific genetic and epigenetic aberrations may enable a noninvasive `liquid biopsy' for diagnosis and monitoring of cancer. Here, we identified an HCC-specific methylation marker panel by comparing HCC tissue and normal blood leukocytes and showed that methylation profiles of HCC tumour DNA and matched plasma ctDNA are highly correlated. Using cfDNA samples from a large cohort of 1,098 HCC patients and 835 normal controls, we constructed a diagnostic prediction model that showed high diagnostic specificity and sensitivity (P < 0.001) and was highly correlated with tumour burden, treatment response, and stage. Additionally, we constructed a prognostic prediction model that effectively predicted prognosis and survival (P < 0.001). Together, these findings demonstrate in a large clinical cohort the utility of ctDNA methylation markers in the diagnosis, surveillance, and prognosis of HCC.

  5. Predicting prognosis in hepatocellular carcinoma after curative surgery with common clinicopathologic parameters

    International Nuclear Information System (INIS)

    Hao, Ke; Sham, Pak C; Poon, Ronnie TP; Luk, John M; Lee, Nikki PY; Mao, Mao; Zhang, Chunsheng; Ferguson, Mark D; Lamb, John; Dai, Hongyue; Ng, Irene O

    2009-01-01

    Surgical resection is one important curative treatment for hepatocellular carcinoma (HCC), but the prognosis following surgery differs substantially and such large variation is mainly unexplained. A review of the literature yields a number of clinicopathologic parameters associated with HCC prognosis. However, the results are not consistent due to lack of systemic approach to establish a prediction model incorporating all these parameters. We conducted a retrospective analysis on the common clinicopathologic parameters from a cohort of 572 ethnic Chinese HCC patients who received curative surgery. The cases were randomly divided into training (n = 272) and validation (n = 300) sets. Each parameter was individually tested and the significant parameters were entered into a linear classifier for model building, and the prediction accuracy was assessed in the validation set Our findings based on the training set data reveal 6 common clinicopathologic parameters (tumor size, number of tumor nodules, tumor stage, venous infiltration status, and serum α-fetoprotein and total albumin levels) that were significantly associated with the overall HCC survival and disease-free survival (time to recurrence). We next built a linear classifier model by multivariate Cox regression to predict prognostic outcomes of HCC patients after curative surgery This analysis detected a considerable fraction of variance in HCC prognosis and the area under the ROC curve was about 70%. We further evaluated the model using two other protocols; leave-one-out procedure (n = 264) and independent validation (n = 300). Both were found to have excellent prediction power. The predicted score could separate patients into distinct groups with respect to survival (p-value = 1.8e-12) and disease free survival (p-value = 3.2e-7). This described model will provide valuable guidance on prognosis after curative surgery for HCC in clinical practice. The adaptive nature allows easy accommodation for future new

  6. Expression quantitative trait loci for PAX8 contributes to the prognosis of hepatocellular carcinoma.

    Directory of Open Access Journals (Sweden)

    Shijie Ma

    Full Text Available Paired-box family member PAX8 encodes a transcription factor that has a role in cell differentiation and cell growth and may participate in the prognosis of hepatocellular carcinoma (HCC. By bioinformatics analysis, we identified several single nucleotide polymorphisms (SNPs within a newly identified long non-coding RNA (lncRNA AC016683.6 as expression quantitative trait loci (eQTLs for PAX8. Hence, we hypothesized that PAX8eQTLs in lncRNA AC016683.6 may influence the HCC prognosis. We then performed a case-only study to assess the association between the two SNPs as well as the prognosis of HCC in 331 HBV-positive HCC patients without surgical treatment. Cox proportional hazard models were used for survival analysis with adjustments for the age, gender, smoking status, drinking status, Barcelona-Clinic Liver Cancer (BCLC stage, and chemotherapy or TACE (transcatheter hepatic arterial chemoembolization status. We found that the G allele of rs1110839 and the T allele of rs4848320 in PAX8was significantly associated with a better prognosis compared with the T allele of rs1110839 and the C allele of rs4848320 (adjusted HR = 0.74, 95% CI = 0.61-0.91, P = 0.004 for rs1110839 and adjusted HR = 0.71, 95% CI = 0.54-0.94, P = 0.015 for rs4848320 in the additive model. Furthermore, the combined effect of the variant genotypes for these two SNPs was more prominent in patients with the BCLC-C stage orpatients with chemotherapy or TACE. Although the exact biological function remains to be explored, our findings suggest a possible association of PAX8eQTLs in lncRNA AC016683.6 with the HCC prognosis inthe Chinese population. Further large and functional studies are needed to confirm our findings.

  7. TMEM88, CCL14 and CLEC3B as prognostic biomarkers for prognosis and palindromia of human hepatocellular carcinoma.

    Science.gov (United States)

    Zhang, Xin; Wan, Jin-Xiang; Ke, Zun-Ping; Wang, Feng; Chai, Hai-Xia; Liu, Jia-Qiang

    2017-07-01

    Hepatocellular carcinoma is one of the most mortal and prevalent cancers with increasing incidence worldwide. Elucidating genetic driver genes for prognosis and palindromia of hepatocellular carcinoma helps managing clinical decisions for patients. In this study, the high-throughput RNA sequencing data on platform IlluminaHiSeq of hepatocellular carcinoma were downloaded from The Cancer Genome Atlas with 330 primary hepatocellular carcinoma patient samples. Stable key genes with differential expressions were identified with which Kaplan-Meier survival analysis was performed using Cox proportional hazards test in R language. Driver genes influencing the prognosis of this disease were determined using clustering analysis. Functional analysis of driver genes was performed by literature search and Gene Set Enrichment Analysis. Finally, the selected driver genes were verified using external dataset GSE40873. A total of 5781 stable key genes were identified, including 156 genes definitely related to prognoses of hepatocellular carcinoma. Based on the significant key genes, samples were grouped into five clusters which were further integrated into high- and low-risk classes based on clinical features. TMEM88, CCL14, and CLEC3B were selected as driver genes which clustered high-/low-risk patients successfully (generally, p = 0.0005124445). Finally, survival analysis of the high-/low-risk samples from external database illustrated significant difference with p value 0.0198. In conclusion, TMEM88, CCL14, and CLEC3B genes were stable and available in predicting the survival and palindromia time of hepatocellular carcinoma. These genes could function as potential prognostic genes contributing to improve patients' outcomes and survival.

  8. TERT-CLPTM1 locus polymorphism (rs401681 is associated with the prognosis of hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Lee HW

    2017-10-01

    Full Text Available Hye Won Lee,1,* Won-Jin Park,2,* Yu-Ran Heo,2 Tae In Park,3 Soo Young Park,4 Jae-Ho Lee2,* 1Department of Pathology, Keimyung University School of Medicine, Daegu, Republic of Korea; 2Department of Anatomy, Keimyung University School of Medicine, Daegu, Republic of Korea; 3Department of Pathology, Kyungpook National University School of Medicine, Daegu, Republic of Korea; 4Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, Republic of Korea *These authors contributed equally to this work Abstract: Telomere length is associated with the development of hepatocellular carcinoma (HCC, and recent studies have focused on the genetic alteration or polymorphism in telomere-maintaining genes. We examined the clinicopathologic and prognostic value of rs401681 polymorphism, located in the TERT-CLPTM1L locus, in HCC. The relationship between rs401681 variants and telomere length was also analyzed in 156 HCC patients. The rs401681 polymorphism had the following genotype frequencies: C/C in 51.3% of the samples, C/T in 39.7%, and T/T in 9.0%. Telomeres in the tumor samples were 4.04-fold longer, on average, than the telomeres in matched normal samples (SD =1.32, and there were no differences in telomere length according to rs401681 polymorphism (p=0.802. Our results indicate that the rs401681 C allele was significantly associated with increased T and International Union for Cancer Control stages (p<0.01. Univariate and multivariate survival analyses showed that HCC with C allele had poorer prognosis (p<0.01. In conclusion, our findings suggest that rs401681 is a possible prognostic biomarker for HCC patients. Keywords: CLPTM1L polymorphism, hepatocellular carcinoma, TERT-CLPTM1L locus, telomere length

  9. Elevated TEAD1 Expression is not an Independent Prognosis Factor of Hepatocellular Carcinoma.

    Science.gov (United States)

    Hu, Xiao; He, Bin; Zhou, Lin; Zheng, Shusen

    2018-05-01

    To explore the expression pattern and clinical significance of TEAD1 in hepatocellular carcinoma (HCC). The prognostic significance of TEAD-1 expression is also evaluated. TEAD1 expression was detected by the immunohistochemistry (IHC) method and western blot. The association between TEAD1 expression of HCC tissues and clinical variables was evaluated by Chi-squared test. Survival analysis was used to determine the prognosis effect of TEAD1. Expression of TEAD1 is significantly increased in HCC tissues compared with adjacent normal liver tissues by IHC (p = 0.002) and western blot (p = 0.020). The difference for the ratio of low, medium, and high staining between HCC and normal tissues is significant (p < 0.001). Higher TEAD1 expression is related to worse histological grade (p = 0.013), bigger tumor size (p = 0.033), and higher serum a-fetoprotein (AFP) level of HCC patients (p = 0.026). No association is found between TEAD1 expression and other clinical features. No statistical difference is found for the overall survival among the low, medium, and high TEAD1 expression groups (p = 0.122). TEAD1 expression is highly expressed in HCC. TEAD1 overexpression is involved in the growth and differentiation of HCC. TEAD1 expression is unable to act as an independent prognosis factor for HCC patients.

  10. Strengthening the case that elevated levels of programmed death ligand 1 predict poor prognosis in hepatocellular carcinoma patients

    Directory of Open Access Journals (Sweden)

    Zhong J

    2016-12-01

    Full Text Available Jian-Hong Zhong,1,* Cheng-Piao Luo,2,* Chun-Yan Zhang,2 Le-Qun Li1 1Hepatobiliary Surgery Department, 2Experimental Department, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, People’s Republic of China *These authors contributed equally to this work Abstract: Immunotherapy targeting programmed death receptor 1 and programmed death ligand 1 (PD-L1 has shown impressive antitumor efficacy in several solid cancers, including advanced hepatocellular carcinoma (HCC. Since response rates of various cancers to such immunotherapy appear to correlate with PD-L1 expression levels, several studies have examined whether PD-L1 expression correlates with HCC pathology and patient prognosis. In this paper, we analyzed the strength and limitations of a recent meta-analysis of associations of PD-L1 with HCC characteristics and patient prognosis. Keywords: hepatocellular carcinoma, programmed death ligand 1, hepatic resection, prognoses

  11. Single nucleotide polymorphisms in MLH1 predict poor prognosis of hepatocellular carcinoma in a Chinese population.

    Science.gov (United States)

    Zhu, Xiaonian; Liu, Wei; Qiu, Xiaoqiang; Wang, Zhigang; Tan, Chao; Bei, Chunhua; Qin, Linyuan; Ren, Yuan; Tan, Shengkui

    2017-10-03

    Hepatocellular carcinoma (HCC) is a malignant cancer causing deleterious health effect worldwide, especially in China. So far clinical cure rate and long-term survival rate of HCC remains low. Most HCC patients after cancer resection have recurrence or metastasis within 5 years. This study aims to explore the genetic association of mutL homolog 1 ( MLH1 ) polymorphisms with HCC risk and prognosis. Four candidate MLH1 polymorphisms, rs1800734, rs10849, rs3774343 and rs1540354 were studied from a hospital-based case-control study including 1,036 cases (HCC patients) and 1,036 controls (non-HCC patients) in Guangxi, China. All these SNPs interacted with environmental risk factors, such as HBV infection, alcohol intake and smoking in the pathogenesis of HCC. However, only rs1800734 had significant difference between cases and controls. Compared to the AA genotype, patients with AG, GG and AG/GG genotype of rs1800734 had an increased risk of HCC [ORs (95% CI) = 1.217 (1.074∼1.536), 1.745 (1.301∼2.591) and 1.291 (1.126∼1.687)] and a decreased survival time [co-dominant, HR (95% CI) = 1.553 (1.257∼1.920); dominant, HR (95% CI) = 2.207 (1.572∼3.100)]. Furthermore, we found that tumor number, tumor staging, metastasis and rs1800734 were associated with the overall survival of HCC patients by multivariate COX regression analysis. No significant difference was found between the other three MLH1 polymorphisms with HCC risk and prognosis. Our study suggests MLH1 SNP, rs1800734 as a new predictor for poor prognosis of HCC patients.

  12. From big data to diagnosis and prognosis: gene expression signatures in liver hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Hong Yang

    2017-03-01

    Full Text Available Background Liver hepatocellular carcinoma accounts for the overwhelming majority of primary liver cancers and its belated diagnosis and poor prognosis call for novel biomarkers to be discovered, which, in the era of big data, innovative bioinformatics and computational techniques can prove to be highly helpful in. Methods Big data aggregated from The Cancer Genome Atlas and Natural Language Processing were integrated to generate differentially expressed genes. Relevant signaling pathways of differentially expressed genes went through Gene Ontology enrichment analysis, Kyoto Encyclopedia of Genes and Genomes and Panther pathway enrichment analysis and protein-protein interaction network. The pathway ranked high in the enrichment analysis was further investigated, and selected genes with top priority were evaluated and assessed in terms of their diagnostic and prognostic values. Results A list of 389 genes was generated by overlapping genes from The Cancer Genome Atlas and Natural Language Processing. Three pathways demonstrated top priorities, and the one with specific associations with cancers, ‘pathways in cancer,’ was analyzed with its four highlighted genes, namely, BIRC5, E2F1, CCNE1, and CDKN2A, which were validated using Oncomine. The detection pool composed of the four genes presented satisfactory diagnostic power with an outstanding integrated AUC of 0.990 (95% CI [0.982–0.998], P < 0.001, sensitivity: 96.0%, specificity: 96.5%. BIRC5 (P = 0.021 and CCNE1 (P = 0.027 were associated with poor prognosis, while CDKN2A (P = 0.066 and E2F1 (P = 0.088 demonstrated no statistically significant differences. Discussion The study illustrates liver hepatocellular carcinoma gene signatures, related pathways and networks from the perspective of big data, featuring the cancer-specific pathway with priority, ‘pathways in cancer.’ The detection pool of the four highlighted genes, namely BIRC5, E2F1, CCNE1 and CDKN2A, should be

  13. Low levels of tumor suppressor candidate 3 predict poor prognosis of patients with hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Sheng XR

    2018-02-01

    Full Text Available Xu-Ren Sheng,1,2,* Song-Ge Xing,2,3,* Run-Dong Wang,2 Kang Chen,2 Wei-Dong Jia1,2 1Department of Liver Surgery, Affiliated Provincial Hospital, Anhui Medical University, 2Anhui Province Key Laboratory of Hepatopancreatobiliary Surgery, 3CAS Key Laboratory of Innate Immunity and Chronic Disease, Innovation Center for Cell Signaling Network, School of Life Sciences, University of Science and Technology of China, Hefei, People’s Republic of China *These authors contributed equally to this work Purpose: The tumor suppressor candidate 3 (TUSC3 has been considered to be closely associated with the occurrence, development and invasion of various malignant tumors. However, the expression of TUSC3 in hepatocellular carcinoma (HCC tissues remains ambiguous. The purpose of this research was to investigate the expression of TUSC3 in HCC tissues and analyze the relationship between TUSC3 levels and clinicopathological characteristics and prognosis of HCC patients. Materials and methods: Immunohistochemistry was used to detect the expression of TUSC3 in HCC and the corresponding para-cancerous tissues from 92 samples of HCC patients. mRNA and protein expression levels of TUSC3 were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR and Western blot assays in 25 paired HCC and corresponding adjacent nontumor tissues. Furthermore, statistical analysis was applied to evaluate the correlation between TUSC3 level and the clinicopathological features and prognosis of HCC patients. Results: Immunohistochemical assay indicated that the expression of TUSC3 was significantly lower in HCC tissues when compared with the corresponding para-cancerous tissues (χ2=11.512, P=0.001. The analysis of clinicopathological characteristics showed that low expression of TUSC3 in HCC tissues was significantly associated with Edmondson grade, Barcelona Clinic Liver Cancer stage and tumor size (P=0.008, 0.009 and 0.020, respectively. Univariate analysis showed

  14. Tumor and liver determinants of prognosis in unresectable hepatocellular carcinoma: a large case cohort study.

    Science.gov (United States)

    Carr, Brian I; Pancoska, Petr; Branch, Robert A

    2009-12-24

    967 patients with unresectable and untransplantable, biopsy-proven hepatocellular carcinoma (HCC) were prospectively evaluated at baseline and followed up till death. Survival was the end point. We found that male gender, ascites, cirrhosis, portal vein thrombosis (PVT), elevated AFP or bilirubin, or alkaline phosphatase, were each statistically significant adverse prognostic factors. Patients with normal AFP survived longer than those with elevated AFP, even in the presence of PVT, large or bilobar tumors or cirrhosis. We used a bivariate analysis to separate patient sub groups based on liver function and tumor characteristics and found clear discrimination in survival between subsets; in addition both cirrhosis and presence of PVT were significant factors. We also used a purely mathematical approach to derive subgroups and a prognostic model for individual patients. Interestingly, the two approaches gave similar predictive information, which opens the possibility of a more detailed mathematical analysis in the future. The results of this large dataset show that amongst non-surgical HCC patients, there are clear subsets with longer survival. The data supports the concept of heterogeneity of HCC. The three factors, bilirubin, AFP, and PVT predominate in prognosis.

  15. Serum alpha-fetoprotein response can predict prognosis in hepatocellular carcinoma patients undergoing radiofrequency ablation therapy

    Energy Technology Data Exchange (ETDEWEB)

    Kao, W.-Y. [Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taiwan (China); Chiou, Y.-Y., E-mail: yychiou@vghtpe.gov.tw [Department of Radiology, Taipei Veterans General Hospital, Taiwan (China); Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Hung, H.-H. [Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taiwan (China); Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Su, C.-W., E-mail: cwsu2@vghtpe.gov.tw [Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taiwan (China); Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Chou, Y.-H. [Department of Radiology, Taipei Veterans General Hospital, Taiwan (China); Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Wu, J.-C. [Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Department of Medical Research and Education, Taipei Veterans General Hospital, Taiwan (China); Huo, T.-I. [Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taiwan (China); Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Huang, Y.-H. [Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taiwan (China); Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan (China); Wu, W.-C. [Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taiwan (China)

    2012-05-15

    Aims: To evaluate the clinical inference of serum alpha-fetoprotein (AFP) response in hepatocellular carcinoma (HCC) patients undergoing percutaneous radiofrequency ablation (RFA). Materials and methods: Three hundred and thirteen previously untreated HCC patients were enrolled in the study. The optimal AFP response was defined as >20% decrease from baseline after 1 month of RFA for those with a baseline AFP level of {>=}100 ng/ml. The impact of AFP response on prognosis was analysed and prognostic factors were assessed. Results: After a median follow-up of 26.7 {+-} 19.1 months, 49 patients died and 264 patients were alive. The cumulative 5 year survival rates were 75.3 and 57.4% in patients with an initial AFP of <100 ng/ml and {>=}100 ng/ml, respectively (p = 0.003). In the 58 patients with a baseline AFP of {>=}100 ng/ml and initial completed tumour necrosis after RFA, the cumulative 5 year survival rates were 62.4 and 25.7% in optimal and non-optimal AFP responders, respectively (p = 0.001). By multivariate analysis, the prothrombin time international normalized ratio >1.1 (p = 0.009), non-optimal AFP response (p = 0.023), and creatinine >1.5 mg/dl (p = 0.021) were independent risk factors predictive of poor overall survival. Besides, the cumulative 5 year recurrence rates were 83.4 and 100% in optimal and non-optimal AFP responders, respectively (p < 0.001). Multivariate analysis demonstrated platelet count {<=}10{sup 5}/mm{sup 3} (p = 0.048), tumour size >2 cm (p = 0.027), and non-optimal AFP response (p < 0.001) were independent risk factors associated with tumour recurrence after RFA. Conclusions: Serum AFP response may be a useful marker for predicting prognosis in HCC patients undergoing RFA.

  16. Zinc finger protein ZBTB20 expression is increased in hepatocellular carcinoma and associated with poor prognosis

    International Nuclear Information System (INIS)

    Wang, Qing; Wang, Hong-yang; Tan, Ye-xiong; Ren, Yi-bin; Dong, Li-wei; Xie, Zhi-fang; Tang, Liang; Cao, Dan; Zhang, Wei-ping; Hu, He-ping

    2011-01-01

    Our previous studies showed that ZBTB20, a new BTB/POZ-domain gene, could negatively regulate α feto-protein and other liver-specific genes, concerning such as bio-transformation, glucose metabolism and the regulation of the somatotropic hormonal axis. The aim of this study is to determine the potential clinical implications of ZBTB20 in hepatocellular carcinoma (HCC). Quantitative real-time RT-PCR and Western blot analyses were used to detect expression levels of ZBTB20 in 50 paired HCC tumorous and nontumorous tissues and in 20 normal liver tissues. Moreover, expression of ZBTB20 was assessed by immunohistochemistry of paired tumor and peritumoral liver tissue from 102 patients who had undergone hepatectomy for histologically proven HCC. And its relationship with clinicopathological parameters and prognosis was investigated. Both messenger RNA and protein expression levels of ZBTB20 were elevated significantly in HCC tissues compared with the paired non-tumor tissues and normal liver tissues. Overexpressed ZBTB20 protein in HCC was significantly associated with vein invasion (P = 0.016). Importantly, the recurrence or metastasis rates of HCCs with higher ZBTB20 expression were markedly greater than those of HCCs with lower expression (P = 0.003, P = 0.00015, respectively). Univariate and multivariate analyses revealed that ZBTB20 overexpression was an independent prognostic factor for HCC. The disease-free survival period and over-all survival period in patients with overexpressed ZBTB20 in HCC was significantly reduced. The expression of ZBTB20 is increased in HCC and associated with poor prognosis in patients with HCC, implicating ZBTB20 as a candidate prognostic marker in HCC

  17. Predictors and prognosis of patients with advanced stage small hepatocellular carcinoma after hepatectomy

    Directory of Open Access Journals (Sweden)

    Wen-ping LV

    2013-01-01

    Full Text Available Objective  To investigate the clinical predictors and prognosis of the patients with advanced stage small hepatocellular carcinoma (SHCC after hepatectomy. Methods  A total of 110 patients with SHCC admitted to the General Hospital of PLA and undergone hepatectomy from Jan. 1995 to Dec. 2009 were included in present retrospective study. Survival analysis was performed by Log-rank test and Kaplan-Meier. The association of SHCC and nine routine clinical parameters was analyzed by the univariate and multivariate logistic regression analysis. Results  Of the 110 patients with SHCC, 31 (28.2% were SHCC in advanced stage, and the 1, 3, 5 year survival rates were 78.6%, 61.6% and 38.5%, respectively, with a median survival time of 48.8 months (95% CI 29.2-68.4 months. Seventy-nine of the 110 patients (71.8% were suffering form early stage SHCC, and the 1, 3, 5 year survival rates were 98.7%, 83.8% and 74.8%, respectively, with a median survival time of 98.0 months (95%CI 73.8-122.2 months. The survival rate was obviously higher in the patients with early stage SHCC than in those with advanced stage SHCC (χ2=13.29, P=0.0003. Multivariate analysis showed that positive AFP was a potential significant predictor of SHCC in advanced stage (RR=14.45; 95%CI 4.05-51.64, P<0.001. Conclusion  The SHCC in advanced stage signifies an ominous prognosis. Positive AFP is a potential significant predictor for advanced stage SHCC.

  18. A new model to estimate prognosis in patients with hepatocellular carcinoma after Yttrium-90 radioembolization.

    Directory of Open Access Journals (Sweden)

    Zhihong Weng

    Full Text Available AIMS: The current prognostic model to estimate the survival in hepatocellular carcinoma (HCC patients treated with transarterial hepatic selective internal radiotherapy (SIRT is not fully characterized. The aim of this study was to establish a new scoring model including assessment of both tumor responses and therapy-induced systemic changes in HCC patients to predict survival at an early time point post-SIRT. METHODS AND MATERIALS: Between 2008 and 2012, 149 HCC patients treated with SIRT were included into this study. CT images and biomarkers in blood tested at one month post-SIRT were analyzed and correlated with clinical outcome. Tumor responses were assessed by RECIST 1.1, mRECIST, and Choi criteria. Kaplan-Meier methods were used to estimate survival curves. Cox regression was used in uni- and multivariable survival analyses and in the establishment of a prognostic model. RESULTS: A multivariate proportional hazards model was created based on the tumor response, the number of tumor nodules, the score of the model for end stage liver disease (MELD, and the serum C-reactive protein levels which were independent predictors of survival in HCC patients at one month post-SIRT. This prognostic model accurately differentiated the outcome of patients with different risk scores in this cohort (P<0.001. The model also had the ability to assign a predicted survival probability for individual patients. CONCLUSIONS: A new model to predict survival of HCC patients mainly based on tumor responses and therapy-induced systemic changes provides reliable prognosis and accurately discriminates the survival at an early time point after SIRT in these patients.

  19. [Elevated expression of CLOCK is associated with poor prognosis in hepatocellular carcinoma].

    Science.gov (United States)

    Li, Bo; Yang, Xiliang; Li, Jiaqi; Yang, Yi; Yan, Zhaoyong; Zhang, Hongxin; Mu, Jiao

    2018-02-01

    Objective To evaluate the expression of circadian locomotor output cycles kaput (CLOCK) and its effects on cell growth in hepatocellular carcinoma (HCC). Methods The expression of CLOCK in 158 pairs of human HCC tissues and matched noncancerous samples was detected by immunohistochemical (IHC) staining. The expression of CLOCK in HCC patients was also verified using the data from GEO and TCGA (a total of 356 cases). The relationship between CLOCK expression and clinicopathological features of HCC patients was analyzed by single factor statistical analysis. Kaplan-Meier survival curves of HCC patients were drawn to study the relationship between the expression level of CLOCK and the survival state. The effect of CLOCK on the growth of HepG2 cells was detected by MTS assay. Results The expression of CLOCK in HCC tissues was significantly higher than that in the adjacent tissues, and the up-regulation of CLOCK expression in HCC tissue was also confirmed in the public data of HCC (356 cases). HCC patients were divided into low CLOCK expression group and high CLOCK expression group. Univariate analysis showed that the expression of CLOCK was related to tumor size, TNM stage, and portal vein invasion in HCC patients. HCC patients with low CLOCK expression had longer overall survival time and relapse-free survival time than those with high CLOCK expression. The proliferation of cells significantly decreased after the expression of CLOCK was knocked down in HepG2 cells. Conclusion The expression of CLOCK in HCC tissues was much higher than that in normal liver tissues, and the high expression of CLOCK indicated the poor prognosis. The knockdown of CLOCK in HCC cells could inhibit the proliferation of HepG2 cells.

  20. Refining prognosis in patients with hepatocellular carcinoma through incorporation of metabolic imaging biomarkers

    Energy Technology Data Exchange (ETDEWEB)

    Takeuchi, Satoshi [Hokkaido University Graduate School of Medicine, Department of Medical Oncology, Sapporo (Japan); The University of Texas MD Anderson Cancer Center, Department of Nuclear Medicine, Houston, TX (United States); Rohren, Eric M. [The University of Texas MD Anderson Cancer Center, Department of Nuclear Medicine, Houston, TX (United States); Baylor College of Medicine, Department of Radiology, Houston, TX (United States); Abdel-Wahab, Reham [The University of Texas MD Anderson Cancer Center, Department of Gastrointestinal Medical Oncology, Houston, TX (United States); Assiut University Hospital, Clinical Oncology Department, Assiut (Egypt); Xiao, Lianchun; Morris, Jeffrey S. [The University of Texas MD Anderson Cancer Center, Department of Biostatistics, Houston, TX (United States); Macapinlac, Homer A. [The University of Texas MD Anderson Cancer Center, Department of Nuclear Medicine, Houston, TX (United States); Hassan, Manal M. [Baylor College of Medicine, Department of Radiology, Houston, TX (United States); Kaseb, Ahmed O. [The University of Texas MD Anderson Cancer Center, Department of Gastrointestinal Medical Oncology, Houston, TX (United States)

    2017-06-15

    {sup 18}F-fluorodeoxyglucose positron emission tomopraphy/computed tomography (FDGPET/CT) has been proven to be useful for imaging many types of cancer; however, its role is not well defined in hepatocellular carcinoma (HCC). We assessed the prognostic value of metabolic imaging biomarkers as established by baseline pretreatment FDG PET/CT in patients with HCC. We retrospectively analyzed the records of patients with HCC who underwent FDG PET/CT before initial treatment from May 2013 through May 2014. Four PET/CT parameters were measured: maximum standardized uptake value (SUV{sub max}), total lesion glycolysis (TLG), metabolic tumor volume (MTV), and tumor-to-normal-liver SUV ratio (TNR). Optimal cut-off values for the PET/CT parameters to stratify patients in terms of overall survival (OS) were determined. Multivariate analysis was performed to determine whether the PET/CT parameters could add to the prognostic value of the Cancer of the Liver Italian Program (CLIP) scoring system and the Barcelona-Clinic Liver Cancer (BCLC) staging system. The analysis included 56 patients. Univariate analysis of the association between OS and continuous variables, including the PET/CT parameters SUV{sub max}, TLG, tumor size, total bilirubin level, and alkaline phosphatase level were significant predictors of OS. SUV{sub max} ≥ 11.7, TLG ≥ 1,341, MTV ≥ 230 mL, and TNR ≥ 4.8 were identified as cut-off values. Multivariate analysis revealed that SUV{sub max} ≥ 11.7 and TNR ≥ 4.8 were independent factors predicting a poor prognosis in both the CLIP scoring system and the BCLC staging system, as was TLG in the BCLC staging system. Pretreatment FDG PET/CT in patients with HCC can add to the prognostic value of standard clinical measures. Incorporation of imaging biomarkers derived from FDG PET/CT into HCC staging systems should be considered. (orig.)

  1. Overexpression of Zwint predicts poor prognosis and promotes the proliferation of hepatocellular carcinoma by regulating cell-cycle-related proteins

    Directory of Open Access Journals (Sweden)

    Ying H

    2018-02-01

    Full Text Available Hanning Ying,1,2 Zhiyao Xu,3 Mingming Chen,1,2 Senjun Zhou,1,2 Xiao Liang,1,2 Xiujun Cai1,2 1Department of General Surgery, 2Key Laboratory of Endoscopic Technique Research of Zhejiang Province, 3Central Lab of Biomedical Research Center, School of Medicine, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, China Introduction: Zwint, a centromere-complex component required for the mitotic spindle checkpoint, has been reported to be overexpressed in different human cancers, but it has not been studied in human hepatocellular carcinoma (HCC.Materials and methods: The role of Zwint in hepatocellular carcinoma cell proliferation capacities was evaluated by using cell counting kit-8 (CCK8, flow cytometry, clone formation and tumor formation assay in nude mice. Western blot analysis and qPCR assay were performed to assess Zwint interacting with cell-cycle-related proteins.Results: We report that ZWINT mRNA and protein expression were upregulated in HCC samples and cell lines. An independent set of 106 HCC-tissue pairs and corresponding noncancerous tissues was evaluated for Zwint expression using immunohistochemistry, and elevated Zwint expression in HCC tissues was significantly correlated with clinicopathological features, such as tumor size and number. Kaplan–Meier survival and Cox regression analysis revealed that high expression of Zwint was correlated with poor overall survival and a greater tendency for tumor recurrence. Ectopic expression of Zwint promoted HCC-cell proliferation, and Zwint expression affected the expression of several cell-cycle proteins, including PCNA, cyclin B1, Cdc25C and CDK1.Conclusion: Our findings suggest that upregulation of Zwint may contribute to the progression of HCC and may be a prognostic biomarker and potential therapeutic target for treating HCC. Keywords: Zwint, hepatocellular carcinoma, HCC, prognosis, cell proliferation, cell cycle

  2. The single-nucleotide polymorphisms in CHD5 affect the prognosis of patients with hepatocellular carcinoma

    Science.gov (United States)

    Zhu, Xiao; Kong, Qingming; Xie, Liwei; Chen, Zhihong; Li, Hongmei; Zhu, Zhu; Huang, Yongmei; Lan, Feifei; Luo, Haiqing; Zhan, Jingting; Ding, Hongrong; Lei, Jinli; Xiao, Qin; Fu, Weiming; Fan, Wenguo; Zhang, Jinfang; Luo, Hui

    2018-01-01

    Previous studies showed that the low expressions of chromodomain-helicase-DNA-binding protein 5 (CHD5) were intensively associated with deteriorative biologic and clinical characteristics as well as outcomes in many tumors. The aim of this study is to determine whether CHD5 single nucleotide polymorphisms (SNPs) contribute to the prognosis of hepatocellular carcima (HCC). The SNPs were selected according to their linkage disequilibrium (LD) in the targeted next-generation sequencing (NGS) and then genotyped with TaqMan probers. We revealed a rare haplotype AG in CHD5 (SNPs: rs12564469-rs9434711) was markedly associated with HCC prognosis. The univariate and multivariate regression analyses revealed the patients with worse overall survival time were those with tumor metastasis and haplotype AG, as well as cirrhosis, poor differentiation and IV-TNM stage. Based on the available public databases, we discovered the significant association between haplotype AG and CHD5 mRNA expressions only existed in Chinese. These data proposed that the potentially genetic haplotype might functionally contribute to HCC prognosis and CHD5 mRNA expressions. PMID:29568352

  3. Overexpression of Rabl3 and Cullin7 is associated with pathogenesis and poor prognosis in hepatocellular carcinoma.

    Science.gov (United States)

    An, Jun; Liu, Zhiyong; Liang, Qiong; Pan, Yuhang; Li, Haifeng; Wang, Ruizhi; Jin, Yi

    2017-09-01

    The expression of Rabl3 and Cullin7 is relevant to the carcinogenesis of certain cancers. However, the relationship of this expression with hepatocellular carcinoma remains unclear. To study the protein expression of Rabl3 and Cullin7 and to evaluate their role in hepatocarcinogenesis, in 162 cases of hepatocellular carcinoma, we used immunohistochemistry to investigate the expression of Rabl3 and Cullin7 in both the cancer tissues and the normal hepatic tissues around the hepatocellular carcinoma. The results demonstrated that the rates of positive Rabl3 and Cullin7 expression were 80.2% and 69.1%, respectively, in hepatocellular carcinoma tissues. However, the rates of positive Rabl3 and Cullin7 expression were 31.5% and 29.0%, respectively, in adjacent normal hepatic tissues. Rabl3 and Cullin7 were expressed at significantly higher rates in hepatocellular carcinoma compared with adjacent normal hepatic tissues (Phepatocellular carcinoma tissues of patients with lymph node metastasis, tumor thrombi in the portal vein and an advanced clinical stage (Phepatocellular carcinoma cohort. Moreover, patients with positive expression for both Rabl3 and Cullin7 had a remarkably shorter survival time compared with patients with negative expression for both proteins (Phepatocellular carcinoma and could be used as a prognostic indicator in patients with hepatocellular carcinoma. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Glutathione treatment of hepatocellular carcinoma

    DEFF Research Database (Denmark)

    Dalhoff, K; Ranek, L; Mantoni, M

    1992-01-01

    This prospective study was undertaken to substantiate observations that glutathione (GSH) inhibits or reverses tumor growth in humans with hepatocellular carcinoma (HCC), a neoplasm with an extremely poor prognosis. Eight patients with biopsy-proven HCC not amenable to surgery were given 5 g of GSH...

  5. Tumor and liver determinants of prognosis in unresectable hepatocellular carcinoma: a case cohort study.

    Science.gov (United States)

    Carr, Brian I; Buch, Shama C; Kondragunta, Venkateswarlu; Pancoska, Petr; Branch, Robert A

    2008-08-01

    A total of 967 patients with unresectable and untransplantable, biopsy-proven hepatocellular carcinoma (HCC) were prospectively evaluated at baseline and followed up till death. Survival was the end-point for all analyses. We found in our overall analysis, that male gender, ascites, cirrhosis, portal vein thrombosis (PVT), elevated alpha-fetoprotein (AFP) or bilirubin or alkaline phosphatases were each statistically significant adverse prognostic factors. Patients with normal AFP survived longer than those with elevated AFP, in the presence of PVT, large or bilobar tumors or cirrhosis. We used a bivariate analysis to separate patient subgroups based on poor liver function and aggressive tumor characteristics. In subgroup analysis based on these subsets, there was clear discrimination in survival between subsets; in addition both cirrhosis and presence of PVT were significant, independent but modest risk factors. The results of this large dataset show that amongst nonsurgical HCC patients, there are clear subsets with longer survival than other subsets. This data also supports the concept of heterogeneity of HCC.

  6. Radiation therapy is a reasonable option for improving the prognosis in hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Kondo, Yasuteru; Kimura, Osamu; Kogure, Takayuki

    2015-01-01

    Radiation therapy (RT) may be suitable for treating patients with hepatocellular carcinoma (HCC) who are difficult to treat with any other option. However, it remains unclear whether RT extends survival in these patients. Among the 957 HCC patients treated at Tohoku University Hospital from January 2007 to December 2013, only 49 patients received RT. We therefore retrospectively analyzed the outcomes of these patients; they were divided into three groups based on the reasons for choosing RT: 27 patients at Stage IV A (67.1 ± 1.6 years, 50.5 ± 2.1 Gy), 9 patients with alternative therapy (42.2 ± 2.4 years, 58.9 ± 1.1 Gy), and 13 patients who received RT after transarterial chemoembolization (TACE) (75.6 ± 2.1 years, 56.5 ± 1.5 Gy). RT was employed to ensure the local control of the lesion. The patients at Stage IV A were treated with radical RT (n=16) or with palliative RT (n=11). In radical RT group, the response rate was 37.5% and the complete response rate was 25%. The survival rate was 12.5 ± 2.6 months after radical RT. This is considered relatively good for Stage IV A. The disease-free survival rate was 13.0 ± 2.8 months after RT. This excellent disease-free survival indicates that RT is an alternative to other treatments. In the TACE group, patients who received the RT had the significantly long disease-free survival rate than only-TACE (18.0 ± 3.8 months vs. 11.2 ± 0.58 months). We propose that RT is effective and safe for HCC. (author)

  7. Preoperative Controlling Nutritional Status (CONUT) Score for Assessment of Prognosis Following Hepatectomy for Hepatocellular Carcinoma.

    Science.gov (United States)

    Takagi, Kosei; Yagi, Takahito; Umeda, Yuzo; Shinoura, Susumu; Yoshida, Ryuichi; Nobuoka, Daisuke; Kuise, Takashi; Araki, Hiroyuki; Fujiwara, Toshiyoshi

    2017-09-01

    Immune-nutritional status has been recently reported as a prognostic factor in hepatocellular carcinoma (HCC). The controlling nutritional status (CONUT) score has been established as a useful tool to evaluate immune-nutritional status. This study aimed to investigate the efficacy of the CONUT score as a prognostic factor in patients undergoing hepatectomy for HCC. A total of 295 patients who underwent curative hepatectomy for HCC between January 2007 and December 2014 were retrospectively analyzed. Patients were divided into two groups according to the CONUT score. The impact of the CONUT score on clinicopathological, surgical, and long-term outcomes was evaluated. Subsequently, the impact of prognostic factors, including the CONUT score, associated with outcomes was assessed using multivariate analyses. Of 295 patients, 118 (40%) belonged to the high CONUT group (CONUT score ≥ 3). The high CONUT group had a significantly lower 5-year recurrence-free survival rate than the low CONUT group (27.9 vs. 41.4%, p = 0.011) and a significantly lower 5-year overall survival rate (61.9 vs. 74.9%, p = 0.006). In multivariate analyses of prognostic factors, the CONUT score was an independent predictor of recurrence-free survival (hazard ratio = 1.64, p = 0.006) and overall survival (hazard ratio = 2.50, p = 0.001). The CONUT score is a valuable preoperative predictor of survival in patients undergoing hepatectomy for HCC.

  8. Predicting prognosis in hepatocellular carcinoma; comparison of staging system in pakistani cohort

    International Nuclear Information System (INIS)

    Sarwar, S.; Khan, A.A.

    2015-01-01

    To determine the clinical, biochemical and radiological prognostic indicators and to compare the performance of six staging systems in patients of hepatocellular carcinoma (HCC). Study Design:Descriptive study. Place and Duration of Study: Department of Gastroenterology, Doctors Hospital, Lahore, from October 2007 to December 2013. Methodology:Patients with HCC were included. Baseline clinical, hematological and radiological variables were noted. Patients were followed for 5 years or till death. Survival predictors were identified using Cox proportional hazard analysis and 6 prognostic staging systems were evaluated by determining homogeneity, discriminatory ability and monotonicity. Results: Of the 228 patients included, male to female ratio was 2.6/1 (165/63) and mean age was 56.5 ± 10.4 years. Majority of patients 189 (82.9%) were anti-HCV positive. Solitary HCC lesion was seen in 121 (53.1%) patients, 16 (7%) had 2 lesions while 73 (32%) had 3 or more lesions. Only 36 (15.8%) patients had palliative therapy for HCC. Survival rate was 45.2%, 25%, 12.3%, 7%, 2.2% and 1% for 6 months, 1, 2, 3, 4 and 5 years respectively. Male gender, portal vein thrombosis, serum albumin < 3.5 g/dl, tumor size =6 cm and alpha fetoprotein (AFP) =147 U/ml were bad prognostic indicators. OKUDA, GRETCH and early stages of CLIP had better homogeneity while CLIP showed superior discriminatory ability and monotonicity for predicting survival. Conclusion: Male gender, presence of portal vein thrombosis, low serum albumin, large tumor size and high AFP level are poor prognostic indicators in patients of HCC. CLIP has better performance in predicting mortality. (author)

  9. Transarterial Chemoembolization for Hepatocellular Carcinomas with Central Bile Duct Invasion: Safety, Prognosis, and Predictive Factors

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Jin Woo; Chung, Jin Wook, E-mail: chungjw@snu.ac.kr [Seoul National University Hospital, Department of Radiology (Korea, Republic of); Cho, Yun Ku [VHS Medical Center, Department of Radiology (Korea, Republic of); Kim, Yoon Jun; Yoon, Jung-Hwan [Seoul National University Hospital, Department of Internal Medicine (Korea, Republic of); Kim, Hyo-Cheol; Jae, Hwan Jun [Seoul National University Hospital, Department of Radiology (Korea, Republic of)

    2015-08-15

    PurposeTo assess the safety and effectiveness of transarterial chemoembolization (TACE) of patients who have hepatocellular carcinomas (HCCs) with central bile duct invasion.Materials and MethodsThe institutional review board approved this retrospective study and waived informed consent. Fifty-three patients, initially treated with TACE for HCCs with central bile duct invasion from January 1999 to September 2012, were included. Clinical, laboratory, and survival data were reviewed. Complications and hospitalization length were evaluated using the χ{sup 2} test, Fisher’s exact test, and logistic regression analysis. Survival was analyzed using the Kaplan–Meier method with log-rank test and Cox proportional hazard model.ResultsSeven patients experienced TACE-related major complications (severe post-embolization syndrome in 3, non-fatal sepsis in 3, and secondary bacterial peritonitis in 1). The overall major complication rate was 13.2 %, but there were no permanent adverse sequelae or deaths within 30 days. Serum total bilirubin ≥3.0 mg/dL was the only significant risk factor for long hospitalization [hazard ratio (HR) = 4.341, p = .022]. The median survival was 12.2 months. Extrahepatic metastasis (HR = 6.145, p < .001), international normalized ratio (PT-INR) ≥1.20 (HR = 4.564, p < .001), vascular invasion (HR = 3.484, p = .001), and intermediate tumor enhancement (HR = 2.417, p = .019) were significantly associated with shorter survival.ConclusionTACE can be a safe and effective treatment for patients who have HCCs with central bile duct invasion. In particular, long-term survival can be expected if patients have strongly enhancing tumors without poor prognostic factors such as extrahepatic metastasis, PT-INR prolongation, and vascular invasion.

  10. No impact of perioperative blood transfusion on prognosis after curative resection for hepatocellular carcinoma: a propensity score matching analysis.

    Science.gov (United States)

    Peng, T; Zhao, G; Wang, L; Wu, J; Cui, H; Liang, Y; Zhou, R; Liu, Z; Wang, Q

    2017-10-27

    The relationship between perioperative blood transfusion and long-term survival after curative resection for hepatocellular carcinoma (HCC) remains controversial. The aim of the present study was to investigate the impact of blood transfusion on the long-term prognosis of HCC patients. Patients with primary HCC who underwent a curative hepatectomy from 2003 to 2011 were enrolled and then retrospectively studied. The clinicopathologic characteristics between patients in the blood transfusion and non-transfusion groups were matched using a propensity score matching (PSM) analysis. Univariate and multivariate Cox regression analyses were used to identify whether perioperative blood transfusion affects long-term survival after resection for HCC. A total of 374 patients were enrolled and 113 patients received perioperative transfusions. The 1-, 3- and 5-year disease-free and overall survival rates of the entire cohort were 65.0, 37.3 and 23.9%, and 90.9, 70.7 and 57.5%, respectively. The disease-free and overall survival rates of the blood transfusion group were significantly worse than the disease-free and overall survival rates of the non-transfusion group in the entire cohort (p blood transfusion was not an independent predictor of disease-free and overall survival in the propensity-matched cohort (p = 0.154, p = 0.667). The present study demonstrates that perioperative blood transfusion has no impact on disease-free and overall survival after curative resection for HCC.

  11. Radiosensitivity of hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Hennequin, C.; Quero, L.; Rivera, S.

    2011-01-01

    The frequency of hepatocellular carcinoma (HCC) is increasing in the western world and the role of radiotherapy is more and more discussed. Classically, hepatocellular carcinoma was considered as a radioresistant tumour: in fact, modern radio-biologic studies, performed on cell lines directly established from patients, showed that hepatocellular carcinoma has the same radiosensitivity than the other epithelial tumours. From clinical studies, its α/β ratio has been estimated to be around 15 Gy. Radiosensitivity of normal hepatic parenchyma is now well evaluated and some accurate NTCP models are available to guide hepatic irradiation. The biology of hepatocellular carcinoma is also better described: the combination of radiotherapy and targeted therapies will be a promising approach in the near future. (authors)

  12. Cryotherapy for hepatocellular carcinoma

    DEFF Research Database (Denmark)

    Awad, Tahany; Thorlund, Kristian; Gluud, Christian

    2009-01-01

    BACKGROUND: Hepatocellular carcinoma is the most common primary malignant cancer of the liver. Evidence for the role of cryotherapy in the treatment of hepatocellular carcinoma is controversial. OBJECTIVES: The aim of this review is to evaluate the potential benefits and harms of cryotherapy...... for the treatment of hepatocellular carcinoma. SEARCH STRATEGY: We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and LILACS until June 2009. We identified further studies by searching...... of benefit but included for the assessment of harm. Both severe and non-severe adverse events were reported, but the true nature and extent of harm was difficult to asses. AUTHORS' CONCLUSIONS: At present, there is no evidence to recommend or refute cryotherapy for patients with hepatocellular carcinoma...

  13. Prognosis of patients with hepatocellular carcinoma treated with sorafenib: a comparison of five models in a large Canadian database.

    Science.gov (United States)

    Samawi, Haider H; Sim, Hao-Wen; Chan, Kelvin K; Alghamdi, Mohammad A; Lee-Ying, Richard M; Knox, Jennifer J; Gill, Parneet; Romagnino, Adriana; Batuyong, Eugene; Ko, Yoo-Joung; Davies, Janine M; Lim, Howard J; Cheung, Winson Y; Tam, Vincent C

    2018-05-15

    Several systems (tumor-node-metastasis [TNM], Barcelona Clinic Liver Cancer [BCLC], Okuda, Cancer of the Liver Italian Program [CLIP], and albumin-bilirubin grade [ALBI]) were developed to estimate the prognosis of patients with hepatocellular carcinoma (HCC) mostly prior to the prevalent use of sorafenib. We aimed to compare the prognostic and discriminatory power of these models in predicting survival for HCC patients treated with sorafenib and to identify independent prognostic factors for survival in this population. Patients who received sorafenib for the treatment of HCC between 1 January 2008 and 30 June 2015 in the provinces of British Columbia and Alberta, and two large cancer centers in Toronto, Ontario, were included. Survival was assessed using the Kaplan-Meier method. Multivariate Cox regression was used to identify predictors of survival. The models were compared with respect to homogeneity, discriminatory ability, monotonicity of gradients, time-dependent area under the curve, and Akaike information criterion. A total of 681 patients were included. 80% were males, 86% had Child-Pugh class A, and 37% of patients were East Asians. The most common etiology for liver disease was hepatitis B (34%) and C (31%). In all model comparisons, CLIP performed better while BCLC and TNM7 performed less favorably but the differences were small. The utility of each system in allocating patients into different prognostic groups varied, for example, TNM poorly differentiated patients in advanced stages (8.7 months (m) (95% CI 6.5-11.5) versus 8.4 m (95% CI 7.0-9.6) for stages III and IV, respectively) while ALBI had excellent discrimination of early grades (15.6 m [95% CI 13.0-18.4] versus 8.3 m [95% CI 7.0-9.2] for grades 1 and 2, respectively). On multivariate analysis, hepatitis C, alcoholism, and prior hepatic resection were independently prognostic of better survival (P < 0.01). In conclusion, none of the prognostic systems was optimal in predicting survival

  14. Increased expression of hepatocyte nuclear factor 4 alpha transcribed by promoter 2 indicates a poor prognosis in hepatocellular carcinoma

    OpenAIRE

    Cai, Shao-hang; Lu, Shi-xun; Liu, Li-li; Zhang, Chris Zhiyi; Yun, Jing-ping

    2017-01-01

    Background: Hepatocyte nuclear factor 4 alpha (HNF4α) plays an important role in tumourigenesis. There is growing evidence indicating that HNF4α transcribed by promoter 1 (P1-HNF4α) is expressed at relatively low levels in HCC and its presence predicts a favourable outcome for hepatocellular carcinoma (HCC) patients. However, the role of HNF4α transcribed by promoter 2 (P2-HNF4α) in HCC remains unclear. Methods: A total of 615 HCC specimens were obtained to construct tissue microarrays and pe...

  15. Chromophobe hepatocellular carcinoma with abrupt anaplasia: a proposal for a new subtype of hepatocellular carcinoma with unique morphological and molecular features

    OpenAIRE

    Wood, Laura D; Heaphy, Christopher M; Daniel, Hubert Darius-J; Naini, Bita V; Lassman, Charles R; Arroyo, May R; Kamel, Ihab R; Cosgrove, David P; Boitnott, John K; Meeker, Alan K; Torbenson, Michael S

    2013-01-01

    Hepatocellular carcinomas exhibit heterogeneous morphologies by routine light microscopy. Although some morphologies represent insignificant variations in growth patterns, others may represent unrecognized subtypes of hepatocellular carcinoma. Identification of these subtypes could lead to separation of hepatocellular carcinomas into discrete groups with unique underlying genetic changes, prognosis, or therapeutic responses. In order to identify potential subtypes, two pathologists independen...

  16. The role of pre-existing diabetes mellitus on hepatocellular carcinoma occurrence and prognosis: a meta-analysis of prospective cohort studies.

    Directory of Open Access Journals (Sweden)

    Wan-Shui Yang

    Full Text Available The impact of pre-existing diabetes mellitus (DM on hepatocellular carcinoma (HCC occurrence and prognosis is complex and unclear. The aim of this meta-analysis is to evaluate the association between pre-existing diabetes mellitus and hepatocellular carcinoma occurrence and prognosis.We searched PubMed, Embase and the Cochrane Library from their inception to January, 2011 for prospective epidemiological studies assessing the effect of pre-existing diabetes mellitus on hepatocellular carcinoma occurrence, mortality outcomes, cancer recurrence, and treatment-related complications. Study-specific risk estimates were combined by using fixed effect or random effect models.The database search generated a total of 28 prospective studies that met the inclusion criteria. Among these studies, 14 reported the risk of HCC incidence and 6 studies reported risk of HCC specific mortality. Six studies provided a total of 8 results for all-cause mortality in HCC patients. Four studies documented HCC recurrence risks and 2 studies reported risks for hepatic decomposition occurrence in HCC patients. Meta-analysis indicated that pre-existing diabetes mellitus (DM was significantly associated with increased risk of HCC incidence [meta-relative risk (RR = 1.87, 95% confidence interval (CI: 1.15-2.27] and HCC-specific mortality (meta-RR = 1.88, 95%CI: 1.39-2.55 compared with their non-DM counterparts. HCC patients with pre-existing DM had a 38% increased (95% CI: 1.13-1.48 risk of death from all-causes and 91% increased (95%CI: 1.41-2.57 risk of hepatic decomposition occurrence compared to those without DM. In DM patients, the meta-RR for HCC recurrence-free survival was 1.93(95%CI: 1.12-3.33 compared with non-diabetic patients.The findings from the current meta-analysis suggest that DM may be both associated with elevated risks of both HCC incidence and mortality. Furthermore, HCC patients with pre-existing diabetes have a poorer prognosis relative to their

  17. Diagnostic Approaches to Metastatic Hepatocellular Carcinoma of the Orbit.

    Science.gov (United States)

    Geske, Michael J; Bloomer, Michele M; Kersten, Robert C; Vagefi, M Reza

    Orbital metastasis of hepatocellular carcinoma is exceedingly rare and caries a grave prognosis. Three cases of metastatic orbital hepatocellular carcinoma in which the primary tumor was initially unknown and the diagnostic challenges encountered are presented. With hepatocellular carcinoma, open biopsy and palliative tumor debulking has an increased bleeding risk due to the highly vascular nature of the tumor and coagulopathy associated with chronic liver disease. As an alternative, fine needle aspiration biopsy should be considered for hepatocellular carcinoma with a readily accessible mass and the availability of an experienced cytopathologist.

  18. Dynamic CT of hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Fujita, Nobuyuki; Shirato, Hiroki; Shinohara, Masahiro; Miyasaka, Kazuo; Morita, Yutaka; Irie, Goro

    1983-03-01

    We performed dynamic CT in 30 cases of hepatocellular carcinoma, and concluded as below. Detecting the stain in the early phase of the dynamic series, it is possible to make a diagnosis of hepatocellular carcinoma. The dynamic CT is effective in a case of small hepatocellular carcinoma in which it is difficult to gain an accurate diagnosis in the routine CT study. The dynamic CT is also effective in the differential diagnosis of hepatic lesions, as other hepatic lesions such as hemangioma and metastatic liver cancer show different patterns compared with hepatocellular carcinoma.

  19. Dynamic CT of hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Fujita, Nobuyuki; Shirato, Hiroki; Shinohara, Masahiro; Miyasaka, Kazuo; Morita, Yutaka; Irie, Goro

    1983-01-01

    We performed dynamic CT in 30 cases of hepatocellular carcinoma, and concluded as below. 1 Decting the stain in the early phase of the dynamic series, it is possible to make a diagnosis of hepatocellular carcinoma. 2 The dinamic CT is effective in a case of small hepatocellular carcinoma in which it is difficult to gain an accurate diagnosis in the routine CT study. 3 The dynamic CT is also effective in the differential diagnosis of hepatic lesions, as other hepatic lesions such as hemangioma and metastatic liver cancer show different patterns compared with hepatocellular carcinoma. (author)

  20. Down-regulated expression of the protein-tyrosine phosphatase 1B (PTP1B) is associated with aggressive clinicopathologic features and poor prognosis in hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Zheng, Long-Yi; Zhou, Dong-Xun; Lu, Jin; Zhang, Wen-Jun; Zou, Da-Jin

    2012-01-01

    Highlights: ► PTP1B protein showed decreased expression in 67.79% of the HCC patients. ► Low PTP1B expression predicts poor prognosis of HCC. ► Low PTP1B expression is correlated with expansion of OV6 + tumor-initiating cells. ► Down-regulation of PTP1B is associated with activation of Wnt/β-Catenin signaling. -- Abstract: The protein-tyrosine phosphatase 1B (PTP1B) is a classical non-transmembrane protein tyrosine phosphatase that plays a key role in metabolic signaling and can exert both tumor suppressing and tumor promoting effects in different cancers depending on the substrate involved and the cellular context. However, the expression level and function of PTP1B in hepatocellular carcinoma (HCC) remain unclear. In this study, PTP1B expression was detected by immunohistochemistry in normal liver tissue (n = 16) and hepatocellular carcinoma (n = 169). The correlations between PTP1B expression level and clinicopathologic features and patient survival were also analyzed. One hundred and eleven of 169 HCC patients (65.7%) had negative or low PTP1B expression in tumorous tissues, whereas normal tissues always expressed strong PTP1B. Decreased PTP1B expression was significantly associated with aggressive clinicopathologic features and poor prognosis. Immunohistochemistry also showed that low PTP1B expression level was correlated with high percentage of OV6 + tumor-initiating cells (T-ICs) and high frequency of nuclear β-Catenin expression in HCC specimens. Our findings demonstrate for the first time that the loss of inhibitory effect of PTP1B may contribute to progression and invasion of HCC through activation of Wnt/β-Catenin signaling and expansion of liver T-ICs. PTP1B may serve as a valuable prognostic biomarker and potential therapeutic target in HCC.

  1. Down-regulated expression of the protein-tyrosine phosphatase 1B (PTP1B) is associated with aggressive clinicopathologic features and poor prognosis in hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Long-Yi [Department of Endocrinology, Changhai Hospital, 168 Changhai Road, Shanghai 200433 (China); Zhou, Dong-Xun [Department of Comprehensive Treatment II, Eastern Hepatobiliary Surgery Hospital, 225 Changhai Road, Shanghai 200438 (China); Lu, Jin [Department of Endocrinology, Changhai Hospital, 168 Changhai Road, Shanghai 200433 (China); Zhang, Wen-Jun [Department of Emergency, Changhai Hospital, 168 Changhai Road, Shanghai 200433 (China); Zou, Da-Jin, E-mail: dajinzou@hotmail.com [Department of Endocrinology, Changhai Hospital, 168 Changhai Road, Shanghai 200433 (China)

    2012-04-13

    Highlights: Black-Right-Pointing-Pointer PTP1B protein showed decreased expression in 67.79% of the HCC patients. Black-Right-Pointing-Pointer Low PTP1B expression predicts poor prognosis of HCC. Black-Right-Pointing-Pointer Low PTP1B expression is correlated with expansion of OV6{sup +} tumor-initiating cells. Black-Right-Pointing-Pointer Down-regulation of PTP1B is associated with activation of Wnt/{beta}-Catenin signaling. -- Abstract: The protein-tyrosine phosphatase 1B (PTP1B) is a classical non-transmembrane protein tyrosine phosphatase that plays a key role in metabolic signaling and can exert both tumor suppressing and tumor promoting effects in different cancers depending on the substrate involved and the cellular context. However, the expression level and function of PTP1B in hepatocellular carcinoma (HCC) remain unclear. In this study, PTP1B expression was detected by immunohistochemistry in normal liver tissue (n = 16) and hepatocellular carcinoma (n = 169). The correlations between PTP1B expression level and clinicopathologic features and patient survival were also analyzed. One hundred and eleven of 169 HCC patients (65.7%) had negative or low PTP1B expression in tumorous tissues, whereas normal tissues always expressed strong PTP1B. Decreased PTP1B expression was significantly associated with aggressive clinicopathologic features and poor prognosis. Immunohistochemistry also showed that low PTP1B expression level was correlated with high percentage of OV6{sup +} tumor-initiating cells (T-ICs) and high frequency of nuclear {beta}-Catenin expression in HCC specimens. Our findings demonstrate for the first time that the loss of inhibitory effect of PTP1B may contribute to progression and invasion of HCC through activation of Wnt/{beta}-Catenin signaling and expansion of liver T-ICs. PTP1B may serve as a valuable prognostic biomarker and potential therapeutic target in HCC.

  2. Common Molecular Subtypes Among Asian Hepatocellular Carcinoma and Cholangiocarcinoma

    DEFF Research Database (Denmark)

    Chaisaingmongkol, Jittiporn; Budhu, Anuradha; Dang, Hien

    2017-01-01

    Intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC) are clinically disparate primary liver cancers with etiological and biological heterogeneity. We identified common molecular subtypes linked to similar prognosis among 199 Thai ICC and HCC patients through systems integratio...

  3. Elevated Preoperative Neutrophil-Lymphocyte Ratio Is Associated with Poor Prognosis in Hepatocellular Carcinoma Patients Treated with Liver Transplantation: A Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Xiao-Dong Sun

    2016-01-01

    Full Text Available This study aims to investigate the prognostic value of neutrophil to lymphocyte ratio (NLR in hepatocellular carcinoma (HCC patients treated with liver transplantation (LT through meta-analysis. Relevant articles were sought in PubMed, Embase, and Wangfang databases up to July 2015. A total of 1687 patients from 10 studies were included in this meta-analysis. Meta-analysis results showed that elevated NLR was significantly associated with poorer overall survival (OS (HR = 2.71, 95% CI: 1.91–3.83 and poorer disease-free survival (DFS (HR = 3.61, 95% CI: 2.23–5.84 in HCC patients treated with LT. Moreover, subgroup analysis showed the significant association between elevated preoperative NLR and poor prognosis was not altered by cutoff values of NLR or types of LT. Therefore, elevated preoperative NLR is associated with poor prognosis in HCC patients treated with LT. Preoperative NLR should be used to predict the prognosis of HCC after LT in our clinical work.

  4. Viral hepatitis and hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Juei-Low, Sung [ed.; National Taiwan University College of Medicine, Taipei (Republic of China Taiwan). Department of Internal Medicine; Ding-Shinn, Chen [ed.; National Taiwan University College of Medicine, Taipei (Republic of China Taiwan). Hepatitis Research Center National Taiwan University College of Medicine, Taipei (Republic of China Taiwan). Graduate Institute of Clinical Medicine

    1990-01-01

    Two papers in this volume are in INIS scope, respectively dealing with MRI in the study of viral hepatitis and hepatocellular carcinoma, and The use of {sup 131}I-labeled Lipidol in the diagnosis of hepato-cellular carcinoma. (H.W.). refs.; figs.; tabs.

  5. Viral hepatitis and hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Sung Juei-Low; Chen Ding-Shinn

    1990-01-01

    Two papers in this volume are in INIS scope, respectively dealing with MRI in the study of viral hepatitis and hepatocellular carcinoma, and The use of 131 I-labeled Lipidol in the diagnosis of hepato-cellular carcinoma. (H.W.). refs.; figs.; tabs

  6. CT of hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Nakamura, H; Tanaka, T; Sai, H; Kawamoto, S; Morimoto, K [Osaka Univ. (Japan). Faculty of Medicine

    1982-06-01

    CT was investigated in 125 cases of hepatocelluar carcinoma and 47 cases of metastatic hepatic neoplasm. The entire contour of each tumor was traced and the average CT value in the tumor was estimated. As a result, the CT value for hepatocellular carcinoma tended to be higher on plain CT and also after contrast enhancement. The CT findings seen frequently were as follows: capsule in 76 cases (60.8%) and septum in 67 cases (53.6%); tumor thrombus in portal vein in 39 cases (31.2%) and that in inferior vena cava in 3 cases (2.4%); localized enlargement of hepatic bile duct in 24 cases (19.2%). These findings were rarely seen in the cases of metastatic hepatic neoplasm. As a relatively outstanding feature of hepatic metastases, a double contour, like concentric circles or contour lines, with a relatively large inner circle or contour line, was found in 21 cases (44.7%). By paying attention to the change of CT value on contrast enhancement and the characteristic image of each case, hepatocellular carcinoma could be differentiated from metastatic hepatic neoplasm with high probability.

  7. Ultrasound manifestation of hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Hwang, M S; Yoo, H S; Park, C Y; Choi, H J; Moon, Y M; Lee, S I [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    1982-06-15

    With the advent of gray scale ultrasonographic equipment, the parenchymal disease of liver is more easily evaluated. Ultrasonography is a non-invasive technique, different from angiography, and performed without discomfort to patient. And also ultrasonography can be used in assessing the liver in cases showing equivocal scintigraphy and in differentiation of solid and cystic masses, first detected on scintigrams. Therefore, the complementary use of ultrasonography, Tc-99m-sulfur colloid scan and angiography provides better diagnostic accuracy for the detection of hepatocellular carcinoma, and moreover, sequential ultrasonographic studies in the same patient are valuable of following the course of hepatocellular carcinoma and monitoring the effectiveness of therapy for hepatocellular carcinoma. In thirty patients with histologically proven hepatocellular carcinoma, an analysis of ultrasound manifestation is made and the results are as follows; 1. Ultrasound manifestation of hepatocellular carcinoma by gray scale showed four different sonographic patterns including discrete echo free, discrete echogenic, ill defined echogenic and mixed patterns. 2. The size of hepatocellular carcinoma by ultrasonographic measurement was larger than 5 cm in diameter in 28 cases. 3. In 7 cases performed with angiography, all echogenicities of hepatocellualr carcinoma were correlated with the findings of vascularity of angiography. 4. In cases combined with liver cirrhosis, the sonographic pattern of hepatocellular carcinoma appeared to be discrete or ill defined echogenic patterns.

  8. Ultrasound manifestation of hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Hwang, M. S.; Yoo, H. S.; Park, C. Y.; Choi, H. J.; Moon, Y. M.; Lee, S. I.

    1982-01-01

    With the advent of gray scale ultrasonographic equipment, the parenchymal disease of liver is more easily evaluated. Ultrasonography is a non-invasive technique, different from angiography, and performed without discomfort to patient. And also ultrasonography can be used in assessing the liver in cases showing equivocal scintigraphy and in differentiation of solid and cystic masses, first detected on scintigrams. Therefore, the complementary use of ultrasonography, Tc-99m-sulfur colloid scan and angiography provides better diagnostic accuracy for the detection of hepatocellular carcinoma, and moreover, sequential ultrasonographic studies in the same patient are valuable of following the course of hepatocellular carcinoma and monitoring the effectiveness of therapy for hepatocellular carcinoma. In thirty patients with histologically proven hepatocellular carcinoma, an analysis of ultrasound manifestation is made and the results are as follows; 1. Ultrasound manifestation of hepatocellular carcinoma by gray scale showed four different sonographic patterns including discrete echo free, discrete echogenic, ill defined echogenic and mixed patterns. 2. The size of hepatocellular carcinoma by ultrasonographic measurement was larger than 5 cm in diameter in 28 cases. 3. In 7 cases performed with angiography, all echogenicities of hepatocellualr carcinoma were correlated with the findings of vascularity of angiography. 4. In cases combined with liver cirrhosis, the sonographic pattern of hepatocellular carcinoma appeared to be discrete or ill defined echogenic patterns

  9. Sarcopenia Impairs Prognosis of Patients with Hepatocellular Carcinoma: The Role of Liver Functional Reserve and Tumor-Related Factors in Loss of Skeletal Muscle Volume.

    Science.gov (United States)

    Imai, Kenji; Takai, Koji; Watanabe, Satoshi; Hanai, Tatsunori; Suetsugu, Atsushi; Shiraki, Makoto; Shimizu, Masahito

    2017-09-22

    Sarcopenia impairs survival in patients with hepatocellular carcinoma (HCC). This study aimed to clarify the factors that contribute to decreased skeletal muscle volume in patients with HCC. The third lumbar vertebra skeletal muscle index (L3 SMI) in 351 consecutive patients with HCC was calculated to identify sarcopenia. Sarcopenia was defined as an L3 SMI value ≤ 29.0 cm²/m² for women and ≤ 36.0 cm²/m² for men. The factors affecting L3 SMI were analyzed by multiple linear regression analysis and tree-based models. Of the 351 HCC patients, 33 were diagnosed as having sarcopenia and showed poor prognosis compared with non-sarcopenia patients ( p = 0.007). However, this significant difference disappeared after the adjustments for age, sex, Child-Pugh score, maximum tumor size, tumor number, and the degree of portal vein invasion by propensity score matching analysis. Multiple linear regression analysis showed that age ( p = 0.015) and sex ( p < 0.0001) were significantly correlated with a decrease in L3 SMI. Tree-based models revealed that sex (female) is the most significant factor that affects L3 SMI. In male patients, L3 SMI was decreased by aging, increased Child-Pugh score (≥56 years), and enlarged tumor size (<56 years). Maintaining liver functional reserve and early diagnosis and therapy for HCC are vital to prevent skeletal muscle depletion and improve the prognosis of patients with HCC.

  10. Histopathology of hepatocellular carcinoma.

    Science.gov (United States)

    Schlageter, Manuel; Terracciano, Luigi Maria; D'Angelo, Salvatore; Sorrentino, Paolo

    2014-11-21

    Hepatocellular carcinoma (HCC) is currently the sixth most common type of cancer with a high mortality rate and an increasing incidence worldwide. Its etiology is usually linked to environmental, dietary or life-style factors. HCC most commonly arises in a cirrhotic liver but interestingly an increasing proportion of HCCs develop in the non-fibrotic or minimal fibrotic liver and a shift in the underlying etiology can be observed. Although this process is yet to be completely understood, this changing scenario also has impact on the material seen by pathologists, presenting them with new diagnostic dilemmas. Histopathologic criteria for diagnosing classical, progressed HCC are well established and known, but with an increase in detection of small and early HCCs due to routine screening programs, the diagnosis of these small lesions in core needle biopsies poses a difficult challenge. These lesions can be far more difficult to distinguish from one another than progressed HCC, which is usually a clear cut hematoxylin and eosin diagnosis. Furthermore lesions thought to derive from progenitor cells have recently been reclassified in the WHO. This review summarizes recent developments and tries to put new HCC biomarkers in context with the WHOs reclassification. Furthermore it also addresses the group of tumors known as combined hepatocellular-cholangiocellular carcinomas.

  11. Increased expression of hepatocyte nuclear factor 4 alpha transcribed by promoter 2 indicates a poor prognosis in hepatocellular carcinoma.

    Science.gov (United States)

    Cai, Shao-Hang; Lu, Shi-Xun; Liu, Li-Li; Zhang, Chris Zhiyi; Yun, Jing-Ping

    2017-10-01

    Hepatocyte nuclear factor 4 alpha (HNF4α) plays an important role in tumourigenesis. There is growing evidence indicating that HNF4α transcribed by promoter 1 (P1-HNF4α) is expressed at relatively low levels in HCC and its presence predicts a favourable outcome for hepatocellular carcinoma (HCC) patients. However, the role of HNF4α transcribed by promoter 2 (P2-HNF4α) in HCC remains unclear. A total of 615 HCC specimens were obtained to construct tissue microarrays and perform immunohistochemistry. The relationship between P2-HNF4α and clinical features of HCC patients were analysed. Kaplan-Meier analysis was conducted to assess the prognostic value of P2-HNF4α. The results showed that the expression of P2-HNF4α in HCC was noticeably increased in HCC tissues compared with the nontumourous tissues. In addition, P1-HNF4α expression was negatively correlated with P2-HNF4α expression ( p  = 0.023). High P2-HNF4α expression was significantly associated with poor differentiation of HCC ( p = 0.002) and vascular invasion ( p = 0.017). Kaplan-Meier analysis showed that P2-HNF4α expression was closely correlated with overall survival in the training group ( p = 0.01), validation group ( p = 0.034), and overall group of patients with HCC ( p P2-HNF4α, different from P1-HNF4α, is markedly upregulated and serves as an oncogene-associated protein in HCC. Our study therefore provides a promising biomarker for prognostic prediction and a potential therapeutic target for HCC.

  12. Synchronous gastric neuroendocrine carcinoma and hepatocellular carcinoma

    DEFF Research Database (Denmark)

    Ewertsen, Caroline; Henriksen, Birthe Merete; Hansen, Carsten Palnæs

    2009-01-01

    of synchronous gastric NEC and hepatocellular carcinoma in a patient with several other precancerous lesions is presented. The patient had anaemia, and a gastric tumour and two duodenal polyps were identified on upper endoscopy. A CT scan of the abdomen revealed several lesions in the liver. The lesions were...... invisible on B-mode sonography and real-time sonography fused with CT was used to identify and biopsy one of the lesions. Histology showed hepatocellular carcinoma. A literature search showed that only one case of a hepatocellular carcinoma synchronous with a gastric NEC has been reported previously. TRIAL...

  13. Morphologic Subtypes of Hepatocellular Carcinoma.

    Science.gov (United States)

    Torbenson, Michael S

    2017-06-01

    Hepatocellular carcinomas can be further divided into distinct subtypes that provide important clinical information and biological insights. These subtypes are distinct from growth patterns and are on based on morphologic and molecular findings. There are 12 reasonably well-defined subtypes as well as 6 provisional subtypes, together making up 35% of all hepatocellular carcinomas. These subtypes are discussed, with an emphasis on their definitions and the key morphologic findings. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Hepatocellular carcinoma: a review

    Directory of Open Access Journals (Sweden)

    Balogh J

    2016-10-01

    Full Text Available Julius Balogh,1,2 David Victor III,1,3,4 Emad H Asham,1,2 Sherilyn Gordon Burroughs,1,2 Maha Boktour,1,2 Ashish Saharia,1,2 Xian Li,1,2 R Mark Ghobrial,1,2 Howard P Monsour Jr,1,3,4 1Sherrie and Alan Conover Center for Liver Disease and Transplantation, 2Division of Transplantation, Department of Surgery, 3Department of Gastroenterology and Transplant Hepatology, 4Department of Medicine, Houston Methodist Hospital, Houston, TX, USA Abstract: Hepatocellular carcinoma (HCC is the most common primary liver malignancy and is a leading cause of cancer-related death worldwide. In the United States, HCC is the ninth leading cause of cancer deaths. Despite advances in prevention techniques, screening, and new technologies in both diagnosis and treatment, incidence and mortality continue to rise. Cirrhosis remains the most important risk factor for the development of HCC regardless of etiology. Hepatitis B and C are independent risk factors for the development of cirrhosis. Alcohol consumption remains an important additional risk factor in the United States as alcohol abuse is five times higher than hepatitis C. Diagnosis is confirmed without pathologic confirmation. Screening includes both radiologic tests, such as ultrasound, computerized tomography, and magnetic resonance imaging, and serological markers such as α-fetoprotein at 6-month intervals. Multiple treatment modalities exist; however, only orthotopic liver transplantation (OLT or surgical resection is curative. OLT is available for patients who meet or are downstaged into the Milan or University of San Francisco criteria. Additional treatment modalities include transarterial chemoembolization, radiofrequency ablation, microwave ablation, percutaneous ethanol injection, cryoablation, radiation therapy, systemic chemotherapy, and molecularly targeted therapies. Selection of a treatment modality is based on tumor size, location, extrahepatic spread, and underlying liver function. HCC is an

  15. Elevated serum levels of Chromogranin A in hepatocellular carcinoma.

    Science.gov (United States)

    Biondi, Antonio; Malaguarnera, Giulia; Vacante, Marco; Berretta, Massimiliano; D'Agata, Velia; Malaguarnera, Michele; Basile, Francesco; Drago, Filippo; Bertino, Gaetano

    2012-01-01

    During the past three decades, the incidence of hepatocellular carcinoma in the United States has tripled. The neuroendocrine character has been observed in some tumor cells within some hepatocellular carcinoma nodules and elevated serum chromogranin A also been reported in patients with hepatocellular carcinoma. The aim of this work was to investigate the role of serum concentration of chromogranin A in patients with hepatocellular carcinoma at different stages. The study population consisted of 96 patients (63 males and 33 females age range 52-84) at their first hospital admission for hepatocellular carcinoma. The control group consisted of 35 volunteers (20 males and 15 females age range 50-80). The hepatocellular carcinoma patients were stratified according the Barcelona-Clinic Liver Cancer classification. Venous blood samples were collected before treatment from each patients before surgery, centrifuged to obtain serum samples and stored at -80° C until assayed. The chromogranin A serum levels were elevated (> 100 ng/ml) in 72/96 patients with hepatocellular carcinoma. The serum levels of chromogranin A were significantly correlated (p<0.05) with alpha-fetoprotein. In comparison with controls, the hepatocellular carcinoma patients showed a significant increase (p<0.001) vs controls. The chromogranin A levels in the Barcelona staging of hepatocellular carcinoma was higher in stage D compared to stage C (p<0.01), to stage B (p<0.001), and to stage A (p<0.001). Molecular markers, such as chromogranin A, could be very useful tools for hepatocellular carcinoma diagnosis. However the molecular classification should be incorporated into a staging scheme, which effectively separated patients into groups with homogeneous prognosis and response to treatment, and thus serves to aid in the selection of appropriate therapy.

  16. The evolutionary scenario of hepatocellular carcinoma in Italy: an update.

    Science.gov (United States)

    Bucci, Laura; Garuti, Francesca; Lenzi, Barbara; Pecorelli, Anna; Farinati, Fabio; Giannini, Edoardo G; Granito, Alessandro; Ciccarese, Francesca; Rapaccini, Gian Lodovico; Di Marco, Maria; Caturelli, Eugenio; Zoli, Marco; Borzio, Franco; Sacco, Rodolfo; Cammà, Calogero; Virdone, Roberto; Marra, Fabio; Felder, Martina; Morisco, Filomena; Benvegnù, Luisa; Gasbarrini, Antonio; Svegliati-Baroni, Gianluca; Foschi, Francesco Giuseppe; Missale, Gabriele; Masotto, Alberto; Nardone, Gerardo; Colecchia, Antonio; Bernardi, Mauro; Trevisani, Franco

    2017-02-01

    Epidemiology of hepatocellular carcinoma is changing worldwide. This study aimed at evaluating the changing scenario of aetiology, presentation, management and prognosis of hepatocellular carcinoma in Italy during the last 15 years. Retrospective analysis of the ITA.LI.CA (Italian Liver Cancer) database including 5192 hepatocellular carcinoma patients managed in 24 centres from 2000 to 2014. Patients were divided into three groups according to the date of cancer diagnosis (2000-2004, 2005-2009 and 2010-2014). The main results were as follows: (i) progressive patient aging; (ii) progressive expansion of non-viral cases and, namely, of "metabolic" hepatocellular carcinomas; (iii) increasing proportion of hepatocellular carcinoma diagnosed during a correct (semi-annual) surveillance programme; (iv) favourable cancer stage migration; (v) increased use of radiofrequency ablation to the detriment of percutaneous ethanol injection; (vi) improved outcomes of ablative and transarterial treatments; (vii) improved overall survival (adjusted for the lead time in surveyed patients), particularly after 2009, of both viral and non-viral patients presenting with an early- or intermediate-stage hepatocellular carcinoma. During the last 15 years several aetiological and clinical features of hepatocellular carcinoma patients have changed, as their management. The observed improvement of overall survival was owing both to the wider use of semi-annual surveillance, expanding the proportion of tumours that qualified for curative treatments, and to the improved outcome of loco-regional treatments. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  17. Treatment options for hepatocellular carcinoma.

    Science.gov (United States)

    Sandhu, Dalbir S; Tharayil, Vivek S; Lai, Jin-Ping; Roberts, Lewis R

    2008-02-01

    Hepatocellular carcinoma (HCC) is frequently diagnosed at advanced stages and has a high mortality rate. With improved survival of patients with cirrhotic liver disease and increased prevalence of chronic hepatitis C viral infections, a rise in the number of HCC cases is being reported worldwide. Early diagnosis and treatment can significantly improve the prognosis of patients with HCC. Although surgical resection is an important potentially curative therapy for liver tumors, in appropriately selected patients, liver transplantation has been shown to achieve excellent survival rates for a solid tumor. Locally ablative and locoregional therapies in the form of percutaneous ethanol injection, radiofrequency ablation, transcatheter arterial chemoembolization and transcatheter arterial radioembolization (TheraSphere) are viable options in patients with unresectable HCC. Unfortunately, the role of systemic therapy has been very limited in the treatment of these patients. Novel treatment options based on an improved understanding of the molecular pathogenesis of HCC are being explored. These targeted molecular therapies are aimed at growth factors and their receptors, intracellular signal transduction and cell cycle control. A substantial improvement in outcomes of intermediate and advanced stage HCC is expected with the advent of these targeted therapies, used in combination with surgical or locoregional therapies. Recent positive results from a large Phase III study of the receptor tyrosine kinase inhibitor, sorafenib, hold great promise in the treatment of HCC.

  18. Alpha-fetoprotein still is a valuable diagnostic and prognosis predicting biomarker in hepatitis B virus infection-related hepatocellular carcinoma.

    Science.gov (United States)

    Yao, Mingjie; Zhao, Jingmin; Lu, Fengmin

    2016-01-26

    Use of serum alpha-fetoprotein (AFP) in clinical practices has been challenged in recent years, due to the lack of specificity and sensitivity. Here we conducted a retrospective study to evaluate the diagnostic and prognostic value of serum AFP among hepatocellular carcinoma (HCC) patients with their pathogenic features taken into consideration. The cohort for this study comprised 318 cases of hepatitis and 731 cases of cirrhosis, as well as 796 HCC patients. Using 11.62ng/mL as a cut-off value, the positive rate of AFP test among serum hepatitis B surface antigen (HBsAg) positive HCC patients was significantly higher than that in those HBsAg negative HCC patients (79.55% vs 56.49%, P < 0.000). Similarly, the median serum AFP level in HCC patients with serum HBsAg positive was significantly higher than that in those HBsAg negative HCC patients (423.89ng/ml vs 40.82ng/ml, P < 0.000). In addition, Kaplan-Meier curve analysis revealed that lower preoperative AFP level implicated a much higher overall survival rate. Of note, such prognosis predicting value was only seen in those chronic HBV infection-related HCC patients, but not among the HCC patients etiologically irrelevant to HBV infection. We believe that serum AFP is of diagnosis and prognostic predicting value for HCC with chronic HBV infection, and strongly suggest use of serum AFP as a biomarker in China and other HBV infection endemic area like Southeast Asia.

  19. Radioembolization of hepatocellular carcinoma.

    Science.gov (United States)

    Van de Wiele, Christophe

    2010-12-01

    In this review paper, available data on radioembolization of unresectable hepatocellular carcinoma (HCC) using commercially available radiopharmaceuticals, respectively (131)I-Lipiodol, Therasphere (glass-microspheres) and SIRspheres (resin-microspheres) are reviewed. In the palliative setting, (131)I-Lipiodol was shown to yield response rates of 17-92% which in patients with portal vein thrombosis (PVT) translate into a survival benefit as evidenced by a phase III randomized trial. Furthermore, in terms of efficacy, (131)I-Lipiodol is as efficacious as trans-arterial chemoembolization (TACE) but far better tolerated. In the adjuvant setting, improved recurrence-free and overall survival when compared to surgery alone have been reported but these results warrant confirmation by randomized prospective trials. Similar to (131)I-Lipiodol, when administered in a palliative setting, radioembolization using (90)Y microspheres was proven effective for selected cases of non-resectable HCC and well tolerated. Available data suggest that Therasphere treatment outperforms TACE both in terms of response as in terms of event-free survival in unresectable HCC. However, this finding needs confirmation by randomized prospective trials. Therasphere treatment was also shown to limit progression of HCC allowing potential candidates for orthotopic liver transplantation (OLT) more time to wait for donor organs as well as to downstage the HCC disease to such an extent that patients that were initially not, as yet become eligible for OLT with a gain in survival. Finally, Therasphere was shown to be safe and efficacious in HCC patients presenting with PVT, reason for which approval was granted for this indication by the FDA.

  20. PGK1 Drives Hepatocellular Carcinoma Metastasis by Enhancing Metabolic Process.

    Science.gov (United States)

    Xie, Huijun; Tong, Guihui; Zhang, Yupei; Liang, Shu; Tang, Kairui; Yang, Qinhe

    2017-07-27

    During the proliferation and metastasis, the tumor cells prefer glycolysis (Warburg effect), but its exact mechanism remains largely unknown. In this study, we demonstrated that phosphoglycerate kinase 1 (PGK1) is an important enzyme in the pathway of metabolic glycolysis. We observed a significant overexpression of PGK1 in hepatocellular carcinoma tissues, and a correlation between PGK1 expression and poor survival of hepatocellular carcinoma patients. Also, the depletion of PGK1 dramatically reduced cancer cell proliferation and metastasis, indicating an oncogenic role of PGK1 in liver cancer progression. Further experiments showed that PGK1 played an important role in MYC -induced metabolic reprogramming, which led to an enhanced Warburg effect. Our results revealed a new effect of PGK1, which can provide a new treatment strategy for hepatocellular carcinoma, as PGK1 is used to indicate the prognosis of hepatocellular carcinoma (HCC).

  1. Imaging and embolization of hepatocellular carcinoma supplied by gonadal artery

    International Nuclear Information System (INIS)

    Wu Hongping; Wang Junjie; Lu Yang; You Kaizhi

    2010-01-01

    Objective: To evaluate radiology and embolization for hepatocellular carcinoma supplied by gonadal artery. Methods: The medical records of 3 patients with hepatocellular carcinoma supplied by gonadal artery from August 2002 to September 2008 were reviewed. The demography, gonadal artery location, modus operandi, imaging features of liver cancer and prognosis were retrospectively analyzed. Results: Anatomic variation of gonadal artery occurred with the gonadal artery arising from the upper abdominal aorta in 1 patient and from the middle suprarenal artery in 2 patients. The blood supply of the hepatocellular carcinoma derived from the gonadal artery in all 3 patients. No complications occurred in the 6-month follow-up after embolization. Conclusion: Hepatocellular carcinoma may be supplied by gonadal artery with anomalous origin. This anatomic variant can be readily demonstrated by imaging to guide embolization. (authors)

  2. Tumor-adjacent tissue co-expression profile analysis reveals pro-oncogenic ribosomal gene signature for prognosis of resectable hepatocellular carcinoma.

    Science.gov (United States)

    Grinchuk, Oleg V; Yenamandra, Surya P; Iyer, Ramakrishnan; Singh, Malay; Lee, Hwee Kuan; Lim, Kiat Hon; Chow, Pierce Kah-Hoe; Kuznetsov, Vladamir A

    2018-01-01

    Currently, molecular markers are not used when determining the prognosis and treatment strategy for patients with hepatocellular carcinoma (HCC). In the present study, we proposed that the identification of common pro-oncogenic pathways in primary tumors (PT) and adjacent non-malignant tissues (AT) typically used to predict HCC patient risks may result in HCC biomarker discovery. We examined the genome-wide mRNA expression profiles of paired PT and AT samples from 321 HCC patients. The workflow integrated differentially expressed gene selection, gene ontology enrichment, computational classification, survival predictions, image analysis and experimental validation methods. We developed a 24-ribosomal gene-based HCC classifier (RGC), which is prognostically significant in both PT and AT. The RGC gene overexpression in PT was associated with a poor prognosis in the training (hazard ratio = 8.2, P = 9.4 × 10 -6 ) and cross-cohort validation (hazard ratio = 2.63, P = 0.004) datasets. The multivariate survival analysis demonstrated the significant and independent prognostic value of the RGC. The RGC displayed a significant prognostic value in AT of the training (hazard ratio = 5.0, P = 0.03) and cross-validation (hazard ratio = 1.9, P = 0.03) HCC groups, confirming the accuracy and robustness of the RGC. Our experimental and bioinformatics analyses suggested a key role for c-MYC in the pro-oncogenic pattern of ribosomal biogenesis co-regulation in PT and AT. Microarray, quantitative RT-PCR and quantitative immunohistochemical studies of the PT showed that DKK1 in PT is the perspective biomarker for poor HCC outcomes. The common co-transcriptional pattern of ribosome biogenesis genes in PT and AT from HCC patients suggests a new scalable prognostic system, as supported by the model of tumor-like metabolic redirection/assimilation in non-malignant AT. The RGC, comprising 24 ribosomal genes, is introduced as a robust and reproducible prognostic model for

  3. Hepatocellular carcinoma in Danish patients

    DEFF Research Database (Denmark)

    Stefansdottir, Jenna; Christensen, Erik; Schiødt, Frank Vinholt

    2017-01-01

    OBJECTIVE: Hepatocellular carcinoma (HCC) is a common cause of cancer, and most HCC patients have underlying cirrhosis. Retrospectively, we aimed to characterize patients with newly diagnosed HCC at a Danish hospital and to investigate survival and identify predictive factors for survival. METHODS...

  4. Evaluation of transcatheter therapy for hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Yamada, Toshihiko

    1990-01-01

    The author proposed improvement of the criteria for the effects of transcatheter therapy for hepatocellular carcinoma. 104 patients were treated by transcatheter therapy. Their responses were determined by the usual criteria. Next, they were classified and evaluated in 3 groups, with the area of lipiodol deposition on CT for over 4 weeks regarded as nacrosis. The result was determined, and its relationship to prognosis was studied in light of the repeated therapy. By the usual criteria, only 10% of patients were judged as PR, and there were no differences between therapies. Many of the NC cases had low AFP levels with therapy. At the initial therapy, the ratio of cases with low AFP levels was higher and the survival time was longer in the A group. So the A group was judged as most effective. Clinically, 10 patients were considered most benefitted by therapy. They were considered the A group, but all were judged as NC. Considering the effects of repeated therapy, 10 patients with NC were judged as the A-max group. Prognosis was poor in patients of the B-max and C-max groups. These results indicate that judgement by the usual criteria was inconsistent with clinical condition. It was improved by regarding the area of lipiodol deposition on CT for over 4 weeks as necrosis. Estimations of effects and prognosis were made more accurate by considering repeated therapy. Thus, the proposed improvement of the criteria by CT is more useful to estimate transcatheter therapy of the hepatocellular carcinoma. (author)

  5. BAG3 and HIF-1 α coexpression detected by immunohistochemistry correlated with prognosis in hepatocellular carcinoma after liver transplantation.

    Science.gov (United States)

    Xiao, Heng; Tong, Rongliang; Cheng, Shaobing; Lv, Zhen; Ding, Chaofeng; Du, Chengli; Xie, Haiyang; Zhou, Lin; Wu, Jian; Zheng, Shusen

    2014-01-01

    The objective is to determine the effects of BAG3 and HIF-1 α expression on the prognosis of HCC patients after liver transplantation. Samples from 31 patients with HCC receiving liver transplantation were collected for this study. The immunohistochemistry was used to detect the expression of BAG3 and HIF-1 α of HCC samples. According to the immunohistochemistry results, BAG3 and HIF-1 α staining were significantly associated with tumor TNM stage (P = 0.004, P = 0.012). A significant association between high BAG3/HIF-1 α levels and a shorter overall survival was detected, so as the combined BAG3 and HIF-1 α analysis. The results suggested that the expression level of BAG3 and HIF-1 α is efficient prognostic parameters in patients with HCC after liver transplantation.

  6. BAG3 and HIF-1α Coexpression Detected by Immunohistochemistry Correlated with Prognosis in Hepatocellular Carcinoma after Liver Transplantation

    Directory of Open Access Journals (Sweden)

    Heng Xiao

    2014-01-01

    Full Text Available Objective. The objective is to determine the effects of BAG3 and HIF-1α expression on the prognosis of HCC patients after liver transplantation. Methods. Samples from 31 patients with HCC receiving liver transplantation were collected for this study. The immunohistochemistry was used to detect the expression of BAG3 and HIF-1α of HCC samples. Results. According to the immunohistochemistry results, BAG3 and HIF-1α staining were significantly associated with tumor TNM stage (P=0.004, P=0.012. A significant association between high BAG3/HIF-1α levels and a shorter overall survival was detected, so as the combined BAG3 and HIF-1α analysis. Conclusion. The results suggested that the expression level of BAG3 and HIF-1α is efficient prognostic parameters in patients with HCC after liver transplantation.

  7. BIOCHEMICAL NUTRITIONAL PROFILE OF LIVER CIRRHOSIS PATIENTS WITH HEPATOCELLULAR CARCINOMA

    Directory of Open Access Journals (Sweden)

    Gabriela Zanatta PORT

    2014-03-01

    Full Text Available Context Liver cirrhosis patients with hepatocellular carcinoma present nutritional alterations and metabolic disorders that negatively impact the prognosis. Objective The objective is to identify alterations in the metabolism of macro and micronutrients among liver cirrhosis patients with and without hepatocellular carcinoma and their relation to the Child-Turcote-Pugh score and Barcelona Clinic Liver Cancer staging. Methods Analytical transversal study, with 31 hepatocellular carcinoma patients and 48 liver cirrhosis patients. Laboratorial exams were carried out. The existence of an association between the biochemical parameters and the disease severity as well as the presence of hepatocellular carcinoma was assessed. Results The metabolic-nutritional profile of liver cirrhosis patients caused by the hepatitis C virus and hepatocellular carcinoma showed alterations, specifically the lipid (total cholesterol, HDL and triglycerides, protein (albumin, creatinine and uric acid, iron (transferrin, iron and ferritin saturation, hematocrit and hemoglobin, zinc and B12 vitamin profiles. There is a relation between nutritional biochemical markers and the Child-Turcote-Pugh, as well as Barcelona Clinic Liver Cancer staging. Conclusions Considering the existence of alterations in the metabolism of nutrients in liver cirrhosis patients with and without hepatocellular carcinoma, and also that conventional nutritional assessment methods present limitations for this population, the biochemical laboratorial exams are valid to complement the diagnosis of the nutritional state in a quick and practical manner.

  8. Protein phosphatase magnesium-dependent 1δ (PPM1D mRNA expression is a prognosis marker for hepatocellular carcinoma.

    Directory of Open Access Journals (Sweden)

    Guang-Bing Li

    Full Text Available Protein phosphatase magnesium-dependent 1δ (PPM1D is an oncogene, overexpressed in many solid tumors, including ovarian cancer and breast cancer. The current study examined the expression and the prognostic value of PPM1D mRNA in human hepatocellular carcinoma (HCC.Total RNA was extracted from 86 HCC and paired non-cancerous liver tissues. PPM1D mRNA expression was determined by real-time quantitative reverse transcriptase-polymerase chain reaction (qPCR. Immunohistochemistry assay was used to verify the expression of ppm1d protein in the HCC and non-cancerous liver tissues. HCC patients were grouped according to PPM1D mRNA expression with the average PPM1D mRNA level in non-cancerous liver tissue samples as the cut-off. Correlations between clinicopathologic variables, overall survival and PPM1D mRNA expression were analyzed.PPM1D mRNA was significantly higher in HCC than in the paired non-cancerous tissue (p<0.01. This was confirmed by ppm1d staining. 56 patients were classified as high expression group and the other 30 patients were categorized as low expression group. There were significant differences between the two groups in term of alpha-fetoprotein (α-FP level (p<0.01, tumor size (p<0.01, TNM stage (p<0.01, recurrence incidence (p<0.01 and family history of liver cancer (p<0.01. The current study failed to find significant differences between the two groups in the following clinical characteristics: age, gender, portal vein invasion, lymphnode metastasis, hepatitis B virus (HBV infection and alcohol intake. Survival time of high expression group was significantly shorter than that of low expression group (median survival, 13 months and 32 months, respectively, p<0.01.Up-regulation of PPM1D mRNA was associated with progressive pathological feature and poor prognosis in HCC patients. PPM1D mRNA may serve as a prognostic marker in HCC.

  9. Sarcomatous Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Wei-Cheng Lee

    2015-09-01

    We reviewed several reports of this subtype of HCC. It was known that sarcomatous HCC is hard to be distinguished with ordinary HCC before surgery. There is no evidence that adjuvant therapy including chemotherapy, radiotherapy and target therapy may improve the survival rate. It would usually be diagnosed as atypical HCC and treated as ordinary HCC, however, the prognosis is much worse; this sarcomatosis type HCC should be seriously considered.

  10. Current management of hepatocellular carcinoma

    Science.gov (United States)

    Tabrizian, Parissa; Roayaie, Sasan; Schwartz, Myron E

    2014-01-01

    Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide and leading cause of death among patients with cirrhosis. Treatment guidelines are based according to the Barcelona Clinic Liver Cancer staging system. The choice among therapeutic options that include liver resection, liver transplantation, locoregional, and systemic treatments must be individualized for each patient. The aim of this paper is to review the outcomes that can be achieved in the treatment of HCC with the heterogeneous therapeutic options currently available in clinical practice. PMID:25132740

  11. Transhemangioma Ablation of Hepatocellular Carcinoma

    International Nuclear Information System (INIS)

    Pua, Uei

    2012-01-01

    Radiofrequency ablation (RFA) is a well-established treatment modality in the treatment of early hepatocellular carcinoma (HCC) [1]. Safe trajectory of the RFA probe is crucial in decreasing collateral tissue damage and unwarranted probe transgression. As a percutaneous technique, however, the trajectory of the needle is sometimes constrained by the available imaging plane. The presence of a hemangioma beside an HCC is uncommon but poses the question of safety related to probe transgression. We hereby describe a case of transhemangioma ablation of a dome HCC.

  12. Transhemangioma Ablation of Hepatocellular Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Pua, Uei, E-mail: druei@yahoo.com [Tan Tock Seng Hospital, Department of Diagnostic Radiology (Singapore)

    2012-12-15

    Radiofrequency ablation (RFA) is a well-established treatment modality in the treatment of early hepatocellular carcinoma (HCC) [1]. Safe trajectory of the RFA probe is crucial in decreasing collateral tissue damage and unwarranted probe transgression. As a percutaneous technique, however, the trajectory of the needle is sometimes constrained by the available imaging plane. The presence of a hemangioma beside an HCC is uncommon but poses the question of safety related to probe transgression. We hereby describe a case of transhemangioma ablation of a dome HCC.

  13. Long non-coding RNA CCAT2 is associated with poor prognosis in hepatocellular carcinoma and promotes tumor metastasis by regulating Snail2-mediated epithelial–mesenchymal transition

    Directory of Open Access Journals (Sweden)

    Xu Y

    2017-02-01

    Full Text Available Yongfu Xu,* Binfeng Wang,* Fabiao Zhang, Aidong Wang, Xuefeng Du, Peng Hu, Yu Zhu, Zheping Fang Department of Hepatobiliary Surgery, Taizhou Hospital of Zhejiang Province, Wenzhou Medical University, Linhai, Zhejiang, People’s Republic of China *These authors contributed equally to this work Abstract: Increasing evidence has demonstrated that aberrant expressions of long non-coding RNAs (lncRNAs are involved in various malignancies, including hepatocellular carcinoma (HCC. This study aimed to investigate the role of lncRNA colon cancer-associated transcript 2 (CCAT2 in the progression of HCC. Quantitative real-time polymerase chain reaction analysis confirmed that CCAT2 was upregulated in HCC cell lines and cancerous tissues compared with normal liver cell line and adjacent normal tissue samples. The level of CCAT2 was positively associated with tumor–node–metastasis stages and vessel invasion. Survival analyses revealed that high CCAT2 expression predicted poor prognostic outcomes, serving as an independent prognostic factor for HCC patients. Patients with high CCAT2 expression had a 1.849-fold increased risk of death compared with those with low CCAT2 expression. Moreover, we also found that knockdown of CCAT2 expression reduced cell migration and invasion in vitro. We further demonstrated that CCAT2 played a key role in enhancing the epithelial–mesenchymal transition (EMT through the regulation of vimentin, E-cadherin and transcription factor snail2 expression. Taken together, our findings showed that high CCAT2 expression is associated with poor survival in HCC patients. CCAT2 promotes HCC progression by regulating Snail2-induced EMT. CCAT2 may be a prognostic biomarker and therapeutic target for HCC. Keywords: long non-coding RNA, CCAT2, hepatocellular carcinoma, epithelial–mesenchymal transition, survival

  14. Ultrasonographic finding of hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Ryu, Han Soo; Woo, Seong Ku; Lim, Jae Hoon; Ko, Young Tae; Kim, Ho Kyun; Kim, Soon Yong [Kyung Hee University Hospital, Seoul (Korea, Republic of)

    1983-12-15

    With the development of gray scale ultrasonography, detection and evaluation of hepatic parenchymal disease including space occupying lesion are easily performed and frequently used in the world. Thrity five cases of histopathologically proven and ultrasonographically suggested hepatocellular carcinoma are retrospectively studied. The results were as follows; 1. Ultrasonographic findings of hepatocellular carcinoma show hyperechoic pattern in 22 cases (63%), hypoechoic pattern in 2 cases (6%), and mixed pattern in 11 cases (31%). 2. The margin of tumor is ill-defined in 19 cases (54%) and well defined in16 cases (46%). 3. The size of tumor by sonographic measurement was large than 5 cm in diameter in 33 cases (94%). 4. The number of tumor is solitary in 19 cases and multiple in 16 cases. The sites of involved lobe were right lobe in 22 cases (63%), left lobe in 2 cases (6%), and both lobes in 11 cases (31%). 5. Associated sonographic findings were hepatomegaly with focal contour change in 25 cases (71%), splenomegaly in 16 cases (46%), cirrhosis of liver in 15 cases (43%), ascites in 11 cases (31%) and tumoral thrombosis in portal vein in 8 cases (23%). 6. The sex ratio is 6 : 1 male predominence and the age ranges from 32 to 76 years with highest incidence in 5th and 6th decades.

  15. Chromophobe hepatocellular carcinoma with abrupt anaplasia: a proposal for a new subtype of hepatocellular carcinoma with unique morphological and molecular features.

    Science.gov (United States)

    Wood, Laura D; Heaphy, Christopher M; Daniel, Hubert Darius-J; Naini, Bita V; Lassman, Charles R; Arroyo, May R; Kamel, Ihab R; Cosgrove, David P; Boitnott, John K; Meeker, Alan K; Torbenson, Michael S

    2013-12-01

    Hepatocellular carcinomas exhibit heterogeneous morphologies by routine light microscopy. Although some morphologies represent insignificant variations in growth patterns, others may represent unrecognized subtypes of hepatocellular carcinoma. Identification of these subtypes could lead to separation of hepatocellular carcinomas into discrete groups with unique underlying genetic changes, prognosis, or therapeutic responses. In order to identify potential subtypes, two pathologists independently screened a cohort of 219 unselected hepatocellular carcinoma resection specimens and divided cases into potential subtypes. One of these promising candidate subtypes was further evaluated using histological and molecular techniques. This subtype was characterized by a unique and consistent set of histological features: smooth chromophobic cytoplasm, abrupt focal nuclear anaplasia (small clusters of tumor cells with marked nuclear anaplasia in a background of tumor cells with bland nuclear cytology), and scattered microscopic pseudocysts--we designate this variant as 'chromophobe hepatocellular carcinoma with abrupt anaplasia'. Thirteen cases were identified (6% of all hepatocellular carcinomas), including 6 men and 7 women with an average age of 61 years. Six cases occurred in cirrhotic livers. Serum AFP was elevated in 6 out of 10 cases. There were a variety of underlying liver diseases, but cases were enrichment for chronic hepatitis B, P=0.006. Interestingly, at the molecular level, this variant was strongly associated with the alternative lengthening of telomere (ALT) phenotype by telomere FISH. ALT is a telomerase-independent mechanism of telomere maintenance and is found in approximately 8% of unselected hepatocellular carcinomas. In contrast, 11/12 (92%) of the cases of chromophobe hepatocellular carcinoma with abrupt anaplasia were ALT-positive. In summary, we propose that chromophobe hepatocellular carcinoma with abrupt anaplasia represents a new subtype of

  16. Percutaneous cryoablation for hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Kyoung Doo Song

    2016-12-01

    Full Text Available Local ablation therapy is considered as a conventional treatment option for patients with early stage hepatocellular carcinoma (HCC. Although radiofrequency (RF ablation is widely used for HCC, the use of cryoablation has been increasing as newer and safer cryoablation systems have developed. The thermodynamic mechanism of freezing and thawing used in cryoablation is the Joule-Thomson effect. Cryoablation destroys tissue via direct tissue destruction and vascular-related injury. A few recent comparative studies have shown that percutaneous cryoablation for HCCs is comparable to percutaneous RF ablation in terms of long term therapeutic outcomes and complications. Cryoablation has several advantages over RF ablation such as well visualization of iceball, no causation of severe pain, and lack of severe damage to great vessels and gallbladder. It is important to know the advantages and disadvantages of cryoablation compared with RF ablation for improvement of therapeutic efficacy and safety.

  17. Medical treatment of hepatocellular carcinoma.

    Science.gov (United States)

    Granito, Alessandro; Bolondi, Luigi

    2009-12-16

    Hepatocellular carcinoma (HCC) is the fifth most common neoplasm and the third leading cause of cancer-related deaths worldwide. Cirrhosis, most often due to viral hepatitis, is the predominant risk factors for HCC and geographical differences in both risk factors and incidence are largely due to epidemiological variations in hepatitis B and C infection. Hepatic function is a relevant parameter in selecting therapy in HCC. The current clinical classification of HCC split patients into 5 stages, with a specific treatment schedule for any stage. As patients with early stages can receive curative treatments, such as surgical resection, liver transplantation or local ablation, surveillance program in high-risk populations has become mandatory. Sorafenib, a multikinase inhibitor, has recently shown survival benefits in patients at advanced stage of disease. Hopefully, new molecular targeted therapies and their combination with sorafenib or interventional and surgical procedures, should expand the therapeutic armamentarium against HCC.

  18. [Radiofrequency ablation of hepatocellular carcinoma].

    Science.gov (United States)

    Widmann, Gerlig; Schullian, Peter; Bale, Reto

    2013-03-01

    Percutaneous radiofrequency ablation (RFA) is well established in the treatment of hepatocellular carcinoma (HCC). Due to its curative potential, it is the method of choice for non resectable BCLC (Barcelona Liver Clinic) 0 and A. RFA challenges surgical resection for small HCC and is the method of choice in bridging for transplantation and recurrence after resection or transplantation. The technical feasibility of RFA depends on the size and location of the HCC and the availability of ablation techniques (one needle techniques, multi-needle techniques). More recently, stereotactic multi-needle techniques with 3D trajectory planning and guided needle placement substantially improve the spectrum of treatable lesions including large volume tumors. Treatment success depends on the realization of ablations with large intentional margins of tumor free tissue (A0 ablation in analogy to R0 resection), which has to be documented by fusion of post- with pre-ablation images, and confirmed during follow-up imaging.

  19. Angiographic findings of hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Han, Man Chung; Cho, Byung Jae; Huh, Seung Jae; Bae, Sang Hoon; Kim, Ung Jin; Kim, Chung Yong; Kim, Noe Kyeong [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    1985-12-15

    From March 1977 to July 1979, 69 cases of angiograms of hepatocellular carcinoma were observed in Seoul National University Hospital. The findings of selective celiac and/or hepatic arteriography in total 69 cases of confirmed hepatocellular carcinoma, with clinical and laboratory findings, were analyzed. The summarized results are as follows; 1. Among 69 cases od hepatoma, 62 were male and 7 were female with sex ratio of 8.9 : 1. Peak incidence is 5th to 7th decades (72.5%). Epigastric pain, indigestion, and palpable mass in right upper quadrant were common symptoms and sign. Laboratory findings showed elevated serum alkaline phosphatase more than 5 Bodansky unit in 75.4%. Alpha-feto protein was positive in 65.2% of all the patients. 2 All 69 cases were classified into 31 cases of massive type, 22 cases of diffuse type, and 16 cases of nodular type, in accordance with angiographic gross anatomy. The frequency of angiographic findings were hypervascularities and tumor vessels (100%), tumor stainings (98.5%), arteriovenous shunt (71.0%), displacement of intrahepatic arteries (66.7%), vascular lakes and channel (59.4%). Encasement of hepatic artery and portal vein regurgitation was respectively 4 cases. Tumor mass in portal vein were 6 cases and tumor mass in hepatic vein was 1 case. 3. Intraarterial infusion of 5-FU was performed in 15 hepatoma patients, and the results were that angiographic improvement was demonstrated in 3 cases, no improvement in 8 cases, and incomplete infusion in 4 cases. 4. The selective celiac and/or hepatic angiograms are excellent diagnostic tools as well as therapeutic management for intraarterial infusion of anticancerous drugs.

  20. Angiographic findings of hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Han, Man Chung; Cho, Byung Jae; Huh, Seung Jae; Bae, Sang Hoon; Kim, Ung Jin; Kim, Chung Yong; Kim, Noe Kyeong

    1985-01-01

    From March 1977 to July 1979, 69 cases of angiograms of hepatocellular carcinoma were observed in Seoul National University Hospital. The findings of selective celiac and/or hepatic arteriography in total 69 cases of confirmed hepatocellular carcinoma, with clinical and laboratory findings, were analyzed. The summarized results are as follows; 1. Among 69 cases od hepatoma, 62 were male and 7 were female with sex ratio of 8.9 : 1. Peak incidence is 5th to 7th decades (72.5%). Epigastric pain, indigestion, and palpable mass in right upper quadrant were common symptoms and sign. Laboratory findings showed elevated serum alkaline phosphatase more than 5 Bodansky unit in 75.4%. Alpha-feto protein was positive in 65.2% of all the patients. 2 All 69 cases were classified into 31 cases of massive type, 22 cases of diffuse type, and 16 cases of nodular type, in accordance with angiographic gross anatomy. The frequency of angiographic findings were hypervascularities and tumor vessels (100%), tumor stainings (98.5%), arteriovenous shunt (71.0%), displacement of intrahepatic arteries (66.7%), vascular lakes and channel (59.4%). Encasement of hepatic artery and portal vein regurgitation was respectively 4 cases. Tumor mass in portal vein were 6 cases and tumor mass in hepatic vein was 1 case. 3. Intraarterial infusion of 5-FU was performed in 15 hepatoma patients, and the results were that angiographic improvement was demonstrated in 3 cases, no improvement in 8 cases, and incomplete infusion in 4 cases. 4. The selective celiac and/or hepatic angiograms are excellent diagnostic tools as well as therapeutic management for intraarterial infusion of anticancerous drugs.

  1. Computed tomographic findings of hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Jo, In Su; Jong, Woo Yung; Lee, Jong Yul; Choi, Han Yong; Kim, Bong Ki

    1987-01-01

    With Development of Computed Tomography, detection of the Hepatocellular Carcinoma are easily performed and frequently used in the world. During 15 months, from December 1985 to February 1987, 59 patients with hepatocellular carcinoma were evaluated with computed tomography in department of radiology at Wallace Memorial Baptist Hospital. The results were as follow: 1. The most prevalent age group was 5th to 7th decades, male to female ratio was 4.9:1. 2. Classification with incidence of computed tomographic appearance of the hepatocellular carcinoma were solitary type 28 cases (48%), multinodular type 24 cases (40%), and diffuse type 7 cases (12%), Association with liver cirrhosis was noted in 22 cases (38%). 3. Inhomogenous internal consistency of hepatocellular carcinoma due to central necrosis were 35 cases (60%). Portal vein invasion by hepatocellular carcinoma was noted in 15 cases (25%), and particularly most common in diffuse type 4 cases (55%). 4. On precontrast scan, all hepatocellular carcinoma were seen as area of low density except for 3 cases(0.5%) of near isodensity which turned out to be remarkable low density on postcontrast scan. 5. In solitary type, posterior segment of right lobe was most common site of involvement 12 cases (43%). In diffuse type, bilobar involvement was most common, 6 cases (85%)

  2. Potentiality of immunotherapy against hepatocellular carcinoma

    Science.gov (United States)

    Tsuchiya, Nobuhiro; Sawada, Yu; Endo, Itaru; Uemura, Yasushi; Nakatsura, Tetsuya

    2015-01-01

    Hepatocellular carcinoma (HCC), the predominant form of primary liver cancer, is the fifth most common cancer worldwide and the second leading cause of cancer-related death. Despite the high incidence, treatment options remain limited for advanced HCC, and as a result prognosis continues to be poor. Current therapeutic options, surgery, chemotherapy and radiotherapy, have only modest efficacy. New treatment modalities to prolong survival and to minimize the risk of adverse response are desperately needed for patients with advanced HCC. Tumor immunotherapy is a promising, novel treatment strategy that may lead to improvements in both treatment-associated toxicity and outcome. The strategies have developed in part through genomic studies that have yielded candidate target molecules and in part through basic biology studies that have defined the pathways and cell types regulating immune response. Here, we summarize the various types of HCC immunotherapy and argue that the newfound field of HCC immunotherapy might provide critical advantages in the effort to improve prognosis of patients with advanced HCC. Already several immunotherapies, such as tumor-associated antigen therapy, immune checkpoint inhibitors and cell transfer immunotherapy, have demonstrated safety and feasibility in HCC patients. Unfortunately, immunotherapy currently has low efficacy in advanced stage HCC patients; overcoming this challenge will place immunotherapy at the forefront of HCC treatment, possibly in the near future. PMID:26420958

  3. Non-transplant therapies for patients with hepatocellular carcinoma and Child-Pugh-Turcotte class B cirrhosis.

    Science.gov (United States)

    Granito, Alessandro; Bolondi, Luigi

    2017-02-01

    Underlying liver cirrhosis is present in most patients with hepatocellular carcinoma, and liver transplantation is the only treatment strategy to cure both diseases. All other hepatocellular carcinoma treatment strategies have to take into account residual liver function that concurs with the patient's prognosis and might limit their feasibility. In patients with hepatocellular carcinoma and Child-Pugh-Turcotte class B (CPT-B), owing to borderline liver function, any intervention might be offset by liver function deterioration. In this setting, the decision for hepatocellular carcinoma treatment requires a comprehensive assessment of liver function, not restricted to the CPT classification, in addition to a careful evaluation of the prognostic effect of hepatocellular carcinoma compared with cirrhosis. In this Review, we provide an overview of the literature regarding the benefits and harms of non-transplant therapies in patients with hepatocellular carcinoma and CPT-B cirrhosis. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Dysregulated Expression of MITF in Subsets of Hepatocellular Carcinoma and Cholangiocarcinoma.

    Science.gov (United States)

    Nooron, Nattakarn; Ohba, Koji; Takeda, Kazuhisa; Shibahara, Shigeki; Chiabchalard, Anchalee

    2017-08-01

    Cholangiocarcinoma represents the second most common primary liver tumor after hepatocellular carcinoma. Mahanine, a carbazole alkaloid derived from Murraya koenigii (Linn.) Spreng, has been used as folk medicine in Thailand, where the liver fluke-associated cholangiocarcinoma is common. The expression of microphthalmia-associated transcription factor (MITF) is maintained at immunohistochemically undetectable levels in hepatocytes and cholangiocytes. To explore the regulation of MITF expression in the liver, we immunohistochemically analyzed the MITF expression using hepatocellular carcinoma and cholangiocarcinoma specimens of the human liver cancer tissue array. MITF immunoreactivity was detected in subsets of hepatocellular carcinoma (6 out of 38 specimens; 16%) and cholangiocarcinoma (2/7 specimens; 29%). Moreover, immunoreactivity for glioma-associated oncogene 1 (GLI1), a transcription factor of the Hedgehog signaling pathway, was detected in 55% of hepatocellular carcinoma (21/38 specimens) and 86% of cholangiocarcinoma (6/7 specimens). Importantly, MITF was detectable only in the GLI1-positive hepatocellular carcinoma and cholangiocarcinoma, and MITF immunoreactivity is associated with poor prognosis in patients with hepatocellular carcinoma. Subsequently, the effect of mahanine was analyzed in HepG2 human hepatocellular carcinoma and HuCCT1 and KKU-100 human cholangiocarcinoma cells. Mahanine (25 µM) showed the potent cytotoxicity in these hepatic cancer cell lines, which was associated with increased expression levels of MITF, as judged by Western blot analysis. MITF is over-expressed in subsets of hepatocellular carcinoma and cholangiocarcinoma, and detectable MITF immunoreactivity is associated with poor prognosis in patients with hepatocellular carcinoma. MITF expression levels may be determined in hepatic cancer cells by the balance between the Hedgehog signaling and the cellular stress.

  5. Hepatocellular carcinoma: Implications for Asia-Pacific Oncology Nurses

    Directory of Open Access Journals (Sweden)

    Deborah A Boyle

    2017-01-01

    Full Text Available Hepatocellular carcinoma (HCC is a prominent malignancy in the Asia-Pacific region. Despite considerable knowledge about it's scope and nature this malignancy remains incurable. This manuscript reviews the epidemiology of this cancer, its pathogenesis, risk factors, potential prevention, surveillance, treatment, and the oncology nurses' role relative to this malignancy. A literature search from the past decade was performed using the PubMed and CINAHL databases using the search terms “hepatocellular carcinoma,” “Asia,” and “nursing issues”. Themes such as etiology, prevention, treatment, and prognosis were included in this synthesis which has particular relevance to oncology nurses within the Asia-Pacific region.

  6. Serological diagnosis of hepatocellular carcinoma: challenges and opportunities

    Directory of Open Access Journals (Sweden)

    LU Fengmin

    2017-07-01

    Full Text Available Serological markers have the features of noninvasiveness and simple operation and thus have become a research hotspot in the diagnosis of hepatocellular carcinoma. This article briefly introduces the role of the conventional serological marker alpha-fetoprotein (AFP in assisting the diagnosis and predicting the prognosis of HBV-related liver cancer, as well as the clinical value of new markers such as alpha-fetoprotein-L3 and abnormal prothrombin/des-γ-carboxy prothrombin. Based on literature review, the possibility of serum Golgi protein 73 used for laboratory auxiliary diagnosis of hepatocellular carcinoma has been denied. The results of the author′s experiment suggest that serum GP73 measurement can be used as a laboratory diagnostic index for progressive liver fibrosis and liver cirrhosis.

  7. [Expression and clinical significance of KIAA1199 in primary hepatocellular carcinoma].

    Science.gov (United States)

    Gu, C J; Ni, Q C; Ni, K; Zhang, S; Qian, H X

    2018-05-29

    Objective: To investigate the expression and clinical significance of KIAA1199 in primary hepatocellular carcinoma. Methods: A total of 136 cases of primary hepatocellular carcinoma tissues and paired adjacent tissues were collected. Immunohistochemistry and Western blot were used to detect the expression of KIAA1199 in primary hepatocellular carcinoma tissues and paired adjacent tissues. The relationship between KIAA1199 and clinicopathological parameter of primary hepatocellular carcinoma was analyzed. Results: The positive rate of KIAA1199 in primary hepatocellular carcinoma was 82.3% (112/136), which was higher than that in paired para-cancerous tissues (14.7%, 20/136). High expression of KIAA1199 was significantly correlated with age, cirrhosis history, tumor size, tumor number, degree of differentiation, TNM staging and microvenous invasion (MVI) ( P 0.05). The Kaplan-Meier survival curves indicated that high KIAA1199 expression was associated with poor survival ( P hepatocellular carcinoma, which is significantly correlated with the clinicopathological features and prognosis, high expression of KIAA1199 increased the risk of death in patients with primary hepatocellular carcinoma.

  8. Nonalcoholic fatty liver disease and hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    LI Liangping

    2016-03-01

    Full Text Available As the etiology of hepatocellular carcinoma (HCC has been changing, the incidence of HCC related to nonalcoholic fatty liver disease (NAFLD is gradually increasing in developed countries in Europe and America and some countries in Asia. This article introduces the close association between NAFLD and HCC, risk factors, clinicopathological features, and prevention and screening, and points out that although the incidence of NAFLD is not as high as that of hepatitis B- or hepatitis C-related HCC, there are a large absolute number of NAFLD patients, especially the high-risk patients with diabetes and obesity, or liver fibrosis/cirrhosis, due to a huge base number of NAFLD patients. NAFLD-related HCC is commonly seen in the elderly with various comorbidities and a poor prognosis. This article also points out that the prevention should focus on the effective treatment of NAFLD. The strict screening of high-risk population is the strategy for the diagnosis of early-stage HCC. At present, the sensitivity of alpha-fetoprotein is relatively low, and imaging examinations including computed tomography are the main screening methods; however, there are no measures for early warning of NAFLD-related HCC.

  9. Current radiologic interventions in hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Masoud, I.; Naeem, M.Q.T.; Saeed, F.; Mirza, S.A.M.; Khan, A.; Bhatti, M.A.

    2006-01-01

    With the rising incidence of chronic liver disease caused by viral hepatitis, hepatocellular carcinoma is showing a corresponding rise worldwide. Surgery remains the mainstay of treatment, but patients unfit for surgery or liver transplantation form the bulk of those presenting with this disease. Palliative treatments are being used to treat those and radiological modalities form the mainstay of the treatment. Radiology plays a major role in the diagnosis, treatment and follow-up of hepatocellular carcinoma. Current radiological treatment modalities include percutaneous ethanol ablation, radiofrequency ablation and trans-arterial chemoembolization. This update highlights the recent advancements in the field and compares their relative merits and demerits. (author)

  10. Surgical Treatment of Hepatocellular Carcinoma

    Science.gov (United States)

    Zamora-Valdes, Daniel; Taner, Timucin; Nagorney, David M.

    2017-01-01

    Hepatocellular carcinoma (HCC) is a major cause of cancer-related death worldwide. In select patients, surgical treatment in the form of either resection or transplantation offers a curative option. The aims of this review are to (1) review the current American Association for the Study of Liver Diseases/European Association for the Study of the Liver guidelines on the surgical management of HCC and (2) review the proposed changes to these guidelines and analyze the strength of evidence underlying these proposals. Three authors identified the most relevant publications in the literature on liver resection and transplantation for HCC and analyzed the strength of evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) classification. In the United States, the liver allocation system provides priority for liver transplantation to patients with HCC within the Milan criteria. Current evidence suggests that liver transplantation may also be indicated in certain patient groups beyond Milan criteria, such as pediatric patients with large tumor burden or adult patients who are successfully downstaged. Patients with no underlying liver disease may also benefit from liver transplantation if the HCC is unresectable. In patients with no or minimal (compensated) liver disease and solitary HCC ≥2 cm, liver resection is warranted. If liver transplantation is not available or contraindicated, liver resection can be offered to patients with multinodular HCC, provided that the underlying liver disease is not decompensated. Many patients may benefit from surgical strategies adapted to local resources and policies (hepatitis B prevalence, organ availability, etc). Although current low-quality evidence shows better overall survival with aggressive surgical strategies, this approach is limited to select patients. Larger and well-designed prospective studies are needed to better define the benefits and limits of such approach. PMID:28975836

  11. New advances in hepatocellular carcinoma

    Science.gov (United States)

    Pascual, Sonia; Herrera, Iván; Irurzun, Javier

    2016-01-01

    Hepatocellular carcinoma (HCC) is the leading cause of deaths in cirrhotic patients and the third cause of cancer related deaths. Most HCC are associated with well known underlying risk factors, in fact, HCC arise in cirrhotic patients in up to 90% of cases, mainly due to chronic viral hepatitis and alcohol abuse. The worldwide prevention strategies are conducted to avoid the infection of new subjects and to minimize the risk of liver disease progression in infected patients. HCC is a condition which lends itself to surveillance as at-risk individuals can readily be identified. The American and European guidelines recommended implementation of surveillance programs with ultrasound every six months in patient at-risk for developing HCC. The diagnosis of HCC can be based on non-invasive criteria (only in cirrhotic patient) or pathology. Accurately staging patients is essential to oncology practice. The ideal tumour staging system in HCC needs to account for both tumour characteristics and liver function. Treatment allocation is based on several factors: Liver function, size and number of tumours, macrovascular invasion or extrahepatic spread. The recommendations in terms of selection for different treatment strategies must be based on evidence-based data. Resection, liver transplant and interventional radiology treatment are mainstays of HCC therapy and achieve the best outcomes in well-selected candidates. Chemoembolization is the most widely used treatment for unresectable HCC or progression after curative treatment. Finally, in patients with advanced HCC with preserved liver function, sorafenib is the only approved systemic drug that has demonstrated a survival benefit and is the standard of care in this group of patients. PMID:27028578

  12. Hepatocellular carcinoma: a clinico pathological study

    International Nuclear Information System (INIS)

    Abbasi, A.; Butt, N.; Bhutto, A.R.; Gulzar, K.; Munir, S.M.

    2010-01-01

    To describe the clinico-pathological and radiological profile of hepatocellular carcinoma. All consecutive patients suspected of having hepatocellular carcinoma (HCC), were admitted and included in this study. Diagnosis of HCC was established by clinical, biochemical, ultrasonographic and histopathologic findings. Patients with primary carcinoma elsewhere in the body, metastatic in the liver, fibrolamellar carcinoma and benign tumours were excluded from the study. At ultrasonography, the details of tumour size and number, portal vein thrombosis and presence of ascites were recorded. Patients were staged according to Okuda staging system. Results were described in mean and percentage values. There were 82 patients with hepatocellular carcinoma including 58 males and 24 females, with male to female ratio of 2.8:1. The mean age of patients was 56.24 +- 13.65 years. Right hypochondrial pain was the main symptom in 52 (63.4%) patients. The duration of symptoms varied from 1 month to 2 years. Tumour size was larger than 50% of liver size in 42 (51.2%) with portal vein thrombosis in 10 (12.19%). Anti HCV was positive in 44 (53.7%), HBsAg in 26 (31.7%) and both were found positive in 2 (2.44%) patients. Ten patients (12.2/%) found negative both for anti-HCV and HBsAg. According to Okuda staging system 18 patients had stage 1, 50 had stage 2 and 14 had stage 3 hepatocellular carcinoma. The mean age of presentation of hepatocellular carcinoma was younger as compared to western countries with potentially large non-resectable lesions. Chronic hepatitis C and B was found to be the major known factors. Patients with chronic hepatitis C and B should undergo vigorous HCC surveillance to detect early, potentially respectable HCC. (author)

  13. Hyperkalaemia after radiofrequency ablation of hepatocellular carcinoma

    NARCIS (Netherlands)

    Verhoevena, BH; Haagsma, EB; Appeltans, BMG; Slooff, MJH; de Jong, KP

    Radiofrequency ablation of liver tumours is a useful therapy for otherwise unresectable tumours. The complication rate is said to be low. In this case report we describe hyperkalaemia after radiofrequency ablation of a hepatocellular carcinoma in a patient with end-stage renal insufficiency. (C)

  14. Radioembolisation for treatment of pediatric hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Hawkins, Clifford Matthew; Kukreja, Kamlesh [Cincinnati Children' s Hospital Medical Center, Department of Radiology, Cincinnati, OH (United States); Geller, James I. [Cincinnati Children' s Hospital Medical Center, Department of Hematology/Oncology, Cincinnati, OH (United States); Schatzman, Carmen; Ristagno, Ross [University of Cincinnati, UC Health, Department of Radiology, Division of Interventional Radiology, Cincinnati, OH (United States)

    2013-07-15

    Transarterial radioembolisation with yttrium-90 (TARE-Y90), a catheter-directed therapy, has been used extensively in adults to treat primary and secondary hepatic malignancies. To our knowledge, the use of this palliative technique has not been described in children. We present two children with unresectable hepatocellular carcinoma (HCC) treated with TARE-Y90. (orig.)

  15. Small hepatocellular carcinoma versus small cavernous hemangioma

    International Nuclear Information System (INIS)

    Choi, B.I.; Park, H.W.; Kim, S.H.; Han, M.C.; Kim, C.W.

    1989-01-01

    To determine the optimal pulse sequence for detection and differential diagnosis of small hepatocellular carcinomas and cavernous hemangiomas less than 5 cm in diameter, the authors have analyzed spin-echo (SE) images of 15 small hepatocellular carcinomas and 31 small cavernous hemangiomas obtained at 2.0 T. Pulse sequences used included repetition times (TRs) of 500 and 2,000 msec and echo times (TEs) of 30,60,90,120,150, and 180 msec. Mean tumor-liver contrast-to-noise ratios on the SE 2,000/60 (TR msec/TE msec) sequence were 23.90 ± 16.33 and 62.10 ± 25.94 for small hepatocellular carcinomas and hemangiomas, respectively, and were significantly greater than for all other pulse sequences. Mean tumor-liver signal intensity ratios on the SE 2,000/150 sequence were 2.34 ± 1.72 and 6.04 ± 2.72 for small hepatocellular carcinomas and hemangiomas, respectively, and were significantly greater than for all other pulse sequences in hemangiomas

  16. Liver transplantation in patients with hepatocellular carcinoma

    NARCIS (Netherlands)

    Polak, Wojciech G.; Soyama, Akihiko; Slooff, Maarten J. H.

    2008-01-01

    Liver transplantation has a definitive place in the treatment of patients with hepatocellular carcinoma (HCC) in a cirrhotic liver. Patients with a tumor load within the Milan criteria have excellent survival comparable to survival in patients with benign indications. When tumor load exceeds the

  17. Hepatocellular carcinoma: risk groups, surveillance and outcome

    NARCIS (Netherlands)

    van Meer, S

    2016-01-01

    The burden of hepatocellular carcinoma (HCC) has changed in the past few decades. Although the majority of HCC cases develops in East Asia and Sub-Saharan Africa, HCC has become an increasing problem in Western countries such as the Netherlands. Surveillance for HCC is controversial because of

  18. Fibrolamellar hepatocellular carcinoma with ovarian metastasis - an unusual presentation.

    Science.gov (United States)

    Ciurea, Silviu Horia; Matei, Emil; Stănescu, CodruŢ Silvian; Lupescu, Ioana Gabriela; Boroş, Mirela; Herlea, Vlad; Luca, Niculina Ioana; DorobanŢu, Bogdan Mihail

    2017-01-01

    Fibrolamellar carcinoma (FLC) has been considered a distinct clinical entity vs. hepatocellular carcinoma, with respect to its epidemiology, etiology, and prognosis. We describe the unusual case of a 23-year-old female patient with FLC and ovarian (Krukenberg) and peritoneal metastases, clinically mimicking an ovarian carcinoma. Multiple recurrences occurred despite initial R0 resection and chemotherapy, requiring surgical treatment. The patient survived five years and died from generalized disease. The particularities of our case are discussed by comparison with the other two similar cases and other date from the literature. To our knowledge, the ovarian involvement encountered in our case is the third case published in literature, being explained by the superficial location of the liver tumor.

  19. Can non-selective beta-blockers prevent hepatocellular carcinoma in patients with cirrhosis?

    DEFF Research Database (Denmark)

    Thiele, Maja; Wiest, Reiner; Gluud, Lise Lotte

    2013-01-01

    Hepatocellular carcinoma is the main liver-related cause of death in patients with compensated cirrhosis. The early phases are asymptomatic and the prognosis is poor, which makes prevention essential. We propose that non-selective beta-blockers decrease the incidence and growth of hepatocellular...... and growth of hepatocellular carcinoma. Rodent and in vitro studies support the hypothesis, but clinical verification is needed. Different study designs may be considered. The feasibility of a randomized controlled trial is limited due to the necessary large number of patients and long follow......-up. Observational studies carry a high risk of bias. The meta-analytic approach may be used if the incidence and mortality of hepatocellular carcinoma can be extracted from trials on variceal bleeding and if the combined sample size and follow up is sufficient....

  20. File list: Unc.Liv.05.AllAg.Carcinoma,_Hepatocellular [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Unc.Liv.05.AllAg.Carcinoma,_Hepatocellular mm9 Unclassified Liver Carcinoma, Hepato...cellular http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Unc.Liv.05.AllAg.Carcinoma,_Hepatocellular.bed ...

  1. File list: His.Liv.10.AllAg.Carcinoma,_Hepatocellular [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available His.Liv.10.AllAg.Carcinoma,_Hepatocellular mm9 Histone Liver Carcinoma, Hepatocellu...lar http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/His.Liv.10.AllAg.Carcinoma,_Hepatocellular.bed ...

  2. Macrophage activation marker soluble CD163 may predict disease progression in hepatocellular carcinoma

    DEFF Research Database (Denmark)

    Kazankov, Konstantin; Rode, Anthony; Simonsen, Kira Schreiner

    2016-01-01

    BACKGROUND: Tumor associated macrophages are present in hepatocellular carcinoma (HCC) and associated with a poor prognosis. The aim of the present study was to investigate the levels and dynamics of soluble (s)CD163, a specific macrophage activation marker, in patients with HCC. METHODS: In a co...

  3. A phase II study of the vitamin D analogue Seocalcitol in patients with inoperable hepatocellular carcinoma

    DEFF Research Database (Denmark)

    Dalhoff, K; Dancey, J; Astrup, L

    2003-01-01

    Hepatocellular carcinoma (HCC) is a common malignant tumour, which has a poor prognosis. Surgical resection can be curative but most patients are inoperable and most chemotherapy agents have minimal activity in this disease. Seocalcitol, a vitamin D analogue, induces differentiation and inhibits...

  4. Peritoneal carcinomatosis: an unusual presentation of fibrolamellar hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Vicente, R.; Garcia-Gutierrez, J. A.; Fernandez, A.; Santalla, F.

    2001-01-01

    Fibrolamellar hepatocellular carcinoma is an uncommon malignant tumor with characteristic clinical, radiological and histopathological features that is usually associated with a more favorable natural course and greater survival than more common variants of hepatocellular carcinoma. We describe an atypical case of a fibrolamellar hepatocellular carcinomas sowing aggressive behaviour in a 20-year-old woman. The lesion presented with massive ascites, and imaging studies revealed extensive peritoneal metastatic spread. (Author) 8 refs

  5. [Care pathway of patients with hepatocellular carcinoma in France: State of play in 2017].

    Science.gov (United States)

    Costentin, Charlotte; Ganne-Carrié, Nathalie; Rousseau, Benoit; Gérolami, René; Barbare, Jean-Claude

    2017-09-01

    Hepatocellular carcinoma is a major public health problem with one of the highest overall mortality compared to other cancers. The median overall survival in France in a hospital population with hepatocellular carcinoma is 9.4 months. Several publications reported a positive impact of hepatocellular carcinoma screening on diagnosis at an early-stage, eligibility for curative treatment and overall survival. However, the identification of patients to be included in a hepatocellular carcinoma screening program and the application of screening recommendations are not optimal. Other studies suggest a potentially negative impact of delayed diagnosis or treatment initiation on the patient's prognosis. Finally, marked variations between French regions and departments have been described in terms of access to curative treatment and overall survival. In this review article, we propose a state of play of the hepatocellular carcinoma patient's care pathway in France with the aim of identifying potential breaking points with negative impact on prognosis and of developing proposals for improvement. Copyright © 2017 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

  6. Research progress of vascular change after TACE in hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Kang Zhen; Xiao Enhua

    2013-01-01

    Mortality rate of hepatocellular carcinoma is high. The majority of the patients are diagnosed in advanced stage and lose surgical opportunities. Many studies have reported transcatheter arterial chemoembolization (TACE) is an effective treatment for unresectable hepatocellular carcinoma, and recommended TACE as a standard treatment for hepatocellular carcinoma of Barcelona Clinical Liver Cancer staging (BCLC staging) B. However, TACE can hardly fully embolize tumor blood supply, TACE postoperative hemodynamics and angiogenesis can induce tumor recurrence and metastasis. This paper reviewed characteristics of vascular changes, mechanisms, diagnosis and treatment methods, new progress in the field of hepatocellular carcinoma after TACE. (authors)

  7. Computed tomography diagnosis of hepatocellular carcinoma rupture haemorrhage

    International Nuclear Information System (INIS)

    Zhi Weike; Jiang Bin; Liu Jinquan; Li Sixia; Zhu Zhichang

    2004-01-01

    Objective: To evaluate the diagnostic value of hepatocellular carcinoma rupture hemorrhage using Computed Tomography. Methods: Six cases diagnosed hepatocellular carcinoma rupture hemorrhage were analyzed by morphic and histologic method and investigated the key point of scan in diagnosis. Result: The correct rate of hepatocellular carcinoma rupture hemorrhage by Computed Tomography is above 83 percent, it characteristic representation is strip and would high-density shadow after enhancement. Conclusion: The characteristic representation of hepatocellular carcinoma rupture hemorrhage is attain by Computed Tomography, which provides effective operation evidences for clinical operation. (authors)

  8. Radio-embolization for hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Raoul, J.L.; Edeline, J.; Pracht, M.; Boucher, E.; Rolland, Y.; Garin, E.

    2011-01-01

    Hepatocellular carcinoma is now a major public health concern. In intermediate stages (one third of hepatocellular carcinoma patients), chemo-embolization is the standard of care despite a poor tolerance and a moderate efficacy. Moreover, despite recent improvements, this technique seems in a dead end. Radio-embolization could be an excellent tool for such patients. Currently 131 I-Lipiodol, 188 Re-Lipiodol, 90 Y-glass or resin microspheres are available. More recent and promising data come from microspheres, but phase II and III studies are needed before drawing any conclusion. In the future, the combination of radio-embolization with systemic chemotherapy or targeted agents (particularly anti-angiogenic drugs) seems very promising. (authors)

  9. Clinical significance of CMTM4 expression in hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Bei CH

    2017-11-01

    Full Text Available Chunhua Bei,1,* Ying Zhang,1,* Riming Wei,1 Xiaonian Zhu,1 Zhigang Wang,1 Wen Zeng,2 Qiuyue Chen,3 Shengkui Tan1 1Department of Epidemiology and Statistics, School of Public Health, Guilin Medical University, 2Department of Hepatobiliary Surgery, The Affiliated Hospital of Guilin Medical University, 3Department of Pathology, 181st Hospital of Chinese People’s Liberation Army, Guilin, People’s Republic of China *These authors contributed equally to this work Abstract: CMTM4 is the most conserved member of chemokine-like factor (CKLF-like MARVEL transmembrane domain-containing (CMTM family on chromosome 16q22.1, a locus that harbors a number of tumor-suppressor genes. In previous studies, CMTM4 was reported to be downregulated and exhibited tumor-suppressor activities by regulating cell growth and cell cycle in clear cell renal cell carcinoma. However, its roles in tumorigenesis of hepatocellular carcinoma (HCC remain poorly studied. This study first investigated the expression of CMTM4 in HCC, and then examined the association between the expression of CMTM4 with the clinicopathological features and prognosis of HCC patients. It was found that CMTM4 was downregulated in HCC tissues, compared with matched adjacent nontumor tissues, as detected by immunohistochemistry. In addition, Kaplan–Meier survival analysis showed that the negative expression of CMTM4 was associated with decreased overall survival rates in patients with HCC. The results of this study suggest CMTM4 plays a role as a tumor suppressor in HCC and CMTM4 negative expression is a risk factor for poor prognosis of HCC. Keywords: chemokine-like factor-like MARVEL transmembrane domain-containing 4, hepatocellular carcinoma, immunohistochemistry, prognosis

  10. Serum immunoreactive calcitonin concentration in hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Dugard, J; Kew, M C; Da Fonseca, M; Levin, J [University of the Witwatersrand, Johannesburg (South Africa)

    1982-08-21

    Having found raised serum calcitonin concentrations in 94% of patients with hepatocellular carcinoma when using a dextran-coated-charcoal radio-immunoassay, we have now repeated the study, using a double-antibody radio-immunoassay, in 102 further patients with hepatocellular carcinoma and 35 matched controls. Serum immunoreactive calcitonin concentrations (iCT) in the controls ranged from 10 to 310 pg/ml (mean 154,6 pg/ml). Values in the tumour patients ranged from 10 to 1,650 pg/ml (mean 302,6 pg/ml). The mean figures were significantly higher in the tumour patients (P smaller than 0,001), 35.5% of them having values above 310 pg/ml. In 65 of the patients serum iCT concentrations were also determined by dextran-coated-charcoal radio-immunoassay. Values ranged from 10 to 10780 pg/ml (mean 2,179 pg/ml). If 1,000 pg/ml is taken as the upper limit of normal, 69% of the patients had raised iCT concentrations. There was a good correlation (r=0,67; P smaller than 0,001) between serum iCT values measured with both methods in 50 patients. If measured by the double-antibody radio-immunoassay method, the serum calcitonin value is not useful as a marker for hepatocellular carcinoma.

  11. Serum immunoreactive calcitonin concentration in hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Dugard, J.; Kew, M.C.; Da Fonseca, M.; Levin, J.

    1982-01-01

    Having found raised serum calcitonin concentrations is 94% of patients with hepatocellular carcinoma when using a dextran-coated-charcoal radio-immunoassay, we have now repeated the study, using a double-antibody radio-immunoassay, in 102 further patients with hepatocellular carcinoma and 35 matched controls. Serum immunoreactive calcitonin concentrations (iCT) in the controls ranged from 10 to 310 pg/ml (mean 154,6 pg/ml). Values in the tumour patients ranged from 10 to 1 650 pg/ml (mean 302,6 pg/ml). The mean figures were significantly higher in the tumour patients (P smaller than 0,001), 35,5% of them having values above 310 pg/ml. In 65 of the patients serum iCT concentrations were also determined by dextran-coated-charcoal radio-immunoassay. Values ranged from 10 to 10780 pg/ml (mean 2 179 pg/ml). If 1 000 pg/ml is taken as the upper limit of normal, 69% of the patients had raised iCT concentrations. There was a good correlation (r=0,67; P smaller than 0,001) between serum iCT values measured with both methods in 50 patients. If measured by the double-antibody radio-immunoassay method, the serum calcitonin value is not useful as a marker for hepatocellular carcinoma

  12. Prognosis of patients with hepatocellular carcinoma. Validation and ranking of established staging-systems in a large western HCC-cohort.

    Directory of Open Access Journals (Sweden)

    Mark op den Winkel

    Full Text Available HCC is diagnosed in approximately half a million people per year, worldwide. Staging is a more complex issue than in most other cancer entities and, mainly due to unique geographic characteristics of the disease, no universally accepted staging system exists to date. Focusing on survival rates we analyzed demographic, etiological, clinical, laboratory and tumor characteristics of HCC-patients in our institution and applied the common staging systems. Furthermore we aimed at identifying the most suitable of the current staging systems for predicting survival.Overall, 405 patients with HCC were identified from an electronic medical record database. The following seven staging systems were applied and ranked according to their ability to predict survival by using the Akaike information criterion (AIC and the concordance-index (c-index: BCLC, CLIP, GETCH, JIS, Okuda, TNM and Child-Pugh. Separately, every single variable of each staging system was tested for prognostic meaning in uni- and multivariate analysis. Alcoholic cirrhosis (44.4% was the leading etiological factor followed by viral hepatitis C (18.8%. Median survival was 18.1 months (95%-CI: 15.2-22.2. Ascites, bilirubin, alkaline phosphatase, AFP, number of tumor nodes and the BCLC tumor extension remained independent prognostic factors in multivariate analysis. Overall, all of the tested staging systems showed a reasonable discriminatory ability. CLIP (closely followed by JIS was the top-ranked score in terms of prognostic capability with the best values of the AIC and c-index (AIC 2286, c-index 0.71, surpassing other established staging systems like BCLC (AIC 2343, c-index 0.66. The unidimensional scores TNM (AIC 2342, c-index 0.64 and Child-Pugh (AIC 2369, c-index 0.63 performed in an inferior fashion.Compared with six other staging systems, the CLIP-score was identified as the most suitable staging system for predicting prognosis in a large German cohort of predominantly non-surgical HCC-patients.

  13. Dysfunctional activation of neurotensin/IL-8 pathway in hepatocellular carcinoma is associated with increased inflammatory response in microenvironment, more epithelial mesenchymal transition in cancer and worse prognosis in patients.

    Directory of Open Access Journals (Sweden)

    Jinpu Yu

    Full Text Available AIM: To investigate the role of neurotensin (NTS in hepatocellular carcinoma (HCC sub- grouping and the clinical and pathological significance of activation of NTS/IL-8 pathway in HCC. METHODS: The genome-wide gene expression profiling were conducted in 10 pairs of cancer tissues and corresponding normal adjacent tissues samples using Affymetrix GeneChip® Human Genome U133 Plus 2.0 microarray to screen differentially expressing genes and enrich dysfunctional activated pathways among different HCC subgroups. The levels of NTS protein and multiple inflammation and epithelial mesenchymal transition (EMT related proteins, including IL-8, VEGF, MMP9, CD68, E-Cadherin, β-Catenin and Vimentin were examined in 64 cases of paraffin-embedded HCC samples using immunohistochemistry (IHC staining method. The clinical outcome and overall survival (OS were compared. RESULTS: A subgroup of HCC characterized by up-regulated NTS expression was accompanied by up-regulated inflammatory responses and EMT. The direct interaction between NTS and IL-8 was identified by pathway enrichment analysis. Significantly increased IL-8 protein was confirmed in 90.91% of NTS(+ HCC samples and significantly positively correlated to the levels of NTS protein in cancer tissues (P = 0.036, which implied activation of NTS/IL-8 pathway in HCC. The levels of VEGF and MMP9 correlated with co-expression of NTS and IL-8. Increased infiltration of CD68(+ macrophages and more cancer cells displaying EMT features were found in NTS(+IL-8(+ samples. The co-expression of NTS and IL-8 in cancer significantly correlated with the clinical outcomes, as the mortality rate of NTS(+IL-8(+ HCC patients is 2.5-fold higher than the others after the surgery (P = 0.022. Accordingly, the OS of NTS(+IL-8(+ HCC patients significantly decreased who are under a higher hazard of death at an expected hazard ratio (HR of 3.457. CONCLUSION: Dysfunctional activation of the NTS/IL-8 pathway was detected in

  14. Transarterial (chemo)embolisation for unresectable hepatocellular carcinoma

    DEFF Research Database (Denmark)

    Oliveri, Roberto S; Wetterslev, Jørn; Gluud, Christian

    2011-01-01

    Hepatocellular carcinoma (HCC) results in more than 600,000 deaths per year. Transarterial embolisation (TAE) and transarterial chemoembolisation (TACE) have become standard loco-regional treatments for unresectable HCC.......Hepatocellular carcinoma (HCC) results in more than 600,000 deaths per year. Transarterial embolisation (TAE) and transarterial chemoembolisation (TACE) have become standard loco-regional treatments for unresectable HCC....

  15. Selective angiography in fifty patients with primary hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Shou-Zhong, Wang; Xing-Rong, Chen; Gong-Xian, Wang

    1983-06-01

    Selective angiography is of great importance in the diagnosis of primary hepatocellular carcinoma. It offers information on the findings, multicentricity, localisation, extension, and type of growth. This paper discusses angiography from the methodical point of view, the findings to be obtained, the types of hepatocellular carcinoma, and the diagnostic efficiency of selective angiography in the evaluation of this type of tumour.

  16. Orbital Metastasis of Hepatocellular Carcinoma: A Case Report ...

    African Journals Online (AJOL)

    Background: Hepatocellular carcinoma is one of the commonest malignancies in Nigeria, however metastasis to the orbit is a rare presentation. Objective: To present a rare case of orbital metastasis of hepatocellular carcinoma. Case Report: A 25-year-old man presented with a 3-month history of pain, progressive swelling ...

  17. Fibrolamellar Hepatocellular Carcinoma Presenting as Obstructive Jaundice: Uncommon Presentation of a Rare Entity

    International Nuclear Information System (INIS)

    Arora, Richa

    2015-01-01

    Fibrolamellar hepatocellular carcinoma is a rare primary malignant liver tumor, significantly different from generic hepatocellular carcinoma with distinct demographics, risk factors, imaging features, histopathology and prognosis. Unlike conventional hepatocellular carcinoma, it presents in young individuals with no preexisting hepatitis or cirrhosis and does not cause elevation of serum alpha feto proteins in most cases. This paper presents a case report of this rare tumor in a young female with an unusual clinical manifestation of obstructive jaundice (which has not been reported so far) along with a review of its imaging and pathological features, with treatment options. Fibrolamellar HCC is a rare variant of classic HCC with different epidemiology, risk factors, clinical manifestations, radiological, pathological and prognostic features. Therefore, it is important to be familiar with the entity for its early diagnosis and management

  18. Metastases of Hepatocellular Carcinoma Misdiagnosed as Isolated Hypertrophic Cardiomyopathy.

    Science.gov (United States)

    Greco, Assunta; De Masi, Roberto; Orlando, Stefania; Metrangolo, Antonio; Zecca, Vittorio; Morciano, Giancarlo; De Donno, Antonella; Bagordo, Francesco; Piccinni, Giancarlo

    At present, cardiac metastasis of hepatocellular carcinoma is rarely mentioned in the literature. We report a hepatocellular carcinoma patient with cardiac metastasis misdiagnosed as hypertrophic cardiomyopathy in 2011. Two years later, on presentation of syncope, an abnormal ventricular septal size was recorded by ultrasound scan, and was subsequently shown by magnetic resonance imaging to be a tumour lesion. A myocardial biopsy confirmed infiltration of hepatocellular carcinoma. This observation underlines the risk of hepatocellular carcinoma cardiac metastasis, manifested in its infiltrative form as hypertrophic cardiomyopathy. In conclusion, we suggest that the ultrasound appearance of hypertrophic cardiomyopathy in hepatocellular carcinoma patients should be seen as a "red flag" and recommend the introduction of magnetic resonance imaging assessment of transplant candidates.

  19. CT diagnosis of rare histological variant of hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Li Huaibo; Feng Zhipeng; Duan Shaoyin; Zhaugn Xiangrong

    2009-01-01

    Objective: To explore and understand the CT findings of 5 rare histological variants of hepatocellular carcinoma. Methods: CT findings of 31 cases of rare histological variants confirmed by surgery and pathology were analyzed retrospectively. Results: 13 cases were clear cell hepatocellular carcinoma. 3 cases of them showed patchy fat density in plain scans. Enhanced CT showed features of 'fast in fast out' which was similar to the common hepatocellular carcinoma. 4 cases belonged to sclerosis hepatocellular carcinoma. They appeared as heterogeneous, slowly enhancement on arterial phase images, and delay enhancement on portal venous phase and delay phase images. 9 cases belonged to mixed hepatocellular carcinoma. 5 cases of them showed inhomogeneous enhancement and 4 without enhancement during arterial phase, 3 cases showed delay enhancement and 4 without during portal venous and delay phase. 3 cases were fibrolamellar hepatocellular carcinoma. All showed obvious and fastly enhancement on arterial phase images, subsided slowly on the portal venous and delay phase images, showing features of 'fast in slow out', no enhancement was seen in the central scar. Shrinkage phenomenon on the surface of liver could be seen on the CT plain scans in sclerosis, mixed and fibrolamellar hepatocellular carcinoma. 2 cases were the type of dense hepatocellular carcinoma. The surrounding part in the 2 cases were slightly enhanced, while the most part of the center were not enhanced similar to necrosis. Conclusion: The CT findings of rate histological variant of hepatocellular carcinoma are characteristic. Analyzing the CT plain and enhancement finding is helpful to the diagnosis of these types of hepatocellular carcinoma. (authors)

  20. Spontaneous regression of a large hepatocellular carcinoma: case report

    Directory of Open Access Journals (Sweden)

    Alqutub, Adel

    2011-01-01

    Full Text Available The prognosis of untreated advanced hepatocellular carcinoma (HCC is grim with a median survival of less than 6 months. Spontaneous regression of HCC has been defined as the disappearance of the hepatic lesions in the absence of any specific therapy. The spontaneous regression of a very large HCC is very rare and limited data is available in the English literature. We describe spontaneous regression of hepatocellular carcinoma in a 65-year-old male who presented to our clinic with vague abdominal pain and weight loss of two months duration. He was found to have multiple hepatic lesions with elevation of serum alpha-fetoprotein (AFP level to 6,500 µg/L (normal <20 µg/L. Computed tomography revealed advanced HCC replacing almost 80% of the right hepatic lobe. Without any intervention the patient showed gradual improvement over a period of few months. Follow-up CT scan revealed disappearance of hepatic lesions with progressive decline of AFP levels to normal. Various mechanisms have been postulated to explain this rare phenomenon, but the exact mechanism remains a mystery.

  1. Hepatocellular carcinoma: treatment with transcatheter arterial chemoembolization

    International Nuclear Information System (INIS)

    Acunas, Buelent; Rozanes, Izzet

    1999-01-01

    This article presents a review of the literature regarding the use of transcatheter arterial chemoembolization (TACE) in the treatment of hepatocellular carcinoma (HCC). There have been two different approaches to the treatment: (a) percutaneous tumor ablation methods which can be divided into injectable and thermal methods; percutaneous ethanol injection (PEI) is the most widely used method, and (b) TACE. PEI is the treatment of choice for single HCCs smaller or equal to 3 cm in size. For patients with large HCCs combined TACE and PEI is probably the most effective nonsurgical treatment. In the presence of multiple HCC nodules, TACE remains the treatment of choice

  2. Hepatitis C Virus and Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Masao Omata

    2013-01-01

    Full Text Available Hepatitis C virus (HCV, a hepatotropic virus, is a single stranded-positive RNA virus of ~9,600 nt. length belonging to the Flaviviridae family. HCV infection causes acute hepatitis, chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC. It has been reported that HCV-coding proteins interact with host-cell factors that are involved in cell cycle regulation, transcriptional regulation, cell proliferation and apoptosis. Severe inflammation and advanced liver fibrosis in the liver background are also associated with the incidence of HCV-related HCC. In this review, we discuss the mechanism of hepatocarcinogenesis in HCV-related liver diseases.

  3. Hepatocellular carcinoma directly invading the duodenum

    International Nuclear Information System (INIS)

    Mohamed, Abdelrehman O.; Joshi, Sandhya; Czechowski, Janusz; Branicki, Frank

    2005-01-01

    Recurrent gastrointestinal bleeding from hepatocellular carcinoma (HCC) invading the duodenum is very rare. We present a case of 50-year-old male who was admitted with a history of recurrent upper gastrointestinal tract (UGIT) bleeding, weight loss and anemia. The patient was known to have a chronic hepatitis C. Endoscopic examination showed grade-2 non-bleeding esophageal varices, and a large ulcerated duodenal mass partially obstructing the duodenal bulb outlet and causing recurrent UGIT bleeding. Pathological evaluation of the mass revealed HCC. (author)

  4. A qualitative signature for early diagnosis of hepatocellular carcinoma based on relative expression orderings.

    Science.gov (United States)

    Ao, Lu; Zhang, Zimei; Guan, Qingzhou; Guo, Yating; Guo, You; Zhang, Jiahui; Lv, Xingwei; Huang, Haiyan; Zhang, Huarong; Wang, Xianlong; Guo, Zheng

    2018-04-23

    Currently, using biopsy specimens to confirm suspicious liver lesions of early hepatocellular carcinoma are not entirely reliable because of insufficient sampling amount and inaccurate sampling location. It is necessary to develop a signature to aid early hepatocellular carcinoma diagnosis using biopsy specimens even when the sampling location is inaccurate. Based on the within-sample relative expression orderings of gene pairs, we identified a simple qualitative signature to distinguish both hepatocellular carcinoma and adjacent non-tumour tissues from cirrhosis tissues of non-hepatocellular carcinoma patients. A signature consisting of 19 gene pairs was identified in the training data sets and validated in 2 large collections of samples from biopsy and surgical resection specimens. For biopsy specimens, 95.7% of 141 hepatocellular carcinoma tissues and all (100%) of 108 cirrhosis tissues of non-hepatocellular carcinoma patients were correctly classified. Especially, all (100%) of 60 hepatocellular carcinoma adjacent normal tissues and 77.5% of 80 hepatocellular carcinoma adjacent cirrhosis tissues were classified to hepatocellular carcinoma. For surgical resection specimens, 99.7% of 733 hepatocellular carcinoma specimens were correctly classified to hepatocellular carcinoma, while 96.1% of 254 hepatocellular carcinoma adjacent cirrhosis tissues and 95.9% of 538 hepatocellular carcinoma adjacent normal tissues were classified to hepatocellular carcinoma. In contrast, 17.0% of 47 cirrhosis from non-hepatocellular carcinoma patients waiting for liver transplantation were classified to hepatocellular carcinoma, indicating that some patients with long-lasting cirrhosis could have already gained hepatocellular carcinoma characteristics. The signature can distinguish both hepatocellular carcinoma tissues and tumour-adjacent tissues from cirrhosis tissues of non-hepatocellular carcinoma patients even using inaccurately sampled biopsy specimens, which can aid early

  5. Novel Investigations of Flavonoids as Chemopreventive Agents for Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Chen-Yi Liao

    2015-01-01

    Full Text Available We would like to highlight the application of natural products to hepatocellular carcinoma (HCC. We will focus on the natural products known as flavonoids, which target this disease at different stages of hepatocarcinogenesis. In spite of the use of chemotherapy and radiotherapy in treating HCC, patients with HCC still face poor prognosis because of the nature of multidrug resistance and toxicity derived from chemotherapy and radiotherapy. Flavonoids can be found in many vegetables, fruits, and herbal medicines that exert their different anticancer effects via different intracellular signaling pathways and serve as antioxidants. In this review, we will discuss seven common flavonoids that exert different biological effects against HCC via different pathways.

  6. Dysregulation of serum microRNA-574-3p and its clinical significance in hepatocellular carcinoma.

    Science.gov (United States)

    Shen, Xianjuan; Xue, Yajing; Cong, Hui; Wang, Xudong; Ju, Shaoqing

    2018-07-01

    Objectives To explore microRNA-574-3p expression in serum of patients with hepatocellular carcinoma and investigate correlations between serum microRNA-574-3p expression and the development and prognosis of hepatocellular carcinoma. Design and methods Serum samples were collected from 70 patients with primary hepatocellular carcinoma, 40 patients with cirrhosis and 45 healthy controls. Serum microRNA-574-3p expression levels were detected by real-time quantitative polymerase chain reaction. The linearity, specificity and reproducibility were evaluated. In addition, the diagnostic value of microRNA-574-3p and its correlations with clinicopathologic features were assessed. Results The relative expression of microRNA-574-3p in hepatocellular carcinoma patients, cirrhosis patients and healthy controls was 2.306 (1.801-3.130), 1.362 (0.994-1.665) and 1.263 (0.765-1.723), respectively, indicating that it was significantly higher in hepatocellular carcinoma patients than that in the other two groups ( U = 439.5, 514.5, both P hepatocellular carcinoma patients, the relative expression of microRNA-574-3p was significantly correlated with hepatitis B virus DNA concentration ( r = 0.348, P = 0.022). Compared with healthy control group, AUC ROC of serum microRNA-574-3p in hepatocellular carcinoma group was 0.837 with 95% CI: 0.763-0.910. Combining microRNA-574-3p, AFU and alpha-fetoprotein together, the sensitivity was highest compared with other markers alone or combined. Conclusions The relative expression of serum microRNA-574-3p in hepatocellular carcinoma patients was significantly higher than that in cirrhosis patients and healthy controls, and it may be an important biomarker in the auxiliary diagnosis of hepatocellular carcinoma.

  7. Radiological imagings of small hepatocellular carcinomas

    Energy Technology Data Exchange (ETDEWEB)

    Miyake, Hidetoshi; Hayashi, Kuniaki; Futagawa, Sakae; Matsunaga, Naofumi; Maeda, Tohru [Nagasaki Univ. (Japan). School of Medicine

    1984-08-01

    Forty three cases of small hepatocellular carcinoma (measuring less than 3 cm in diameter on imaging modalities) were detected during a period of four years and two months. There were two cases in which hepatoma measured 1 cm in diameter, twenty four cases between 1 and 2 cm, and seventeen cases between 2 and 3 cm. The relative role of each modality and AFP value in the detection of these tumors was evaluated. The detection rate of small hepatocellular carcinoma by liver scintigraphy, ultrasonography (US), computed tomography (CT) and angiography was 8%, 74%, 70% and 95%, respectively. The sensitivity of serum AFP value was 67% (either measuring more than 200ng/ml or showing a tendency of steady rising even if below the level of 200ng/ml). Most hepatomas less than 2 cm in size were hypoechoic on US, and those above 2 cm in size were hyperechoic with peripheral sonolucency (halo). Almost all cases were described as low density area on both plain and enhancement CT. Angiography was the best method for detecting small hepatomas. It may be recommended to perform angiography on every patient with liver cirrhosis at the time of diagnosis of this disease. Periodic examinations by AFP, US and CT should be done if the angiography was negative. Evaluation by US in every three months and by CT in every twelve months may be appropriate.

  8. Skeletal metastases from primary hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Kim, So Sun; Huh, Jin Do; Kim, Ho Joon; Chun, Byung Hee; Joh, Young Duk; Chang, Hee Kyung; Huh, Man Ha

    1988-01-01

    In order to detect and to evaluate the frequency, the distribution, and the radiological findings of skeletal metastases from hepatocellular carcinoma, the authors retrospectively analyzed radiographic, scintigraphic, and CT findings of 257 patients with hepatocellular carcinoma. The results were as follows: 1. Skeletal metastases were demonstrated in 21 patients (8.2%). 2. Frequent symptoms were pain, limitation of motion, paralysis, and mass. In nine of them the initial symptoms were due to skeletal metastases. 3. The common sites of metastases were spine (13 cases), ribs (8 cases), pelvis (8 cases) and femur (6 cases). Humerus, skull and sternum were also frequently involved. 4. Plain film findings were purely osteolytic in all cases and pathologic fractures were noted in 5 cases. 5. The lesions appear expansible in 7 cases, and 4 of them showed associated soft tissue masses on CT scans. 6. Bone scans were performed in 13 cases of them and showed increased radiotracer uptake in all. 7. Angiographic studies of 3 cases showed hypervascularity of the metastatic lesions as well as the primary hepatic tumor.

  9. Prognostic significance of XRCC4 expression in hepatocellular carcinoma

    Science.gov (United States)

    Huang, Xiao-Ying; Yao, Jin-Guang; Wang, Chao; Wei, Zhong-Hong; Ma, Yun; Wu, Xue-Min; Luo, Chun-Ying; Xia, Qiang; Long, Xi-Dai

    2017-01-01

    Background Our previous investigations have shown that the variants of X-ray repair complementing 4 (XRCC4) may be involved in hepatocellular carcinoma (hepatocarcinoma) tumorigenesis. This study aimed to investigate the possible prognostic significance of XRCC4 expression for hepatocarcinoma patients and possible value for the selection of transarterial chemoembolization (TACE) treatment. Materials and Methods We conducted a hospital-based retrospective analysis (including 421 hepatocarcinoma cases) to analyze the effects of XRCC4 on hepatocarcinoma prognosis and TACE. The levels of XRCC4 expression were tested using immunohistochemistry. The sensitivity of cancer cells to anti-cancer drug doxorubicin was evaluated using the half-maximal inhibitory concentration (IC50). Results XRCC4 expression was significantly correlated with pathological features including tumor stage, liver cirrhosis, and micro-vessel density. XRCC4 expression was an independent prognostic factor of hepatocarcinoma, and TACE treatments had no effects on prognosis of hepatocarcinoma patients with high XRCC4 expression. More intriguingly, TACE improved the prognosis of hepatocarcinoma patients with low XRCC4 expression. Functionally, XRCC4 overexpression increased while XRCC4 knockdown reduced the IC50 of cancer cells to doxorubicin. Conclusions These results suggest that XRCC4 may be an independent prognostic factor for hepatocarcinoma patients, and that decreasing XRCC4 expression may be beneficial for post-operative adjuvant TACE treatment in hepatocarcinoma. PMID:29152133

  10. Metastatic hepatocellular carcinoma on the mandible: a case report

    International Nuclear Information System (INIS)

    Kim, Jin Soo; Kim, Jae Duk

    2005-01-01

    Hepatocellular carcinoma is one of the most common cancer worldwide, primarily affecting those in regions with a high prevalence of viral hepatitis. However, the metastasis of hepatocellular carcinoma to the oral cavity is a rare phenomenon. This report presents a case of metastatic hepatocellular carcinoma in the left mandibular angle and ramus region of a 62-year-old man. Panoramic radiograph revealed an ill-defined radiolucent lesion extending from the retained root of the mandibular left second molar into the ascending ramus. The lesion had irregular and ill-defined margins.

  11. Clinical and laboratory features of hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Andrés Cárdenas

    2007-02-01

    Full Text Available

    The clinical presentation of hepatocellular carcinoma (HCC differs between patients in developing countries (African and Chinese populations from those in industrialized countries. In industrialized countries, HCC co-exists with symptomatic cirrhosis in 80% of cases and clinical manifestations are usually related to those of the underlying disease. On the other hand, patients from developing countries have HCC and cirrhosis in approximately 40% of cases. Underlying cirrhosis in many cases is not advanced and does not produce any symptoms or associated symptoms are masked by those of the tumor (right upper quadrant pain, mass in the upper abdomen, weight loss and weakness. In a subset of patients, there are no clinical manifestations as HCC may occur in the context of hepatitis B infection without cirrhosis.

    Clinical Manifestations

    In Western countries, nearly 35% percent of patients with HCC are asymptomatic. Some of the most common clinical manifestations include: abdominal pain (53-58% of patients, especially in epigastrium or right upper quadrant, abdominal mass (30%, weight loss, malaise, anorexia, cachexia, jaundice or fever.

    Physical Exam

    Physical findings vary with the stage of disease. The patient may exhibit slight or moderate wasting when first seen. In patients with cirrhosis, typical stigmata of chronic liver disease may be present. In advanced stages of HCC the liver may be enlarged and there is significant tenderness. An arterial bruit may be heard over the liver

  12. Effect of smoking on survival of patients with hepatocellular carcinoma.

    Science.gov (United States)

    Kolly, Philippe; Knöpfli, Marina; Dufour, Jean-François

    2017-11-01

    Lifestyle factors such as smoking, obesity and physical activity have gained interest in the field of hepatocellular carcinoma. These factors play a significant role in the development of hepatocellular carcinoma. Several studies revealed the impact of tobacco consumption on the development of hepatocellular carcinoma and its synergistic effects with viral etiologies (hepatitis B and C). The effects of smoking on survival in patients with a diagnosed hepatocellular carcinoma have not yet been investigated in a Western cohort where hepatitis C infection is a major risk factor. Using data from a prospective cohort of patients with hepatocellular carcinoma who were followed at the University Hospital of Bern, Switzerland, survival was compared by Kaplan-Meier analysis in smokers and nonsmokers, and multivariate Cox regression was applied to control for confounding variables. Of 238 eligible hepatocellular carcinoma patients, 64 were smokers at the time of inclusion and 174 were nonsmokers. Smokers had a significant worse overall survival than nonsmokers (hazard ratio 1.77, 95% confidence interval: 1.22-2.58, P=.003). Analysis of patients according to their underlying liver disease, revealed that smoking, and not nonsmoking, affected survival of hepatitis B virus and C virus-infected patients only. In this subgroup, smoking was an independent predictor for survival (hazard ratio 2.99, 95% confidence interval: 1.7-5.23, Phepatocellular carcinoma. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Increased risk of hepatocellular carcinoma in patients with chronic hepatitis C

    DEFF Research Database (Denmark)

    Hallager, Sofie; Weis, Nina

    2014-01-01

    Chronic hepatitis C (CHC) frequently leads to cirrhosis with an increased risk of hepatocellular carcinomas (HCC). CHC therapy is currently changing for the better whereas prognosis for HCC remains dismal if not detected early and thus regular screening in cirrhotic CHC patients for HCC...... is recommended. CHC is known to be underdiagnosed in Denmark where it is up to the involved physician to screen for risk factors for CHC and increase the patient's chance of a cure for CHC with therapy....

  14. Spontaneous rupture of adrenal metastasis from hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Chae Hun; Kim, Hyun Jin; Park, Soo Youn; Hwang, Seong Su; Choi, Hyun Joo [St. Vincent Hospital, Suwon (Korea, Republic of)

    2007-03-15

    Rupture of adrenal tumor from various primary origins is a rather rare event. We report here on a ruptured adrenal metastasis from hepatocellular carcinoma, and this ruptured metastasis was observed at the time of the initial diagnosis.

  15. Immunization With AFP + GM CSF Plasmid Prime and AFP Adenoviral Vector Boost in Patients With Hepatocellular Carcinoma

    Science.gov (United States)

    2015-12-01

    Hepatocellular Carcinoma; Hepatoma; Liver Cancer, Adult; Liver Cell Carcinoma; Liver Cell Carcinoma, Adult; Cancer of Liver; Cancer of the Liver; Cancer, Hepatocellular; Hepatic Cancer; Hepatic Neoplasms; Hepatocellular Cancer; Liver Cancer; Neoplasms, Hepatic; Neoplasms, Liver

  16. Imaging findings of mimickers of hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Tae Kyoung Kim

    2015-12-01

    Full Text Available Radiological imaging plays a crucial role in the diagnosis of hepatocellular carcinoma (HCC as the noninvasive diagnosis of HCC in high-risk patients by typical imaging findings alone is widely adopted in major practice guidelines for HCC. While imaging techniques have markedly improved in detecting small liver lesions, they often detect incidental benign liver lesions and non-hepatocellular malignancy that can be misdiagnosed as HCC. The most common mimicker of HCC in cirrhotic liver is nontumorous arterioportal shunts that are seen as focal hypervascular liver lesions on dynamic contrast-enhanced cross-sectional imaging. Rapidly enhancing hemangiomas can be easily misdiagnosed as HCC especially on MR imaging with liver-specific contrast agent. Focal inflammatory liver lesions mimic HCC by demonstrating arterial-phase hypervascularity and subsequent washout on dynamic contrast-enhanced imaging. It is important to recognize the suggestive imaging findings for intrahepatic cholangiocarcinoma (CC as the management of CC is largely different from that of HCC. There are other benign mimickers of HCC such as angiomyolipomas and focal nodular hyperplasia-like nodules. Recognition of their typical imaging findings can reduce false-positive HCC diagnosis.

  17. Diagnosis of small hepatocellular carcinoma by incremental dynamic CT

    International Nuclear Information System (INIS)

    Uchida, Masafumi; Kumabe, Tsutomu; Edamitsu, Osamu

    1993-01-01

    Thirty cases of pathologically confirmed small hepatocellular carcinoma were examined by Incremental Dynamic CT (ICT). ICT scanned the whole liver with single-breath-hold technique; therefore, effective early contrast enhancement could be obtained for diagnosis. Among the 30 tumors, 26 were detected. The detection rate was 87%. A high detection rate was obtained in tumors more than 20 mm in diameter. Twenty-two of 26 tumors could be diagnosed correctly. ICT examination was useful for detection of small hepatocellular carcinoma. (author)

  18. Cerebrovascular Accidents Associated with Sorafenib in Hepatocellular Carcinoma

    OpenAIRE

    Saif, Muhammad W.; Isufi, Iris; Peccerillo, Jennifer; Syrigos, Kostas N.

    2011-01-01

    Sorafenib is an oral angiogenetic multikinase inhibitor approved in the treatment of renal and hepatocellular carcinoma. Bleeding and venous thrombotic events have been described with angiogenetic agents but cerebrovascular accidents are rarely reported. We report two cases of patients with hepatocellular carcinoma who developed a cerebrovascular accident while on sorafenib. Neither patient had any risk factors for the cerebrovascular events apart from gender and age in the second patient. La...

  19. Haptocorrin as marker of disease progression in fibrolamellar hepatocellular carcinoma

    DEFF Research Database (Denmark)

    Lildballe, Dorte Launholt; Nguyen, Khoa Tran; Poulsen, Steen Seier

    2011-01-01

    No valid markers are routinely available to follow disease progression in patients with fibrolamellar hepatocellular carcinoma (FLHCC). We report data suggesting that the vitamin B12 binding protein haptocorrin (HC) may prove a suitable marker.......No valid markers are routinely available to follow disease progression in patients with fibrolamellar hepatocellular carcinoma (FLHCC). We report data suggesting that the vitamin B12 binding protein haptocorrin (HC) may prove a suitable marker....

  20. Hepatocellular Carcinoma: An Unusual Complication of Longstanding Wilson Disease.

    Science.gov (United States)

    Gunjan, Deepak; Shalimar; Nadda, Neeti; Kedia, Saurabh; Nayak, Baibaswata; Paul, Shashi B; Gamanagatti, Shivanand Ramachandra; Acharya, Subrat K

    2017-06-01

    Wilson disease is caused by the accumulation of copper in the liver, brain or other organs, due to the mutation in ATP7B gene, which encodes protein that helps in excretion of copper in the bile canaliculus. Clinical presentation varies from asymptomatic elevation of transaminases to cirrhosis with decompensation. Hepatocellular carcinoma is a known complication of cirrhosis, but a rare occurrence in Wilson disease. We present a case of neurological Wilson disease, who later developed decompensated cirrhosis and hepatocellular carcinoma.

  1. Evaluation of CT in hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Nakao, Norio; Miura, Yukio; Ohnishi, Mitsunori; Kamikon-ya, Norihiko; Sakamoto, Yoshisato; Miura, Takashi; Sakamoto, Kiyoshi; Takayasu, Yoshio

    1985-06-01

    In order to evaluate the diagnostic ability of CT in hepatocellular carcinoma, four kinds of CT images were comparatively studied by the accuracy and ROC (receiver operating characteristic) curve analysis. As a result, it was clarified that CT images were evaluated more objectively by ROC curve analysis than by accuracy. The diagnostic ability of existence and differentiation of tumor in the liver were higher in order of plain CT, contrast enhanced CT (CECT), bolus CT and CT arteriography (CTA). Therefore, in an usual CT examination intended to make differential diagnosis in space occupying liver disease, bolus CT seems to be indispensable, and also CTA is essential where diagnosis is difficult even by bolus CT.

  2. Models of Hepatocellular Carcinoma and Biomarker Strategy

    Energy Technology Data Exchange (ETDEWEB)

    Bagi, Cedo M., E-mail: cedo.bagi@pfizer.com; Andresen, Catharine J. [Global Science & Technology, PGRD, Pfizer Inc, Groton, CT 06340 (United States)

    2010-07-07

    The overwhelming need to improve preclinical models in oncology has stimulated research efforts to refine and validate robust orthotopic models that closely mimic the disease population and therefore have the potential to better predict clinical outcome with novel therapies. Sophisticated technologies including bioluminescence, contrast enhanced ultrasound imaging, positron emission tomography, computed tomography and magnetic resonance imaging have been added to existing serum- and histology-based biomarkers to assist with patient selection and the design of clinical trials. The rationale for the use of human hepatocellular carcinoma (HCC) cell lines, implementation of xenograft and orthotopic animal models and utilization of available biomarkers have been discussed, providing guidelines to facilitate preclinical research for the development of treatments for HCC patients.

  3. Embolotherapy in the management of hepatocellular carcinoma.

    Science.gov (United States)

    Mojtahedi, Alireza; Yang, Xiaoming; Goswami, Gaurav K

    2008-09-01

    Hepatocellular carcinoma (HCC) ranks fifth in frequency of cancers worldwide. The incidence of HCC in the United States is rising, primarily due to the number of patients who were infected by hepatitis in the 1960s and 1970s coupled with the rising migrant population from Asia, where hepatitis is widely prevalent. Up to 80% of the patients present with multicentric HCC and advanced liver disease or comorbidities that restrict the option of resection or liver transplantation. The dual blood supply (arterial and portal) to the liver with predominantly arterial supply to the tumor has made embolotherapy a cornerstone in the management of inoperable HCC. The techniques have become refined not only due to the development of microcatheter angiographic capabilities, but also in the ability to deliver a wide variety of therapeutic agents to these tumors. This article reviews the fundamental principles of bland embolization, chemoembolization, and radioembolization in the management of HCC.

  4. Hepatocellular carcinoma detected by iodized oil

    International Nuclear Information System (INIS)

    Yumoto, Y.; Jinno, K.; Tokuyama, K.

    1985-01-01

    This study assesses the diagnostic value of Lipiodol (iodized oil) and computed tomography (CT) in detecting hepatocellular carcinoma (HCC). Twenty-four patients who were suspected of having HCC received injections of a small amount of Lipiodol, along with an antitumor agent, in the hepatic artery following routine celiac angiography. CT scans obtained 7-10 days after Lipiodol administration demonstrated HCC in distinct contrast to the surrounding noncancerous parenchyma. In particular, the CT-Lipiodol procedure disclosed many small HCC lesions that were not shown by celiac angiography, scintigraphy, CT with an without contrast medium enhancement, and ultrasonography. Although this procedure may miss very small or highly fibrotic lesions, it is recommended for patients suspected of having HCC and for patients for whom hepatic resection is being considered

  5. Laparoscopic RFA with splenectomy for hepatocellular carcinoma.

    Science.gov (United States)

    Hu, Kunpeng; Lei, Purun; Yao, Zhicheng; Wang, Chenhu; Wang, Qingliang; Xu, Shilei; Xiong, Zhiyong; Huang, He; Xu, Ruiyun; Deng, Meihai; Liu, Bo

    2016-07-27

    The treatment of hepatocellular carcinoma (HCC) is complicated and challenging because of the frequent presence of cirrhosis. Therefore, we propose a novel surgical approach to minimize the invasiveness and risk in patients with HCC, hypersplenism, and esophagogastric varices. This was a retrospective study carried out in 25 patients with HCC and hypersplenism and who underwent simultaneous laparoscopic-guided radio-frequency ablation and laparoscopic splenectomy with endoscopic variceal ligation. Tumor size was restricted to a single nodule of splenectomy. Laparoscopic-guided radio-frequency ablation with laparoscopic splenectomy and endoscopic variceal ligation could be an available technique for patients with HCC <3 cm, hypersplenism, and esophagogastric varices. This approach may help to minimize the surgical risks and results in a fast increase in platelet counts with an acceptable rate of complications.

  6. Computed tomographic findings of hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Eun, Chung Kie [Kyung Hee University College of Medicine, Seoul (Korea, Republic of)

    1982-09-15

    It is well known that CT is very useful in the evaluation of hepatocellular carcinoma. The computed tomographic findings of 56 patients diagnosed as hepatocellular carcinoma were reviewed and analyzed. The results were as follows: 1. The male to female ratio was 3 : 1 and the age ranged from 31 to 73 years with average age of 54 years. 2. Alpha-fetoprotein was positive in 19 out of 38 cases (50%). HBsAg was positive in 8 out of 33 cases (24%). 3. All lesions were seen as areas of low density except 1 case (0%) of isodensity, and 40 cases (72%) appeared to be solitary while 15 (26%) were multifocal. The low density was homogenous in 13 cases (24%) and inhomogenous in 42 cases (76%), and 18 cases out of 42 cases inhomogenous low density showed peripheal and/or central nodular enhancement. The additional findings were contour changes in 37 cases (66%), metastasis in 35 cases (63%), splenomegaly in 23 cases (42%) and ascities in 22 cases (39%). 4. In postcontrast scans, 41 cases (80%) out of 51 cases showed the change of density after contrast infusion. The presence and extent of tumors were better seen after contrast infusion in 30 cases (59%), better seen before contrast infusion in 11 cases (21%) and no significant difference before and after contrast infusion in 10 cases (20%). 5. The sites of involved lobe were right lobe in 38 cases (68%), left lobe in 5 cases (9%) and both lobes in 13 cases (23%). 6. 35 cases (63%) showed evidence of metastasis to regional lymph nodes, organ or tissues.

  7. Liver Transplantation for Alcoholic Liver Disease and Hepatocellular Carcinoma.

    Science.gov (United States)

    Burra, Patrizia; Zanetto, Alberto; Germani, Giacomo

    2018-02-09

    Hepatocellular carcinoma is one of the main important causes of cancer-related death and its mortality is increasingly worldwide. In Europe, alcohol abuse accounts for approximately half of all liver cancer cases and it will become the leading cause of hepatocellular carcinoma in the next future with the sharp decline of chronic viral hepatitis. The pathophysiology of alcohol-induced carcinogenesis involves acetaldehyde catabolism, oxidative stress and chronic liver inflammation. Genetic background plays also a significant role and specific patterns of gene mutations in alcohol-related hepatocellular carcinoma have been characterized. Survival is higher in patients who undergo specific surveillance programmes than in patients who do not. However, patients with alcohol cirrhosis present a significantly greater risk of liver decompensation than those with cirrhosis due to other aetiologies. Furthermore, the adherence to screening program can be suboptimal. Liver transplant for patients with Milan-in hepatocellular carcinoma represents the best possible treatment in case of tumour recurrence/progression despite loco-regional or surgical treatments. Long-term result after liver transplantation for alcohol related liver disease is good. However, cardiovascular disease and de novo malignancies can significantly hamper patients' survival and should be carefully considered by transplant team. In this review, we have focused on the evolution of alcohol-related hepatocellular carcinoma epidemiology and risk factors as well as on liver transplantation in alcoholic patients with and without hepatocellular carcinoma.

  8. Inflammation-Dependent IL18 Signaling Restricts Hepatocellular Carcinoma Growth by Enhancing the Accumulation and Activity of Tumor-Infiltrating Lymphocytes.

    Science.gov (United States)

    Markowitz, Geoffrey J; Yang, Pengyuan; Fu, Jing; Michelotti, Gregory A; Chen, Rui; Sui, Jianhua; Yang, Bin; Qin, Wen-Hao; Zhang, Zheng; Wang, Fu-Sheng; Diehl, Anna Mae; Li, Qi-Jing; Wang, Hongyang; Wang, Xiao-Fan

    2016-04-15

    Chronic inflammation in liver tissue is an underlying cause of hepatocellular carcinoma. High levels of inflammatory cytokine IL18 in the circulation of patients with hepatocellular carcinoma correlates with poor prognosis. However, conflicting results have been reported for IL18 in hepatocellular carcinoma development and progression. In this study, we used tissue specimens from hepatocellular carcinoma patients and clinically relevant mouse models of hepatocellular carcinoma to evaluate IL18 expression and function. In a mouse model of liver fibrosis that recapitulates a tumor-promoting microenvironment, global deletion of the IL18 receptor IL18R1 enhanced tumor growth and burden. Similarly, in a carcinogen-induced model of liver tumorigenesis, IL18R1 deletion increased tumor burden. Mechanistically, we found that IL18 exerted inflammation-dependent tumor-suppressive effects largely by promoting the differentiation, activity, and survival of tumor-infiltrating T cells. Finally, differences in the expression of IL18 in tumor tissue versus nontumor tissue were more predictive of patient outcome than overall tissue expression. Taken together, our findings resolve a long-standing contradiction regarding a tumor-suppressive role for IL18 in established hepatocellular carcinoma and provide a mechanistic explanation for the complex relationship between its expression pattern and hepatocellular carcinoma prognosis. Cancer Res; 76(8); 2394-405. ©2016 AACR. ©2016 American Association for Cancer Research.

  9. Correlations of matrix metalloproteinase content and expression with invasion and metastasis of hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Zhang Zhichao; Jia Mingku; Sun Yaxin

    2006-01-01

    Objective: To investigate the correlations of serum matrix metalloproteinase-2, -9 (MMP-2, MMP-9) contents and tissue expressions in hepatocellular carcinoma with tumor invasion and metastasis. Methods: Serum MMP-2, MMP-9 contents were detected in 40 patient with hepatocellular carcinoma and 20 healthy controls by ELISA; the expressions and distributions of MMP-2 and MMP-9 in 40 patients and 10 normal tissues were detected by immunohistochemical method. Results: Serum MMP-2, MMP-9 contents were significantly elevated in cancer samples compared with normal serum (P<0.01), the significant difference was found between contents in the presence and the absence of lymph node metastasis (P<0.05). In hepatocellular carcinoma, the expressions of MMP-2, MMP-9 were increased significantly compared with normal tissue. The expressions of MMP-2, MMP-9 were correlated with histological grade and lymph node metastasis (P<0.05). Conclusion: The serum of MMP-2 and MMP-9 contents and their expressions may provide reliable information for hepatocellular carcinoma prognosis. (authors)

  10. Guide for diagnosis and treatment of hepatocellular carcinoma

    Science.gov (United States)

    Attwa, Magdy Hamed; El-Etreby, Shahira Aly

    2015-01-01

    Hepatocellular carcinoma (HCC) is ranked as the 5th common type of cancer worldwide and is considered as the 3rd common reason for cancer-related deaths. HCC often occurs on top of a cirrhotic liver. The prognosis is determined by several factors; tumour extension, alpha-fetoprotein (AFP) concentration, histologic subtype of the tumour, degree of liver dysfunction, and the patient’s performance status. HCC prognosis is strongly correlated with diagnostic delay. To date, no ideal screening modality has been developed. Analysis of recent studies showed that AFP assessment lacks adequate sensitivity and specificity for effective surveillance and diagnosis. Many tumour markers have been tested in clinical trials without progressing to routine use in clinical practice. Thus, surveillance is still based on ultrasound (US) examination every 6 mo. Imaging studies for diagnosis of HCC can fall into one of two main categories: routine non-invasive studies such as US, computed tomography (CT), and magnetic resonance imaging, and more specialized invasive techniques including CT during hepatic arteriography and CT arterial portography in addition to the conventional hepatic angiography. This article provides an overview and spotlight on the different diagnostic modalities and treatment options of HCC. PMID:26140083

  11. Research advances in proton beam therapy for hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    DAI Shuyang

    2013-10-01

    Full Text Available Hepatocellular carcinoma (HCC, one of the most common malignancies with high prevalence and mortality rate, usually results in poor prognosis and limited survival. A comprehensive analysis on the number and location of tumors, Child-Pugh grade, and Barcelona Clinic Liver Cancer stage will help the development of suitable treatment programs and improve prediction of prognosis. A majority of patients are complicated by cirrhosis, enlarged tumor, multiple lesions, vascular invasion, and even cancer embolus in the portal vein. With the growth of knowledge about the radiation tolerance of normal tissue and the advances in radiotherapy techniques, radiotherapy has become an important tool for step-down therapy and adjuvant therapy for liver cancer. Proton beam therapy (PBT is emerging as a novel radiotherapy for the management of HCC, which, benefiting from the effect of Bragg Peak from PBT, effectively decreases the toxicity of traditional radiotherapies to the liver and does little harm to the uninvolved liver tissue or the surrounding structures while intensifying the destruction in targeted malignant lesions. Furthermore, several previous studies on the treatment of HCC with PBT revealed excellent local control. The distinctive biophysical attributes of PBT in the treatment of HCC, as well as the available literature regarding clinical outcomes and toxicity of using PBT for HCC, are reviewed. Current evidence provides limited indications for PBT, which suggests that further study on the relationship between liver function and PBT is required to gain further insight into its indication and standardization.

  12. Diagnostic value of α-fetoprotein in hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Hernández Perera, Julio César

    2009-01-01

    In the world the hepatocellular carcinoma (HCC) is the fifth to sixth most common malignancy. An increase in its incidence is looming in Cuba as a result of the population aging and the increase of morbi-mortality due to liver cirrhosis (CH). α-fetoprotein (AFP) by SUMA®, was used in this work as a tumor marker technique in 189 Cirrhotic patients evaluated at the CIMEQ, between January 1999 and September 2005. The main factors associated with an elevation of AFP were HCC, viral cirrhosis, and the age of 50 years or more. Presented CHC 22 (11.64%) patients, who had an average age of 55 years and the predominant sex was male (86,36%). The most important cause associated with this malignant disease was viral CH, mainly the virus of hepatitis C. This tumor marker showed a sensitivity and specificity of 68.18% and 92.17%, respectively. When combined with abdominal ultrasound was increase 86.36% sensitivity and 100% specificity. Elevated AFP levels associated with tumor prognosis factors. It can be concluded that the AFP had value in the diagnosis of HCC. This work is the first of its kind carried out in Cuba, and allows the design of a workable strategy for the research, monitoring and prognosis of HCC, having a wide network of laboratories SUMA®,, with a low cost per each determination. (author)

  13. Infrequent widespread microsatellite instability in hepatocellular carcinomas.

    Science.gov (United States)

    Yamamoto, H; Itoh, F; Fukushima, H; Kaneto, H; Sasaki, S; Ohmura, T; Satoh, T; Karino, Y; Endo, T; Toyota, J; Imai, K

    2000-03-01

    Widespread or high-frequency microsatellite instability (MSI) due to the defective DNA mismatch repair (MMR) occurs in the majority of hereditary non-polyposis colorectal cancer and a subset of sporadic malignant tumors. The incidence of MSI and underlying DNA MMR defects have been well characterized in gastrointestinal carcinogenesis, but not in hepatocarcinogenesis. To address the issue, we analyzed 55 Japanese hepatocellular carcinomas using several indicators of DNA MMR defects, such as microsatellite analysis, loss of heterozygosity (LOH) and mutation analysis of MMR genes, methylation of hMLH1 promoter, and frameshift mutations of mononucleotide repeat sequences within possible target genes. Mutation of beta2-microglobulin gene, which is presumably involved in MSI-positive tumor cell escape from immune surveillance was also examined. Some of these analyses were also carried out in 9 human liver cancer cell lines. None of the 3 quasi-monomorphic mononucleotide markers sensitive for MSI, BAT26, BAT25, and BAT34C4 presented shortened unstable alleles in any of the carcinoma, cirrhosis, chronic hepatitis tissues, or cell lines. LOH at MMR genes was infrequent (4.4 approximately 7.1%), and no mutations were detected. Neither hMLH1 hypermethylation nor frameshift mutation in the target genes was detected. No mutations were found in beta2-microglobulin. Widespread MSI due to the defective DNA MMR appears to play little if any part in Japanese hepatocarcinogenesis.

  14. Management of hepatocellular carcinoma: Predictive value of immunohistochemical markers for postoperative survival

    Science.gov (United States)

    Niu, Zhao-Shan; Niu, Xiao-Jun; Wang, Mei

    2015-01-01

    Hepatocellular carcinoma (HCC) accounts for over 90% of all primary liver cancers. With an ever increasing incidence trend year by year, it has become the third most common cause of death from cancer worldwide. Hepatic resection is generally considered to be one of the most effective therapies for HCC patients, however, there is a high risk of recurrence in postoperative HCC. In clinical practice, there exists an urgent need for valid prognostic markers to identify patients with prognosis, hence the importance of studies on prognostic markers in improving the prediction of HCC prognosis. This review focuses on the most promising immunohistochemical prognostic markers in predicting the postoperative survival of HCC patients. PMID:25624992

  15. Hep par-1: a novel immunohistochemical marker for differentiating hepatocellular carcinoma from metastatic carcinoma

    International Nuclear Information System (INIS)

    Hanif, R.

    2014-01-01

    To evaluate the diagnostic utility of Hep par-1 in differentiating hepatocellular carcinoma from metastatic carcinoma taking histopathology as a gold standard. Study Design: Comparative cross-sectional study. Place and Duration of Study: Pathology Department, Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, from April 2007 to February 2008. Methodology: Hep par-1 immunohistochemical stain was performed on 60 cases of liver carcinoma, 30 cases each of metastatic and hepatocellular carcinoma. Information regarding patient age, gender, sign and symptoms, radiographic findings, histological grade of tumour, and expression of Hep par-1 on hepatocellular and metastatic carcinoma were recorded on proforma sheet. Sensitivity, specificity, positive and negative predictive values, and accuracy of Hep par-1 were calculated using the formulas. Results: Hep par-1 expression was noted in 25 out of 30 cases of hepatocellular carcinoma (83%). Out of 30 cases of metastatic carcinoma, only one case expressed staining in < 5% tumour cells and remaining 29 cases showed no reactivity. The age of the patients with hepatocellular carcinoma ranged from 40 to 76 years with a median age of 60.5 years and 40 - 75 years for metastatic carcinomas with a median age of 57.5 years. Conclusion: Hep par-1 is a reliable immunohistochemical marker for cases of hepatocellular carcinoma (HCC). It can be used along with other markers in morphologically difficult cases when differential diagnosis lies between poorly differentiated HCC and metastatic carcinoma of liver. (author)

  16. Scintigraphic demonstration of a metastasizing hepato-cellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Heintz, P; Gratz, K F; Schwarzrock, R; Schober, O; Neuhaus, P; Creutzig, H

    1986-01-01

    Adenomas and hepato cellular carcinomas cannot be differentiated by nuclear medicine: both exhibit masked radiodrug trapping at reduced perfusion. Two patients revealed specific accumulation in extrahepatic foci unknown before; hence, the diagnosis of a metastasizing hepatocellular carcinoma had to be verified. One case is demonstrated in full detail. (orig./SHA).

  17. Antiviral therapy for prevention of hepatocellular carcinoma in chronic hepatitis C

    DEFF Research Database (Denmark)

    Kimer, Nina; Dahl, Emilie Kristine; Gluud, Lise Lotte

    2012-01-01

    To determine whether antiviral therapy reduces the risk of developing hepatocellular carcinoma (HCC) in chronic hepatitis C.......To determine whether antiviral therapy reduces the risk of developing hepatocellular carcinoma (HCC) in chronic hepatitis C....

  18. Radiofrequency (thermal) ablation versus no intervention or other interventions for hepatocellular carcinoma

    DEFF Research Database (Denmark)

    Weis, Sebastian; Franke, Annegret; Mössner, Joachim

    2013-01-01

    Hepatocellular carcinoma is the fifth most common cancer worldwide. Percutaneous interventional therapies, such as radiofrequency (thermal) ablation (RFA), have been developed for early hepatocellular carcinoma. RFA competes with other interventional techniques such as percutaneous ethanol...

  19. A Gene Expression Signature Associated With Overall Survival in Patients With Hepatocellular Carcinoma Suggests a New Treatment Strategy

    DEFF Research Database (Denmark)

    Gillet, Jean-Pierre; Andersen, Jesper B; Madigan, James P

    2015-01-01

    Despite improvements in the management of liver cancer, the survival rate for individuals with hepatocellular carcinoma (HCC) remains dismal. The survival benefit of systemic chemotherapy for the treatment of liver cancer is only marginal. Although the reasons for treatment failure...... are multifactorial, intrinsic resistance to chemotherapy plays a primary role. Here, we analyzed the expression of 377 multidrug resistance-associated genes in two independent cohorts of patients with advanced hepatocellular carcinoma, with the aim of finding ways to improve survival in this poor-prognosis cancer...

  20. Circulating CD147 predicts mortality in advanced hepatocellular carcinoma.

    Science.gov (United States)

    Lee, Aimei; Rode, Anthony; Nicoll, Amanda; Maczurek, Annette E; Lim, Lucy; Lim, Seok; Angus, Peter; Kronborg, Ian; Arachchi, Niranjan; Gorelik, Alexandra; Liew, Danny; Warner, Fiona J; McCaughan, Geoffrey W; McLennan, Susan V; Shackel, Nicholas A

    2016-02-01

    The glycoprotein CD147 has a role in tumor progression, is readily detectable in the circulation, and is abundantly expressed in hepatocellular carcinoma (HCC). Advanced HCC patients are a heterogeneous group with some individuals having dismal survival. The aim of this study was to examine circulating soluble CD147 levels as a prognostic marker in HCC patients. CD147 was measured in 277 patients (110 HCC, 115 chronic liver disease, and 52 non-liver disease). Clinical data included etiology, tumor progression, Barcelona Clinic Liver Cancer (BCLC) stage, and treatment response. Patients with HCC were stratified into two groups based upon the 75th percentile of CD147 levels (24 ng/mL). CD147 in HCC correlated inversely with poor survival (P = 0.031). Increased CD147 predicted poor survival in BCLC stages C and D (P = 0.045), and CD147 levels >24 ng/mL predicted a significantly diminished 90-day and 180-day survival time (hazard ratio [HR] = 6.1; 95% confidence interval [CI]: 2.1-63.2; P = 0.0045 and HR = 2.8; 95% CI: 1.2-12.6; P = 0.028, respectively). In BCLC stage C, CD147 predicted prognosis; levels >24 ng/mL were associated with a median survival of 1.5 months compared with 6.5 months with CD147 levels ≤24 ng/mL (P = 0.03). CD147 also identified patients with a poor prognosis independent from treatment frequency, modality, and tumor size. Circulating CD147 is an independent marker of survival in advanced HCC. CD147 requires further evaluation as a potential new prognostic measure in HCC to identify patients with advanced disease who have a poor prognosis. © 2015 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  1. MicroRNA gene polymorphisms and environmental factors increase patient susceptibility to hepatocellular carcinoma.

    Directory of Open Access Journals (Sweden)

    Yin-Hung Chu

    Full Text Available BACKGROUND: Micro RNAs (miRNAs are small RNA fragments that naturally exist in the human body. Through various physiological mechanisms, miRNAs can generate different functions for regulating RNA protein levels and balancing abnormalities. Abnormal miRNA expression has been reported to be highly related to several diseases and cancers. Single-nucleotide polymorphisms (SNPs in miRNAs have been reported to increase patient susceptibility and affect patient prognosis and survival. We adopted a case-control research design to verify the relationship between miRNAs and hepatocellular carcinoma. METHODOLOGY/PRINCIPAL FINDINGS: A total of 525 subjects, including 377 controls and 188 hepatocellular carcinoma patients, were selected. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP and real-time PCR were used to analyze miRNA146a (rs2910164, miRNA149 (rs2292832, miRNA196 (rs11614913, and miRNA499 (rs3746444 genetic polymorphisms between the control group and the case group. The results indicate that people who carry the rs3746444 CT or CC genotypes may have a significantly increased susceptibility to hepatocellular carcinoma (adjusted odds ratio [AOR] = 2.84, 95% confidence interval [CI] = 1.88-4.30. In addition, when combined with environmental risk factors, such as smoking and alcohol consumption, interaction effects were observed between gene polymorphisms and environmental factors (odds ratio [OR] = 4.69, 95% CI = 2.52-8.70; AOR = 3.38, 95% CI = 1.68-6.80. CONCLUSIONS: These results suggest that a significant association exists between miRNA499 SNPs and hepatocellular carcinoma. Gene-environment interactions of miRNA499 polymorphisms, smoking, and alcohol consumption might alter hepatocellular carcinoma susceptibility.

  2. Overexpression of Cullin7 is associated with hepatocellular carcinoma progression and pathogenesis.

    Science.gov (United States)

    An, Jun; Zhang, Zhigang; Liu, Zhiyong; Wang, Ruizhi; Hui, Dayang; Jin, Yi

    2017-12-06

    Overexpression of Cullin7 is associated with some types of malignancies. However, the part of Cullin7 in hepatocellular carcinoma remains unclear. The aim of this study was to investigate the role of Cullin7 in pathogenesis and the progression of hepatocellular carcinoma. In the present study, the expression of Cullin7 in hepatocellular carcinoma cell lines and five surgical hepatocellular carcinoma specimens was detected with quantitative reverse transcription PCR and western blotting. In addition, the protein expression of Cullin7 was examined in 162 cases of archived hepatocellular carcinoma using immunohistochemistry. We found elevated expression of both mRNA and protein levels of Cullin7 in hepatocellular carcinoma cell lines, and Cullin7 protein was significantly upregulated in hepatocellular carcinoma compared with paired normal hepatic tissues. The immunohistochemistry analysis revealed that overexpression of Cullin7 occurred in 69.1% of hepatocellular carcinoma samples, which was a significantly higher rate than that in adjacent normal hepatic tissue (P hepatocellular carcinoma HepG2 cells, we revealed that Cullin7 could significantly enhance cell proliferation, growth, migration and invasion. Conversely, knocking down Cullin7 expression with short hairpin RNAi in hepatocellular carcinoma HepG2 cells inhibited cell proliferation, growth, migration and invasion. Our studies provide evidence that overexpression of Cullin7 plays an important role in the pathogenesis and progression of hepatocellular carcinoma and may be a valuable marker for hepatocellular carcinoma management.

  3. File list: Oth.Liv.50.AllAg.Carcinoma,_Hepatocellular [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Liv.50.AllAg.Carcinoma,_Hepatocellular mm9 TFs and others Liver Carcinoma, Hepa...tocellular SRX467209 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Liv.50.AllAg.Carcinoma,_Hepatocellular.bed ...

  4. File list: NoD.Liv.10.AllAg.Carcinoma,_Hepatocellular [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.Liv.10.AllAg.Carcinoma,_Hepatocellular mm9 No description Liver Carcinoma, Hepa...tocellular http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/NoD.Liv.10.AllAg.Carcinoma,_Hepatocellular.bed ...

  5. File list: Oth.Liv.10.AllAg.Carcinoma,_Hepatocellular [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Liv.10.AllAg.Carcinoma,_Hepatocellular mm9 TFs and others Liver Carcinoma, Hepa...tocellular SRX467209 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Liv.10.AllAg.Carcinoma,_Hepatocellular.bed ...

  6. File list: DNS.Liv.05.AllAg.Carcinoma,_Hepatocellular [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Liv.05.AllAg.Carcinoma,_Hepatocellular mm9 DNase-seq Liver Carcinoma, Hepatocel...lular http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Liv.05.AllAg.Carcinoma,_Hepatocellular.bed ...

  7. File list: ALL.Liv.20.AllAg.Carcinoma,_Hepatocellular [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Liv.20.AllAg.Carcinoma,_Hepatocellular mm9 All antigens Liver Carcinoma, Hepato...cellular SRX467209,SRX467208 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Liv.20.AllAg.Carcinoma,_Hepatocellular.bed ...

  8. File list: InP.Liv.10.AllAg.Carcinoma,_Hepatocellular [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Liv.10.AllAg.Carcinoma,_Hepatocellular mm9 Input control Liver Carcinoma, Hepat...ocellular SRX467208 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Liv.10.AllAg.Carcinoma,_Hepatocellular.bed ...

  9. File list: DNS.Liv.50.AllAg.Carcinoma,_Hepatocellular [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Liv.50.AllAg.Carcinoma,_Hepatocellular mm9 DNase-seq Liver Carcinoma, Hepatocel...lular http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Liv.50.AllAg.Carcinoma,_Hepatocellular.bed ...

  10. File list: InP.Liv.50.AllAg.Carcinoma,_Hepatocellular [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Liv.50.AllAg.Carcinoma,_Hepatocellular mm9 Input control Liver Carcinoma, Hepat...ocellular SRX467208 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Liv.50.AllAg.Carcinoma,_Hepatocellular.bed ...

  11. File list: NoD.Liv.05.AllAg.Carcinoma,_Hepatocellular [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available NoD.Liv.05.AllAg.Carcinoma,_Hepatocellular mm9 No description Liver Carcinoma, Hepa...tocellular http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/NoD.Liv.05.AllAg.Carcinoma,_Hepatocellular.bed ...

  12. File list: Oth.Liv.05.AllAg.Carcinoma,_Hepatocellular [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Liv.05.AllAg.Carcinoma,_Hepatocellular mm9 TFs and others Liver Carcinoma, Hepa...tocellular SRX467209 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Liv.05.AllAg.Carcinoma,_Hepatocellular.bed ...

  13. File list: DNS.Liv.20.AllAg.Carcinoma,_Hepatocellular [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Liv.20.AllAg.Carcinoma,_Hepatocellular mm9 DNase-seq Liver Carcinoma, Hepatocel...lular http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Liv.20.AllAg.Carcinoma,_Hepatocellular.bed ...

  14. File list: Pol.Liv.50.AllAg.Carcinoma,_Hepatocellular [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Liv.50.AllAg.Carcinoma,_Hepatocellular mm9 RNA polymerase Liver Carcinoma, Hepa...tocellular http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Liv.50.AllAg.Carcinoma,_Hepatocellular.bed ...

  15. File list: Oth.Liv.20.AllAg.Carcinoma,_Hepatocellular [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Liv.20.AllAg.Carcinoma,_Hepatocellular mm9 TFs and others Liver Carcinoma, Hepa...tocellular SRX467209 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Liv.20.AllAg.Carcinoma,_Hepatocellular.bed ...

  16. File list: Pol.Liv.10.AllAg.Carcinoma,_Hepatocellular [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Liv.10.AllAg.Carcinoma,_Hepatocellular mm9 RNA polymerase Liver Carcinoma, Hepa...tocellular http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Liv.10.AllAg.Carcinoma,_Hepatocellular.bed ...

  17. Hepatocellular carcinomas supplied by inferior phrenic arteries.

    Science.gov (United States)

    Tanabe, N; Iwasaki, T; Chida, N; Suzuki, S; Akahane, T; Kobayashi, N; Ishii, M; Toyota, T

    1998-07-01

    To assess the arterial supply to hepatocellular carcinomas (HCCs) by inferior phrenic arteries (IPA). A total of 126 consecutive cases of HCC were studied by contract-enhanced CT and conventional arteriography. Blood supply from an IPA was suspected when the size of the HCC mass as seen on contrast-enhanced CT did not match the size of the tumor mass as seen on hepatic arteriography. Inferior phrenic arteriography was employed to confirm these findings. HCCs fed by the IPA were analyzed in terms of size, location, and history of prior treatment. In 14 (11%) of the 126 cases, the tumor was found to have a blood supply from an IPA. Eleven of these tumors were located in segments 2 and 7. Three tumors, which had not been treated previously, had a blood supply from an IPA. Six tumors were almost exclusively fed by an IPA and were located in segments 1, 1, and 4. HCCs located in segments which form the bare area of the liver (S1, S2, S7) can be supplied by an IPA. This should be suspected when a lesion or part of a lesion is identified on contrast-enhanced CT but not on hepatic arteriography.

  18. Diagnostic and therapeutic management of hepatocellular carcinoma

    Science.gov (United States)

    Bellissimo, Francesco; Pinzone, Marilia Rita; Cacopardo, Bruno; Nunnari, Giuseppe

    2015-01-01

    Hepatocellular carcinoma (HCC) is an increasing health problem, representing the second cause of cancer-related mortality worldwide. The major risk factor for HCC is cirrhosis. In developing countries, viral hepatitis represent the major risk factor, whereas in developed countries, the epidemic of obesity, diabetes and nonalcoholic steatohepatitis contribute to the observed increase in HCC incidence. Cirrhotic patients are recommended to undergo HCC surveillance by abdominal ultrasounds at 6-mo intervals. The current diagnostic algorithms for HCC rely on typical radiological hallmarks in dynamic contrast-enhanced imaging, while the use of α-fetoprotein as an independent tool for HCC surveillance is not recommended by current guidelines due to its low sensitivity and specificity. Early diagnosis is crucial for curative treatments. Surgical resection, radiofrequency ablation and liver transplantation are considered the cornerstones of curative therapy, while for patients with more advanced HCC recommended options include sorafenib and trans-arterial chemo-embolization. A multidisciplinary team, consisting of hepatologists, surgeons, radiologists, oncologists and pathologists, is fundamental for a correct management. In this paper, we review the diagnostic and therapeutic management of HCC, with a focus on the most recent evidences and recommendations from guidelines. PMID:26576088

  19. Updates in the Management of Hepatocellular Carcinoma

    Science.gov (United States)

    Frenette, Catherine

    2011-01-01

    Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death, and its increasing incidence worldwide is a cause for concern. Fortunately, advances in diagnostic and therapeutic approaches have contributed to earlier detection and treatment. As cancer epidemiology studies continue to elucidate the natural history of liver diseases, greater understanding of HCC has led to improved risk stratification and earlier enrollment of high-risk patients in cancer screening and surveillance programs. Improved survival rates among HCC patients also reflect significant advances in available treatment options. Advances in surgical techniques are pushing the boundaries of resection for localized disease, and progress in the field of transplantation has led to refinements in listing criteria and improved post-transplantation outcomes. The evolving field of locoregional therapies—including percutaneous ablation and transarterial chemoembolization—continues to provide novel therapeutic options that can be used in place of, or in addition to, surgical approaches. Recent advances in systemic multikinase inhibitor therapies have also demonstrated significant benefits for advanced-stage disease, and these therapies also show promise as adjuvant treatments for earlier-stage disease. This article provides an update on the management of HCC, with a focus on revised guidelines for screening and an in-depth discussion of emerging novel therapies. PMID:21346848

  20. Genetic alterations in hepatocellular carcinoma: An update

    Science.gov (United States)

    Niu, Zhao-Shan; Niu, Xiao-Jun; Wang, Wen-Hong

    2016-01-01

    Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. Although recent advances in therapeutic approaches for treating HCC have improved the prognoses of patients with HCC, this cancer is still associated with a poor survival rate mainly due to late diagnosis. Therefore, a diagnosis must be made sufficiently early to perform curative and effective treatments. There is a need for a deeper understanding of the molecular mechanisms underlying the initiation and progression of HCC because these mechanisms are critical for making early diagnoses and developing novel therapeutic strategies. Over the past decade, much progress has been made in elucidating the molecular mechanisms underlying hepatocarcinogenesis. In particular, recent advances in next-generation sequencing technologies have revealed numerous genetic alterations, including recurrently mutated genes and dysregulated signaling pathways in HCC. A better understanding of the genetic alterations in HCC could contribute to identifying potential driver mutations and discovering novel therapeutic targets in the future. In this article, we summarize the current advances in research on the genetic alterations, including genomic instability, single-nucleotide polymorphisms, somatic mutations and deregulated signaling pathways, implicated in the initiation and progression of HCC. We also attempt to elucidate some of the genetic mechanisms that contribute to making early diagnoses of and developing molecularly targeted therapies for HCC. PMID:27895396

  1. CT findings of exophytic hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Sang Jin; Cho, June Sik; Kim, Hyung Lyul; Lee, Chung Keun; Kim, Dae Hong; Rhee, Byung Chull [Chungnam National University College of Medicine, Daejeon (Korea, Republic of)

    1993-11-15

    We retrospectively evaluated the characteristic computed tomographic(CT) findings in nine patients with exohepatic hepatocellular carcinoma(HCC) pathologically prove by surgery(n=2) or percutaneous needle biopsy(n=7). The CT findings of exphepatic HCC were correlated with clinical findings and compared with those of usual HCC. Lesions were in the left lobe(n=7) and right lobe(n=2) of the liver. All lesions showed a well-marginated hypodense mass with capsular enhancement on enhanced CT scan. The patterns of capsular enhancement were complete in five and partial in four case. The portal vein thrombosis was seen only in one case. There was no difference between exohepatic HCC and usual HCC in clinical findings such as increased {alpha}-fetoprotein({alpha}-FP), positive hepatitis B surface antigen(HBsAg), and underlying liver cirrhosis. In conclusion, the CT findings of exohepatic HCC were a well-defined hyperdense mass with complete or partial capsular enhancement and these findings may be useful in differentiation from the tumors of adjacent organs.

  2. Ectopic hepatocellular carcinoma in a dog.

    Science.gov (United States)

    Burton, I R; Limpus, K; Thompson, K G; Owen, M C; Worth, A J

    2005-12-01

    A 14-year-old neutered male Bearded Collie was presented with a history of recurrent, intermittent urinary incontinence of 7 years duration. A large, firm, non-painful mass was found in the mid-abdominal region on palpation. Ultrasonography of the mass revealed a compartmentalised structure with mixed echogenicity, and which did not appear to be associated with any of the abdominal organs. Ultrasound-guided fine needle aspirates contained several clusters of epithelial cells with cytological features of hepatocytes. At exploratory laparotomy, the mass was found in the gastrosplenic ligament within the greater omentum. PATHOLOGICAL FINDINGS AND DIAGNOSIS: Histopathologically, the mass consisted of sheets of hepatocytes, but without the characteristic hepatic architecture. The cells showed moderate variation in nuclear size and were sometimes binucleate. A diagnosis of hepatocellular carcinoma (HCC) in the mesentery was made. The presence of ectopic hepatic tissue has been reported rarely in man and cats, but not in the dog. Neoplastic transformation of ectopic hepatic tissue is seen in man. This is the first report of the presentation, clinical findings and treatment of a dog with ectopic HCC.

  3. Repeated proton beam therapy for hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Hashimoto, Takayuki; Tokuuye, Koichi; Fukumitsu, Nobuyoshi; Igaki, Hiroshi; Hata, Masaharu; Kagei, Kenji; Sugahara, Shinji; Ohara, Kiyoshi; Matsuzaki, Yasushi; Akine, Yasuyuki

    2006-01-01

    Purpose: To retrospectively evaluate the safety and effectiveness of repeated proton beam therapy for newly developed or recurrent hepatocellular carcinoma (HCC). Methods and Materials: From June 1989 through July 2000, 225 patients with HCC underwent their first course of proton beam therapy at University of Tsukuba. Of them, 27 with 68 lesions who had undergone two or more courses were retrospectively reviewed in this study. Median interval between the first and second course was 24.5 months (range 3.3-79.8 months). Median total dose of 72 Gy in 16 fractions and 66 Gy in 16 fractions were given for the first course and the rest of the courses, respectively. Results: The 5-year survival rate and median survival period from the beginning of the first course for the 27 patients were 55.6% and 62.2 months, respectively. Five-year local control rate for the 68 lesions was 87.8%. Of the patients, 1 with Child-Pugh class B and another with class C before the last course suffered from acute hepatic failure. Conclusions: Repeated proton beam therapy for HCC is safe when the patient has a target in the peripheral region of the liver and liver function is Child-Pugh class A

  4. Hepatocellular carcinoma: a systems biology perspective

    Directory of Open Access Journals (Sweden)

    Lorenza Alice D'alessandro

    2013-02-01

    Full Text Available Hepatocellular carcinomas (HCC have different etiology and heterogenic genomic alterations lead to high complexity. The molecular features of HCC have largely been studied by gene expression and proteome profiling focusing on the correlations between the expression of specific markers and clinical data. Integration of the increasing amounts of data in databases has facilitated the link of genomic and proteomic profiles of HCC to disease state and clinical outcome. Despite the current knowledge, specific molecular markers remain to be identified and new strategies are required to establish novel targeted therapies. In the last years, mathematical models reconstructing gene and protein networks based on experimental data of HCC have been developed providing powerful tools to predict candidate interactions and potential targets for therapy. Furthermore, the combination of dynamic and logical mathematical models with quantitative data allows detailed mechanistic insights into system properties. To address effects at the organ level, mathematical models reconstructing the three-dimensional organization of liver lobules were developed. In the future, integration of different modeling approaches capturing the effects at the cellular up to the organ level is required to address the complex properties of HCC and to enable the discovery of new targets for HCC prevention or treatment.

  5. Hepatocellular carcinomas supplied by inferior phrenic arteries

    International Nuclear Information System (INIS)

    Tanabe, N.; Iwasaki, T.; Akahane, T.; Kobayashi, N.; Ishii, M.; Toyota, T.; Chida, N.; Suzuki, S.

    1998-01-01

    Purpose: To assess the arterial supply to hepatocellular carcinomas (HCCs) by inferior phrenic arteries (IPA). Material and Methods: A total of 126 consecutive cases of HCC were studied by contrast-enhanced CT and conventional arteriography. Blood supply from an IPA was suspected when the size of the HCC mass as seen on contrast-enhanced CT did not match the size of the tumor mass as seen on hepatic arteriography. Inferior phrenic arteriography was employed to confirm these findings. HCCs fed by the IPA were analyzed in terms of size, location, and history of prior treatment. Results: In 14 (11%) of the 126 cases, the tumor was found to have a blood supply from an IPA. Eleven of these tumors were located in segments 2 and 7. Three tumors, which had not been treated previously, had a blood supply from an IPA. Six tumors were almost exclusively fed by an IPA and were located in segments 7, 1, and 4. Conclusion: HCCs located in segments which form the bare area of the liver (S1, S2, S7) can be supplied by an IPA. This should be suspected when a lesion or part of a lesion is identified on contrast-enhanced CT but not on hepatic arteriography. (orig.)

  6. Hepatocellular carcinomas supplied by inferior phrenic arteries

    Energy Technology Data Exchange (ETDEWEB)

    Tanabe, N.; Iwasaki, T.; Akahane, T.; Kobayashi, N.; Ishii, M.; Toyota, T. [Tohoku Univ. School of Medicine (Japan). Third Dept. of Internal Medicine; Chida, N.; Suzuki, S. [National Sendai Hospital (Japan). Dept. of Gastroenterology

    1998-07-01

    Purpose: To assess the arterial supply to hepatocellular carcinomas (HCCs) by inferior phrenic arteries (IPA). Material and Methods: A total of 126 consecutive cases of HCC were studied by contrast-enhanced CT and conventional arteriography. Blood supply from an IPA was suspected when the size of the HCC mass as seen on contrast-enhanced CT did not match the size of the tumor mass as seen on hepatic arteriography. Inferior phrenic arteriography was employed to confirm these findings. HCCs fed by the IPA were analyzed in terms of size, location, and history of prior treatment. Results: In 14 (11%) of the 126 cases, the tumor was found to have a blood supply from an IPA. Eleven of these tumors were located in segments 2 and 7. Three tumors, which had not been treated previously, had a blood supply from an IPA. Six tumors were almost exclusively fed by an IPA and were located in segments 7, 1, and 4. Conclusion: HCCs located in segments which form the bare area of the liver (S1, S2, S7) can be supplied by an IPA. This should be suspected when a lesion or part of a lesion is identified on contrast-enhanced CT but not on hepatic arteriography. (orig.)

  7. Prognostic factors in transcatheter arterial chemoembolization of hepatocellular carcinoma : analysis of more than 3 year survivors

    International Nuclear Information System (INIS)

    Seo, Heung Suk

    1999-01-01

    To determine which prognostic factors contribute to long-term survival after transcatheter arterial chemoembolization(TACE) of hepatocellular carcinoma. In 100 patients who expired within one year and 84 who survived or have survived for more than 3 years after TACE, prognostic factors were retrospectively evaluated. TACE was accomplished by hepatic arterial infusion of a suspension of Lipiodol and anticancer drugs(Mitomycin-C and Adriamycin), either alone or followed by gelfoam embolization. Fisher's exact test of probability was used to determine which prognostic factors were statistically significant. Statistically significant prognostic factors were as follows : Child classification(p 0.05). The prognosis of patients with hepatocellular carcinoma treated by TACE was affected favorably by good liver function(Child classification A), low alpha-fetoprotein value, nodular or massive-type tumor, patent main and first-order portal vein, and hypervascular tumor

  8. FBX8 Acts as an Invasion and Metastasis Suppressor and Correlates with Poor Survival in Hepatocellular Carcinoma.

    Directory of Open Access Journals (Sweden)

    Feifei Wang

    Full Text Available F-box only protein 8 (FBX8, a novel component of F-box proteins, is lost in several cancers and has been associated with invasiveness of cancer cells. However, its expression pattern and role in the progression of hepatocellular carcinoma remain unclear. This study investigated the prognostic significance of FBX8 in hepatocellular carcinoma samples and analyzed FBX8 function in hepatocellular carcinoma cells by gene manipulation.The expression of FBX8 was detected in 120 cases of clinical paraffin-embedded hepatocellular carcinoma tissues, 20 matched pairs of fresh tissues and five hepatocellular carcinoma cell lines by immunohistochemistry with clinicopathological analyses, real-time RT-PCR or Western blot. The correlation of FBX8 expression with cell proliferation and invasion in five HCC cell lines was analyzed. Moreover, loss of function and gain of function assays were performed to evaluate the effect of FBX8 on cell proliferation, motility, invasion in vitro and metastasis in vivo.We found that FBX8 was obviously down-regulated in HCC tissues and cell lines (P<0.05. The FBX8 down-regulation correlated significantly with poor prognosis, and FBX8 status was identified as an independent significant prognostic factor. Over-expression of FBX8 decreased proliferation, migration and invasion in HepG2 and 97H cells, while knock-down of FBX8 in 7721 cells showed the opposite effect. FBX8 negatively correlated with cell proliferation and invasion in 7701, M3, HepG2 and 97H cell lines. In vivo functional assays showed FBX8 suppressed tumor growth and pulmonary metastatic potential in mice. Our results indicate that down-regulation of FBX8 significantly correlates with invasion, metastasis and poor survival in hepatocellular carcinoma patients. It may be a useful biomarker for therapeutic strategy and control in hepatocellular carcinoma treatment.

  9. Analysis of prognostic factors in patients with hepatocellular carcinoma after transcatheter hepatic arterial chemoembolization(TAE)

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Tae Gwon; Byun, Kyung Hwan; Oh, Hyun Han; Ryeom, Hun Kyu; Kim, Yong Joo [Kyungpook National Univ. Hospital, Taegu (Korea, Republic of)

    1996-07-01

    To evaluate long-term survival rates and prognostic factors of patients with hepatocellular carcinoma after TAE. 225 patients with hepatocellular carcinoma treated with TAE between January 1988 and December 1994 were studied. Hepatocellular carcinoma was diagnosed either histologically(n=13) or clinically on the basis of findings characteristic for hepatocellular carcinoma obtained using such as diagnostic imaging methods such as ultrasonography, CT, MRI, and angiography as well as on the basis of high serum alpha-fetoprotein level(n=212). TAE was carried out between one and six times(mean, 1.4 time) using a mixture of lipiodol and Adriamycin, together with Gelfoam. Cumulative survival rates from the day of the first TAE were obtained by the Kaplan-Meier method. Parameters likely to influence the prognosis were subjected to univariate analysis using the log-rank test Cumulative survival rates at the end of the first, second, third, fourth, and fifth year were 55.9%, 32.6%, 21.9%, 17.9%, and 15.0%, respectively. The mean survival time was 727{+-}76 days. Several factors, including Child-Pugh classification, Okuda's stage, tumor size, presence of portal vein invasion by tumor, of arterio-portal shunt, and of extrahepatic metastases, catheter selection level, and number of TAE showed significant correlation with the outcome. Degrees of Lipiodol accumulation in a tumor on follow up CT were also correlated with survival rates. TAE is an effective measure for prolonging the patient's life expectancy and evaluation of prognostic factor is helpful for prognosis and in deciding on the optimal therapeutic modality.

  10. Combined Primary Neuroendocrine Carcinoma and Hepatocellular Carcinoma of the Liver

    Directory of Open Access Journals (Sweden)

    Chii-Shuenn Yang

    2009-08-01

    Full Text Available We report a unique case of combined primary neuroendocrine carcinoma (NEC and hepatocellular carcinoma (HCC of the liver in a 65-year-old male patient. The patient underwent segmental resection of the liver and regional lymph node dissection for a tumor mass that measured 7.5 cm in diameter in the right lobe, with regional lymphadenopathy. Histologically, the hepatic tumor was composed of predominantly small-cell NEC, but admixed with a small island of moderately differentiated HCC. We speculate that the NEC originated from a poorly differentiated tumor clone of an HCC that underwent neuroendocrine differentiation, and that this tumor was now at the end stage of the transitional period from HCC to NEC, based on the small amount of disappearing HCC. Ki-67 and p53 expression were higher in the NEC than in the HCC, and the lymph nodes showed only metastatic NEC. Therefore, this kind of tumor had a more aggressive clinical course in accordance with being an NEC rather than a conventional HCC. Three months after operation, the patient had multiple recurrent tumor nodules within the liver, spreading the metastasis to the adrenal glands and para-aortic lymph nodes. The patient died 1 year after operation.

  11. Factors associated with tumor size of hepatocellular carcinoma

    Science.gov (United States)

    Siregar, G. A.; Buulolo, B. A.

    2018-03-01

    Determining the association of age and laboratory parameters with tumor size of hepatocellular carcinoma (HCC). The study was at Adam Malik Hospital Medan from June- December 2016. 100 HCC patients were enrolled; those with excluding liver metastatic. Baseline characteristics of gender, age, obtaining etiology of HCC. Liver function tests, viral marker, and INR were done. Based on tumor size from abdomen CT, patients were three groups: tumor size below 3 cm, 3-5 cm, and above 5 cm size. Patients were also divided based on Child-Pugh class. Correlation of age and laboratory results with tumor size of HCC patients were analyzed. Age have negative correlation with tumor size in HCC patients (r=-0.297, p=0.032) while AFP have positive correlation with tumor size (r0.446, p=<0.001). Total bilirubin, AST, and ALT have negative correlation but non-significant (r=-0.045, -0.078, - 0.126 respectively). Albumin and INR have positive correlation but non-significant (r=0.021, 0.112 respectively). Our study suggests that older age correlates with smaller tumor size, while AFP level has a significant correlation with tumor size in HCC patients. AFP level may be a useful marker for determining the prognosis of HCC patients.

  12. ANGIOGENESIS INHIBITORS FOR THE TREATMENT OF HEPATOCELLULAR CARCINOMA

    Directory of Open Access Journals (Sweden)

    Massimiliano Berretta

    2016-11-01

    Full Text Available Background: Angiogenesis inhibitors have become an important therapeutic approach in the treatment of hepatocellular carcinoma (HCC patients. The achievement of Sorafenib in prolonging overall survival of patients with HCC makes therapeutic inhibition of angiogenesis a fundamental element of the treatment of HCC. Considering the heterogeneous aspects of HCC and to enhance therapeutic efficacy, overcome drug resistance and reduce toxicity, the combination of antiangiogenic drugs with antiblastic chemotherapy (AC, radiotherapy or other targeted drugs have been evaluated. The issue is further complicated by the combination of antiangiogenesis with other AC or biologic drugs. To date, there is no planned approach to determine which patients are more responsive to a given type of antiangiogenic treatment. Conclusion: Large investments in the clinical research are essential to improve treatment response and minimize toxicities for patients with HCC. Future investigations will need to focus on utilizing patterns of genetic information to classify HCC into groups that display similar prognosis and treatment sensitivity, and combining targeted therapies with AC producing enhanced anti-tumor effect. In this review the current panel of available antiangiogenic therapies for the treatment of HCC have been analyzed. In addition current clinical trials are also reported herein.

  13. Transcatheter arterial chemoembolization of hepatocellular carcinoma with portal vein invasion

    International Nuclear Information System (INIS)

    Lee, Young Rahn; Lee, Ki Yeol; Cho, Seong Beom; Cha, In Ho; Chung, Kyoo Byung

    1993-01-01

    Transcatheter arterial chemoembolization(TACE) is an imperative method for the management of inoperable hepatocellular carcinoma(HCC). It is well known that primary HCC frequently invades the portal venous system and forms a tumor thrombus obstructing the portal blood flow which makes unfavorable prognosis of patient. We retrospectively reviewed 58 patients who reviewed TACE(minimum 3 times) of HCC invading into portal venous system. Group 1(n=29) which showed peripheral portal vein invasion had better clinical and laboratory response. Group 2(n=17) which showed first order portal branch invasion had similar response to Group 3(n=12), which had main portal invasion. Group 1 showed no difference in survival time between TAC and TACE, but, in Group 2 and 3, embolization with chemotherapy made longer survival than chemotherapy only. Clinical level of AFP was meaningful in Group 1 and 2 as decreasing value. Our results provides that careful selection of TAE and case by case Coil/Gelfoam embolization can improve the mean survival and clinical response when HCC evidently invades portal venous system

  14. Adrenalectomy for metastases from hepatocellular carcinoma - a single center experience.

    Science.gov (United States)

    Popescu, Irinel; Alexandrescu, Sorin; Ciurea, Silviu; Brasoveanu, Vlad; Hrehoret, Doina; Gangone, Eliza; Boros, Mirela; Herlea, Vlad; Croitoru, Adina

    2007-05-01

    Adrenal metastases (AM) from hepatocellular carcinoma (HCC) are rarely seen in clinical practice. The treatment is not standardized, the indications and efficacy of different therapeutic approaches being still controversial. Between January 1995 and December 2005, 174 patients underwent liver resection for HCC in our center. AM were detected in four patients (2.3%): three of them had HCC and synchronous AM, and the remaining one developed AM 10 months after liver resection. All the patients with AM were treated by adrenalectomy (simultaneously with liver resection in synchronous metastases), followed by systemic chemotherapy. Non-resectable multifocal liver recurrences occurred in two patients, one of them having also a contralateral adrenal metastasis; these two patients are presently alive 26 and 43 months after adrenalectomy, respectively. Another patient died by liver recurrence 27 months postoperatively. The fourth patient is disease-free at 17 months after the initial operation. Adrenalectomy for AM from HCC should be performed whenever the primary tumor is well therapeutically controlled and the patient has a good performance status. Adrenalectomy offers the chance of more than 2 years survival in many patients. However, once AM are detected, the prognosis remains poor.

  15. Diagnosis and treatment of hepatocellular carcinoma: An update

    Science.gov (United States)

    Tejeda-Maldonado, Javier; García-Juárez, Ignacio; Aguirre-Valadez, Jonathan; González-Aguirre, Adrián; Vilatobá-Chapa, Mario; Armengol-Alonso, Alejandra; Escobar-Penagos, Francisco; Torre, Aldo; Sánchez-Ávila, Juan Francisco; Carrillo-Pérez, Diego Luis

    2015-01-01

    Hepatocellular carcinoma (HCC) is one of the most common malignancies leading to high mortality rates in the general population; in cirrhotic patients, it is the primary cause of death. The diagnosis is usually delayed in spite of at-risk population screening recommendations, i.e., patients infected with hepatitis B or C virus. Hepatocarcinogenesis hinges on a great number of genetic and molecular abnormalities that lead to tumor angiogenesis and foster their dissemination potential. The diagnosis is mainly based on imaging studies such as computed tomography and magnetic resonance, in which lesions present a characteristic classical pattern of early arterial enhancement followed by contrast medium “washout” in late venous phase. On occasion, when imaging studies are not conclusive, biopsy of the lesion must be performed to establish the diagnosis. The Barcelona Clinic Liver Cancer staging method is the most frequently used worldwide and recommended by the international guidelines of HCC management. Currently available treatments include tumor resection, liver transplant, sorafenib and loco-regional therapies (alcoholization, radiofrequency ablation, chemoembolization). The prognosis of hepatocarcinoma is determined according to the lesion’s stage and in cirrhotic patients, on residual liver function. Curative treatments, such as liver transplant, are sought in patients diagnosed in early stages; patients in more advanced stages, were not greatly benefitted by chemotherapy in terms of survival until the advent of target molecules such as sorafenib. PMID:25848464

  16. Magnetic Resonance Imaging Finding of Metastatic Hepatocellular Carcinoma in Ovary: A Case Report

    International Nuclear Information System (INIS)

    Kwak, Soon Hyuk; Cho, Bum Sang; Kang, Min Ho; Lee, Seung Young; Han, Gi Seok; Cha, Sang Hoon; Park, Kil Sun; Kim, Sung Jin; Choi, Song Yi

    2011-01-01

    Hepatocellular carcinoma is the most common primary malignant tumor of liver. Metastasis of hepatocellular carcinoma occurs in various organs, but metastasis to the ovary is extremely rare. We report MRI finding of metastatic hepatocellular carcinoma of the ovary in a 37-year-old woman who was treated hepatocellular carcinoma transarterial chemoembolization and radiofrequency ablation a year ago. Pelvic MRI revealed a mass in pelvic cavity with heterogeneous signal intensity and centripetal enhancement. Surgical excision and pathologic examination confirmed metastatic hepatocellular carcinoma in the ovary.

  17. How to detect hepatocellular carcinoma in cirrhosis

    Energy Technology Data Exchange (ETDEWEB)

    Ward, Janice; Robinson, Philip J. [Department of Clinical Radiology, St. James' s University Hospital, Beckett Street, Leeds LS9 7TF (United Kingdom)

    2002-09-01

    Cirrhosis predisposes to hepatocellular carcinoma (HCC) which develops by sequential steps of de-differentiation of hepatocytes from regenerative nodules via borderline (dysplastic) nodules to frankly malignant HCC. Effective treatment depends on early recognition of HCC, so the key tasks for imaging are firstly recognising the presence of a suspicious lesion, and secondly differentiating between benign, borderline and malignant nodules. Screening of high-risk cirrhotic patients with sonography and measurement of alpha fetoprotein (AFP) is helpful but will not reliably differentiate small HCC from benign or dysplastic nodules. Large HCCs can usually be recognised by their characteristic morphology on imaging, but the appearances of smaller benign and malignant nodules show considerable overlap on unenhanced sonography, CT and MRI. Increasing degrees of histological malignancy are associated with increasing arterialisation and loss of portal blood supply, so the recognition of HCC requires the use of dynamic imaging with contrast-enhanced CT or T1-weighted MRI with gadolinium enhancement. Sonography with microbubble contrast media now offers another method for detecting arterialised nodules; however, some non-malignant nodules show arterial hypervascularity and a minority of HCCs are hypovascular, so the assessment of perfusion does not conclusively distinguish benign from malignant lesions. Kupffer cell function is another attribute of liver tissue which can be explored using MRI with superparamagnetic iron oxide particles (SPIO). Experience thus far suggests that uptake of SPIO is an effective discriminator between benign and malignant nodules. The combination of SPIO with gadolinium-enhanced MRI offers the opportunity for imaging characterisation of cirrhotic nodules by cellular function as well as by blood supply, and this approach is now proposed as the examination of choice for detecting HCC in cirrhosis. (orig.)

  18. Epidemiology of hepatocellular carcinoma in India.

    Science.gov (United States)

    Acharya, Subrat K

    2014-08-01

    Indian data on epidemiology of HCC is not available. Cancer is not a reportable disease in India and the cancer registries in India are mostly urban. National cancer registry program of the Indian Council of Medical Research (ICMR) has been recently expanded to include 21 population based and 6 hospital based cancer registries. The last published registry data by ICMR available in the cancer registry website (www.ncrpindia.org) was in 2008 which provides information on various cancers from 2006 to 2008. The other source of information was the report published by International Agency for Research on Cancer (WHO). According to these available data the age adjusted incidence rate of hepatocellular carcinoma (HCC) in India for men ranges from 0.7 to 7.5 and for women 0.2 to 2.2 per 100,000 population per year. The male:female ratio for HCC in India is 4:1. The age of presentation varies from 40 to 70 years. According to a study conducted by verbal autopsy in 1.1 million homes representing the whole country, the age standardized mortality rate for HCC in India for men is 6.8/100,000 and for women is 5.1/100,000. According to another study the incidence of HCC in cirrhotics in India is 1.6% per year. The unpublished data from various tertiary care centers suggest that the incidence of HCC is increasing in India. There is a need for a multi-centric HCC registry under the aegis of INASL.

  19. Dichlorodiphenyltrichloroethane (DDT) and risk of hepatocellular carcinoma

    Science.gov (United States)

    Persson, E. Christina; Graubard, Barry I.; Evans, Alison A.; London, W. Thomas; Weber, Jean-Philippe; LeBlanc, Alain; Chen, Gang; Lin, Wenyao; McGlynn, Katherine A.

    2014-01-01

    Dichlorodiphenyltrichloroethane (p,p’-DDT), an organochlorine pesticide known to have deleterious health effects in humans, has been linked to hepatocellular carcinoma (HCC) in rodents. A recent study has reported that p,p’-DDT and its most persistent metabolite, dichlorodiphenyldichloroethylene (p,p’-DDE), may also be associated with HCC in humans. To examine whether there is an association between p,p’-DDT and/or p,p’-DDE in a population at high-risk of developing HCC. A nested case-control study was conducted within the 83,794 person Haimen City Cohort in China. Sera and questionnaire data were collected from all participants between 1992 and 1993. The current study included 473 persons who developed HCC and 492 who did not, frequency matched on sex, age and area of residence. p,p’-DDT and p,p’-DDE levels were determined by mass spectrometry. Hepatitis B viral infection status (based on hepatitis B virus surface antigen; HBsAg) was also determined. Adjusting for age, sex, area of residence, HBsAg, family history of HCC, history of acute hepatitis, smoking, alcohol, occupation (farmers) and levels of p,p’-DDT or p,p’-DDE, odds ratios (OR) and 95% confidence intervals (CI) were calculated via unconditional logistic regression, p,p’-DDT and/or p,p’-DDE serum levels were significantly associated with sex, area of residence, occupation, alcohol consumption and cigarette smoking. Overall, the highest quintile of p,p’-DDT was associated with an increased risk of HCC, OR= 2.96 95% CI; 1.19–7.40. There were no statistically significant associations with p,p’-DDE. Overall, these results suggest that recent exposure to p,p’-DDT may increase risk of HCC. PMID:22290210

  20. Targeting cancer stem cells in hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    He AR

    2014-12-01

    Full Text Available Aiwu Ruth He,1 Daniel C Smith,1 Lopa Mishra2 1Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, 2Department of Gastroenterology, Hepatology, and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX, USA Abstract: The poor outcome of patients with hepatocellular carcinoma (HCC is attributed to recurrence of the disease after curative treatment and the resistance of HCC cells to conventional chemotherapy, which may be explained partly by the function of liver cancer stem cells (CSCs. Liver CSCs have emerged as an important therapeutic target against HCC. Numerous surface markers for liver CSCs have been identified, and include CD133, CD90, CD44, CD13, and epithelial cell adhesion molecules. These surface markers serve not only as tools for identifying and isolating liver CSCs but also as therapeutic targets for eradicating these cells. In studies of animal models and large-scale genomic analyses of human HCC samples, many signaling pathways observed in normal stem cells have been found to be altered in liver CSCs, which accounts for the stemness and aggressive behavior of these cells. Antibodies and small molecule inhibitors targeting the signaling pathways have been evaluated at different levels of preclinical and clinical development. Another strategy is to promote the differentiation of liver CSCs to less aggressive HCC that is sensitive to conventional chemotherapy. Disruption of the tumor niche essential for liver CSC homeostasis has become a novel strategy in cancer treatment. To overcome the challenges in developing treatment for liver CSCs, more research into the genetic makeup of patient tumors that respond to treatment may lead to more effective therapy. Standardization of HCC CSC tumor markers would be helpful for measuring the CSC response to these agents. Herein, we review the current strategies for developing treatment to eradicate liver CSCs and to improve the outcome for patients with

  1. Angiogenic Blockade and Radiotherapy in Hepatocellular Carcinoma

    International Nuclear Information System (INIS)

    Chi, Kwan-Hwa; Liao, Chao-Sheng; Chang, Chih-Chia; Ko, Hui-Ling; Tsang, Yuk-Wah; Yang, Kuo-Ching; Mehta, Minesh P.

    2010-01-01

    Purpose: We report our preliminary experience of combining sunitinib and helical tomotherapy in patients with advanced HCC. Methods and Materials: Records of patients with advanced hepatocellular carcinoma (HCC) treated with helical tomotherapy and sunitinib after radiation therapy (RT) from March 2007 to August 2008 were retrospectively reviewed. We report acute toxicities, radiologic response, serial α-fetoprotein (AFP) kinetics, and survival. Results: Of 23 evaluable patients, 60% had ≥2 hepatic lesions, extrahepatic disease was present in 5 (21.7%), and all received 2 tablets (25 mg) of sunitinib at least 1 week before, during, and 2 weeks after RT. Thirteen patients continued maintenance sunitinib after RT until disease progression. Hypofractionated RT with a median target dose of 52.5 Gy/15 fractions was delivered. An objective response was achieved in 74% of patients. The 1-year survival rate was 70%, with median survival of 16 months. Multivariate analysis showed that maintenance sunitinib was the most significant factor for survival. The time to progression was 10 months in the maintenance group compared with 4 months in the control group. Eighteen out of 21 patients with elevated AFP (85.7%) had ≥50% decline of AFP within 2 months after RT. There were three episodes of upper gastrointestinal bleeding and one episode of pancreatitis; 10 patients had ≥Grade 2 elevation of liver enzymes, and 15 had ≥Grade 2 thrombocytopenia. Conclusions: These preliminary results suggest that sunitinib and helical tomotherapy yield high Response Evaluation Criteria in Solid Tumors (RECIST) and AFP response rates in advanced HCC with an acceptable safety profile. Maintenance sunitinib after RT potentially prolongs survival. A randomized trial is warranted.

  2. Hemodynamic characteristics of early stage hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Kudo, Masatoshi; Tomita, Shusuke; Tochio, Hitoshi

    1992-01-01

    Hemodynamic characteristics were studied by using in vivo vascular imaging techniques in 17 resected early stage hepatocellular carcinoma (e-HCC) by comparing them with 49 resected advanced HCCs (ad-HCC) less than 3 cm in diameter. In this study, e-HCC was defined as the nodule being uniformly composed of well-differentiated HCC or adenomatous hyperplastic nodule containing well-differentiated HCC foci within the nodule. In vivo vascular imaging techniques are as follows; US angiography with intraarterial CO 2 microbubbles were performed to assess the tumor arterial vascularity, and CT during arterial portography (CTAP) was performed to assess the portal perfusion within the nodule. Of 17 e-HCC nodules 5 were hypervascular, 5 were isovascular, 4 were hypovascular, and 3 were vascular spot in hypovascular pattern in contrast to 49 ad-HCC nodules, 43 of which were hypervascular and 6 were isovascular. Of 14 e-HCCs, 9 nodules showed perfusion defect and 5 did not on CTAP, whereas all 37 ad-HCCs on which CTAP was performed, showed perfusion defect. Forty-one percent (7/17) of e-HCC showed fatty metamorphosis in contrast to 8% (4/49) of ad-HCC. In conclusion, hemodynamic characteristics of e-HCC are summarized as follows. (1) Arterial tumor neovascularization is relatively low. (2) Portal perfusion is present in some of e-HCC cases. (3) Hypoperfusion state both from arterial and portal supply is present in some of e-HCC cases. (4) Vascular spot in hypovascular pattern is characteristic arterial pattern in AH containing HCC foci. (5) Fatty metamorphosis may be related with hypoperfusion state of the nodule in e-HCC. (author)

  3. Specific diagnosis of hepatocellular carcinoma by delayed hepatobiliary imaging

    International Nuclear Information System (INIS)

    Hasegawa, Y.; Nakano, S.; Ibuka, K.

    1986-01-01

    For assessment of the value of delayed hepatobiliary imaging with technetium 99m (/sup 99m/Tc)-(Sn)-N-pyridoxyl-5-methyltryptophan (/sup 99m/Tc-PMT) for specific diagnosis of hepatocellular carcinoma, 88 patients with various malignant and benign liver diseases (49 with hepatocellular carcinoma, 4 with cholangiocellular carcinoma, 10 with metastatic liver carcinoma, 2 with liver cysts, 2 with liver hemangioma, 1 with liver abscess, 2 with intrahepatic lithiasis, 12 with liver cirrhosis, and 6 with chronic hepatitis) were studied. In 20 (41%) of the 49 patients with hepatocellular carcinoma, greater uptake of /sup 99m/Tc-PMT by the tumor than by the surrounding liver tissue was seen in delayed hepatobiliary images, whereas in eight patients (16%), equilibrated uptake was seen. No increased uptake of the radioisotope by hepatic lesions was seen in 21 patients with localized liver diseases other than hepatoma. Moreover, in 18 patients with diffuse liver diseases, no focal accumulation of the radioisotope was seen in delayed /sup 99m/Tc-PMT images. In addition, of 28 patients with hepatocellular carcinoma in whom the serum alpha-fetoprotein level showed little or no increase, 12 showed increased uptake of /sup 99m/Tc-PMT by the tumor. In assessing delayed /sup 99m/Tc-PMT images, however, it was necessary to consider following complications: accumulation of tracer in obstructed and dilated biliary trees; retention of radioactivity in nonneoplastic liver tissues; difficulties in evaluating /sup 99m/Tc-PMT uptake by small hepatic tumors; overlapping of radioactivity in the gut and gallbladder in delayed /sup 99m/Tc-PMT images of tumors. This study indicates that delayed /sup 99m/Tc-PMT images can be useful in the diagnosis of hepatocellular carcinoma

  4. SERUM LEPTIN LEVENS AND HEPATOCELLULAR CARCINOMA: REVIEW ARTICLE.

    Science.gov (United States)

    Andrighetto, Luiza Vitelo; Poziomyck, Aline Kirjner

    2016-01-01

    Hepatocellular carcinoma is one of the most frequent types of malignant tumors in the world. There is growing evidence of the relationship between it development and obesity. The mechanism that links obesity to cancer is still not fully understood; however, it is essential to the understanding the adipose tissue in metabolic changes related to obesity and hepatocellular carcinoma. To review the influence of serum leptin levels in patients with hepatocelular carcinoma. Systematic review of the literature based on the methodology of the Cochrane Institute. The search for articles was in the database: Science Direct, Scielo, Medline, Lilacs e Pubmed. The key words used were hepatocellular carcinoma, leptin, adipokine. After evaluation of individual studies, were selected seven studies. The results previously studied are still inconsistent and contradictory, and leptin can be effectively involved in the occurrence and development of hepatocellular carcinoma. Therefore, it is necessary to develop prospective, well-designed and conducted focusing on the role and specific mechanisms of this hormone in patients with hepatocellular carcinoma, so that new correlations can be properly supported. O carcinoma hepatocelular é um dos tipos mais frequentes de tumores malignos no mundo. Há crescentes evidências da relação entre o seu desenvolvimento e a obesidade. O mecanismo que os relaciona ainda não é completamente entendido. Entretanto é essencial a compreensão do tecido adiposo nas alterações metabólicas relacionadas à obesidade e ao câncer. Revisar a influência dos níveis séricos de leptina em pacientes com carcinoma hepatocelular. Trata-se de revisão bibliográfica baseada na metodologia do Instituto Cochrane; a busca de dados foi realizada na base de dados Science Direct, Scielo, Medline, Lilacs e Pubmed, empregando as seguintes descritores: hepatocellular carcinoma, leptin, adipokine. Após avaliação individual dos artigos selecionaram-se sete estudos

  5. Expression features and prognostic significance of Yes-associated protein in hepatocellular carcinoma and cholangiocellular carcinoma

    Directory of Open Access Journals (Sweden)

    WANG Chun

    2017-07-01

    Full Text Available ObjectiveTo investigate the expression of Yes-associated protein (YAP in hepatocellular carcinoma (HCC and cholangiocellular carcinoma (CC and its association with clinical prognosis. MethodsSamples were collected from 190 patients who were treated in The Second Hospital Affiliated to Chongqing Medical University from July 2004 to July 2009, among whom 110 had HCC and 80 had CC. The difference in YAP expression and its association were analyzed in both groups, and patients′ prognosis was compared between the two groups. The chi-square test was used to investigate the association between YAP expression and clinicopathological features of HCC and CC, and the Kaplan-Meier method and the log-rank test were used to assess tumor-free survival rate and overall survival rate. A univariate Cox regression analysis was used to evaluate the influence of YAP expression on the prognosis of patients with HCC and CC. ResultsThe CC group had higher expression of YAP than the HCC group (68.7% vs 56.3%, P=0.036. High YAP expression in HCC and CC was significantly associated with tumor size (P<0.001 and P=0.024, alpha fetoprotein (P=0.009 and 0034, liver cirrhosis (P=0032 and 0.006, vascular invasion (P=0.011 and 0.028, and intrahepatic metastasis (P=0.049 and 0030. In both groups, the patients with high YAP expression had significantly lower tumor-free survival rate and overall survival rate than those with low YAP expression(all P<005. Multivariate analysis showed that high YAP expression is an adverse prognostic factor for tumor-free survival and overall survival in both groups (all P<005. ConclusionHigh YAP expression is frequently found in patients with HCC and CC, and high YAP expression is associated with low survival rate.

  6. Leptomeningeal metastasis from hepatocellular carcinoma with other unusual metastases: a case report

    International Nuclear Information System (INIS)

    Pan, Zhenyu; Yang, Guozi; Yuan, Tingting; Pang, Xiaochuan; Wang, Yongxiang; Qu, Limei; Dong, Lihua

    2014-01-01

    Leptomeningeal metastasis, which results from metastasis of tumors to the arachnoid and pia mater, can lead to the dissemination of tumor cells throughout the subarachnoid space via the cerebral spinal fluid, and frequently with a poor prognosis. The primary tumor in adults is most often breast cancer, lung cancer, or melanoma. Although leptomeningeal metastasis due to cholangiocarcinoma has been reported, to the best of our knowledge there is no cytologically confirmed report of leptomeningeal metastasis from hepatocellular carcinoma. We herein report a case of leptomeningeal metastasis from hepatocellular carcinoma in a 53-year-old woman with concomitant systemic metastases to the lung, bone, brain, kidney, adrenal gland, subcutaneous tissues, and abdominal pelvis. The neurological symptoms of the patient were relieved after treatment with methotrexate intra-cerebral spinal fluid chemotherapy concurrent with whole brain radiotherapy. To our knowledge this is the first report of leptomeningeal metastasis from hepatocellular carcinoma confirmed by cytology. Treatment with methotrexate intra-cerebral spinal fluid chemotherapy concurrent with whole brain radiotherapy was effective

  7. [Hepatocellular carcinoma originated in the caudate lobe. Surgical strategy for resection. A propos of a case].

    Science.gov (United States)

    Martínez-Mier, Gustavo; Esquivel-Torres, Sergio; Calzada-Grijalva, José Francisco; Grube-Pagola, Peter

    2015-01-01

    Hepatocellular carcinoma originating from the caudate lobe has a worse prognosis than other hepatocellular carcinoma in another segment of the liver. An isolated caudate lobe resection of the liver represents a significant technical challenge. Caudate lobe resection can be performed along with a lobectomy or as an isolated liver resection. There are very few reports about isolated caudate lobe liver resection. We report a case of successful isolated resection of hepatocellular carcinoma in the caudate lobe with excellent long-term survival. A 74 years old female with 8cm mass lesion in the caudate lobe without clinical or biochemical evidence of liver cirrhosis, serum alpha-fetoprotein 3.7 U/l, and negative hepatitis serology was evaluated for surgery. Complete resection of the lesion in 270minutes with Pringle maneuver for 13minutes was satisfactorily performed. Patient was discharged ten days after surgery without complications. Patient is currently asymptomatic, without deterioration of liver function and 48 month tumor free survival after the procedure. Isolated caudate lobe resection is an uncommon but technically possible procedure. In order to achieve a successful resection, one must have a detailed knowledge of complete liver anatomy. Tumor free margins must be obtained to provide long survival for these patients who have a malignancy in this anatomic location. Copyright © 2015. Published by Masson Doyma México S.A.

  8. Liver resection for non-cirrhotic hepatocellular carcinoma in south ...

    African Journals Online (AJOL)

    Background. We describe the clinicopathologic features and outcome of South African patients who have undergone hepatic resection for hepatocellular carcinoma (HCC) arising in a non-cirrhotic liver. Methods. We utilised the prospective liver resection database in the Surgical Gastroenterology Unit at Groote Schuur ...

  9. Rottlerin upregulates DDX3 expression in hepatocellular carcinoma.

    Science.gov (United States)

    Wang, Zhong; Shen, Gen-Hai; Xie, Jia-Ming; Li, Bin; Gao, Quan-Gen

    2018-01-01

    Rottlerin has been reported to exert its anti-tumor activity in various types of human cancers. However, the underlying molecular mechanism has not been fully elucidated. In the current study, we explored whether rottlerin exhibits its tumor suppressive function in hepatocellular carcinoma cells. Our MTT assay results showed that rottlerin inhibited cell growth in hepatocellular carcinoma cells. Moreover, we found that rottlerin induced cell apoptosis and caused cell cycle arrest at G1 phase. Furthermore, our wound healing assay result demonstrated that rottlerin retarded cell migration in hepatocellular carcinoma cells. Additionally, rottlerin suppressed cell migration and invasion. Notably, we found that rottlerin upregulated DDX3 expression and subsequently downregulated Cyclin D1 expression and increased p21 level. Importantly, down-regulation of DDX3 abrogated the rottlerin-mediated tumor suppressive function, whereas overexpression of DDX3 promoted the anti-tumor activity of rottlerin. Our study suggests that rottlerin exhibits its anti-cancer activity partly due to upregulation of DDX3 in hepatocellular carcinoma cells. Copyright © 2017 Elsevier Inc. All rights reserved.

  10. Infection of hepatitis C virus genotypes in hepatocellular carcinoma ...

    African Journals Online (AJOL)

    The aim of this retrospective study was to investigate the infection of hepatitis C virus (HCV) genotypes in hepatocellular carcinoma (HCC) patients from rural areas of Faisalabad region. Among 179 HCC subjects, men and women were 51 and 49%, respectively. All samples positive for HCV RNA by qualitative PCR were ...

  11. Magnetic Nanoparticles for Hepatocellular Carcinoma Diagnosis and Therapy

    DEFF Research Database (Denmark)

    Ungureanu, Bogdan Silviu; Teodorescu, Cristian-Mihail; Săftoiu, Adrian

    2016-01-01

    Hepatocellular carcinoma (HCC) is the most common primary tumor of the liver, ranking as the second most common cause of death from cancer worldwide. Magnetic nanoparticles (MNPs) have been used so far in tumor diagnosis and treatment, demonstrating great potential and promising results...

  12. Metabolomic profiles of hepatocellular carcinoma in a European prospective cohort

    NARCIS (Netherlands)

    Fages, Anne; Duarte-Salles, Talita; Stepien, Magdalena; Ferrari, Pietro; Fedirko, Veronika; Pontoizeau, Clement; Trichopoulou, Antonia; Aleksandrova, Krasimira; Tjonneland, Anne; Olsen, Anja; Clavel-Chapelon, Franoise; Boutron-Ruault, Marie-Christine; Severi, Gianluca; Kaaks, Rudolf; Kuhn, Tilman; Floegel, Anna; Boeing, Heiner; Lagiou, Pagona; Bamia, Christina; Trichopoulos, Dimitrios; Palli, Domenico; Pala, Valeria; Panico, Salvatore; Tumino, Rosario; Vineis, Paolo; Bueno-de-Mesquita, H. Bas; Peeters, Petra H.; Weiderpass, Elisabete; Agudo, Antonio; Molina-Montes, Esther; Maria Huerta, Jose; Ardanaz, Eva; Dorronsoro, Miren; Sjoberg, Klas; Ohlsson, Bodil; Khaw, Kay-Tee; Wareham, Nick; Travis, Ruth C.; Schmidt, Julie A.; Cross, Amanda; Gunter, Marc; Riboli, Elio; Scalbert, Augustin; Romieu, Isabelle; Elena-Herrmann, Benedicte; Jenab, Mazda

    2015-01-01

    Background: Hepatocellular carcinoma (HCC), the most prevalent form of liver cancer, is difficult to diagnose and has limited treatment options with a low survival rate. Aside from a few key risk factors, such as hepatitis, high alcohol consumption, smoking, obesity, and diabetes, there is

  13. Co-ordinate activation of lipogenic enzymes in hepatocellular carcinoma.

    Science.gov (United States)

    Yahagi, Naoya; Shimano, Hitoshi; Hasegawa, Kiyoshi; Ohashi, Kenichi; Matsuzaka, Takashi; Najima, Yuho; Sekiya, Motohiro; Tomita, Sachiko; Okazaki, Hiroaki; Tamura, Yoshiaki; Iizuka, Yoko; Ohashi, Ken; Nagai, Ryozo; Ishibashi, Shun; Kadowaki, Takashi; Makuuchi, Masatoshi; Ohnishi, Shin; Osuga, Jun-ichi; Yamada, Nobuhiro

    2005-06-01

    Hepatocellular carcinoma is a very common neoplastic disease in countries where hepatitis viruses B and/or C are prevalent. Small hepatocellular carcinoma lesions detected by ultrasonography at an early stage are often hyperechoic because they are composed of well-differentiated cancer cells that are rich in triglyceride droplets. The triglyceride content of hepatocytes depends in part on the rate of lipogenesis. Key lipogenic enzymes, such as fatty acid synthase, are co-ordinately regulated at the transcriptional level. We therefore examined the mRNA expression of lipogenic enzymes in human hepatocellular carcinoma samples from 10 patients who had undergone surgical resection. All of the samples exhibited marked elevation of expression of mRNA for lipogenic enzymes, such as fatty acid synthase, acetyl-CoA carboxylase and ATP citrate lyase, compared with surrounding non-cancerous liver tissue. In contrast, the changes in mRNA expression of SREBP-1, a transcription factor that regulates a battery of lipogenic enzymes, did not show a consistent trend. In some cases where SREBP-1 was elevated, the main contributing isoform was SREBP-1c rather than SREBP-1a. Thus, lipogenic enzymes are markedly induced in hepatocellular carcinomas, and in some cases SREBP-1c is involved in this activation.

  14. Chronic hepatitis C presenting with a diagnosis of hepatocellular carcinoma

    DEFF Research Database (Denmark)

    Hallager, Sofie; Weis, Nina

    2014-01-01

    Chronic hepatitis C (CHC) affects around 16,000 individuals in Denmark of whom about 50% are diagnosed. In the presence of CHC and cirrhosis the annual risk of hepatocellular carcinoma (HCC) is 1-5%. We report on two patients who presented with disseminated HCC at the time of CHC diagnosis...

  15. Screening for hepatocellular carcinoma by Egyptian physicians

    Institute of Scientific and Technical Information of China (English)

    Sahar; M; Hassany; Ehab; F; Abdou; Moustafa; Mohamed; El; Taher; Afaf; Adel; Abdeltwab; Hubert; E; Blum

    2015-01-01

    AIM: To assess the practice of Egyptian physicians in screening patients for hepatocellular carcinoma(HCC). METHODS: The study included 154 physicians from all over Egypt caring for patients at risk for HCC. The study was based on a questionnaire with 20 items. Each questionnaire consisted of two parts:(1) personal information regarding the physician(name, age, specialty and type of health care setting); and(2) professional experience in the care of patients at risk for HCC development(screening, knowledge about the cause and natural course of liver diseases and HCC risk). RESULTS: Sixty-eight percent of doctors with an MD degree, 48% of doctors with a master degree or a diploma and 40% of doctors with a Bachelor of Medicine, Bachelor of Surgery certificate considered the hepatitis C virus(HCV) genotype as risk factor for HCC development(P < 0.05). Ninety percent of physicians specialized in tropical medicine, internal medicine or gastroenterology and 67% of physicians in other specialties advise patients to undergo screening for HCV and hepatitis B virus infection as well as liver cirrhosis(P < 0.05). Eighty-six percent of doctors in University Hospitals and 69% of Ministry of Health(MOH) doctors consider HCV infection as the leading cause of HCC in Egypt(P < 0.05). Seventy-two percent of doctors with an MD degree, 55% of doctors with a master degree or a diploma, 56% of doctors with an MBBCH certificate, 74% of doctors in University Hospitals and 46% of MOH hospital doctors consider abdominal ultrasonography as the most important investigation in HCC screening(P < 0.05). Sixty-five percent of physicians in tropical medicine, internal medicine or gastroenterology and 37% of physicians in other specialties recommend as HCC screening interval of 3 mo(P < 0.05). Seventy-one percent of doctors with an MD degree, 50% of doctors with a master degree or diploma and 60% of doctors with an MBBCH certificate follow the same recommendation.CONCLUSION: In Egypt, physicians

  16. Can non-selective beta-blockers prevent hepatocellular carcinoma in patients with cirrhosis?

    Science.gov (United States)

    Thiele, Maja; Wiest, Reiner; Gluud, Lise Lotte; Albillos, Agustín; Krag, Aleksander

    2013-11-01

    Hepatocellular carcinoma is the main liver-related cause of death in patients with compensated cirrhosis. The early phases are asymptomatic and the prognosis is poor, which makes prevention essential. We propose that non-selective beta-blockers decrease the incidence and growth of hepatocellular carcinoma via a reduction of the inflammatory load from the gut to the liver and inhibition of angiogenesis. Due to their effect on the portal pressure, non-selective beta-blockers are used for prevention of esophageal variceal bleeding. Recently, non-hemodynamic effects of beta-blockers have received increasing attention. Blockage of β-adrenoceptors in the intestinal mucosa and gut lymphatic tissue together with changes in type and virulence of the intestinal microbiota lead to reduced bacterial translocation and a subsequent decrease in the portal load of pathogen-associated molecular patterns. This may reduce hepatic inflammation. Blockage of β-adrenoceptors also decrease angiogenesis by inhibition of vascular endothelial growth factors. Because gut-derived inflammation and neo-angiogenesis are important in hepatic carcinogenesis, non-selective beta-blockers can potentially reduce the development and growth of hepatocellular carcinoma. Rodent and in vitro studies support the hypothesis, but clinical verification is needed. Different study designs may be considered. The feasibility of a randomized controlled trial is limited due to the necessary large number of patients and long follow-up. Observational studies carry a high risk of bias. The meta-analytic approach may be used if the incidence and mortality of hepatocellular carcinoma can be extracted from trials on variceal bleeding and if the combined sample size and follow up is sufficient. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. Tie2-Expressing Monocytes Are Associated with Identification and Prognoses of Hepatitis B Virus Related Hepatocellular Carcinoma after Resection

    OpenAIRE

    He, Yi-Feng; Wang, Chao-Qun; Yu, Yao; Qian, Jing; Song, Kang; Sun, Qi-Man; Zhou, Jian

    2015-01-01

    Background Tie2-expressing monocytes (TEMs) are found in various tumors, involved in forming tumor blood vessels and expressing several important proangiogenic factors. The goals of this study were to evaluate the value of TEMs in diagnosing and predicting the prognosis of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Methods Flow cytometry was performed to identify and count TEMs in peripheral blood monocytes from HCC patients (n = 84) receiving hepatectomy, HBV cirrhotic p...

  18. Hepatocellular carcinoma arising from hepatocellular adenoma in a hepatitis B virus-associated cirrhotic liver

    International Nuclear Information System (INIS)

    Seo, J.M.; Lee, S.J.; Kim, S.H.; Park, C.K.; Ha, S.Y.

    2012-01-01

    Hepatocellular adenoma (HCA) is a rare, benign proliferation of hepatocytes that occurs mostly in a normal liver and in extreme rare cases, occurs in a cirrhotic liver. Hepatocellular carcinomas (HCC) arising within HCA through malignant transformation is rare. The specific incidence and mechanism of malignant transformation has not been established, but the long term use of oral contraceptives is considered a causative agent. We report a case of HCC arising from HCA detected in a hepatitis B-related cirrhotic liver with serial radiologic images.

  19. Hepatocellular carcinoma arising from hepatocellular adenoma in a hepatitis B virus-associated cirrhotic liver

    Energy Technology Data Exchange (ETDEWEB)

    Seo, J.M. [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Lee, S.J., E-mail: lucia@skku.edu [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Kim, S.H. [Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Park, C.K.; Ha, S.Y. [Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2012-04-15

    Hepatocellular adenoma (HCA) is a rare, benign proliferation of hepatocytes that occurs mostly in a normal liver and in extreme rare cases, occurs in a cirrhotic liver. Hepatocellular carcinomas (HCC) arising within HCA through malignant transformation is rare. The specific incidence and mechanism of malignant transformation has not been established, but the long term use of oral contraceptives is considered a causative agent. We report a case of HCC arising from HCA detected in a hepatitis B-related cirrhotic liver with serial radiologic images.

  20. Current management of hepatocellular carcinoma: An Eastern perspective

    Science.gov (United States)

    Yim, Hyung Joon; Suh, Sang Jun; Um, Soon Ho

    2015-01-01

    Hepatocellular carcinoma (HCC) is one of the leading causes of cancer death, especially in Eastern areas. With advancements in diagnosis and treatment modalities for HCC, the survival and prognosis of HCC patients are improving. However, treatment patterns are not uniform between areas despite efforts to promote a common protocol. Although many hepatologists in Asian countries may adopt the principles of the Barcelona Clinic Liver Cancer staging system, they are also independently making an effort to expand the indications of each treatment and to combine therapies for better outcomes. Several expanded criteria for liver transplantation in HCC have been developed in Asian countries. Living donor liver transplantation is much more commonly performed in these countries than deceased donor liver transplantation, and it may be preceded by other treatments such as the down-staging of tumors. Local ablation therapies are often combined with transarterial chemoembolization (TACE) and the outcome is comparable to that of surgical resection. The indications of TACE are expanding, and there are new types of transarterial therapies. Although data on drug-eluting beads, TACE, and radioembolization in Asian countries are still relatively sparse compared with Western countries, these methods are gradually gaining popularity because of better tolerability and the possibility of improved response rates. Hepatic arterial infusion chemotherapy and radiotherapy are not included in Western guidelines, but are currently being used actively in several Asian countries. For more advanced HCCs, appropriate combinations of TACE, radiotherapy, and sorafenib can be considered, and emerging data indicate improved outcomes of combination therapies compared with single therapies. To include these paradigm shifts into newer treatment guidelines, more studies may be needed, but they are certainly in progress. PMID:25852267

  1. US Findings of Small Hepatocellular Carcinoma : Analysis of 274 cases

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Hye Weon; Lee, Hak Jong; Kim, Tae Kyung; Han, Joon Koo; Choi, Byung Ihn [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    1996-12-15

    The prognosis of hepatocellular carcinoma (HCC) is very poor because of the difficulty in early detection and association with the liver cirrhosis. Because the surgical resection or transarterial chemoembolization is the most effective treatment, the detection of the small HCCs is important. The purpose of this study was to assess the frequencies of a suggestive sonographic morphology of small HCC. In 222 patients with small HCCs less than 5 cm in diameter, each sonographic feature of 274 nodules was analyzed. HCCs were diagnosed pathologically (n = 83) or by elevated serum alpha-fetoprotein levels and characteristic angiographic {delta} Lipiodol CT findings (n = 191). The diameters of the tumors were as follows : {<=} 2 cm (n = 90),2{approx}3 cm (n = 87), and 3{approx}5 cm (n = 97). The frequencies of sonographic morphology of small HCCs including echo pattern, peripheral hypoechoic halo, lateral shadow, posterior acoustic enhancement, and the mosaic pattern were assessed. For statistical analysis of the differences of echo pattern, Chi-square test was used and for evaluation of the differences of the sonographic characteristics according to the tumor size, Friedman Two-Way ANOVA test was used. Overall, characteristics of small HCCs less than 5 cm were peripheral halo (70%), posterior enhancement (43%), and mosaic pattern (39%). In small HCCs less than 3 cm hyper echoic masses are more common than hypoechoic masses, which is different from previous peports. The smaller the mass, the more frequent the incidence of high or low echo pattern. Mixed echo pattern, peripheral halo, and mosaic pattern increased isoecho, lateral shadow, and posterior acoustic enhancement between 2 cm, 2{approx}3 cm, and 3{approx}5 cm size nodules.The understanding about the sonographic characteristics of small HCCs according to the size may be useful for the detection and characterization of the small HCCs

  2. BLZF1 expression is of prognostic significance in hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Run-Yue, E-mail: ry_huang@hotmail.com [Department of Rheumatology, The Second Affiliated Hospital, Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou 510006 (China); Su, Shu-Guang [Department of Pathology, The Affiliated Hexian Memorial Hospital of Southern Medical University, Guangzhou (China); Wu, Dan-Chun [Department of Rheumatology and Immunology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou (China); Fu, Jia [Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou 510060 (China); Zeng, Xing, E-mail: zengxing-china@163.com [Department of Rheumatology, The Second Affiliated Hospital, Guangzhou University of Chinese Medicine (Guangdong Provincial Hospital of Chinese Medicine), Guangzhou 510006 (China)

    2015-11-20

    BLZF1, a member of b-ZIP family, has been implicated in epigenetic regulation and Wnt/β-catenin signaling. Its expression and clinical significance in human cancers remain largely unknown. In this study, we showed that BLZF1 expression was reduced in hepatocellular carcinoma (HCC) tissues, compared to the paracarcinoma tissues, at both mRNA and protein levels. Results of immunohistochemistry revealed that BLZF1 was presented in both nuclear and cytoplasm. Decreased expression of nuclear and cytosolic BLZF1 in HCC was depicted in 68.2% and 79.2% of the 634 cases. Nuclear BLZF1 expression was significantly associated with tumor multiplicity (P = 0.048) and tumor capsule (P = 0.028), while cytosolic BLZF1 expression was correlated with serum AFP level (P = 0.017), tumor differentiation (P = 0.001) and tumor capsule (P = 0.003). Kaplan–Meier analysis indicated both nuclear and cytosolic BLZF1 expression was associated with poor overall survival. Low nuclear BLZF1 also indicated unfavorable disease-free survival and high tendency of tumor recurrence. Furthermore, multiple Cox regression analysis revealed nuclear BLZF1 as an independent factor for overall survival (Hazard Ratio (HR) = 0.827, 95% confident interval (95%CI): 0.697–0.980, P = 0.029). The prognostic value of BLZF1 was further confirmed by stratified analyses. Collectively, our data suggest BLZF1 is a novel unfavorable biomarker for prognosis of patients with HCC. - Highlights: • BLZF1 expression was much lower in HCC tissues. • Low BLZF1 expression was associated with poor outcomes in a cohort of 634 HCC patients. • Multiple Cox regression analysis indicated nuclear BLZF1 as an independent predictor for overall survival.

  3. Seminal vesicle metastasis after partial hepatectomy for hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Gong, Li; Zheng, Minwen; Li, Yanhong; Zhang, Wendong; Bu, Wangjun; Shi, Lifang; Zhang, Wei; Yan, Hong

    2011-01-01

    Metastasis to the seminal vesicle is extremely rare for hepatocellular carcinoma (HCC). To our knowledge, it has been not reported in literature. The purpose of the present paper was to report a case of metastasis to the seminal vesicle after HCC resection, along with its histological features and immunohistochemical characteristics. A 46-year-old Chinese man was admitted to our hospital due to abdominal distension. He had a history of HCC related to hepatitis B virus infection. Moreover, left partial hepatectomy was performed in another hospital 28 months ago, and right partial hepatectomy for HCC recurrence in our hospital 4 months ago. After resection, radiofrequency ablation therapy had been performed. About 27 months after the initial operation, contrast-enhanced computed tomography (CT) of the pelvic cavity revealed a mass with homogeneous enhancement in the seminal vesicle. Transrectal needle biopsy revealed a poorly differentiated adenocarcinoma. Therefore, seminal vesiculectomy was resected. The histological diagnosis of the removed tumor was compatible with the original HCC. Immunohistochemical examination demonstrated that the tumor cells were positive for glypican-3 (GPC3), alpha-fetoprotein (AFP), hepatocyte paraffin-1 (Hep Par 1), cytokeratin 18 (CK 18), and hepatocyte antigen, which confirmed that the seminal vesicle tumor was a metastatic tumor of HCC. However, CT subsequently revealed multiple metastatic foci in the abdominal and pelvic cavities in May 2009 and August 2009, respectively. The seminal vesicle is an extremely rare metastatic site for HCC, and the prognosis is very poor. A combination of clinical and pathological features is necessary for a correct diagnosis, and primary tumor should be excluded before diagnosing metastatic foci

  4. The androgen receptor as an emerging target in hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Kanda T

    2015-06-01

    Full Text Available Tatsuo Kanda, Osamu Yokosuka Department of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, Chiba, Japan Abstract: Hepatocellular carcinoma (HCC is one of the male-dominant liver diseases with poor prognosis, although treatments for HCC have been progressing in the past decades. Androgen receptor (AR is a member of the nuclear receptor superfamily. Previous studies reported that AR was expressed in human HCC and non-HCC tissues. AR is activated both ligand-dependently and ligand-independently. The latter is associated with a mitogen-activated protein kinase–, v-akt murine thymoma viral oncogene homolog 1–, or signal-transducer and activator of transcription–signaling pathway, which has been implicated in the development of HCC. It has been reported that more than 200 RNA expression levels are altered by androgen treatment. In the liver, androgen-responsive genes are cytochrome P450s, transforming growth factor , vascular endothelial growth factor, and glucose-regulated protein 78 kDa, which are also associated with human hepatocarcinogenesis. Recent studies also revealed that AR plays a role in cell migration and metastasis. It is possible that cross-talk among AR-signaling, endoplasmic reticulum stress, and innate immune response is important for human hepatocarcinogenesis and HCC development. This review shows that AR could play a potential role in human HCC and represent one of the important target molecules for the treatment of HCC. Keywords: vascular endothelial growth factor, angiogenesis, glucose-regulated protein 78 kDa, hepatocarcinogenesis, molecular targets 

  5. Serum Autoantibody Measurement for the Detection of Hepatocellular Carcinoma

    Science.gov (United States)

    Middleton, Catrin H.; Irving, William; Robertson, John F. R.; Murray, Andrea; Parsy-Kowalska, Celine B.; Macdonald, Isabel K.; McElveen, Jane; Allen, Jared; Healey, Graham F.; Thomson, Brian J.; Ryder, Stephen J.; Holdenrieder, Stefan; Chapman, Caroline J.

    2014-01-01

    Background Individuals with liver disease, and especially those with Hepatitis B or C, are at an increased risk of developing hepatocellular carcinoma (HCC) which is the third most common cause of cancer-related death worldwide. Inadequate screening tests largely account for presentation of advanced tumours and high mortality rates. Early detection of HCC amongst high-risk groups is paramount in improving prognosis. This research aimed to further characterise the previously described humoral immune response raised to tumour-associated antigens (TAAs) in the serum of patients with HCC. Methods Serum from 96 patients with confirmed HCC, 96 healthy controls matched for age and sex, 78 patients with confirmed liver cirrhosis and 91 patients with confirmed chronic liver disease were analysed for the presence of IgG autoantibodies raised to 41 recombinant TAAs/antigen fragments by ELISA. Results Varying autoantibody specificities (97–100%) and sensitivities (0–10%) were observed to individual TAAs. A 21-antigen panel achieved a specificity of 92% and sensitivity of 45% for the detection of HCC. This same panel identified 21% of 169 high-risk controls as having elevated autoantibody levels. A reproducible panel of 10 antigens achieved a specificity of 91% and sensitivity of 41% in HCC. 15% of 152 high-risk controls gave positive results with this panel. Conclusions This minimally invasive blood test has the potential to offer advantages over currently available tools for the identification of HCC amongst pre-disposed patients. Results are comparable to current gold standards in HCC (Ultrasonography) and to similar tests in other cancers (EarlyCDT-Lung). PMID:25093332

  6. Serum autoantibody measurement for the detection of hepatocellular carcinoma.

    Directory of Open Access Journals (Sweden)

    Catrin H Middleton

    Full Text Available BACKGROUND: Individuals with liver disease, and especially those with Hepatitis B or C, are at an increased risk of developing hepatocellular carcinoma (HCC which is the third most common cause of cancer-related death worldwide. Inadequate screening tests largely account for presentation of advanced tumours and high mortality rates. Early detection of HCC amongst high-risk groups is paramount in improving prognosis. This research aimed to further characterise the previously described humoral immune response raised to tumour-associated antigens (TAAs in the serum of patients with HCC. METHODS: Serum from 96 patients with confirmed HCC, 96 healthy controls matched for age and sex, 78 patients with confirmed liver cirrhosis and 91 patients with confirmed chronic liver disease were analysed for the presence of IgG autoantibodies raised to 41 recombinant TAAs/antigen fragments by ELISA. RESULTS: Varying autoantibody specificities (97-100% and sensitivities (0-10% were observed to individual TAAs. A 21-antigen panel achieved a specificity of 92% and sensitivity of 45% for the detection of HCC. This same panel identified 21% of 169 high-risk controls as having elevated autoantibody levels. A reproducible panel of 10 antigens achieved a specificity of 91% and sensitivity of 41% in HCC. 15% of 152 high-risk controls gave positive results with this panel. CONCLUSIONS: This minimally invasive blood test has the potential to offer advantages over currently available tools for the identification of HCC amongst pre-disposed patients. Results are comparable to current gold standards in HCC (Ultrasonography and to similar tests in other cancers (EarlyCDT-Lung.

  7. Intraparenchymal Hemorrhage due to Brain Metastasis of Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Rafael Sartori Balbinot

    2017-09-01

    Full Text Available Although extrahepatic metastases from hepatocellular carcinoma (HCC are present in only 5–15% of cases, they are certainly factors associated with poor prognosis. The main sites include lung, lymph nodes, bones, and adrenal glands, in descending order. Metastasis in the central nervous system is extremely rare, and the incidences vary from 0.6 to 1.7%. We report a case of a 54-year-old man previously diagnosed with alcohol-induced cirrhosis of the liver and HCC. The patient was admitted presenting progressive left hemiparesis and headache which started 2 days earlier, with no history of cranioencephalic trauma. After admission, cranial computed tomography revealed an intraparenchymal hemorrhage area with surrounding edema in the right frontal lobe. An angioresonance requested showed a large extra-axial mass lesion located in the right frontal region with well-defined contours and predominantly hypointense signal on T2 sequence. At first, the radiological findings suggested meningioma as the first diagnostic hypothesis. However, the patient underwent surgery. The tumor was completely removed, and the morphological and immunohistochemical findings were consistent with metastatic hepatocarcinoma associated with meningioma. In postoperative care, the patient did not recover from the left hemiparesis and manifested Broca’s aphasia. He had a survival time of 24 weeks, presenting acute liver failure as his cause of death. There is a lack of evidence supporting a specific management of patients with brain metastasis from HCC. Furthermore, there are no studies that evaluate different modalities of therapeutics in brain metastasis of HCC due to the rarity of this condition. Therefore, management must be individualized depending on probable prognostic factors in these patients.

  8. CASC2/miR-24/miR-221 modulates the TRAIL resistance of hepatocellular carcinoma cell through caspase-8/caspase-3.

    Science.gov (United States)

    Jin, Xiaoxin; Cai, Lifeng; Wang, Changfa; Deng, Xiaofeng; Yi, Shengen; Lei, Zhao; Xiao, Qiangsheng; Xu, Hongbo; Luo, Hongwu; Sun, Jichun

    2018-02-23

    Hepatocellular carcinoma is one of the most common solid tumors in the digestive system. The prognosis of patients with hepatocellular carcinoma is still poor due to the acquisition of multi-drug resistance. TNF Related Apoptosis Inducing Ligand (TRAIL), an attractive anticancer agent, exerts its effect of selectively inducing apoptosis in tumor cells through death receptors and the formation of the downstream death-inducing signaling complex, which activates apical caspases 3/8 and leads to apoptosis. However, hepatocellular carcinoma cells are resistant to TRAIL. Non-coding RNAs, including long non-coding RNAs (lncRNAs) and miRNAs have been regarded as major regulators of normal development and diseases, including cancers. Moreover, lncRNAs and miRNAs have been reported to be associated with multi-drug resistance. In the present study, we investigated the mechanism by which TRAIL resistance of hepatocellular carcinoma is affected from the view of non-coding RNA regulation. We selected and validated candidate miRNAs, miR-24 and miR-221, that regulated caspase 3/8 expression through direct targeting, and thereby affecting TRAIL-induced tumor cell apoptosis TRAIL resistance of hepatocellular carcinoma. In addition, we revealed that CASC2, a well-established tumor suppressive long non-coding RNA, could serve as a "Sponge" of miR-24 and miR-221, thus modulating TRAIL-induced tumor cell apoptosis TRAIL resistance of hepatocellular carcinoma. Taken together, we demonstrated a CASC2/miR-24/miR-221 axis, which can affect the TRAIL resistance of hepatocellular carcinoma through regulating caspase 3/8; through acting as a "Sponge" of miR-24 and miR-221, CASC2 may contribute to improving hepatocellular carcinoma TRAIL resistance, and finally promoting the treatment efficiency of TRAIL-based therapies.

  9. Long-term survival after liver transplant for recurrent hepatocellular carcinoma with bile duct tumor thrombus: case report.

    Science.gov (United States)

    Liu, Chao; Wang, Jie

    2012-12-01

    Hepatocellular carcinoma with bile duct tumor thrombus is considered an aggressive malignancy, and the prognosis of liver transplant for it remains obscure. A 42-year-old man with recurrent hepatocellular carcinoma and a history of surgical resection was admitted to our hospital with a 10-day history of yellowish urine and itchy skin. There were 3 lesions in the right lobe with the diameter of 2 cm each. A mass was found in the upper part of common bile duct, and the intrahepatic bile duct was dilated. His serum alpha-fetoprotein level was 2476 μg/L, total bilirubin level was 327 μmol/L, direct bilirubin level was 261 μmol/L, and alanine aminotransferase was 714 U/L. There was no main portal vein thrombus or extrahepatic metastases. Because of his poor liver function, he was listed for a liver transplant. During the wait (30 d), he underwent 9 episodes of plasmapheresis to decrease the serum level of bilirubin. He had an orthotopic liver transplant with the graft from a deceased donor. After the liver transplant, he received 5 cycles of chemotherapy with the regimen of oxaliplatin and 5-fluorouracil. This patient has survived without recurrence of hepatocellular carcinoma for more than 82 months and remains in good condition. Liver transplant may have a favorable result for hepatocellular carcinoma patient with a bile duct tumor thrombus, within the Milan criteria.

  10. Clinical utility of imaging for evaluation of hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Murakami T

    2014-07-01

    Full Text Available Takamichi Murakami,1 Masakatsu Tsurusaki,1 Tomoko Hyodo,1 Yasuharu Imai2 1Department of Radiology, Kinki University Faculty of Medicine, 2Department of Hepatology and Gastroenterology, Ikeda Municipal Hospital, Osaka, Japan Abstract: The hemodynamics of a hepatocellular nodule is the most important imaging parameter used to characterize various hepatocellular nodules in liver cirrhosis, because sequential changes occur in the feeding vessels and hemodynamic status during hepatocarcinogenesis. Therefore, the imaging criteria for hepatocellular carcinoma (HCC are also usually based on vascular findings, eg, early arterial uptake followed by washout in the portal venous and equilibrium phases. Contrast-enhanced ultrasonography, dynamic multidetector-row computed tomography (MDCT, and dynamic magnetic resonance (MR imaging with gadopentetate dimeglumine (Gd-DTPA are useful for detecting hypervascular HCC on the basis of vascular criteria but are not as useful for hypovascular HCC. Contrast-enhanced MR imaging with gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA, a hepatocyte-specific MR contrast agent, is superior to dynamic MDCT and dynamic MR imaging with Gd-DTPA in detecting both hypervascular and hypovascular HCC. Moreover, Gd-EOB-DTPA-enhanced MR imaging can display each histologically differentiated HCC as hypointense relative to the liver parenchyma. 18F-fluorodeoxyglucose positron emission tomography imaging might not be suitable for the screening and detection of HCC, given its lower diagnostic performance. However, this technique plays an important role in determining whether HCC has spread beyond the liver. Keywords: hepatocellular carcinoma, evaluation, imaging, clinical utility

  11. Diagnostic imaging and interventional radiology of hepatocellular carcinoma: A multicenter study on 290 cases

    International Nuclear Information System (INIS)

    Dalla Palma, Ludovico; Puzzi Mucelli, Roberto; Sponza, Massimo; De Santis, Mario; Gandini, Giovanni; Matricardi, Luigi; Rossi, Cristina

    1997-01-01

    The authors report of a multicenter study on the diagnosis and interventional therapy of hepatocellular carcinoma (HCC).The first aim -diagnostic - was to evaluate the sensitivity of 4 imaging techniques, namely ultrasonography (US), Computed Tomography (CT), digital arteriography (DSA) and Lipiodol CT (LCT), in hepatocellular carcinoma detection. The accuracy of these techniques was also investigated in tumor staging, which is important for treatment planning.The second aim - treatment - consisted in assessing the therapeutic efficacy of intraarterial chemoembolization (CEAT) versus percutaneous ethanol injection (PEI) in non advanced hepatocellular carcinoma and of intraarterial chemoembolization versus no treatment (NT) in advanced hepatocellular carcinoma. Treatment efficacy was evaluated with the following randomized protocols

  12. INFLUENCE OF HEPATOCELLULAR CARCINOMA ETIOLOGY IN THE SURVIVAL AFTER RESECTION.

    Science.gov (United States)

    Lopes, Felipe de Lucena Moreira; Coelho, Fabricio Ferreira; Kruger, Jaime Arthur Pirolla; Fonseca, Gilton Marques; Araujo, Raphael Leonardo Cunha de; Jeismann, Vagner Birk; Herman, Paulo

    2016-01-01

    Hepatocellular carcinoma (HCC) is the most frequent type of primary liver cancer and its incidence is increasing around the world in the last decades, making it the third cause of death by cancer in the world. Hepatic resection is one of the most effective treatments for HCC with five-year survival rates from 50-70%, especially for patients with a single nodule and preserved liver function. Some studies have shown a worse prognosis for HCC patients whose etiology is viral. That brings us to the question about the existence of a difference between the various causes of HCC and its prognosis. To compare the prognosis (overall and disease-free survival at five years) of patients undergoing hepatectomy for the treatment of HCC with respect to various causes of liver disease. Was performed a review of medical records of patients undergoing hepatectomy between 2000 and 2014 for the treatment of HCC. They were divided into groups according to the cause of liver disease, followed by overall and disease-free survival analysis for comparison. There was no statistically significant difference in the outcomes of the groups of patients divided according to the etiology of HCC. Overall and disease-free survival at five years of the patients in this sample were 49.9% and 40.7%, respectively. From the data of this sample, was verified that there was no prognostic differences among the groups of HCC patients of the various etiologies. O carcinoma hepatocelular (CHC) é o mais frequente tipo de câncer primário do fígado e a sua incidência vem aumentando nas últimas décadas, tornando-o hoje a terceira causa de morte por câncer no mundo. A ressecção hepática é um dos tratamentos mais eficazes para ele com taxas de sobrevida em cinco anos de 50-70%, especialmente para pacientes com nódulo único e função hepática preservada. Alguns estudos mostraram pior prognóstico para os pacientes com CHC cuja causa é a infecção por vírus B ou C. Isso leva à questão sobre a

  13. Molecular pathogenesis of hepatocellular carcinoma and impact of therapeutic advances

    Science.gov (United States)

    Dhanasekaran, Renumathy; Bandoh, Salome; Roberts, Lewis R.

    2016-01-01

    Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality and has an increasing incidence worldwide. HCC can be induced by multiple etiologies, is influenced by many risk factors, and has a complex pathogenesis. Furthermore, HCCs exhibit substantial heterogeneity, which compounds the difficulties in developing effective therapies against this highly lethal cancer. With advances in cancer biology and molecular and genetic profiling, a number of different mechanisms involved in the development and progression of HCC have been identified. Despite the advances in this area, the molecular pathogenesis of hepatocellular carcinoma is still not completely understood. This review aims to elaborate our current understanding of the most relevant genetic alterations and molecular pathways involved in the development and progression of HCC, and anticipate the potential impact of future advances on therapeutic drug development. PMID:27239288

  14. CTP synthase forms the cytoophidium in human hepatocellular carcinoma.

    Science.gov (United States)

    Chang, Chia-Chun; Jeng, Yung-Ming; Peng, Min; Keppeke, Gerson Dierley; Sung, Li-Ying; Liu, Ji-Long

    2017-12-15

    CTP synthase (CTPS) can aggregate into an intracellular macrostructure, the cytoophidium, in various organisms including human cells. Previous studies have shown that assembly of human CTPS cytoophidia may be correlated with the cellular metabolic status, and is able to promote the activity of CTPS. A correlation between the cytoophidium and cancer metabolism has been proposed but not yet been revealed. In the current study we provide clear evidence of the presence of CTPS cytoophidia in various human cancers and some non-cancerous tissues. Moreover, among 203 tissue samples of hepatocellular carcinoma, 56 (28%) samples exhibited many cytoophidia, whereas no cytoophidia were detected in adjacent non-cancerous hepatocytes for all samples. Our findings suggest that the CTPS cytoophidium may participate in the adaptive metabolism of human hepatocellular carcinoma. Copyright © 2017. Published by Elsevier Inc.

  15. Efficacy of intrahepatic absolute alcohol in unrespectable hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Farooqi, J.I.; Hameed, K.; Khan, I.U.; Shah, S.

    2001-01-01

    To determine efficacy of intrahepatic absolute alcohol injection in researchable hepatocellular carcinoma. A randomized, controlled, experimental and interventional clinical trial. Gastroenterology Department, PGMI, Hayatabad Medical Complex, Peshawar during the period from June, 1998 to June, 2000. Thirty patients were treated by percutaneous, intrahepatic absolute alcohol injection sin repeated sessions, 33 patients were not given or treated with alcohol to serve as control. Both the groups were comparable for age, sex and other baseline characteristics. Absolute alcohol therapy significantly improved quality of life of patients, reduced the tumor size and mortality as well as showed significantly better results regarding survival (P< 0.05) than the patients of control group. We conclude that absolute alcohol is a beneficial and safe palliative treatment measure in advanced hepatocellular carcinoma (HCC). (author)

  16. Cerebrovascular accidents associated with sorafenib in hepatocellular carcinoma.

    Science.gov (United States)

    Saif, Muhammad W; Isufi, Iris; Peccerillo, Jennifer; Syrigos, Kostas N

    2011-01-01

    Sorafenib is an oral angiogenetic multikinase inhibitor approved in the treatment of renal and hepatocellular carcinoma. Bleeding and venous thrombotic events have been described with angiogenetic agents but cerebrovascular accidents are rarely reported. We report two cases of patients with hepatocellular carcinoma who developed a cerebrovascular accident while on sorafenib. Neither patient had any risk factors for the cerebrovascular events apart from gender and age in the second patient. Laboratory data were noncontributory. The head CT scan did not reveal acute abnormalities. No hemodynamically significant stenosis was visible in the carotid ultrasound, and the echocardiogram showed normal size of the heart chambers and normal systolic function of the left ventricle. Sorafenib was discontinued in both cases. Physicians should monitor patients receiving sorafenib for neurologic symptoms, and in the absence of other etiology, prompt discontinuation of this drug should be considered.

  17. Simple Sugar Intake and Hepatocellular Carcinoma: Epidemiological and Mechanistic Insight

    Directory of Open Access Journals (Sweden)

    Juan Carlos Laguna

    2014-12-01

    Full Text Available Sugar intake has dramatically increased during the last few decades. Specifically, there has been a clear trend towards higher consumption of fructose and high fructose corn syrup, which are the most common added sugars in processed food, soft drinks and other sweetened beverages. Although still controversial, this rising trend in simple sugar consumption has been positively associated with weight gain and obesity, insulin resistance and type 2 diabetes mellitus and non-alcoholic fatty liver disease. Interestingly, all of these metabolic alterations have also been related to the development of hepatocellular carcinoma. The purpose of this review is to discuss the evidence coming from epidemiological studies and data from animal models relating the consumption of simple sugars, and specifically fructose, with an increased risk of hepatocellular carcinoma and to gain insight into the putative molecular mechanisms involved.

  18. Chemokine receptor CXCR7 regulates the invasion, angiogenesis and tumor growth of human hepatocellular carcinoma cells

    Directory of Open Access Journals (Sweden)

    Li Fan

    2010-04-01

    Full Text Available Abstract Background In spite of recent advances in diagnostic and therapeutic measures, the prognosis of hepatocellular carcinoma (HCC patients remains poor. Therefore, it is crucial to understand what factors are involved in promoting development of HCC. Evidence is accumulating that members of the chemokine receptor family are viewed as promising therapeutic targets in the fight against cancer. More recent studies have revealed that chemokine receptor CXCR7 plays an important role in cancer development. However, little is known about the effect of CXCR7 on the process of HCC cell invasion and angiogenesis. The aim of this study is to investigate the expression of CXCR7 in hepatocellular carcinoma tissues and cell lines and to evaluate the role of CXCR7 in tumor growth, angiogenesis and invasion of HCC cells. Methods We constructed CXCR7 expressing shRNA, and CXCR7shRNA was subsequently stably transfected into human HCC cells. We evaluated the effect of CXCR7 inhibition on cell invasion, adhesion, VEGF secretion, tube formation and tumor growth. Immunohistochemistry was done to assess the expression of CXCR7 in human hepatocellular carcinoma tissues and CD31 in tumor of mice. We also evaluated the effect of VEGF stimulation on expression of CXCR7. Results CXCR7 was overexpressed in hepatocellular carcinoma tissues. We showed that high invasive potential HCC cell lines express high levels of CXCR7. In vitro, CXCL12 was found to induce invasion, adhesion, tube formation, and VEGF secretion in SMMC-7721 cells. These biological effects were inhibited by silencing of CXCR7 in SMMC-7721 cells. In addition, we also found that VEGF stimulation can up-regulate CXCR7 expression in SMMC-7721 cells and HUVECs. More importantly, enhanced expression of CXCR7 by VEGF was founctional. In vivo, tumor growth and angiogenesis were suppressed by knockdown of CXCR7 in SMMC-7721 cells. However, silencing of CXCR7 did not affect metastasis of tumor in vivo

  19. Diaphragmatic Hernia After Radiofrequency Ablation for Hepatocellular Carcinoma

    International Nuclear Information System (INIS)

    Yamagami, Takuji; Yoshimatsu, Rika; Matsushima, Shigenori; Tanaka, Osamu; Miura, Hiroshi; Nishimura, Tsunehiko

    2011-01-01

    We describe a 71-year-old woman with a hepatocellular carcinoma who underwent percutaneous radiofrequency ablation (RF) with a single internally cooled electrode under computed tomography (CT) fluoroscopic guidance. Nine months after the procedure, CT images showed herniation of the large intestine into the right pleural cavity. To our knowledge this complication of RF performed with a single internally cooled electrode under CT guidance has not been previously reported.

  20. The Multifaceted Role of Podoplanin Expression in Hepatocellular Carcinoma

    OpenAIRE

    Cioca, Andreea; Ceausu, Amalia R.; Marin, Irina; Raica, Marius; Cimpean, Anca Maria

    2017-01-01

    The role of podoplanin in hepatocellular carcinoma (HCC) is not clear yet. The aim of our study was to evaluate the expression of podoplanin in HCC and to determine its role in hepatocarcinogenesis. We performed immunohistochemistry with monoclonal D2-40 antibody, on paraffin-embedded tissue sections of 72 patients diagnosed with HCC. Lymphatic vessels density (LVD) was increased in patients who had vascular invasion at the time of diagnosis (P=0.018) and in those with associated cirrhosis (P...

  1. Micronutrient Synergy in the Fight against Hepatocellular Carcinoma

    OpenAIRE

    Roomi, M. Waheed; Roomi, Nusrath W.; Kalinovsky, Tatiana; Niedzwiecki, Aleksandra; Rath, Matthias

    2012-01-01

    The incidence of hepatocellular carcinoma (HCC), once thought to be a rare tumor in North America, has rapidly increased in recent years in the United States. Current treatment modalities to halt the progression of this disease are only marginally effective. The mainstay treatment is liver transplantation, which is often confronted with donor shortage. Invasion, metastasis and recurrence contribute to the high mortality rate of this disease. Matrix metalloproteinases (MMPs) that degrade the e...

  2. Dose response relationship in local radiotherapy for hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Park, Hee Chul; Seong, Jin Sil; Han, Kwang Hyub; Chon, Chae Yoon; Moon, Young Myoung; Song, Jae Seok; Suh, Chang Ok

    2001-01-01

    In this study, it was investigated whether dose response relation existed or not in local radiotherapy for primary hepatocellular carcinoma. From January 1992 to March 2000, 158 patients were included in present study. Exclusion criteria included the presence of extrahepatic metastasis, liver cirrhosis of Child's class C, tumors occupying more than two thirds of the entire liver, and performance status on the ECOG scale of more than 3. Radiotherapy was given to the field including tumor with generous margin using 6, 10-MV X-ray. Mean tumor dose was 48.2±7.9 Gy in daily 1.8 Gy fractions. Tumor response was based on diagnostic radiologic examinations such as CT scan, MR imaging, hepatic artery angiography at 4-8 weeks following completion of treatment. Statistical analysis was done to investigate the existence of dose response relationship of local radiotherapy when it was applied to the treatment of primary hepatocellular carcinoma. An objective response was observed in 106 of 158 patients, giving a response rate of 67. 1%. Statistical analysis revealed that total dose was the most significant factor in relation to tumor response when local radiotherapy was applied to the treatment of primary hepatocellular carcinoma. Only 29.2% showed objective response in patients treated with dose less than 40 Gy, while 68.6% and 77.1 % showed major response in patients with 40-50 Gy and more than 50 Gy, respectively. Child-Pugh classification was significant factor in the development of ascites, overt radiation induced liver disease and gastroenteritis. Radiation dose was an important factor for development of radiation induced gastroduodenal ulcer. Present study showed the existence of dose response relationship in local radiotherapy for primary hepatocellular carcinoma. Only radiotherapy dose was a significant factor to predict the objective response. Further study is required to predict the maximal tolerance dose in consideration of liver function and non-irradiated liver

  3. Radiofrequency ablation of hepatocellular carcinoma: Mono or multipolar?

    Science.gov (United States)

    Cartier, Victoire; Boursier, Jérôme; Lebigot, Jérôme; Oberti, Frédéric; Fouchard-Hubert, Isabelle; Aubé, Christophe

    2016-03-01

    Thermo-ablation by radiofrequency is recognized as a curative treatment for early-stage hepatocellular carcinoma. However, local recurrence may occur because of incomplete peripheral tumor destruction. Multipolar radiofrequency has been developed to increase the size of the maximal ablation zone. We aimed to compare the efficacy of monopolar and multipolar radiofrequency for the treatment of hepatocellular carcinoma and determine factors predicting failure. A total of 171 consecutive patients with 214 hepatocellular carcinomas were retrospectively included. One hundred fifty-eight tumors were treated with an expandable monopolar electrode and 56 with a multipolar technique using several linear bipolar electrodes. Imaging studies at 6 weeks after treatment, then every 3 months, assessed local effectiveness. Radiofrequency failure was defined as persistent residual tumor after two sessions (primary radiofrequency failure) or local tumor recurrence during follow-up. This study received institutional review board approval (number 2014/77). Imaging showed complete tumor ablation in 207 of 214 lesions after the first session of radiofrequency. After a second session, only two cases of residual viable tumor were observed. During follow-up, there were 46 local tumor recurrences. Thus, radiofrequency failure occurred in 48/214 (22.4%) cases. By multivariate analysis, technique (P radiofrequency failure. Failure rate was lower with the multipolar technique for tumors radiofrequency, multipolar radiofrequency improves tumor ablation with a subsequent lower rate of local tumor recurrence. © 2015 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  4. Thymostimulin in advanced hepatocellular carcinoma: A phase II trial

    Directory of Open Access Journals (Sweden)

    Behl Susanne

    2008-03-01

    Full Text Available Abstract Background Thymostimulin is a thymic peptide fraction with immune-mediated cytotoxicity against hepatocellular carcinoma in vitro. In a phase II trial, we investigated safety and efficacy including selection criteria for best response in advanced or metastasised hepatocellular carcinoma. Methods 44 patients (84 % male, median age 69 years not suitable or refractory to conventional therapy received thymostimulin 75 mg subcutaneously five times per week for a median of 8.2 months until progression or complete response. 3/44 patients were secondarily accessible to local ablation or chemoembolisation. Primary endpoint was overall survival, secondary endpoint tumor response or progression-free survival. A multivariate Cox's regression model was used to identify variables affecting survival. Results Median survival was 11.5 months (95% CI 7.9–15.0 with a 1-, 2- and 3-year survival of 50%, 23% and 9%. In the univariate analysis, a low Child-Pugh-score (p = 0.01, a low score in the Okuda- and CLIP-classification (p Conclusion Outcome in our study rather depended on liver function and intrahepatic tumor growth (presence of liver cirrhosis and Okuda stage in addition to response to thymostimulin, while an invasive HCC phenotype had no influence in the multivariate analysis. Thymostimulin could therefore be considered a safe and promising candidate for palliative treatment in a selected target population with advanced hepatocellular carcinoma, in particular as component of a multimodal therapy concept. Trial registration Current Controlled Trials ISRCTN29319366.

  5. Hepatocellular carcinoma: computed tomography assessment after invasive treatment

    International Nuclear Information System (INIS)

    Kozima, Shigeru; Larranaga, Nebil; Wulfson, Gabriela; Eisele, Guillermo; Ridruejo, Ezequiel; Mando, Oscar; Perazzo, Florencia

    2008-01-01

    Objective: To show the computed tomography (CT) usefulness after treatment with transcatheter arterial quimioembolization and radiofrequency ablation of hepatocellular carcinoma. Material and methods: In a period between march 2006 to april 2008 a total of 90 patient presenting 148 nodular lesions with diagnosis of hepatocellular carcinoma were controlled with triphasic CT. All the lesions were treated with minimally invasive procedure. For the treatment, the patients were classified in two groups following Milan criteria. The first group, constituted by 75 patients with 109 nodules, was treated with quimioembolization. The second group, of 15 patients with 25 nodules, was treated with radiofrequency ablation. In our population, a subgroup of 10 patients was treated with both methods. Results: Of 90 patients after CT control on a month, 3 months and for each 3 months during 2 years, on 63 cases (70%) was observed homogeneous accumulation of iodized oil, partial defect without enhancement or absence of enhancement on treated lesions. In these patients a new treatment after initial one was not performed. The remaining 27 patients (30%) underwent new treatment because we founded partial defect or absence of iodized oil with enhancement or peripheral enhancement on arterial phase in treated lesions. In this last group, 16 treated patients (17.7%) had new nodular enhancement on the remaining hepatic parenquimal. Conclusion: The CT unenhanced and the arterial phase on a month and for each 3 months, allow monitoring the effectiveness, residual disease and/or relapse of hepatocellular carcinoma after minimally invasive treatment. (authors) [es

  6. Hepatitis infections, aflatoxin and hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Pierre Hainaut

    2007-02-01

    Full Text Available

    The incidence rates of hepatocellular carcinoma (HCC show large geographic variations, globally reflecting the prevalence of two main aetiologic factors, hepatitis B (HBV and/or C (HCV virus infection and exposure to high levels of aflatoxin in the diet (Chen et al. 1997. The highest incidence rates are observed in regions where most of the population is exposed to both factors, such as in parts of eastern Asia and in sub-Saharan Africa (Parkin et al. 2001. These high incidences are consistent with the fact that HBV chronicity and exposure to aflatoxin have a multiplicative effect of risk for HCC. Depending on aetiology and geographic area, mutations in TP53 show striking differences in prevalence and pattern. In Europe and the US, where alcohol is a major risk factor in addition to viral infections, mutations occur in about 25% of HCC and show as much diversity in their type and codon position as in most other epithelial cancers. However, in high incidence areas such as Mozambique, Senegal, The Gambia (Africa and Qidong county (China, TP53 is mutated in over 50% of the cases and the vast majority of these mutations are a single missense, hotspot mutation at codon 249, AGG to AGT, resulting in the substitution of arginine into serine (249ser. This mutation is uncommon in regions where aflatoxin is not present at significant levels in the diet. In areas of intermediate exposure to aflatoxin, as for example in Thailand, the prevalence of the 249ser mutation is intermediate between high- and low-incidence areas. Thus, there is a dose-dependent relationship between exposure to aflatoxin, incidence of HCC and prevalence of 249ser mutation. Aflatoxins are toxic and carcinogenic metabolites produced by several varieties of molds, mainly Aspergillus flavus and Aspergillus parasiticum. These molds contaminate a wide range of traditional agricultural products in countries

  7. Albumin Suppresses Human Hepatocellular Carcinoma Proliferation and the Cell Cycle

    Directory of Open Access Journals (Sweden)

    Shunsuke Nojiri

    2014-03-01

    Full Text Available Many investigations have revealed that a low recurrence rate of hepatocellular carcinoma (HCC is associated with high serum albumin levels in patients; therefore, high levels of serum albumin are a major indicator of a favorable prognosis. However, the mechanism inhibiting the proliferation of HCC has not yet been elucidated, so we investigated the effect of serum albumin on HCC cell proliferation. Hep3B was cultured in MEM with no serum or containing 5 g/dL human albumin. As control samples, Prionex was added to generate the same osmotic pressure as albumin. After 24-h incubation, the expressions of α-fetoprotein (AFP, p53, p21, and p57 were evaluated with real-time PCR using total RNA extracted from the liver. Protein expressions and the phosphorylation of Rb (retinoblastoma were determined by Western blot analysis using total protein extracted from the liver. For flow cytometric analysis of the cell cycle, FACS analysis was performed. The percentages of cell cycle distribution were evaluated by PI staining, and all samples were analyzed employing FACScalibur (BD with appropriate software (ModFit LT; BD. The cell proliferation assay was performed by counting cells with using a Scepter handy automated cell counter (Millipore. The mRNA levels of AFP relative to Alb(−: Alb(−, Alb(+, and Prionex, were 1, 0.7 ± 0.2 (p < 0.001 for Alb(−, and 1 ± 0.3, respectively. The mRNA levels of p21 were 1, 1.58 ± 0.4 (p = 0.007 for Alb(− and p = 0.004 for Prionex, and 0.8 ± 0.2, respectively. The mRNA levels of p57 were 1, 4.4 ± 1.4 (p = 0.002 for Alb(− and Prionex, and 1.0 ± 0.1, respectively. The protein expression levels of Rb were similar in all culture media. The phosphorylation of P807/811 and P780 of Rb protein was reduced in Alb(+. More cells in the G0/G1 phase and fewer cells in S and G2/M phases were obtained in Alb(+ than in Alb(− (G0/G1: 60.9%, 67.7%, 61.5%; G2/M: 16.5%, 13.1%, 15.6%; S: 22.6%, 19.2%, 23.0%, Alb(−, Alb

  8. Grp78 promotes the invasion of hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Li Hongdan

    2010-01-01

    Full Text Available Abstract Background Glucose regulated protein 78 (Grp78 is involved in the invasion and metastasis in many human cancers including gastric cancer, breast cancer, prostate cancer. But the role of Grp78 in the invasion of human hepatocellular carcinoma has not been reported. In this article, we examined if Grp78 was associated with the invasion of hepatocellular carcinoma and explored the possible underlying mechanism. Methods The Grp78 and FAK expression levels in 44 patients with hepatocellular carcinoma were examined using immunohistochemistry. Grp78 overexpressing SMMC7721 cells were established by pcDNA3.1 (+-Grp78 transfection and screened by G418. Grp78 and FAK levels in Grp78 overexpressing cells were down-regulated by siRNA transfection. The invasion status of tumor cells was evaluated by transwell assay in vitro, and chick embryo metastasis model in vivo. Cell spreading was determined by cell spreading assay, and quantitatively measured by Orisis software HUG. Grp78, pY397 FAK, pY576/577 FAK and FAK levels were detected by western blot. RhoA activity was detected by GST pulldown assay. The distribution of actin cytoskeleton was observed by fluorescent staining. Results Grp78 expression levels in 44 patients with hepatocellular carcinoma were negatively correlated with tumor grading, and positively correlated with portal invasion and intra-hepatic invasion. Overexpression of Grp78 in SMMC7721 cells promoted the invasion of cancer cells in vitro and in vivo, and this increase in tumor cell invasion was blocked by Grp78 siRNA knockdown. Our results also revealed that overexpression of Grp78 in SMMC7721 cells accelerated the process of cell spreading and promoted lamellipodia formation. Further analysis showed that overexpression of Grp78 in SMMC7721 cells increased pY397 and pY576/577 levels of FAK. Grp78 siRNA knockdown decreased FAK activation and activity. Our results also revealed that Grp78 overexpression in SMMC7721 cells decreased

  9. Grp78 promotes the invasion of hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Su, Rongjian; Li, Zhen; Li, Hongdan; Song, Huijuan; Bao, Cuifen; Wei, Jia; Cheng, Liufang

    2010-01-01

    Glucose regulated protein 78 (Grp78) is involved in the invasion and metastasis in many human cancers including gastric cancer, breast cancer, prostate cancer. But the role of Grp78 in the invasion of human hepatocellular carcinoma has not been reported. In this article, we examined if Grp78 was associated with the invasion of hepatocellular carcinoma and explored the possible underlying mechanism. The Grp78 and FAK expression levels in 44 patients with hepatocellular carcinoma were examined using immunohistochemistry. Grp78 overexpressing SMMC7721 cells were established by pcDNA3.1 (+)-Grp78 transfection and screened by G418. Grp78 and FAK levels in Grp78 overexpressing cells were down-regulated by siRNA transfection. The invasion status of tumor cells was evaluated by transwell assay in vitro, and chick embryo metastasis model in vivo. Cell spreading was determined by cell spreading assay, and quantitatively measured by Orisis software HUG. Grp78, pY397 FAK, pY576/577 FAK and FAK levels were detected by western blot. RhoA activity was detected by GST pulldown assay. The distribution of actin cytoskeleton was observed by fluorescent staining. Grp78 expression levels in 44 patients with hepatocellular carcinoma were negatively correlated with tumor grading, and positively correlated with portal invasion and intra-hepatic invasion. Overexpression of Grp78 in SMMC7721 cells promoted the invasion of cancer cells in vitro and in vivo, and this increase in tumor cell invasion was blocked by Grp78 siRNA knockdown. Our results also revealed that overexpression of Grp78 in SMMC7721 cells accelerated the process of cell spreading and promoted lamellipodia formation. Further analysis showed that overexpression of Grp78 in SMMC7721 cells increased pY397 and pY576/577 levels of FAK. Grp78 siRNA knockdown decreased FAK activation and activity. Our results also revealed that Grp78 overexpression in SMMC7721 cells decreased RhoA-GTP level, and Grp78 siRNA knockdown rescued Rho

  10. Autophagy‑mediated adaptation of hepatocellular carcinoma cells to hypoxia‑mimicking conditions constitutes an attractive therapeutic target.

    Science.gov (United States)

    Owada, Satoshi; Endo, Hitoshi; Shida, Yukari; Okada, Chisa; Ito, Kanako; Nezu, Takahiro; Tatemichi, Masayuki

    2018-04-01

    Hepatocellular carcinoma has extremely poor prognosis. In cancerous liver tissues, aberrant proliferation of cancer cells leads to the creation of an area where an immature vascular network is formed. Since oxygen is supplied to cancer tissues through the bloodstream, a part of the tumor is exposed to hypoxic conditions. As hypoxia is known to severely reduce the effectiveness of existing anticancer agents, novel valid therapeutic targets must be identified for the treatment of hepatocellular carcinoma. Generally, autophagy has been reported to play an important role in the adaptation of cancer cells to hypoxia. However, the exact role and significance of this process vary depending on the cancer type, requiring detailed analysis in individual primary tumors and cell lines. In the present study, we examined autophagy induced by cobalt chloride, a hypoxia‑mimicking agent, in hepatocellular carcinoma cells with the aim to evaluate the validity of this process as a potential therapeutic target. We observed that treatment with cobalt chloride induced autophagy, including the intracellular quality control mechanism, in an AMPK‑dependent manner. Furthermore, treatment with autophagy inhibitors (bafilomycin and LY294002) resulted in significant, highly‑selective cytotoxicity and apoptosis activation under hypoxia‑mimicking conditions. The knockdown of AMPK also revealed significant cytotoxicity in hypoxia‑mimicking conditions. These results clearly demonstrated that autophagy, especially mitophagy, was induced by the AMPK pathway when hepatocellular carcinoma cells were subjected to hypoxic conditions and played an important role in the adaptation of these cells to such conditions. Thus, autophagy may constitute an attractive therapeutic target for the treatment of hepatocellular carcinoma.

  11. Histological assessment of the efficacy of drug-eluting beads in portal tumor thrombosis of hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Yusuke Imai, MD

    2017-03-01

    Full Text Available A 58-year-old man was diagnosed with advanced hepatocellular carcinoma with portal vein tumor thrombosis (PVTT. The tumors were multiple and existed in both lobes. Drug-eluting beads transcatheter arterial chemoembolization (DEB-TACE was performed for the tumors in the left lobe. Embosphere and Hepasphere were selected for embolization of the arterioportal shunt, followed by loaded epirubicin infusion into the left hepatic artery. Computed tomography showed reduction of PVTT. However, liver failure progressed, and the patient died 67 days after DEB-TACE. Autopsy showed that the beads reached the tumor thrombosis in the portal vein. The prognosis of hepatocellular carcinoma with PVTT is poor. Although there are no established treatments for unresectable PVTT, DEB-TACE might be a useful option for such cases.

  12. A middle-aged man with a troubled liver: Combination therapy in advanced (BCLC Stage C hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Zamri Zuhdi

    2018-03-01

    Full Text Available Advanced hepatocellular carcinoma carries a bad prognosis with a survival of only few months. Barcelona Clinic Liver Cancer (BCLC Guidelines recommended sorafenib monotherapy as the treatment modality for advanced BCLC Stage C disease, citing a two-month increase in survival rates. Here, we highlight a case with advanced HCC (BCLC Stage C treated with combination therapy of liver resection and Sorafenib therapy. The patient’s current survival rate was beyond 10 months. We also discuss the current evidence on liver resection with Sorafenib therapy in hepatocellular carcinoma. The description of the case may benefit in future diagnosis and treatment. [Arch Clin Exp Surg 2018; 7(1.000: 29-32

  13. Hook1 inhibits malignancy and epithelial-mesenchymal transition in hepatocellular carcinoma.

    Science.gov (United States)

    Sun, Xu; Zhang, Qi; Chen, Wei; Hu, Qida; Lou, Yu; Fu, Qi-Han; Zhang, Jing-Ying; Chen, Yi-Wen; Ye, Long-Yun; Wang, Yi; Xie, Shang-Zhi; Hu, Li-Qiang; Liang, Ting-Bo; Bai, Xue-Li

    2017-07-01

    Hook1 is a member of the hook family of coiled-coil proteins, which is recently found to be associated with malignant tumors. However, its biological function in hepatocellular carcinoma is yet unknown. Here, we evaluated the Hook1 levels in human hepatocellular carcinoma samples and matched peritumoral tissues by real-time polymerase chain reaction. Small interfering RNA knockdown and a transforming growth factor-β-induced epithelial-mesenchymal transition model were employed to investigate the biological effects of Hook1 in hepatocellular carcinoma. Our results indicated that Hook1 levels were significantly lower in hepatocellular carcinoma tissues than in the peritumoral tissues. In addition, Hook1 expression was significantly associated with hepatocellular carcinoma malignancy. Hook1 was downregulated after transforming growth factor-β-induced epithelial-mesenchymal transition. Moreover, Hook1 knockdown promoted epithelial-mesenchymal transition and attenuated the sensitivity of hepatocellular carcinoma cells to doxorubicin. In summary, our results indicate that downregulation of Hook1 plays a pivotal role in hepatocellular carcinoma progression via epithelial-mesenchymal transition. Hook1 may be used as a novel marker and therapeutic molecular target in hepatocellular carcinoma.

  14. Hepatocellular Carcinoma in Tyrosinemia Type 1 Without Clear Increase of AFP

    NARCIS (Netherlands)

    van Ginkel, Willem G.; Gouw, Annette S. H.; van der Jagt, Eric J.; de Jong, Koert P.; Verkade, Henkjan J.; van Spronsen, Francjan J.

    Patients with hereditary tyrosinemia type 1 have an elevated risk of developing hepatocellular carcinoma, especially if initiation of treatment with 2-(2-nitro-4-trifluoro-methylbenzoyl)-1,3-cyclohexanedione is delayed. Hepatocellular carcinoma can usually be suspected when there are increased

  15. Efficacy of hepatic arterial infusion chemotherapy in advanced hepatocellular carcinoma

    Science.gov (United States)

    Baek, Yang Hyun; Kim, Kyoung Tae; Lee, Sung Wook; Jeong, Jin Sook; Park, Byeong Ho; Nam, Kyung Jin; Cho, Jin Han; Kim, Young Hoon; Roh, Young Hoon; Lee, Hyung Sik; Choi, Young Min; Han, Sang Young

    2012-01-01

    AIM: To investigate the efficacy of hepatic arterial infusion chemotherapy (HAIC) using floxuridine (FUDR) in patients with advanced hepatocellular carcinoma (HCC) confined to the liver. METHODS: Thirty-four patients who had advanced HCC with unresectability or unsuccessful previous therapy in the absence of extrahepatic metastasis were treated with intra-arterial FUDR chemotherapy at our hospital between March 2005 and May 2008. Among the 34 patients, 9 patients were classified as Child class C, and 18 patients had portal vein tumor thrombus (PVTT). One course of chemotherapy consisted of continuous infusion of FUDR (0.3 mg/kg during day 1-14) and dexamethasone (10 mg on day 1, 4, 7 and 11), and this treatment was repeated every 28 d. RESULTS: Two patients (5.9%) displayed a complete response, and 12 patients (35.3%) had a partial response. The tumor control rate was 61.8%. The median overall survival times were 15.3 mo, 12.4 mo and 4.3 mo for the patients who were classified as Child class A, Child class B and Child class C, respectively (P = 0.0392). The progression-free survival was 12.9 mo, 7.7 mo and 2.6 mo for the patients who were classified as Child class A, Child class B and Child class C, respectively (P = 0.0443). The cumulative survival differed significantly according to the Child-Pugh classification and the presence of PVTT. In addition to hepatic reserve capacity and PVTT, the extent of HCC was an independent factor in determining a poor prognosis. The most common adverse reactions to HAIC were mucositis, diarrhea and peptic ulcer disease, but most of these complications were improved by medical treatment and/or a delay of HAIC. CONCLUSION: The present study demonstrates that intra-arterial FUDR chemotherapy is a safe and effective treatment for advanced HCC that is recalcitrant to other therapeutic modalities, even in patients with advanced cirrhosis. PMID:22807613

  16. Trends and practices in diagnosis and treatment of hepatocellular carcinoma

    International Nuclear Information System (INIS)

    2010-01-01

    Hepatocellular carcinoma (HCC), or primary liver cancer, is one of the most common causes of cancer and cancer death globally, and has an increasing incidence. It is currently the fifth most common cancer among men and eighth among women. In some Asian and African countries, its incidence is similar to that of lung cancer. It carries a very poor prognosis; the majority of patients die within a year, making it the third most common cause of cancer death. Currently, the main treatments offering the chance of cure are surgical resection and liver transplantation. However, owing to late presentation and underlying liver cirrhosis, these are suitable only for a small minority of patients. Therefore, new investigative protocols in radiotherapy using the most advanced technologies have been developed with some promise of cure and effective palliation. However, no uniform recommendations exist and the use of radiotherapy is limited by pre-existing liver disease. The IAEA has extensive projects in radiation oncology in low and middle income countries, including areas in Asia and Africa where HCC is a common problem. Since there has been a reported significant increase in the use of radiotherapy in HCC, an expert review was considered timely to assess the role of radiotherapy within the entire framework of HCC management. This publication developed from the need to address this issue. A meeting on the current knowledge of HCC epidemiology and management protocols was convened in October 2008. The given task was to define the current role of radiotherapy in the management of HCC. The greatest number of patients requiring optimal management protocols for HCC lives in Asia and sub-Saharan Africa, where in many countries access to radiotherapy and cancer care in general is limited and resources for research and access to the most advanced technologies are not available. This review is intended for use in training courses and as a source of information on treatment decisions. It

  17. Prognostic value of Notch-1 expression in hepatocellular carcinoma: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Wu T

    2015-10-01

    Full Text Available Tao Wu,1 Min Jiao,1 Li Jing,1 Min-Cong Wang,1 Hai-Feng Sun,2 Qing Li,1 Yi-Yang Bai,1 Yong-Chang Wei,1 Ke-Jun Nan,1 Hui Guo1 1Department of Medical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, 2Department of Oncology, Shaanxi Cancer Hospital, Xi’an, People’s Republic of China Abstract: Association of Notch-1 expression with prognosis of patients with hepatocellular carcinoma (HCC remains controversial. We conducted a meta-analysis to reevaluate the association of Notch-1 expression with clinicopathological characteristics and prognosis of HCC. PubMed, Embase, Web of Science, and China National Knowledge Infrastructure were searched to look for relevant studies. The association between Notch-1 expression and clinicopathological parameters and overall survival (OS was then reassessed using the meta-analysis for odds ratio (OR or hazard ratio (HR and 95% confidence interval (CI. A total of seven studies, including 810 HCC patients, were eligible for the meta-analysis. Our data showed that high Notch-1 expression was able to predict poor OS (HR 1.50, 95% CI 1.17–1.83, P=0.0001. The pooled OR showed that high Notch-1 expression was significantly associated with tumor metastasis (OR 0.37, 95% CI 0.16–0.86, P=0.02 and tumor size >5 cm (OR 0.48, 95% CI 0.26–0.88, P=0.02. In contrast, there was no association between high Notch-1 expression and tumor differentiation, late TNM stage, tumor number, and portal vein invasion of HCC. In conclusion, Notch-1 overexpression might predict poorer survival and more aggressive behavior in patients with HCC. Keywords: hepatocellular carcinoma, Notch-1, prognosis, clinicopathological features, meta-analysis

  18. Intraoperative ultrasound for prediction of hepatocellular carcinoma biological behaviour: Prospective comparison with pathology.

    Science.gov (United States)

    Santambrogio, Roberto; Cigala, Claudia; Barabino, Matteo; Maggioni, Marco; Scifo, Giovanna; Bruno, Savino; Bertolini, Emanuela; Opocher, Enrico; Bulfamante, Gaetano

    2018-02-01

    Preoperative prediction of both microinvasive hepatocellular carcinoma and histological grade of hepatocellular carcinoma is pivotal to treatment planning and prognostication. The aim of this study was to evaluate whether some intraoperative ultrasound features correlate with both the presence of same histological patterns and differentiation grade of hepatocellular carcinoma on the histological features of the primary resected tumour. All patients with single, small hepatocellular carcinoma that underwent hepatic resection were included in this prospective double-blind study: the intraoperative ultrasound patterns of nodule were registered and compared with similar histological features. A total of 179 patients were enclosed in this study: 97 (54%) patients (34% in HCC ≤2 cm) had a microinvasive hepatocellular carcinoma at ultrasound examination, while 82 (46%) patients (41% in HCC ≤2 cm) at histological evaluation. Statistical analysis showed that diameters ≤2 cm, presence of satellites and microinvasive hepatocellular carcinoma at ultrasound examination were the variables with the strongest association with the histological findings. In the multivariate analysis, the vascular microinfiltration and infiltrative hepatocellular carcinoma aspect were independent predictors for grading. In patients with cirrhosis and hepatocellular carcinoma, the prevalence of microinvasive hepatocellular carcinoma is high, even in cases of HCC ≤2 cm. Intraoperative ultrasound findings strongly correlated with histopathological criteria in detecting microinvasive patterns and are useful to predict neoplastic differentiation. The knowledge of these features prior to treatment are highly desired (this can be obtained by an intraoperative ultrasound examination), as they could help in providing optimal management of patients with hepatocellular carcinoma. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  19. Prognostic factors in transcatheter arterial chemoembolization of hepatocellular carcinoma : analysis of more than 3 year survivors

    Energy Technology Data Exchange (ETDEWEB)

    Seo, Heung Suk [Hanyang Univ. College of Medicine, Seoul (Korea, Republic of)

    1999-06-01

    To determine which prognostic factors contribute to long-term survival after transcatheter arterial chemoembolization(TACE) of hepatocellular carcinoma. In 100 patients who expired within one year and 84 who survived or have survived for more than 3 years after TACE, prognostic factors were retrospectively evaluated. TACE was accomplished by hepatic arterial infusion of a suspension of Lipiodol and anticancer drugs(Mitomycin-C and Adriamycin), either alone or followed by gelfoam embolization. Fisher's exact test of probability was used to determine which prognostic factors were statistically significant. Statistically significant prognostic factors were as follows : Child classification(p<0.01), alpha-fetoprotein value(p<0.05), type of tumor(p<0.01), portal vein status(p<0.01), and vascularity of the tumor(p<0.05). HBsAg, tumor size, and method of chemoembolization were not statistically significant(p>0.05). The prognosis of patients with hepatocellular carcinoma treated by TACE was affected favorably by good liver function(Child classification A), low alpha-fetoprotein value, nodular or massive-type tumor, patent main and first-order portal vein, and hypervascular tumor.

  20. Prognostic factors in the treatment of locally advanced hepatocellular carcinoma with radiotherapy and arterial infusion

    International Nuclear Information System (INIS)

    Wang, Y.; Jin, Y.; Zhang, Z.

    2000-01-01

    Prognostic factors in the treatment of local advanced hepatocellular carcinoma with radiotherapy, transcatheter arterial embolization and arterial infusion. The treatment effects of radiotherapy and combination modality therapy for the local advanced hepatocellular carcinoma (HCC) were retrospectively reviewed. Three hundred and fifty-six patients of HCC (187 recurrent cases after surgical resection) were treated by: radiotherapy only ; bi-therapeutic method: hepatic artery ligation (HAL) and/or hepatic artery embolization (HAE) plus radiotherapy; and tri-therapeutic method (bi-therapeutic method plus hepatic artery infusion) from 1975 to 1996. Kaplan-Meier method has been used to evaluate the survival rates. There were no significant differences among these three treatment groups in the symptom relied rate, but the mean relief time period was much shorter in radiotherapy alone group (2.5 vs 44 months, P 0.05). There were evident differences in five-year survivals among these three treatment groups: 0 % for radiotherapy alone, 22.8 % for bi-therapeutic method and 38.8 % for tri-therapeutic method (P < 0.01). The prognosis was influenced by Okuda classification. Non-resectable local advanced HCC can be treated by the combination modality therapy, including radiotherapy, with a quite high cure rate. Radiotherapy alone can relief the symptoms. (authors)

  1. Clinicopathological and prognostic significance of OCT4 in patients with hepatocellular carcinoma: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Liang CJ

    2017-12-01

    Full Text Available Chaojie Liang,* Yingchen Xu,* Hua Ge, Guangming Li, Jixiang Wu Department of General Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, China *These authors contributed equally to this work Background and aims: Octamer-binding transcription factor 4 (OCT4 has been implicated in the development of hepatocellular carcinoma (HCC, although the findings are controversial. We conducted a meta-analysis to assess the correlation between OCT4 and the clinicopathological characteristics and the prognostic value in HCC.Methods: An electronic search for relevant articles was conducted in PubMed, Cochrane Library, Web of Science, EMBASE database, Chinese CNKI, and Chinese WanFang database. Correlations between OCT4 expression and clinicopathological features and survival outcomes were analyzed. Pooled odds ratios and hazard ratios with 95% CIs were calculated using STATA 14.2 software.Results: A total of 10 trials with 985 patients were included. Positive OCT4 expression was correlated with tumor size, tumor numbers, differentiation, and TNM stage. OCT4 expression was not correlated with gender, age, hepatitis B surface antigen, alfa-fetoprotein, liver cirrhosis, vascular invasion, or tumor encapsulation. OCT4 expression was associated with poor 3- and 5-year overall survival, and disease-free survival rate.Conclusion: OCT4 expression was associated with tumor size, tumor numbers, differentiation, and TNM stage in HCC. OCT4 may be a useful prognostic biomarker for HCC. Keywords: octamer-binding transcription factor 4, hepatocellular carcinoma, prognosis, meta-analysis

  2. The effect of chemo-embolization on E-cadherin expression of primary hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Xiao Enhua; Hu Guodong; Liu Pengcheng; Hu Daoyu; Liu Shaochun; Hao Chunrong

    2001-01-01

    Objective: To study the significance of E-cadherin (E-cad) expression of primary hepatocellular carcinoma (PHC), and the effect of the different chemo-embolization treatment on E-cad. Methods:Ninety-eight histopathological verified PHC specimens were obtained. The patients were treated with surgical resection alone (57 cases), and second stage surgical resection after four kinds of chemo-embolization (41 cases). Strept avidin-biotin complex (SABC) immunohistochemical staining with monoclonal antibody against human E-cad was used to observe the E-cad in all specimens. The experimental results were compared with the surgical and clinical findings. Results: The metastatic rates in E-cad (+) and (-) were 43.3%, 70.4% respectively (x 2 = 4.22, P 0.05). The E-cad expression of trabecular and clear cell PHC was higher than that of solid and poorly differentiated PHC. After chemo-embolization, the E-cad expression of the former decreased, the latter increased. The E-cad expression decreased as pathologic grades increasing. After chemo-embolization, the E-cad expression increased as pathological grades increasing. The metastatic rates in interventional group and surgical resection alone were 48.8%, 56.1% respectively (P > 0.05). Conclusions: The increased expression of E-cad would restrain PHC from metastasis. It could act as a prognosis-predictive marker. The effect of chemo-embolization on E-cadherin expression of primary hepatocellular carcinoma had histopathologic difference

  3. Synergistic Antitumor Effect of Doxorubicin and Tacrolimus (FK506 on Hepatocellular Carcinoma Cell Lines

    Directory of Open Access Journals (Sweden)

    Francesca Capone

    2014-01-01

    Full Text Available Hepatocellular carcinoma is the fifth most common cancer worldwide and shows a complex clinical course, poor response to pharmacological treatment, and a severe prognosis. Thus, the aim of this study was to investigate whether tacrolimus (FK506 has synergistic antitumor effects with doxorubicin on two human hepatocellular carcinoma cell lines, Huh7 and HepG2. Cell viability was analyzed by Sulforhodamine B assay and synergic effect was evaluated by the software CalcuSyn. Cell apoptosis was evaluated using Annexin V and Dead Cell assay. Apoptosis-related protein PARP-1 cleaved and autophagy-related protein expressions (Beclin-1 and LC3B were measured by western blotting analysis. Cytokines concentration in cellular supernatants after treatments was studied by Bio-Plex assay. Interestingly the formulation with doxorubicin and tacrolimus induced higher cytotoxicity level on tumor cells than single treatment. Moreover, our results showed that the mechanisms involved were (i a strong cell apoptosis induction, (ii contemporaneous decrease of autophagy activation, understood as prosurvival process, and (iii downregulation of proinflammatory cytokines. In conclusion, future studies could relate to the doxorubicin/tacrolimus combination effects in mice models bearing HCC in order to see if this formulation could be useful in HCC treatment.

  4. Effects of marital status on survival of hepatocellular carcinoma by race/ethnicity and gender.

    Science.gov (United States)

    Wu, Wenrui; Fang, Daiqiong; Shi, Ding; Bian, Xiaoyuan; Li, Lanjuan

    2018-01-01

    It is well demonstrated that being married is associated with a better prognosis in multiple types of cancer. However, whether the protective effect of marital status varied across race/ethnicity and gender in patients with hepatocellular carcinoma remains unclear. Therefore, we aimed to evaluate the roles of race/ethnicity and gender in this relationship. We identified eligible patients from Surveillance, Epidemiology and End Results (SEER) database during 2004-2012. Overall and cancer-specific survival differences across marital status were compared by Kaplan-Meier curves. We also estimated crude hazard ratios (CHRs) and adjusted hazard ratios (AHRs) with 95% confidence intervals (CIs) for marital status associated with survival by race/ethnicity and gender in Cox proportional hazard models. A total of 12,168 eligible patients diagnosed with hepatocellular carcinoma were included. We observed that married status was an independent protective prognostic factor for overall and cancer-specific survival. In stratified analyses by race/ethnicity, the AHR of overall mortality (unmarried vs married) was highest for Hispanic (AHR =1.25, 95% CI, 1.13-1.39; P married patients obtained better survival advantages. Race/ethnicity and gender could influence the magnitude of associations between marital status and risk of mortality.

  5. Spinal cord injury after conducting transcatheter arterial chemoembolization for costal metastasis of hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Sang Jung Park

    2012-09-01

    Full Text Available Transcatheter arterial chemoembolization (TACE has been used widely to treat patients with unresectable hepatocellular carcinoma. However, this method can induce various adverse events caused by necrosis of the tumor itself or damage to nontumor tissues. In particular, neurologic side effects such as cerebral infarction and paraplegia, although rare, may cause severe sequelae and permanent disability. Detailed information regarding the treatment process and prognosis associated with this procedure is not yet available. We experienced a case of paraplegia that occurred after conducting TACE through the intercostal artery to treat hepatocellular carcinoma that had metastasized to the rib. In this case, TACE was attempted to relieve severe bone pain, which had persisted even after palliative radiotherapy. A sudden impairment of sensory and motor functions after TACE developed in the trunk below the level of the sternum and in both lower extremities. The patient subsequently received steroid pulse therapy along with supportive care and continuous rehabilitation. At the time of discharge the patient had recovered sufficiently to enable him to walk by himself, although some paresthesia and spasticity remained.

  6. Computed tomography of liver tumors, 2. Differential diagnosis between hepatocellular carcinoma and metastatic hepatic tumor by dynamic CT scanning

    Energy Technology Data Exchange (ETDEWEB)

    Naito, Akira; Fukuoka, Haruhito; Kashiwado, Kouzou; Ichiki, Toshio; Makidono, Yoko [Hiroshima Red Cross Hospital (Japan)

    1984-02-01

    Differential diagnosis between hepatocellular carcinoma and metastatic hepatic tumor was attempted using dynamic CT scanning. Homogeneous and patchy types were peculiar to hepatocellular carcinoma, and ring-like type to metastatic hepatic tumor. However, with no enhancement, hepatocellular carcinoma could not be denied. Hepatocellular carcinoma was characterized by the enhancement shown on the early stage of dynamic CT. Ring enhancement was not visualized on dynamic CT but visualized on conventional contrast enhanced CT in hepatocellular carcinomas; it was visualized on conventional contrast enhanced CT and on dynamic CT in metastatic hepatic tumors.

  7. Yttrium-90 microspheres for the treatment of hepatocellular carcinoma.

    Science.gov (United States)

    Geschwind, Jean Francois H; Salem, Riad; Carr, Brian I; Soulen, Michael C; Thurston, Kenneth G; Goin, Kathleen A; Van Buskirk, Mark; Roberts, Carol A; Goin, James E

    2004-11-01

    Unresectable hepatocellular carcinoma is extremely difficult to treat. TheraSphere consists of yttrium-90 (a pure beta emitter) microspheres, which are injected into the hepatic arteries. This article reviews the safety and survival of patients with hepatocellular carcinoma who were treated with yttrium-90 microspheres. Eighty patients were selected from a database of 108 yttrium-90 microsphere-treated patients and were staged by using Child-Pugh, Okuda, and Cancer of the Liver Italian Program scoring systems. Patients were treated with local, regional, and whole-liver approaches. Survival from first treatment was analyzed with Kaplan-Meier and Cox regression methods. Adverse events and complications of treatment were coded by using the Southwest Oncology Group toxicity scoring system. Patients received liver doses ranging from 47 to 270 Gy. Thirty-two patients (40%) received more than 1 treatment. Survival correlated with pretreatment Cancer of the Liver Italian Program scores ( P = .002), as well as with the individual Cancer of the Liver Italian Program components, Child-Pugh class, alpha-fetoprotein levels, and percentage of tumor replacement. Patients classified as Okuda stage I (n = 54) and II (n = 26) had median survival durations and 1-year survival rates of 628 days and 63%, and 384 days and 51%, respectively ( P = .02). One patient died of liver failure judged as possibly related to treatment. Thus, in selected patients with hepatocellular carcinoma, yttrium-90 microsphere treatment is safe and well tolerated. On the basis of these results, a randomized controlled trial is warranted comparing yttrium-90 microsphere treatment with transarterial chemoembolization by using the Cancer of the Liver Italian Program system for prospective stratified randomization.

  8. Henoch-Schönlein Purpura Complicated by Hepatocellular Carcinoma.

    Science.gov (United States)

    Akizue, Naoki; Suzuki, Eiichiro; Yokoyama, Masayuki; Inoue, Masanori; Wakamatsu, Toru; Saito, Tomoko; Kusakabe, Yuko; Ogasawara, Sadahisa; Ooka, Yoshihiko; Tawada, Akinobu; Maru, Yugo; Matsue, Hiroyuki; Chiba, Tetsuhiro

    2017-11-15

    Although Henoch-Schönlein purpura (HSP) is known to be accompanied by malignancies, cases with hepatobiliary cancer are extremely rare. A 62-year-old man with palpable purpura rapidly extending to both lower legs was admitted to our hospital. He was undergoing follow-up for cirrhosis caused by chronic hepatitis B virus infection and hepatocellular carcinoma (HCC). He had renal dysfunction with hematuria and proteinuria and abdominal pain. Based on the clinical presentation and skin biopsy findings, he was diagnosed with HSP. The administration of steroids resulted in the rapid improvement of the patient's symptoms and he was discharged 12 days after admission.

  9. CT diagnosis of abdominal lymph node metastases in hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Tanaka, T; Nakamura, H; Choi, S; Morimoto, K; Kawamoto, S; Hori, S; Tokunaga, K; Yoskioka, H; Kuroda, C

    1985-08-01

    CT scanning is useful for diagnosing abdominal lymph node metastasis. Using this technique, histologically confirmed abdominal lymph node metastases were detected in nine of 49 patients (33 autopsy cases and 16 laparotomy cases) with hepatocellular carcinoma (hepatoma). Among the 49 patients, three had periportal (6.1%), six peripancreatic (12.2.%) and six para-aortic adenopathies (12.2%). Two of the patients had adenopathy at all three sites. Retrospectively, CT detected two periportal, four peripancreatic and all six para-aortic adenopathies. Most of the hepatomas with adenopathy showed infiltrative growth; tumour thrombosis of the portal vein was a common complication.

  10. Computed tomography of hepatocellular carcinoma. Comparison with scintigraphy and ultrasonography

    Energy Technology Data Exchange (ETDEWEB)

    Kaneko, Kuniyuki; Nakata, Hajime; Honda, Hiroshi [University of Occupational and Environmental Health, Kitakyushu, Fukuoka (Japan)

    1983-09-01

    The detectability of hepatocellular carcinoma by computed tomography (CT) was evaluated on 76 cases. The detectability by plain CT was 93% with only slight improvement following a drip infusion of contrast medium. A comparison of scintigraphy, ultrasonography, and CT was also done on 63 cases. From the standpoint of the overall detectability of the tumor, CT was as good as ultrasonography or scintigraphy. Several cases were positive only on either CT or ultrasonography but no case was positive on scintigraphy alone. We believe that the combination of CT and ultrasonography is the most reliable as the screening method.

  11. Hepatocellular carcinoma complicating cystic fibrosis related liver disease.

    LENUS (Irish Health Repository)

    O'Donnell, D H

    2012-02-01

    Early diagnosis and treatment of the respiratory and gastrointestinal complications of cystic fibrosis (CF) have led to improved survival with many patients living beyond the fourth decade. Along with this increased life expectancy is the risk of further disease associated with the chronic manifestations of their condition. We report a patient with documented CF related liver disease for which he was under routine surveillance that presented with histologically proven hepatocellular carcinoma (HCC). It is important that physicians are aware of this association as increased vigilance may lead to earlier diagnosis and perhaps, a better outcome.

  12. Research advances in regorafenib in treatment of hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    CHEN Weibo

    2017-12-01

    Full Text Available Hepatocellular carcinoma (HCC is the most common malignant liver tumor, and there are limited systemic treatments for patients with advanced HCC. Regorafenib is an oral multi-kinase inhibitor, and phase III clinical trial has shown that regorafenib can significantly extend the median survival of patients with advanced HCC by 2.8 months, which makes it a second-line drug approved by FDA for the treatment of advanced HCC, just after sorafenib. This article reviews the basic and clinical research on regorafenib in the field of HCC.

  13. Recent advances in targeted drug therapy for hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    FAN Yongqiang

    2018-02-01

    Full Text Available More and more clinical trials have proved the efficacy of targeted drugs in the treatment of hepatocellular carcinoma (HCC. With the development of science and technology, more and more targeted drugs have appeared. In recent years, targeted drugs such as regorafenib and ramucirumab have shown great potential in related clinical trials. In addition, there are ongoing clinical trials for second-line candidate drugs, such as c-Met inhibitors tivantinib and cabozantinib and a VEGFR-2 inhibitor ramucirumab. This article summarizes the advances in targeted drug therapy for HCC and related trial data, which provides a reference for further clinical trials and treatment.

  14. Bone metastases as initial presentation of hepatocellular carcinoma.

    Science.gov (United States)

    Monteserin, Luzdivina; Mesa, Alicia; Fernandez-Garcia, Maria Soledad; Gadanon-Garcia, Arantza; Rodriguez, Manuel; Varela, María

    2017-10-18

    Extra-hepatic spread is present in 5% to 15% of patients with hepatocellular carcinoma (HCC) at the time of diagnosis. The most frequent sites are lung and regional lymph nodes. Here, we report 3 cases of unsuspected HCC with symptoms due to bone lesions as initial presentation. Morphological characteristics and immunohistochemistry from the examined bone were the key data for diagnosis. None of the patients had an already known chronic liver disease. Differential diagnoses with HCC upon ectopic liver disease or hepatoid adenocarcinoma were shown. Therapy with the orally active multikinase inhibitor sorafenib plus symptomatic treatment was indicated.

  15. Prebiotics: A Novel Approach to Treat Hepatocellular Carcinoma.

    Science.gov (United States)

    Fatima, Naz; Akhtar, Tasleem; Sheikh, Nadeem

    2017-01-01

    Hepatocellular carcinoma is one of the fatal malignancies and is considered as the third leading cause of death. Mutations, genetic modifications, dietary aflatoxins, or impairments in the regulation of oncogenic pathways may bring about liver cancer. An effective barrier against hepatotoxins is offered by gut-liver axis as a change in gut permeability and expanded translocation of lipopolysaccharides triggers the activation of Toll-like receptors which stimulate the process of hepatocarcinogenesis. Prebiotics, nondigestible oligosaccharides, have a pivotal role to play when it comes to inducing an antitumor effect. A healthy gut flora balance is imperative to downregulation of inflammatory cytokines and reducing lipopolysaccharides induced endotoxemia, thus inducing the antitumor effect.

  16. Research advances in Hedgehog signaling pathway in hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    LIU Jia

    2015-02-01

    Full Text Available Hedgehog (Hh signaling pathway is present in many animals and plays an important role in regulating embryonic development and differentiation. Aberrant activation of Hh signaling contributes to the pathogenesis of many malignancies. Recent studies have shown that dysregulated Hh signaling pathway participates in the tumorigenesis, tumor invasion, and metastasis of hepatocellular carcinoma (HCC. Investigation of the relationship between Hh signaling pathway and HCC will help elucidate the molecular mechanism of pathogenesis of HCC and provide a new insight into the development of novel anticancer therapy and therapeutic target.

  17. Extrahepatic spread of hepatocellular carcinoma: a pictorial review

    International Nuclear Information System (INIS)

    Hong, Seong Sook; Kim, Tae Kyoung; Sung, Kyu-Bo; Kim, Pyo Nyun; Ha, Hyun Kwon; Kim, Ah Young; Lee, Moon-Gyu

    2003-01-01

    Although extrahepatic spread of hepatocellular carcinoma (HCC) is uncommon, it can be found anywhere in the body. Most extrahepatic metastases of HCC occur in patients with advanced-stage intrahepatic tumor, but incidental extrahepatic lesions have also occasionally been found in patients with early-stage intrahepatic HCC. The detection of extrahepatic metastatic disease is crucial when planning therapy for patients with HCC and should be used to avoid unnecessary surgical intervention. In this study we illustrate the radiologic findings of extrahepatic metastases of HCC involving various sites. The presumed mechanism of extrahepatic extension of HCC is also discussed. (orig.)

  18. Delayed hepatobiliary imaging in the diagnosis of hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Chen, S.; Ma, Z.; Tang, Z.

    2000-01-01

    In recent years, the use of ultrasonography (US), X-CT and MRI has reduced the employment of isotopic explorations in the detection of hepatocellular carcinoma (HCC). But sometime the results of US, X-CT or MRI were different and diagnosis was very difficult. This present investigation was aimed to assess the usefulness of delayed hepatobiliary imaging in the diagnosis of HCC in these patients. Forty-eight patients consisting of 33 males and 15 females were entered into the research protocol. The mean age was 46 yr old (range 12-71 yr old). All of the patients were performed by surgery and verified histologically after nuclear examination. The subject was in a supine position under a gamma camera (Elscint, Apex Ap-6) and 555 MBq of Tc-99m-PMT were injected intravenously. The initial scinphotos obtained within 1 min after injection were used to image the blood pool phase. Subsequently, hepatic scans were obtained at 5 min, 1,2 and 5 hr. Anterior, right lateral and posterior hepatic images were recorded. According to the radioactive uptake by the lesion in delayed phase, the negative (no or minor uptake), positive (equal or greater uptake) or very strong positive (almost equal to the activity, of gallbladder) were judged. The positive were considered as diagnostic of HCC. And the very strong positive, were considered as diagnostic of benign hepatoma, such as adenoma or FNH. Thirty-seven of the forty-eight patients were HCC based on histology. Delayed imaging revealed increased or equilibrated uptake of radioactivity by the tumors in 22 of 37 patients with hepatocellular carcinoma. The sensitivity was 59.5%. One patient final diagnosis based on histology was focal nodular regenerative hyperplasia, and only the diagnosis with delayed hepatobiliary imaging before surgery was correct. Compared with US, X-CT and MRI, delayed hepatobiliary imaging had the highest specificity for diagnosis of hepatocellular carcinoma. In recent group, the specificity of Tc-99m-PMT delayed

  19. CT determinants of prognosis in pancreatic carcinoma

    International Nuclear Information System (INIS)

    Schreiber, A.E.; Honda, H.; Berbaum, K.; Franken, E.A.; Lu, C.H.

    1988-01-01

    Abdominal CT scans of 61 patients with pathologically proved pancreatic carcinoma were analyzed to determine the radiographic features that predict length of survival. Excluded from study were patients who underwent definitive surgical procedures (Whipple procedure or pancreatectomy) or who received radiation or chemotherapy. Scans were evaluated in 18 radiographic and clinicopathologic categories. Multifactorial regression analysis indicated that the factors that most accurately predict the length of patient survival are (1) size, (2) associated lymphadenopathy, (3) hepatic metastasis, (4) hepatoduodenal ligament involvement, and (5) involvement of the mesentery and/or peritoneum

  20. Primary hepatocellular carcinoma localised by a radiolabelled monoclonal antibody

    Energy Technology Data Exchange (ETDEWEB)

    Markham, N; Ritson, A; James, O; Curtin, N; Bassendine, M; Sikora, K

    1986-01-01

    A rat monoclonal antibody, YPC2/38.8, was selected from a panel of antibodies derived by immunising rats with fresh human colorectal carcinoma. It was found to bind to a 30,000 dalton protein present on the cell surface of normal colon and liver. This protein was increased 10-fold on primary hepatocellular carcinoma (PHC) cells. After labelling with /sup 131/I, YPC2/38.8 was shown to localise human PHCs grown as xenografts in immunosuppressed mice. The authors conclude that YPC2/38.8 may have potential for diagnostic localisation and possibly thence for the selective targeting of drugs or toxins in patients with PHC arising in a liver unaffected by significant parenchymal disease. 16 refs.; 4 figs.; 1 table.

  1. PKCα promotes generation of reactive oxygen species via DUOX2 in hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Wang, Jiajun; Shao, Miaomiao; Liu, Min; Peng, Peike; Li, Lili; Wu, Weicheng; Wang, Lan; Duan, Fangfang; Zhang, Mingming; Song, Shushu; Jia, Dongwei; Ruan, Yuanyuan; Gu, Jianxin

    2015-01-01

    Hepatocellular carcinoma (HCC) remains the second leading cause of cancer-related death worldwide, and elevated rates of reactive oxygen species (ROS) have long been considered as a hallmark of almost all types of cancer including HCC. Protein kinase C alpha (PKCα), a serine/threonine kinase among conventional PKC family, is recognized as a major player in signal transduction and tumor progression. Overexpression of PKCα is commonly observed in human HCC and associated with its poor prognosis. However, how PKCα is involved in hepatocellular carcinogenesis remains not fully understood. In this study, we found that among the members of conventional PKC family, PKCα, but not PKCβI or βII, promoted ROS production in HCC cells. PKCα stimulated generation of ROS by up-regulating DUOX2 at post-transcriptional level. Depletion of DUOX2 abrogated PKCα-induced activation of AKT/MAPK pathways as well as cell proliferation, migration and invasion in HCC cells. Moreover, the expression of DUOX2 and PKCα was well positively correlated in both HCC cell lines and patient samples. Collectively, our findings demonstrate that PKCα plays a critical role in HCC development by inducing DUOX2 expression and ROS generation, and propose a strategy to target PKCα/DUOX2 as a potential adjuvant therapy for HCC treatment. - Highlights: • PKCα promotes the generation of ROS in hepatocellular carcinoma. • PKCα induces ROS production by up-regulating DUOX2 at post-transcriptional level. • DUOX2 is required for PKCα-induced AKT/MAPK activation and tumor progression in HCC. • The expression of PKCα is positively correlated with DUOX2 in HCC

  2. PKCα promotes generation of reactive oxygen species via DUOX2 in hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jiajun; Shao, Miaomiao; Liu, Min; Peng, Peike; Li, Lili; Wu, Weicheng; Wang, Lan [Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, 200032 Shanghai (China); Duan, Fangfang [Institute of Biomedical Science, Fudan University, Shanghai (China); Zhang, Mingming; Song, Shushu [Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, 200032 Shanghai (China); Jia, Dongwei, E-mail: jiadongwei@fudan.edu.cn [Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, 200032 Shanghai (China); Ruan, Yuanyuan, E-mail: yuanyuanruan@fudan.edu.cn [Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, 200032 Shanghai (China); Gu, Jianxin [Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, 200032 Shanghai (China); Institute of Biomedical Science, Fudan University, Shanghai (China)

    2015-08-07

    Hepatocellular carcinoma (HCC) remains the second leading cause of cancer-related death worldwide, and elevated rates of reactive oxygen species (ROS) have long been considered as a hallmark of almost all types of cancer including HCC. Protein kinase C alpha (PKCα), a serine/threonine kinase among conventional PKC family, is recognized as a major player in signal transduction and tumor progression. Overexpression of PKCα is commonly observed in human HCC and associated with its poor prognosis. However, how PKCα is involved in hepatocellular carcinogenesis remains not fully understood. In this study, we found that among the members of conventional PKC family, PKCα, but not PKCβI or βII, promoted ROS production in HCC cells. PKCα stimulated generation of ROS by up-regulating DUOX2 at post-transcriptional level. Depletion of DUOX2 abrogated PKCα-induced activation of AKT/MAPK pathways as well as cell proliferation, migration and invasion in HCC cells. Moreover, the expression of DUOX2 and PKCα was well positively correlated in both HCC cell lines and patient samples. Collectively, our findings demonstrate that PKCα plays a critical role in HCC development by inducing DUOX2 expression and ROS generation, and propose a strategy to target PKCα/DUOX2 as a potential adjuvant therapy for HCC treatment. - Highlights: • PKCα promotes the generation of ROS in hepatocellular carcinoma. • PKCα induces ROS production by up-regulating DUOX2 at post-transcriptional level. • DUOX2 is required for PKCα-induced AKT/MAPK activation and tumor progression in HCC. • The expression of PKCα is positively correlated with DUOX2 in HCC.

  3. Prevention of hepatocellular carcinoma: potential targets, experimental models, and clinical challenges

    Science.gov (United States)

    Hoshida, Yujin; Fuchs, Bryan C.; Tanabe, Kenneth K.

    2013-01-01

    Chronic fibrotic liver diseases such as viral hepatitis eventually develop liver cirrhosis, which causes occurrence of hepatocellular carcinoma (HCC). Given the limited therapeutic efficacy in advanced HCC, prevention of HCC development could be an effective strategy for improving patient prognosis. However, there is still no established therapy to meet the goal. Studies have elucidated a wide variety of molecular mechanisms and signaling pathways involved in HCC development. Genetically-engineered or chemically-treated experimental models of cirrhosis and HCC have been developed and shown their potential value in investigating molecular therapeutic targets and diagnostic biomarkers for HCC prevention. In this review, we overview potential targets of prevention and currently available experimental models, and discuss strategies to translate the findings into clinical practice. PMID:22873223

  4. Deep convolutional neural network for the classification of hepatocellular carcinoma and intrahepatic cholangiocarcinoma

    Science.gov (United States)

    Midya, Abhishek; Chakraborty, Jayasree; Pak, Linda M.; Zheng, Jian; Jarnagin, William R.; Do, Richard K. G.; Simpson, Amber L.

    2018-02-01

    Liver cancer is the second leading cause of cancer-related death worldwide.1 Hepatocellular carcinoma (HCC) is the most common primary liver cancer accounting for approximately 80% of cases. Intrahepatic cholangiocarcinoma (ICC) is a rare liver cancer, arising in patients with the same risk factors as HCC, but treatment options and prognosis differ. The diagnosis of HCC is based primarily on imaging but distinguishing between HCC and ICC is challenging due to common radiographic features.2-4 The aim of the present study is to classify HCC and ICC in portal venous phase CT. 107 patients with resected ICC and 116 patients with resected HCC were included in our analysis. We developed a deep neural network by modifying a pre-trained Inception network by retraining the final layers. The proposed method achieved the best accuracy and area under the receiver operating characteristics curve of 69.70% and 0.72, respectively on the test data.

  5. Research advances in tumor markers for the diagnosis of hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    YANG Guimin

    2018-01-01

    Full Text Available Hepatocellular carcinoma (HCC is a malignant tumor with a high fatality rate in the world, and alpha-fetoprotein (AFP is the most commonly used tumor marker for HCC diagnosis. However, AFP does not have a satisfactory sensitivity or specificity and may lead to missed diagnosis when the tumor is small in the early stage of HCC. This article summarizes the clinical value of new tumor markers in the diagnosis, treatment monitoring, and prognosis judgment of HCC and analyzes the future prospects of the measurement of tumor markers for HCC. It is pointed out that combined determination of several tumor markers helps to improve the sensitivity and specificity of HCC diagnosis, and the screening and optimization of combined determination of tumor markers, noninvasive and efficient tumor markers, and individualized treatment are research hotspots in future.

  6. Pekinenin E Inhibits the Growth of Hepatocellular Carcinoma by Promoting Endoplasmic Reticulum Stress Mediated Cell Death

    Directory of Open Access Journals (Sweden)

    Lu Fan

    2017-06-01

    Full Text Available Hepatocellular carcinoma (HCC is a malignant primary liver cancer with poor prognosis. In the present study, we report that pekinenin E (PE, a casbane diterpenoid derived from the roots of Euphorbia pekinensis, has a strong antitumor activity against human HCC cells both in vitro and in vivo. PE suppressed the growth of human HCC cells Hep G2 and SMMC-7721. In addition, PE-mediated endoplasmic reticulum (ER stress caused increasing expressions of C/EBP homologous protein (CHOP, leading to apoptosis in HCC cells both in vitro and in vivo. Inhibition of ER stress with CHOP small interfering RNA or 4-phenyl-butyric acid partially reversed PE-induced cell death. Furthermore, PE induced S cell cycle arrest, which could also be partially reversed by CHOP knockdown. In all, these findings suggest that PE causes ER stress-associated cell death and cell cycle arrest, and it may serve as a potent agent for curing human HCC.

  7. Non-coding RNAs: New therapeutic targets and opportunities for hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Yu Cuiyun

    2016-02-01

    Full Text Available Non-coding RNAs (ncRNA are RNA molecules without protein coding functions owing to the lack of an open reading frame (ORF. Based on the length, ncRNAs can be divided into long and short ncRNAs; short ncRNAs include miRNAs and piRNAs. Hepatocellular carcinoma (HCC is among the most frequent forms of cancer worldwide and its incidence is increasing rapidly. Studies have found that ncRNAs are likely to play a crucial role in a variety of biological processes including the pathogenesis and progression of HCC. In this review, we summarized the regulation mechanism and biological functions of ncRNAs in HCC with respect to its application in HCC diagnosis, therapy and prognosis.

  8. Primary hepatic peripheral T-cell lymphoma mimicking hepatocellular carcinoma: a case report.

    Science.gov (United States)

    Lee, Jisun; Park, Kil Sun; Kang, Min Ho; Kim, Yook; Son, Seung-Myoung; Choi, Hanlim; Choi, Jae-Woon; Ryu, Dong Hee

    2017-08-01

    Peripheral T-cell lymphomas (PTCLs) are aggressive neoplasms which may involve the liver. The imaging manifestations of hepatic lymphoma are highly variable and show overlapping appearances of numerous other hepatic diseases. As the management and prognosis of lymphoma differ markedly from those of other malignant diseases, prompt diagnosis and early effective treatment are very important. Here, we report an atypical case of primary PTCL not otherwise specified involving the liver that exhibited a solitary hepatic mass mimicking hepatocellular carcinoma (HCC) on CT. Liver biopsy is not commonly recommended in highly suspicious cases of HCC. However, in a patient without risk factors for HCC, consideration of other diagnostic possibilities is required and needle biopsy may be a more rational choice. An imaging approach, based on a careful review of clinical and laboratory findings is essential to prevent false-positive diagnosis of HCC and subsequent invasive treatment.

  9. Circulating Tumor Cells Measurements in Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Franck Chiappini

    2012-01-01

    Full Text Available Liver cancer is the fifth most common cancer in men and the seventh in women. During the past 20 years, the incidence of HCC has tripled while the 5-year survival rate has remained below 12%. The presence of circulating tumor cells (CTC reflects the aggressiveness nature of a tumor. Many attempts have been made to develop assays that reliably detect and enumerate the CTC during the development of the HCC. In this case, the challenges are (1 there are few markers specific to the HCC (tumor cells versus nontumor cells and (2 they can be used to quantify the number of CTC in the bloodstream. Another technical challenge consists of finding few CTC mixed with million leukocytes and billion erythrocytes. CTC detection and identification can be used to estimate prognosis and may serve as an early marker to assess antitumor activity of treatment. CTC can also be used to predict progression-free survival and overall survival. CTC are an interesting source of biological information in order to understand dissemination, drug resistance, and treatment-induced cell death. Our aim is to review and analyze the different new methods existing to detect, enumerate, and characterize the CTC in the peripheral circulation of patients with HCC.

  10. Resected Hepatocellular Carcinoma in a Patient with Crohn's Disease on Azathioprine

    Science.gov (United States)

    Heron, Valérie; Fortinsky, Kyle Joshua; Spiegle, Gillian; Hilzenrat, Nir; Szilagyi, Andrew

    2016-01-01

    Hepatocellular carcinoma rarely occurs in patients without underlying cirrhosis or liver disease. While inflammatory bowel disease has been linked to certain forms of liver disease, hepatocellular carcinoma is exceedingly rare in these patients. We report the twelfth case of hepatocellular carcinoma in a patient with Crohn's disease. The patient is a 61-year-old with longstanding Crohn's disease who was treated with azathioprine and was found to have elevated liver enzymes and a new 3-cm liver mass on ultrasound. A complete workup for underlying liver disease was unremarkable and liver biopsy revealed hepatocellular carcinoma. The patient underwent a hepatic resection, and there is no evidence of recurrence at the 11-month follow-up. The resection specimen showed no evidence of cancer despite the initial biopsy revealing hepatocellular carcinoma. This case represents the third biopsy-proven complete spontaneous regression of hepatocellular carcinoma. Although large studies have failed to show a definite link between azathioprine and hepatocellular carcinoma, the relationship remains concerning given the multiple case reports suggesting a possible association. Clinicians should exercise a high degree of suspicion in patients with Crohn's disease who present with elevated liver enzymes, especially those on azathioprine therapy. PMID:27403102

  11. Resected Hepatocellular Carcinoma in a Patient with Crohn’s Disease on Azathioprine

    Directory of Open Access Journals (Sweden)

    Valérie Heron

    2016-05-01

    Full Text Available Hepatocellular carcinoma rarely occurs in patients without underlying cirrhosis or liver disease. While inflammatory bowel disease has been linked to certain forms of liver disease, hepatocellular carcinoma is exceedingly rare in these patients. We report the twelfth case of hepatocellular carcinoma in a patient with Crohn’s disease. The patient is a 61-year-old with longstanding Crohn’s disease who was treated with azathioprine and was found to have elevated liver enzymes and a new 3-cm liver mass on ultrasound. A complete workup for underlying liver disease was unremarkable and liver biopsy revealed hepatocellular carcinoma. The patient underwent a hepatic resection, and there is no evidence of recurrence at the 11-month follow-up. The resection specimen showed no evidence of cancer despite the initial biopsy revealing hepatocellular carcinoma. This case represents the third biopsy-proven complete spontaneous regression of hepatocellular carcinoma. Although large studies have failed to show a definite link between azathioprine and hepatocellular carcinoma, the relationship remains concerning given the multiple case reports suggesting a possible association. Clinicians should exercise a high degree of suspicion in patients with Crohn’s disease who present with elevated liver enzymes, especially those on azathioprine therapy.

  12. Sonographic evolution of hepatocellular carcinoma associated with cirrhosis

    International Nuclear Information System (INIS)

    Mazzola, G.; Virdone, R.; Orlando, A.; Turri, A.; Caltagirone, M.; Fusco, G.; Parisi, P.; Cottone, M.

    1989-01-01

    To study the sonographic (US) evolution of hepatocellular carcinoma, 53 tumors in 45 untreated patients were observed regulary with real-time US for a period of 6 to 56 months. At the beginning, 25 tumors were hypoechoic, 18 isoechoic, 4 hyperechoic, and 6 had mixed hypo/hyper echopatterns. At the follow-up, 7 initially hypoechoic tumors had changed to hyperechoic or to mixed echopatterns; 8 hypoechoic tumors had becom isoechoic; 9 of the 25 initially hypoechoic neoplastic lesions had maintained the same echodensity. Ten of the 15 initially isoechoic tumors had changed to mixed echopatterns and 5 had remained unchanged. Three initially isoechoic lesions and a hypoechoic one had turned into diffuse patterns; 2 initially hyperechoic neoplastic lesions had remained unchanged; 1 had switched into hypoechoic, and 1 changed to mixed echopattern; 4 out of 6 tumors with echopattern had remained unchanged, 1 had become hyperechoic and 1 hypoechoic. The current study has proven variou tumors ≤3 cm in diameter to be isoechoic and most tumors >3 in diameter to have mixed hypo/hyper echopatterns. The echogenicity of small hepatocellular carcinomas increases with the tumor growth and remains unchanged when they do not increase in size

  13. High-resolution characterization of a hepatocellular carcinoma genome.

    Science.gov (United States)

    Totoki, Yasushi; Tatsuno, Kenji; Yamamoto, Shogo; Arai, Yasuhito; Hosoda, Fumie; Ishikawa, Shumpei; Tsutsumi, Shuichi; Sonoda, Kohtaro; Totsuka, Hirohiko; Shirakihara, Takuya; Sakamoto, Hiromi; Wang, Linghua; Ojima, Hidenori; Shimada, Kazuaki; Kosuge, Tomoo; Okusaka, Takuji; Kato, Kazuto; Kusuda, Jun; Yoshida, Teruhiko; Aburatani, Hiroyuki; Shibata, Tatsuhiro

    2011-05-01

    Hepatocellular carcinoma, one of the most common virus-associated cancers, is the third most frequent cause of cancer-related death worldwide. By massively parallel sequencing of a primary hepatitis C virus-positive hepatocellular carcinoma (36× coverage) and matched lymphocytes (>28× coverage) from the same individual, we identified more than 11,000 somatic substitutions of the tumor genome that showed predominance of T>C/A>G transition and a decrease of the T>C substitution on the transcribed strand, suggesting preferential DNA repair. Gene annotation enrichment analysis of 63 validated non-synonymous substitutions revealed enrichment of phosphoproteins. We further validated 22 chromosomal rearrangements, generating four fusion transcripts that had altered transcriptional regulation (BCORL1-ELF4) or promoter activity. Whole-exome sequencing at a higher sequence depth (>76× coverage) revealed a TSC1 nonsense substitution in a subpopulation of the tumor cells. This first high-resolution characterization of a virus-associated cancer genome identified previously uncharacterized mutation patterns, intra-chromosomal rearrangements and fusion genes, as well as genetic heterogeneity within the tumor.

  14. Intraarterial digital subtraction angiography applied to diagnosis of hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Nishizawa, Sadahiko; Sano, Akira; Imanaka, Kazufumi; Sasai, Keisuke; Nagae, Toshiyuki; Mizutani, Masaru; Hatabu, Hiroto; Sadatou, Norihiro; Kuroda, Yasumasa

    1985-12-01

    This paper deals with diagnostic values of intraarterial digital subtraction angiography (IADSA) for evaluating hepatocellular carcinoma. The present series consists of 44 patients with hepatocellular carcinoma, who underwent IADSA combined with conventional hepatic angiography 67 times in total. The evaluated vessels by IADSA included 70 hepatic arteries and 36 portal veins. Comparative studies on the image quality of IADSA with conventional angiography were made in referring to the tumor stain for arteriograms and resolution of intrahepatic portal branches for portograms. Diagnostic superiority including equality of DSA image to conventional was noted in arteriograms: 72.7 % in the right lobe and 86 % in the left. Most deteriorated DSA images were caused by misregistration artifacts. IADSA portography revealed basically diagnostic values to demonstrate lobar, segmental or more peripheral branches in about 95 % of cases studied. DSA, characterized by high contrast resolution and real-time subtraction, offered important and effective informations for interventional angiography as well as resectability of the tumors, requiring less contrast medium.

  15. Hepatocellular carcinoma: a retrospective analysis of 118 cases

    International Nuclear Information System (INIS)

    Aman-ur-Rehman; Murad, S.

    2002-01-01

    Objective: This study aimed at documenting the spectrum of clinico pathological variations in hepatocellular carcinoma (HCC). Design: It was a retrospective study. Place and duration of Study: This study was conducted at the Institute of Nuclear Medicine and Oncology (INMOL) Hospital, Lahore from March 1997 to December 2000. Patients and Methods: The profiles of 118 patients with a biopsy proven hepatocellular carcinoma were analyzed in this period. The data collected was age, sex, clinical presentation and laboratory investigations including liver function tests, alpha fetoprotein and hepatitis profile. Results: Weight loss, jaundice and right upper quadrant abdominal pain were the main presenting symptoms. Out of 118 patients, alpha fetoprotein values were raised in 63(53.38%) patients 106 (89.83%) patients were found to have or have had HBV infections, and 92 (77.96%) patients were anti-HCV positive. Eighty-three (70.33%) patients were cirrhotic. History of alcohol abuse was bound in three patients. Conclusion: The common association of HCC with cirrhosis and hepatitis B and C suggests that vaccination against HBV on nationwide basis can decrease prevalence of this malignancy. There is a need to generate public awareness regarding the transmission of these viruses. Early diagnosis and intervention is also important to the successful management of HCC. (author)

  16. Proteomic Studies of Cholangiocarcinoma and Hepatocellular Carcinoma Cell Secretomes

    Directory of Open Access Journals (Sweden)

    Chantragan Srisomsap

    2010-01-01

    Full Text Available Cholangiocarcinoma (CCA and hepatocellular carcinoma (HCC occur with relatively high incidence in Thailand. The secretome, proteins secreted from cancer cells, are potentially useful as biomarkers of the diseases. Proteomic analysis was performed on the secreted proteins of cholangiocarcinoma (HuCCA-1 and hepatocellular carcinoma (HCC-S102, HepG2, SK-Hep-1, and Alexander cell lines. The secretomes of the five cancer cell lines were analyzed by SDS-PAGE combined with LC/MS/MS. Sixty-eight proteins were found to be expressed only in HuCCA-1. Examples include neutrophil gelatinase-associated lipocalin (lipocalin 2, laminin 5 beta 3, cathepsin D precursor, desmoplakin, annexin IV variant, and annexin A5. Immunoblotting was used to confirm the presence of lipocalin 2 in conditioned media and cell lysate of 5 cell lines. The results showed that lipocalin 2 was a secreted protein which is expressed only in the conditioned media of the cholangiocarcinoma cell line. Study of lipocalin 2 expression in different types of cancer and normal tissues from cholangiocarcinoma patients showed that lipocalin 2 was expressed only in the cancer tissues. We suggest that lipocalin 2 may be a potential biomarker for cholangiocarcinoma.

  17. Safety validation of decision trees for hepatocellular carcinoma.

    Science.gov (United States)

    Wang, Xian-Qiang; Liu, Zhe; Lv, Wen-Ping; Luo, Ying; Yang, Guang-Yun; Li, Chong-Hui; Meng, Xiang-Fei; Liu, Yang; Xu, Ke-Sen; Dong, Jia-Hong

    2015-08-21

    To evaluate a different decision tree for safe liver resection and verify its efficiency. A total of 2457 patients underwent hepatic resection between January 2004 and December 2010 at the Chinese PLA General Hospital, and 634 hepatocellular carcinoma (HCC) patients were eligible for the final analyses. Post-hepatectomy liver failure (PHLF) was identified by the association of prothrombin time 50 μmol/L (the "50-50" criteria), which were assessed at day 5 postoperatively or later. The Swiss-Clavien decision tree, Tokyo University-Makuuchi decision tree, and Chinese consensus decision tree were adopted to divide patients into two groups based on those decision trees in sequence, and the PHLF rates were recorded. The overall mortality and PHLF rate were 0.16% and 3.0%. A total of 19 patients experienced PHLF. The numbers of patients to whom the Swiss-Clavien, Tokyo University-Makuuchi, and Chinese consensus decision trees were applied were 581, 573, and 622, and the PHLF rates were 2.75%, 2.62%, and 2.73%, respectively. Significantly more cases satisfied the Chinese consensus decision tree than the Swiss-Clavien decision tree and Tokyo University-Makuuchi decision tree (P decision trees. The Chinese consensus decision tree expands the indications for hepatic resection for HCC patients and does not increase the PHLF rate compared to the Swiss-Clavien and Tokyo University-Makuuchi decision trees. It would be a safe and effective algorithm for hepatectomy in patients with hepatocellular carcinoma.

  18. Nanosecond pulsed electric field ablation of hepatocellular carcinoma.

    Science.gov (United States)

    Beebe, Stephen J; Chen, Xinhua; Liu, Jie A; Schoenbach, Karl H

    2011-01-01

    Hepatocellular carcinoma often evades effective therapy and recurrences are frequent. Recently, nanosecond pulsed electric field (nsPEF) ablation using pulse power technology has emerged as a local-regional, non-thermal, and non-drug therapy for skin cancers. In the studies reported here we use nsPEFs to ablate murine, rat and human HCCs in vitro and an ectopic murine Hepa 1-6 HCC in vivo. Using pulses with 60 or 300 ns and electric fields as high as 60 kV/cm, murine Hepa 1-6, rat N1S1 and human HepG2 HCC are readily eliminated with changes in caspase-3 activity. Interestingly caspase activities increase in the mouse and human model and decrease in the rat model as electric field strengths are increased. In vivo, while sham treated control mice survived an average of 15 days after injection and before humane euthanasia, Hepa 1-6 tumors were eliminated for longer than 50 days with 3 treatments using one hundred pulses with 100 ns at 55 kV/cm. Survival was 40% in mice treated with 30 ns pulses at 55 kV/cm. This study demonstrates that nsPEF ablation is not limited to effectively treating skin cancers and provides a rationale for treating orthotopic hepatocellular carcinoma in pre-clinical applications and ultimately in clinical trials.

  19. Evaluating hepatocellular carcinoma cell lines for tumour samples using within-sample relative expression orderings of genes.

    Science.gov (United States)

    Ao, Lu; Guo, You; Song, Xuekun; Guan, Qingzhou; Zheng, Weicheng; Zhang, Jiahui; Huang, Haiyan; Zou, Yi; Guo, Zheng; Wang, Xianlong

    2017-11-01

    Concerns are raised about the representativeness of cell lines for tumours due to the culture environment and misidentification. Liver is a major metastatic destination of many cancers, which might further confuse the origin of hepatocellular carcinoma cell lines. Therefore, it is of crucial importance to understand how well they can represent hepatocellular carcinoma. The HCC-specific gene pairs with highly stable relative expression orderings in more than 99% of hepatocellular carcinoma but with reversed relative expression orderings in at least 99% of one of the six types of cancer, colorectal carcinoma, breast carcinoma, non-small-cell lung cancer, gastric carcinoma, pancreatic carcinoma and ovarian carcinoma, were identified. With the simple majority rule, the HCC-specific relative expression orderings from comparisons with colorectal carcinoma and breast carcinoma could exactly discriminate primary hepatocellular carcinoma samples from both primary colorectal carcinoma and breast carcinoma samples. Especially, they correctly classified more than 90% of liver metastatic samples from colorectal carcinoma and breast carcinoma to their original tumours. Finally, using these HCC-specific relative expression orderings from comparisons with six cancer types, we identified eight of 24 hepatocellular carcinoma cell lines in the Cancer Cell Line Encyclopedia (Huh-7, Huh-1, HepG2, Hep3B, JHH-5, JHH-7, C3A and Alexander cells) that are highly representative of hepatocellular carcinoma. Evaluated with a REOs-based prognostic signature for hepatocellular carcinoma, all these eight cell lines showed the same metastatic properties of the high-risk metastatic hepatocellular carcinoma tissues. Caution should be taken for using hepatocellular carcinoma cell lines. Our results should be helpful to select proper hepatocellular carcinoma cell lines for biological experiments. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Effects of marital status on survival of hepatocellular carcinoma by race/ethnicity and gender

    Directory of Open Access Journals (Sweden)

    Wu W

    2018-01-01

    Full Text Available Wenrui Wu,1,2 Daiqiong Fang,1,2 Ding Shi,1,2 Xiaoyuan Bian,1,2 Lanjuan Li1,2 1State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, 2Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, People’s Republic of China Purpose: It is well demonstrated that being married is associated with a better prognosis in multiple types of cancer. However, whether the protective effect of marital status varied across race/ethnicity and gender in patients with hepatocellular carcinoma remains unclear. Therefore, we aimed to evaluate the roles of race/ethnicity and gender in this relationship.Patients and methods: We identified eligible patients from Surveillance, Epidemiology and End Results (SEER database during 2004–2012. Overall and cancer-specific survival differences across marital status were compared by Kaplan–Meier curves. We also estimated crude hazard ratios (CHRs and adjusted hazard ratios (AHRs with 95% confidence intervals (CIs for marital status associated with survival by race/ethnicity and gender in Cox proportional hazard models.Results: A total of 12,168 eligible patients diagnosed with hepatocellular carcinoma were included. We observed that married status was an independent protective prognostic factor for overall and cancer-specific survival. In stratified analyses by race/ethnicity, the AHR of overall mortality (unmarried vs married was highest for Hispanic (AHR =1.25, 95% CI, 1.13–1.39; P<0.001 and lowest for Asian or Pacific Islander (AHR =1.13; 95% CI, 1.00–1.28; P=0.042. Stratified by gender, the AHR was higher in males (AHR =1.27; 95% CI, 1.20–1.33; P<0.001.Conclusion: We demonstrated that married patients obtained better survival advantages. Race/ethnicity and gender could influence the magnitude of associations between marital status and risk of mortality. Keywords: primary hepatocellular

  1. Dopamine-induced SULT1A3/4 promotes EMT and cancer stemness in hepatocellular carcinoma.

    Science.gov (United States)

    Zou, Juan; Li, Hong; Huang, Qianling; Liu, Xiaomin; Qi, Xiaoxiao; Wang, Ying; Lu, Linlin; Liu, Zhongqiu

    2017-10-01

    hepatocellular carcinoma prognosis.

  2. Abdominal lymph node metastases of hepatocellular carcinoma diagnosed by computed tomography and angiography

    Energy Technology Data Exchange (ETDEWEB)

    Nakamura, Hironobu; Oi, Hiromichi [Osaka Univ. (Japan). Research Inst. for Microbial Diseases; Tanaka, Takeshi; Sai, Soomi; Hori, Shinichi

    1984-04-01

    CT scans of 164 patients with hepatocellular carcinoma were studied, and abdominal lymph node metastases were detected in 13 cases. Most of these lymph node metastases occured in periportal, peripancreatic and paraaortic lymph nodes. Ten instances of each these metastases were identified by CT. Six of the patients had metastases in all three sites. In 9 of 13 cases, lymph node metastases were demonstrated by angiography and various degrees of contrast material stain were seen. Lymph node metastasis of hepatocellular carcinoma is apt to be hypervascular. Most of hepatocellular carcinoma with lymph node metastasis showed infiltrative growth, and tumor thrombosis in the portal vein was commonly complicated.

  3. [A single metastasis in the carpal bones as the first clinical manifestation of a hepatocellular carcinoma].

    Science.gov (United States)

    Corrales Pinzón, R; Alonso Sánchez, J M; de la Mano González, S; El Karzazi Tarazona, K

    2014-01-01

    Hepatocellular carcinoma is the most common primary tumor of the liver. Spreading outside the liver usually takes place in advanced stages of the disease, and bone is the third most common site of metastases. We present a case of hepatocellular carcinoma in which the first clinical manifestation was a single metastasis to the carpal bones. The interest of this case lies in the way this hepatocellular carcinoma manifested as well as in the unusual site of the metastasis. Copyright © 2012 SERAM. Published by Elsevier Espana. All rights reserved.

  4. c-MET receptor tyrosine kinase as a molecular target in advanced hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Granito A

    2015-04-01

    Full Text Available Alessandro Granito,1 Elena Guidetti,1 Laura Gramantieri2,3 1Dipartimento di Scienze Mediche e Chirurgiche Università di Bologna, Bologna, Italy; 2Dipartimento dell'Apparato Digerente, Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; 3Centro di Ricerca Biomedica Applicata (CRBA, Azienda Ospedaliero-Universitaria Policlinico S Orsola-Malpighi e Università di Bologna, Bologna, Italy Abstract: c-MET is the membrane receptor for hepatocyte growth factor (HGF, also known as scatter factor or tumor cytotoxic factor, a mitogenic growth factor for hepatocytes. HGF is mainly produced by cells of mesenchymal origin and it mainly acts on neighboring epidermal and endothelial cells, regulating epithelial growth and morphogenesis. HGF/MET signaling has been identified among the drivers of tumorigenesis in human cancers. As such, c-MET is a recognized druggable target, and against it, targeted agents are currently under clinical investigation. c-MET overexpression is a common event in a wide range of human malignancies, including gastric, lung, breast, ovary, colon, kidney, thyroid, and liver carcinomas. Despite c-MET overexpression being reported by a large majority of studies, no evidence for a c-MET oncogenic addiction exists in hepatocellular carcinoma (HCC. In particular, c-MET amplification is a rare event, accounting for 4%–5% of cases while no mutation has been identified in c-MET oncogene in HCC. Thus, the selection of patient subgroups more likely to benefit from c-MET inhibition is challenging. Notwithstanding, c-MET overexpression was reported to be associated with increased metastatic potential and poor prognosis in patients with HCC, providing a rationale for its therapeutic inhibition. Here we summarize the role of activated HGF/MET signaling in HCC, its prognostic relevance, and the implications for therapeutic approaches in HCC. Keywords: hepatocellular carcinoma, c-MET, clinical trials

  5. Identification of potential prognostic microRNA biomarkers for predicting survival in patients with hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Liao X

    2018-04-01

    Full Text Available Xiwen Liao,1 Guangzhi Zhu,1 Rui Huang,2 Chengkun Yang,1 Xiangkun Wang,1 Ketuan Huang,1 Tingdong Yu,1 Chuangye Han,1 Hao Su,1 Tao Peng1 1Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China; 2Department of Hematology, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China Background: The aim of the present study was to identify potential prognostic microRNA (miRNA biomarkers for hepatocellular carcinoma (HCC prognosis prediction based on a dataset from The Cancer Genome Atlas (TCGA. Materials and methods: A miRNA sequencing dataset and corresponding clinical parameters of HCC were obtained from TCGA. Genome-wide univariate Cox regression analysis was used to screen prognostic differentially expressed miRNAs (DEMs, and multivariable Cox regression analysis was used for prognostic signature construction. Comprehensive survival analysis was performed to evaluate the prognostic value of the prognostic signature. Results: Five miRNAs were regarded as prognostic DEMs and used for prognostic signature construction. The five-DEM prognostic signature performed well in prognosis prediction (adjusted P < 0.0001, adjusted hazard ratio = 2.249, 95% confidence interval =1.491–3.394, and time-dependent receiver–operating characteristic (ROC analysis showed an area under the curve (AUC of 0.765, 0.745, 0.725, and 0.687 for 1-, 2-, 3-, and 5-year HCC overall survival (OS prediction, respectively. Comprehensive survival analysis of the prognostic signature suggests that the risk score model could serve as an independent factor of HCC and perform better in prognosis prediction than other traditional clinical indicators. Functional assessment of the target genes of hsa-mir-139 and hsa-mir-5003 indicates that they were significantly enriched in multiple biological processes and pathways, including cell proliferation and cell migration

  6. Detection of hepatocellular carcinoma with multi-slice spiral CT by ...

    African Journals Online (AJOL)

    STORAGESEVER

    2010-06-07

    Jun 7, 2010 ... The purpose of the study is to evaluate the effect of iodine concentration of contrast material on detection of hepatocellular carcinoma with multi-slice spiral computed tomography (CT) by using double-arterial phase and portal venous phase enhanced scanning. Ninety-four (94) patients with hepatocellular ...

  7. Ultrasound and computed tomographic demonstration of portal vein thrombosis in hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Pauls, C H

    1981-07-15

    Two cases of multinodular hepatocellular carcinoma (HCC) in which ultrasound and computed tomography (CT) revealed portal vein thrombosis are presented. The diagnostic value of determining the presence of portal vein thrombosis in patients with suspected HCC is discussed.

  8. Hepatocellular carcinoma localized in the bile duct lumen: two case report

    Energy Technology Data Exchange (ETDEWEB)

    Bae, Kyeung Kug; Chang, Jay Chun [Yeungnam Univ. School of Medicine, Seoul (Korea, Republic of)

    1998-10-01

    Intrabile duct tumor growth of hepatocellular carcinoma is an uncommon manifestation, but intraluminal bile duct hepatocellular carcinoma without primary hepatic parenchymal lesions is extremely rare. To our knowledge, only a few case reports have been published. We encountered two cases of primary hepatocellular carcinoma arising in the bile duct;serum alpha-fetoprotein levels were within the normal limits. Both showed the following characteristic radiologic features: (1) Cholangiography revealed filling defects within the dilated bile duct; (2) two-phase abdominal CT showed enhancement during the arterial-dominant phase and washout during the tissue equilibrium phase, as in typical HCC; and (3) hepateic arteriography revealed hypervascular tumor staining. Surgery was performed and the resected specimen showed no detectable primary hepatic parenchymal mass;on the basis of the pathologic finding, intraluminal bile duct hepatocellular carcinoma was confirmed. We cautiously assume that this peculiar type of HCC may arise primarily from bile duct mucosa.=20.

  9. The application of Fasudil in treating vascular spasm occurred in interventional treatment for hepatocellular carcinomas

    International Nuclear Information System (INIS)

    Fan Xiaoqiang; Shen Jie; Zhang Xuena; Liu Qiuru; Ma Aiying

    2011-01-01

    Objective: To explore an effective way to treat the vascular spasm occurred during TACE for hepatocellular carcinomas. Methods: During interventional chemoembolization for hepatocellular carcinomas, Fasudil of 2.5 mg was injected via the catheter if vessel spasm occurred, which was followed by DSA to determine the dilatation of the arteries. Adverse effect was observed and recorded. Results: After the injection of Fasudil the vascular spasm was completely relieved in all the 30 cases. The interventional procedure for hepatocellular carcinomas was successfully accomplished in all patients. No obvious side effect occurred. Conclusion: The injection of Fasudil via the catheter is an effective and safe method to eliminate vessel spasm occurred during TACE for hepatocellular carcinomas. (authors)

  10. Hemothorax caused by spontaneous rupture of hepatocellular carcinoma in the pleural cavity: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Seo, Hin Hee; Ohm, Joon Young [Dept. of Radiology, Chungnam National University Hospital, Daejeon (Korea, Republic of); Kim, Song Soo; Kim, Jin Hwan [Dept. of Radiology, Chungnam National University School of Medicine, Daejeon(Korea, Republic of)

    2017-07-15

    Hemothorax resulting from ruptured hepatocellular carcinoma (HCC) is extremely rare and is generally caused by ruptured intrathoracic metastatic lesions. However, we report a rare case of hemothorax resulting from intrathoracic rupture of primary HCC.

  11. Single-domain monoclonal antibodies for the treatment of hepatocellular carcinoma | NCI Technology Transfer Center | TTC

    Science.gov (United States)

    The National Cancer Institute seeks parties to license human monoclonal antibodies and immunoconjugates and co-develop, evaluate, and/or commercialize large-scale antibody production and hepatocellular carcinoma (HCC) xenograft mouse models.

  12. Expression characteristics and diagnostic value of annexin A2 in hepatocellular carcinoma

    OpenAIRE

    Zhang, Hai-Jian; Yao, Deng-Fu; Yao, Min; Huang, Hua; Wu, Wei; Yan, Mei-Juan; Yan, Xiao-Di; Chen, Jie

    2012-01-01

    AIM: To investigate the characteristics and diagnostic value of annexin A2 (ANXA2) expression in cancerous tissues and sera of patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC).

  13. Diagnostic performance of tumor markers AFP and PIVKA-II in Chinese hepatocellular carcinoma patients.

    Science.gov (United States)

    Huang, Shujing; Jiang, Feifei; Wang, Ying; Yu, Yanhua; Ren, Siqian; Wang, Xiaowei; Yin, Peng; Lou, Jinli

    2017-06-01

    Alpha-fetoprotein is an effective biomarker as an aid in hepatocellular carcinoma detection in many countries. However, alpha-fetoprotein has its limitations, especially in early hepatocellular carcinoma diagnosis. Protein induced by vitamin K absence or antagonist-II is another biomarker that is used for hepatocellular carcinoma detection. The aim of this study is to compare the diagnostic performance of alpha-fetoprotein and protein induced by vitamin K absence or antagonist-II alone and in combination to explore improving biomarker performance as an aid in early hepatocellular carcinoma detection. In this study a total of 582 serum samples including 132 hepatocellular carcinoma patients, 250 non-hepatocellular carcinoma patients, and 200 healthy volunteers were collected. Alpha-fetoprotein and protein induced by vitamin K absence or antagonist-II levels were measured by both chemiluminescent enzyme immunoassay on LUMIPULSE platform and by chemiluminescent microparticle immunoassay on ARCHITECT platform. Receiver operation characteristic curve analyses were performed for each biomarker and in combination. The results showed that Alpha-fetoprotein and protein induced by vitamin K absence or antagonist-II in combination have shown higher area under the curve compared to alpha-fetoprotein alone for diagnosis in whole patients (0.906 vs 0.870) in hepatocellular carcinoma early-stage patients (0.809 vs 0.77) and in hepatitis B virus-related hepatocellular carcinoma patients (0.851 vs 0.788) with ARCHITECT platform. Protein induced by vitamin K absence or antagonist-II showed higher area under the curve than alpha-fetoprotein for diagnosis of hepatitis B virus-related hepatocellular carcinoma patients (0.901 vs 0.788).We conclude that Combining alpha-fetoprotein and protein induced by vitamin K absence or antagonist-II may improve the diagnostic value for early detection of hepatocellular carcinoma. Protein induced by vitamin K absence or antagonist-II performs better

  14. Current status of liver diseases in Korea: hepatocellular carcinoma.

    Science.gov (United States)

    Song, Il Han; Kim, Kyung Sik

    2009-12-01

    Primary liver cancer, most of which is hepatocellular carcinoma (HCC), is the third common leading cancer in Korea. During the last two decades, the incidence rate of primary liver cancer has shown a modest decrease, but its mortality rate has slightly increased. The incidence of HCC, according to age, peaks in the late sixth decade in men and in the early seventh decade in women. Hepatitis B virus (HBV) is the most important risk factor, which represents approximately 70% of all HCC, and hepatitis C virus (HCV) and alcohol are the next in order of major risk factors for the development of HCC in Korea. HBV-associated HCC occurs 10 years earlier than HCV-associated HCC due to a more prolonged exposure to HBV, which is vertically transmitted almost from HBsAg-positive mother in HBV-endemic area. National Cancer Control Institute, which was reorganized in 2005, is now working for several national projects such as National Cancer Registration Program, National R&D Program for Cancer Control and National Cancer Screening Program. International collaboration for the clinico-epidemiologic research would be needed to provide the specific measures for managing HCC in diverse etiologic situations. Finally, the mechanisms of hepatitis virus-associated hepatocellular carcinogenesis might be clarified to provide insights into the advanced therapeutic and preventive approaches for HCC in Korea, where the majority of HCC originate from chronic HBV and HCV infections.

  15. High MRPS23 expression contributes to hepatocellular carcinoma proliferation and indicates poor survival outcomes.

    Science.gov (United States)

    Pu, Meng; Wang, Jianlin; Huang, Qike; Zhao, Ge; Xia, Congcong; Shang, Runze; Zhang, Zhuochao; Bian, Zhenyuan; Yang, Xishegn; Tao, Kaishan

    2017-07-01

    Hepatocellular carcinoma is one of the most prevalent neoplasms and the leading cause of cancer-related mortality worldwide. Mitochondrial ribosomal protein S23 is encoded by a nuclear gene and participates in mitochondrial protein translation. Mitochondrial ribosomal protein S23 overexpression has been found in many types of cancer. In this study, we explored mitochondrial ribosomal protein S23 expression in primary hepatocellular carcinoma tissues compared with matched adjacent non-tumoral liver tissues using mitochondrial ribosomal protein S23 messenger RNA and protein levels collected from public databases and clinical samples. Immunohistochemistry was performed to analyze the relationship between mitochondrial ribosomal protein S23 and various clinicopathological features. The results indicated that mitochondrial ribosomal protein S23 was significantly overexpressed in hepatocellular carcinoma. High mitochondrial ribosomal protein S23 expression was correlated with the tumor size and tumor-metastasis-node stage. Moreover, patients with high mitochondrial ribosomal protein S23 expression levels presented poorer survival rates. Mitochondrial ribosomal protein S23 was an independent prognostic factor for survival, especially at the early stage of hepatocellular carcinoma. In addition, the downregulation of mitochondrial ribosomal protein S23 decreased the proliferation of hepatocellular carcinoma in vitro and in vivo. In conclusion, we verified for the first time that mitochondrial ribosomal protein S23 expression was upregulated in hepatocellular carcinoma. High mitochondrial ribosomal protein S23 levels can predict poor clinical outcomes in hepatocellular carcinoma, and this protein plays a key role in tumor proliferation. Therefore, mitochondrial ribosomal protein S23 may be a potential therapeutic target for hepatocellular carcinoma.

  16. Synergistic effect of oral corticosteroids use on risk of hepatocellular carcinoma in high risk populations.

    Science.gov (United States)

    Lai, Shih-Wei; Lin, Cheng-Li; Liao, Kuan-Fu

    2018-06-01

    Little evidence is available on the relationship between oral corticosteroids use and hepatocellular carcinoma. The objective of this study was to investigate whether oral corticosteroids use correlates with the risk of hepatocellular carcinoma in high risk populations in Taiwan. Using representative claims database established from the Taiwan National Health Insurance Program with a population coverage rate of 99.6%, we identified 102,182 subjects aged 20-84 years with newly diagnosed hepatocellular carcinoma in 2000-2011 as the cases and 102,182 randomly selected subjects aged 20-84 years without hepatocellular carcinoma as the matched controls. In subjects with any one of comorbidities including alcohol-related disease, chronic liver disease, and diabetes mellitus, the adjusted OR of hepatocellular carcinoma was 29.9 (95% CI 28.7, 31.1) for subjects with never use of oral corticosteroids, and the adjusted OR would increase to 33.7 (95% CI 32.3, 35.3) for those with ever use of oral corticosteroids. The adjusted OR of hepatocellular carcinoma was 1.03 for subjects with increasing cumulative duration of oral corticosteroids use for every one year (95% CI 1.01, 1.06), with a duration-dependent effect. The largest OR occurred in subjects with ever use of oral corticosteroids and concurrently comorbid with alcohol-related disease, chronic liver disease, and diabetes mellitus (adjusted OR 122.7, 95% CI 108.5, 138.8). There is a synergistic effect between oral corticosteroids use and the traditional risk factors on the risk of hepatocellular carcinoma. People with risk factors for hepatocellular carcinoma should receive regular ultrasound surveillance, particularly when they currently use oral corticosteroids. Copyright © 2018 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

  17. Mutant woodchuck hepatitis virus genomes from virions resemble rearranged hepadnaviral integrants in hepatocellular carcinoma.

    OpenAIRE

    Kew, M C; Miller, R H; Chen, H S; Tennant, B C; Purcell, R H

    1993-01-01

    Although hepadnaviruses are implicated in the etiology of hepatocellular carcinoma, the pathogenic mechanisms involved remain uncertain. Clonally propagated integrations of hepadnaviral DNA into cellular DNA can be demonstrated in most virally induced hepatocellular carcinomas. Integration occurs at random sites in cellular DNA, but the highly preferred sites in viral DNA are adjacent to the directly repeated sequence DR1, less often DR2, or in the cohesive overlap region. Integrants invariab...

  18. Serologic and molecular biomarkers for recurrence of hepatocellular carcinoma after liver transplantation

    DEFF Research Database (Denmark)

    Pommergaard, Hans-Christian; Burcharth, Jakob Hornstrup Frølunde; Rosenberg, Jacob

    2016-01-01

    INTRODUCTION: Recurrence after liver transplantation (LT) for hepatocellular carcinoma (HCC) is a major cause of mortality. Knowledge on biomarkers may contribute to better surveillance based on the patients' risk of recurrence. Reviewing the literature, we aimed to identify serological...... and molecular biomarkers for recurrence of hepatocellular carcinoma after liver transplantation. METHODS: A literature search was performed in the databases PubMed and Scopus to identify observational studies evaluating serological or molecular biomarkers for recurrence of HCC after LT using adjusted analysis...

  19. A Hepatocellular Carcinoma Case in a Patient Who had Immunity to Hepatitis B Virus Earlier.

    Science.gov (United States)

    Ates, Ihsan; Kaplan, Mustafa; Demirci, Selim; Altiparmak, Emin

    2016-01-01

    Hepatocellular carcinoma (HCC) is the most common malignant tumor of the liver. Hepatitis B virus infection is one of the most important etilogical factors of HCC. In this case report, a patient with HCC previously infected and having ongoing immunity against hepatitis B virus will be discussed. Ates I, Kaplan M, Demirci S, Altiparmak E. A Hepatocellular Carcinoma Case in a Patient Who had Immunity to Hepatitis B Virus Earlier. Euroasian J Hepato-Gastroenterol 2016;6(1):82-83.

  20. Defining Hepatocellular Carcinoma Subtypes and Treatment Responses in Patient-Derived Tumorgrafts

    Science.gov (United States)

    2017-10-01

    Hepatocellular carcinoma (HCC) is the 6th most common cancer and 3rd leading cause of cancer-related death worldwide. We know that HCC subtypes exist because...italicized descriptions of section contents in your submitted reports. 1. INTRODUCTION: Hepatocellular carcinoma (HCC) is the 6th most common cancer and 3rd...know the results or have not been harvested to assess tumor engraftment in liver. Overall, we have found that there is a good engraftment rate

  1. Low dose irradiation facilitates hepatocellular carcinoma genesis involving HULC.

    Science.gov (United States)

    Li, Yuan; Ge, Chang; Feng, Guoxing; Xiao, Huiwen; Dong, Jiali; Zhu, Changchun; Jiang, Mian; Cui, Ming; Fan, Saijun

    2018-03-24

    Irradiation exposure positive correlates with tumor formation, such as breast cancer and lung cancer. However, whether low dose irradiation induces hepatocarcinogenesis and the underlying mechanism remain poorly defined. In the present study, we reported that low dose irradiation facilitated the proliferation of hepatocyte through up-regulating HULC in vitro and in vivo. Low dose irradiation exposure elevated HULC expression level in hepatocyte. Deletion of heightened HULC erased the cells growth accelerated following low dose irradiation exposure. CDKN1, the neighbor gene of HULC, was down-regulated by overexpression of HULC following low dose irradiation exposure via complementary base pairing, resulting in promoting cell cycle process. Thus, our findings provide new insights into the mechanism of low dose irradiation-induced hepatocarcinogenesis through HULC/CDKN1 signaling, and shed light on the potential risk of low dose irradiation for the development of hepatocellular carcinoma in pre-clinical settings. © 2018 Wiley Periodicals, Inc.

  2. Clinical significance of computed tomographic arteriography for minute hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Itoh, H; Matsui, O; Suzuki, M; Ida, M; Kitagawa, K [Kanazawa Univ. (Japan). School of Medicine

    1982-03-01

    Computed tomographic arteriography (CTA) can clearly demonstrate minute hepatocellular carcinoma (H.C.C.) more than 2 cm in diameter as an enhanced mass lesion. In this case the precise localization of H.C.C. becomes so obvious that CTA plays an important role to evaluate its resectability. However, H.C.C. of the size from 2 cm to 1 cm indiameter, which is visualized with celiac and infusion hepatic angiography, becomes more difficult in detection, and particularly H.C.C. of less than 1 cm in diameter can hardly be recognized, nor be diagnosed as a malignant nodule by CTA, therefore it appears that in these sizes of H.C.C. the detectability of CTA is not superior to the hepatic angiography.

  3. Hepatocellular Carcinoma in Patients with Chronic Hepatitis C

    Directory of Open Access Journals (Sweden)

    Dmitry Konstantinov

    2016-09-01

    Full Text Available The purpose of the study was to examine the clinical and epidemiological data in patients with chronic hepatitis C (CHC and hepatocellular carcinoma (HCC before they sought specialized medical care. The study included 92 patients with CHC. All patients were divided into 2 groups: Group 1 consisted of CHC patients with HCC (n=45, and Group 2 (n=47 consisted of CHC patients without HCC. With the development of HCC in CHC patients, clinical manifestations were absent only in 2.2% of patients. Determining factors in HCC development are male sex, mature age, the maintained HCV replication, moderate and severe fibrosis, disease duration of more than 10 years, and the lack of effect of antiviral treatment.

  4. Hepatocellular carcinoma with cavernous transformation of the protal vein

    Energy Technology Data Exchange (ETDEWEB)

    Seo, Heung Suk; Lee, Seung Ro; Hahm, Chang Kok [Hanyang University College of Medicine, Seoul (Korea, Republic of)

    1985-10-15

    Twenty cases of hepatocellular carcinoma were examined by selective celiac and superior mesenteric arteriography. Obstruction of the main portal vein due to tumor thrombus was revealed in 7 cases and 3 of these cases had cavernous transformation of the portal vein (CTPV). The authors intended in this study to evaluate CTPV group and non-CTPV group clinically and radiologically. The results obtained are as follows: 1. The duration of illness was shorter in CTPV group than non- CTPV group. 2. There was no significant difference in tumor size between two groups ,and main portion of tumor was located in the right lobe in both groups. 3. Arterio portal shunt was present in 2 of 4 cases in non-CTPV group, but was no present at all in CRPV groups. 5. There wa no significant difference in blood chemistry between two groups. 6. CTPV may play an important role maintain the hepatic blood flow.

  5. Vitamin D and K signaling pathways in hepatocellular carcinoma.

    Science.gov (United States)

    Louka, Manal L; Fawzy, Ahmed M; Naiem, Abdelrahman M; Elseknedy, Mustafa F; Abdelhalim, Ahmed E; Abdelghany, Mohamed A

    2017-09-20

    Hepatocellular carcinoma (HCC) is a primary liver malignancy, and is now the six most common in between malignancies. Early diagnosis of HCC with prompt treatment increases the opportunity of patients to survive. With the advances in understanding the molecular biology of HCC, new therapeutic strategies to treat HCC have emerged. There is a growing consensus that vitamins are important for the control of various cancers. Biochemical evidence clearly indicates that HCC cells are responsive to the inhibitory effect of vitamin D, vitamin D analogues and vitamin K. In this review, we summarize the mechanisms used by vitamin D and K to influence the development of HCC and the latest development of vitamin analogues for potential HCC therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Immunostimulatory monoclonal antibodies for hepatocellular carcinoma therapy. Trends and perspectives

    Directory of Open Access Journals (Sweden)

    Guillermo D. Mazzolini

    2018-01-01

    Full Text Available Hepatocellular carcinoma (HCC is the second cause of cancer-related death in the world and is the main cause of death in cirrhotic patients. Unfortunately, the incidence of HCC has grown significantly in the last decade. Curative treatments such as surgery, liver transplantation or percutaneous ablation can only be applied in less than 30% of cases. The multikinase inhibitor sorafenib is the first line therapy for advanced HCC. Regorafenib is the standard of care for second-line patients. However, novel and more specific potent therapeutic approaches for advanced HCC are still needed. The liver constitutes a unique immunological microenvironment, although anti-tumor immunity seems to be feasible with the use of checkpoint inhibitors such as nivolumab. Efficacy may be further increased by combining checkpoint inhibitors or by applying loco-regional treatments. The success of immune checkpoint blockade has renewed interest in immunotherapy in HCC

  7. Functional Roles and Therapeutic Applications of Exosomes in Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Laura Santangelo

    2017-01-01

    Full Text Available Exosomes are important in intercellular communication. They assure the horizontal transfer of specific functional contents (i.e., proteins, lipids, RNA molecules, and circulating DNA from donor to recipient cells. Notably, tumor-derived exosomes (TDEs appear to be an important vehicle of specific signals in cancer, impacting on tumor growth and metastasis. Recent researches point to the characterization of exosomes in Hepatocellular Carcinoma (HCC, the major adult liver malignancy. In this review, we summarize current findings on HCC exosomes, focusing on the identification of noncoding RNAs as exosome-enriched functional regulators and new potential biomarkers. The great potential of exosomes in future HCC diagnostic and therapeutic approaches is underlined.

  8. Prebiotics: A Novel Approach to Treat Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Naz Fatima

    2017-01-01

    Full Text Available Hepatocellular carcinoma is one of the fatal malignancies and is considered as the third leading cause of death. Mutations, genetic modifications, dietary aflatoxins, or impairments in the regulation of oncogenic pathways may bring about liver cancer. An effective barrier against hepatotoxins is offered by gut-liver axis as a change in gut permeability and expanded translocation of lipopolysaccharides triggers the activation of Toll-like receptors which stimulate the process of hepatocarcinogenesis. Prebiotics, nondigestible oligosaccharides, have a pivotal role to play when it comes to inducing an antitumor effect. A healthy gut flora balance is imperative to downregulation of inflammatory cytokines and reducing lipopolysaccharides induced endotoxemia, thus inducing the antitumor effect.

  9. Imaging of hepatocellular carcinoma; Bildgebung des hepatozellulaeren Karzinoms

    Energy Technology Data Exchange (ETDEWEB)

    Lincke, Therese; Zech, Christoph [Universitaetsspital Basel (Switzerland). Klinik fuer Radiologie und Nuklearmedizin; Boll, Daniel

    2016-12-15

    Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. Besides the improvement in diagnostics and therapy the quantity of new cases and fatalities per year are equal. The main risk factors for HCC developing are liver cirrhosis (causing 90% of HCCs), non-alcoholic fatty liver disease and chronic hepatitis B infection. Therefore, it is recommended to perform an ultrasound screening on patients at risk every 6 month to detect HCC-lesions early. HCC can be definitely diagnosed by imaging techniques using contrast agent such as contrast-enhanced-ultrasound (CEUS), contrast-enhanced-MRI (CE-MRI) and contrast-enhanced-CT (CE-CT). MRI has several advantages compared to the other modalities due to the multi-parametric approach and a higher sensitivity for tumor detection.

  10. Herbal Medicine and Hepatocellular Carcinoma: Applications and Challenges

    Directory of Open Access Journals (Sweden)

    Yan Li

    2011-01-01

    Full Text Available Use of herbal medicine in the treatment of liver cancer has a long tradition. The compounds derived from the herb and herbal composites are of considerable interest among oncologists. In the past, certain herbal compounds and herbal composite formulas have been studied through in vitro and in vivo as an anti-hepatocellular carcinoma (HCC agent, enhancing our knowledge about their biologic functions and targets. However there is a significant distinction between the herbal medicine and the herbal production even though both are the plant-based remedies used in the practice. In this article, for the sake of clarity, the effective herbal compounds and herbal composite formulas against HCC are discussed, with emphasizing the basic conceptions of herbal medicine in order to have a better understanding of the prevention and treatment of HCC by herbal active compounds and herbal composite formulas.

  11. Research progress in c-Met and hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    WANG Changqing

    2015-06-01

    Full Text Available c-Met plays a pivotal role in the development and progression of hepatocellular carcinoma (HCC, which can lead to proliferation, survival, cytoskeleton reorganization, separation and diffusion, and angiogenesis of tumor cells. Moreover, c-Met is an important prognostic factor for HCC. In HCC, c-Met acts as an activator of a series of signaling pathways, including PI3K/AKT/mTOR, ERK/MAPK, and Rac-Pak. In recent years, it has been reported that small-molecule kinase inhibitors can abolish phosphorylation at the intracellular carboxyl terminal of c-Met, and then inhibit the recruitment of signal convertors and downstream signaling pathways, which finally achieve anti-tumor activities. Based on the carcinogenic activity of c-Met in HCC, this paper points out that selective inhibitors of c-Met hold promise for targeted therapies for HCC.

  12. Radioembolization for hepatocellular carcinoma using TheraSphere®.

    Science.gov (United States)

    Ali, Safiyya Mohamed

    2011-01-01

    Hepatocellular carcinoma (HCC) is the most common primary malignancy of the liver. Radioembolization with yttrium-90 (Y90) microspheres is a new concept in radiation therapy for HCC. This review focuses on the indications, efficacy, side effects, and future direction of Y90 therapy, using TheraSphere® , in HCC patients. Comprehensive literature reviews have described the clinical and scientific evidence of Y90 therapy. The Radioembolization Brachytherapy Oncology Consortium has concluded that there is sufficient evidence to support the safe and effective use of this locoregional therapy in HCC patients, including those with portal vein thrombosis. There are currently no randomized clinical trials done on TheraSphere® and none of the studies so far have shown a survival benefit. Thus, although it represents a very promising therapy with excellent initial results, it cannot be fully recommended yet, till well-designed, large, randomized clinical studies are conducted showing survival benefits.

  13. Y-90 microshperes in the treatment of unresectable hepatocellular carcinoma.

    Science.gov (United States)

    Al-Kalbani, Abdullah; Kamel, Yasser

    2008-04-01

    A small percentage of patients with hepatocellular carcinoma (HCC) are candidates for curative treatment in form of resection or transplantation. There are different treatment options for unresectable HCC-like local ablative therapies and recently systemic therapy with Sorafenib. All of these have variable response rate and had been proven to improve survival. In the last few years, there is a growing interest in TheraSphere radioembolization. It consists of yttrium90 (Y-90) embedded into nonbiodegradable glass microspheres. It is selectively administered by intraarterial hepatic injection giving high doses of radiation to the tumor and sparing the liver parenchyma. It has been shown to improve survival and used as a bridge to transplantation and to downstage tumors for resection. Therasphere seems to have favorable safety profile and has been used in patients with portal vein thrombosis with successful outcome.

  14. CYCLOOXYGENASE-2 AND HEPATOCELLULAR CARCINOMA: THE PROTEOMICS OF ASSOCIATION

    Directory of Open Access Journals (Sweden)

    Jaya Gandhi

    2011-12-01

    Full Text Available Hepatocellular carcinoma represents one of the most common malignancies worldwide with a rising incidence in western countries. Chronic inflammation is recognised as a threat factor for cancer progression. Cyclooxygenase-2 is the major mediator of inflammation. Various studies on Cox-2 suggest its possible association with HCC differentiation. Sufficient genetic and pharmacologic evidences implicate its crucial role in neoplasia and it is also now clear that Cox-2 plays a crucial role in tumor progression. Cox-2 overexpression is associated with maintaining tumor microenvironment and has crucial implication for angiogenesis. Cox-2 operates in multifactorial fashion. Cox-2 selective inhibition has been reported as a successful tool in suppressing angiogenesis and metastasis. The pharmacological suppression of Cox-2 represents a bright future as a therapeutic tool for treatment of various malignancies. This review is an attempt to discuss the critical issue of overexpression of Cox-2 and its role in the development of HCC in particular and cancer in general.

  15. Research advances in cellular immunotherapy for primary hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    ZHANG Ye

    2014-09-01

    Full Text Available The present therapy for primary hepatocellular carcinoma (HCC consists of surgery as well as local radiotherapy and chemotherapy. However, the majority of patients are susceptible to recurrence after comprehensive treatment, and the overall treatment outcome is not ideal due to the lack of effective drugs and strategies. Increasing evidence has demonstrated that the immune system is closely related to the development, progression, metastasis, and recurrence of HCC. Thus, immune therapy, especially cellular immunotherapy, could regulate immune function and induce specific antitumor immunity to achieve the goal of controlling HCC and reducing its recurrence and metastasis, which has become an essential part in the comprehensive treatment of HCC. The findings in preclinical and clinical studies on cellular immunotherapy for HCC data are reviewed, and the current problems are discussed.

  16. Hyperintense hepatocellular carcinoma on gadolinium-enhanced hepatic MRI

    International Nuclear Information System (INIS)

    Yoshikawa, Jun; Matsui, Osamu; Kadoya, Masumi; Gabata, Toshifumi; Arai, Kazunori; Takashima, Tsutomu

    1992-01-01

    We reported a phenomenon in which some hepatocellular carcinomas (HHCs) visualized as hypointense on plain T1 weighted MR images became hyperintense on gadolinium-DTPA (Gd-DTPA) (0.06∼0.23 mmol/kg) enhanced delayed images. Gd-DTPA enhanced images (using a super conducting magnet operating at 1.5T) of 44 HCCs were studied in comparison with contrast enhanced CT using 30∼80g of iodine. Six of 44 HCCs (14%) which were visualized as hypointense on plain T1 weighted image became hyperintense on delayed Gd-DTPA enhanced images. Although these were visualized as low intensity areas on both plain and enhanced CT, the contrast between HCC and the surrounding liver was small on post contrast CT. These findings were thought to be due to a stronger enhancement effect of Gd-DTPA than that of iodine. (author)

  17. Transarterial chemoembolization through collateral vessels in hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Ji Hye; Han, Joon Koo; Chung, Jin Wook; Park, Jae Hyung; Han, Man Chung [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    1993-11-15

    We performed 70 procedures of transarterial chemoembolization (TAE) through extrahepatic collateral vessels (n=27) or parasitic feeders (n=18) in 45 hepatocellular carcinoma patients. The collaterals developed after interruption of the hepatic artery due to repeated TAE (n=17), surgical ligation (n=7)and primary celiac occlusion (n=3). Radiologic findings suggest the existence of parasitic or collateral supply for hepatocellular carcinoma were 1) a focal defect of Lipiodol retention on CT or plain film after TAE via the hepatic artery, 2) dilated and tortuous vessels around the mass on angiography, 3) persistent elevation of the level of serum alpha-fetoprotein or continuous clinical symptoms in spite of sufficient devascularization of the tumor via the hepatic artery, and 4) radiological findings of direct invasion into adjacent organ. The sites of the catheter placement were the inferior phrenic artery(n=19), omental branches(n=16), periportal collaterals (n=6), pancreaticodenal arcade (n=3), gastroduodenal artery(n=3), internal mammary artery (n=2), intercosal artery (n=2), lateral thoracic artery (n=1), bronchial artery (n=1), and colic branches (n=1). Masses feeded by the inferior phrenic and chest wall collaterals were usually located at the dome area of the liver, and the omental and gastroduodenal collaterals developed in the masses located at the inferior tip of the liver. After TAE via collateral vessels, 37 patients underwent follow-up study. In 18 cases(48%), the tumor favorably responded to TAE. Specific complications of collateral TAE were epigastric soreness (n=10), severe shoulder pain (n=4), and embolization of the spinal artery during embolization through the intercostal artery (n=1). In conclusion, various extrahepatic collateals are important alternative or addition routes for effective chemoembolization in patients with advanced hepatoma, and early recognition of the parasitic supply and the effort to perform TAE via collaterals is very

  18. Micronutrient Synergy in the Fight against Hepatocellular Carcinoma

    International Nuclear Information System (INIS)

    Roomi, M. Waheed; Roomi, Nusrath W.; Kalinovsky, Tatiana; Niedzwiecki, Aleksandra; Rath, Matthias

    2012-01-01

    The incidence of hepatocellular carcinoma (HCC), once thought to be a rare tumor in North America, has rapidly increased in recent years in the United States. Current treatment modalities to halt the progression of this disease are only marginally effective. The mainstay treatment is liver transplantation, which is often confronted with donor shortage. Invasion, metastasis and recurrence contribute to the high mortality rate of this disease. Matrix metalloproteinases (MMPs) that degrade the extracellular matrix (ECM) have been associated with the progression, invasion and metastasis of the disease. We have developed strategies to strengthen the ECM collagen and inhibit MMPs through micronutrients such as lysine, proline and ascorbic acid. Addition of epigallocatechin gallate or green tea extract to these micronutrients synergistically enhanced anti-carcinogenic activity in HepG2 cells. Addition of certain other micronutrients, such as N-acetylcysteine, selenium, copper and zinc (NM) synergistically enhanced the anticancer activity of the mixture in a model of hepatocellular carcinoma using HepG2 cells. In vitro studies using HepG2 demonstrated that NM was very effective in inhibiting cell proliferation (by MTT assay), MMPs secretion (by gelatinase zymography), cell invasion (through Matrigel) and induction of apoptosis (by live green caspase). In addition, NM was shown to down-regulate urokinase plasminogen activator (by fibrin zymography) and up-regulate tissue inhibitors of metalloproteinases (by reverse zymography) in another HCC cell line, SK-Hep-1. MMP-2 and MMP-9 activities were further modulated by phorbol 12-myristate 13-acetate (PMA) induction and inhibited by NM. In previous studies, NM inhibited Sk-Hep-1 xenografts in nude mice and also inhibited hepatic metastasis of B16FO melanoma cells. Our results suggest that NM is an excellent candidate for therapeutic use in the treatment HCC by inhibiting critical parameters in cancer development and progression

  19. Transarterial chemoembolization through collateral vessels in hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Kim, Ji Hye; Han, Joon Koo; Chung, Jin Wook; Park, Jae Hyung; Han, Man Chung

    1993-01-01

    We performed 70 procedures of transarterial chemoembolization (TAE) through extrahepatic collateral vessels (n=27) or parasitic feeders (n=18) in 45 hepatocellular carcinoma patients. The collaterals developed after interruption of the hepatic artery due to repeated TAE (n=17), surgical ligation (n=7)and primary celiac occlusion (n=3). Radiologic findings suggest the existence of parasitic or collateral supply for hepatocellular carcinoma were 1) a focal defect of Lipiodol retention on CT or plain film after TAE via the hepatic artery, 2) dilated and tortuous vessels around the mass on angiography, 3) persistent elevation of the level of serum alpha-fetoprotein or continuous clinical symptoms in spite of sufficient devascularization of the tumor via the hepatic artery, and 4) radiological findings of direct invasion into adjacent organ. The sites of the catheter placement were the inferior phrenic artery(n=19), omental branches(n=16), periportal collaterals (n=6), pancreaticodenal arcade (n=3), gastroduodenal artery(n=3), internal mammary artery (n=2), intercosal artery (n=2), lateral thoracic artery (n=1), bronchial artery (n=1), and colic branches (n=1). Masses feeded by the inferior phrenic and chest wall collaterals were usually located at the dome area of the liver, and the omental and gastroduodenal collaterals developed in the masses located at the inferior tip of the liver. After TAE via collateral vessels, 37 patients underwent follow-up study. In 18 cases(48%), the tumor favorably responded to TAE. Specific complications of collateral TAE were epigastric soreness (n=10), severe shoulder pain (n=4), and embolization of the spinal artery during embolization through the intercostal artery (n=1). In conclusion, various extrahepatic collateals are important alternative or addition routes for effective chemoembolization in patients with advanced hepatoma, and early recognition of the parasitic supply and the effort to perform TAE via collaterals is very

  20. Micronutrient Synergy in the Fight against Hepatocellular Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Roomi, M. Waheed; Roomi, Nusrath W.; Kalinovsky, Tatiana; Niedzwiecki, Aleksandra, E-mail: a.niedz@drrath.com; Rath, Matthias [Dr. Rath Research Institute, 1260 Memorex Drive, Santa Clara, CA 95050 (United States)

    2012-03-23

    The incidence of hepatocellular carcinoma (HCC), once thought to be a rare tumor in North America, has rapidly increased in recent years in the United States. Current treatment modalities to halt the progression of this disease are only marginally effective. The mainstay treatment is liver transplantation, which is often confronted with donor shortage. Invasion, metastasis and recurrence contribute to the high mortality rate of this disease. Matrix metalloproteinases (MMPs) that degrade the extracellular matrix (ECM) have been associated with the progression, invasion and metastasis of the disease. We have developed strategies to strengthen the ECM collagen and inhibit MMPs through micronutrients such as lysine, proline and ascorbic acid. Addition of epigallocatechin gallate or green tea extract to these micronutrients synergistically enhanced anti-carcinogenic activity in HepG2 cells. Addition of certain other micronutrients, such as N-acetylcysteine, selenium, copper and zinc (NM) synergistically enhanced the anticancer activity of the mixture in a model of hepatocellular carcinoma using HepG2 cells. In vitro studies using HepG2 demonstrated that NM was very effective in inhibiting cell proliferation (by MTT assay), MMPs secretion (by gelatinase zymography), cell invasion (through Matrigel) and induction of apoptosis (by live green caspase). In addition, NM was shown to down-regulate urokinase plasminogen activator (by fibrin zymography) and up-regulate tissue inhibitors of metalloproteinases (by reverse zymography) in another HCC cell line, SK-Hep-1. MMP-2 and MMP-9 activities were further modulated by phorbol 12-myristate 13-acetate (PMA) induction and inhibited by NM. In previous studies, NM inhibited Sk-Hep-1 xenografts in nude mice and also inhibited hepatic metastasis of B16FO melanoma cells. Our results suggest that NM is an excellent candidate for therapeutic use in the treatment HCC by inhibiting critical parameters in cancer development and progression

  1. Hepatocellular carcinoma with bile duct involvement : computed Tomographic (CT) findings

    International Nuclear Information System (INIS)

    Lee, Joon Woo; Han, Joon Koo; Kim, Tae Kyoung; And others

    2000-01-01

    To describe the radiologic features of computed tomography (CT) in hepatocellular carcinoma (HCC) with bile duct involvement. We retrospectively analyzed the two phase spiral CT findings of 31 patients in whom HCC with bile duct invasion (n=3D28) or compression (n=3D3), was diagnosed. Eight of these underwent follow up CT after transarterial chemoembolization. We analyzed the size, type, location, enhancement pattern, and lipiodol retention of parenchymal and intraductal masses, as well as their lymphadenopathy. In all patients with bile duct invasion, single or multiple masses were demonstrated in the bile ducts. Intraductal masses showed the same enhancement characteristics as the parenchymal mass (kappa 0.550, p less than 0.001), and were contiguous to this mass. In 14 of 28 patients, intraductal masses filled the peripheral intrahepatic bile ducts and extended to the common bile ducts. In the other 14, the parenchymal mass extended to the area of the porta hepatis and then directly invaded the large ducts. In nine of the 28 patients, there was a hypoattenuated cleft between the intraductal mass and ductal wall. In six, a parenchymal mass was not apparent (n=3D2), or was smaller than 2cm (n=3D4). In five of eight patients (62.5%), follow-up CT after transarterial chemoembolization showed compact or partial lipiodol retention within the intraductal mass. In patients with bile duct compression, perihilar lymph nodes were noted along with the dilated intrahepatic duct but no intra ductal mass was demonstrated in the duct. Hepatocellular carcinomas cause bile duct dilatation either by direct invasion or by extrinsic compression of the bile duct with surrounding enlarged nodes. For the diagnosis of this condition, CT is helpful. (author)

  2. Micronutrient Synergy in the Fight against Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Aleksandra Niedzwiecki

    2012-03-01

    Full Text Available The incidence of hepatocellular carcinoma (HCC, once thought to be a rare tumor in North America, has rapidly increased in recent years in the United States. Current treatment modalities to halt the progression of this disease are only marginally effective. The mainstay treatment is liver transplantation, which is often confronted with donor shortage. Invasion, metastasis and recurrence contribute to the high mortality rate of this disease. Matrix metalloproteinases (MMPs that degrade the extracellular matrix (ECM have been associated with the progression, invasion and metastasis of the disease. We have developed strategies to strengthen the ECM collagen and inhibit MMPs through micronutrients such as lysine, proline and ascorbic acid. Addition of epigallocatechin gallate or green tea extract to these micronutrients synergistically enhanced anti-carcinogenic activity in HepG2 cells. Addition of certain other micronutrients, such as N-acetylcysteine, selenium, copper and zinc (NM synergistically enhanced the anticancer activity of the mixture in a model of hepatocellular carcinoma using HepG2 cells. In vitro studies using HepG2 demonstrated that NM was very effective in inhibiting cell proliferation (by MTT assay, MMPs secretion (by gelatinase zymography, cell invasion (through Matrigel and induction of apoptosis (by live green caspase. In addition, NM was shown to down-regulate urokinase plasminogen activator (by fibrin zymography and up-regulate tissue inhibitors of metalloproteinases (by reverse zymography in another HCC cell line, SK-Hep-1. MMP-2 and MMP-9 activities were further modulated by phorbol 12-myristate 13-acetate (PMA induction and inhibited by NM. In previous studies, NM inhibited Sk-Hep-1 xenografts in nude mice and also inhibited hepatic metastasis of B16FO melanoma cells. Our results suggest that NM is an excellent candidate for therapeutic use in the treatment HCC by inhibiting critical parameters in cancer development and

  3. A nomogram incorporating six easily obtained parameters to discriminate intrahepatic cholangiocarcinoma and hepatocellular carcinoma.

    Science.gov (United States)

    Wang, Mengmeng; Gao, Yuzhen; Feng, Huijuan; Warner, Elisa; An, Mingrui; Jia, Jian'an; Chen, Shipeng; Fang, Meng; Ji, Jun; Gu, Xing; Gao, Chunfang

    2018-03-01

    Intrahepatic cholangiocarcinoma (ICC) and hepatocellular carcinoma (HCC) are the most prevalent histologic types of primary liver cancer (PLC). Although ICC and HCC share similar risk factors and clinical manifestations, ICC usually bears poorer prognosis than HCC. Confidently discriminating ICC and HCC before surgery is beneficial to both treatment and prognosis. Given the lack of effective differential diagnosis biomarkers and methods, construction of models based on available clinicopathological characteristics is in need. Nomograms present a simple and efficient way to make a discrimination. A total of 2894 patients who underwent surgery for PLC were collected. Of these, 1614 patients formed the training cohort for nomogram construction, and thereafter, 1280 patients formed the validation cohort to confirm the model's performance. Histopathologically confirmed ICC was diagnosed in 401 (24.8%) and 296 (23.1%) patients in these two cohorts, respectively. A nomogram integrating six easily obtained variables (Gender, Hepatitis B surface antigen, Aspartate aminotransferase, Alpha-fetoprotein, Carcinoembryonic antigen, Carbohydrate antigen 19-9) is proposed in accordance with Akaike's Information Criterion (AIC). A score of 15 was determined as the cut-off value, and the corresponding discrimination efficacy was sufficient. Additionally, patients who scored higher than 15 suffered poorer prognosis than those with lower scores, regardless of the subtype of PLC. A nomogram for clinical discrimination of ICC and HCC has been established, where a higher score indicates ICC and poor prognosis. Further application of this nomogram in multicenter investigations may confirm the practicality of this tool for future clinical use. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  4. Evaluation of prognostic factors on recurrence after curative resections for hepatocellular carcinoma.

    Science.gov (United States)

    Han, Jae Hyun; Kim, Dong Goo; Na, Gun Hyung; Kim, Eun Young; Lee, Soo Ho; Hong, Tae Ho; You, Young Kyoung

    2014-12-07

    To select appropriate patients before surgical resection for hepatocellular carcinoma (HCC), especially those with advanced tumors. From January 2000 to December 2012, we retrospectively analyzed the medical records of 298 patients who had undergone surgical resections for HCC with curative intent at our hospital. We evaluated preoperative prognostic factors associated with histologic grade of tumor, recurrence and survival, especially the findings of pre-operative imaging studies such as positron emission tomography-computed tomography (PET-CT) and magnetic resonance imaging (MRI). And then, we established a scoring system to predict recurrence and survival after surgery dividing the patients into two groups based on a tumor size of 5 cm. Of the 298 patients, 129 (43.3%) developed recurrence during the follow-up period. The 5 year disease free survival and overall survival were 47.0% and 58.7% respectively. In multivariate analysis, a serum alpha-fetoprotein (AFP) level of > 100 ng/mL and a standardized uptake value (SUV) of PET-CT of > 3.5 were predictive factors for histologic grade of tumor, recurrence, and survival. Tumor size of > 5 cm and a relative enhancement ratio (RER) calculated from preoperative MRI were also significantly associated with prognosis in univariate analysis. We established a scoring system to predict prognosis using AFP, SUV, and RER. In those with tumors of > 5 cm, it showed predicted both recurrence (P = 0.005) and survival (P = 0.001). The AFP, tumor size, SUV and RER are useful for prognosis preoperatively. An accurate prediction of prognosis is possible using our scoring system in large size tumors.

  5. Peritoneal carcinomatosis: an unusual presentation of fibrolamellar hepatocellular carcinoma; Carcinomatosis peritoneal como forma de presentacion infrecuente del hepatocarcinoma fibrolamelar

    Energy Technology Data Exchange (ETDEWEB)

    Vicente, R; Garcia-Gutierrez, J A; Fernandez, A; Santalla, F [Hospital Comarcal de la Axarquia. Malaga (Spain)

    2001-07-01

    Fibrolamellar hepatocellular carcinoma is an uncommon malignant tumor with characteristic clinical, radiological and histopahtological features that is usually associated with a more favorable natural course and greater survival than more common variants of hepatocellular carcinoma. We describe an atypical case of a fibrolamellar hepatocellular carcinomas sowing aggressive behaviour in a 20-year-old woman. The lesion presented with massive ascites, and imaging studies revealed extensive peritoneal metastatic spread. (Author) 8 refs.

  6. Eag1 channels as potential early-stage biomarkers of hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Chávez-López MG

    2016-09-01

    Full Text Available María de Guadalupe Chávez-López,1 Violeta Zúñiga-García,1 Julio Isael Pérez-Carreón,2 Arturo Avalos-Fuentes,3 Yesenia Escobar,4 Javier Camacho1 1Department of Pharmacology, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, 2Instituto Nacional de Medicina Genómica, 3Department of Physiology, Biophysics and Neuroscience, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, 4Centro de Investigación Clínica Acelerada Sc, Mexico City, Mexico Abstract: Hepatocellular carcinoma (HCC is a major cause of cancer death worldwide. HCC is usually asymptomatic at potential curative stages, and it has very poor prognosis if detected later. Thus, the identification of early biomarkers and novel therapies is essential to improve HCC patient survival. Ion channels have been proposed as potential tumor markers and therapeutic targets for several cancers including HCC. Especially, the ether à-go-go-1 (Eag1 voltage-gated potassium channel has been suggested as an early marker for HCC. Eag1 is overexpressed during HCC development from the cirrhotic and the preneoplastic lesions preceding HCC in a rat model. The channel is also overexpressed in human HCC. Astemizole has gained great interest as a potential anticancer drug because it targets several proteins involved in cancer including Eag1. Actually, in vivo studies have shown that astemizole may have clinical utility for HCC prevention and treatment. Here, we will review first some general aspects of HCC including the current biomarkers and therapies, and then we will focus on Eag1 channels as promising tools in the early diagnosis of HCC. Keywords: ion channels, Eag1, hepatocellular carcinoma, astemizole, diethylnitrosamine

  7. A clinical perspective of the link between metabolic syndrome and hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Cauchy F

    2015-02-01

    Full Text Available François Cauchy, Jacques BelghitiHPB and Liver Transplantation Unit, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris, Clichy, FranceAbstract: Metabolic syndrome (MS, which is defined as a constellation of clinico-biological features closely related to insulin-resistance has reached epidemic levels in Western Europe and Northern America. Non-alcoholic fatty liver disease (NAFLD represents the hepatic manifestation of MS. As its incidence parallels that of MS, NAFLD is currently becoming one of the most frequent chronic liver diseases in Western countries. On one hand, MS favors the development of hepatocellular carcinoma (HCC either through NAFLD liver parenchymal alterations (steatosis; steatohepatitis; fibrosis, or in the absence of significant underlying liver parenchyma changes. In this setting, HCC are often diagnosed incidentally, tend to be larger than in patients developing HCC on cirrhosis and therefore frequently require major liver resections. On the other hand, MS patients are at increased risk of both liver-related postoperative complications and increased cardiorespiratory events leading to non-negligible mortality rates following liver surgery. These deleterious effects seem to be related to the existence of impaired liver function even in the absence of severe fibrosis but also higher cardiorespiratory sensitivity in a setting of MS/NAFLD. Hence, specific medical and surgical improvements in the perioperative management of these patients are required. These include complete preoperative cardiorespiratory work-up and the wide use of preoperative liver volume modulation. Finally, the long-term prognosis after curative surgery for MS-related HCC does not seem to be worse than for other HCC occurring on classical chronic liver diseases. This is probably related to less aggressive tumor behavior with lower micro vascular invasion and decreased rates of poorly differentiated lesions. In this setting, several medical therapies

  8. Serine/arginine rich splicing factor 2 expression and clinic pathological features indicating a prognostic factor in human hepatocellular carcinoma patients.

    Science.gov (United States)

    Wang, Pingan; Guo, Lingyu; Li, Kaipeng; Ning, Shanglei; Shi, Weichen; Liu, Zhaochen; Chen, Yuxin

    2018-02-14

    This research was aimed to study the expression of Serine/arginine rich splicing factor 2 (SRSF2) in tissues of hepatocellular carcinoma, and explore the relationship between the expression and the clinic pathological and prognosis of human hepatocellular carcinoma (HCC). One hundred and fifty-three pairs HCC tissues and adjacent normal tissue were collected from January 2010 to March 2013. The expression of SRSF2 gene was detected by immunohistochemistry, western blotting and real-time quantitative polymerase chain reaction (PCR), and the relationship between the expression and the clinic pathological and prognosis of HCC being analyzed. In 153 cases of hepatocellular carcinoma, SRSF2 was highly expressed in 93 cases, low expression of 60 cases, immunohistochemistry score (6.50 ± 2.82), which was significantly higher than that in adjacent normal tissues (2.94 ± 1.23) (Phepatocellular carcinoma was positively correlated (r = 0.704, Phepatocellular carcinoma were 74.19%, 44.09%, 26.88%, 24.73% and 21.51% at 1 year, 2 years, 3 years, 4 years and 5 years respectively, which were lower than those of SRSF2 low expression group (93.33%, 71.67%, 56.67%, 51.67% and 50.00%). SRSF2 is highly expressed in hepatocellular carcinoma and its expression increases with the degree of tumor differentiation and TNM staging. It is related to lymph node metastasis and metastasis of tumor cells, and is positively related to serum alpha fetoprotein content, and affects the postoperative survival time of HCC patients.

  9. Does age affect prognosis in salivary gland carcinoma patients?

    DEFF Research Database (Denmark)

    Bjørndal, Kristine; Larsen, Stine R; Therkildsen, Marianne H

    2016-01-01

    in the young group were WHO performance status 0 and in disease stage I + II, and they presented with significantly more histological low grade tumors. In multivariate analysis, chronological age seemed to be of no prognostic significance to salivary gland carcinoma patients as opposed to performance status......, disease stage and histological grade. CONCLUSIONS: Salivary gland carcinoma patients over the age of 70 years have a poor prognosis compared to younger patients, which can be explained by higher disease stages, more histological high grade subtypes and a poorer performance status at the time of diagnosis.......AIM: To compare incidence, histology, treatment modalities, disease stages, and outcome in elderly patients (≥70 years) compared to younger (

  10. Expression of p53, Bcl-2, VEGF, Ki67 and PCNA and prognostic significance in hepatocellular carcinoma.

    Science.gov (United States)

    Stroescu, Cezar; Dragnea, Adrian; Ivanov, Bogdan; Pechianu, Catalin; Herlea, Vlad; Sgarbura, Olivia; Popescu, Andra; Popescu, Irinel

    2008-12-01

    Hepatocellular carcinoma is one of the most common malignant tumors that carry a poor prognosis. To improve the long-term outlook for HCC, an accurate prognosis is important. To study the immunohistochemical expressions of p53, Ki67, Bcl-2, VEGF and PCNA and their potential role as prognostic factors in patients with radical resection of hepatocellular carcinoma. Forty-seven formalin-fixed paraffin-embedded tumor samples from patients with HCC receiving liver resection were investigated immunohistochemically for the expression of cellular proliferation markers PCNA, Ki67, p53, Bcl-2 and VEGF and their correlation with tumor characteristics and survival time after resection. p53 was expressed in a higher percentage (85.7 vs. 42.1%) in undifferentiated histological tumor grades (Edmondson Steiner G3/G4 vs. G1/G2). Patients with p53 accumulating tumors showed a worse survival than patients with p53 non-accumulating tumors (median 9.5 vs. 16.5 months). Over-expression of VEGF was found in 38.3% of all HCCs. VEGF expression was significantly correlated with p53 expression and recurrence rates. The results showed that the labeling index of PCNA and expression of p53 are correlated. The high labeling index of PCNA or over-expression of p53 resulted in high risk of tumor recurrence, more aggressive growth and poor survival. High labeling index of PCNA, p53 nuclear accumulation and VEGF high expression are associated with poor survival in patients with HCC.

  11. GPX4 and GPX7 Over-Expression in Human Hepatocellular Carcinoma Tissues

    Science.gov (United States)

    Guerriero, E.; Capone, F.; Accardo, M.; Sorice, A.; Costantini, M.; Colonna, G.; Castello, G.

    2015-01-01

    Hepatocellular carcinoma (HCC) is the most common type of liver cancer and is still one of the most fatal cancers. Hence, it needs to identify always new putative markers to improve its diagnosis and prognosis. The selenium is an essential trace mineral implicated as a key factor in the early stage of cancer and exerts its biological function through the selenoproteins. In the last years our group has been studying the involvement of some selenoproteins in HCC. However, no many data are reported in literature about the correlation between HCC and the glutathione peroxidases (GPXs), both selenium and non selenium-containing GPXs. In this paper we have evaluated the GPX4 and GPX7 expression in some paraffin-embedded tissues from liver biopsy of patients with hepatitis C virus (HCV)-related cirrhosis and HCC by immunohistochemistry and RT-qPCR analysis. Our results evidenced that i) GPX4 and GPX7 had a statistically significant over-expression in HCC tissues compared to cirrhotic counterparts used as non tumor tissues, and ii) their expression was higher in grade III HCC tissues with respect to grade I-II samples. Therefore, we propose to use GPX4 and GPX7 as possible markers for improving HCC diagnosis/prognosis. PMID:26708178

  12. Progress and Prospects of Long Noncoding RNAs (lncRNAs in Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Chen Li

    2015-05-01

    Full Text Available Hepatocellular carcinoma (HCC is one of the most frequently occurring cancers with poor prognosis, and novel diagnostic or prognostic biomarkers and therapeutic targets for HCC are urgently required. With the advance of high-resolution microarrays and massively parallel sequencing technology, lncRNAs are suggested to play critical roles in the tumorigenesis and development of human HCC. To date, dysregulation of many HCC-related lncRNAs such as HULC, HOTAIR, MALAT1, and H19 have been identified. From transcriptional “noise” to indispensable elements, lncRNAs may re-write the central dogma. Also, lncRNAs found in body fluids have demonstrated their utility as fluid-based noninvasive markers for clinical use and as therapeutic targets for HCC. Even though several lncRNAs have been characterized, the underlying mechanisms of their contribution to HCC remain unknown, and many important questions about lncRNAs need resolving. A better understanding of the molecular mechanism in HCC-related lncRNAs will provide a rationale for novel effective lncRNA-based targeted therapies. In this review, we highlight the emerging roles of lncRNAs in HCC, and discuss their potential clinical applications as biomarkers for the diagnosis, prognosis, monitoring and treatment of HCC.

  13. Liver Transplantation for Hepatocellular Carcinoma beyond Milan Criteria: Multidisciplinary Approach to Improve Outcome

    Science.gov (United States)

    Kornberg, A.

    2014-01-01

    The implementation of the Milan criteria (MC) in 1996 has dramatically improved prognosis after liver transplantation (LT) in patients with hepatocellular carcinoma (HCC). Liver transplantation has, thereby, become the standard therapy for patients with “early-stage” HCC on liver cirrhosis. The MC were consequently adopted by United Network of Organ Sharing (UNOS) and Eurotransplant for prioritization of patients with HCC. Recent advancements in the knowledge about tumor biology, radiographic imaging techniques, locoregional interventional treatments, and immunosuppressive medications have raised a critical discussion, if the MC might be too restrictive and unjustified keeping away many patients from potentially curative LT. Numerous transplant groups have, therefore, increasingly focussed on a stepwise expansion of selection criteria, mainly based on tumor macromorphology, such as size and number of HCC nodules. Against the background of a dramatic shortage of donor organs, however, simple expansion of tumor macromorphology may not be appropriate to create a safe extended criteria system. In contrast, rather the implementation of reliable prognostic parameters of tumor biology into selection process prior to LT is mandatory. Furthermore, a multidisciplinary approach of pre-, peri-, and posttransplant modulating of the tumor and/or the patient has to be established for improving prognosis in this special subset of patients. PMID:27335840

  14. Significance of genetic variants in DLC1 and their association with hepatocellular carcinoma

    Science.gov (United States)

    XIE, CHENG-RONG; SUN, HONG-GUANG; SUN, YU; ZHAO, WEN-XIU; ZHANG, SHENG; WANG, XIAO-MIN; YIN, ZHEN-YU

    2015-01-01

    DLC1 has been shown to be downregulated or absent in hepatocellular carcinoma (HCC) and is associated with tumorigenesis and development. However, only a small number of studies have focused on genetic variations of DLC1. The present study performed exon sequencing for the DLC1 gene in HCC tissue samples from 105 patients to identify functional genetic variation of DLC1 and its association with HCC susceptibility, clinicopathological features and prognosis. A novel missense mutation and four non-synonymous single nucleotide polymorphisms (SNPs; rs3816748, rs11203495, rs3816747 and rs532841) were identified. A significant correlation of rs3816747 polymorphisms with HCC susceptibility was identified. Compared to individuals with the GG genotype of rs3816747, those with the GA (odds ratio (OR)=0.486; P=0.037) or GA+AA genotype (OR=0.51; P=0.039) were associated with a significantly decreased HCC risk. Furthermore, patients with the GC+CC genotype of rs3816748, the TC+CC genotype of rs11203495 or the GA+AA genotype of rs3816747 had small-sized tumors compared with those carrying the wild-type genotype. No significant association of DLC1 SNPs with the patients' prognosis was found. These results indicated that genetic variations in the DLC1 gene may confer a risk for HCC. PMID:26095787

  15. miR-34a: Multiple Opposing Targets and One Destiny in Hepatocellular Carcinoma.

    Science.gov (United States)

    Yacoub, Radwa Alaa; Fawzy, Injie Omar; Assal, Reem Amr; Hosny, Karim Adel; Zekri, Abdel-Rahman Nabawy; Esmat, Gamal; El Tayebi, Hend Mohamed; Abdelaziz, Ahmed Ihab

    2016-12-28

    Background and Aims: The role of miR-34a in hepatocellular carcinoma (HCC) is controversial and several unresolved issues remain, including its expression pattern and relevance to tumor etiology, tumor stage and prognosis, and finally, its impact on apoptosis. Methods: miR-34a expression was assessed in hepatitis C virus (HCV)-induced non-metastatic HCC tissues by RT-Q-PCR. Huh-7 cells were transfected with miR-34a mimics and the impact of miR-34a was examined on 84 pro-apoptotic/anti-apoptotic genes using PCR array; its net effect was tested on cell viability via MTT assay. Results: miR-34a expression was up-regulated in HCC tissues. Moreover, miR-34a induced a large set of pro-apoptotic/anti-apoptotic genes, with a net result of triggering apoptosis and repressing cell viability. Conclusions: HCC-related differential expression of miR-34a could be etiology-based or stage-specific, and low expression of miR-34a may predict poor prognosis. This study's findings also emphasize the role of miR-34a in apoptosis.

  16. Characterization of the oncogenic function of centromere protein F in hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Dai, Yongdong; Liu, Lulu; Zeng, Tingting; Zhu, Ying-Hui [State Key Laboratory of Oncology in Southern China, Sun Yat-Sen University Cancer Center, Guangzhou (China); Li, Jiangchao [Vascular Biology Research Institute, Guangdong Pharmaceutical University, Guangzhou (China); Chen, Leilei [Department of Clinical Oncology, The University of Hong Kong, Pokfulam, Hong Kong (China); Li, Yan; Yuan, Yun-Fei [State Key Laboratory of Oncology in Southern China, Sun Yat-Sen University Cancer Center, Guangzhou (China); Ma, Stephanie, E-mail: stefma@hku.hk [Department of Clinical Oncology, The University of Hong Kong, Pokfulam, Hong Kong (China); State Key Laboratory for Liver Research, The University of Hong Kong, Pokfulam, Hong Kong (China); Guan, Xin-Yuan, E-mail: xyguan@hkucc.hku.hk [State Key Laboratory of Oncology in Southern China, Sun Yat-Sen University Cancer Center, Guangzhou (China); Department of Clinical Oncology, The University of Hong Kong, Pokfulam, Hong Kong (China); State Key Laboratory for Liver Research, The University of Hong Kong, Pokfulam, Hong Kong (China)

    2013-07-12

    Highlights: •Overexpression of CENPF is frequently detected in HCC. •Upregulation of CENPF serves as an independent prognosis factor in HCC patients. •CENPF functions as an oncogene in HCC by promoting cell G2/M transition. -- Abstract: Centromere protein F (CENPF) is an essential nuclear protein associated with the centromere-kinetochore complex and plays a critical role in chromosome segregation during mitosis. Up-regulation of CENPF expression has previously been detected in several solid tumors. In this study, we aim to study the expression and functional role of CENPF in hepatocellular carcinoma (HCC). We found CENPF was frequently overexpressed in HCC as compared with non-tumor tissue. Up-regulated CENPF expression in HCC was positively correlated with serum AFP, venous invasion, advanced differentiation stage and a shorter overall survival. Cox regression analysis found that overexpression of CENPF was an independent prognosis factor in HCC. Functional studies found that silencing CENPF could decrease the ability of the cells to proliferate, form colonies and induce tumor formation in nude mice. Silencing CENPF also resulted in the cell cycle arrest at G2/M checkpoint by down-regulating cell cycle proteins cdc2 and cyclin B1. Our data suggest that CENPF is frequently overexpressed in HCC and plays a critical role in driving HCC tumorigenesis.

  17. An Analysis of Surgical Treatment for the Spontaneous Rupture of Hepatocellular Carcinoma.

    Science.gov (United States)

    Sada, Haruki; Ohira, Masahiro; Kobayashi, Tsuyoshi; Tashiro, Hirotaka; Chayama, Kazuaki; Ohdan, Hideki

    2016-01-01

    The prognosis of spontaneous rupture of hepatocellular carcinoma (HCC) remains unclear. We investigated the prognosis of patients with ruptured HCC based on the treatments and prognostic factors associated with long-term survival. The prognoses of 64 consecutive patients treated for ruptured HCC from 1986 to 2013 were analyzed according to their methods of treatment. The prognostic factors of 16 surgical patients were identified, and their overall survival (OS) and recurrence rates were compared to 1,157 surgical patients who underwent surgery for non-ruptured HCC. The surgical outcomes were also compared using a propensity score matching method. Surgery was associated with a better OS. Curative resection was the only independent prognostic factor in surgical patients with ruptured HCC (p = 0.040). Although the OS of surgical patients with non-ruptured HCC was found to be significantly better than that of the patients with ruptured HCC, no significant difference in OS was observed after propensity score matching. A curative resection should be the objective of treatment, assuming the suitability of the patient's clinical condition. When the liver function reserve and tumor extension of patients with ruptured and non-ruptured HCC are similar, then their surgical outcomes may not be significantly different. © 2015 S. Karger AG, Basel.

  18. Knockdown of long noncoding RNA linc-ITGB1 suppresses migration, invasion of hepatocellular carcinoma via regulating ZEB1.

    Science.gov (United States)

    Yu, W-W; Wang, K; Liao, G-J

    2017-11-01

    This research focuses on the influence of linc-ITGB1 on the metastasis of hepatocellular carcinoma and further explores its underlying mechanism. A total of 70 hepatocellular carcinoma patients were chosen for our study. RT-qPCR was used for detecting the expression level of linc-ITGB1 in their cancer tissues. Moreover, the expression level of linc-ITGB1 was also detected in hepatocellular carcinoma cell lines. Furthermore, whether linc-ITGB1 could affect the migrated and invaded ability of hepatocellular carcinoma cells was determined by wound healing assay and transwell assay. We further explored the potential mechanism by RT-qPCR and Western blot assay. Linc-ITGB1 expression level in hepatocellular carcinoma tissues was remarkably higher than that in adjacent tissues. Moreover, migrated and invaded ability of hepatocellular carcinoma cells was inhibited through knockdown of linc-ITGB1. Further study revealed that silenced linc-ITGB1 inhibited the expression of ZEB1 and then suppressed epithelial to mesenchymal transition (EMT), which was important during the metastasis of hepatocellular carcinoma. Moreover, the inhibition of cell invasion by silenced linc-ITGB1 could be rescued through overexpression of ZEB1 in hepatocellular carcinoma. The results indicate that linc-ITGB1, a novel oncogene in tumorigenesis, could promote the metastasis and EMT via ZEB1, which may offer a possible therapeutic target in hepatocellular carcinoma.

  19. Spinal cord compression secondary to bone metastases from hepatocellular carcinoma

    Science.gov (United States)

    Doval, Dinesh Chandra; Bhatia, Komal; Vaid, Ashok Kumar; Pavithran, Keechelat; Sharma, Jai Bhagwan; Hazarika, Digant; Jena, Amarnath

    2006-01-01

    Bone metastases are rare in primary hepatocellular carcinoma (HCC). Spinal cord compression (SCC) due to bone metastases occur commonly in patients with lung and breast carcinomas, and metastatic HCC is an unusual cause of SCC. Spinal cord compression is an oncologic emergency and treatment delays can lead to irreversible consequences. Thus, the awareness that SCC could be a potential complication of bone metastases due to HCC is of significance in initiation of early treatment that can improve the quality of life and survival of the patients, if diagnosed earlier. This paper describes four cases of primary HCC with varied manifestations of SCC due to bone metastases. The first patient presented primarily with the symptoms of bone pains corresponding to the bone metastases sites rather than symptoms of associated hepatic pathology and eventually developed SCC. The second patient, diagnosed as having HCC, developed extradural SCC leading to paraplegia during the course of illness, for which he underwent emergency laminectomy with posterior fixation. The third patient developed SCC soon after the primary diagnosis and had to undergo emergency laminectomy. Post laminectomy he had good neurological recovery. The Fourth patient presented primarily with radicular pains rather than frank paraplegia as the first manifestation of SCC. PMID:16937544

  20. Evaluation of Photoelectron Therapy Effect on Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    bahram Mofid

    2007-10-01

    Full Text Available Mofid B1, Navabpoor M2, Alizadeh Azimi M3 1. Assistant professor, Department of Radiotherapy, Faculty of Para-Medicine, Shahid Beheshti University of medical sciences 2. Instructor, Department of Technology of radiology, Faculty of Para-Medicine, Shahid Beheshti University of medical sciences Abstract Background: Photoelectron therapy method has been usad successfully, on the body phantom, cancer cells culture and animals. In this method, drugs containing x-Ray opaque factors–with high atomic numbers–are injected into the patient’s vein. After appropriate drug accumulation, about at least ten percent of the total injected amounts, 200kev. up to 300kev. of localized x-Ray beams is radiated to the site of the tumor. The Ethic Committee of Shahid Beheshti University of Medical Education and Health Services authorized the implementation of this new cancer treatment method, initially only on the group of patients who suffered from hepato-cellular carcinoma. Hepato cellular carcinoma is one of the most current malignancies of liver. In some cases, in addition to surgery, several approaches exist to come near the aim of predominating hepato-cellular carcinoma such as chemotherapy, current Radiation Therapy, Radio-Frequency application (RF, Trans-Artepical Chemo Embolization, (TACE, and Percutaneous Ethanol Injection (PEI. The effectiveness of the above-mentioned methods is about 10%-47%, applied alone or along side each other. Materials and methods: This study was a clinical-trial one. In this study, first, lipiodol (an x-ray opaque material with a high atomic number was transferred into the main vessel terminating to the tumor by angio-catheterization. Then,200kev. up to 250kev. of localized x-ray was radiated to the site of the tumor in one session. The drug volume was proportionally selected to the volume of the tumor, and the irradiation intensity was between 400 to 600cent.Gy. the beam energy absorption capacity of this drug is as times as

  1. Alpha-fetoprotein-producing esophageal adenocarcinoma: a mimicker of hepatocellular carcinoma.

    Science.gov (United States)

    Wang, Jeremy; Liu, Wendy; Parikh, Keyur; Post, Anthony Benjamin

    2017-02-01

    Alpha-fetoprotein (AFP)-producing esophageal adenocarcinoma (EAC) is a rare occurrence. Elevation of serum AFP is commonly associated with hepatocellular carcinoma and yolk sac tumors, but rarely with esophageal carcinoma. Here, we report a rare case of AFP-producing EAC. A 51-year-old man presented with two weeks of acid reflux and a 35-lb weight loss. Laboratory data were notable for transaminitis and AFP was 2524 ng/mL. Computed tomography of the abdomen revealed abnormal thickening of the esophagus and multiple metastatic masses throughout the liver. Biopsy of one of the masses revealed adenocarcinoma of gastrointestinal origin. Subsequent upper endoscopy revealed an esophageal mass with biopsy notable for ulcerated dysplastic glandular mucosa with likely underlying malignancy. The patient underwent palliative esophageal stent placement but died two months later. Elevated AFP levels are an unusual occurrence in EAC. Prognosis is poor given its advanced presenting stage and high metastatic potential. Most cases are unsuccessfully treated with surgery and chemotherapy. Serial measurement of serum AFP may be useful for monitoring clinical status and treatment response. Clinicians should consider AFP-producing EAC in their differential diagnosis in the work-up of a liver mass in the setting of elevated AFP or liver function impairment, especially in the absence of chronic liver disease.

  2. c-MET receptor tyrosine kinase as a molecular target in advanced hepatocellular carcinoma.

    Science.gov (United States)

    Granito, Alessandro; Guidetti, Elena; Gramantieri, Laura

    2015-01-01

    c-MET is the membrane receptor for hepatocyte growth factor (HGF), also known as scatter factor or tumor cytotoxic factor, a mitogenic growth factor for hepatocytes. HGF is mainly produced by cells of mesenchymal origin and it mainly acts on neighboring epidermal and endothelial cells, regulating epithelial growth and morphogenesis. HGF/MET signaling has been identified among the drivers of tumorigenesis in human cancers. As such, c-MET is a recognized druggable target, and against it, targeted agents are currently under clinical investigation. c-MET overexpression is a common event in a wide range of human malignancies, including gastric, lung, breast, ovary, colon, kidney, thyroid, and liver carcinomas. Despite c-MET overexpression being reported by a large majority of studies, no evidence for a c-MET oncogenic addiction exists in hepatocellular carcinoma (HCC). In particular, c-MET amplification is a rare event, accounting for 4%-5% of cases while no mutation has been identified in c-MET oncogene in HCC. Thus, the selection of patient subgroups more likely to benefit from c-MET inhibition is challenging. Notwithstanding, c-MET overexpression was reported to be associated with increased metastatic potential and poor prognosis in patients with HCC, providing a rationale for its therapeutic inhibition. Here we summarize the role of activated HGF/MET signaling in HCC, its prognostic relevance, and the implications for therapeutic approaches in HCC.

  3. Synergistic growth inhibition by sorafenib and vitamin K2 in human hepatocellular carcinoma cells.

    Science.gov (United States)

    Zhang, Yafei; Zhang, Bicheng; Zhang, Anran; Zhao, Yong; Zhao, Jie; Liu, Jian; Gao, Jianfei; Fang, Dianchun; Rao, Zhiguo

    2012-09-01

    Sorafenib is an oral multikinase inhibitor that has been proven effective as a single-agent therapy in hepatocellular carcinoma, and there is a strong rationale for investigating its use in combination with other agents. Vitamin K2 is nearly non-toxic to humans and has been shown to inhibit the growth of hepatocellular carcinoma. In this study, we evaluated the effects of a combination of sorafenib and vitamin K2 on the growth of hepatocellular carcinoma cells. Flow cytometry, 3-(4,5-dimethyl-2-thiazolyl-2,5-diphenyl-2H-tetrazolium bromide) and nude mouse xenograft assays were used to examine the effects of sorafenib and vitamin K2 on the growth of hepatocellular carcinoma cells. Western blotting was used to elucidate the possible mechanisms underlying these effects. Assays for 3-(4,5-dimethyl-2-thiazolyl-2,5-diphenyl-2H-tetrazolium bromide) revealed a strong synergistic growth-inhibitory effect between sorafenib and vitamin K2. Flow cytometry showed an increase in cell cycle arrest and apoptosis after treatment with a combination of these two drugs at low concentrations. Sorafenib-mediated inhibition of extracellular signal-regulated kinase phosphorylation was promoted by vitamin K2, and downregulation of Mcl-1, which is required for sorafenib-induced apoptosis, was observed after combined treatment. Vitamin K2 also attenuated the downregulation of p21 expression induced by sorafenib, which may represent the mechanism by which vitamin K2 promotes the inhibitory effects of sorafenib on cell proliferation. Moreover, the combination of sorafenib and vitamin K2 significantly inhibited the growth of hepatocellular carcinoma xenografts in nude mice. Our results determined that combined treatment with sorafenib and vitamin K2 can work synergistically to inhibit the growth of hepatocellular carcinoma cells. This finding raises the possibility that this combined treatment strategy might be promising as a new therapy against hepatocellular carcinoma, especially for patients

  4. Ultrasonographic detection of hepatocellular carcinoma: correlation of preoperative ultrasonography and resected liver pathology

    International Nuclear Information System (INIS)

    Lim, J.H.; Kim, S.H.; Lee, W.J.; Choi, D.; Kim, S.H.; Lim, H.K.

    2006-01-01

    AIM: The aim of this study was to determine the sensitivity of ultrasonography for detecting hepatocellular carcinoma in patients who underwent surgical liver resection. MATERIALS AND METHODS: The preoperative ultrasonography reports of 103 patients who underwent hepatic resection surgery were retrospectively reviewed. The patients had chronic liver disease with good liver function and a relatively normal liver echotexture. The presence of a mass or masses in the resected part of the liver segments on preoperative ultrasonography was regarded as possible hepatocellular carcinoma, and these results were compared with the surgically resected hepatic lobes or segments. Accuracy for detection was assessed on a lesion-by-lesion basis, on a segment-by-segment basis, and on a patient basis. RESULTS: One hundred and fifty-seven hepatocellular carcinomas were found in 244 hepatic segments of 103 patients. One hundred and one of 157 hepatocellular carcinomas were detected using ultrasonography in 97 patients resulting in a sensitivity of 64%. In six patients, a solitary hepatocellular carcinoma was missed in each patient, a patient sensitivity being 94%. Using ultrasonography, 87 of 100 (87%) hepatocellular carcinomas larger than 2 cm in diameter, and 14 of 57 (25%) hepatocellular carcinomas 2 cm or smaller in diameter were revealed. On the basis of segment-by-segment analysis, the sensitivity was 78% (99 of 127 segments), specificity was 97% (114 of 117 segments), accuracy was 87% (213 of 244 segments), positive predictive value was 97% (99 of 102 segments), and negative predictive value was 80% (114 of 142 segments). CONCLUSION: In patients with chronic liver disease and good hepatic function, ultrasonography has a sensitivity of 94% in the identification of affected patients, but for individual lesions, the sensitivity is only 64%

  5. Changing incidence patterns of hepatocellular carcinoma among age groups in Taiwan.

    Science.gov (United States)

    Hung, Giun-Yi; Horng, Jiun-Lin; Yen, Hsiu-Ju; Lee, Chih-Ying; Lin, Li-Yih

    2015-12-01

    This study examined and compared the incidence patterns of hepatocellular carcinoma among age groups in Taiwan, 30 years after a universal hepatitis B virus immunization program was launched. Data for hepatocellular carcinoma diagnosed in 2003-2011 were collected from the population-based Taiwan Cancer Registry. Age-standardized incidence rates were calculated to analyze and compare the changes in incidence rates and trends. More specific analyses were performed on four age groups separated by sex. A total of 82,856 patients were diagnosed with hepatocellular carcinoma in 2003-2011 in Taiwan, yielding an age-standardized incidence rate of 32.97 per 100,000 person-years. Hepatocellular carcinoma was predominantly diagnosed in middle-aged adults (50.1%) and elderly people (49.1%), in contrast to the low incidences in children (0.04%) and adolescents and young adults (0.8%). Striking variations in trends were found for children (annual percent change: -16.6%, 2003-2010) and adolescents and young adults (annual percent change: -7.9%, 2003-2011). The incidence rate of hepatocellular carcinoma in children decreased to zero in 2011; only a slight decline in trends occurred for the middle-aged group (annual percent change: -2%, 2003-2011), and a slight upward trend was observed for elderly people (1.3%), specifically in women (1.7%). In Taiwan, hepatitis B virus-related hepatocellular carcinoma was nearly eradicated in children in 2011. The findings on age-specific incidence patterns and trends of hepatocellular carcinoma suggest that different control strategies for treating this devastating disease in the future be made according to age. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  6. Glycogen metabolism in radiation induced hepatocellular carcinoma in Swiss albino mice

    International Nuclear Information System (INIS)

    Gupta, N.K.; Kumar, Ashok

    1988-01-01

    Glycogen content and the activities of phosphorylase, glycogen sythetase (GS), glucose 6-phosphatase (G6Pase), phosphohexose isomerase (PHI), glucose 6-phosphodehydrogenase were biochemically determined in the heparocellular carcinoma induced in swiss albino mice following radiocalcium internal irradiation. The content glycogen and the activities of phosphorylase, glycogen synthetase, G6Pase, PHI, GPT and GOT are considerably reduced in the hepatocellular carcinoma compared to that in control liver. However, the activity of G6PDH shows an increased activity. Results indicate that the decreas ed glycogen content in the hepatocellular carcinoma is due to the reduced glycogen synthetase activity and utilization of glucose by HMP pathway. (author). 2 tabs., 24 refs

  7. Factors Predicting Survival after Transarterial Chemoembolization of Unresectable Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Farina M. Hanif

    2014-10-01

    Full Text Available Background: Transarterial chemoembolization is the preferred treatment for unresectable, intermediate-stage hepatocellular carcinoma. Survival after transarterial chemoembolization can be highly variable. The purpose of this study is to identify the factors that predict overall survival of patients with unresectable hepatocellular carcinoma who undergo transarterial chemoembolization as the initial therapy. Methods:We included patients who underwent transarterial chemoembolization from 2007 to 2012 in this study. Patient’s age, gender, cause of cirrhosis, Child-Turcotte-Pugh score, model of end-stage liver disease score, Cancer of the Liver Italian Program score, Okuda stage, alpha- fetoprotein level, site, size and number of tumors were recorded. Radiological response to transarterial chemoembolization was assessed by computerized tomography scan at 1 and 3 months after the procedure. Repeat sessions of transarterial chemoembolization were performed according to the response. We performed survival assessment and all patients were assessed for survival at the last follow-up. Results: Included in this study were 71 patients of whom there were 57 (80.3 % males, with a mean age of 51.9±12.1 years (range: 18-76 years. The mean follow-up period was 12.5±10.7 months. A total of 31 (43.7% patients had only one session of transarterial chemoembolization, 17 (23.9% underwent 2 and 11 (15.5% had 3 or more sessions. On univariate analysis, significant factors that predicted survival included serum bilirubin (P=0.02, esophageal varices (P=0.002, Cancer of the Liver Italian Program score (P=0.003, tumor size (P=0.005, >3 sessions of transarterial chemoembolization (P=0.006 and patient's age (P=0.001. Cox regression analysis showed that tumor size of 1 transarterial chemoembolization session (P=0.004 were associated with better survival. Conclusion: Our study demonstrates that survival after transarterial chemoem- bolization is predicted by tumor size

  8. Ursodeoxycholic acid induces apoptosis in hepatocellular carcinoma xenografts in mice

    Science.gov (United States)

    Liu, Hui; Xu, Hong-Wei; Zhang, Yu-Zhen; Huang, Ya; Han, Guo-Qing; Liang, Tie-Jun; Wei, Li-Li; Qin, Cheng-Yong; Qin, Cheng-Kun

    2015-01-01

    AIM: To evaluate the efficacy of ursodeoxycholic acid (UDCA) as a chemotherapeutic agent for the treatment of hepatocellular carcinoma (HCC). METHODS: BALB/c nude mice were randomized into four groups 24 h before subcutaneous injection of hepatocarcinoma BEL7402 cells suspended in phosphate buffered saline (PBS) into the right flank. The control group (n = 10) was fed a standard diet while treatment groups (n = 10 each) were fed a standard daily diet supplemented with different concentrations of UDCA (30, 50 and 70 mg/kg per day) for 21 d. Tumor growth was measured once each week, and tumor volume (V) was calculated with the following equation: V = (L × W2) × 0.52, where L is the length and W is the width of the xenograft. After 21 d, mice were killed under ether anesthesia, and tumors were excised and weighed. Apoptosis was evaluated through detection of DNA fragmentation with gel electrophoresis and the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay. Western blot analysis was performed to determine the expression of apoptosis-related proteins BAX, BCL2, APAF1, cleaved caspase-9, and cleaved caspase-3. RESULTS: UDCA suppressed tumor growth relative to controls. The mean tumor volumes were the following: control, 1090 ± 89 mm3; 30 mg/kg per day, 612 ± 46 mm3; 50 mg/kg per day, 563 ± 38 mm3; and 70 mg/kg per day, 221 ± 26 mm3. Decreased tumor volumes reached statistical significance relative to control xenografts (30 mg/kg per day, P < 0.05; 50 mg/kg per day, P < 0.05; 70 mg/kg per day, P < 0.01). Increasing concentrations of UDCA led to increased DNA fragmentation observed on gel electrophoresis and in the TUNEL assay (control, 1.6% ± 0.3%; 30 mg/kg per day, 2.9% ± 0.5%; 50 mg/kg per day, 3.15% ± 0.7%, and 70 mg/kg per day, 4.86% ± 0.9%). Western blot analysis revealed increased expression of BAX, APAF1, cleaved-caspase-9 and cleaved-caspase-3 proteins, which induce apoptosis, but decreased expression of BCL2

  9. Leptin signaling molecular actions and drug target in hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Jiang N

    2014-11-01

    Full Text Available Nan Jiang,1,* Rongtong Sun,2,* Qing Sun3 1Shandong University School of Medicine, Jinan, Shandong Province, People’s Republic of China; 2Weihai Municipal Hospital, Weihai, Shandong Province, People’s Republic of China; 3Department of Pathology, QianFoShan Hospital Affiliated to Shandong University, Jinan, Shandong Province, People’s Republic of China *These authors contributed equally to this work Abstract: Previous reports indicate that over 13 different tumors, including hepatocellular carcinoma (HCC, are related to obesity. Obesity-associated inflammatory, metabolic, and endocrine mediators, as well as the functioning of the gut microbiota, are suspected to contribute to tumorigenesis. In obese people, proinflammatory cytokines/chemokines including tumor necrosis factor-alpha, interleukin (IL-1 and IL-6, insulin and insulin-like growth factors, adipokines, plasminogen activator inhibitor-1, adiponectin, and leptin are found to play crucial roles in the initiation and development of cancer. The cytokines induced by leptin in adipose tissue or tumor cells have been intensely studied. Leptin-induced signaling pathways are critical for biological functions such as adiposity, energy balance, endocrine function, immune reaction, and angiogenesis as well as oncogenesis. Leptin is an activator of cell proliferation and anti-apoptosis in several cell types, and an inducer of cancer stem cells; its critical roles in tumorigenesis are based on its oncogenic, mitogenic, proinflammatory, and pro-angiogenic actions. This review provides an update of the pathological effects of leptin signaling with special emphasis on potential molecular mechanisms and therapeutic targeting, which could potentially be used in future clinical settings. In addition, leptin-induced angiogenic ability and molecular mechanisms in HCC are discussed. The stringent binding affinity of leptin and its receptor Ob-R, as well as the highly upregulated expression of both

  10. Ursodeoxycholic acid induces apoptosis in hepatocellular carcinoma xenografts in mice.

    Science.gov (United States)

    Liu, Hui; Xu, Hong-Wei; Zhang, Yu-Zhen; Huang, Ya; Han, Guo-Qing; Liang, Tie-Jun; Wei, Li-Li; Qin, Cheng-Yong; Qin, Cheng-Kun

    2015-09-28

    To evaluate the efficacy of ursodeoxycholic acid (UDCA) as a chemotherapeutic agent for the treatment of hepatocellular carcinoma (HCC). BALB/c nude mice were randomized into four groups 24 h before subcutaneous injection of hepatocarcinoma BEL7402 cells suspended in phosphate buffered saline (PBS) into the right flank. The control group (n = 10) was fed a standard diet while treatment groups (n = 10 each) were fed a standard daily diet supplemented with different concentrations of UDCA (30, 50 and 70 mg/kg per day) for 21 d. Tumor growth was measured once each week, and tumor volume (V) was calculated with the following equation: V = (L × W(2)) × 0.52, where L is the length and W is the width of the xenograft. After 21 d, mice were killed under ether anesthesia, and tumors were excised and weighed. Apoptosis was evaluated through detection of DNA fragmentation with gel electrophoresis and the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay. Western blot analysis was performed to determine the expression of apoptosis-related proteins BAX, BCL2, APAF1, cleaved caspase-9, and cleaved caspase-3. UDCA suppressed tumor growth relative to controls. The mean tumor volumes were the following: control, 1090 ± 89 mm(3); 30 mg/kg per day, 612 ± 46 mm(3); 50 mg/kg per day, 563 ± 38 mm(3); and 70 mg/kg per day, 221 ± 26 mm(3). Decreased tumor volumes reached statistical significance relative to control xenografts (30 mg/kg per day, P < 0.05; 50 mg/kg per day, P < 0.05; 70 mg/kg per day, P < 0.01). Increasing concentrations of UDCA led to increased DNA fragmentation observed on gel electrophoresis and in the TUNEL assay (control, 1.6% ± 0.3%; 30 mg/kg per day, 2.9% ± 0.5%; 50 mg/kg per day, 3.15% ± 0.7%, and 70 mg/kg per day, 4.86% ± 0.9%). Western blot analysis revealed increased expression of BAX, APAF1, cleaved-caspase-9 and cleaved-caspase-3 proteins, which induce apoptosis, but decreased expression of BCL2 protein, which

  11. Outcomes of emergent embolisation of ruptured hepatocellular carcinoma in a western population

    International Nuclear Information System (INIS)

    Monroe, E.J.; Kogut, M.J.; Ingraham, C.R.; Kwan, S.W.; Hippe, D.S.; Padia, S.A.

    2015-01-01

    Aim: To evaluate the authors' experience with interventional radiological management of tumour rupture in hepatocellular carcinoma (HCC) in a Western population. Materials and methods: A retrospective review was performed of all consecutive patients treated at a single institution with transcatheter embolisation for ruptured HCC between 2000 and 2013. Patient age, sex, aetiology of liver disease, degree of underlying liver dysfunction, and clinical presentation were assessed. Embolisation was performed in a selective fashion when possible. Success, complications, and survival were assessed. Results: Twenty-three patients were treated with embolisation for ruptured HCC. Of these patients, nine, nine, and five patients were Child–Pugh Class A, B, and C respectively. Embolisation was successful in 22 patients; one patient remained haemodynamically unstable and transfusion dependent despite embolisation. No major complications occurred. Median survival time was 260 days and the 30 day and 1 year survival rates were 83% and 45%, respectively. Child–Pugh class B or C (p = 0.04), Model for End-Stage Liver Disease score greater than 10 (p = 0.04), lobar embolisation (p = 0.04), and presence of portal vein thrombosis (p = 0.01) were significantly associated with worse prognosis. Conclusion: Transcatheter embolisation is effective at controlling haemorrhage in patients with ruptured HCC. Although major procedural complications are low, embolisation should proceed with an understanding of poor prognosis in patients with decompensated liver disease. Superselective embolisation is associated with improved prognosis and should be performed when feasible. -- Highlights: •We reviewed our outcomes after transcatheter embolization of ruptured HCC in a western population. •Overall survival in the setting of ruptured HCC remains poor despite successful embolization. •Worse liver function, portal vein thrombosis, and lobar embolization were all associated with

  12. Particle radiotherapy, a novel external radiation therapy, versus liver resection for hepatocellular carcinoma accompanied with inferior vena cava tumor thrombus: A matched-pair analysis.

    Science.gov (United States)

    Komatsu, Shohei; Kido, Masahiro; Asari, Sadaki; Toyama, Hirochika; Ajiki, Tetsuo; Demizu, Yusuke; Terashima, Kazuki; Okimoto, Tomoaki; Sasaki, Ryohei; Fukumoto, Takumi

    2017-12-01

    Hepatocellular carcinoma accompanied with inferior vena cava tumor thrombus carries a dismal prognosis, and the feasibility of local treatment has remained controversial. The present study aimed to compare the outcomes of particle radiotherapy and liver resection in patients with hepatocellular carcinoma with inferior vena cava tumor thrombus. Thirty-one and 19 patients, respectively, underwent particle radiotherapy and liver resection for hepatocellular carcinoma with inferior vena cava tumor thrombus. A matched-pair analysis was undertaken to compare the short- and long-term outcomes according to tumor stage determined using the tumor-node-metastasis classification. Both stages IIIB and IV (IVA and IVB) patients were well-matched for 12 factors, including treatment policy and patient and tumor characteristics. The median survival time of matched patients with stage IIIB tumors in the particle radiotherapy group was greater than that in the liver resection group (748 vs 272 days, P = .029), whereas no significant difference was observed in the median survival times of patients with stage IV tumors (239 vs 311 days, respectively). There were significantly fewer treatment-related complications of grade 3 or greater in the particle radiotherapy group (0%) than in the liver resection group (26%). Particle radiotherapy is potentially preferable in hepatocellular carcinoma patients with stage IIIB inferior vena cava tumor thrombus and at least equal in efficiency to liver resection in those with stage IV disease, while causing significantly fewer complications. Considering the relatively high survival and low invasiveness of particle radiotherapy when compared to liver resection, this approach may represent a novel treatment modality for hepatocellular carcinoma with inferior vena cava tumor thrombus. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Hepatocellular carcinoma with neuroendocrine differentiation: clinical and imaging findings in five patients

    International Nuclear Information System (INIS)

    Park, Seong Hoon; Kang, Myeong Jin; Cho, Jin Han

    2008-01-01

    To describe the clinical and imaging findings of hepatocellular carcinoma with neuroendocrine differentiation, which is an extremely rare variant of hepatocellular carcinoma. We collected five patients who had histopathologically proven hepatocellular carcinoma with neuroendocrine differentiation, and described morphologic feature, enhancement pattern of tumors, extrahepatic manifestation and clinical findings. At CT, the tumor size ranged from 8 to 17 cm (mean: 12 cm) in maximum diameter. The tumor margin was well-defined and smooth in four patients and all tumors were heterogeneously hypoattenuating. Four tumor showed rim enhancement on arterial and portal phases. Local invasion to the portal vein, intrahepatic duct and gallbladder were seen. Extrahepatic manifestations included hepatic metastases, lymph node metastasis. At ultrasonography, the tumor showed heterogeneously hyperechoic in all patients and hypoechoic rim was found in four patients. Of four patients who were followed up, one survived for 16 months after initial diagnosis, while the other three died within 3 months after initial diagnosis. As described above, clinical and imaging findings of hepatocellular carcinoma with neuroendocrine differentiation were not specific. However, this rare variant of hepatocellular carcinoma could be considered when hepatic tumor is found in an advanced stage and shows persistent rim enhancement at CT

  14. Anticancer effects of deproteinized asparagus polysaccharide on hepatocellular carcinoma in vitro and in vivo.

    Science.gov (United States)

    Xiang, Jianfeng; Xiang, Yanjie; Lin, Shengming; Xin, Dongwei; Liu, Xiaoyu; Weng, Lingling; Chen, Tao; Zhang, Minguang

    2014-04-01

    Hepatocellular carcinoma (HCC) is one of the most aggressive malignancies in the world whose chemoprevention became increasingly important in HCC treatment. Although the anticancer effects of asparagus constituents have been investigated in several cancers, its effects on hepatocellular carcinoma have not been fully studied. In this study, we investigated the anticancer effects of the deproteinized asparagus polysaccharide on the hepatocellular carcinoma cells using the in vitro and in vivo experimental model. Our data showed that deproteinized asparagus polysaccharide might act as an effective inhibitor on cell growth in vitro and in vivo and exert potent selective cytotoxicity against human hepatocellular carcinoma Hep3B and HepG2 cells. Further study showed that it could potently induce cell apoptosis and G2/M cell cycle arrest in the more sensitive Hep3B and HepG2 cell lines. Moreover, deproteinized asparagus polysaccharide potentiated the effects of mitomycin both in vitro and in vivo. Mechanistic studies revealed that deproteinized asparagus polysaccharide might exert its activity through an apoptosis-associated pathway by modulating the expression of Bax, Bcl-2, and caspase-3. In conclusion, deproteinized asparagus polysaccharide exhibited significant anticancer activity against hepatocellular carcinoma cells and could sensitize the tumoricidal effects of mitomycin, indicating that it is a potential therapeutic agent (or chemosensitizer) for liver cancer therapy.

  15. Giant ectopic liver, hepatocellular carcinoma and pachydermia-a rare genetic syndrome?

    Directory of Open Access Journals (Sweden)

    Miny Peter

    2011-08-01

    Full Text Available Abstract Ectopic liver is a very uncommon developmental anomaly that predisposes to the development of hepatocellular carcinoma. We describe the second documented case of a hepatocellular carcinoma developing in the primary liver of a patient with a rare and uncharacterized genetic symptom complex. Also present was the largest ectopic liver ever reported, measuring 12 cm in diameter which contained a solitary focus of metastatic hepatocellular carcinoma. The primary hepatocellular carcinoma is believed to have arisen in the native liver from a hepatic adenoma that was diagnosed 15 years earlier. The patient's uncharacterised condition featured prominent thick, yellow skin over the dorsum of the fingers, and was associated with follicular hyperkeratosis, abnormal plantar creases, digital clubbing, misshaped ears, a lingua plicata and an angioleiomyolipoma of the right kidney. This unique case of hepatocellular carcinoma arising from liver cell adenoma in a patient with an uncharacterised condition featuring a large ectopic liver invites discussion of the role of local factors in carcinogenesis in the parent liver but not the ectopic liver. It also underlines the imperative ongoing need for clinical autopsies.

  16. Mechanical Stress Promotes Cisplatin-Induced Hepatocellular Carcinoma Cell Death

    Directory of Open Access Journals (Sweden)

    Laila Ziko

    2015-01-01

    Full Text Available Cisplatin (CisPt is a commonly used platinum-based chemotherapeutic agent. Its efficacy is limited due to drug resistance and multiple side effects, thereby warranting a new approach to improving the pharmacological effect of CisPt. A newly developed mathematical hypothesis suggested that mechanical loading, when coupled with a chemotherapeutic drug such as CisPt and immune cells, would boost tumor cell death. The current study investigated the aforementioned mathematical hypothesis by exposing human hepatocellular liver carcinoma (HepG2 cells to CisPt, peripheral blood mononuclear cells, and mechanical stress individually and in combination. HepG2 cells were also treated with a mixture of CisPt and carnosine with and without mechanical stress to examine one possible mechanism employed by mechanical stress to enhance CisPt effects. Carnosine is a dipeptide that reportedly sequesters platinum-based drugs away from their pharmacological target-site. Mechanical stress was achieved using an orbital shaker that produced 300 rpm with a horizontal circular motion. Our results demonstrated that mechanical stress promoted CisPt-induced death of HepG2 cells (~35% more cell death. Moreover, results showed that CisPt-induced death was compromised when CisPt was left to mix with carnosine 24 hours preceding treatment. Mechanical stress, however, ameliorated cell death (20% more cell death.

  17. Mechanical Stress Promotes Cisplatin-Induced Hepatocellular Carcinoma Cell Death

    Science.gov (United States)

    Riad, Sandra; Bougherara, Habiba

    2015-01-01

    Cisplatin (CisPt) is a commonly used platinum-based chemotherapeutic agent. Its efficacy is limited due to drug resistance and multiple side effects, thereby warranting a new approach to improving the pharmacological effect of CisPt. A newly developed mathematical hypothesis suggested that mechanical loading, when coupled with a chemotherapeutic drug such as CisPt and immune cells, would boost tumor cell death. The current study investigated the aforementioned mathematical hypothesis by exposing human hepatocellular liver carcinoma (HepG2) cells to CisPt, peripheral blood mononuclear cells, and mechanical stress individually and in combination. HepG2 cells were also treated with a mixture of CisPt and carnosine with and without mechanical stress to examine one possible mechanism employed by mechanical stress to enhance CisPt effects. Carnosine is a dipeptide that reportedly sequesters platinum-based drugs away from their pharmacological target-site. Mechanical stress was achieved using an orbital shaker that produced 300 rpm with a horizontal circular motion. Our results demonstrated that mechanical stress promoted CisPt-induced death of HepG2 cells (~35% more cell death). Moreover, results showed that CisPt-induced death was compromised when CisPt was left to mix with carnosine 24 hours preceding treatment. Mechanical stress, however, ameliorated cell death (20% more cell death). PMID:25685789

  18. Value of radiofrequency ablation in the treatment of hepatocellular carcinoma

    Science.gov (United States)

    Feng, Kai; Ma, Kuan-Sheng

    2014-01-01

    Hepatocellular carcinoma (HCC) is a malignant disease that substantially affects public health worldwide. It is especially prevalent in east Asia and sub-Saharan Africa, where the main etiology is the endemic status of chronic hepatitis B. Effective treatments with curative intent for early HCC include liver transplantation, liver resection (LR), and radiofrequency ablation (RFA). RFA has become the most widely used local thermal ablation method in recent years because of its technical ease, safety, satisfactory local tumor control, and minimally invasive nature. This technique has also emerged as an important treatment strategy for HCC in recent years. RFA, liver transplantation, and hepatectomy can be complementary to one another in the treatment of HCC, and the outcome benefits have been demonstrated by numerous clinical studies. As a pretransplantation bridge therapy, RFA extends the average waiting time without increasing the risk of dropout or death. In contrast to LR, RFA causes almost no intra-abdominal adhesion, thus producing favorable conditions for subsequent liver transplantation. Many studies have demonstrated mutual interactions between RFA and hepatectomy, effectively expanding the operative indications for patients with HCC and enhancing the efficacy of these approaches. However, treated tumor tissue remains within the body after RFA, and residual tumors or satellite nodules can limit the effectiveness of this treatment. Therefore, future research should focus on this issue. PMID:24876721

  19. Multiple Ectopic Hepatocellular Carcinomas Arising in the Abdominal Cavity

    Directory of Open Access Journals (Sweden)

    Toru Miyake

    2012-09-01

    Full Text Available Ectopic hepatocellular carcinoma (HCC is a very rare clinical entity that is defined as HCC arising from extrahepatic liver tissue. This report presents a case of ectopic multiple HCC arising in the abdominal cavity. A 42-year-old otherwise healthy male presented with liver dysfunction at a general health checkup. Both HCV antibody and hepatitis B surface antigen were negative. Laboratory examination showed elevations in serum alpha-fetoprotein and PIVKA-II. Ultrasonography and computed tomography revealed multiple nodular lesions in the abdominal cavity with ascites without a possible primary tumor. Exploratory laparoscopy was performed, which revealed bloody ascites and multiple brown nodular tumors measuring approximately 10 mm in size that were disseminated on the perineum and mesentery. A postoperative PET-CT scan was performed but it did not reveal any evidence of a tumor in the liver. The tumors resected from the peritoneum were diagnosed as HCC. The present case of HCC was thought to have possibly developed from ectopic liver on the peritoneum or mesentery.

  20. Recent advances in multidisciplinary management of hepatocellular carcinoma

    Science.gov (United States)

    Gomaa, Asmaa I; Waked, Imam

    2015-01-01

    The incidence of hepatocellular carcinoma (HCC) is increasing, and it is currently the second leading cause of cancer-related death worldwide. Potentially curative treatment options for HCC include resection, transplantation, and percutaneous ablation, whereas palliative treatments include trans-arterial chemoembolization (TACE), radioembolization, and systemic treatments. Due to the diversity of available treatment options and patients’ presentations, a multidisciplinary team should decide clinical management of HCC, according to tumor characteristics and stage of liver disease. Potentially curative treatments are suitable for very-early- and early-stage HCC. However, the vast majority of HCC patients are diagnosed in later stages, where the tumor characteristics or progress of liver disease prevent curative interventions. For patients with intermediate-stage HCC, TACE and radioembolization improve survival and are being evaluated in addition to potentially curative therapies or with systemic targeted therapy. There is currently no effective systemic chemotherapy, immunologic, or hormonal therapy for HCC, and sorafenib is the only approved molecular-targeted treatment for advanced HCC. Other targeted agents are under investigation; trials comparing new agents in combination with sorafenib are ongoing. Combinations of systemic targeted therapies with local treatments are being evaluated for further improvements in HCC patient outcomes. This article provides an updated and comprehensive overview of the current standards and trends in the treatment of HCC. PMID:25866604

  1. Tissue- and Serum-Associated Biomarkers of Hepatocellular Carcinoma

    Science.gov (United States)

    Chauhan, Ranjit; Lahiri, Nivedita

    2016-01-01

    Hepatocellular carcinoma (HCC), one of the leading causes of cancer deaths in the world, is offering a challenge to human beings, with the current modes of treatment being a palliative approach. Lack of proper curative or preventive treatment methods encouraged extensive research around the world with an aim to detect a vaccine or therapeutic target biomolecule that could lead to development of a drug or vaccine against HCC. Biomarkers or biological disease markers have emerged as a potential tool as drug/vaccine targets, as they can accurately diagnose, predict, and even prevent the diseases. Biomarker expression in tissue, serum, plasma, or urine can detect tumor in very early stages of its development and monitor the cancer progression and also the effect of therapeutic interventions. Biomarker discoveries are driven by advanced techniques, such as proteomics, transcriptomics, whole genome sequencing, micro- and micro-RNA arrays, and translational clinics. In this review, an overview of the potential of tissue- and serum-associated HCC biomarkers as diagnostic, prognostic, and therapeutic targets for drug development is presented. In addition, we highlight recently developed micro-RNA, long noncoding RNA biomarkers, and single-nucleotide changes, which may be used independently or as complementary biomarkers. These active investigations going on around the world aimed at conquering HCC might show a bright light in the near future. PMID:27398029

  2. Multidisciplinary perspective of hepatocellular carcinoma: A Pacific Northwest experience

    Science.gov (United States)

    Yeh, Matthew M; Yeung, Raymond S; Apisarnthanarax, Smith; Bhattacharya, Renuka; Cuevas, Carlos; Harris, William P; Hon, Tony Lim Kiat; Padia, Siddharth A; Park, James O; Riggle, Kevin M; Daoud, Sayed S

    2015-01-01

    Hepatocellular carcinoma (HCC) is the most rapidly increasing type of cancer in the United States. HCC is a highly malignant cancer, accounting for at least 14000 deaths in the United States annually, and it ranks third as a cause of cancer mortality in men. One major difficulty is that most patients with HCC are diagnosed when the disease is already at an advanced stage, and the cancer cannot be surgically removed. Furthermore, because almost all patients have cirrhosis, neither chemotherapy nor major resections are well tolerated. Clearly there is need of a multidisciplinary approach for the management of HCC. For example, there is a need for better understanding of the fundamental etiologic mechanisms that are involved in hepatocarcinogenesis, which could lead to the development of successful preventive and therapeutic modalities. It is also essential to define the cellular and molecular bases for malignant transformation of hepatocytes. Such knowledge would: (1) greatly facilitate the identification of patients at risk; (2) prompt efforts to decrease risk factors; and (3) improve surveillance and early diagnosis through diagnostic imaging modalities. Possible benefits extend also to the clinical management of this disease. Because there are many factors involved in pathogenesis of HCC, this paper reviews a multidisciplinary perspective of recent advances in basic and clinical understanding of HCC that include: molecular hepatocarcinogenesis, non-invasive diagnostics modalities, diagnostic pathology, surgical modality, transplantation, local therapy and oncological/target therapeutics. PMID:26085907

  3. Computed tomography of hepatocellular carcinoma: Usefulness of dynamic CT

    Energy Technology Data Exchange (ETDEWEB)

    Takemoto, Kazumasa; Inoue, Yuichi; Matsuoka, Toshiyuki; Nakatsuka, Haruki; Oda, Junro [Osaka City Univ. (Japan). Faculty of Medicine

    1983-04-01

    Dynamic computed tomography (CT) scans in 65 hepatocellular carcinomas were analyzed and compared to plain and drip infusion contrast CT scans of those. Scans were obtained before, 10, 30, and 50 seconds after an intravenous bolus injection of 50ml 65% Angiografin. By this method, 49 hepatomas had moderate to marked enhancement at the arterial phase while the enhancement of normal liver parenchyma was only slight at the arterial phase and peaked at the portal phase. Compared to a drip infusion contrast CT, a dynamic CT had advantages to detect an isodense hepatoma in 4 and daughter tumors in 16 both of which were not appreciated by a plain and a drip infusion contrast CT. The tumor extension was also better delineated by a dynamic CT because a part of hepatoma had an isodense area. An arterio-portal shunt was visualized in one. Tumor thrombus in the portal vein was clearly demonstrated in 6 at the portal phase of a dynamic CT. Since a dynamic CT is convenient to perform without any special program or soft wear and gives us very useful information, we believe that it should be routinely employed as a part of a liver CT examination.

  4. A Surgical Perspective on Targeted Therapy of Hepatocellular Carcinoma

    Science.gov (United States)

    Faltermeier, Claire; Busuttil, Ronald W.; Zarrinpar, Ali

    2015-01-01

    Hepatocellular carcinoma (HCC), the second leading cause of cancer deaths worldwide, is difficult to treat and highly lethal. Since HCC is predominantly diagnosed in patients with cirrhosis, treatment planning must consider both the severity of liver disease and tumor burden. To minimize the impact to the patient while treating the tumor, techniques have been developed to target HCC. Anatomical targeting by surgical resection or locoregional therapies is generally reserved for patients with preserved liver function and minimal to moderate tumor burden. Patients with decompensated cirrhosis and small tumors are optimal candidates for liver transplantation, which offers the best chance of long-term survival. Yet, only 20%–30% of patients have disease amenable to anatomical targeting. For the majority of patients with advanced HCC, chemotherapy is used to target the tumor biology. Despite these treatment options, the five-year survival of patients in the United States with HCC is only 16%. In this review we provide a comprehensive overview of current approaches to target HCC. We also discuss emerging diagnostic and prognostic biomarkers, novel therapeutic targets identified by recent genomic profiling studies, and potential applications of immunotherapy in the treatment of HCC. PMID:28943622

  5. Radiofrequency ablation of hepatocellular carcinoma: pros and cons.

    Science.gov (United States)

    Rhim, Hyunchul; Lim, Hyo K

    2010-09-01

    Among locoregional treatments for hepatocellular carcinoma (HCC), radiofrequency ablation (RFA) has been accepted as the most popular alternative to curative transplantation or resection, and it shows an excellent local tumor control rate and acceptable morbidity. The benefits of RFA have been universally validated by the practice guidelines of international societies of hepatology. The main advantages of RFA include 1) it is minimally invasive with acceptable morbidity, 2) it enables excellent local tumor control, 3) it has promising long-term survival, and 4) it is a multimodal approach. Based on these pros, RFA will play an important role in managing the patient with early HCC (smaller than 3 cm with fewer than four tumors). The main limitations of current RFA technology in hepatic ablation include 1) limitation of ablation volume, 2) technically infeasible in some tumors due to conspicuity and dangerous location, and 3) the heat-sink effect. Many technical approaches have been introduced to overcome those limitations, including a novel guiding modality, use of artificial fluid or air, and combined treatment strategies. RFA will continue to play a role as a representative ablative modality in the management of HCC, even in the era of targeted agents.

  6. Targeting hepatocellular carcinoma: what did we discover so far?

    Directory of Open Access Journals (Sweden)

    Ana Filipa Brito

    2016-10-01

    Full Text Available Hepatocellular carcinoma (HCC is increasingly considered an issue of global importance. Its rates of incidence and mortality have been markedly increasing over the last decades. Among risk factors, some should be highlighted, namely the infections by hepatitis B and C virus, as well as clinical cases of cirrhosis. HCC is characterized as asymptomatic disease in the initial stages which most often leads to a late diagnosis. At molecular and genetic level HCC represents a highly complex tumor entity, including a wide variety of mutations, thus accounting for different mechanisms of resistance towards therapeutic approaches. In particular, mutations of the TP53 gene, as well as a deregulation between the expression of pro- and anti-apoptotic proteins of the BCL-2 family are observed. Regarding treatment modalities, surgical procedures offer the best chance of cure, however, due to a late diagnosis, most of concerned patients cannot be subjected to them. Chemotherapy and radiotherapy are also ineffective, and currently, the treatment with sorafenib is the most commonly used systemic therapy although it can only increase the patient survival for some months. In this sense, a quick and accurate investigation is of utmost importance in order to develop ways of early diagnosis as well as new therapies for HCC.

  7. Transcatheter arterial embolization for bone metastases from hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Uemura, Akihiro; Fujimoto, Hajime; Osaka, Iwao; Yasuda, Shigeo; Goto, Nobuaki; Shinozaki, Masami; Ito, Hisao

    2001-01-01

    The objective of this study was to determine which of the following three methods is the most effective for the treatment of bone metastases from hepatocellular carcinoma (HCC): transcatheter arterial embolization (TAE); combination of TAE and external radiotherapy; or external radiotherapy alone. Thirty-nine metastatic bone lesions from HCC in 33 patients were retrospectively reviewed. Each lesion underwent either TAE alone (group A, n=11), TAE followed by radiotherapy (group B, n=17), or radiotherapy alone (group C, n=11). They were evaluated on the following subjects: pain relief; improvement of daily activities; and complications. Each treatment was effective for pain relief (89-94%) and improvement of daily activities (73-82%). The mean time interval from the beginning of each treatment to the onset of initial pain relief was 4.7 days in group A, 4.8 days in group B, and 15 days in group C. Recurrence of the pain after the initial pain relief was noted in 75% in group A, 20% in group B, and 88% in group C. Pyrexia and local pain commonly occurred after TAE. In conclusion, TAE is effective in relieving pain immediately and in improving the patients' daily activities. The combination of TAE and radiotherapy is recommended for permanent pain relief. (orig.)

  8. Regorafenib for the treatment of unresectable hepatocellular carcinoma.

    Science.gov (United States)

    Rimassa, Lorenza; Pressiani, Tiziana; Personeni, Nicola; Santoro, Armando

    2017-07-01

    Sorafenib is the standard of care for patients with advanced hepatocellular carcinoma (HCC) and well preserved liver function. However, until recent approval of regorafenib by the Food and Drug Administration (FDA), no effective therapeutic options were available for patients resistant to sorafenib. Areas covered: The present article reviews the preclinical and clinical data of regorafenib, putting them into the context of current and future landscape of treatment options for patients with HCC. Recently, the randomized, placebo-controlled, Phase III RESORCE trial, demonstrated a statistically and clinically significant increase in overall survival from 7.8 months with placebo to 10.6 months with regorafenib in patients progressing on sorafenib. Furthermore, the study showed a significant improvement in all the other efficacy endpoints. Main adverse events were hypertension, hand-foot skin reaction, fatigue and diarrhea, with no negative impact on quality of life. Expert commentary: Regorafenib is a recently approved treatment option for HCC patients who have been previously treated with sorafenib. The RESORCE trial demonstrates the beneficial effect of a sequential approach involving two multikinase inhibitors, namely sorafenib and regorafenib, whose antitumor activity extends beyond their antiangiogenic functions.

  9. Reversibility of regorafenib effects in hepatocellular carcinoma cells

    Science.gov (United States)

    D’Alessandro, Rosalba; Refolo, Maria G.; Lippolis, Catia; Messa, Caterina; Cavallini, Aldo; Rossi, Roberta; Resta, Leonardo; Di Carlo, Antonio

    2013-01-01

    Purpose Multikinase growth inhibitors inhibit their target kinases with varying potency. Patients often require lower doses or therapy breaks due to drug toxicities. To evaluate the effects of drug withdrawal on hepatocellular carcinoma cells after incubation with growth-inhibitory concentrations of regorafenib, cell growth, migration and invasion, and signaling were examined. Methods Cell proliferation, motility, and invasion were analyzed by MTT, wound healing, and invasion assays, respectively, and MAPK pathway protein markers were analyzed by Western blot. Results After regorafenib removal, cell growth, migration, and invasion recovered. Repeated drug exposure resulted in changes in cell growth patterns. Recovery could be blocked by sub-growth-inhibitory concentrations of either doxorubicin or vitamin K1. Recovery of growth was associated with increased phospho-JNK, phospho-p38, and phospho-STAT3 levels. The recovery of growth, migration, and signaling were blocked by a JNK inhibitor. Conclusions Removal of regorafenib from growth-inhibited cells resulted in a JNK-dependent recovery of growth and migration. PMID:23959464

  10. Regorafenib delays the proliferation of hepatocellular carcinoma by inducing autophagy.

    Science.gov (United States)

    Han, Rui; Li, Shixin

    2018-04-02

    The aim of the present study was to investigate the effects of regorafenib on hepatocellular carcinoma autophagy, thereby supressing the malignancy of HCC. First, HepG2 and Hep3B cell autophagy was investigated using GFP-LC3 transfection after the treatment of regorafenib. Then, the activation of Akt/mTOR signaling was analyzed using western blot. Our data showed that liver cancer cell autophagy was significantly induced by 20 μM regorafenib using GFP-LC3 transfection. Meanwhile, regorafenib-induced cell death could largely be abolished by 3-MA or CQ treatment, suggesting that regorafenib-induced HepG2 cell death was partially dependent on autophagy. Moreover, the activation of Akt/mTOR signaling was inhibited by regorafenib pre-incubation. MTT assay showed the combination use of regorafenib and CDDP led to a stronger growth inhibitory effect on HepG2 and Hep3B cells. In summary, regorafenib may acts an adjunctive therapy for liver cancer patients via modulating autophagy-dependent cell death even when apoptosis resistance is induced in cancer cells.

  11. Transarterial chemoembolization with drug-eluting beads in hepatocellular carcinoma

    Science.gov (United States)

    Nam, Hee Chul; Jang, Bohyun; Song, Myeong Jun

    2016-01-01

    Transarterial chemoembolization (TACE) is a widely used standard treatment for patients with hepatocellular carcinoma (HCC) who are not suitable candidates for curative treatments. The rationale for TACE is that intra-arterial chemotherapy using lipiodol and chemotherapeutic agents, followed by selective vascular embolization, results in a strong cytotoxic effect as well as ischemia (conventional TACE). Recently, drug-eluting beads (DC Beads®) have been developed for transcatheter treatment of HCC to deliver higher doses of the chemotherapeutic agent and to prolong contact time with the tumor. DC Beads® can actively sequester doxorubicin hydrochloride from solution and release it in a controlled sustained fashion. Treatment with DC Beads® substantially reduced the amount of chemotherapeutic agent that reached the systemic circulation compared with conventional, lipiodol-based regimens, significantly reducing drug-related adverse events. In this article, we describe the treatment response, survival, and safety of TACE used with drug-eluting beads for the treatment of HCC and discuss future therapeutic possibilities. PMID:27833376

  12. Initial clinical outcomes of proton beam radiotherapy for hepatocellular carcinoma.

    Science.gov (United States)

    Yu, Jeong Il; Yoo, Gyu Sang; Cho, Sungkoo; Jung, Sang Hoon; Han, Youngyih; Park, Seyjoon; Lee, Boram; Kang, Wonseok; Sinn, Dong Hyun; Paik, Yong-Han; Gwak, Geum-Youn; Choi, Moon Seok; Lee, Joon Hyeok; Koh, Kwang Cheol; Paik, Seung Woon; Park, Hee Chul

    2018-03-01

    This study aimed to evaluate the initial outcomes of proton beam therapy (PBT) for hepatocellular carcinoma (HCC) in terms of tumor response and safety. HCC patients who were not indicated for standard curative local modalities and who were treated with PBT at Samsung Medical Center from January 2016 to February 2017 were enrolled. Toxicity was scored using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Tumor response was evaluated using modified Response Evaluation Criteria in Solid Tumors (mRECIST). A total of 101 HCC patients treated with PBT were included. Patients were treated with an equivalent dose of 62-92 GyE 10 . Liver function status was not significantly affected after PBT. Greater than 80% of patients had Child-Pugh class A and albumin-bilirubin (ALBI) grade 1 up to 3-months after PBT. Of 78 patients followed for three months after PBT, infield complete and partial responses were achieved in 54 (69.2%) and 14 (17.9%) patients, respectively. PBT treatment of HCC patients showed a favorable infield complete response rate of 69.2% with acceptable acute toxicity. An additional follow-up study of these patients will be conducted.

  13. Interventional Oncology in Hepatocellular Carcinoma: Progress Through Innovation.

    Science.gov (United States)

    Mu, Lin; Chapiro, Julius; Stringam, Jeremiah; Geschwind, Jean-François

    The clinical management of hepatocellular carcinoma has evolved greatly in the last decade mostly through recent technical innovations. In particular, the application of cutting-edge image guidance has led to minimally invasive solutions for complex clinical problems and rapid advances in the field of interventional oncology. Many image-guided therapies, such as transarterial chemoembolization and radiofrequency ablation, have meanwhile been fully integrated into interdisciplinary clinical practice, whereas others are currently being investigated. This review summarizes and evaluates the most relevant completed and ongoing clinical trials, provides a synopsis of recent innovations in the field of intraprocedural imaging and tumor response assessment, and offers an outlook on new technologies, such as radiopaque embolic materials. In addition, combination therapies consisting of locoregional therapies and systemic molecular targeted agents (e.g., sorafenib) remain of major interest to the field and are also discussed. Finally, we address the many substantial advances in immune response pathways that have been related to the systemic effects of locoregional therapies. Knowledge of these new developments is crucial as they continue to shape the future of cancer treatment, further establishing interventional oncology along with surgical, medical, and radiation oncology as the fourth pillar of cancer care.

  14. Downregulation of CCR1 inhibits human hepatocellular carcinoma cell invasion

    International Nuclear Information System (INIS)

    Wu Xiaofeng; Fan Jia; Wang Xiaoying; Zhou Jian; Qiu Shuangjian; Yu Yao; Liu Yinkun; Tang Zhaoyou

    2007-01-01

    CC chemokine receptor 1 (CCR1) has an important role in the recruitment of leukocytes to the site of inflammation. The migration and metastasis of tumor cells shares many similarities with leukocyte trafficking, which is mainly regulated by chemokine receptor-ligand interactions. CCR1 is highly expressed in hepatocellular carcinoma (HCC) cells and tissues with unknown functions. In this study, we silenced CCR1 expression in the human HCC cell line HCCLM3 using artificial microRNA (miRNA)-mediated RNA interference (RNAi) and examined the invasiveness and proliferation of CCR1-silenced HCCLM3 cells and the matrix metalloproteinase (MMP) activity. The miRNA-mediated knockdown expression of CCR1 significantly inhibited the invasive ability of HCCLM3 cells, but had only a minor effect on the cellular proliferation rate. Moreover, CCR1 knockdown significantly reduced the secretion of MMP-2. Together, these findings indicate that CCR1 has an important role in HCCLM3 invasion and that CCR1 might be a new target of HCC treatment

  15. Aberrant Lipid Metabolism in Hepatocellular Carcinoma Revealed by Liver Lipidomics

    Directory of Open Access Journals (Sweden)

    Zhao Li

    2017-11-01

    Full Text Available Background: The aim of this study was to characterize the disorder of lipid metabolism in hepatocellular carcinoma (HCC. HCC is a worldwide disease. The research into the disorder of lipid metabolism in HCC is very limited. Study of lipid metabolism in liver cancer tissue may have the potential to provide new insight into HCC mechanisms. Methods: A lipidomics study of HCC based on Ultra high performance liquid chromatography-electronic spray ionization-QTOF mass spectrometer (UPLC-ESI-QTOF MS and Matrix assisted laser desorption ionization-fourier transform ion cyclotron resonance mass spectrometer (MALDI-FTICR MS was performed. Results: Triacylglycerols (TAGs with the number of double bond (DB > 2 (except 56:5 and 56:4 TAG were significantly down-regulated; conversely, others (except 52:2 TAG were greatly up-regulated in HCC tissues. Moreover, the more serious the disease was, the higher the saturated TAG concentration and the lower the polyunsaturated TAG concentration were in HCC tissues. The phosphatidylcholine (PC, phosphatidylethanolamine (PE and phosphatidylinositol (PI were altered in a certain way. Sphingomyelin (SM was up-regulated and ceramide (Cer were down-regulated in HCC tissues. Conclusions: To our knowledge, this is the first such report showing a unique trend of TAG, PC, PE and PI. The use of polyunsaturated fatty acids, like eicosapentanoic and docosahexanoic acid, as supplementation, proposed for the treatment of Non-alcoholic steatohepatitis (NASH, may also be effective for the treatment of HCC.

  16. Surgical outcomes of hepatocellular carcinoma invading hepatocaval confluence.

    Science.gov (United States)

    Li, Wei; Wu, Hong; Han, Jun

    2016-12-01

    Combined liver and inferior vena cava (IVC) resection followed by IVC and/or hepatic vein reconstruction (HVR) is a curative operation for selected patients with hepatocellular carcinoma (HCC) invading the hepatocaval confluence. The present study aimed to elucidate the prognostic factors for patients with HCC invading the hepatocaval confluence. Forty-two consecutive patients underwent hepatectomy, combined with IVC replacement and/or HVR for HCC between January 2009 and December 2014 were included in this study. The cases were divided into three groups based on the surgical approaches of HVR: group 1 (n=13), tumor invaded the hepatocaval confluence but with one or two hepatic veins intact in the residual liver, thus only the replacement of IVC, not HVR; group 2 (n=23), the hepatic vein of the residual liver was also partially invaded, and the hepatic vein defect was repaired with patches locally; group 3 (n=6), three hepatic veins at the hepatocaval confluence were infiltrated, and the hepatic vein remnant was re-implanted onto the side of the tube graft. The patient characteristics, intra- and postoperative results, and long-term overall survival were compared among the three groups. The survival-related factors were analyzed by univariate and multivariate analysis. The group 1 had higher preoperative alpha-fetoprotein level (PHVR (PHVR (group 1). HVR was one of the unfavorable prognostic factors of overall survival.

  17. The multifaceted role of podoplanin expression in hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Andreea Cioca

    2017-02-01

    Full Text Available The role of podoplanin in hepatocellular carcinoma (HCC is not clear yet. The aim of our study was to evaluate the expression of podoplanin in HCC and to determine its role in hepatocarcinogenesis. We performed immunohistochemistry with monoclonal D2-40 antibody, on paraffin-embedded tissue sections of 72 patients diagnosed with HCC. Lymphatic vessels density (LVD was increased in patients who had vascular invasion at the time of diagnosis (P=0.018 and in those with associated cirrhosis (P=0.006. Tumor cells showing podoplanin expression were correlated with histological grade (P=0.040. Podoplanin-expressing cancer associated fibroblasts (CAFs were correlated with both LVD (P=0.019 and tumor cells (P=0.015. Our results sustain the dual role of podoplanin in HCC by its involvement in both HCC tumorigenesis, lymphatic neovascularization and tumor invasion invasiveness. A possible crosstalk between epithelial and stromal tumor cells in HCC tumor microenvironment may be mediated by podoplanin, but this hypothesis needs further studies to elucidate this interrelation.

  18. The multifaceted role of podoplanin expression in hepatocellular carcinoma.

    Science.gov (United States)

    Cioca, Andreea; Ceausu, Amalia R; Marin, Irina; Raica, Marius; Cimpean, Anca M

    2017-02-13

    The role of podoplanin in hepatocellular carcinoma (HCC) is not clear yet. The aim of our study was to evaluate the expression of podoplanin in HCC and to determine its role in hepatocarcinogenesis. We performed immunohistochemistry with monoclonal D2-40 antibody, on paraffin-embedded tissue sections of 72 patients diagnosed with HCC. Lymphatic vessels density (LVD) was increased in patients who had vascular invasion at the time of diagnosis (P=0.018) and in those with associated cirrhosis (P=0.006). Tumor cells showing podoplanin expression were correlated with histological grade (P=0.040). Podoplanin-expressing cancer associated fibroblasts (CAFs) were correlated with both LVD (P=0.019) and tumor cells (P=0.015). Our results sustain the dual role of podoplanin in HCC by its involvement in both HCC tumorigenesis, lymphatic neovascularization and tumor invasion invasiveness. A possible crosstalk between epithelial and stromal tumor cells in HCC tumor microenvironment may be mediated by podoplanin, but this hypothesis needs further studies to elucidate this interrelation.

  19. Liver transplantation for hepatocellular carcinoma: the Hong Kong experience.

    Science.gov (United States)

    Ng, Kelvin K; Lo, Chung Mau; Chan, See Ching; Chok, Kenneth S; Cheung, Tan-To; Fan, Sheung Tat

    2010-09-01

    Orthotopic liver transplantation (OLT) is the best treatment option for selected patients with hepatocellular carcinoma (HCC) with the background of cirrhosis since this treatment modality can cure both diseases at once. Over the years, the applicability of OLT for HCC has evolved. In Asia, including Hong Kong, a shortage of deceased donor liver grafts is a universal problem having to be faced in all transplant centers. Living-donor liver transplant (LDLT) has therefore been developed to counteract organ shortage and the high prevalence of HCC. The application of LDLT for HCC is a complex process involving donor voluntarism, selection criteria for the recipient and justification with respect to long-term survival in comparison to the result of deceased donor liver transplant. This article reviews the authors' experience with OLT for HCC patients in Hong Kong, with emphasis on the applicability and outcome of LDLT for HCC. Donor voluntarism has a significant impact on the application of LDLT. "Fast-track" LDLT in the setting of recurrence following curative treatment carries a high risk of recurrence even though the tumor stage fulfills the standard criteria. Although the survival outcome may be worse following LDLT than DDLT for HCC, LDLT is still the main treatment option for patients with transplantable HCC in Hong Kong, and a reasonable survival outcome can be achieved in selected patients with extended indications. It is particularly true that LDLT provides the only hope for patients with advanced HCC under the constricting problem of organ shortage.

  20. Changes in arginase isoenzymes pattern in human hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Chrzanowska, Alicja; Krawczyk, Marek; Baranczyk-Kuzma, Anna

    2008-01-01

    Hepatocellular carcinoma (HCC) is one of the most common tumors worldwide affecting preferentially patients with liver cirrhosis. The studies were performed on tissues obtained during surgery from 50 patients with HCC, 40 with liver cirrhosis and 40 control livers. It was found that arginase activity in HCC was nearly 5- and 15-fold lower than in cirrhotic and normal livers, respectively. Isoenzymes AI (so-called liver-type arginase) and AII (extrahepatic arginase) were identified by Western blotting in all studied tissues, however the amount of AI, as well as the expression of AI-mRNA were lower in HCC, in comparison with normal liver, and those of AII were significantly higher. Since HCC is arginine-dependent, and arginine is essential for cells growth, the decrease of AI may preserve this amino acid within tumor cells. Concurrently, the rise of AII can increase the level of polyamines, compounds crucial for cells proliferation. Thus, both arginase isoenzymes seem to participate in liver cancerogenesis.

  1. Improving clinical trial design for hepatocellular carcinoma treatments

    Directory of Open Access Journals (Sweden)

    Robert G. Gish

    2011-12-01

    Full Text Available Despite its place as the third leading cause of cancer deaths worldwide, there are currently no approved chemotherapeutic agents, devices or techniques to treat hepatocellular carcinoma. Importantly, there have been no phase III studies demonstrating survival benefit, nor any randomized studies of treatment except for transarterial chemoembolization and most recently sorafenib. The importance of well-designed clinical trials of agents to treat HCC has never been greater. However, general clinical study design issues, combined with HCC-specific issues pose significant challenges in structuring such studies. HCC-related challenges include the heterogeneity of this cancer and the fact that it is frequently accompanied by significant comorbidities at diagnosis, such as active hepatitis B or C virus replication, substantial past or on-going alcohol use, and cirrhosis, itself often a fatal disease. The recently published comparison of a newer treatment, nolatrexed to doxorubicin, and comments about this study’s initial HCC diagnostic criteria, staging system, comparator therapy and choice of endpoints have provided a platform to discuss the challenges unique to the design of HCC clinical trials. The difficulty in accurately framing study results obtained from the constantly changing HCC clinical landscape and approaches to meet these challenges will be reviewed.

  2. Small hepatocellular carcinomas in chronic liver disease: Detection with SPECT

    Energy Technology Data Exchange (ETDEWEB)

    Kudo, M.; Hirasa, M.; Takakuwa, H.; Ibuki, Y.; Fujimi, K.; Miyamura, M.; Tomita, S.; Komori, H.; Todo, A.; Kitaura, Y.

    1986-06-01

    Single-photon emission computed tomography (SPECT) performed using a rotating gamma camera was compared with ..cap alpha../sub 1/-fetoprotein (AFP) assay, conventional liver scintigraphy, ultrasound (US) imaging, computed tomography (CT), and selective celiac angiography in 40 patients with a total of 50 small hepatocellular carcinomas (HCCs;<5 cm). The detection rates of US and CT were determined on an initial screening study and on a second, more precisely focused study. The detection rate of small HCCs by the various modalities was as follows: AFP, 13%; liver scintigraphy, 36%; SPECT, 72%; initial screening US, 80%; second, more precise US studies, 94%; initial screening CT, 64%; second, more precise CT study, 82%; angiography, 88%. Although SPECT was inferior to the initial screening US examination in detecting HCCs less than 2 cm in size, its sensitivity was identical to that of the initial screening US study for detecting HCCs of 2-5 cm. The combination of SPECT and US was an excellent method for the early detection of HCCs, yielding a detection rate of 94%.

  3. Transcatheter Arterial Chemoembolization Based on Hepatic Hemodynamics for Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Satoru Murata

    2013-01-01

    Full Text Available Hepatocellular carcinoma (HCC is the sixth most common cancer and the third leading cause of cancer-related deaths in the world. The Barcelona Clinic Liver Cancer (BCLC classification has recently emerged as the standard classification system for clinical management of patients with HCC. According to the BCLC staging system, curative therapies (resection, transplantation, and percutaneous ablation can improve survival in HCC patients diagnosed at an early stage and offer potential long-term curative effects. Patients with intermediate-stage HCC benefit from transcatheter arterial chemoembolization (TACE, and those diagnosed at an advanced stage receive sorafenib, a multikinase inhibitor, or conservative therapy. Most patients receive palliative or conservative therapy only, and approximately 50% of patients with HCC are candidates for systemic therapy. TACE is often recommended for advanced-stage HCC patients all over the world because these patients desire therapy that is more effective than systemic chemotherapy or conservative treatment. This paper aims to summarize both the published data and important ongoing studies for TACE and to discuss technical improvements in TACE for advanced-stage HCC.

  4. Treatment of hepatocellular carcinoma: A single-center experience

    International Nuclear Information System (INIS)

    Florio, Francesco; Nardella, Michele; Balzano, Silverio; Caturelli, Eugenio; Siena, Domenico; Cammisa, Mario

    1997-01-01

    Purpose. The comparative efficacy of transcatheter arterial chemoembolization (TACE) and percutaneous ethanol injection (PEI) in the treatment of hepatocellular carcinoma (HCC) was investigated. Methods. Two hundred and sixty consecutive patients were retrospectively analyzed: 156 had received between one and six chemoembolization sessions at 3-month intervals, 33 had had PEI, and the remaining 71 patients refused any treatment. The follow-up ranged from 3 to 36 months. Survival rates were statistically analyzed by life-table analysis. Results. Patients' survival was affected by the number of nodules and by the Child's and Okuda's classes; no relationship was found between survival rates and the histologic grade or vascular supply of the tumor. In the case of a single lesion of Okuda's class I, TACE was more effective than PEI. In multifocal HCC, TACE was better than no treatment in Okuda's class I and Child's class A. Conclusion. We suggest TACE as the treatment of choice in Child A or Okuda I patients with multifocal HCCs; it seems of little help in Child B-C or Okuda II-III patients

  5. Radiotherapy for hepatocellular carcinoma. Regarding solitary tumor on radiologic examinations

    International Nuclear Information System (INIS)

    Kawashima, Mitsuhiko; Tokuuye, Koichi; Sumi, Minako; Kagami, Yashikazu; Murayama, Shigeyuki; Nakayama, Hidetsugu; Imai, Atsushi; Ando, Kou; Ikeda, Hiroshi

    1997-01-01

    To evaluate the effect of radiotherapy (RT) on hepatocellular carcinoma (HCC) that appears as a solitary nodule on radiologic studies. We irradiated 17 patients with solitary HCC lesions (25-150 mm in diameter) with approximately 60 Gy (range 50-70 Gy). Patients underwent dynamic CT and/or ultrasound imaging at 3-month intervals after treatment. Patients were classified based on lesion size, degree of cirrhosis (Child A. 6; Child B, 6; Child C, 5), and whether they had received other therapy such as transarterial chemoembolization (TACE). The responses were classified as complete, partial, no change, or progression. The median survival was 12.8 months for all 17 patients, with 1-, 2-, and 3-year cumulative survival rates of 59%, 35% and 24%, respectively. Patients classified as Child A showed significantly longer survival than those classified as either Child B (p<0.04) or C (p<0.01). Four of the five Child C patients died of liver failure within 6 months after RT despite the absence of tumor recurrence. The initial tumor diameter, concurrent treatment with TACE, and radiation dose showed no significant effect on survival. Survival in patients with solitary HCC lesions appears to be affected mainly by the degree of liver dysfunction, and not the initial tumor diameter, radiation dose, or concurrent use of TACE. (author)

  6. Tissue- and Serum-Associated Biomarkers of Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Ranjit Chauhan

    2016-01-01

    Full Text Available Hepatocellular carcinoma (HCC, one of the leading causes of cancer deaths in the world, is offering a challenge to human beings, with the current modes of treatment being a palliative approach. Lack of proper curative or preventive treatment methods encouraged extensive research around the world with an aim to detect a vaccine or therapeutic target biomolecule that could lead to development of a drug or vaccine against HCC. Biomarkers or biological disease markers have emerged as a potential tool as drug/vaccine targets, as they can accurately diagnose, predict, and even prevent the diseases. Biomarker expression in tissue, serum, plasma, or urine can detect tumor in very early stages of its development and monitor the cancer progression and also the effect of therapeutic interventions. Biomarker discoveries are driven by advanced techniques, such as proteomics, transcriptomics, whole genome sequencing, micro- and micro-RNA arrays, and translational clinics. In this review, an overview of the potential of tissue- and serum-associated HCC biomarkers as diagnostic, prognostic, and therapeutic targets for drug development is presented. In addition, we highlight recently developed micro-RNA, long noncoding RNA biomarkers, and single-nucleotide changes, which may be used independently or as complementary biomarkers. These active investigations going on around the world aimed at conquering HCC might show a bright light in the near future.

  7. Hepatocellular Carcinoma in Pakistan: National Trends and Global Perspective

    Science.gov (United States)

    Hafeez Bhatti, Abu Bakar; Dar, Faisal Saud; Waheed, Anum; Shafique, Kashif; Sultan, Faisal; Shah, Najmul Hassan

    2016-01-01

    Hepatocellular carcinoma (HCC) ranks second amongst all causes of cancer deaths globally. It is on a rise in Pakistan and might represent the most common cancer in adult males. Pakistan contributes significantly to global burden of hepatitis C, which is a known risk factor for HCC, and has one of the highest prevalence rates (>3%) in the world. In the absence of a national cancer registry and screening programs, prevalence of hepatitis and HCC only represents estimates of the real magnitude of this problem. In this review, we present various aspects of HCC in Pakistan, comparing and contrasting it with the global trends in cancer care. There is a general lack of awareness regarding risk factors of HCC in Pakistani population and prevalence of hepatitis C has increased. In addition, less common risk factors are also on a rise. Majority of patients present with advanced HCC and are not eligible for definitive treatment. We have attempted to highlight issues that have a significant bearing on HCC outcome in Pakistan. A set of strategies have been put forth that can potentially help reduce incidence and improve HCC outcome on national level. PMID:26955390

  8. Hepatocellular Carcinoma in Pakistan: National Trends and Global Perspective

    Directory of Open Access Journals (Sweden)

    Abu Bakar Hafeez Bhatti

    2016-01-01

    Full Text Available Hepatocellular carcinoma (HCC ranks second amongst all causes of cancer deaths globally. It is on a rise in Pakistan and might represent the most common cancer in adult males. Pakistan contributes significantly to global burden of hepatitis C, which is a known risk factor for HCC, and has one of the highest prevalence rates (>3% in the world. In the absence of a national cancer registry and screening programs, prevalence of hepatitis and HCC only represents estimates of the real magnitude of this problem. In this review, we present various aspects of HCC in Pakistan, comparing and contrasting it with the global trends in cancer care. There is a general lack of awareness regarding risk factors of HCC in Pakistani population and prevalence of hepatitis C has increased. In addition, less common risk factors are also on a rise. Majority of patients present with advanced HCC and are not eligible for definitive treatment. We have attempted to highlight issues that have a significant bearing on HCC outcome in Pakistan. A set of strategies have been put forth that can potentially help reduce incidence and improve HCC outcome on national level.

  9. Yttrium 90 microspheres for the treatment of hepatocellular carcinoma.

    Science.gov (United States)

    Memon, Khairuddin; Lewandowski, Robert J; Riaz, Ahsun; Salem, Riad

    2013-01-01

    Yttrium-90 microspheres are radioactive particles which are increasingly being employed for treating patients with unresectable hepatocellular carcinoma (HCC). The procedure is called radioembolization. It involves the injection of micron-sized embolic particles loaded with a radioisotope by use of transarterial techniques. Because of the sensitivity of liver parenchyma and relative insensitivity of tumor, external radiation has played a limited role in treating HCC. (90)Y administered via arterial route directs the highly concentrated radiation to the tumor while healthy liver parenchyma is relatively spared due to its preferential blood supply from portal venous blood. This technique has proven useful for the majority of patients with HCC as most of them present in advanced stage, beyond potentially curative options (resection/liver transplantation). (90)Y microspheres can be used in downstaging large tumors to bring within transplantable criteria, in patients with portal venous thrombosis due to tumor invasion and as palliative therapy. There are two available devices for (90)Y administration; TheraSphere® (glass based) and SIR-Spheres® (resin based). The procedure is performed on an outpatient basis. The incidence of complications is comparatively less and may include nausea, fatigue, abdominal pain, hepatic dysfunction, biliary injury, fibrosis, radiation pneumonitis, GI ulcers, and vascular injury; however, these can be avoided by meticulous pretreatment assessment, careful patient selection, and adequate dosimetry. This article explores the technical and clinical aspects of (90)Y radioembolization with keeping emphasis on patient selection, uses, and complications.

  10. Hepatitis B Virus Infection, Genetic Susceptibility and Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Juan Wen

    2015-12-01

    Full Text Available Liver cancer is a sever cancer burden in the world, especially in developing countries. Its late diagnosis and high mortality rate urges early prediction. Hepatocellular carcinoma (HCC is the major histopathological type of liver cancer. Chronic infection with hepatitis B virus (HBV is a well-established risk factor for HCC. On one side, HBV sequence variation may influence the outcome of HBV infection and the development of HCC. At least ten HBV genotypes (A to J are identified. Several HBV genotypes and mutations in pre-S and pre-core/core promoter regions are closely associated with HCC pathogenesis, and have been regarded as biomarkers to predict the occurrence of HCC. On the other side, only a small fraction of chronic hepatitis B patients developed HCC, and some HCC cases were diagnosed with no known predisposing risk factors, suggesting host genetic variations may also play important roles in the carcinogenesis. In this review, we summarized current findings of HBV genotypes and mutations, host genetic variations and their interactions involved in HCC carcinogenesis. Understanding the key viral and host genetic variations is essential for generating effective predictive biomarkers for HCC development.

  11. Review of hepatocellular carcinoma: Epidemiology, etiology, and carcinogenesis

    Directory of Open Access Journals (Sweden)

    Yezaz Ahmed Ghouri

    2017-01-01

    Full Text Available Since the 1970s, the epidemic of hepatocellular carcinoma (HCC has spread beyond the Eastern Asian predominance and has been increasing in Northern hemisphere, especially in the United States (US and Western Europe. It occurs more commonly in males in the fourth and fifth decades of life. Among all cancers, HCC is one of the fastest growing causes of death in the US and poses a significant economic burden on healthcare. Chronic liver disease due to hepatitis B virus or hepatitis C virus and alcohol accounts for the majority of HCC cases. Incidence of nonalcoholic fatty liver disease has been on the risem and it has also been associated with the development of HCC. Its pathogenesis varies based on the underlying etiological factor although majority of cases develop in the setting of background cirrhosis. Carcinogenesis of HCC includes angiogenesis, chronic inflammation, and tumor macroenvironment and microenvironment. There is a significant role of both intrinsic genetic risk factors and extrinsic influences such as alcohol or viral infections that lead to the development of HCC. Understanding its etiopathogenesis helps select appropriate diagnostic tests and treatments.

  12. Review of hepatocellular carcinoma: Epidemiology, etiology, and carcinogenesis.

    Science.gov (United States)

    Ghouri, Yezaz Ahmed; Mian, Idrees; Rowe, Julie H

    2017-01-01

    Since the 1970s, the epidemic of hepatocellular carcinoma (HCC) has spread beyond the Eastern Asian predominance and has been increasing in Northern hemisphere, especially in the United States (US) and Western Europe. It occurs more commonly in males in the fourth and fifth decades of life. Among all cancers, HCC is one of the fastest growing causes of death in the US and poses a significant economic burden on healthcare. Chronic liver disease due to hepatitis B virus or hepatitis C virus and alcohol accounts for the majority of HCC cases. Incidence of nonalcoholic fatty liver disease has been on the risem and it has also been associated with the development of HCC. Its pathogenesis varies based on the underlying etiological factor although majority of cases develop in the setting of background cirrhosis. Carcinogenesis of HCC includes angiogenesis, chronic inflammation, and tumor macroenvironment and microenvironment. There is a significant role of both intrinsic genetic risk factors and extrinsic influences such as alcohol or viral infections that lead to the development of HCC. Understanding its etiopathogenesis helps select appropriate diagnostic tests and treatments.

  13. A Surgical Perspective on Targeted Therapy of Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Claire Faltermeier

    2015-09-01

    Full Text Available Hepatocellular carcinoma (HCC, the second leading cause of cancer deaths worldwide, is difficult to treat and highly lethal. Since HCC is predominantly diagnosed in patients with cirrhosis, treatment planning must consider both the severity of liver disease and tumor burden. To minimize the impact to the patient while treating the tumor, techniques have been developed to target HCC. Anatomical targeting by surgical resection or locoregional therapies is generally reserved for patients with preserved liver function and minimal to moderate tumor burden. Patients with decompensated cirrhosis and small tumors are optimal candidates for liver transplantation, which offers the best chance of long-term survival. Yet, only 20%–30% of patients have disease amenable to anatomical targeting. For the majority of patients with advanced HCC, chemotherapy is used to target the tumor biology. Despite these treatment options, the five-year survival of patients in the United States with HCC is only 16%. In this review we provide a comprehensive overview of current approaches to target HCC. We also discuss emerging diagnostic and prognostic biomarkers, novel therapeutic targets identified by recent genomic profiling studies, and potential applications of immunotherapy in the treatment of HCC.

  14. Galectin-1-Induced Autophagy Facilitates Cisplatin Resistance of Hepatocellular Carcinoma.

    Directory of Open Access Journals (Sweden)

    Yu-Chi Su

    Full Text Available Hepatocellular carcinoma (HCC is one of the most common cancers in Taiwan. Although chemotherapy is the primary treatment for HCC patients, drug resistance often leads to clinical failure. Galectin-1 is a beta-galactoside binding lectin which is up-regulated in HCC patients and promotes tumor growth by mediating cancer cell adhesion, migration and proliferation, but its role in chemoresistance of HCC is poorly understood. In this study we found that galectin-1 is able to lead to chemoresistance against cisplatin treatment, and subsequent inhibition has reversed the effect of cell death in HCC cells. Moreover, galectin-1 was found to induce autophagic flux in HCC cells. Inhibition of autophagy by inhibitors or knockdown of Atg5 cancels galectin-1-induced cisplatin resistance in HCC cells. Increase of mitophagy triggered by galectin-1 was found to reduce the mitochondrial potential loss and apoptosis induced by cisplatin treatment. Finally, using an in situ hepatoma mouse model, we clearly demonstrated that inhibition of galectin-1 by thiodigalactoside could significantly augment the anti-HCC effect of cisplatin. Taken together, our findings offer a new insight into the chemoresistance galectin-1 causes against cisplatin treatment, and points to a potential approach to improve the efficacy of cisplatin in the treatment of HCC patients.

  15. Diagnostic and prognostic potential of serum miR-132/212 cluster in patients with hepatocellular carcinoma.

    Science.gov (United States)

    Wang, Feng; Wang, Jun; Ju, Linlin; Chen, Lin; Cai, Weihua; Yang, Jialin

    2018-01-01

    Background It has been reported that both of the miR-132/212 (micro-RNA) cluster members, miR-132 and miR-212, are downregulated in hepatocellular carcinoma. Nevertheless, the expression pattern and clinical utility of serum miR-132/212 in hepatocellular carcinoma are still unknown. Methods In this study, serum concentrations of miR-132 and miR-212 were measured in 80 hepatocellular carcinoma patients, 51 controls with chronic liver diseases and 42 healthy volunteers by using quantitative real-time polymerase chain reaction. Results In hepatocellular carcinoma patients, serum concentrations of miR-132 and miR-212 were significantly reduced and strongly correlated (r = 0.603, p hepatocellular carcinoma. Moreover, the combination of serum miR-132, miR-212 and alpha-fetoprotein improved the diagnostic efficiency for hepatocellular carcinoma, especially in sensitivity and negative predictive value. Serum miR-132 was associated with tumour differentiation degree ( p = 0.021) and tumour-node-metastasis stage ( p = 0.002); serum miR-212 correlated with tumour size ( p = 0.023) and tumour-node-metastasis stage ( p = 0.007). Kaplan-Meier analyses indicated poorer overall survival in hepatocellular carcinoma patients with lower serum concentrations of miR-132 ( p hepatocellular carcinoma.

  16. Linc-POU3F3 is overexpressed in hepatocellular carcinoma and regulates cell proliferation, migration and invasion.

    Science.gov (United States)

    Li, Yichun; Li, Yannan; Wang, Dan; Meng, Qingdong

    2018-06-12

    Linc-POU3F3 showed an up-regulated tendency and functioned as tumor promoter in glioma, esophageal cancer and colorectal cancer. There was no report about the expression pattern and clinical value of linc-POU3F3 in hepatocellular carcinoma. Thus, the purpose of our study is to explore the clinical significance and biological role of linc-POU3F3 in hepatocellular carcinoma. Our results suggested that levels of linc-POU3F3 were dramatically increased in hepatocellular carcinoma tissues and cell lines compared with paired normal hepatic tissues and normal hepatic cell line, respectively. Levels of linc-POU3F3 were positively correlated with clinical stage, tumor size, vascular invasion and metastasis. Moreover, high-expression of linc-POU3F3 was an independent prognostic factor for hepatocellular carcinoma patients. The gain- and loss-of-function experiments showed that linc-POU3F3 expression significantly promoted tumor cell proliferation, migration and invasion. In addition, linc-POU3F3 expression was negatively correlated with POU3F3 mRNA and protein expressions in hepatocellular carcinoma tissues, and negatively regulated POU3F3 mRNA and protein expressions in hepatocellular carcinoma cells. In conclusion, our study supports the first evidence that linc-POU3F3 plays an oncogenic role in hepatocellular carcinoma, and represents a potential therapeutic strategy for hepatocellular carcinoma patients. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

  17. The imunocytochemical advances in prognosis of metastasis radioiodine resistant of papillary thyroid carcinoma

    International Nuclear Information System (INIS)

    Zelyins'ka, G.V.

    2015-01-01

    The topical issues is the problem of prognosis of metastasis radioiodine resistant metastasis. We offered the methods of prognosis of metastasis radioiodine resistant of papillary thyroid carcinoma with the help of immunocytochemical detection of the cytokeratin 17 and thyroid peroxidase. With the purpose of prognosis of metastasis radioiodine resistibility the cytokeratin 17 is taped in punctates of primary papillary carcinomas. This approach allows predict response of metastases on radioiodine therapy to choose proper therapeutic approach

  18. Surgical management and clinical prognosis of adrenocortical carcinoma.

    Science.gov (United States)

    Dong, Dexin; Li, Hanzhong; Yan, Weigang; Ji, Zhigang; Mao, Quanzong

    2012-01-01

    To study the relationship between surgical management and prognosis of adrenocortical carcinoma (ACC) in order to guide the surgical management of ACC. Clinical data of 45 cases of ACC treated in our hospital were retrospectively analyzed. The 45 cases included 3 cases in stage I, 12 cases in stage II, 7 cases in stage III, and 23 cases in stage IV. 17 cases underwent complete excision, 14 cases underwent palliative excision, 8 cases had non-operative treatment and 6 cases gave up treatment. All patients were followed up from 2 to 141 months. The average survival time of 31 patients with surgery was 32.46 months, and the average survival time of 14 patients without surgery was 4.75 months. There were statistically significant differences between the two groups (p 0.05). Surgery is considered to be the only method to cure ACC. For ACC in stage I and II, tumor resection is the most effective treatment, and second surgical operation is recommended for local recurrence. For ACC in stage III, extensive surgical operation is recommended, and for ACC in stage IV, surgical operation has no effect on the prognosis. Copyright © 2012 S. Karger AG, Basel.

  19. Radiation recall dermatitis triggered by sorafenib after radiation therapy for hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Gwi Eon; Song, Hee Sung; Kim, Young Suk [Jeju National University Hospital, Jeju National University School of Medicine, Jeju (Korea, Republic of); Ahn, Ki Jung [Dept. of Radiation Oncology, Inje University Busan Paik Hospital, Inje University of Medicine, Busan (Korea, Republic of)

    2017-09-15

    Sorafenib is widely used for unresectable and metastatic hepatocellular carcinomas. Radiation recall dermatitis (RRD) is an acute inflammatory reaction confined to previously irradiated skin that occurs after the administration of certain drugs. RRD after sorafenib treatment is rare; five cases have been reported thus far. We describe a 44-year-old man irradiated for chest wall bone metastasis from hepatocellular carcinoma. Eight days after radiotherapy completion, systemic therapy for metastatic hepatocellular carcinoma was initiated with sorafenib treatment. Eleven days after starting sorafenib, the patient complained of erythematous rash with pruritus in the chest wall, in a location consistent with the previous radiation field. Sorafenib was continued at the same dose, despite the RRD. The skin reaction subsided over the next 2 weeks without any medical intervention.

  20. Chondroitin sulfate iron colloid as MR contrast agent in differentiation between hepatocellular carcinoma and adenomatous hyperplasia

    Energy Technology Data Exchange (ETDEWEB)

    Suto, Y. (Department of Radiology, Tottori Univ. School of Medicine, Yonago (Japan)); Kato, T. (Department of Radiology, Tottori Univ. School of Medicine, Yonago (Japan)); Matsuo, T. (Department of Radiology, Tottori Univ. School of Medicine, Yonago (Japan)); Kamba, M. (Department of Radiology, Tottori Univ. School of Medicine, Yonago (Japan)); Shimatani, Y. (Department of Radiology, Tottori Univ. School of Medicine, Yonago (Japan)); Ohuchi, Y. (Department of Radiology, Tottori Univ. School of Medicine, Yonago (Japan)); Nakamura, K. (Department of Radiology, Tottori Univ. School of Medicine, Yonago (Japan)); Ohta, Y. (Department of Radiology, Tottori Univ. School of Medicine, Yonago (Japan))

    1993-05-01

    Using a 1.5 T MR imaging unit, T1- and T2-weighted images were obtained before and after i.v. administration of chondroitin sulfate iron colloid (CSIC) in order to differentiate hepatocellular carcinoma (n=20) from adenomatous hyperplasia without atypia (n=16). Differentiation was made from the tumor-liver contrast to noise ratio (CNR) and visual evaluation of the nodule, with reference to signal intensity relative to that of the surrounding liver. The CNR of adenomatous hyperplasia was on T1-weighted images significantly decreased after CSIC administration (p<0.01). On T2-weighted images, there was no significant difference in CNR after CSIC administration. On the other hand, the CNR of hepatocellular carcinoma was significantly increased after CSIC administration on both T1- and T2-weighted images (p<0.01). CSIC reflects intratumor reticuloendothelial cellular functions, and is therefore useful in differentiating hepatocellular carcinoma from adenomatous hyperplasia without atypia. (orig.).

  1. Mitochondrial fission promotes cell migration by Ca2+ /CaMKII/ERK/FAK pathway in hepatocellular carcinoma.

    Science.gov (United States)

    Sun, Xiacheng; Cao, Haiyan; Zhan, Lei; Yin, Chun; Wang, Gang; Liang, Ping; Li, Jibin; Wang, Zhe; Liu, Bingrong; Huang, Qichao; Xing, Jinliang

    2018-07-01

    Mitochondrial dynamics of fission and fusion plays critical roles in a diverse range of important cellular functions, and its deregulation has been increasingly implicated in human diseases. Previous studies have shown that increased mitochondrial fission significantly promoted the proliferation of hepatocellular carcinoma (HCC) cells. However, how they influence the migration of tumour cells remained largely unknown. In the present study, we further investigated the effect of mitochondrial fission on the migration and metastasis of hepatocellular carcinoma cells. Moreover, the underlying molecular mechanisms and therapeutic application were explored. Our data showed that dynamin-1-like protein expression was strongly increased in distant metastasis of hepatocellular carcinoma when compared to primary hepatocellular carcinoma. In contrast, the mitochondrial fusion protein mitofusin 1 showed an opposite trend. Moreover, the expression of dynamin-1-like protein and mitofusin 1 was significantly associated with the disease-free survival of hepatocellular carcinoma patients. In addition, our data further showed that mitochondrial fission significantly promoted the reprogramming of focal-adhesion dynamics and lamellipodia formation in hepatocellular carcinoma cells mainly by activating typical Ca 2+ /CaMKII/ERK/FAK pathway. Importantly, treatment with mitochondrial division inhibitor-1 significantly decreased calcium signalling in hepatocellular carcinoma cells and had a potential treatment effect for hepatocellular carcinoma metastasis in vivo. Taken together, our findings demonstrate that mitochondrial fission plays a critical role in the regulation of hepatocellular carcinoma cell migration, which provides strong evidence for this process as a drug target in hepatocellular carcinoma metastasis treatment. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  2. An Ecological Study of the Association between Air Pollution and Hepatocellular Carcinoma Incidence in Texas.

    Science.gov (United States)

    Cicalese, Luca; Raun, Loren; Shirafkan, Ali; Campos, Laura; Zorzi, Daria; Montalbano, Mauro; Rhoads, Colin; Gazis, Valia; Ensor, Katherine; Rastellini, Cristiana

    2017-11-01

    Primary liver cancer is a significant cause of cancer-related death in both the United States and the world at large. Hepatocellular carcinoma comprises 90% of these primary liver cancers and has numerous known etiologies. Evaluation of these identified etiologies and other traditional risk factors cannot explain the high incidence rates of hepatocellular carcinoma in Texas. Texas is home to the second largest petrochemical industry and agricultural industry in the nation; industrial activity and exposure to pathogenic chemicals have never been assessed as potential links to the state's increased incidence rate of hepatocellular carcinoma. The association between the county-level concentrations of 4 air pollutants known to be linked to liver cancer, vinyl chloride, arsenic, benzene, and 1,3-butadiene, and hepatocellular carcinoma rates was evaluated using nonparametric generalized additive logistic regression and gamma regression models. Hepatocellular carcinoma incidence rates for 2000-2013 were evaluated in comparison to 1996 and 1999 pollution concentrations and hepatocellular carcinoma rates for the subset of 2006-2013 were evaluated in comparison to 2002 and 2005 pollution concentrations, respectively. The analysis indicates that the relationship between the incidence of liver cancer and air pollution and risk factors is nonlinear. There is a consistent significant positive association between the incidence of liver cancer and hepatitis C prevalence rates (gamma all years, p < 0.05) and vinyl chloride concentrations (logistic 2002 and 2005, p < 0.0001; gamma 2002 and 2005, p < 0.05). This study suggests that vinyl chloride is a significant contributor to the incidence of liver cancer in Texas. The relationship is notably nonlinear. Further, the study supports the association between incidence of liver cancer and prevalence of hepatitis B.

  3. The experimental study on tropism of magnetic labeled bone marrow mesenchymal stem cells for hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Chen Shuangqing; Wang Peijun; Li Minghua; Zhang Wei; Dai gonghua

    2009-01-01

    Objective: To label rat bone marrow mesenchymal stem cells with superparamagnetic iron oxide (SPIO) and to explore the tropism of BMSCs for hepatocellular carcinoma cells after transplantation in vivo. Methods: BMSCs from bone marrow of Sprague-Dawly (SD) rats were cultured isolated and purified. Labeled BMSCs was achieved using Feridex. Twenty-four hepatocellular carcinoma models of SD rats were induced two weeks before transplantation. The models were divided into three groups in random: the labeled BMSCs and unlabeled BMSCs were transplanted respectively into the rat's livers of experimental group (n=12) and control group A (n=6) via spleens, and no transplant was done for control group B (n=6). MR imaging was performed to monitor the transplanted cells after 1,3,7,14 d using 1.5 T MR system. Signal intensity ratio (SI/SI * ) between tumor and hepatic tissue on T 2 * WI were measured and compared by one-factor analysis of variance. After MR imaging, Prussian blue staining was performed. MR imaging findings were compared with histological sections. Results: Prussian blue staining confirmed the labeling efficiency of BMSCs was above 90%. SI/SI * of experimental group before and 1, 3, 7, 14 d after transplantation were 3.18±0.21, 1.98±0.20, 2.38±0.28, 2.70±0.25 and 3.16±0.24 respectively. Following transplantation of BMSCs, signal intensity decrease was found in hepatocellular carcinoma of experimental group (F=56.65, P 2 * WI (P>0.05). A large number of Prussian blue staining positive cells were found in hepatocellular carcinoma in experimental group. Histological section with Prussian blue staining had a good correlation with the signal intensity changes on MR images at different time. Conclusion: BMSCs display significant tropism to hepatocellular carcinoma and may be an ideal gene therapy vehicle against hepatocellular carcinoma. (authors)

  4. Preclinical evaluation of transcriptional targeting strategy for human hepatocellular carcinoma in an orthotopic xenograft mouse model.

    Science.gov (United States)

    Sia, Kian Chuan; Huynh, Hung; Chung, Alexander Yaw Fui; Ooi, London Lucien Peng Jin; Lim, Kiat Hon; Hui, Kam Man; Lam, Paula Yeng Po

    2013-08-01

    Gene regulation of many key cell-cycle players in S-, G(2) phase, and mitosis results from transcriptional repression in their respective promoter regions during the G(0) and G(1) phases of cell cycle. Within these promoter regions are phylogenetically conserved sequences known as the cell-cycle-dependent element (CDE) and cell-cycle genes homology regions (CHR) sites. Thus, we hypothesize that transcriptional regulation of cell-cycle regulation via the CDE/CHR region together with liver-specific apolipoprotein E (apoE)-hAAT promoter could bring about a selective transgene expression in proliferating human hepatocellular carcinoma. We show that the newly generated vector AH-6CC-L2C could mediate hepatocyte-targeted luciferase gene expression in tumor cells and freshly isolated short-term hepatocellular carcinoma cultures from patient biopsy. In contrast, normal murine and human hepatocytes infected with AH-6CC-L2C expressed minimal or low luciferase activities. In the presence of prodrug 5-fluorocytosine (5-FC), AH-6CC-L2C effectively suppressed the growth of orthotopic hepatocellular carcinoma patient-derived xenograft mouse model via the expression of yeast cytosine deaminase (yCD) that converts 5-FC to anticancer metabolite 5-fluoruracil. More importantly, we show that combination treatment of AH-6CC-L2C with an EZH2 inhibitor, DZNep, that targets EpCAM-positive hepatocellular carcinoma, can bring about a greater therapeutic efficacy compared with a single treatment of virus or inhibitor. Our study showed that targeting proliferating human hepatocellular carcinoma cells through the transcriptional control of therapeutic gene could represent a feasible approach against hepatocellular carcinoma.

  5. Overexpression of protein O-fucosyltransferase 1 accelerates hepatocellular carcinoma progression via the Notch signaling pathway

    International Nuclear Information System (INIS)

    Ma, Lijie; Dong, Pingping; Liu, Longzi; Gao, Qiang; Duan, Meng; Zhang, Si; Chen, She; Xue, Ruyi; Wang, Xiaoying

    2016-01-01

    Aberrant activation of Notch signaling frequently occurs in liver cancer, and is associated with liver malignancies. However, the mechanisms regulating pathologic Notch activation in hepatocellular carcinoma (HCC) remain unclear. Protein O-fucosyltransferase 1 (Pofut1) catalyzes the addition of O-linked fucose to the epidermal growth factor-like repeats of Notch. In the present study, we detected the expression of Pofut1 in 8 HCC cell lines and 253 human HCC tissues. We reported that Pofut1 was overexpressed in HCC cell lines and clinical HCC tissues, and Pofut1 overexpression clinically correlated with the unfavorable survival and high disease recurrence in HCC. The in vitro assay demonstrated that Pofut1 overexpression accelerated the cell proliferation and migration in HCC cells. Furthermore, Pofut1 overexpression promoted the binding of Notch ligand Dll1 to Notch receptor, and hence activated Notch signaling pathway in HCC cells, indicating that Pofut1 overexpression could be a reason for the aberrant activation of Notch signaling in HCC. Taken together, our findings indicated that an aberrant activated Pofut1-Notch pathway was involved in HCC progression, and blockage of this pathway could be a promising strategy for the therapy of HCC. - Highlights: • Pofut1 overexpression in HCC was correlated with aggressive tumor behaviors. • Pofut1 overexpression in HCC was associated with poor prognosis. • Pofut1 promoted cell proliferation, migration and invasion in hepatoma cells. • Pofut1 activated Notch signaling pathway in hepatoma cells.

  6. DNA methylation, microRNAs, and their crosstalk as potential biomarkers in hepatocellular carcinoma

    Science.gov (United States)

    Anwar, Sumadi Lukman; Lehmann, Ulrich

    2014-01-01

    Epigenetic alterations have been identified as a major characteristic in human cancers. Advances in the field of epigenetics have contributed significantly in refining our knowledge of molecular mechanisms underlying malignant transformation. DNA methylation and microRNA expression are epigenetic mechanisms that are widely altered in human cancers including hepatocellular carcinoma (HCC), the third leading cause of cancer related mortality worldwide. Both DNA methylation and microRNA expression patterns are regulated in developmental stage specific-, cell type specific- and tissue-specific manner. The aberrations are inferred in the maintenance of cancer stem cells and in clonal cell evolution during carcinogenesis. The availability of genome-wide technologies for DNA methylation and microRNA profiling has revolutionized the field of epigenetics and led to the discovery of a number of epigenetically silenced microRNAs in cancerous cells and primary tissues. Dysregulation of these microRNAs affects several key signalling pathways in hepatocarcinogenesis suggesting that modulation of DNA methylation and/or microRNA expression can serve as new therapeutic targets for HCC. Accumulative evidence shows that aberrant DNA methylation of certain microRNA genes is an event specifically found in HCC which correlates with unfavorable outcomes. Therefore, it can potentially serve as a biomarker for detection as well as for prognosis, monitoring and predicting therapeutic responses in HCC. PMID:24976726

  7. Multiple Roles of Autophagy in the Sorafenib Resistance of Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Ting Sun

    2017-11-01

    Full Text Available Hepatocellular carcinoma (HCC is the second leading cause of cancer-related death worldwide, and prognosis remains unsatisfactory since the disease is often diagnosed at the advanced stages. Currently, the multikinase inhibitor sorafenib is the only drug approved for the treatment of advanced HCC. However, primary or acquired resistance to sorafenib develops, generating a roadblock in HCC therapy. Autophagy is an intracellular lysosomal pathway involved in protein and organelle degradation, with an astonishing number of connections to human disease and physiology. Current understanding of the role of autophagy in the progression of cancer and the response to cancer therapy remains controversial. Sorafenib is able to induce autophagy in HCC, but the effect of autophagy is indistinct. Some studies established that sorafenib-induced autophagy serves as a pro-survival response. However, other studies found that sorafenib-induced autophagy improves the lethality of sorafenib against HCC cells. The mechanisms underlying autophagy and sorafenib resistance remain elusive. The purpose of this review is to summarize the progress of research focused on autophagy and sorafenib resistance and to update current knowledge of how cellular autophagy impacts sorafenib sensitivity in HCC treatment.

  8. Antiangiogenic treatment in hepatocellular carcinoma: the balance of efficacy and safety

    Science.gov (United States)

    Welker, Martin-Walter; Trojan, Joerg

    2013-01-01

    Hepatocellular carcinoma (HCC) is a severe complication of advanced liver disease with a worldwide incidence of more than 600,000 patients per year. Liver function, clinical performance status, and tumor size are considered in the Barcelona Clinic Liver Cancer (BCLC) system. While curative treatment options are available for early stages, most patients present with intermediate- or advanced-stage HCC, burdened with a poor prognosis, substantially influenced by the degree of liver-function impairment. Hypervascularization is a major characteristic of HCC, and antiangiogenic treatments are the basis of treatment in noncurative stages, including interventional and pharmacological treatments. Currently, the tyrosine-kinase inhibitor sorafenib is still the only approved drug for HCC. Further improvements in survival in patients with intermediate- and advanced-stage HCC may be anticipated by both multimodal approaches, such as combination of interventional and systemic treatments, and new systemic treatment options. Until now, the Phase III development of other tyrosine-kinase inhibitors in patients with advanced HCC has failed due to minor efficacy and/or increased toxicity compared to sorafenib. However, promising Phase II data have been reported with MET inhibitors in this hard-to-treat population. This review gives a critical overview of antiangiogenic drugs and strategies in intermediate- and advanced-stage HCC, with a special focus on safety. PMID:24204170

  9. Links between human LINE-1 retrotransposons and hepatitis virus-related hepatocellular carcinoma

    Science.gov (United States)

    Honda, Tomoyuki

    2016-05-01

    Hepatocellular carcinoma (HCC) accounts for approximately 80% of liver cancers, the third most frequent cause of cancer mortality. The most prevalent risk factors for HCC are infections by hepatitis B or hepatitis C virus. Findings suggest that hepatitis virus-related HCC might be a cancer in which LINE-1 retrotransposons, often termed L1, activity plays a potential role. Firstly, hepatitis viruses can suppress host defense factors that also control L1 mobilization. Secondly, many recent studies also have indicated that hypomethylation of L1 affects the prognosis of HCC patients. Thirdly, endogenous L1 retrotransposition was demonstrated to activate oncogenic pathways in HCC. Fourthly, several L1 chimeric transcripts with host or viral genes are found in hepatitis virus-related HCC. Such lines of evidence suggest a linkage between L1 retrotransposons and hepatitis virus-related HCC. Here, I briefly summarize current understandings of the association between hepatitis virus-related HCC and L1. Then, I discuss potential mechanisms of how hepatitis viruses drive the development of HCC via L1 retrotransposons. An increased understanding of the contribution of L1 to hepatitis virus-related HCC may provide unique insights related to the development of novel therapeutics for this disease.

  10. Lactate Dehydrogenase Is an Important Prognostic Indicator for Hepatocellular Carcinoma after Partial Hepatectomy

    Directory of Open Access Journals (Sweden)

    Jing-Ping Zhang

    2015-12-01

    Full Text Available Preoperative serum lactate dehydrogenase (LDH has been used as a prognostic indicator for patients with hepatocellular carcinoma (HCC treated with sorafenib or undergoing transcatheter arterial chemoembolization, but its significance in predicting survival of HCC patients who received curative resection remains undefined. A total of 683 patients with histopathologically confirmed HCC were enrolled in this study. The prognostic significance of preoperative serum LDH was determined by Kaplan-Meier analysis and a Cox proportional hazards regression model. The association between the preoperative serum LDH and clinicopathological parameters was evaluated by the χ2 test or linear regression analysis when appropriate. Higher preoperative serum LDH level was associated with worse prognosis. In a multivariate Cox proportional hazards analysis, the preoperative serum LDH level could predict overall survival and recurrence independently. Higher preoperative serum LDH level is associated with the elevated serum alpha-fetoprotein, the presence of hepatitis B surface antigen, larger tumor size, the presence of macrovascular invasion, the advanced tumor–lymph node–metastasis stage, worse tumor differentiation, and Child-Pugh B. Preoperative serum LDH level was an inexpensive, simple, convenient, and routinely measured biomarker exhibiting a potential to select patients at high risk with poor clinical outcome for appropriate treatment strategies.

  11. Serum YKL-40 independently predicts outcome after transcatheter arterial chemoembolization of hepatocellular carcinoma.

    Directory of Open Access Journals (Sweden)

    Cheng-Bao Zhu

    Full Text Available Transcatheter arterial chemoembolization (TACE is the most widely used treatment option for unresectable hepatocellular carcinoma (HCC. Elevated serum YKL-40 level has been shown to predict poor prognosis in HCC patients undergoing resection. This study was designed to validate the prognostic significance of serum YKL-40 in patients with HCC undergoing TACE treatment.Serum YKL-40 level was determined by enzyme-linked immunosorbent assay. Overall survival (OS was evaluated with the Kaplan-Meier method and compared by the log-rank test. Multivariate study with Cox proportional hazard model was used to evaluate independent prognostic variables of OS.The median pretreatment serum YKL-40 in HCC patients with was significantly higher than that in healthy controls (P<0.001. The YKL-40 could predict survival precisely either in a dichotomized or continuous fashion (P<0.001 and P = 0.001, respectively. Multivariate Cox regression analysis indicated that serum YKL-40 was an independent prognostic factor for OS in HCC patients (P = 0.001. In further stratified analyses, YKL-40 could discriminate the outcomes of patients with low and high alpha-fetoprotein (AFP level (P = 0.006 and 0.016, respectively. Furthermore, the combination of serum YKL-40 and AFP had more capacity to predict patients' outcomes.Serum YKL-40 was demonstrated to be an independent prognostic biomarker in HCC patients treated with TACE. Our results need confirmation in an independent study.

  12. Preoperative neutrophil-lymphocyte ratio is an independent prognostic factor for hepatocellular carcinoma after radical resection

    Directory of Open Access Journals (Sweden)

    ZHANG Tingting

    2015-06-01

    Full Text Available ObjectiveTo evaluate the effect and predictive value of preoperative neutrophil-lymphocyte ratio (NLR on the prognosis of patients undergoing radical resection for hepatocellular carcinoma (HCC. MethodsThe clinical data of 245 patients who received radical resection for HCC in our hospital from 2004 to 2009 were retrospectively analyzed. The effects of clinicopathological parameters including NLR on overall survival (OS time were assessed by univariate analysis using the log-rank test. The significant variables were further analyzed by multivariate analysis using the Cox regression model. ResultsUsing NLR=1.5, 2, and 3 as cut-off points, the patients were divided into four groups. The median OS time in groups with NLR<1.5, 1.5≤NLR<2, 2≤NLR<3, and NLR≥3 was 39.6, 38.3, 25.4, and 19.9 months, respectively (P=0.003. Multivariate analysis showed that preoperative NLR, levels of alpha-fetoprotein and alanine aminotransferase in peripheral blood, number of tumor nodules, maximum size of tumor, and portal vein tumor thrombus were independent prognostic factors for HCC (P<0.05. ConclusionPreoperative NLR in peripheral blood is a novel prognostic biomarker for HCC after radical resection.

  13. Management of hepatitis B virus infection during treatment for hepatitis B virus-related hepatocellular carcinoma

    Science.gov (United States)

    Kubo, Shoji; Takemura, Shigekazu; Tanaka, Shogo; Shinkawa, Hiroji; Nishioka, Takayoshi; Nozawa, Akinori; Kinoshita, Masahiko; Hamano, Genya; Ito, Tokuji; Urata, Yorihisa

    2015-01-01

    Although liver resection is considered the most effective treatment for hepatocellular carcinoma (HCC), treatment outcomes are unsatisfactory because of the high rate of HCC recurrence. Since we reported hepatitis B e-antigen positivity and high serum hepatitis B virus (HBV) DNA concentrations are strong risk factors for HCC recurrence after curative resection of HBV-related HCC in the early 2000s, many investigators have demonstrated the effects of viral status on HCC recurrence and post-treatment outcomes. These findings suggest controlling viral status is important to prevent HCC recurrence and improve survival after curative treatment for HBV-related HCC. Antiviral therapy after curative treatment aims to improve prognosis by preventing HCC recurrence and maintaining liver function. Therapy with interferon and nucleos(t)ide analogs may be useful for preventing HCC recurrence and improving overall survival in patients who have undergone curative resection for HBV-related HCC. In addition, reactivation of viral replication can occur after liver resection for HBV-related HCC. Antiviral therapy can be recommended for patients to prevent HBV reactivation. Nevertheless, further studies are required to establish treatment guidelines for patients with HBV-related HCC. PMID:26217076

  14. Antiangiogenic treatment in hepatocellular carcinoma: the balance of efficacy and safety

    Directory of Open Access Journals (Sweden)

    Welker MW

    2013-10-01

    Full Text Available Martin-Walter Welker, Joerg TrojanMedizinische Klinik 1, Universitätsklinikum Frankfurt, GermanyAbstract: Hepatocellular carcinoma (HCC is a severe complication of advanced liver disease with a worldwide incidence of more than 600,000 patients per year. Liver function, clinical performance status, and tumor size are considered in the Barcelona Clinic Liver Cancer (BCLC system. While curative treatment options are available for early stages, most patients present with intermediate- or advanced-stage HCC, burdened with a poor prognosis, substantially influenced by the degree of liver-function impairment. Hypervascularization is a major characteristic of HCC, and antiangiogenic treatments are the basis of treatment in noncurative stages, including interventional and pharmacological treatments. Currently, the tyrosine-kinase inhibitor sorafenib is still the only approved drug for HCC. Further improvements in survival in patients with intermediate- and advanced-stage HCC may be anticipated by both multimodal approaches, such as combination of interventional and systemic treatments, and new systemic treatment options. Until now, the Phase III development of other tyrosine-kinase inhibitors in patients with advanced HCC has failed due to minor efficacy and/or increased toxicity compared to sorafenib. However, promising Phase II data have been reported with MET inhibitors in this hard-to-treat population. This review gives a critical overview of antiangiogenic drugs and strategies in intermediate- and advanced-stage HCC, with a special focus on safety.Keywords: HCC, sorafenib, antiangiogenesis, TACE, MET

  15. Peritumoral ductular reaction: a poor postoperative prognostic factor for hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Xu, Minhui; Wei, Lixin; Xie, Feng; Qian, Guangyang; Jing, Yingying; Zhang, Shanshan; Gao, Lu; Zheng, Tao; Wu, Mengchao; Yang, Jiamei

    2014-01-01

    The role of ductular reaction (DR) in hepatocellular carcinoma (HCC) remains to be elucidated. In this study, we tried to uncover possible effect by correlating peritumoral DR in a necroinflammatory microenvironment with postoperative prognosis in HCC. The expression of peritumoral DR/CK19 by immunohistochemistry, necroinflammation and fibrosis were assessed from 106 patients receiving curative resection for HCC. Prognostic values for these and other clinicopathologic factors were evaluated. Peritumoral DR significantly correlated with necroinflammation (r = 0.563, p = 3.4E-10), fibrosis (r = 0.435, p = 3.1E-06), AFP level (p = 0.010), HBsAg (p = 4.9E-4), BCLC stage (p = 0.003), TNM stage (p = 0.002), multiple nodules (p = 0.004), absence of tumor capsule (p = 0.027), severe microscopic vascular invasion (p = 0.031) and early recurrence (p = 0.010). Increased DR was significantly associated with decreased RFS/OS (p = 4.8E-04 and p = 2.6E-05, respectively) in univariate analysis and were identified as an independent prognostic factor (HR = 2.380, 95% CI = 1.250-4.534, p = 0.008 for RFS; HR = 4.294, 95% CI = 2.255-8.177, p = 9.3E-6 for OS) in multivariate analysis. These results suggested that peritumoral DR in a necroinflammatory microenvironment was a poor prognostic factor for HCC after resection

  16. Cancer stem cells in hepatocellular carcinoma: Therapeutic implications based on stem cell biology.

    Science.gov (United States)

    Chiba, Tetsuhiro; Iwama, Atsushi; Yokosuka, Osamu

    2016-01-01

    Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third most frequent cause of cancer-related death worldwide. Despite advances in its diagnosis and treatment, the prognosis of patients with advanced HCC remains unfavorable. Recent advances in stem cell biology and associated technologies have enabled the identification of minor components of tumorigenic cells, termed cancer stem cells (CSC) or tumor-initiating cells, in cancers such as HCC. Furthermore, because CSC play a central role in tumor development, metastasis and recurrence, they are considered to be a therapeutic target in cancer treatment. Hepatic CSC have been successfully identified using functional and cell surface markers. The analysis of purified hepatic CSC has revealed the molecular machinery and signaling pathways involved in their maintenance. In addition, epigenetic transcriptional regulation has been shown to be important in the development and maintenance of CSC. Although inhibitors of CSC show promise as CSC-targeting drugs, novel therapeutic approaches for the eradication of CSC are yet to be established. In this review, we describe recent progress in hepatic CSC research and provide a perspective on the available therapeutic approaches based on stem cell biology. © 2015 The Japan Society of Hepatology.

  17. Hepatocellular carcinoma displays distinct DNA methylation signatures with potential as clinical predictors.

    Directory of Open Access Journals (Sweden)

    Hector Hernandez-Vargas

    Full Text Available BACKGROUND: Hepatocellular carcinoma (HCC is characterized by late detection and fast progression, and it is believed that epigenetic disruption may be the cause of its molecular and clinicopathological heterogeneity. A better understanding of the global deregulation of methylation states and how they correlate with disease progression will aid in the design of strategies for earlier detection and better therapeutic decisions. METHODS AND FINDINGS: We characterized the changes in promoter methylation in a series of 30 HCC tumors and their respective surrounding tissue and identified methylation signatures associated with major risk factors and clinical correlates. A wide panel of cancer-related gene promoters was analyzed using Illumina bead array technology, and CpG sites were then selected according to their ability to classify clinicopathological parameters. An independent series of HCC tumors and matched surrounding tissue was used for validation of the signatures. We were able to develop and validate a signature of methylation in HCC. This signature distinguished HCC from surrounding tissue and from other tumor types, and was independent of risk factors. However, aberrant methylation of an independent subset of promoters was associated with tumor progression and etiological risk factors (HBV or HCV infection and alcohol consumption. Interestingly, distinct methylation of an independent panel of gene promoters was strongly correlated with survival after cancer therapy. CONCLUSION: Our study shows that HCC tumors exhibit specific DNA methylation signatures associated with major risk factors and tumor progression stage, with potential clinical applications in diagnosis and prognosis.

  18. Natural killer cell dysfunction in hepatocellular carcinoma and NK cell-based immunotherapy

    Science.gov (United States)

    Sun, Cheng; Sun, Hao-yu; Xiao, Wei-hua; Zhang, Cai; Tian, Zhi-gang

    2015-01-01

    The mechanisms linking hepatitis B virus (HBV) and hepatitis C virus (HCV) infection to hepatocellular carcinoma (HCC) remain largely unknown. Natural killer (NK) cells account for 25%–50% of the total number of liver lymphocytes, suggesting that NK cells play an important role in liver immunity. The number of NK cells in the blood and tumor tissues of HCC patients is positively correlated with their survival and prognosis. Furthermore, a group of NK cell-associated genes in HCC tissues is positively associated with the prolonged survival. These facts suggest that NK cells and HCC progression are strongly associated. In this review, we describe the abnormal NK cells and their functional impairment in patients with chronic HBV and HCV infection, which contribute to the progression of HCC. Then, we summarize the association of NK cells with HCC based on the abnormalities in the numbers and phenotypes of blood and liver NK cells in HCC patients. In particular, the exhaustion of NK cells that represents lower cytotoxicity and impaired cytokine production may serve as a predictor for the occurrence of HCC. Finally, we present the current achievements in NK cell immunotherapy conducted in mouse models of liver cancer and in clinical trials, highlighting how chemoimmunotherapy, NK cell transfer, gene therapy, cytokine therapy and mAb therapy improve NK cell function in HCC treatment. It is conceivable that NK cell-based anti-HCC therapeutic strategies alone or in combination with other therapies will be great promise for HCC treatment. PMID:26073325

  19. Molecular Imaging of Hepatocellular Carcinoma Xenografts with Epidermal Growth Factor Receptor Targeted Affibody Probes

    Directory of Open Access Journals (Sweden)

    Ping Zhao

    2013-01-01

    Full Text Available Hepatocellular carcinoma (HCC is a highly aggressive and lethal cancer. It is typically asymptomatic at the early stage, with only 10%–20% of HCC patients being diagnosed early enough for appropriate surgical treatment. The delayed diagnosis of HCC is associated with limited treatment options and much lower survival rates. Therefore, the early and accurate detection of HCC is crucial to improve its currently dismal prognosis. The epidermal growth factor receptor (EGFR has been reported to be involved in HCC tumorigenesis and to represent an attractive target for HCC imaging and therapy. In this study, an affibody molecule, Ac-Cys-ZEGFR:1907, targeting the extracellular domain of EGFR, was used for the first time to assess its potential to detect HCC xenografts. By evaluating radio- or fluorescent-labeled Ac-Cys-ZEGFR:1907 as a probe for positron emission tomography (PET or optical imaging of HCC, subcutaneous EGFR-positive HCC xenografts were found to be successfully imaged by the PET probe. Thus, affibody-based PET imaging of EGFR provides a promising approach for detecting HCC in vivo.

  20. MTBP inhibits the Erk1/2-Elk-1 signaling in hepatocellular carcinoma

    Science.gov (United States)

    Ranjan, Atul; Iyer, Swathi V.; Ward, Christopher; Link, Tim; Diaz, Francisco J.; Dhar, Animesh; Tawfik, Ossama W.; Weinman, Steven A.; Azuma, Yoshiaki; Izumi, Tadahide; Iwakuma, Tomoo

    2018-01-01

    Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, and the prognosis of HCC patients, especially those with metastasis, remains extremely poor. This is partly due to unclear molecular mechanisms underlying HCC metastasis. Our previous study indicates that MDM2 Binding Protein (MTBP) suppresses migration and metastasis of HCC cells. However, signaling pathways regulated by MTBP remain unknown. To identify metastasis-associated signaling pathways governed by MTBP, we have performed unbiased luciferase reporter-based signal array analyses and found that MTBP suppresses the activity of the ETS-domain transcription factor Elk-1, a downstream target of Erk1/2 MAP kinases. MTBP also inhibits phosphorylation of Elk-1 and decreases mRNA expression of Elk-1 target genes. Reduced Elk-1 activity is caused by inhibited nuclear translocation of phosphorylated Erk1/2 (p-Erk) by MTBP and subsequent inhibition of Elk-1 phosphorylation. We also reveal that MTBP inhibits the interaction of p-Erk with importin-7/RanBP7 (IPO7), an importin family member which shuttles p-Erk into the nucleus, by binding to IPO7. Moreover, high levels of MTBP in human HCC tissues are correlated with cytoplasmic localization of p-Erk1/2. Our study suggests that MTBP suppresses metastasis, at least partially, by down-modulating the Erk1/2-Elk-1 signaling pathway, thus identifying a novel regulatory mechanism of HCC metastasis by regulating the subcellular localization of p-Erk. PMID:29765550

  1. Significance of Aurora B overexpression in hepatocellular carcinoma. Aurora B Overexpression in HCC

    International Nuclear Information System (INIS)

    Lin, Zhong-Zhe; Jeng, Yung-Ming; Hu, Fu-Chang; Pan, Hung-Wei; Tsao, Hsin-Wei; Lai, Po-Lin; Lee, Po-Huang; Cheng, Ann-Lii; Hsu, Hey-Chi

    2010-01-01

    To investigate the significance of Aurora B expression in hepatocellular carcinoma (HCC). The Aurora B and Aurora A mRNA level was measured in 160 HCCs and the paired nontumorous liver tissues by reverse transcription-polymerase chain reaction. Mutations of the p53 and β-catenin genes were analyzed in 134 and 150 tumors, respectively, by direct sequencing of exon 2 to exon 11 of p53 and exon 3 of β-catenin. Anticancer effects of AZD1152-HQPA, an Aurora B kinase selective inhibitor, were examined in Huh-7 and Hep3B cell lines. Aurora B was overexpressed in 98 (61%) of 160 HCCs and in all 7 HCC cell lines examined. The overexpression of Aurora B was associated with Aurora A overexpression (P = 0.0003) and p53 mutation (P = 0.002) and was inversely associated with β-catenin mutation (P = 0.002). Aurora B overexpression correlated with worse clinicopathologic characteristics. Multivariate analysis confirmed that Aurora B overexpression was an independent poor prognostic factor, despite its interaction with Aurora A overexpression and mutations of p53 and β-catenin. In Huh-7 and Hep3B cells, AZD1152-HQPA induced proliferation blockade, histone H3 (Ser10) dephosphorylation, cell cycle disturbance, and apoptosis. Aurora B overexpression is an independent molecular marker predicting tumor invasiveness and poor prognosis of HCC. Aurora B kinase selective inhibitors are potential therapeutic agents for HCC treatment

  2. Hepatocellular Carcinoma: Current Management and Future Development—Improved Outcomes with Surgical Resection

    Directory of Open Access Journals (Sweden)

    Yoji Kishi

    2011-01-01

    Full Text Available Currently, surgical resection is the treatment strategy offering the best long-term outcomes in patients with hepatocellular carcinoma (HCC. Especially for advanced HCC, surgical resection is the only strategy that is potentially curative, and the indications for surgical resection have expanded concomitantly with the technical advances in hepatectomy. A major problem is the high recurrence rate even after curative resection, especially in the remnant liver. Although repeat hepatectomy may prolong survival, the suitability may be limited due to multiple tumor recurrence or background liver cirrhosis. Multimodality approaches combining other local ablation or systemic therapy may help improve the prognosis. On the other hand, minimally invasive, or laparoscopic, hepatectomy has become popular over the last decade. Although the short-term safety and feasibility has been established, the long-term outcomes have not yet been adequately evaluated. Liver transplantation for HCC is also a possible option. Given the current situation of donor shortage, however, other local treatments should be considered as the first choice as long as liver function is maintained. Non-transplant treatment as a bridge to transplantation also helps in decreasing the risk of tumor progression or death during the waiting period. The optimal timing for transplantation after HCC recurrence remains to be investigated.

  3. Expression of cytoskeleton regulatory protein Mena in human hepatocellular carcinoma and its prognostic significance.

    Science.gov (United States)

    Hu, Kunpeng; Wang, Jiani; Yao, Zhicheng; Liu, Bo; Lin, Yuan; Liu, Lei; Xu, Lihua

    2014-05-01

    The molecular mechanisms of the development and progression of hepatocellular carcinoma (HCC) are poorly understood. The main objective of this study was to analyze the expression of Enabled [mammalian Ena (Mena)] protein and its clinical significance in human HCC. The Mena expression was examined at mRNA and protein levels by real-time quantitative polymerase chain reaction and Western blotting analysis in ten paired HCC tissues and the adjacent normal tissues. The expression of Mena protein in 81 specimens of HCC tissues was determined by immunohistochemistry. Associations of Mena expression with the clinicopathological features were analyzed, and prognosis of HCC patients was evaluated. The result shows the expression of Mena mRNA and protein was higher in HCC than in the adjacent normal tissues in ten paired samples. Mena was mainly accumulated in the cytoplasm of tumor cells and over-expressed in 40.74% (33/81) patients by immunohistochemical staining. Over-expression of Mena was significantly associated with poor cellular differentiation (P = 0.025), advanced tumor stage (P = 0.003) and worse disease-free survival (DFS, P Mena is an independent prognostic factor for DFS in multivariate analysis (HR 2.309, 95% CI 1.104-4.828; P = 0.026). Mena is up-regulated in HCC and associated with tumor differentiation and clinical stage. Mena may be an independent prognostic marker for DFS of HCC patients.

  4. Overexpression of protein O-fucosyltransferase 1 accelerates hepatocellular carcinoma progression via the Notch signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Ma, Lijie [Liver Surgery Department, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai (China); Dong, Pingping [Department of Gastroenterology and Hepatology, Shanghai Institute of Liver Diseases, Zhongshan Hospital of Fudan University, Shanghai (China); Liu, Longzi; Gao, Qiang; Duan, Meng [Liver Surgery Department, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai (China); Zhang, Si; Chen, She [Key Laboratory of Glycoconjugate Research Ministry of Public Health, Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai (China); Xue, Ruyi, E-mail: xue.ruyi@zs-hospital.sh.cn [Department of Gastroenterology and Hepatology, Shanghai Institute of Liver Diseases, Zhongshan Hospital of Fudan University, Shanghai (China); Wang, Xiaoying, E-mail: xiaoyingwang@fudan.edu.cn [Liver Surgery Department, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai (China)

    2016-04-29

    Aberrant activation of Notch signaling frequently occurs in liver cancer, and is associated with liver malignancies. However, the mechanisms regulating pathologic Notch activation in hepatocellular carcinoma (HCC) remain unclear. Protein O-fucosyltransferase 1 (Pofut1) catalyzes the addition of O-linked fucose to the epidermal growth factor-like repeats of Notch. In the present study, we detected the expression of Pofut1 in 8 HCC cell lines and 253 human HCC tissues. We reported that Pofut1 was overexpressed in HCC cell lines and clinical HCC tissues, and Pofut1 overexpression clinically correlated with the unfavorable survival and high disease recurrence in HCC. The in vitro assay demonstrated that Pofut1 overexpression accelerated the cell proliferation and migration in HCC cells. Furthermore, Pofut1 overexpression promoted the binding of Notch ligand Dll1 to Notch receptor, and hence activated Notch signaling pathway in HCC cells, indicating that Pofut1 overexpression could be a reason for the aberrant activation of Notch signaling in HCC. Taken together, our findings indicated that an aberrant activated Pofut1-Notch pathway was involved in HCC progression, and blockage of this pathway could be a promising strategy for the therapy of HCC. - Highlights: • Pofut1 overexpression in HCC was correlated with aggressive tumor behaviors. • Pofut1 overexpression in HCC was associated with poor prognosis. • Pofut1 promoted cell proliferation, migration and invasion in hepatoma cells. • Pofut1 activated Notch signaling pathway in hepatoma cells.

  5. Menahydroquinone-4 Prodrug: A Promising Candidate Anti-Hepatocellular Carcinoma Agent.

    Science.gov (United States)

    Enjoji, Munechika; Watase, Daisuke; Matsunaga, Kazuhisa; Kusuda, Mariko; Nagata-Akaho, Nami; Karube, Yoshiharu; Takata, Jiro

    2015-07-22

    Recently, new therapeutics have been developed for hepatocellular carcinoma (HCC). However, the overall survival rate of HCC patients is still unsatisfactory; one of the reasons for this is the high frequency of recurrence after radical treatment. Consequently, to improve prognosis, it will be important to develop a novel anti-tumor agent that is especially effective against HCC recurrence. For clinical application, long-term safety, together with high anti-tumor efficacy, is desirable. Recent studies have proposed menahydroquinone-4 1,4-bis- N,N -dimethylglycinate hydrochloride (MKH-DMG), a prodrug of menahydroquinone-4 (MKH), as a promising candidate for HCC treatment including the inhibition of recurrence; MKH-DMG has been shown to achieve good selective accumulation of MKH in tumor cells, resulting in satisfactory inhibition of cell proliferation in des-γ-carboxyl prothrombin (DCP)-positive and DCP-negative HCC cell lines. In a spleen-liver metastasis mouse model, MKH-DMG has been demonstrated to have anti-proliferation and anti-metastatic effects in vivo . The characteristics of MKH-DMG as a novel anti-HCC agent are presented in this review article.

  6. Hepatocellular carcinoma in patients with chronic hepatitis C and cirrhosis in Denmark

    DEFF Research Database (Denmark)

    Hallager, Sofie; Ladelund, Steen; Kjaer, Mette S

    2018-01-01

    Cirrhosis in patients with chronic hepatitis C increases the risk of hepatocellular carcinoma (HCC) and surveillance with ultrasound (US) and alpha-fetoprotein (AFP) is recommended. This study aimed to estimate changes in the HCC incidence rate (IR) over time, HCC stage and prognosis, and AFP...... and US performed in patients with hepatitis C and cirrhosis. Eligible patients were identified in the Danish Database for Hepatitis B and C and data from national health registries and patient charts were obtained. Tumor stage was based on Barcelona-Clinic Liver Cancer stage, TNM classification and size...... and number of lesions combined into stage 0 - 3. We included 1,075 patients with hepatitis C and cirrhosis, free of HCC and liver transplant at baseline. During 4,988 person years (PY) 115 HCC cases were diagnosed. The HCC incidence rate increased from 0.8/100 PY [CI95% 0.4 - 1.5] in 2002-2003 to 2.9/100 PY...

  7. Detection of Metastases of Primary Hepatocellular Carcinoma with {sup 99m}Tc-HIDA Scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Huh, Dae Suk [Seoul National University College of Medicine, Seoul (Korea, Republic of); Hong, Kee Suk; Hong, Seong Woon; Lee, Jhin Oh; Kang, Tae Woong [Cancer Reseach Hospital, Korea Advanced Energy Institute, Seoul (Korea, Republic of)

    1983-03-15

    {sup 99m}Tc-Sulfur Colloid is concentrated in Kupffer cells of the liver, whereas the new biliary agents such as {sup 99m}Tc-HIDA are processed by hepatic parenchymal cells. The distant metastatic lesions in skull and lung of the primary hepatocellular carcinoma in 38-year old Korean male were detected with {sup 99m}Tc-HIDA scintigraphy. The chest PA, skull bone X-ray and radionuclide scintigraphic studies are illustrated. This observation suggests that {sup 99m}Tc-HIDA scintigraphy is useful for detection of distant metastases of primary hepatocellular carcinoma.

  8. Relation of Serum Alkaline Phosphatase to liver scintigram in patients with hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Nishimura, H; Harada, T; Nawata, J; Hayakawa, M; Nishioka, M; Takemoto, T; Yokoyama, T; Takahashi, M

    1982-12-01

    Serum Alkaline Phosphatase (ALP) was studied in relation to liver scintigrams of 54 patients with hepatocellular carcinoma. The ALP activity was higher with larger tumors and in multiple tumors. Within the single tumor group, the activity was higher when the tumor was located in the hilum than in the periphery. The incidence of ALP-1 isoenzyme (bile ALP) roughly paralleled the total ALP activity. These results suggest that the variation of serum ALP seen in each individual patients with hepatocellular carcinoma reflects the volume of cholestatic liver tissue, which is changed by the number, size and localization of the tumor nodules in the liver.

  9. Dynamic computed tomography of hepatocellular carcinoma with particular reference to capsule

    Energy Technology Data Exchange (ETDEWEB)

    Otsuji, Hideaki [Nara Prefectural Hospital (Japan); Uchida, Hideo; Ohishi, H

    1983-11-01

    Dynamic CT of 117 hepatocellular carcinoma was analyzed about the capsule. Capsules were detected in 57 cases (49%) and they were classified into three types. The tumor showed high density during 15 to 26 sec after bolus injection of conrast medium, but the capsule was not enhanced. Incidence of the capsule enhanced as ring high density was 73% during 37 to 90 sec and over 90% after 4 min. Dynamic CT was very useful in the elucidation of hemodynamics of capsules of hepatocellular carcinoma.

  10. A hepatectomized case of hepatocellular carcinoma after fast neutron irradiation therapy

    International Nuclear Information System (INIS)

    Nagashima, Tohru; Ryu, Takamasa; Watanabe, Yoshiji

    1985-01-01

    A 51-year-old male patient with hepatocellular carcinoma was treated preoperatively by fast neutron radiotherapy (910 rad/7 fractions/15 days) with a field of 8 x 6 cm. Radiation-associated liver function disturbance was scarcely observed. No side effect, such as loss of appetite and general fatigue, was encountered. According to the classification of Ohoshi and Shimosato, histological effect of radiation was graded as II sub(A). There is no preoperative fast neutron radiotherapy for hepatocellular carcinoma in Japan in the literature. (Namekawa, K.)

  11. Prognostic role of sirt1 in hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Song, S.; Zhang, H.

    2014-01-01

    To determine the clinical significance of silent mating type information regulation 2 homolog 1 (SIRT1) expression in Hepatocellular Carcinoma (HCC) and its association with P53 and Yes-associated protein 2 (YAP2) expression. Study Design: Observational study. Place and Duration of Study: Department of General Surgery, China-Japan Union Hospital of Jilin University, Changchun, China, from January 2000 to January 2010. Methodology: Tissue microarray technique and immunohistochemistry were conducted to detect the expression of SIRT1, P53 and YAP2 proteins in 300 self-paired HCC samples. Associations with clinicopathologic manifestations were analyzed, overall survival analysis and multivariate analysis were performed. Results: By tissue microarray technique and immunohistochemistry on 300 self-paired HCC samples, it was found that SIRT1, P53 and YAP2 were significantly overexpressed in HCC tumor tissues compared with adjacent non-tumor tissues. SIRT1 immunostaining localized both in the nucleus (145/300, 48.3%) and the cytoplasm (70/300, 23.3%), and the overexpression of nuclear SIRT1 was positively related to the overexpression of P53 and YAP2. Survival analysis showed that nuclear SIRT1, P53 and YAP2 overexpression predicted poor overall survival while cytoplasmic SIRT1 overexpression predicted longer overall survival. Multivariate analysis showed nuclear SIRT1 and P53 overexpression as independent tumor promoters while cytoplasmic SIRT1 overexpression as an independent tumor suppressor. Conclusion: SIRT1 was overexpressed in HCC and the expression was positively related to P53 and YAP2 expression. As the nuclear SIRT1 functions as a tumor promoter and cytoplasmic SIRT1 functions as a tumor suppressor, the role of SIRT1 in HCC should be reconsidered. (author)

  12. Prognostic implication of NQO1 overexpression in hepatocellular carcinoma.

    Science.gov (United States)

    Lin, Lijuan; Sun, Jie; Tan, Yan; Li, Zhenling; Kong, Fanyong; Shen, Yue; Liu, Chao; Chen, Litian

    2017-11-01

    To explore the role of NQO1 overexpression for prognostic implication in hepatocellular carcinoma (HCC), NQO1 mRNA levels were detected in HCC fresh tissue samples of HCC and nontumor tissues, respectively. One hundred fifty-six cases of HCC meeting strict follow-up criteria were selected for immunohistochemical staining of NQO1 protein. Correlations between NQO1 overexpression and clinicopathological features of HCC were evaluated using χ 2 tests, survival rates were calculated using the Kaplan-Meier method, and the relationship between prognostic factors and patient 5-year survival was analyzed using Cox proportional hazards analysis. In results, the levels of NQO1 mRNA were significantly up-regulated in 14 fresh tissue samples of HCC. Immunohistochemical analysis showed that the NQO1 expression and overexpression rates were significantly higher in HCC samples compared with either adjacent nontumor tissues or normal liver tissues. NQO1 overexpression correlated to tumor size, venous infiltration and late pTNM stage of HCC. NQO1 overexpression was also related to low disease-free survival and 5-year survival rates. In the late-stage group, disease-free and 5-year survival rates of patients with NQO1 overexpression were significantly lower than those of patients without NQO1 expression. Further analysis using a Cox proportional hazards regression model revealed that NQO1 expression emerged as a significant independent hazard factor for the 5-year survival rate of patients with HCC. Therefore, NQO1 plays an important role in the progression of HCC. NQO1 may potentially be used as an independent biomarker for prognostic evaluation of HCC. Copyright © 2017. Published by Elsevier Inc.

  13. Tumour seeding after percutaneous cryoablation for hepatocellular carcinoma

    Science.gov (United States)

    Wang, Chun-Ping; Wang, Hong; Qu, Jian-Hui; Lu, Yin-Ying; Bai, Wen-Lin; Dong, Zheng; Gao, Xu-Dong; Rong, Guang-Hua; Zeng, Zhen; Yang, Yong-Ping

    2012-01-01

    AIM: To assess the rate and risk factors for tumour seeding in a large cohort of patients. METHODS: Over an 8-year period, 1436 hepatocellular carcinoma (HCC) patients with 2423 tumour nodules underwent 3015 image-guided percutaneous cryoablation sessions [1215 guided by ultrasonography and 221 by spiral computed tomography (CT)]. Follow-up CT or magnetic resonance imaging was performed every 3 mo. The detailed clinical data were recorded to analyse the risk factors for seeding. RESULTS: The median follow-up time was 18 (range 1-90) mo. Seeding was detected in 11 patients (0.76%) at 1-24 (median 6.0) mo after cryoablation. Seeding occurred along the needle tract in 10 patients and at a distant location in 1 patient. Seeded tumours usually showed similar imaging and histopathological features to the primary HCCs. Univariate analyses identified subcapsular tumour location and direct subcapsular needle insertion as risk factors for seeding. Multivariate analysis showed that only direct subcapsular needle insertion was an independent risk factor for seeding (P = 0.017; odds ratio 2.57; 95%CI: 1.47-3.65). Seeding after cryoablation occurred earlier in patients with poorly differentiated HCC than those with well or moderately differentiated HCC [1.33 ± 0.577 mo vs 11.12 ± 6.896 mo; P = 0.042; 95%CI: (-19.115)-(-0.468)]. CONCLUSION: The risk of seeding after cryoablation for HCC is small. Direct puncture of subcapsular tumours should be avoided to minimise seeding. PMID:23236233

  14. Hepatocellular carcinoma after radiofrequency ablation: recurrent pattern and influenting factor

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Myong Jin; Nam, Kyung Jin; Oh, Jong Young; Choi, Jong Chul; Park, Byeong Ho; Lee, Yung Il [College of Medicine, DongA Univ., Pusan (Korea, Republic of)

    2002-02-01

    To evaluate patterns of recurrence and factors which influence them in radiofreqency (RF) ablation for the treatment of hepatocellular carcinoma (HCC). Between May 1999 and March 2000, 69 patients with 82 HCCs underwent RF ablation for complete necrosis. They were diagnosed by tissue biopsy or tumor marker, and the results of triphasic spiral CT. The indications were that nodular lesions were clearly visualized at sonography, less than 5 cm in size and less than four in number, and that patients had no history of previous treatment. Local therapeutic efficacy such as complete necrosis and marginal recurrence, and new lesions were evaluated by means of triphasic spiral CT performed at least six months after the completion of ablation. We then analyzed the correlation between local therapeutic efficacy and various influential factors such as tumor size, whether the tumor was attached to the portal vein, gross morphology, Child-Pugh classification, and {alpha}-fetoprotein level vefore the procedure, as well as the correlation between new lesions and influential factors which included the {alpha}-fetoprotein level before the procedure, Child-Pugh classification, and multiplicity per person. During a mean follow-up period of 8.95 (range, 6-14) months after RF ablation, the rate of complete necrosis and of marginal recurrence was 91% and 12%, respectively. When a tumor was larger and was attached to a large branch of the portal vien, the incidence of incomplete necrosis and marginal recurrence was greater. The occurrence rate of new lesion was 19.4%. When the {alpha}-fetoprotein level before the procedure was higher and a tumor was multiple in number, new lesions occurred more frequently. Sufficient knowledge of patterns of recurrence and the factors which influence them might improve the therapeutic effects of RF ablation in patients with HCC.

  15. Antibody Arrays Identify Potential Diagnostic Markers of Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Brian J. Peter

    2008-01-01

    Full Text Available Hepatocellular carcinoma (HCC is the third leading cause of cancer deaths worldwide. Effective treatment of HCC patients is hampered by the lack of sensitive and specific diagnostic markers of HCC. Alpha-fetoprotein (AFP, the currently used HCC marker, misses 30%–50% of HCC patients, who therefore remain undiagnosed and untreated. In order to identify novel diagnostic markers that can be used individually or in combination with AFP, we used an antibody array platform to detect the levels of candidate proteins in the plasma of HCC patients (n = 48 and patients with chronic hepatitis B or C viral infections (n = 19 (both of which are the major risk factors of HCC. We identified 7 proteins that significantly differentiate HCC patients from hepatitis patients (p < 0.05 (AFP, CTNNB, CSF1, SELL, IGFBP6, IL6R, and VCAM1.Importantly, we also identified 8 proteins that significantly differentiate HCC patients with ‘normal’ levels of AFP (<20 ng/ml from hepatitis patients (p < 0.05 (IL1RN, IFNG, CDKN1A, RETN, CXCL14, CTNNB, FGF2, and SELL. These markers are potentially important complementary markers to AFP. Using an independent immunoassay method in an independent group of 23 HCC patients and 22 hepatitis patients, we validated that plasma levels of CTNNB were significantly higher in the HCC group (p = 0.020. In conclusion, we used an antibody array platform to identify potential circulating diagnostic markers of HCC, some of which may be valuable when used in combination with AFP. The clinical utility of these newly identified HCC diagnostic markers needs to be systematically evaluated.

  16. High dose vitamin K3 infusion in advanced hepatocellular carcinoma.

    Science.gov (United States)

    Sarin, Shiv K; Kumar, Manoj; Garg, Sanjay; Hissar, Syed; Pandey, Chandana; Sharma, Barjesh C

    2006-09-01

    The survival of patients with unresectable advanced hepatocellular carcinoma (HCC) with portal vein thrombosis is dismal. Current therapeutic options have limited efficacy. Vitamin K has been shown to have antitumor effect on HCC cells both in cell lines and patients with advanced HCC. The aim of this study was to assess the clinical efficacy of high dose vitamin K3 in the treatment of advanced HCC with portal vein thrombosis. Forty-two consecutive patients with advanced HCC (Stage C according to BCLC staging system) with portal vein thrombosis were randomized into two groups: (i) high dose vitamin K3 (n = 23); and (ii) placebo (n = 19). The vitamin K3 was administered by i.v. infusion of 50 mg/day with daily increase of dose by 50 mg for 6 days, followed by 20 mg i.m. twice daily for 2 weeks. Of the 23 patients treated with vitamin K, one (4.3%) achieved complete response and three (13%) partial response, for a total of four (17.4%) objective responders overall. The overall mean survival was 8.9 +/- 8.8 months (median: 6; range 1-37 months) in the vitamin K group and 6.8 +/- 5.3 months (median: 5; range 1.5-21 months) in the placebo group (P = 0.552). The mean duration of survival was longer in patients in the vitamin K group who achieved objective response (22.5 +/- 12.2; median: 21; range 11-37 months) as compared to patients not achieving objective response (6.1 +/- 4.6; median: 5; range 1-16 months) (P = 0.0.002). Portal vein thrombosis resolved with complete patency in one (4.35%) patient. Treatment with high dose vitamin K produces objective response in 17% patients with improved survival in patients achieving objective response; however, it does not affect the overall survival.

  17. Treatment of hepatocellular carcinoma in Child-Pugh B patients.

    Science.gov (United States)

    Piscaglia, Fabio; Terzi, Eleonora; Cucchetti, Alessandro; Trimarchi, Chiara; Granito, Alessandro; Leoni, Simona; Marinelli, Sara; Pini, Patrizia; Bolondi, Luigi

    2013-10-01

    The frequency with which patients in Child-Pugh B having hepatocellular carcinoma are treated following the international guidelines according to the Barcelona Clinic Liver Cancer stages is unknown. To investigate treatment allocation for Child-Pugh B patients in different tumour stages, with particular interest in the intermediate stage. Patients were retrospectively identified from a consecutively collected series. Treatment was carried out primarily according to the guidelines. Of 86 Child-Pugh B patients, 45 were Barcelona early stage, of which the Child-Pugh scores were 46.7% B7, 33.3% B8, 20.0% B9; 27 patients were intermediate stage (B7 59.3%, B8 37.0% and B9 3.7% respectively), 12 were advanced (41.7% B7, 25.0% B8 and 33.3% B9) and 2 were terminal (both B9). In the intermediate stage, transarterial chemoembolization (or ablation) was performed in 68.8% of the Child-Pugh B7 patients, 50% of the B8 patients and 0% of the B9 patients. Median survival of the intermediate patients was 8.0 months (9.0 in B7 vs. 6.0 in -B8/B9, P=0.048). Survival of the intermediate stage patients undergoing chemoembolisation was 22.0 months in Child-Pugh B7 and 6.0 in B8. Approximately half of the intermediate stage patients can undergo locoregional treatment with good survival when in the Child-Pugh B7. The Child-Pugh numeric score impacts survival, suggesting that this tumour stage be refined. Copyright © 2013 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  18. Biomarkers for hepatocellular carcinoma: diagnostic and therapeutic utility

    Directory of Open Access Journals (Sweden)

    Ferrín G

    2015-04-01

    Full Text Available Gustavo Ferrín,1,2 Patricia Aguilar-Melero,1 Manuel Rodríguez-Perálvarez,1,2 José Luis Montero-Álvarez,1,2 Manuel de la Mata1,2 1Liver Unit, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC, Hospital Universitario Reina Sofía, Córdoba, Spain; 2Centro de Investigación Biomédica en Red (CIBER, Enfermedades Hepáticas y Digestivas, Instituto de Salud Carlos III, Madrid, Spain Abstract: Because of the high prevalence and associated-mortality of hepatocellular carcinoma (HCC, early diagnosis of the disease is vital for patient survival. In this regard, tumor size is one of the two main prognostic factors for surgical resection, which constitutes the only curative treatment for HCC along with liver transplantation. However, techniques for HCC surveillance and diagnosis that are currently used in clinical practice have certain limitations that may be inherent to the tumor development. Thus, it is important to continue efforts in the search for biomarkers that increase diagnostic accuracy for HCC. In this review, we focus on different biological sources of candidate biomarkers for HCC diagnosis. Although those biomarkers identified from biological samples obtained by noninvasive methods have greater diagnostic value, we have also considered those obtained from liver tissue because of their potential therapeutic value. To date, sorafenib is the only US Food and Drug Administration-approved antineoplastic for HCC. However, this therapeutic agent shows very low tumor response rates and frequently causes acquired resistance in HCC patients. We discuss the use of HCC biomarkers as therapeutic targets themselves, or as targets to increase sensitivity to sorafenib treatment. Keywords: diagnosis, sorafenib, therapy

  19. Lobaplatin arrests cell cycle progression in human hepatocellular carcinoma cells

    Directory of Open Access Journals (Sweden)

    Chen Chang-Jie

    2010-10-01

    Full Text Available Abstract Background Hepatocellular carcinoma (HCC still is a big burden for China. In recent years, the third-generation platinum compounds have been proposed as potential active agents for HCC. However, more experimental and clinical data are warranted to support the proposal. In the present study, the effect of lobaplatin was assessed in five HCC cell lines and the underlying molecular mechanisms in terms of cell cycle kinetics were explored. Methods Cytotoxicity of lobaplatin to human HCC cell lines was examined using MTT cell proliferation assay. Cell cycle distribution was determined by flow cytometry. Expression of cell cycle-regulated genes was examined at both the mRNA (RT-PCR and protein (Western blot levels. The phosphorylation status of cyclin-dependent kinases (CDKs and retinoblastoma (Rb protein was also examined using Western blot analysis. Results Lobaplatin inhibited proliferation of human HCC cells in a dose-dependent manner. For the most sensitive SMMC-7721 cells, lobaplatin arrested cell cycle progression in G1 and G2/M phases time-dependently which might be associated with the down-regulation of cyclin B, CDK1, CDC25C, phosphorylated CDK1 (pCDK1, pCDK4, Rb, E2F, and pRb, and the up-regulation of p53, p21, and p27. Conclusion Cytotoxicity of lobaplatin in human HCC cells might be due to its ability to arrest cell cycle progression which would contribute to the potential use of lobaplatin for the management of HCC.

  20. Hepatocellular Carcinoma Surveillance Among Cirrhotic Patients With Commercial Health Insurance.

    Science.gov (United States)

    Goldberg, David S; Valderrama, Adriana; Kamalakar, Rajesh; Sansgiry, Sujit S; Babajanyan, Svetlana; Lewis, James D

    2016-03-01

    To evaluate hepatocellular carcinoma (HCC) surveillance rates among commercially insured patients, and evaluate factors associated with compliance with surveillance recommendations. Most HCC occurs in patients with cirrhosis. American Association for the Study of Liver Diseases and European Association for the Study of the Liver guidelines each recommend biannual HCC surveillance for cirrhotic patients to diagnose HCC at an early, curable stage. However, compliance with these guidelines in commercially insured patients is unknown. We used the Truven Health Analytics databases from 2006 to 2010, using January 1, 2006 as the anchor date for evaluating outcomes. The primary outcome was continuous surveillance measure, defined as the proportion of time "up-to-date" with surveillance (PTUDS), with the 6-month interval immediately following each ultrasound categorized as "up-to-date." During a median follow-up of 22.9 (interquartile range, 16.3 to 33.9) months among 8916 cirrhotic patients, the mean PTUDS was 0.34 (SD, 0.29), and the median was 0.31 (interquartile range, 0.03 to 0.52). These values increased only modestly with inclusion of serum alpha-fetoprotein testing, contrast-enhanced abdominal computed tomographic scans or magnetic resonance imagings, and/or extension of up-to-date time to 12 months. Being diagnosed by a nongastroenterology provider and increasing age were significantly associated with decreased HCC surveillance (Psurveillance (Psurveillance rates remained low. HCC surveillance rates in commercially insured at-risk patients remain poor despite formalized guidelines, highlighting the need to develop interventions to improve surveillance rates.

  1. Local Arterial Therapies in the Management of Unresectable Hepatocellular Carcinoma.

    Science.gov (United States)

    Mouli, Samdeep K; Goff, Laura W

    2017-10-27

    Most patients with hepatocellular carcinoma present with intermediate to advanced disease, where curative therapies are no longer an option. These patients with intermediate to advanced disease represent a heterogeneous population with regard to tumor burden, liver function, and performance status. While the Barcelona Clinic Liver Cancer (BCLC) staging system offers guidelines for the management of these patients, strict adherence to these guidelines may limit treatment options for these patients. Several locoregional therapies exist for these patients, including conventional transarterial chemoembolization (cTACE), transarterial embolization (TAE), drug-eluting embolization (DEE), and radioembolization. Evidence is also emerging for the role of radiation therapy including most notably stereotactic body radiation therapy and proton therapy, although at the current time, clinical trial participation is encouraged. While cTACE is traditionally recommended for BCLC B disease, both cTACE and radioembolization are increasingly used for patients with intermediate disease, as well as in select patients with BCLC A and C disease. TAE and DEE are limited in their use currently, due to lack of clear survival benefits or clinical advantages over cTACE. While several studies have demonstrated similar OS between cTACE and radioembolization, radioembolization provides a longer time to progression and fewer toxicities compared to cTACE. This is particularly relevant in the setting of advanced BCLC B and early BCLC C disease, where patients may have limited reserve. Radioembolization also has additional roles as an alternative to ablation, inducing liver hypertrophy, treating patients with PVT, and downstaging lesions to transplant. Ongoing studies will further define the role of locoregional treatment potentially in combination with and in light of developments in systemic therapy.

  2. A systems biology-based classifier for hepatocellular carcinoma diagnosis.

    Directory of Open Access Journals (Sweden)

    Yanqiong Zhang

    Full Text Available AIM: The diagnosis of hepatocellular carcinoma (HCC in the early stage is crucial to the application of curative treatments which are the only hope for increasing the life expectancy of patients. Recently, several large-scale studies have shed light on this problem through analysis of gene expression profiles to identify markers correlated with HCC progression. However, those marker sets shared few genes in common and were poorly validated using independent data. Therefore, we developed a systems biology based classifier by combining the differential gene expression with topological features of human protein interaction networks to enhance the ability of HCC diagnosis. METHODS AND RESULTS: In the Oncomine platform, genes differentially expressed in HCC tissues relative to their corresponding normal tissues were filtered by a corrected Q value cut-off and Concept filters. The identified genes that are common to different microarray datasets were chosen as the candidate markers. Then, their networks were analyzed by GeneGO Meta-Core software and the hub genes were chosen. After that, an HCC diagnostic classifier was constructed by Partial Least Squares modeling based on the microarray gene expression data of the hub genes. Validations of diagnostic performance showed that this classifier had high predictive accuracy (85.88∼92.71% and area under ROC curve (approximating 1.0, and that the network topological features integrated into this classifier contribute greatly to improving the predictive performance. Furthermore, it has been demonstrated that this modeling strategy is not only applicable to HCC, but also to other cancers. CONCLUSION: Our analysis suggests that the systems biology-based classifier that combines the differential gene expression and topological features of human protein interaction network may enhance the diagnostic performance of HCC classifier.

  3. Regorafenib in advanced hepatocellular carcinoma (HCC): considerations for treatment.

    Science.gov (United States)

    Kim, Kyung; Jha, Reena; Prins, Petra A; Wang, Hongkun; Chacha, Monica; Hartley, Marion L; He, Aiwu Ruth

    2017-11-01

    We report our institutional observations of ten patients with advanced hepatocellular carcinoma (HCC) (seven and three were Child-Pugh class A and B, respectively) who received compassionate regorafenib therapy between June 2016 and January 2017. These patients did not fit the rigid criteria of a clinical trial and represented the use of regorafenib in an everyday clinic situation. Regorafenib (160 mg P.O. daily) was administered to patients on a 4-week cycle (3 weeks on, 1 week off) until disease progression (assessed using mRECIST criteria) or discontinuation secondary to toxicity (assessed using CTCAE criteria). Relevant clinical data were abstracted from patient medical records and reviewed retrospectively. The median duration of patient treatment was 6.6 weeks, and the median time to disease progression was 12.5 weeks. Most common treatment emergent adverse events were fatigue, diarrhea, and hand-foot skin reaction. Elevated AST and ALT were the most commonly observed laboratory-assessed adverse events, which reached grade 3 status in the Child-Pugh class B patients only. We observed intolerance to regorafenib treatment in one patient who had previously received a liver transplant. We also saw lithium toxicity in one patient receiving long-term lithium treatment, suggesting a potential and unexpected drug-drug interaction with regorafenib. Taken together, our observations indicate that regorafenib is beneficial in the treatment of patients with advanced HCC who progressed on or demonstrated intolerance to sorafenib therapy; however, careful selection and close monitoring of patients is necessary to maximize the benefit while minimizing the toxicities of regorafenib treatment.

  4. STAT3 mediates regorafenib-induced apoptosis in hepatocellular carcinoma.

    Science.gov (United States)

    Tai, Wei-Tien; Chu, Pei-Yi; Shiau, Chung-Wai; Chen, Yao-Li; Li, Yong-Shi; Hung, Man-Hsin; Chen, Li-Ju; Chen, Pei-Lung; Su, Jung-Chen; Lin, Ping-Yi; Yu, Hui-Chuan; Chen, Kuen-Feng

    2014-11-15

    Here, we aim to investigate the molecular mechanism of regorafenib and verify the potential druggable target for the treatment of hepatocellular carcinoma (HCC). HCC cell lines (PLC5, HepG2, Hep3B, SK-Hep1, and HA59T) were used to investigate the in vitro effect of regorafenib. Phosphatase activity was analyzed in HCC cells and purified SHP-1 proteins. PLC5-bearing mice were used to test the therapeutic efficiency of 20 and 40 mg/kg/d treatment with regorafenib ([Formula: see text] mice). The clinical relevance of STAT3 signaling was investigated with 142 tumor samples from different patients with HCC. Descriptive statistical analysis was used to compare the baseline characteristics of patients and the expression of p-STAT3. Regorafenib inhibited STAT3-related signaling in a dose-dependent manner and was a more potent inhibitor of STAT3 than sorafenib. Regorafenib increased SHP-1 phosphatase activity in purified SHP-1 protein directly. N-SH2 domain deletion and D61A mutants mimicking open-form SHP-1 partially abolished regorafenib-induced STAT3 inhibition and apoptosis. Importantly, a higher level of expression of STAT3 was found in patients with advanced clinical stages (P = 0.009) and poorly differentiated tumors (P = 0.035). Regorafenib induced significant tumor inhibition by relieving the autoinhibited N-SH2 domain of SHP-1 directly and inhibiting p-STAT3 signals. STAT3 may be suitable as a prognostic marker of HCC development, and may be a druggable target for HCC-targeted therapy using regorafenib. ©2014 American Association for Cancer Research.

  5. Living donor liver transplantation for hepatocellular carcinoma achieves better outcomes.

    Science.gov (United States)

    Lin, Chih-Che; Chen, Chao-Long

    2016-10-01

    Liver transplantation (LT) for hepatocellular carcinoma (HCC) at Kaohsiung Chang Gung Memorial Hospital mainly relies on live donor LT (LDLT). Owing to taking the risk of LD, we are obligated to adopt strict selection criteria for HCC patients and optimize the pre-transplant conditions to ensure a high disease-free survival similar to those without HCC, even better than deceased donor LT (DDLT). Better outcomes are attributed to excellent surgical results and optimal patient selection. The hospital mortality of primary and salvage LDLT are lower than 2% in our center. Although Taiwan Health Insurance Policy extended the Milan to University of California, San Francisco (UCSF) criteria in 2006, selection criteria will not be consolidated to take into account only by the morphologic size/number of tumors but also by their biology. The criteria are divided into modifiable image morphology, alpha fetoprotein (AFP), and positron emission tomography (PET) scan with standard uptake value (SUV) and unmodifiable unfavorable pathology such as HCC combined with cholangiocarcinoma (CC), sarcomatoid type, and poor differentiation. Downstaging therapy is necessary for HCC patients beyond criteria to fit all modifiable standards. The upper limit of downstaging treatment seems to be extended by more effective drug eluting transarterial chemoembolization in cases without absolute contraindications. In contrast, the pitfall of unmodifiable tumor pathology should be excluded by the findings of pretransplant core biopsy/resection if possible. More recently, achieving complete tumor necrosis in explanted liver could almost predict no recurrence after transplant. Necrotizing therapy is advised if possible before transplant even the tumor status within criteria to minimize the possibility of tumor recurrence. LDLT with low surgical mortality in experienced centers provides the opportunities of optimizing the pre-transplant tumor conditions and timing of transplant to achieve better

  6. Local radiotherapy for patients with unresectable hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Park, Won; Lim, Do Hoon; Paik, Seung Woon; Koh, Kwang Cheol; Choi, Moon Seok; Park, Cheol Keun; Yoo, Byung Chul; Lee, Jeong Eun; Kang, Min Kyu; Park, Young Je; Nam, Hee Rim; Ahn, Yong Chan; Huh, Seung Jae

    2005-01-01

    Purpose: To evaluate the response to local radiotherapy (RT) for unresectable hepatocellular carcinoma (HCC) and to analyze the dose-response relationship and the treatment-related morbidities. Methods and materials: Between 1998 and 2002, 59 patients who were treated with localized RT were evaluated. RT was delivered with a curative intent, and the radiation dose was 30-55 Gy (biologic effective dose of 39.0-70.2 Gy 10 using the α/β ratio of 10 Gy) with 2-3 Gy as a daily dose. The tumor response was evaluated by the change in maximum tumor size on serial CT scans, and the morbidity was evaluated by the Common Terminology Criteria for Adverse Events v3.0. Results: An objective tumor response was achieved in 39 of 59 patients (66.1%) with complete response (CR) in 5 patients and partial response (PR) in 34 patients. More than 50 Gy 10 had a significant response; CR or PR was 72.8% with >50 Gy 10 and 46.7% with ≤50 Gy 10 (p = 0.0299). The 2-year overall survival rate after RT was 27.4% (median survival time: 10 months), and this was affected by the tumor response (p = 0.0640); the 2-year overall survival rate after RT was 50.0% for CR and 21.8% for PR. There was no Grade 3 or 4 acute toxicity, and 3 patients (5.1%) developed gastric or duodenal ulcer. Conclusions: Radiotherapy for unresectable HCC resulted in 66.1% of tumor response with acceptable toxicity, and the radiation dose seems to be a significant prognostic factor in RT response for HCC

  7. Stereotactic Body Radiation Therapy in Recurrent Hepatocellular Carcinoma

    International Nuclear Information System (INIS)

    Huang, Wen-Yen; Jen, Yee-Min; Lee, Meei-Shyuan; Chang, Li-Ping; Chen, Chang-Ming; Ko, Kai-Hsiung; Lin, Kuen-Tze; Lin, Jang-Chun; Chao, Hsing-Lung; Lin, Chun-Shu; Su, Yu-Fu; Fan, Chao-Yueh; Chang, Yao-Wen

    2012-01-01

    Purpose: To examine the safety and efficacy of Cyberknife stereotactic body radiation therapy (SBRT) and its effect on survival in patients of recurrent hepatocellular carcinoma (HCC). Methods and Materials: This was a matched-pair study. From January 2008 to December 2009, 36 patients with 42 lesions of unresectable recurrent HCC were treated with SBRT. The median prescribed dose was 37 Gy (range, 25 to 48 Gy) in 4–5 fractions over 4–5 consecutive working days. Another 138 patients in the historical control group given other or no treatments were selected for matched analyses. Results: The median follow-up time was 14 months for all patients and 20 months for those alive. The 1- and 2-year in-field failure-free rates were 87.6% and 75.1%, respectively. Out-field intrahepatic recurrence was the main cause of failure. The 2-year overall survival (OS) rate was 64.0%, and median time to progression was 8.0 months. In the multivariable analysis of all 174 patients, SBRT (yes vs. no), tumor size (≤4 cm vs. >4 cm), recurrent stage (stage IIIB/IV vs. I) and Child-Pugh classification (A vs. B/C) were independent prognostic factors for OS. Matched-pair analysis revealed that patients undergoing SBRT had better OS (2-year OS of 72.6% vs. 42.1%, respectively, p = 0.013). Acute toxicities were mild and tolerable. Conclusion: SBRT is a safe and efficacious modality and appears to be well-tolerated at the dose fractionation we have used, and its use correlates with improved survival in this cohort of patients with recurrent unresectable HCC. Out-field recurrence is the major cause of failure. Further studies of combinations of SBRT and systemic therapies may be reasonable.

  8. Imaging manifestation of hepatocellular carcinoma with bile duct tumor thrombi

    International Nuclear Information System (INIS)

    Liu Qingyu; Chen Jianyu; Liang Biling; Hu Tao

    2008-01-01

    Objective: To analyze the imaging features of hepatocellular carcinoma(HCC) with bile duct tumor thrombi. Methods: Thirteen patients with bile duct tumor thrombi proved pathologically underwent imaging examination. MR and CT were performed in 3 cases, and 2 cases had CT only and 8 cases had MRI only. Ultrasonography(US) was performed in all 13 patients. The accuracy of bile duct tumor thrombi detection was compared between US, CT and MRI with Fisher test. Results: Liver tumors and bile duct tumor thrombi were demonstrated in all patients on CT or MRI. Presence of intraluminal soft tissue mass was found in four of five cases on CT, and mild enhancement of the intraluminal mass in the arterial phase was noted, dilated bile duct distal to tumor thrombi was detected in all five patients. Eleven Tumor thrombi showed slight low signal intensity on T 1 WI, slight high signal intensity on T 2 WI, and mild to moderate contrast enhancement on the contrast-enhanced MR images. The MRCP findings of tumor thrombi were as follows: interruption, stricture of the bile ducts or irregular filling defect in the bile ducts with dilated intrahepatic ducts, bile duet was abruptly interrupted or showed a 'rat-tail' stricture (n=5); the common bile duct was filled with tumor thrombi, intrahepatic bile duct dilatation and missing common bile duct was noted on MRCP (n=2). Bile duct tumor thrombi were correctly diagnosed in 7 cases on US, and 12 cases on CT or MRI. Six cases were misdiagnosed or miss-diagnosed on US, and 4 cases were misdiagnosed on CT or MRI. There was no significant difference between US and CT/MRI in diagnosis of bile duct tumor thrombi (P=0.270). Conclusion: CT or MR imaging is useful for the diagnosis of HCC with biliary tumor thrombi and for evaluating the extension of thrombi. (authors)

  9. Epidemiology of hepatocellular carcinoma: target population for surveillance and diagnosis.

    Science.gov (United States)

    Tang, An; Hallouch, Oussama; Chernyak, Victoria; Kamaya, Aya; Sirlin, Claude B

    2018-01-01

    Hepatocellular carcinoma (HCC) is the sixth most common cancer and the second leading cause of cancer mortality worldwide. Incidence rates of liver cancer vary widely between geographic regions and are highest in Eastern Asia and sub-Saharan Africa. In the United States, the incidence of HCC has increased since the 1980s. HCC detection at an early stage through surveillance and curative therapy has considerably improved the 5-year survival. Therefore, medical societies advocate systematic screening and surveillance of target populations at particularly high risk for developing HCC to facilitate early-stage detection. Risk factors for HCC include cirrhosis, chronic infection with hepatitis B virus (HBV), hepatitis C virus (HCV), excess alcohol consumption, non-alcoholic fatty liver disease, family history of HCC, obesity, type 2 diabetes mellitus, and smoking. Medical societies utilize risk estimates to define target patient populations in which imaging surveillance is recommended (risk above threshold) or in which the benefits of surveillance are uncertain (risk unknown or below threshold). All medical societies currently recommend screening and surveillance in patients with cirrhosis and subsets of patients with chronic HBV; some societies also include patients with stage 3 fibrosis due to HCV as well as additional groups. Thus, target population definitions vary between regions, reflecting cultural, demographic, economic, healthcare priority, and biological differences. The Liver Imaging Reporting and Data System (LI-RADS) defines different patient populations for surveillance and for diagnosis and staging. We also discuss general trends pertaining to geographic region, age, gender, ethnicity, impact of surveillance on survival, mortality, and future trends.

  10. Bland Embolization of Hepatocellular Carcinoma Using Superabsorbent Polymer Microspheres

    International Nuclear Information System (INIS)

    Osuga, Keigo; Hori, Shinichi; Hiraishi, Kumiko; Sugiura, Takashi; Hata, Yasuhiro; Higashihara, Hiroki; Maeda, Noboru; Tomoda, Kaname; Nakamura, Hironobu

    2008-01-01

    The purpose of this study was to investigate the clinical outcomes of bland embolization using superabsorbent polymer microspheres (SAP-TAE) as an initial therapeutic option for previously untreated hepatocellular carcinoma (HCC) ineligible for resection or ablation. Fifty-nine patients with previously untreated HCC unamenable to surgery or ablation underwent bland embolization using 100- to 200-μm reconstituted SAP particles (SAP-TAE) as the initial treatment. SAP-TAE was repeated as needed based on tumor response but was switched to chemoembolization when necessary to control residual or progressive tumor. Early tumor response was assessed by contrast-enhanced CT according to RECIST and EASL criteria 1 month after the initial SAP-TAE. The overall survival was calculated using the Kaplan-Meier method. The overall mean follow-up period was 30.6 months (range, 7-59 months). A total of 121 sessions of SAP-TAE were performed, with 1-5 sessions per patient (mean, 2.1 sessions). The mean period of repeated SAP-TAE was 15.6 months (range, 1-51 months), and it exceeded 1 and 2 years in 32 (54%) and 15 (25%) patients, respectively. Thirteen (22%) patients underwent repeated SAP-TAE alone, and the remaining 46 (78%) patients underwent subsequent chemoembolization. No major complication was observed and postembolization syndrome was minimal after SAP-TAE in all patients. Response rate was 14% and 66% by RECIST and EASL criteria, respectively. Overall survival rates were 100% and 83% at 1 and 2 years, respectively, and median survival time was 30 months. In conclusion, SAP-TAE was a safe and repeatable option as the induction therapy for HCC unamenable to surgery or ablation, despite the high incidence of converting to TACE during the total course.

  11. Family history influences the early onset of hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Chung-Hwa Park; Seung-Hee Jeong; Hyeon-Woo Yim; Jin Dong Kim; Si Hyun Bae; Jong Young Choi; Seung Kew Yoon

    2012-01-01

    AIM:To evaluate the relationship between a positive family history of primary liver cancer and hepatocellular carcinoma (HCC) development in Korean HCC patients.METHODS:We studied a total of 2242 patients diagnosed with HCC between January 1990 and July 2008,whose family history of primary liver cancer was clearly described in the medical records.RESULTS:Of the 2242 patients,165 (7.4%) had a positive family history of HCC and 2077 (92.6%) did not.The male to female ratio was 3.6:1,and the major causes of HCC were chronic hepatitis B virus (HBV) infection in 75.1%,chronic hepatitis C virus infection in 13.2% and alcohol in 3.1%.The median ages at diagnosis in the positive-and negative-history groups were 52 years (range:29-79 years) and 57 years (range:18-89 years),respectively (P < 0.0001).Furthermore,among 1713 HCC patients with HBV infection,the number of patients under 45 years of age out of 136 patients with positive family history was 26 (19.1%),whereas those out of 1577 patients with negative family history was 197 (12.5%),suggesting that a positive family history may be associated with earlier development of HCC in the Korean population (P =0.0028).CONCLUSION:More intensive surveillance maybe recommended to those with a positive family history of HCC for earlier diagnosis and proper management especially when HBV infection is present.

  12. Sorafenib prescribed by gastroenterologists and hepatologists for hepatocellular carcinoma

    Science.gov (United States)

    Kaplan, David E.; Mehta, Rajni; D’Addeo, Kathryn; Valderrama, Adriana; Taddei, Tamar H.

    2018-01-01

    Abstract Sorafenib is the only Food and Drug Administration (FDA)-approved first-line therapy shown to have survival benefit for patients with advanced hepatocellular carcinoma (HCC). Patients with advanced HCC are often but not exclusively transferred from non-oncologists to oncologists to initiate systemic therapy. The objective of this study was to assess whether sorafenib prescribing by non-oncologists has any impact on utilization, adverse effects, cost or outcome. This was a retrospective cohort study utilizing data from patients prescribed sorafenib for HCC within Veterans Health Administration hospitals with 100% chart abstraction to confirm HCC diagnosis, identify prescribing provider specialty (oncology versus gastroenterology/hepatology), and obtain data required for cancer staging by the Barcelona Clinic Liver Cancer (BCLC) system. The primary outcome was overall survival from the time of sorafenib prescription. A total of 4903 patients who prescribed sorafenib for HCC were identified, for whom 340 patients (6.9%) were prescribed drug by a non-oncologist (Onc). BCLC Stage, age, Child–Turcotte–Pugh score, and comorbidity indices were similar between patients prescribed sorafenib by oncologists and non-oncologists. Oncologists more often discontinued sorafenib due to progression, whereas non-oncologists were more likely to continue sorafenib until death resulting in greater pill utilization and cost. Overall survival in both unadjusted and multivariable models showed no significant impact of prescriber type on survival (222 vs 217 days, P = .96), confirmed with propensity-matched subcohorts. Similar survival outcomes were observed for patients with HCC prescribed sorafenib by non-oncologists and oncologists, suggesting that non-oncologists with expertise in the management of HCC can safely and effectively administer sorafenib. PMID:29369224

  13. Role of sex steroid receptors in pathobiology of hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Mamta Kalra; Jary Mayes; Senait Assefa; Anil K Kaul; Rashmi Kaul

    2008-01-01

    The striking gender disparity observed in the incidence of hepatocellular carcinoma (HCC) suggests an important role of sex hormones in HCC pathogenesis. Though the studies began as early as in 1980s, the precise role of sex hormones and the significance of their receptors in HCC still remain poorly understood and perhaps contribute to current controversies about the potential use of hormonal therapy in HCC. A comprehensive review of the existing literature revealed several shortcomings associated with the studies on estrogen receptor (ER) and androgen receptor (AR) in normal liver and HCC. These shortcomings include the use of less sensitive receptor ligand binding assays and immunohistochemistry studies for ERα alone until 1996 when ERβ isoform was identified. The animal models of HCC utilized for studies were primarily based on chemical-induced hepatocarcinogenesis with less similarity to virus-induced HCC pathogenesis. However, recent in vitro studies in hepatoma cells provide newer insights for hormonal regulation of key cellular processes including interaction of ER and AR with viral proteins. In light of the above facts, there is an urgent need for a detailed investigation of sex hormones and their receptors in normal liver and HCC. In this review, we systematically present the information currently available on androgens, estrogens and their receptors in normal liver and HCC obtained from in vitro, in vivo experimental models and clinical studies. This information will direct future basic and clinical research to bridge the gap in knowledge to explore the therapeutic potential of hormonal therapy in HCC. 2008 The WJG Press. All rights reserved.

  14. Survival prediction model for postoperative hepatocellular carcinoma patients.

    Science.gov (United States)

    Ren, Zhihui; He, Shasha; Fan, Xiaotang; He, Fangping; Sang, Wei; Bao, Yongxing; Ren, Weixin; Zhao, Jinming; Ji, Xuewen; Wen, Hao

    2017-09-01

    This study is to establish a predictive index (PI) model of 5-year survival rate for patients with hepatocellular carcinoma (HCC) after radical resection and to evaluate its prediction sensitivity, specificity, and accuracy.Patients underwent HCC surgical resection were enrolled and randomly divided into prediction model group (101 patients) and model evaluation group (100 patients). Cox regression model was used for univariate and multivariate survival analysis. A PI model was established based on multivariate analysis and receiver operating characteristic (ROC) curve was drawn accordingly. The area under ROC (AUROC) and PI cutoff value was identified.Multiple Cox regression analysis of prediction model group showed that neutrophil to lymphocyte ratio, histological grade, microvascular invasion, positive resection margin, number of tumor, and postoperative transcatheter arterial chemoembolization treatment were the independent predictors for the 5-year survival rate for HCC patients. The model was PI = 0.377 × NLR + 0.554 × HG + 0.927 × PRM + 0.778 × MVI + 0.740 × NT - 0.831 × transcatheter arterial chemoembolization (TACE). In the prediction model group, AUROC was 0.832 and the PI cutoff value was 3.38. The sensitivity, specificity, and accuracy were 78.0%, 80%, and 79.2%, respectively. In model evaluation group, AUROC was 0.822, and the PI cutoff value was well corresponded to the prediction model group with sensitivity, specificity, and accuracy of 85.0%, 83.3%, and 84.0%, respectively.The PI model can quantify the mortality risk of hepatitis B related HCC with high sensitivity, specificity, and accuracy.

  15. Multimodal treatment of hepatocellular carcinoma: an eastern European experience.

    Science.gov (United States)

    Dima, Simona Olimpia; Iacob, Speranţa; Botea, Florin; Matei, Emil; Dorobanfu, Bogdan; Vasile, Serban; Alexandrescu, Sorin; Croitoru, Adina; Dumitrascu, Traian; Stroescu, Cezar; Herlea, Vlad; Popescu, Irinel

    2009-01-01

    The aim of the present study was to evaluate the outcomes of a multimodal treatment approach of hepatocellular carcinoma (HCC) in a tertiary hepatobiliary specialty center. A total of 294 consecutive patients treated for HCC were retrospectively analyzed. Two hundred sixteen patients (73.4%) were men and 78 (26.6%) were women. Liver resection (LR) was performed in 201 patients (68.4%), liver transplantation (LT) in 19 patients (6.5%), radiofrequency ablation (RFA) in 74 patients (25.1%), and 56 (19%) patients received adjuvant systemic chemotherapy. The median follow-up was 15.7 mo (range 0.1-90.3). Five-year overall survival and recurrence rates were 28% and 26.8%, respectively. Serum AFP > 43.8ng/ml (p = 0.005), BCLC C/D (p = 0.006) and JIS 3/4/5 classifications (p = 0.02) were independent negative prognostic factors for overall survival, while JIS 3/4/5 (p = 0.01) and BCLC C/D (p = 0.01) classifications, tumors larger than 6.5cm (p = 0.001) and RFA (p = 0.02) were independent predictors for recurrence. The current treatment of HCC should be multimodal, and therapeutic modalities and their combinations should be tailored to each patient. LT represents the best therapeutic option for patients with HCC in the setting of cirrhosis. Resection remains a good option in cirrhotic patients, while RFA is a safe and effective procedure for small tumors.

  16. Autopsy cases of hepatocellular carcinoma in atomic bomb survivors

    International Nuclear Information System (INIS)

    Fujihara, Megumu; Kurihara, Kanji; Aimitsu, Shiomi; Yukaya, Hirofumi; Hamada, Tadao.

    1994-01-01

    Since 1956, 388 autopsy cases of hepatocellular carcinoma (HCC) have been obtained at the Hiroshima Red Cross and A-Bomb Survivors Hospital, which consisted of those of proximately exposed 52 A-bomb survivors (mean age, 63.8 years), 105 distally exposed A-bomb survivors (mean age, 64.2 years), and the other 231 non-exposed patients (mean age, 60.6 years). Since 1985, the incidence of HCC tended to be higher in both proximately and distally exposed groups than the non-exposed group. There was no consistent tendency for the incidence of HCC by ages at autopsy and A-bombing. The incidence of liver cirrhosis was approximately 2 times higher in males than females in the non-exposed group, although no gender difference existed after 1981. In the exposed group, the incidence was similar in male and female groups. Approximately 90% of HCC patients had coexistent liver cirrhosis. Liver cirrhosis was associated with HCC in 50-60%. No significant differences in these incidences were observed between the exposed and non-exposed groups. The proportion of liver cirrhosis associated with HCC became constant in patients over the age of 40 in the non-exposed group. In the exposed group, on the other hand, the proportion reached the peak in those in their fifties and sixties. Survival time tended to be longer in the exposed group than the non-exposed group. The patients in the non-exposed group tended to have histologically atypical type and metastases, as compared with those in the exposed group. (N.K.)

  17. Qualitative diagnosis of small hepatocellular carcinoma by MRI

    International Nuclear Information System (INIS)

    Inoue, Etsuo; Kuroda, Chikazumi; Fujita, Makoto

    1994-01-01

    This study evaluated the usefulness of magnetic resonance imaging (MRI) in the qualitative diagnosis of small hepatocellular carcinoma (HCC). A total of 20 nodules w