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Sample records for advanced hepatocellular carcinoma

  1. New advances in hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Sonia; Pascual; Iván; Herrera; Javier; Irurzun

    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 withwell 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 atrisk 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.

  2. Advances in hepatocellular carcinoma: Nonalcoholic steatohepatitis-related hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Fauzia; Z; Khan; Ryan; B; Perumpail; Robert; J; Wong; Aijaz; Ahmed

    2015-01-01

    An increase in the prevalence of obesity and diabetes mellitus has been associated with the rise in non-alcoholic fatty liver disease(NAFLD). Two-thirds of the obese and diabetic populations are estimated to develop NAFLD. Currently, NAFLD is the most common etiology for chronic liver disease globally. The clinical spectrum of NAFLD ranges from simple steatosis, an accumulation of fat greater than 5% of liver weight, to nonalcoholic steatohepatitis(NASH), a more aggressive form with necroinflammation and fibrosis. Among the patients who develop NASH, up to 20% may advance to cirrhosis and are at risk for complications of end-stage liver disease. One of the major complications observed in patients with NASH-related cirrhosis is hepatocellular carcinoma(HCC), which has emerged as the sixth most common cancer and second leading etiology of cancer-related deaths worldwide. The incidence of HCC in the United States alone has tripled over the last three decades. In addition, emerging data are suggesting that a small proportion of patients with NAFLD may be at higher risk for HCC in the absence of cirrhosis - implicating obesity and diabetes mellitus as potential risk factors for HCC.

  3. Sorafenib in advanced hepatocellular carcinoma

    DEFF Research Database (Denmark)

    Køstner, Anne Helene; Sørensen, M; Olesen, René Krøjgaard;

    2013-01-01

    Advanced HCC is a clinical challenge with limited treatment options. The multikinase inhibitor sorafenib is the first and only agent showing a survival benefit in these patients. In this study we evaluate the efficacy and tolerability of sorafenib in an unselected patient population. Furthermore ...

  4. Evolution of systemic therapy of advanced hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Thomas Yau; Pierre Chan; Richard Epstein; Ronnie T Poon

    2008-01-01

    Hepatocellular carcinoma (HCC) commonly occurs in hepatitis B endemic areas, especially in Asian countries. HCC is highly refractory to cytotoxic chemotherapy. This resistance is partly related to its tumor biology, pharmacokinetic properties, and both intrinsic and acquired drug resistance. There is no convincing evidence thus far that systemic chemotherapy improves overall survival in advanced HCC patients.Other systemic approaches, such as hormonal therapy and immunotherapy, have also disappointing results. Recently, encouraging results have been shown in using sorafenib in the treatment of advanced HCC patients. In this review, we concisely summarize the evolution of developments in the systemic therapy of advanced HCC.

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

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    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.

  6. Hepatocellular carcinoma:current management and recent advances

    Institute of Scientific and Technical Information of China (English)

    Wan-Yee Lau; Eric C. H. Lai

    2008-01-01

    BACKGROUND:Hepatocellular carcinoma (HCC) is a major health problem worldwide. It is the iffth most common cancer in the world, and the third most common cause of cancer-related death. Without speciifc treatment, the prognosis is very poor. The goal of management is"cancer control"-a reduction in its incidence and mortality as well as an improvement in the quality of life of patients with HCC and their families. This article aims to review the current management of HCC and its recent advances. DATA SOURCES:A MEDLINE database search was performed to identify relevant article using the keywords"hepatocellular carcinoma", "hepatectomy", "liver transplantation", and"local ablative therapy". Additional papers and book chapters were identiifed by a manual search of the references from the key articles. RESULTS:Liver resection and liver transplantation remain the options that give the best chance of a cure. Recent evidence suggests that local ablative therapy may offer comparable survival results in patients with small HCC, and preserved liver function. Transarterial chemoembolization (TACE) is the most promising palliative modality for unresectable HCC, but other techniques, such as transarterial radioembolization (TARE), and local ablative therapy, have also shown comparable results. CONCLUSIONS:Early diagnosis of HCC remains a key goal in improving the prognosis of patients. During the last two decades, operative mortality and surgical outcome of liver resection and liver transplantation for HCC have improved. Progress also has been made in multi-modality therapy which can increase the chance of survival and improve the quality of life for patients with advanced HCC.

  7. Therapeutic options for intermediate-advanced hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Zong-Ming Zhang; Jin-Xing Guo; Zi-Chao Zhang; Nan Jiang; Zhen-Ya Zhang; Li-Jie Pan

    2011-01-01

    Hepatocellular carcinoma (HCC) is one of the most common malignancies, ranking the sixth in the world, with 55% of cases occurring in China. Usually, patients withHCC did not present until the late stage of the disease,thus limiting their therapeutic options. Although surgical resection is a potentially curative modality for HCC,most patients with intermediate-advanced HCC are not suitable candidates. The current therapeutic modalities for intermediate-advanced HCC include: (1) surgical procedures,such as radical resection, palliative resection,intraoperative radiofrequency ablation or cryosurgical ablation, intraoperative hepatic artery and portal vein chemotherapeutic pump placement, two-stage hepatectomy and livertransplantation; (2) interventional treatment,such as transcatheter arterial chemoembolization,portal vein embolization and image-guided locoregional therapies; and (3) molecularly targeted therapies. So far, how to choose the therapeutic modalities remains controversial. Surgeons are faced with the challenge of providing the most appropriate treatment for patients with intermediate-advanced HCC. This review focuses on the optional therapeutic modalities for intermediateadvanced HCC.

  8. Hepatocellular carcinoma: Advances in diagnosis, management, and long term outcome.

    Science.gov (United States)

    Bodzin, Adam S; Busuttil, Ronald W

    2015-05-28

    Hepatocellular carcinoma (HCC) remains a common and lethal malignancy worldwide and arises in the setting of a host of diseases. The incidence continues to increase despite multiple vaccines and therapies for viruses such as the hepatitis B and C viruses. In addition, due to the growing incidence of obesity in Western society, there is anticipation that there will be a growing population with HCC due to non-alcoholic fatty liver disease. Due to the growing frequency of this disease, screening is recommended using ultrasound with further imaging using magnetic resonance imaging and multi-detector computed tomography used for further characterization of masses. Great advances have been made to help with the early diagnosis of small lesions leading to potential curative resection or transplantation. Resection and transplantation maybe used in a variety of patients that are carefully selected based on underlying liver disease. Using certain guidelines and clinical acumen patients may have good outcomes with either resection or transplantation however many patients are inoperable at time of presentation. Fortunately, the use of new locoregional therapies has made down staging patients a potential option making them potential surgical candidates. Despite a growing population with HCC, new advances in viral therapies, chemotherapeutics, and an expanding population of surgical and transplant candidates might all contribute to improved long-term survival of these patients.

  9. Sorafenib in Liver Function Impaired Advanced Hepatocellular Carcinoma

    Institute of Scientific and Technical Information of China (English)

    You-xin Ji; Lei Sun; Zong-chun Zhang; Zhong-fa Zhang; Ke-tao Lan; Ke-ke Nie; Chuan-xin Geng; Shi-chao Liu; Ling Zhang; Xing-jun Zhuang; Xiao Zou

    2014-01-01

    Objective To explore the efficacy and safty of sorafenib in Child-Pugh class B to class C hepatocellular carcinoma (HCC). Methods In this three-center open-label study from November 2011 to May 2013, we randomly assigned 189 patients with advanced Child-Pugh class B or C HCC patients into two groups, one group with 95 patient to receive sorafenib (400 mg a time, twice a day) and the other group with 94 patients to receive best supportive care. The primary end points were progression-free survival and overall survival. Results The median progression-free survival was 2.2 months and 1.9 months in the sorafenib group and best supportive care group respectively (Hazard ratio in the sorafenib group, 0.55; 95% confidence interval, 0.40-0.75;P=0.002). The median overall survival was 4.0 months and 3.5 months in the sorafenib group and best supportive care group respectively (Hazard ratio in the sorafenib group, 0.48;95%confidence interval, 0.35-0.68;P Conclusions Sorafenib is safe in patients with liver function impaired advanced HCC. It is effective in terms of progression-free survival and overall survival compared with best supportive care. Liver functions are the important predictive factors.

  10. Systemic chemo-immunotherapy for advanced-stage hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Xiao-Yu Yin; Ming-De Lü; Li-Jian Liang; Jia-Ming Lai; Dong-Ming Li; Ming Kuang

    2005-01-01

    AIM: To evaluate the therapeutic efficacy of systemic chemo-immunotherapy for advanced hepatocellular carcinoma (HCC).METHODS: Twenty-six patients with advanced HCC were treated by using systemic chemo-immunotherapy (PIAF regimen), which consisted of cisplatin (20 mg/m2) intravenously daily for 4 consecutive day, doxorubicin (40 mg/m2)intravenously on day 1, 5-fiuorouracil (400 mg/m2)intravenously daily for 4 consecutive day, and human recombinant α-interferon-2a (5 Mu/m2) subcutaneous injection daily for 4 consecutive day. The treatment was repeated every 3 wk, with a maximum of six cycles.RESULTS: A total of 90 cycles of PIAF treatment were administered, with a mean number of 3.9 cycles per patient.Eight patients received six cycles of treatment (group A),and the remaining 18 were subjected to two to five cycles (group B). There were 0 complete response, 4 partial responses, 9 static diseases and 13 progressive diseases,with a disease control rate of 50% (13/26). The 1-year survival rate was 24.3%, with a median survival time of 6.0 mo. Group A had a remarkably better survival as compared with group B, the 1- and 2-year survival rates were 62.5% vs 6.1% and 32.3% vs 0%, and a median survival time was 12.5 mo vs 5.0 mo (P = 0.001).CONCLUSION: Systemic chemo-immunotherapy using PIAF regimen represented an effective treatment and could improve the survival rate and prolong the survival time in selected patients with advanced HCC.

  11. Hepatocellular carcinoma: Advances in diagnosis, management, and long term outcome

    OpenAIRE

    Bodzin, AS; Busuttil, RW

    2015-01-01

    © 2015 Baishideng Publishing Group Inc. Hepatocellular carcinoma (HCC) remains a common and lethal malignancy worldwide and arises in the setting of a host of diseases. The incidence continues to increase despite multiple vaccines and therapies for viruses such as the hepatitis B and C viruses. In addition, due to the growing incidence of obesity in Western society, there is anticipation that there will be a growing population with HCC due to non-alcoholic fatty liver disease. Due to the grow...

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

    Institute of Scientific and Technical Information of China (English)

    Yang Hyun Baek; Kyoung Tae Kim; Sung Wook Lee; Jin Sook Jeong; Byeong Ho Park; Kyung Jin Nam; Jin Han Cho

    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 12.9mo,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.

  13. Cyberknife treatment for advanced or terminal stage hepatocellular carcinoma

    Science.gov (United States)

    Kato, Hiroyuki; Yoshida, Hideo; Taniguch, Hiroyoshi; Nomura, Ryutaro; Sato, Kengo; Suzuki, Ichiro; Nakata, Ryo

    2015-01-01

    AIM: To investigate the safety and efficacy of the Cyberknife treatment for patients with advanced or terminal stage hepatocellular carcinoma (HCC). METHODS: Patients with HCC with extrahepatic metastasis or vascular or bile duct invasion were enrolled between May 2011 and June 2015. The Cyberknife was used to treat each lesion. Treatment response scores were based on Response Evaluation Criteria in Solid Tumors v1.1. The trends of tumor markers, including alpha fetoprotein (AFP) and proteins induced by vitamin K absence II (PIVKA II) were assessed. Prognostic factors for tumor response and tumor markers were evaluated with Fisher’s exact test and a logistic regression model. Survival was evaluated with the Kaplan-Meier method and multivariate analysis was performed using the Cox proportional hazards model. RESULTS: Sixty-five patients with 95 lesions were enrolled. Based on the Barcelona Clinic Liver Cancer classification, all patients were either in the advanced or terminal stage of the disease. The target lesions were as follows: 52 were bone metastasis; 9, lung metastasis; 7, brain metastasis; 9, portal vein invasion; 4, hepatic vein invasion; 4, bile duct invasion; and 10 other lesion types. The response rate and disease control rate were 34% and 53%, respectively. None of the clinical factors correlated significantly with tumor response. Fiducial marker implantation was associated with better control of both AFP (HR = 0.152; 95%CI: 0.026-0.887; P = 0.036) and PIVKA II (HR = 0.035; 95%CI: 0.003-0.342; P = 0.004). The median survival time was 9 mo (95%CI: 5-15 mo). Terminal stage disease (HR = 9.809; 95%CI: 2.589-37.17, P < 0.001) and an AFP of more than 400 ng/mL (HR = 2.548; 95%CI: 1.070-6.068, P = 0.035) were associated with worse survival. A radiation dose higher than 30 Gy (HR = 0.274; 95%CI: 0.093-0.7541, P = 0.012) was associated with better survival. In the 52 cases of bone metastasis, 36 patients (69%) achieved pain relief. One patient had cerebral

  14. Prometheus' spirit: quality survival in advanced hepatocellular carcinoma after gemcitabine and cisplatin-based chemotherapy.

    Science.gov (United States)

    Doval, D C; Pande, S B; Sharma, J B; Pavithran, K; Jena, A; Vaid, A K

    2008-10-01

    In advanced virus-induced hepatocellular carcinoma (HCC) associated with cirrhosis, the average survival is four months. We report a 56-year-old man with a large-volume advanced HCC, in whom gemcitabine and cisplatin-based chemotherapy resulted in near-complete regression, and quality survival of 24 months.

  15. The Role of Receptor for Advanced Glycation End Products (RAGE in the Proliferation of Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Wei Tian

    2012-05-01

    Full Text Available The receptor for advanced glycation end products (RAGE is oncogenic and overexpressed in human cancers, but its role in hepatocellular carcinoma remains unclear. Here we demonstrated that RAGE is overexpressed in primary hepatocellular carcinoma (PHC compared to adjacent para-neoplastic liver samples. Serum endogenous secretory RAGE levels were also increased in PHC patients (p < 0.01. Moreover, we demonstrated that RAGE regulates cellular proliferation in Hepatocellular carcinoma (HCC. Knockdown of RAGE by specific siRNA inhibited cellular growth in the hepatocellular carcinoma cell line, Huh7, whereas the RAGE ligand, high mobility group box 1 protein (HMGB1 increased cellular proliferation. In addition, knockdown of RAGE by siRNA arrested cells in the G1 phase and inhibited DNA synthesis (p < 0.01, while HMGB1 protein decreased the number of cells in the G1 phase and increased the number in the S phase (p < 0.05. Furthermore, quantitative real time RT-PCR (qRT-PCR and Western Blot results demonstrated that RAGE and HMGB1 positively regulate NF-κB p65 expression in Huh7 cells. These studies suggest that RAGE and RAGE ligands are important targets for therapeutic intervention in hepatocellular carcinoma.

  16. Thalidomide induces complete remission of advanced hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Cheng-Hung Chien

    2014-06-01

    Full Text Available Hepatocellular carcinoma (HCC is one of the most prevalent human cancers in the world, but its prognosis is extremely poor. HCC is considered a hypervascular tumor. Thalidomide, which has been known to inhibit growth factor-induced neovascularization, is a convenient alternative to target therapy such as sorafenib. We report a 65-year-old male patient with alcoholic liver cirrhosis that was diagnosed having multiple HCCs during surveillance. The patient was assessed as inoperable and unsuited for transhepatic arterial chemoembolization or systemic chemotherapy. After discussing the therapeutic alternatives, he decided to receive low-dose thalidomide (100 mg daily therapy. Fortunately, follow-up liver biochemical tests, serum α-fetoprotein level, and dynamic computed tomography showed complete remission of the HCCs 4.5 months after thalidomide treatment and this was documented for more than 22 months without evidence of tumor recurrence.

  17. Advanced Hepatocellular Carcinoma with Subtotal Occlusion of the Inferior Vena Cava and a Right Atrial Mass

    Directory of Open Access Journals (Sweden)

    Christian Steinberg

    2013-01-01

    Full Text Available Hepatocellular carcinoma usually metastasizes to regional lymph nodes, lung, and bones but can rarely invade the inferior vena cava with intravascular extension to the right atrium. We present the case of a 75-year-old man who was admitted for generalized oedema and was found to have advanced HCC with invasion of the inferior vena cava and endovascular extension to the right atrium. In contrast to the great majority of hepatocellular carcinoma, which usually develops on the basis of liver cirrhosis due to identifiable risk factors, none of those factors were present in our patient.

  18. Yttrium-90 Radioembolization of Hepatocellular Carcinoma-Performance, Technical Advances, and Future Concepts.

    Science.gov (United States)

    Molvar, Christopher; Lewandowski, Robert

    2015-12-01

    Hepatocellular carcinoma (HCC) is a lethal tumor, claiming over half a million lives per year. Treatment of HCC is commonly performed without curative intent, and palliative options dominate, including catheter-based therapies, namely, transarterial chemoembolization and yttrium-90 ((90)Y) radioembolization. This review will showcase the performance of (90)Y radioembolization for the treatment of HCC, focusing on recent seminal data and technical advances. In particular, novel radioembolization treatment concepts are discussed and compared with conventional HCC therapy.

  19. Liver cancer - hepatocellular carcinoma

    Science.gov (United States)

    Primary liver cell carcinoma; Tumor - liver; Cancer - liver; Hepatoma ... Hepatocellular carcinoma accounts for most liver cancers. This type of cancer occurs more often in men than women. It is usually diagnosed in people age 50 or ...

  20. Managing patients receiving sorafenib for advanced hepatocellular carcinoma: a case study.

    Science.gov (United States)

    Hull, Diana; Armstrong, Ceri

    2010-05-01

    Despite improvements in cytotoxic chemotherapy agents over the last 50 years, the outlook for patients with many of the most common solid tumours has remained poor. However, in recent years a number of targeted therapies have been licensed in the European Union for use in these cancer types. One such therapy, a tyrosine kinase inhibitor (sorafenib) is now used to treat patients with advanced hepatocellular carcinoma (HCC) and metastatic renal cell carcinoma. This article will explore the role of the oncology nurse in managing patients receiving sorafenib for advanced HCC. A brief overview of sorafenib as a current treatment approved for advanced HCC in the palliative setting is presented. This is followed by a case study-based discussion with particular reference to some of the key care coordination challenges facing the oncology nurse. The management of treatment-related adverse events and the importance of using a multidisciplinary team approach is also reviewed.

  1. Evaluation of antiangiogenic efficacy in advanced hepatocellular carcinoma: Biomarkers and functional imaging

    Institute of Scientific and Technical Information of China (English)

    Mohamed; Bouattour; Audrey; Payancé; Johanna; Wassermann

    2015-01-01

    Many years after therapeutic wilderness, sorafenib finally showed a clinical benefit in patients with advanced hepatocellular carcinoma. After the primary general enthusiasm worldwide, some disappointments emerged particularly since no new treatment could exceed or at least match sorafenib in this setting. Without these new drugs, research focused on optimi-zing care of patients treated with sorafenib. One challenging research approach deals with identifying prognostic and predictive biomarkers of sorafenib in this population. The task still seems difficult; however appropriate investigations could resolve this dilemma, as observed for some malignancies where other drugs were used.

  2. Sneddon-Wilkinson disease induced by sorafenib in a patient with advanced hepatocellular carcinoma.

    Science.gov (United States)

    Tajiri, Kazuto; Nakajima, Takahiko; Kawai, Kengo; Minemura, Masami; Sugiyama, Toshiro

    2015-01-01

    Sorafenib is the standard treatment for patients with advanced hepatocellular carcinoma (HCC), although it is known to cause a variety of dermatologic adverse events. Subcorneal pustular dermatosis (SCPD), also known as Sneddon-Wilkinson disease, is a rare skin eruption that accompanies various systemic disorders and may become chronically progressive. We herein describe the case of a patient who developed SCPD after sorafenib administration. The dermatologic reaction was improved by the cessation of sorafenib and worsened by its readministration. Clinicians treating HCC patients with sorafenib should be aware of the possibility of SCPD.

  3. Sorafenib induced tumor lysis syndrome in an advanced hepatocellular carcinoma patient

    Institute of Scientific and Technical Information of China (English)

    Wu-Shiung Huang; Chang-Hsu Yang

    2009-01-01

    A 55-year-old male patient with hepatitis B-related liver cirrhosis was found to have advanced hepatocellular carcinoma. His AFP was initially 9828 mg/L and rapidly dropped to 5597 mg/L in ten days after oral sorafenib treatment. However, he developed acute renal failure, hyperkalemia, and hyperuricemia 30 d after receiving the sorafenib treatment. Tumor lysis syndrome was suspected and intensive hemodialysis was performed. Despite intensive hemodialysis and other supportive therapy, he developed multiple organ failure (liver, renal, and respiratory failure) and metabolic acidosis. The patient expired 13 d after admission.

  4. Chemotherapy with enteric-coated tegafur/uracil for advanced hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Toru Ishikawa

    2008-01-01

    Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide, including Japan.Although the development of imaging modalities has made the early diagnosis of HCC possible, surgically resectable cases are relatively uncommon because of hepatic function reserve and/or an advanced stage at presentation. Several modalities, such as transcatheter arterial chemoembolization, percutaneous ethanol injection, microwave coagulation therapy and radiofrequency ablation are reportedly useful in treating patients with non-resectable disease. However,unfortunately, many HCC patients have tumor recurrence.The overall prognosis of patients with HCC is very poor,and treatment of the advanced form is still problematic.In this article, we review the clinical efficacy and toxicity of enteric-coated tegafur/uracil in the treatment of patients with advanced non-resectable HCC.

  5. Efficacy and safety of sorafenib in patients with advanced hepatocellular carcinoma : Subanalyses of a phase III trial

    NARCIS (Netherlands)

    Bruix, Jordi; Raoul, Jean-Luc; Sherman, Morris; Mazzaferro, Vincenzo; Bolondi, Luigi; Craxi, Antonio; Galle, Peter R.; Santoro, Armando; Beaugrand, Michel; Sangiovanni, Angelo; Porta, Camillo; Gerken, Guido; Marrero, Jorge A.; Nadel, Andrea; Shan, Michael; Moscovici, Marius; Voliotis, Dimitris; Llovet, Josep M.

    2012-01-01

    Background & Aims: The Sorafenib Hepatocellular Carcinoma (HCC) Assessment Randomized Protocol (SHARP) trial demonstrated that sorafenib improves overall survival and is safe for patients with advanced HCC. In this trial, 602 patients with well-preserved liver function (>95% Child-Pugh A) were rando

  6. Optimized management of advanced hepatocellular carcinoma: Four long-lasting responses to sorafenib

    Institute of Scientific and Technical Information of China (English)

    Giovanni Abbadessa; Lorenza Rimassa; Tiziana Pressiani; Cynthia Carrillo-Infante; Emanuele Cucchi; Armando Santoro

    2011-01-01

    The therapeutic options for hepatocellular carcinoma (HCC) have been so far rather inadequate. Sorafenib has shown an overall survival benefit and has become the new standard of care for advanced HCC. Nevertheless, in clinical practice, some patients are discontinuing this drug because of side effects, and misinterpretation of radiographic response may contribute to this. We highlight the importance of prolonged sorafenib adadministration, even at reduced dose, and of qualitative and careful radiographic evaluation. We observed two partial and two complete responses, one histologically confirmed, with progression-free survival ranging from 12 to 62 mo. Three of the responses were achieved following substantial dose reductions, and a gradual change in lesion density preceded or paralleled tumor shrinkage, as seen by computed tomography. This report supports the feasibility of dose adjustments to allow prolonged administration of sorafenib, and highlights the need for new imaging criteria for a more appropriate characterization of response in HCC.

  7. Neoadjuvant sorafenib combined with gemcitabine plus oxaliplatin in advanced hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Nicolas Williet; Julien Taieb; Olivier Dubreuil; Tarek Boussaha; Isabelle Trouilloud; Bruno Landi; Martin Housset; Muriel Botti; Philippe Rougier; Jacques Belghiti

    2011-01-01

    This paper reports the first case of a patient with hepatocellular carcinoma with lymph node metastasis treated by sorafenib combined with gemcitabine plus oxaliplatin,with a partial response and normalization of α fetoprotein,which allowed curative surgery. The potential synergy between these three drugs needs to be confirmed,and is currently being investigated in a randomized phase Ⅱ trial.

  8. DNA methylation in hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Iris Tischoff; Andrea Tannapfel

    2008-01-01

    As for many other tumors, development of hepatocellular carcinoma (HCC) must be understood as a multistep process with accumulation of genetic and epigenetic alterations in regulatory genes, leading to activation of oncogenes and inactivation or loss of tumor suppressor genes (TSG). In the last decades, in addition to genetic alterations, epigenetic inactivation of (tumor suppressor) genes by promoter hypermethylation has been recognized as an important and alternative mechanism in tumorigenesis. In HCC, aberrant methylation of promoter sequences occurs not only in advanced tumors, it has been also observed in premalignant conditions just as chronic viral hepatitis B or C and cirrhotic liver. This review discusses the epigenetic alterations in hepatocellular carcinoma focusing DNA methylation.

  9. Tumor suppressor and hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Juliette Martin; Jean-Frangois Dufour

    2008-01-01

    A few signaling pathways are driving the growth of hepatocellular carcinoma. Each of these pathways possesses negative regulators. These enzymes, which normally suppress unchecked cell proliferation, are circumvented in the oncogenic process, either the over-activity of oncogenes is sufficient to annihilate the activity of tumor suppressors or tumor suppressors have been rendered ineffective. The loss of several key tumor suppressors has been described in hepatocellular carcinoma. Here, we systematically review the evidence implicating tumor suppressors in the development of hepatocellular carcinoma.

  10. Immunology of hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Hepatocellular carcinoma (HCC) is primarily a malignancyof the liver, advancing from a damaged, cirrhoticliver to HCC. Globally, HCC is the sixth most prevalentcancer and the third-most prevalent reason for neoplasticdisease-related deaths. A diverse array ofinfiltrating immunocytes regulates the developmentand progression of HCC, as is the case in many othercancers. An understanding of the various immunecomponents during HCC becomes necessary so thatnovel therapeutic strategies can be designed to combatthe disease. A dysregulated immune system (includingchanges in the number and/or function of immunecells, cytokine levels, and the expression of inhibitoryreceptors or their ligands) plays a key role in thedevelopment of HCC. Alterations in either the innateor adaptive arm of the immune system and cross-talkbetween them make the immune system tolerant totumors, leading to disease progression. In this review,we have discussed the status and roles of variousimmune effector cells (e.g. , dendritic cells, natural killercells, macrophages, and T cells), their cytokine profile,and the chemokine-receptor axis in promoting orimpeding HCC.

  11. Effect of pravastatin on survival in patients with advanced hepatocellular carcinoma. A randomized controlled trial.

    Science.gov (United States)

    Kawata, S; Yamasaki, E; Nagase, T; Inui, Y; Ito, N; Matsuda, Y; Inada, M; Tamura, S; Noda, S; Imai, Y; Matsuzawa, Y

    2001-04-06

    Chemotherapy is not effective for hepatocellular carcinoma (HCC). HMG-CoA redutase inhibitors have cytostatic activity for cancer cells, but their clinical usefulness is unknown. To investigate whether pravastatin, a potent HMG-CoA reductase inhibitor, prolongs survival in patients with advanced HCC, this randomized controlled trial was conducted between February 1990 and February 1998 at Osaka University Hospital. 91 consecutive patients <71 years old (mean age 62) with unresectable HCC were enroled in this study. 8 patients were withdrawn because of progressive liver dysfunction; 83 patients were randomized to standard treatment with or without pravastatin. All patients underwent transcatheter arterial embolization (TAE) followed by oral 5-FU 200 mg(-1)d for 2 months. Patients were then randomly assigned to control (n = 42) and pravastatin (n = 41) groups. Pravastatin was administered at a daily dose of 40 mg. The effect of pravastatin on tumour growth was assessed by ultrasonography. Primary endpoint was death due to progression of HCC. The duration of pravastatin administration was 16.5 +/- 9.8 months (mean +/- SD). No patients in either group were lost to follow-up. Median survival was 18 months in the pravastatin group versus 9 months in controls (P = 0.006). The Cox proportional hazards model showed that pravastatin was a significant factor contributing to survival. Pravastatin prolonged the survival of patients with advanced HCC, suggesting its value for adjuvant treatment.

  12. Orthotopic liver transplantation after the combined use of locoregional therapy and sorafenib for advanced hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Yoo EJ

    2013-06-01

    Full Text Available Eun Jin Yoo,1,* Hye Sun Shin,1,* Seung Up Kim,1,2,7 Dong Jin Joo,3,4 Jun Yong Park,1,2,7 Gi Hong Choi,3 Do Young Kim,1,2,7 Sang Hoon Ahn,1,2,7 Jinsil Seong,5 Myung Joo Koh,6 Kwang-Hyub Han,1,2,7 Chae Yoon Chon1,2,7 1Department of Internal Medicine, 2Institute of Gastroenterology, 3Department of Surgery, 4Research Institute for Transplantation, 5Department of Radiation Oncology, 6Department of Pathology, Yonsei University College of Medicine, Seoul, South Korea; 7Liver Cirrhosis Clinical Research Center, Seoul, South Korea *These authors contributed equally to this work Abstract: We herein report a patient with advanced hepatitis B virus-related hepatocellular carcinoma (HCC beyond the Milan criteria. He underwent orthotopic liver transplantation after successful HCC downstaging that satisfied the University of California, San Francisco criteria, using concurrent chemoradiation therapy with a combination of repeated hepatic arterial infusion chemotherapy (HAIC and sorafenib. A 52-year-old male was diagnosed with advanced hepatitis B virus-related HCC beyond the Milan criteria. He underwent concurrent chemoradiation therapy (50 Gy with 20 fractions over 5 weeks with HAIC using 5-fluorouracil at a dose of 500 mg/day, which was administered during the first and fifth weeks of radiation therapy as an initial treatment modality. This was followed by the combined use of HAIC using 5-fluorouracil (500 mg/m2 for 5 hours on days 1–3 and cisplatin (60 mg/m2 for 2 hours on day 2 every 4 weeks (twelve cycles and sorafenib (from the third to the twelfth cycle of HAIC to treat the remaining HCC. Because a remarkable decrease in the tumor burden that satisfied the University of California, San Francisco criteria was observed after these combination treatments, the patient underwent orthotopic liver transplantation with curative aim and survived for 11 months without evidence of HCC recurrence. Keywords: hepatocellular carcinoma, liver transplantation

  13. Patterns of treatment and costs of intermediate and advanced hepatocellular carcinoma management in four Italian centers

    Science.gov (United States)

    Colombo, Giorgio Lorenzo; Cammà, Calogero; Attili, Adolfo Francesco; Ganga, Roberto; Gaeta, Giovanni Battista; Brancaccio, Giuseppina; Franzini, Jean Marie; Volpe, Marco; Turchetti, Giuseppe

    2015-01-01

    Background Hepatocellular carcinoma (HCC) is a severe health condition associated with high hospitalizations and mortality rates, which also imposes a relevant economic burden. Purpose The aim of the present survey is to investigate treatment strategies and related costs for HCC in the intermediate and advanced stages of the disease. Patients and methods The survey was conducted in four Italian centers through structured interviews with physicians. Information regarding the stage of disease, treatments performed, and related health care resource consumption was included in the questionnaire. Direct health care cost per patient associated with the most relevant treatments such as sorafenib, transarterial chemoembolization (TACE), and transarterial radioembolization (TARE) was evaluated. Results Between 2013 and 2014, 285 patients with HCC were treated in the four participating centers; of these, 80 were in intermediate stage HCC (Barcelona Clinic Liver Cancer Classification [BCLC] B), and 57 were in the advanced stage of the disease (BCLC C). In intermediate stage HCC, the most frequent first-line treatment was TACE (63%) followed by sorafenib (15%), radiofrequency ablation (14%), and TARE (1.3%). In the advanced stage of HCC, the most frequently used first-line therapy was sorafenib (56%), followed by best supportive care (21%), TACE (18%), and TARE (3.5%). The total costs of treatment per patient amounted to €12,214.54 with sorafenib, €13,418.49 with TACE, and €26,106.08 with TARE. Both in the intermediate and in the advanced stage of the disease, variability in treatment patterns among centers was observed. Conclusion The present analysis raises for the first time the awareness of the overall costs incurred by the Italian National Healthcare System for different treatments used in intermediate and advanced HCC. Further investigations would be important to better understand the effective health care resource usage. PMID:26527877

  14. 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...... status) comparing cryotherapy with or without co-intervention(s) to placebo, no treatment, or other control interventions were considered for the review. Due to the absence of randomised clinical trials, we searched for quasi-randomised studies as well as prospective cohort studies and retrospective...... for the assessment of benefit as the study results were stratified according to both the type of hepatic malignancy (primary or secondary) and the intervention group. This retrospective study compared percutaneous cryotherapy with percutaneous radiofrequency. The remaining studies were excluded for the analyses...

  15. Successful treatment of hypovascular advanced hepatocellular carcinoma with lipiodol-targetting intervention radiology

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    We report a case of hypovascular advanced hepatocellular carcinoma (HCC) successfully treated with a novel combination therapy of percutaneous ethanollipiodol injection (PELI) and intervention radiology (IVR),lipiodol-targetting IVR (Lipi-IVR). The present case had a hypovascular HCC (3 cm in diameter) located in the S6 region of the liver. Although the tumor was not detectable at all by both of early and late phase of helical dynamic computed tomography (CT), it could be detected by ultrasonography (US) as a low echoic space occupying lesion (SOL) beside the gallbladder and right kidney. Serum levels of alpha fetoprotein (AFP)and AFP-L3 were extremely high. Combination therapy of PELI, firstly reported in our department, and IVR (PELI and IVR, lipiodol-targetting IVR) was performed twice for the treatment. PELI could effectively visualize the location of the tumor for IVR treatment and show the presence of a thin blood vessel branching from the right hepatic artery flowing into the lipiodol deposit.After treatment, the serum levels of AFP and AFP-L3 were rapidly decreased to normal and maintained for more than eight months. Thus, this case expressing the tremendous effect might give us insight into the effectiveness of the novel combination therapy of PELI and IVR for the treatment of hypovascular HCC.

  16. Chemotherapies and targeted therapies in advanced hepatocellular carcinoma: from laboratory to clinic.

    Science.gov (United States)

    Voiculescu, Mihai; Winkler, Robert E; Moscovici, Marius; Neuman, Manuela G

    2008-09-01

    Chronic liver diseases alone or in conjunction with other risk factors result in increased liver damage leading to inflammation and fibrosis of the liver and rising rates of liver cirrhosis, hepatic decompensation and hepatocellular carcinoma (HCC). This review will address the determinants of liver injury at the initiation of the tumor and the risk factors for rapid disease progression. Regardless of the etiology, the unifying feature of these tumors are their propensity to arise upon a background of inflammation and fibrosis. Liver disease is often associated with enhanced hepatocyte apoptosis, which is the case in viral and autoimmune hepatitis, cholestatic diseases, and metabolic disorders. Disruption of apoptosis is responsible for HCC. The mechanisms by which apoptosis occurs in the liver might provide insights into HCC and suggest possible treatments. We aim to better understand the factors that distinguish a relatively long course of HCC from one with rapid progression. We will accomplish this task with three integrated ideas: 1 - the role of epidemiology in establishing the risk factors of co-morbidity with alcohol and hepatitis viruses; 2 - the role of apoptosis and anti-apoptotic signals in the progression of HCC; and 3 - the role of new advancements that have emerged in the field of molecular-directed chemotherapeutics in HCC in recent years. This review will also aim to describe the molecular targeted therapies of non-resectable HCC and the ways of effective combination in this otherwise chemo-resistant tumor.

  17. Advances in liver-directed gene therapy for hepatocellular carcinoma by non-viral delivery systems.

    Science.gov (United States)

    Ding, Buyun; Li, Tao; Zhang, Jian; Zhao, Lixia; Zhai, Guangxi

    2012-04-01

    Hepatocellular carcinoma (HCC) is a malignancy with a high mortality. Gene therapy provides a promising way for the treatment of HCC. Efficient gene delivery system, suitable gene target and appropriate way of administration together determine the effect of gene therapy for HCC. In recent years, employing non-viral gene delivery systems in gene therapy for HCC has attracted a lot of attention. Compared with viral vectors, non-viral gene delivery systems are nearly non-immunogenic, relatively safer, less expensive to produce and can carry a good many of genetic materials. But the transfection efficiency of these vectors still needs to be improved. And the liver targeting is another problem that needs to be solved. Attaching ligands to the non-viral vectors to enhance the targeting ability to the specific receptor and targeting to molecular targets of HCC are the effective strategies. Adopting suitable ways of administration is also a factor that plays an important role to achieve liver targeting. This review introduced the advances in liver-targeted gene therapy by non-viral vectors including the efforts to overcome the low transfection efficiency and enhance the liver targeting effect.

  18. [Hepatocellular carcinoma. Part 2. Treatment].

    Science.gov (United States)

    Conte, V P

    2000-01-01

    Recent improvements on the therapeutical management of hepatocellular carcinoma are revised with special attention to evaluate the role of surgery for the disease. Considering that definitive surgical intervention is not feasible in most cases because of extreme tumor extension, multiplicity of tumor foci, and associated advanced liver cirrhosis at the time of diagnosis, others forms of treatment are listed, such as transcatheterarterial chemoembolization, percutaneous ethanol and acetic acid injections, and chemotherapy only to a small portion of patients with no indication for standard treatments. The emerging role of retinoic acid metabolism blocking agents, was examined and may offer a significant new potential treatment for cancer, inclusive the possibility of combining other anticancer drugs with exogenous retinoids or modulation of endogenous retinoids as a real opportunity to advance our ability to treat or prevent human cancer effectively Octreotide, nitrosamine and other drugs are analyzed and is concluded that improves survival and is a valuable alternative in the treatment of inoperable hepatocellular carcinoma. The potential role of intersticial laser coagulation for patients with irresectable hepatic tumors was investigated, and in terms of experience, it has now been developed sufficiently to study its effect on these patients survival. The homeostatic control of angiogenesis and its influences on the tumor growth and for migration of metastatic cells, was focused in this concise review, given that hepatocytes are the source of much of the precursor pool, regulation of angiogenesis may be regarded as a new liver function with important consequences for tissue repair and cancer. Early hepatocellular carcinoma and its recognition in routine clinical practice contributes to improved patients survival. Recombinant-Interferon-alpha therapy surely prevents, the development of cirrhosis or hepatocellular carcinoma in about one-third of patients, with

  19. Advanced hepatocellular carcinoma and sorafenib:Diagnosis, indications, clinical and radiological follow-up

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Advanced stage hepatocellular carcinoma (HCC) is acategory of disease defined by radiological, clinical andhepatic function parameters, comprehending a widerange of patients with different general conditions. Themain therapeutic option is represented by sorafenibtreatment, a multi-kinase inhibitor with anti-proliferativeand anti-angiogenic effect. Trans-arterial Radio Embolizationalso represents a promising new approach tointermediate/advanced HCC. Post-marketing clinicalstudies showed that only a portion of patients actuallybenefits from sorafenib treatment, and an even smallerpercentage of patients treated shows partial/completeresponse on follow-up examinations, up against relevantcosts and an incidence of drug related adverse effects.Although the treatment with sorafenib has shown asignificant increase in mean overall survival in differentstudies, only a part of patients actually shows realbenefits, while the incidence of drug related significantadverse effects and the economic costs are relativelyhigh. Moreover, only a small percentage of patientsalso shows a response in terms of lesion dimensionsreduction. Being able to properly differentiate patientswho are responding to the therapy from non-respondersas early as possible is then still difficult and couldbe a pivotal challenge for the future; in fact it couldspare several patients a therapy often difficult to bear,directing them to other second line treatments (many ofwhich are at the moment still under investigation). Forthis reason, some supplemental criteria to be added tothe standard modified Response Evaluation Criteriain Solid Tumors evaluation are being searched for. Inparticular, finding some parameters (cellular density,perfusion grade and enhancement rate) able to predictthe sensitivity of the lesions to anti-angiogenic agentscould help in stratifying patients in terms of treatmentresponsiveness before the beginning of the therapyitself, or in the first weeks of sorafenib treatment

  20. Transcatheter arterial chemoembolization and radiation therapy for treatment-naive patients with locally advanced hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sang Won [Dept. of Radiation Oncology, Yeungnam University Medical Center, Daegu (Korea, Republic of); Oh, Dong Ryul; Park, Hee Chul; Lim, Do Hoon; Shin, Sung Wook; Cho, Sung Ki; Gwak, Geum Youn; Choi, Moon Seok; Paik, Yong Han; Paik, Seung Woon [Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2013-12-15

    To evaluate the safety and efficacy of transcatheter arterial chemoembolization (TACE) followed by radiotherapy (RT) in treatment-naive patients with locally advanced hepatocellular carcinoma (HCC). Eligibility criteria were as follows: newly diagnosed with HCC, the Barcelona Clinic Liver Cancer stage C, Child-Pugh class A or B, and no prior treatment for HCC. Patients with extrahepatic spread were excluded. A total of 59 patients were retrospectively enrolled. All patients were treated with TACE followed by RT. The time interval between TACE and RT was 2 weeks as per protocol. A median RT dose was 47.25 Gy10 as the biologically effective dose using the α/β = 10 (range, 39 to 65.25 Gy10). At 1 month, complete response was obtained in 3 patients (5%), partial response in 27 patients (46%), stable disease in 13 patients (22%), and progressive disease in 16 patients (27%). The actuarial one- and two-year OS rates were 60.1% and 47.2%, respectively. The median OS was 17 months (95% confidence interval, 5.6 to 28.4 months). The median time to progression was 4 months (range, 1 to 35 months). Grade 3 or greater liver enzyme elevation occurred in only two patients (3%) after RT. Grade 3 gastroduodenal toxicity developed in two patients (3%). The combination treatment of TACE followed by RT with two-week interval was safe and it showed favorable outcomes in treatment-naive patients with locally advanced HCC. A prospective randomized trial is needed to validate these results.

  1. Patterns of treatment and costs of intermediate and advanced hepatocellular carcinoma management in four Italian centers

    Directory of Open Access Journals (Sweden)

    Colombo GL

    2015-10-01

    Full Text Available Giorgio Lorenzo Colombo,1 Calogero Cammà,2 Adolfo Francesco Attili,3 Roberto Ganga,4 Giovanni Battista Gaeta,5 Giuseppina Brancaccio,5 Jean Marie Franzini,6 Marco Volpe,6 Giuseppe Turchetti7 1Department of Drug Sciences, University of Pavia, Pavia, Italy; 2Section of Gastroenterology, Di.Bi.M.I.S., University of Palermo, Palermo, Italy; 3Department of Clinical Medicine, University of Rome (La Sapienza Rome, Italy; 4Clinical Medicine Division, Ospedale Brotzu, Cagliari, Italy; 5Viral Hepatitis Unit, Second University, Naples, Italy; 6Business Integration Partners S.p.A., Milan, Italy; 7Scuola Superiore Sant’Anna, Pisa, Italy Background: Hepatocellular carcinoma (HCC is a severe health condition associated with high hospitalizations and mortality rates, which also imposes a relevant economic burden.Purpose: The aim of the present survey is to investigate treatment strategies and related costs for HCC in the intermediate and advanced stages of the disease. Patients and methods: The survey was conducted in four Italian centers through structured interviews with physicians. Information regarding the stage of disease, treatments performed, and related health care resource consumption was included in the questionnaire. Direct health care cost per patient associated with the most relevant treatments such as sorafenib, transarterial chemoembolization (TACE, and transarterial radioembolization (TARE was evaluated.Results: Between 2013 and 2014, 285 patients with HCC were treated in the four participating centers; of these, 80 were in intermediate stage HCC (Barcelona Clinic Liver Cancer Classification [BCLC] B, and 57 were in the advanced stage of the disease (BCLC C. In intermediate stage HCC, the most frequent first-line treatment was TACE (63% followed by sorafenib (15%, radiofrequency ablation (14%, and TARE (1.3%. In the advanced stage of HCC, the most frequently used first-line therapy was sorafenib (56%, followed by best supportive care (21

  2. Oncogenic viruses and hepatocellular carcinoma.

    Science.gov (United States)

    Ben Ari, Ziv; Weitzman, Ella; Safran, Michal

    2015-05-01

    About 80% of hepatocellular carcinoma (HCC) is caused by hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infections especially in the setting of established cirrhosis or advanced fibrosis, making HCC prevention a major goal of antiviral therapy. HCC tumors are highly complex and heterogeneous resulting from the aberrant function of multiple molecular pathways. The roles of HCV or HBV in promoting HCC development are still either directly or indirectly are still speculative, but the evidence for both effects is compelling. In patients with chronic hepatitis viral infection, cirrhosis is not a prerequisite for tumorigenesis.

  3. Three-dimensional conformal radiotherapy for portal vein tumor thrombosis alone in advanced hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Ju Hye Kim Dong Hyun; Ki, Yong Kan; Kim, Dong Won; Kim, Won Taek; Heo, Jeong; Woo, Hyun Young [Pusan National University Hospital, Pusan National University School of Medicine, Busan (Korea, Republic of); Nam, Ji Ho [Dept.of Radiation Oncology, Pusan National University Yangsan Hospital, Yangsan (Korea, Republic of)

    2014-09-15

    We sought to evaluate the clinical outcomes of 3-dimensional conformal radiation therapy (3D-CRT) for portal vein tumor thrombosis (PVTT) alone in patients with advanced hepatocellular carcinoma. We retrospectively analyzed data on 46 patients who received 3D-CRT for PVTT alone between June 2002 and December 2011. Response was evaluated following the Response Evaluation Criteria in Solid Tumors. Prognostic factors and 1-year survival rates were compared between responders and non-responders. Thirty-seven patients (80.4%) had category B Child-Pugh scores. The Eastern Cooperative Oncology Group performance status score was 2 in 20 patients. Thirty patients (65.2%) had main or bilateral PVTT. The median irradiation dose was 50 Gy (range, 35 to 60 Gy) and the daily median dose was 2 Gy (range, 2.0 to 2.5 Gy). PVTT response was classified as complete response in 3 patients (6.5%), partial response in 12 (26.1%), stable disease in 19 (41.3%), and progressive disease in 12 (26.1%). There were 2 cases of grade 3 toxicities during or 3 months after radiotherapy. Twelve patients in the responder group (15 patients) received at least 50 Gy irradiation, but about 84% of patients in the non-responder group received less than 50 Gy. The 1-year survival rate was 66.8% in responders and 27.4% in non-responders constituting a statistically significant difference (p = 0.008). Conformal radiotherapy for PVTT alone could be chosen as a palliative treatment modality in patients with unfavorable conditions (liver, patient, or tumor factors). However, more than 50 Gy of radiation may be required.

  4. Skin toxicity predicts efficacy to sorafenib in patients with advanced hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Masako; Shomura; Tatehiro; Kagawa; Koichi; Shiraishi; Shunji; Hirose; Yoshitaka; Arase; Tetsuya; Mine; Jun; Koizumi

    2014-01-01

    AIM:To study the relationship between adverse events(AEs),efficacy,and nursing intervention for sorafenibtherapy in patients with hepatocellular carcinoma(HCC).METHODS:We enrolled 37 consecutive patients withadvanced HCC who received sorafenib therapy.Relationships among baseline characteristics as well as AEoccurrence and tumor response,overall survival(OS),and treatment duration were analyzed.The nursingintervention program consisted of education regardingself-monitoring and AEs management,and telephoneRESULTS:A total of 37 patients were enrolled in the study,comprising 30 males(81%) with a median age of 71 years.The disease control rate at 3 mo was 41%,and the median OS and treatment duration were 259 and 108 d,respectively.Nursing intervention was given to 24 patients(65%).Every patient exhibited some kinds of AEs,but no patients experienced G4 AEs.Frequently observed AEs > G2 included anorexia(57%),skin toxicity(57%),and fatigue(54%).Factors significantly associated with longer OS in multivariate analysis demonstrated that age ≤ 70 years,presence of > G2 skin toxicity,and absence of > G2 hypoalbuminemia.The disease control rate in patients with > G2 skin toxicity was 13/20(65%),which was significantly higher compared with that in patients with no or G1 skin toxicity.Multivariate analysis revealed that nursing intervention and > G2 skin toxicity were independent significant predictors for longer treatment duration.CONCLUSION:Skin toxicity was associated with favorable outcomes with sorafenib therapy for advanced HCC.Nursing intervention contributed to better adher-ence,which may improve the efficacy of sorafenib.

  5. Is hepatic arterial infusion chemotherapy effective treatment for advanced hepatocellular carcinoma resistant to transarterial chemoembolization?

    Institute of Scientific and Technical Information of China (English)

    Hiroyuki Kirikoshi; Shin Maeda; Atsushi Nakajima; Satoru Saito; Masato Yoneda; Hironori Mawatari; Koji Fujita; Kento Imajo; Shingo Kato; Kaori Suzuki; Noritoshi Kobayashi; Kensuke Kubota

    2012-01-01

    AIM:To evaluate the effectiveness of hepatic arterial infusion chemotherapy (HAIC) for advanced hepatocellular carcinoma (HCC) resistant to transarterial chemoembolization (TACE).METHODS:This study was conducted on 42 patients who received HAIC for advanced HCC between 2001 and 2010 at our hospital.5-fluorouracil (5-FU) was administered continuously for 24 h from day 1 to day 5 every 2-4 wk via an injection reservoir.Intra-arterial cisplatin or subcutaneous interferon was administered in combination with the 5-FU.The patients enrolled in this retrospective study were divided into two groups according to whether or not they fulfilled the criteria for resistance to TACE proposed by the Japan Society of Hepatology in 2010 (written in Japanese); one group of patients who did not fulfill the criteria for TACE resistance (group A,n =23),and another group who fulfilled the criteria for TACE resistance (group B,n =19).We compared the outcomes in terms of the response and survival rates between the two groups.RESULTS:Both the response rate and tumor suppression rate following HAIC were significantly superior in group A than in group B (response rate:48% vs 16%,P =0.028,tumor suppression rate:87% vs 53%,P =0.014).Furthermore,both the progression-free survival rate and survival time were significantly superior in group A than in group B (3-,6-,12-,and 24-mo =83%,70%,29% and 20% vs 63%,42%,16% and 0%,respectively,P =0.040,and 9.8 mo vs 6.2 mo,P =0.040).A multivariate analysis (Cox proportional hazards regression model) showed that resistance to TACE was an independent predictor of poor survival (P =0.007).CONCLUSION:HAIC administrating 5-FU was not effective against advanced HCC resistant to TACE.Other tools for treatment,i.e.,molecular-targeting agents may be considered for these cases.

  6. Thalidomide-based multidisciplinary treatment for patients with advanced hepatocellular carcinoma: A retrospective analysis

    Institute of Scientific and Technical Information of China (English)

    Yang-Yuan Chen; Hsu-Heng Yen; Kun-Ching Chou; Shun-Sheng Wu

    2012-01-01

    AIM: To evaluate the efficacy of thalidomide in combination with other therapies to treat patients with advanced hepatocellular carcinoma (HCC). METHODS: We performed a retrospective analysis of all patients with HCC who were treated with thalidomide for at least two months. The medical records of patients with HCC who were treated at our institution between April 2003 and March 2008 were reviewed. Image studies performed before and after treatment, tumor response, overall survival, and the decrease in α-fetoprotein (AFP) levels were evaluated. RESULTS: A total of 53 patients with HCC received either 100 or 200 mg/d of thalidomide. The patient population consisted of 9 women and 44 men with a median age of 61 years. Thirty patients (56.6%) were classified as Child-Pugh A, and 12 patients (22.6%) were classified as Child-Pugh B. Twenty-six patients had portal vein thrombosis (49.1%), and 25 patients had extrahepatic metastasis (47.1%). The median duration of thalidomide treatment was 6.0 mo. Six of the 53 patients achieved a confirmed response (11.3%), one achieved a complete response (1.9%) and 5 achieved a partial response (9.4%). The disease control rate (CR+PR+SD) was 28.3% (95% CI:17.8-42.4), and the median overall survival rate was 10.5 mo. The 1-and 2-year survival rates were 45% and 20%, respectively. Only one complete response patient showed an improved overall survival rate of 66.8 mo. Sixteen patients (30.2%) showed more than a 50% decrease in their serum AFP levels from baseline, indicating a better response rate (31.3%), disease control rate (43.8%), and overall survival time (20.7 mo). The therapy was well tolerated, and no significant toxicities were observed. CONCLUSION: Thalidomide was found to be safe for advanced HCC patients, demonstrating anti-tumor activity including response, survival, and AFP decreases of greater than 50% from baseline.

  7. Cutaneous metastases of hepatocellular carcinoma.

    Science.gov (United States)

    Lazaro, M; Serrano, M L; Allende, I; Ratón, J A; Acebo, E; Diaz-Perez, J L

    2009-12-01

    Cutaneous metastases are an unusual finding that may present as the first sign of an internal neoplasia. A case of cutaneous metastases of hepatocellular carcinoma, which may often involve other organs but very rarely metastases to the skin, is reported.

  8. Hepatocellular Carcinoma (HCC)

    Science.gov (United States)

    Helmberger, Thomas K.

    Hepatocellular carcinoma (HCC) is considered to be one of the most common malignancies worldwide, and the most common one in Africa and Asia. Over the last decade, a rising incidence of up to 10-15/100,000 per population has been seen in the Western world, with an estimate of 250,000 deaths and more than a million worldwide per year. By the year 2010, the World Health Organization expects that HCC will be the leading cause of cancer mortality surpassing lung cancer. This increasing incidence is most likely related to an increasing prevalence of chronic hepatitis C (HC) and B (HB) virus infections and other diseases inducing chronic inflammation (Befeler and Di Bisceglie 2002; Llovet et al. 2003).

  9. Genetics of hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Andreas Teufel; Frank Staib; Stephan Kanzler; Arndt Weinmann; Henning Schulze-Bergkamen; Peter R Galle

    2007-01-01

    The completely assembled human genome has made it possible for modern medicine to step into an era rich in genetic information and high-throughput genomic analysis. These novel and readily available genetic resources and analytical tools may be the key to unravel the molecular basis of hepatocellular carcinoma (HCC). Moreover, since an efficient treatment for this disease is lacking, further understanding of the genetic background of HCC will be crucial in order to develop new therapies aimed at selected targets. We report on the current status and recent developments in HCC genetics. Special emphasis is given to the genetics and regulation of major signalling pathways involved in HCC such as p53, Wntsignalling, TGFβ, Ras, and Rb pathways. Furthermore, we describe the influence of chromosomal aberrations as well as of DNA methylation. Finally, we report on the rapidly developing field of genomic expression profiling in HCC, mainly by microarray analysis.

  10. Surgery and Hepatocellular Carcinoma

    Science.gov (United States)

    Akamatsu, Nobuhisa; Cillo, Umberto; Cucchetti, Alessandro; Donadon, Matteo; Pinna, Antonio Daniele; Torzilli, Guido; Kokudo, Norihiro

    2016-01-01

    The optimal surgical strategy for hepatocellular carcinoma (HCC) is under active debate. Bio-markers of the liver functional reserve as well as volumetric analysis of the future liver remnant are essential for safe liver resection of HCC. The present algorithms applied to surgical strategies for HCC are not ideal because many patients who could potentially undergo safe resection are deemed liver transplant candidates in Western countries, whereas the opposite is the case in Eastern countries. In addition, there is too much focus on expanded criteria for patients with HCC to undergo liver transplantation. The transplantation benefit for patients with HCC should be considered based not only on the individual's benefit, but also on the effect of other patients waiting for LT for other indications. PMID:27995087

  11. 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

  12. Effectiveness and safety of proton beam therapy for advanced hepatocellular carcinoma with portal vein tumor thrombosis

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Sung Uk; Park, Joong-Won; Kim, Tae Hyun; Kim, Yeon-Joo; Woo, Sang Myung; Koh, Young-Hwan; Lee, Woo Jin; Park, Sang-Jae; Kim, Dae Yong; Kim, Chang-Min [National Cancer Center, Center for Liver Cancer, Research Institute and Hospital, Goyang-si, Gyeonggi-do (Korea, Republic of)

    2014-09-15

    To evaluate the clinical effectiveness and safety of proton beam therapy (PBT) in advanced hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT). Twenty-seven HCC patients with PVTT underwent PBT, including 22 patients with modified International Union Against Cancer (mUICC) stage IVA,five patients with stage IVB primary tumors, and 16 with main PVTT. A median dose of 55 GyE (range, 50-66 GyE) in 20-22 fractions was delivered to a target volume encompassing both the PVTT and primary tumor. Overall, treatment was well tolerated, with no toxicity of grade ≥ 3. Median overall survival (OS) times in all patients and in stage IVA patients were 13.2 months and 16 months, respectively. Assessments of PVTT response showed complete response in 0 of 27 (0 %) patients, partial response in 15 (55.6 %), stable disease in 10 (37 %), and progressive disease in 2 (7.4 %) patients, with an objective response rate of 55.6 %. PVTT responders showed significantly higher actuarial 1-year local progression-free survival (LPFS; 85.6 % vs. 51.3 %), relapse-free survival (RFS; 20 % vs. 0 %) and OS (80 % vs. 25 %) rates than nonresponders (p < 0.05 each). Multivariate analysis showed that PVTT response and mUICC stage were independent prognostic factors for OS. Our data suggest that PBT could improve LPFS, RFS, and OS in advanced HCC patients with PVTT and it is feasible and safe for these patients. (orig.) [German] In der vorliegenden Arbeit wurde versucht, die klinische Wirksamkeit und Sicherheit der Protonenstrahltherapie (PBT) fuer Patienten mit fortgeschrittenem Leberzellkarzinom (HCC) in Verbindung mit Portadertumorthrombosen (PVTT) zu bewerten. Ausgefuehrt wurde die PBT fuer 27 HCC-Patienten mit PVTT, einschliesslich 22 Patienten im mUICC-Stadium (''International Union Against Cancer'') IVA sowie 5 Patienten mit Primaertumor im Stadium IVB und 16 Patienten mit PVTT im primaeren Stadium nach der geaenderten UICC-Klassifikation. Eine

  13. Synchronous gastric neuroendocrine carcinoma and hepatocellular carcinoma

    DEFF Research Database (Denmark)

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

    2009-01-01

    UNLABELLED: Gastric neuroendocrine carcinomas (NECs) are rare tumours that are divided into four subtypes depending on tumour characteristics. Patients with NECs are known to have an increased risk of synchronous and metachronous cancers mainly located in the gastrointestinal tract. A case...... 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...

  14. Transarterial Therapies for Hepatocellular Carcinoma

    Science.gov (United States)

    Lanza, Ezio; Donadon, Matteo; Poretti, Dario; Pedicini, Vittorio; Tramarin, Marco; Roncalli, Massimo; Rhee, Hyungjin; Park, Young Nyun; Torzilli, Guido

    2016-01-01

    Background The treatment of hepatocellular carcinoma (HCC) is still a major health issue because of its increasing incidence and because of the complexity of its management. Transarterial embolization (TAE) and transarterial chemoembolization (TACE) are two widely used locoregional therapies in the treatment of HCC, especially for unresectable intermediate and advanced HCCs. Summary The modern use of TAE and TACE opens new scenarios for the treatment of unresectable HCC and has yielded interesting results. The present work describes the role of transarterial therapies for HCC and focuses on the different Western and Eastern approaches to the study of response predictors. Key Messages Recent refinements in interventional radiology techniques and in HCC patient selection have facilitated better local control of the disease. The molecular profiling of HCC to predict the response to TACE and TAE will greatly help clinicians identify the optimum therapy. PMID:27995085

  15. Genetic heterogeneity of hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Unsal, H.; Isselbacher, K.J. (Massachusetts General Hospital Cancer Center, Charlestown, MA (United States)); Yakicier, C.; Marcais, C.; Ozturk, M. (Institut National de la Sante et de la Recherche Medicale, Lyon (France)); Kew, M. (Univ. of Witwatersrand, Johannesburg (South Africa)); Volkmann, M. (Univ. of Heidelberg (Germany)); Zentgraf, H. (Deutsches Krebsforschungszentrum, Heidelberg (Germany))

    1994-01-18

    The authors studied 80 hepatocellular carcinomas from three continents for p53 gene (TP53) mutations and hepatitis B virus (HBV) sequences. p53 mutations were frequent in tumors from Mozambique but not in tumors from South Africa, China, and Germany. Independent of geographic origin, most tumors were positive for HBV sequences. X gene coding sequences of HBV were detected in 78% of tumors, whereas viral sequences in the surface antigen- and core antigen-encoding regions were present in less than 35% of tumors. These observations indicate that hepatocellular carcinomas are genetically heterogeneous. Mozambican-types of hepatocellular carcinomas are characterized by a high incidence of p53 mutations related to aflatoxins. In other tumors, the rarity of p53 mutations combined with the frequent presence of viral X gene coding sequences suggests a possible interference of HBV with the wild-type p53 function.

  16. Role of regorafenib as second-line therapy and landscape of investigational treatment options in advanced hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Trojan J

    2016-09-01

    Full Text Available Jörg Trojan, Oliver Waidmann Medizinische Klinik 1, Universitätsklinikum Frankfurt, Germany Abstract: Sorafenib is still the only systemic drug approved for the treatment of advanced hepatocellular carcinoma (HCC. In recent years, several investigational agents mainly targeting angiogenesis failed in late-phase clinical development due to either toxicity or lack of benefit. Recently, data of the RESORCE trial, a placebo-controlled Phase III study that evaluated the efficacy and safety of regorafenib in patients with HCC and documented disease progression after systemic first-line treatment with sorafenib, were presented at the ESMO World Congress on Gastrointestinal Cancer, 2016. Regorafenib treatment resulted in a 2.8-month survival benefit compared to placebo (10.6 months vs 7.8 months. Side effects were consistent with the known profile of regorafenib. The approval of regorafenib for this indication is expected in 2017. Further candidate agents in Phase III evaluation for second-line treatment of patients with HCC are the MET inhibitors tivantinib and cabozantinib, the vascular endothelial growth factor receptor-2 antibody ramucirumab, and the programmed death receptor-1 (PD-1 blocking antibody pembrolizumab. Furthermore, results from two first-line trials with either the tyrosine kinase inhibitor lenvatinib or the PD-1 antibody nivolumabin in comparison to sorafenib are awaited in the near future and might further change the treatment sequence of advanced HCC. Keywords: hepatocellular carcinoma, receptor tyrosine kinase inhibitor, sorafenib, regorafenib, lenvatinib, tivantinib, cabozantinib, ramucirumab, immunotherapy, anti-CTLA-4, anti-PD-1, oncolytic virus

  17. Treatment of hepatocellular carcinoma: present and future.

    Science.gov (United States)

    Genco, Chiara; Cabibbo, Giuseppe; Maida, Marcello; Brancatelli, Giuseppe; Galia, Massimo; Alessi, Nicola; Butera, Giuseppe; Genova, Claudio; Romano, Piero; Raineri, Maurizio; Giarratano, Antonello; Midiri, Massimo; Cammà, Calogero

    2013-04-01

    Hepatocellular carcinoma is a major health problem. It is the sixth most common cancer worldwide and the third most common cause of cancer-related death. Despite the availability of several treatment opportunities, diagnosis is still made in an advanced phase, limiting application of most therapeutic choices that currently are based on the Barcelona Clinic Cancer Liver Classification and include surgical resection, orthotopic liver transplantation and ablative methods for very early and early disease, arterial chemoembolization for intermediate stages and systemic therapy with sorafenib for advanced hepatocellular carcinoma. Thanks to novel advancements in knowledge of molecular pathogenesis of this tumor, many new systemic agents and locoregional treatments are in different stages of clinical development and they represent an important promise of further improvements in patients' survival.

  18. Effective treatment strategies other than sorafenib for thepatients with advanced hepatocellular carcinoma invadingportal vein

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Patients with hepatocellular carcinoma (HCC) accompanyingportal vein tumor thrombosis (PVTT) haverelatively few therapeutic options and an extremely poorprognosis. These patients are classified into barcelona clinic liver cancer stage C and sorafenib is suggested asthe standard therapy of care. However, overall survival(OS) gain from sorafenib is unsatisfactory and bettertreatment modalities are urgently required. Therefore,we critically appraised recent data for the varioustreatment strategies for patients with HCC accompanyingPVTT. In suitable patients, even surgical resection can beconsidered a potentially curative strategy. Transarterialchemoembolization (TACE) can be performed effectivelyand safely in a carefully chosen population of patientswith reserved liver function and sufficient collateral bloodflow nearby the blocked portal vein. A recent metaanalysisdemonstrated that TACE achieved a substantialimprovement of OS in HCC patients accompanyingPVTT compared with best supportive care. In addition,transarterial radioembolization (TARE) using yttrium-90microspheres achieves quality-of-life advantages and isas effective as TACE. A large proportion of HCC patientsaccompanying PVTT are considered to be proper forTARE. Moreover, TACE or TARE achieved comparableoutcomes to sorafenib in recent studies and it was alsoreported that the combination of radiotherapy withTACE achieved a survival gain compared to sorafenib inHCC patients accompanying PVTT. Surgical resectionbasedmultimodal treatments, transarterial approachesincluding TACE and TARE, and TACE-based appropriatecombination strategies may improve OS of HCC patientsaccompanying PVTT.

  19. Harnessing the RNA interference pathway to advance treatment and prevention of hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Patrick Arbuthnot; Liam Jed Thompson

    2008-01-01

    Primary liver cancer is the fifth most common malignancy in the world and is a leading cause of cancer-related mortality. Available treatment for hepatocellular carcinoma (HCC), the commonest primary liver cancer, is rarely curative and there is a need to develop therapy that is more effective. Specific and powerful gene silencing that can be achieved by activating RNA interference (RNAi) has generated enthusiasm for exploiting this pathway for HCC therapy. Many studies have been carried out with the aim of silencing HCC-related cellular oncogenes or the hepatocarcinogenic hepatitis B virus (HBV) and hepatitis C virus (HCV). Proof of principle studies have demonstrated promising results, and an early clinical trial assessing RNAi-based HBV therapy is currently in progress. Although the data augur well, there are several significant hurdles that need to be overcome before the goal of RNAi-based therapy for HCC is realized. Particularly important are the efficient and safe delivery of RNAi effecters to target malignant tissue and the limitation of unintended harmful non-specific effects.

  20. New Insights in Hepatocellular Carcinoma

    NARCIS (Netherlands)

    C.D.M. Witjes (Carlijn)

    2012-01-01

    textabstractHepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the third most common cause of cancer mortality. HCC is one of the few cancers with well-defined major risk factors. Worldwide, in 80% of the cases HCC develops in cirrhotic livers, and cirrhosis is the stronges

  1. Efficacy and safety of bevacizumab for the treatment of advanced hepatocellular carcinoma: a systematic review of phase II trials.

    Directory of Open Access Journals (Sweden)

    Ping Fang

    Full Text Available BACKGROUND: Hepatocellular carcinoma (HCC is a common cancer associated with a poor prognosis. Bevacizumab is a monoclonal antibody that binds vascular endothelial growth factor, a mediator of tumor angiogenesis. Bevacizumab is currently under investigation as treatment for HCC. We performed a systematic review of the efficacy and safety of bevacizumab for the treatment of advanced HCC. METHODS: PubMed, the Cochrane Library, and Google Scholar were searched using the terms "bevacizumab AND hepatocellular carcinoma AND (advanced OR unresectable". Phase II trials of bevacizumab for the treatment of advanced HCC were included. Outcomes of interest included progression-free and overall survival (PFS and OS, tumor response, and toxicities. RESULTS: A total of 26 records were identified. Of these, 18 were excluded. Hence, eight trials involving 300 patients were included. Bevacizumab was given as monotherapy (n = 1 trial or in combination with erlotinib (n = 4 trials, capecitabine (n = 1 trial, capecitabine+oxaliplatin (n = 1 trial, or gemcitabine+oxaliplatin (n = 1 trial. Most trials (five of eight reported median PFS and OS between 5.3 months and 9.0 months and 5.9 and 13.7 months, respectively. The disease control rate was consistent in five of eight trials, ranging from 51.1% to 76.9%. The response and partial response rates ranged from 0 to 23.7%, but were around 20% in four trials. Only one patient had a complete response. Frequently reported Grade 3/4 toxicities were increased aspartate transaminase/alanine transaminase (13%, fatigue (12%, hypertension (10%, diarrhea (8%, and neutropenia (5%. Thirty patients experienced gastrointestinal bleeding (grade 1/2 = 18, grade 3/4 = 12, typically due to esophageal varices. CONCLUSIONS: Bevacizumab shows promise as an effective and tolerable treatment for advanced HCC. The reported efficacy of bevacizumab appears to compare favorably with that of sorafenib, the only currently

  2. Cyclooxygenases in hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Melchiorre Cervello; Giuseppe Montalto

    2006-01-01

    Many epidemiological studies demonstrate that treatment with non-steroidal anti-inflammatory drugs (NSAIDs) reduce the incidence and mortality of certain malignancies, especially gastrointestinal cancer. The cyclooxygenase (COX) enzymes are well-known targets of NSAIDs. However, conventional NSAIDs nonselectively inhibit both the constitutive form COX-1, and the inducible form COX-2. Recent evidence indicates that COX-2 is an important molecular target for anticancer therapies. Its expression is undetectable in most normal tissues, and is highly induced by proinflammatory cytokines, mitogens, tumor promoters and growth factors. It is now well-established that COX-2 is chronically overexpressed in many premalignant, malignant, and metastastic cancers, including hepatocellular carcinoma (HCC). Overexpression of COX-2 in patients with HCC is generally higher in welldifferentiated HCCs compared with less-differentiated HCCs or histologically normal liver, suggesting that COX-2 may be involved in the early stages of hepatocarcinogenesis, and increased expression of COX-2 in noncancerous liver tissue has been significantly associated with shorter disease-free survival in patients with HCC.In tumors, overexpression of COX-2 leads to an increase in prostaglandin (PG) levels, which affect many mechanisms involved in carcinogenesis, such as angiogenesis, inhibition of apoptosis, stimulation of cell growth as well as the invasiveness and metastatic potential of tumor ceils. The availability of novel agents that selectively inhibit COX-2 (COXIB), has contributed to shedding light on the role of this molecule. Experimental studies on animal models of liver cancer have shown that NSAIDs, including both selective and non-selective COX-2 inhibitors, exert chemopreventive as well as therapeutic effects. However, the key mechanism by which COX-2 inhibitors affect HCC cell growth is as yet not fully understood. Increasing evidence suggests the involvement of molecular targets other

  3. Current management strategy of hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Bernardino Rampone; Beniamino Schiavone; Antonio Martino; Carmine Viviano; Giuseppe Confuorto

    2009-01-01

    Hepatocellular carcinoma (HCC) still remains a considerable challenge for surgeons. Surgery, including liver transplantation, is the most important therapeutic approach for patients with this disease. HCC is frequently diagnosed at advanced stages and has a poor prognosis with a high mortality rate even when surgical resection has been considered potentially curative. This brief report summarizes the current status of the management of this malignancy and includes a short description of new pharmacological approaches in HCC treatment.

  4. Systemic gemcitabine combined with intra-arterial low-dose cisplatin and 5-fluorouracil for advanced hepatocellular carcinoma: Seven cases

    Institute of Scientific and Technical Information of China (English)

    Kiminori Uka; Kazuaki Chayama; Hiroshi Aikata; Shintaro Takaki; Tomokazu Kawaoka; Hiromi Saneto; Daiki Mild; Shoichi Takahashi; Naoyuld Toyota; Katsuhide Ito

    2008-01-01

    The combination of intra-arterial low-dose cisplatin and 5-fluorouracil (5-FU) is effective against advanced hepatocellular carcinoma (HCC).Systemic gemcitabine chemotherapy seems effective in many cancers.We report the results of combination therapy with systemic gemcitabine, intra-arterial low-dose cisplatin and 5-FU (GEMFP).Seven patients with non-resectable advanced HCC were treated with GEMFP.One course of chemotherapy consisted of daily intra-arterial cisplatin (20 mg/body weight/hour on day z, 10 mg/body weight per 0.5 h on d 2-5 and 8-12), followed by 5-FU (250 mg/body weight per 5 h on d 1-5 and 8-12) via an injection port.Gemcitabine at 1000 mg/m2 was administered intravenously at 0.5 h on d 1 and 8.The objective response was 57%.The response to GEMFP was as follows: complete response (no patients), partial response (four patients), stable disease (three patients),and progressive disease (no patients).The median survival period was 8 mo (range, 5-55).With regard to the National Cancer Institute Common Toxicity Criteria (NCI-CTC) grade 3 or 4 adverse reactions, seven (100%),seven, six (86%) and one (14%) patients developed leukopenia, neutropenia, thrombocytopenia and anemia,respectively.GEMFP may potentially be effective for nonresectable advanced HCC, but it has severe hematologic toxicity.

  5. Complete Metabolic Response with Recanalization of Portal Vein Tumor Thrombosis after Sunitinib in a Patient with Advanced Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Michele Basso

    2010-11-01

    Full Text Available The prognosis of patients with advanced hepatocellular carcinoma (HCC is very poor. The outcome of these patients is particularly bleak when the disease is complicated by portal vein tumor thrombosis (PVTT, since the increased portal pressure often causes serious gastrointestinal bleedings. Before the introduction of sorafenib (SOR, a tyrosine kinase inhibitor, no effective treatment was available for patients with advanced disease. SOR is now considered the standard treatment even for patients with tumor thrombosis, although the well-known interference between tyrosine kinase inhibitors and the coagulation pathway calls for caution against their use in this setting. Here, we report the case of a 74-year-old male patient with advanced HCC and PVTT treated with sunitinib (SUN, another multikinase inhibitor. During the third cycle, our patient experienced a life-threatening hematemesis with hemorrhagic shock that required intensive care treatment and SUN discontinuation. However, he completely recovered, and the PET/CT scan performed 1 year after the adverse effect demonstrated no evidence of the tumor together with portal vein recanalization. The short course of SUN causing both tumor response and gastrointestinal bleeding warrants further studies on the effectiveness of SUN in this setting as well as on the duration of treatment with multikinase inhibitors in patients with tumor thrombosis.

  6. Efifcacy of sorafenib therapy in patients with advanced hepatocellular carcinoma in Indian population

    Institute of Scientific and Technical Information of China (English)

    Alit Abraham; Charumathi Purushothaman; Dhanya Damien; Jackson James; Prudence Attilade Rodrigues; Gursharan Singh

    2016-01-01

    Aim: Hepatocelular carcinoma (HCC) is the fourth most common type of cancer and the third leading cause of cancer-related mortality. Sorafenib is an oral multikinase inhibitor that is used for unresectable advanced HCC. It is only approved systemic therapy for advanced HCC.Methods: A retrospective prospective study conducted in a multispeciality hospital with 50 patients who received sorafenib. The primary outcome of the study was to ifnd out the survival rate of patients treated with sorafenib. The secondary outcome of the study was to explore the efifcacy and safety of sorafenib in a progression of HCC.Results: The median overal survival in the Indian population was found as 114 days (3.8 months) after sorafenib therapy. The efifcacy of the drug sorafenib was assessed by the survival days which were based on the changes in laboratory values such as haematological and clinical biochemistry. The adverse drug reaction documented in this study was vomiting, abdominal pain; fatigue; anorexia; hyperbilirubinemia; diarrhoea; hand-foot syndrome; rash; rectal bleeding; insomnia; constipation; thrombocytopenia and abdominal discomfort.Conclusion: Sorafenib improves the overal survival of the patients with advanced HCC in Indian population up to 3.8 months. It is a safe and effective treatment for patients with advanced HCC in Indian population. The survival of patients was found to be depended on the liver function.

  7. Hepatocellular carcinoma: Therapy and prevention

    Institute of Scientific and Technical Information of China (English)

    Hubert E Blum

    2005-01-01

    Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. The major etiologies and risk factors for the development of HCC are well defined and some of the multiple steps involved in hepatocarcinogenesis have been elucidated in recent years. Despite these scientific advances and the implementation of measures for the early detection of HCC in patients at risk, patient survival has not improved during the last three decades. This is due to the advanced stage of the disease at the time of clinical presentation and limited therapeutic options. The therapeutic options fall into five main categories: surgical interventions including tumor resection and liver transplantation, percutaneous interventions including ethanol injection and radiofrequency thermal ablation, transarterial interventions including embolization and chemoembolization, radiation therapy and drugs as well as gene and immune therapies. These therapeutic strategies have been evaluated in part in randomized controlled clinical trials that are the basis for therapeutic recommendations. Though surgery, percutaneous and transarterial interventions are effective in patients with limited disease (1-3 lesions, <5 cm in diameter) and compensated underlying liver disease (cirrhosis Child A), at the time of diagnosis more than 80% patients present with multicentric HCC and advanced liver disease or comorbidities that restrict the therapeutic measures to best supportive care. In order to reduce the morbidity and mortality of HCC, early diagnosis and the development of novel systemic therapies for advanced disease, including drugs, gene and immune therapies as well as primary HCC prevention are of paramount importance. Furthermore, secondary HCC prevention after successful therapeutic interventions needs to be improved in order to make an impact on the survival of patients with HCC. New technologies, including gene expression profiling and proteomic analyses, should allow to further

  8. Proteomics in Discovery of Hepatocellular Carcinoma Biomarkers

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective: To discover new proteomic biomarkers of hepatocellular carcinoma. Methods: Surface enhanced laser desorption/ionization time-of-flight (SELDI-TOF) mass spectrometry was used to discover biomarkers for differentiating hepatocellular carcinoma and chronic liver disease. A population of 50 patients with hepatocellular carcinoma and 33 patients with chronic liver disease was studied. Results: Twelve proteomic biomarkers of hepatocellular carcinoma were detected in this study. Three proteomic biomarkers were highly expressed in hepatocellular carcinoma and nine proteomic biomarkers were highly expressed in chronic liver disease. The most valuable proteomic biomarker with m/z=11498 had no similar diagnostic value as α-fetoprotein. Conclusion:Some of the twelve proteomic biomarkers may become new biomarkers of hepatocellular carcinoma.

  9. Phase 2 Study of Combined Sorafenib and Radiation Therapy in Patients With Advanced Hepatocellular Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Shang-Wen, E-mail: sjfchiou@gmail.com [Department of Radiation Oncology, China Medical University Hospital, Taichung, Taiwan (China); School of Medicine, Taipei Medical University, Taipei, Taiwan (China); School of Medicine, China Medical University, Taichung, Taiwan (China); Lin, Li-Ching [Department of Radiation Oncology, Chi-Mei Hospital, Tainan, Taiwan (China); School of Medicine, Taipei Medical University, Taipei, Taiwan (China); Kuo, Yu-Cheng [Department of Radiation Oncology, China Medical University Hospital, Taichung, Taiwan (China); Department of Biomedical Imaging and Radiological Science, China Medical University, Taichung, Taiwan (China); Liang, Ji-An [Department of Radiation Oncology, China Medical University Hospital, Taichung, Taiwan (China); School of Medicine, China Medical University, Taichung, Taiwan (China); Kuo, Chia-Chun [Department of Radiation Oncology, Taipei Medical University Hospital, Taipei, Taiwan (China); Chiou, Jeng-Fong [Department of Radiation Oncology, Taipei Medical University Hospital, Taipei, Taiwan (China); School of Medicine, Taipei Medical University, Taipei, Taiwan (China)

    2014-04-01

    Purpose: This phase 2 study evaluated the efficacy of radiation therapy (RT) with concurrent and sequential sorafenib therapy in patients with unresectable hepatocellular carcinoma (HCC). Methods and Materials: Forty patients with unresectable HCC unfit for transarterial chemoembolization were treated with RT with concurrent and sequential sorafenib. Sorafenib was administered from the commencement of RT at a dose of 400 mg twice daily and continued to clinical or radiologic progression, unacceptable adverse events, or death. All patients had underlying Child-Pugh A cirrhosis. The maximal tumor diameter ranged from 3.0 cm to 15.5 cm. Coexisting portal vein thrombosis was found in 24 patients and was irradiated simultaneously. The cumulative RT dose ranged from 40 Gy to 60 Gy (median, 50 Gy). Image studies were done 1 month after RT and then every 3 months thereafter. Results: Thirty-three (83%) completed the allocated RT. During RT, the incidence of hand-foot skin reactions ≥ grade 2 and diarrhea were 37.5% and 25%, respectively, and 35% of patients had hepatic toxicities grade ≥2. Twenty-two (55.0%) patients achieved complete or partial remission at the initial assessment, and 18 (45%) had stable or progressive disease. The 2-year overall survival and infield progression-free survival (IFPS) were 32% and 39%, respectively. A Cancer of the Liver Italian Program (CLIP) score ≥2 was associated with an inferior outcome in overall survival. Six patients (15%) developed treatment-related hepatic toxicity grade ≥3 during the sequential phase, and 3 of them were fatal. Conclusions: When RT and sorafenib therapy were combined in patients with unresectable HCC, the initial complete or partial response rate was 55% with a 2-year IFPS of 39%. A CLIP score ≥2 was associated with an inferior outcome in overall survival. Hepatic toxicities are a major determinant of the safety; the combination should be used with caution and needs further investigation.

  10. Successful treatment of advanced hepatocellular carcinoma by combined administration of 5-fiuorouracil and pegylated interferon-α

    Institute of Scientific and Technical Information of China (English)

    Kazutaka Kurokohchi; Kouichi Takaguchi; Keiji Kita; Tsutomu Masaki; Shigeki Kuriyama

    2005-01-01

    We report a case of hepatocellular carcinoma (HCC) treated successfully by transarterial chemoembolization (TACE) followed by combination therapy of 5-fiuorouracil (5-FU)and pegylated interferon-α (PEG-IFN-α). In the present case, the patient had massive and advanced HCC with a diameter of over 8 cm located in segment 7 (S7) of the liver.Furthermore, the tumor invaded into the major branch of the portal vein (Vp3). After TACE, combined administration of 5-FU and PEG-IFN-α was performed for 5 mo. HCC was totally eradicated and the serum levels of tumor markers were markedly decreased by the treatment. Although it has been reported that the combined use of conventional IFN-α and 5-FU showed striking effects on HCC in some cases, this case may suggest the more promising effect of PEG-IFN-α with a long-lasting effect, in the combined use with 5-FU for the treatment of massive advanced HCC.

  11. Targeted therapies in hepatocellular carcinoma.

    Science.gov (United States)

    Bronte, F; Bronte, G; Cusenza, S; Fiorentino, E; Rolfo, C; Cicero, G; Bronte, E; Di Marco, V; Firenze, A; Angarano, G; Fontana, T; Russo, A

    2014-01-01

    The onset of hepatocellular carcinoma (HCC) is related to the development of non-neoplastic liver disease, such as viral infections and cirrhosis. Even though patients with chronic liver diseases undergo clinical surveillance for early diagnosis of HCC, this cancer is often diagnosed in advanced stage. In this case locoregional treatment is not possible and systemic therapies are the best way to control it. Until now sorafenib, a Raf and multi-kinase inhibitor has been the best, choice to treat HCC systemically. It showed a survival benefit in multicenter phase III trials. However the proper patient setting to treat is not well defined, since the results in Child-Pugh B patients are conflicting. To date various new target drugs are under developed and other biological treatments normally indicated in other malignancies are under investigation also for HCC. These strategies aim to target the different biological pathways implicated in HCC development and progression. The target drugs studied in HCC include anti-VEGF and anti-EGFR monoclonal antibodies, tyrosine kinase inhibitors and mTOR inhibitors. The most important challenge is represented by the best integration of these drugs with standard treatments to achieve improvement in overall survival and quality of life.

  12. Asian consensus workshop report: expert consensus guideline for the management of intermediate and advanced hepatocellular carcinoma in Asia.

    Science.gov (United States)

    Han, Kwang-Hyub; Kudo, Masatochi; Ye, Sheng-Long; Choi, Jong Young; Poon, Roonni Tung-Ping; Seong, Jinsil; Park, Joong-Won; Ichida, Takafumi; Chung, Jin Wook; Chow, Pierce; Cheng, Ann-Lii

    2011-01-01

    Hepatocellular carcinoma (HCC) is a highly prevalent disease in many Asian countries, accounting for 80% of victims worldwide. Screening programs improve the detection of early HCC and have a positive impact on survival, but the majority of HCC patients in Asia still present with advanced stage disease. The treatment outcomes of HCC are affected by multiple variables, including liver function, performance status of the patient, and tumor stage. Therefore, it is not easy to apply a multidisciplinary therapeutic approach for optimal management. At present, limited numbers of HCC patients are eligible for curative therapies such as surgery or ablation in Asia. Therefore, most patients are eligible for only palliative treatments. For optimal management, the treatment choice is guided by staging systems and treatment guidelines. Numerous staging systems have been proposed and treatment guidelines vary by region. According to the Barcelona Clinic Liver Cancer (BCLC) guideline based on evidence from randomized clinical trials, only transarterial chemoembolization (TACE) is recommended for intermediate stage HCC and sorafenib for advanced stage HCC. However, treatment guidelines from Asian countries have adopted several other therapeutic modalities such as a surgical approach, hepatic arterial infusion chemotherapy, external radiation, and their combinations based on clinical experiences for intermediate and advanced stage HCC. Although TACE is the main therapeutic modality in the intermediate stage, overall therapeutic outcomes depend on the tumor size. In the advanced stage, the prognosis depends on the tumor status, e.g. major vessel invasion or extrahepatic spread. Thus, a new staging system representing prognoses suitable for Asian HCC patients and a corresponding optimal treatment algorithm should be further investigated using evidence-based data, which will finally bring about an Asian consensus for the management of intermediate and advanced stage HCC.

  13. [Tumor markers for hepatocellular carcinoma].

    Science.gov (United States)

    Tateishi, Ryosuke; Enooku, Kenichiro; Shiina, Shuichiro; Koike, Kazuhiko

    2012-05-01

    Three tumor markers for hepatocellular carcinoma (HCC) are available in Japan: alpha-fetoprotein (AFP), protein induced by vitamin K absence or antagonists-II (PIVKA-II), and Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein (AFP-L3). Although AFP has drawbacks in its specificity, it is widely utilized in treatment evaluation and prognosis prediction. PIVKA-II is a unique marker that does not correlate with AFP value and can predict microvascular invasion. AFP-L3 is a highly specific marker and strong predictor of poor prognosis. These three markers are indispensable in every aspect of clinical practice of hepatocellular carcinoma including surveillance, diagnosis, treatment evaluation, and prognosis prediction.

  14. Contribution of the toxic advanced glycation end-productsreceptor axis in nonalcoholic steatohepatitis-related hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Jun-ichi; Takino; Kentaro; Nagamine; Takamitsu; Hori; Akiko; Sakasai-Sakai; Masayoshi; Takeuchi

    2015-01-01

    Hepatocellular carcinoma(HCC) is one of the most common malignancies worldwide. The main etiologies of HCC are hepatitis B virus and hepatitis C virus(HCV), and non-hepatitis B/non-hepatitis C HCC(NBNCHCC) has also been identified as an etiological factor. Although the incidence of HCV-related HCC in Japan has decreased slightly in recent years, that of NBNC-HCC has increased. The onset mechanism of NBNC-HCC, which has various etiologies, remains unclear; however, nonalcoholic steatohepatitis(NASH), a severe form of nonalcoholic fatty liver disease, is known to be an important risk factor for NBNC-HCC. Among the different advanced glycation end-products(AGEs) formed by the Maillard reaction, glyceraldehyde-derived AGEs, the predominant components of toxic AGEs(TAGE), have been associated with NASH and NBNC-HCC, including NASH-related HCC. Furthermore, the expression of the receptor for AGEs(RAGE) has been correlated with the malignant progression of HCC. Therefore, TAGE induce oxidative stress by binding with RAGE may, in turn, lead to adverse effects, such as fibrosis and malignant transformation, in hepatic stellate cells and tumor cells during NASH or NASH-related HCC progression. The aim of this review was to examine the contribution of the TAGE-RAGE axis in NASH-related HCC.

  15. Contribution of the toxic advanced glycation end-products-receptor axis in nonalcoholic steatohepatitis-related hepatocellular carcinoma.

    Science.gov (United States)

    Takino, Jun-Ichi; Nagamine, Kentaro; Hori, Takamitsu; Sakasai-Sakai, Akiko; Takeuchi, Masayoshi

    2015-10-18

    Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide. The main etiologies of HCC are hepatitis B virus and hepatitis C virus (HCV), and non-hepatitis B/non-hepatitis C HCC (NBNC-HCC) has also been identified as an etiological factor. Although the incidence of HCV-related HCC in Japan has decreased slightly in recent years, that of NBNC-HCC has increased. The onset mechanism of NBNC-HCC, which has various etiologies, remains unclear; however, nonalcoholic steatohepatitis (NASH), a severe form of nonalcoholic fatty liver disease, is known to be an important risk factor for NBNC-HCC. Among the different advanced glycation end-products (AGEs) formed by the Maillard reaction, glyceraldehyde-derived AGEs, the predominant components of toxic AGEs (TAGE), have been associated with NASH and NBNC-HCC, including NASH-related HCC. Furthermore, the expression of the receptor for AGEs (RAGE) has been correlated with the malignant progression of HCC. Therefore, TAGE induce oxidative stress by binding with RAGE may, in turn, lead to adverse effects, such as fibrosis and malignant transformation, in hepatic stellate cells and tumor cells during NASH or NASH-related HCC progression. The aim of this review was to examine the contribution of the TAGE-RAGE axis in NASH-related HCC.

  16. Re-evaluation of antitumor effects of combination chemotherapy with interferon-α and 5-fluorouracil for advanced hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Munechika Enjoji; Shusuke Morizono; Kazuhiro Kotoh; Motoyuki Kohjima; Yuzuru Miyagi; Tsuyoshi Yoshimoto; Makoto Nakamuta

    2005-01-01

    AIM: To evaluate the efficacy of combination chemotherapy with interferon-α (IFNα) and 5-fluorouracil (5-FU) in patients with advanced hepatocellular carcinoma (HCC).METHODS: Twenty-eight HCC patients in advanced stage were enrolled in the study. They were treated with IFNα/5-FU combination chemotherapy. One cycle of therapy lasted for 4 wk. IFNα (3× 106 units) was subcutaneously injected thrice weekly on days 1, 3, and 5 for 3 wk, and 5-FU (500 mg/d) was administered via the proper hepatic artery for 5 consecutive days per week for 3 wk. No drugs were administered during the 4th wk. The effect of combination chemotherapy was evaluated in each patient after every cycle based on the reduction of tumor volume.RESULTS: After the 1st cycle of therapy, 16 patients showed a partial response (PR, 57.1%) but none showed a complete response (CR, 0%). At the end of therapy,the number of patients who showed a CR, PR, or no response (NR) was 1, 10, and 17, respectively. The response rate for therapy (CR+PR) was 21.5%. Biochemical tests before therapy were compared between responsive (CR+PR) and non-responsive (NR) patients, but no significant differences were found for any of the parameters examined, indicating that no reasonable predictors could be identified in our analysis.CONCLUSION: Attempts should be made to discriminate between responders and non-responders by evaluating tumor size after the first cycle of IFNα/5-FU combination chemotherapy. For non-responders, therapy should not proceed to the next cycle, and instead, different combination of anticancer drugs should be explored.

  17. Effectiveness of combined (131)I-chTNT and radiofrequency ablation therapy in treating advanced hepatocellular carcinoma.

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    Tu, Jianfei; Ji, Jiansong; Wu, Fazong; Wang, Yonghui; Zhang, Dengke; Zhao, Zhongwei; Ying, Xihui

    2015-03-01

    To investigate the effectiveness of monoclonal antibody ((131)I-chTNT) and radiofrequency ablation (RFA) combination therapy in treating middle-advanced stage hepatocellular carcinoma (HCC). Thirty-four patients diagnosed with HCC patients, divided into two groups comprised of 22 and 12 cases were included in this retrospective study. The two groups received RFA with or without ((131)I-chTNT) therapy, respectively. The patients in these groups were followed up for a median of 31 and 35 months, respectively. Patient survival was evaluated using Kaplan-Meier method and safety profiles were determined by analyzing liver, thyroid, and bone marrow toxicities. This retrospective study showed that survival time of the patients who received combination therapy was significantly longer than that of the RFA group (P = 0.052). The median progress-free survival of patients in the two groups was 23 and 7 months, respectively, and the difference was significant (P = 0.04). Tumor recurred in 3.5-8.7 months in four of the combination group patients, among which three had newly developed lesions. The red blood cells and platelets counts were not altered on day 7 and 1 month of the treatment, however, number of white blood cells was significantly increased on day 7 which was reversed back to the normal range in 2 weeks. The ALT and AST were also not significantly altered on day 7 and 1 month of therapy. In middle-advanced stage HCC patients, the combination of (131)I-chTNT and RFA therapy was found to be significantly more effective than the RFA treatment alone as assessed in short-term follow-up. However, the dose we used was insufficient to completely block the local recurrence of the lesions with a diameter of 5 cm or larger.

  18. The Efficacy of Continued Sorafenib Treatment after Radiologic Confirmation of Progressive Disease in Patients with Advanced Hepatocellular Carcinoma.

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    Yoshiyuki Wada

    Full Text Available Whether radiologically detected progressive disease (PD is an accurate metric for discontinuing sorafenib treatment in patients with hepatocellular carcinoma (HCC is unclear. We investigated the efficacy of sorafenib treatment after radiologic confirmation of PD in patients with advanced HCC.We retrospectively analyzed HCC patients treated with sorafenib at Kyushu Medical Center. Six of the 92 patients with radiologically confirmed PD were excluded because they were classified as Child-Pugh C or had an Eastern Cooperative Oncology Group (ECOG performance status (PS ≥3; 86 patients were ultimately enrolled.Among the 86 patients, 47 continued sorafenib treatment after radiologic confirmation of PD (the continuous group, whereas 39 did not (the discontinuous group. The median survival time (MST in the continuous group after confirmation was 12.9 months compared with 4.5 months in the discontinuous group (p <0.01. The time to progression in the continuous group after confirmation was 2.6 months compared with 1.4 months in the discontinuous group (p <0.01; it was 4.2 months and 2.1 months in patients who had received sorafenib ≥4 months and <4 months, respectively, before confirmation (p = 0.03. In these subgroups, the post-PD MST was 16.7 months and 9.6 months, respectively (p < 0.01. Independent predictors of overall survival after radiologic detection of PD were (hazard ratio, confidence interval: ECOG PS <2 (0.290, 0.107-0.880, Barcelona Clinical Liver Cancer stage B (0.146, 0.047-0.457, serum α-fetoprotein level ≥400 ng/mL (2.801, 1.355-5.691, and post-PD sorafenib administration (0.279, 0.150-0.510.Continuing sorafenib treatment after radiologic confirmation of PD increased survival in patients with advanced HCC. Therefore, radiologically detected PD is not a metric for discontinuation of sorafenib treatment in such patients.

  19. Genetic alteration in hepatocellular carcinoma

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    Kim, Yoo Chul; Kang, Tae Woong; Lee, Jin Oh [Korea Cancer Center Hospital of Korea Atomic Energy Research Institute, Seoul (Korea, Republic of)

    1994-12-01

    Cancer of stomach, colon and liver are a group of the most common cancer in Korea. However, results with current therapeutic modalities are still unsatisfactory. The intensive efforts have been made to understand basic pathogenesis and to find better therapeutic tools for the treatment of this miserable disease. We studied the alteration of tumor suppressor genes and oncogenes in hepatocellular carcinoma in Korea. We found that alteration of Rb gene, APC were 33 %, 13 % respectively. But alterations of oncogenes such as myc, ras and mdm2 were rarely found. Our results suggests that HBV may act as oncogenic role in hepatocarcinogenesis instead of oncogenes. 6 figs, 2 tabs. (Author).

  20. Management of large hepatocellular carcinoma.

    Science.gov (United States)

    Amarapurkar, D N

    2004-04-01

    Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world. There is increasing incidence of HCC in India. More than 70% of HCC are not suitable for curative treatment. Majority of the HCCs are large when diagnosed all over the world. There is no standard treatment for large HCCs. Different palliative treatments like arterial embolization/chemoembolization, intraarterial lipoidol chemotherapy, hormonal compounds like tamoxifene, octerotide systemic chemotherapy, immuno therapy with interferon, internal radiation with 131I or 99Yttrium. Arterial chemoembolization is the treatment of choice with proved efficacy in selected group of patients. The newer modalities and strategies need to be tried in controlled randomized trials.

  1. Hepatocellular Carcinoma: Therapeutic Guidelines and Medical Treatment

    Science.gov (United States)

    Kudo, Masatoshi; Trevisani, Franco; Abou-Alfa, Ghassan K; Rimassa, Lorenza

    2016-01-01

    Western and Eastern perspectives on therapeutic guidelines for hepatocellular carcinoma (HCC) have many commonalities but may also differ in certain aspects, as described in this article. In view of the limited therapeutic options for advanced HCC, evidence-based therapies are few, and thus there is a dependence on consensus-based guidelines. This article focuses on the Italian Association for the Study of the Liver guidelines and the Japanese approaches to therapy, while drawing attention to certain controversies from other academic bodies where applicable and appropriate. PMID:27995084

  2. Hepatitis C Virus and Hepatocellular Carcinoma

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    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. Surgical Treatment for Hepatocellular Carcinoma

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    Ahmad A Madkhali

    2015-01-01

    Full Text Available Hepatocellular carcinoma (HCC is an epithelial tumor derived from hepatocytes; it accounts for 80% of all primary liver cancers and ranks globally as the fourth leading cause of cancer-related deaths. HCC treatment is a multidisciplinary and a multimodal task, with surgery in the form of liver resection and liver transplantation (LT representing the only potentially curative modality. However, there are variable opinions and discussions about applying these surgical options and using other supporting treatments. This article is a narrative review that includes articles published from 1984 to 2013 located by searching scientific databases such as PubMed, SCOPUS, and Elsevier, with the main keyword of hepatocellular carcinoma in addition to other keywords such as liver transplantation, liver resection, transarterial chemoembolization, portal vein embolization, bridging therapy, and downstaging. In this review, we focus mainly on the surgical treatment options offered for HCC, in order to illustrate the current relevant data available in the literature to help in applying these surgical options and to use other supporting treatment modalities when appropriate.

  4. Nonalcoholic steatohepatitis and hepatocellular carcinoma: Brazilian survey

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    Helma P. Cotrim

    2016-05-01

    Full Text Available OBJECTIVE: The majority of cases of hepatocellular carcinoma have been reported in individuals with cirrhosis due to chronic viral hepatitis and alcoholism, but recently, the prevalence has become increasingly related to nonalcoholic steatohepatitis around the world. The study aimed to evaluate the clinical and histophatological characteristics of hepatocellular carcinoma in Brazilians' patients with nonalcoholic steatohepatitis at the present time. METHODS: Members of the Brazilian Society of Hepatology were invited to complete a survey regarding patients with hepatocellular carcinoma related to nonalcoholic steatohepatitis. Patients with a history of alcohol intake (>20 g/day and other liver diseases were excluded. Hepatocellular carcinoma diagnosis was performed by liver biopsy or imaging methods according to the American Association for the Study of Liver Diseases’ 2011 guidelines. RESULTS: The survey included 110 patients with a diagnosis of hepatocellular carcinoma and nonalcoholic fatty liver disease from nine hepatology units in six Brazilian states (Bahia, Minas Gerais, Rio de Janeiro, São Paulo, Paraná and Rio Grande do Sul. The mean age was 67±11 years old, and 65.5% were male. Obesity was observed in 52.7% of the cases; diabetes, in 73.6%; dyslipidemia, in 41.0%; arterial hypertension, in 60%; and metabolic syndrome, in 57.2%. Steatohepatitis without fibrosis was observed in 3.8% of cases; steatohepatitis with fibrosis (grades 1-3, in 27%; and cirrhosis, in 61.5%. Histological diagnosis of hepatocellular carcinoma was performed in 47.2% of the patients, with hepatocellular carcinoma without cirrhosis accounting for 7.7%. In total, 58 patients with cirrhosis had their diagnosis by ultrasound confirmed by computed tomography or magnetic resonance imaging. Of these, 55% had 1 nodule; 17%, 2 nodules; and 28%, ≥3 nodules. CONCLUSIONS: Nonalcoholic steatohepatitis is a relevant risk factor associated with hepatocellular carcinoma in

  5. The effects of low dose chemotherapy for advanced hepatocellular carcinoma through percutaneously implanted intra-arterial port system

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    Lee, Hyun Seok; Won, Je Hwan; Yoo, Byung Moo; Kim, Young Soo; Cho, Sung Won [Ajou Univ. College of Medicine, Suwon (Korea, Republic of); Park, Dong Won [Suwon Medical Center, Suwon (Korea, Republic of)

    2001-07-01

    To investigate the effects of low-dose FP (5-Fluorouracil[5FU]+Cispatin[CDDP]) therapy through a percutaneously implanted intra-arterial port system in patients with advanced hepatocellular carcinoma (HCC). Twenty-five patients with advanced HCCs and portal vein thrombosis, or large HCCs which were unresectable or for which transarterial chemoembolization was thought to be ineffective, underwent intra-arterial port implantation. The mean maxinal diameter of these tumors was 13.7 (range, 5-21.5) cm, and they were located at the right lobe (n=18), the left lobe(n=3), or throughout the liver (n=4). Tumor thrombosis was detected in the main (n=14), right (n=3) and left portal vein(n=1), the right portal vein and inferior vena cava(n=2), and the inferior vena cava(n=1). The four others patients had no portal vein thrombosis. All intra-arterial port implantations were performed percutaneously in the angiographic ward through the right or left common femoral artery. The port chamber was implanted in the inguinal area and fixed using histoacryl. For intra-arterial chemotherapy, 5-FU (250 mg/day) and CDDP (10 mg/day) were used for five days every four weeks. In order to observe changes in tumor size, follow-up CT scanning was performed every two months. Implantation of the port system was successful in all cases, and patients underwent between one and eleven (mena, 3.9) sessions of chemotherapy. Port-and catheter-related complications, namely dislodgement of the catheter(n=2), wound infection(n=2), migration of the coil(n=1) and catheter occlusion(n=1) occurred in six patients (24%), and chemotherapy-related complications, namely liver failure(n=3) and gastric ulcer bleeding(n=1), in four (16%). A complete response, i. e. the disappearance of tumor thrombosis of the portal vein, was achieved in one patient (4%), a partial response in three (12%), and a minor response in four (16%); the overall response rate was 32% and the mean survival period was 7.6 months. Low-dose FP

  6. Thymostimulin versus placebo for palliative treatment of locally advanced or metastasised hepatocellular carcinoma: a phase III clinical trial

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    Dollinger Matthias M

    2010-08-01

    Full Text Available Abstract Background Thymostimulin is a thymic peptide fraction with immune-mediated cytotoxicity against hepatocellular carcinoma (HCC in vitro and palliative efficacy in advanced HCC in two independent phase II trials. The aim of this study was to assess the efficacy of thymostimulin in a phase III trial. Methods The study was designed as a prospective randomised, placebo-controlled, double-blind, multicenter clinical phase III trial. Between 10/2002 and 03/2005, 135 patients with locally advanced or metastasised HCC (Karnofsky ≥60%/Child-Pugh ≤ 12 were randomised to receive thymostimulin 75 mg s.c. 5×/week or placebo stratified according to liver function. Primary endpoint was twelve-month survival, secondary endpoints overall survival (OS, time to progression (TTP, tumor response, safety and quality of life. A subgroup analysis according to liver function, KPS and tumor stage (Okuda, CLIP and BCLC formed part of the protocol. Results Twelve-month survival was 28% [95%CI 17-41; treatment] and 32% [95%CI 19-44; control] with no significant differences in median OS (5.0 [95% CI 3.7-6.3] vs. 5.2 [95% CI 3.5-6.9] months; p = 0.87, HR = 1.04 [95% CI 0.7-1.6] or TTP (5.3 [95%CI 2.0-8.6] vs. 2.9 [95%CI 2.6-3.1] months; p = 0.60, HR = 1.13 [95% CI 0.7-1.8]. Adjustment for liver function, Karnofsky status or tumor stage did not affect results. While quality of life was similar in both groups, fewer patients on thymostimulin suffered from accumulating ascites and renal failure. Conclusions In our phase III trial, we found no evidence of any benefit to thymostimulin in the treatment of advanced HCC and there is therefore no justification for its use as single-agent treatment. The effect of thymostimulin on hepato-renal function requires further confirmation. Trial Registration Current Controlled Trials ISRCTN64487365.

  7. Hepatocellular carcinoma and industrial epidemics

    Institute of Scientific and Technical Information of China (English)

    Alain Braillon; Gérard Dubois

    2011-01-01

    Worldwide, the burden of the non viral causes of hepatocellular carcinoma (HCC) is usually underestimated. Clearly industrial goods, tobacco, alcohol and processed foods are the agents of new epidemics in modern times which far outscore the burden of infectious agents on morbidity and mortality. Smoking, a dose-related contributing factor for HCC, receives too little attention in clinical practice. In France, tobacco, hepatitis B and C virus and alcohol are the main risk factors for HCC mortality (33%, 31% and 26%, respectively). In developing countries, where tobacco consumption is dramatically increasing, this epidemic may soon surpass hepatitis B. Obesity and diabetes are the contributing factors too. The role of industrial processed foods in the increase of the prevalence of obesity and diabetes cannot be ignored.

  8. Metastatic Hepatocellular Carcinoma Responsive to Pembrolizumab.

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    Truong, Phu; Rahal, Ahmad; Kallail, K James

    2016-01-01

    Hepatocellular carcinoma (HCC) is an aggressive liver tumor that occurs with chronic liver disease. Surgical resection is the mainstay of therapy for localized disease whereas therapeutic options for advanced disease are limited. The innovative blockade of immune checkpoints with targeted immunotherapies, such as monoclonal antibodies against programmed death receptor 1 (PD-1), have shown promise in the treatment of solid malignancies. The PD-1 inhibiting antibodies, nivolumab and pembrolizumab prolonged overall survival in randomized trials in metastatic melanoma and advanced non-small cell lung cancer. This is a report of a 75-year-old male patient with metastatic HCC who was initially treated with the standard of therapy sorafenib. After failure of sorafenib therapy, pembrolizumab was started. There was a dramatic response to pembrolizumab with decrease in tumor size and drop in alfa fetoprotein. To the best of our knowledge, this is the first case report of metastatic HCC responsive to pembrolizumab after failure of sorafenib.

  9. A Phase II Study of Cixutumumab (IMC-A12, NSC742460) in Advanced Hepatocellular Carcinoma

    Science.gov (United States)

    Abou-Alfa, Ghassan K.; Capanu, Marinela; O’Reilly, Eileen M.; Ma, Jennifer; Chou, Joanne F.; Gansukh, Bolorsukh; Shia, Jinru; Kalin, Marcia; Katz, Seth; Abad, Leslie; Reidy-Lagunes, Diane L.; Kelsen, David P.; Chen, Helen X.; Saltz, Leonard B.

    2014-01-01

    Background and Aims IGF-IR is implicated in hepatic carcinogenesis. This and preliminary evidence of biological activity of anti-IGF-1R monoclonal antibody cixutumumab in phase I trials prompted this phase II study. Methods Patients with advanced HCC, Child-Pugh A-B8, received cixutumumab 6 mg/kg weekly, in a Simon two-stage design study, with the primary endpoints being 4-month PFS and RECIST-defined response rate. Tissue and circulating markers plus different HCC scoring systems were evaluated for correlation with PFS and OS. Results As a result of pre-specified futility criteria, only stage 1 was accrued: N= 24: median age 67.5 years (range 49–83), KPS 80% (70–90%), 20 males (83%), 9 stage III (37%)/15 stage IV (63%), 18 Child-Pugh A (75%), 11 HBV (46%) /10 HCV (42%)/11 alcoholic cirrhosis (46%)/2 NASH (8%), 11 (46%) diabetic. Median number of doses: 7 (range 1–140). Grade 3/4 toxicities > 10% included: diabetes, elevated liver function tests, hyponatremia, and lymphopenia. Four-month PFS was 30% (95% CI 13–48), and there were no objective responses. Median overall survival was 8 months (95%CI 5.8– 14). IGF-R1 staining did not correlate with outcome. Elevated IGFBP-1 correlated with improved PFS (1.2 [95%CI 1–1.4]; p 0.009) and OS (1.2 [95%CI 1.1–1.4]; p 0.003). Conclusions Cixutumumab monotherapy did not have clinically meaningful activity in this unselected HCC population. Grade 3–4 hyperglycemia occurred in 46% of patients. Elevated IGFBP-1 correlated with improved PFS and OS. PMID:24045151

  10. Hepatocellular carcinoma:A comprehensive review

    Institute of Scientific and Technical Information of China (English)

    Lisa; P; Waller; Vrushak; Deshpande; Nikolaos; Pyrsopoulos

    2015-01-01

    Hepatocellular carcinoma(HCC) is rapidly becoming one of the most prevalent cancers worldwide. With a rising rate, it is a prominent source of mortality. Patients with advanced fibrosis, predominantly cirrhosis and hepatitis B are predisposed to developing HCC. Individuals withchronic hepatitis B and C infections are most commonly afflicted. Different therapeutic options, including liver resection, transplantation, systemic and local therapy, must be tailored to each patient. Liver transplantation offers leading results to achieve a cure. The Milan criteria is acknowledged as the model to classify the individuals that meet requirements to undergo transplantation. Mean survival remains suboptimal because of long waiting times and limited donor organ resources. Recent debates involve expansion of these criteria to create options for patients with HCC to increase overall survival.

  11. Immunological landscape and immunotherapy of hepatocellular carcinoma.

    Science.gov (United States)

    Prieto, Jesús; Melero, Ignacio; Sangro, Bruno

    2015-12-01

    Advanced hepatocellular carcinoma (HCC) is a serious therapeutic challenge and targeted therapies only provide a modest benefit in terms of overall survival. Novel approaches are urgently needed for the treatment of this prevalent malignancy. Evidence demonstrating the antigenicity of tumour cells, the discovery that immune checkpoint molecules have an essential role in immune evasion of tumour cells, and the impressive clinical results achieved by blocking these inhibitory receptors, are revolutionizing cancer immunotherapy. Here, we review the data on HCC immunogenicity, the mechanisms for HCC immune subversion and the different immunotherapies that have been tested to treat HCC. Taking into account the multiplicity of hyperadditive immunosuppressive forces acting within the HCC microenvironment, a combinatorial approach is advised. Strategies include combinations of systemic immunomodulation and gene therapy, cell therapy or virotherapy.

  12. Second laparoscopic resection for recurrent hepatocellular carcinoma after initial laparoscopic

    Institute of Scientific and Technical Information of China (English)

    LIANG Xiao; CAI Xiu-jun; YU Hong; WANG Yi-fan; LIANG Yue-long

    2009-01-01

    @@ With the development of laparoscopic techniques,laparoscopic hepatectomy is feasible for hepatocellular carcinoma as reported in recent years.Although several reports have been published on laparoscopic surgery for metastatic liver cancer,1,2 few of them deals with second laparoscopic resection of recurrent hepatocellular carcinoma. We report a case of second laparoscopic resection for recurrent hepatocellular carcinoma after initial laparoscopic hepatectomy.

  13. Salvage therapy for hepatocellular carcinoma with thalidomide

    Institute of Scientific and Technical Information of China (English)

    Tsang-En Wang; Chin-Roa Kao; Shee-Chan Lin; Wen-Hsiung Chang; Cheng-Hsin Chu; Johson Lin; Ruey-Kuen Hsieh

    2004-01-01

    AIM: To evaluate the clinical benefit of thalidomide in patients with advanced hepatocellular carcinoma (hepatoma).METHODS: From March 2000 to July 2002, patients who had advanced hepatocellular carcinoma and failed to or were unsuited for aggressive treatment, were enrolled and took thalidomide 150 to 300 mg/d. All cases were followed till April 2003. Data collection included viral hepatitis, grade of cirrhosis, total dosage of thalidomide, side effect, stage of hepatoma by Okuda and CLIP classification, and prognosis.The subjects were divided into A and B groups, depending on 5 000 mg dosage of thalidomide. Survival time of all cases and in the two subgroups was evaluated.RESULTS: Ninety-nine patients with hepatoma were enrolled,81 men and 18 females with median age 58±14.1 years.Eighty-six percent had viral hepatitis and one case was alcoholism. Hepatoma was diagnosed with histology, alphafetoprotein (aFP) >400 ng/mL, or image examination, there were 30, 33 and 36 cases respectively. At the time of thalidomide therapy, more than 81% had cirrhotic status.Twenty-two patients were in group A (<5 000 mg) with median survival time about 25 days, for 77 cases in group B (≥5 000 mg) the median survival time was about 109 days.Six subjects had partial response. Most adverse effects were skin rush, neuropathy, somnolence, and constipation.CONCLUSION: Several patients responded to thalidomide therapy. As a single drug therapy, thalidomide might not have good therapeutic effect for all cases, but a small ratio of patients had exciting response, the resistance or tumor escape would develop after long-term use. Up to now, no defined facts could be used to predict response. The effect of thalidomide on hepatoma might be associated with the dosage. As salvage therapy, thalidomide has its value.Combination or adjuvant therapy will be the next trial.

  14. Surgical management of hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Tony CY Pang; Vincent WT Lam

    2015-01-01

    Hepatocellular carcinoma (HCC) is the second mostcommon cause of death from cancer worldwide.Standard potentially curative treatments are eitherresection or transplantation. The aim of this paper isto provide an overview of the surgical managementof HCC, as well as highlight current issues in hepaticresection and transplantation. In summary, due to therelationship between HCC and chronic liver disease,the management of HCC depends both on tumourrelatedand hepatic function-related considerations. Assuch, HCC is currently managed largely through nonsurgicalmeans as the criteria, in relation to the aboveconsiderations, for surgical management is still largelyrestrictive. For early stage tumours, both resectionand transplantation offer fairly good survival outcomes(5 years overall survival of around 50%). Selectiontherefore would depend on the level of hepatic functionderangement, organ availability and local expertise.Patients with intermediate stage cancers have limitedoptions, with resection being the only potential forcure. Otherwise, locoregional therapy with transarterialchemoembolization or radiofrequency ablation are viableoptions. Current issues in resection and transplantationare also briefly discussed such as laparoscopic resection,ablation vs resection, anatomical vs non-anatomicalresection, transplantation vs resection, living donor livertransplantation and salvage liver transplantation.

  15. Interventional treatments for hepatocellular carcinoma

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    Yong-Song Guan; Yuan Liu

    2006-01-01

    BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most frequent primary malignant tumors in the world. Hepatic resection and liver transplantation are considered optimal for potential treatment of HCC. However, only 20%of HCCs can be surgically treated. And most of surgically-noneligible patients have to receive interventional managements including local ablation and transarterial chemoembolization (TACE). In this paper, we review the interventional treatments of HCC. DATA SOURCES:A literature search of PubMed database was conducted and research articles were reviewed. RESULTS: Percutaneous ethanol injection (PEI) is usually applied to small HCC for a complete necrosis. Radiofrequency ablation, an alternative to PEI, also causes tumor necrosis and needs fewer times of ablation. Other methods such as acetic acid injection, laser, microwave, etc have enriched local ablation for HCC. High intensity focus ultrasound (HIFU) is thought to be promising. TACE, another common modality, can improve the survival rate of patients with HCC. The newly developed embolic agents and adjuvant rAd-p53 gene therapy are well reported. CONCLUSIONS:Surgically-noneligible HCC can be treated with interventional procedures. Each method has its advantages and disadvantages. However, it is still pressing to develop ablative methods as well as new embolic agents for a better prognosis of HCC.

  16. Hepatocellular carcinoma: epidemiology and risk factors

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    Kew MC

    2014-08-01

    Full Text Available Michael C Kew Department of Medicine, Groote Schuur Hospital and University of Cape Town, Cape Town, South Africa Abstract: Hepatocellular carcinoma is one of the major malignant tumors in the world today. The number of new cases of the tumor increases year by year, and hepatocellular carcinoma almost always runs a fulminant course and carries an especially grave prognosis. It has a low resectability rate and a high recurrence rate after surgical intervention, and responds poorly to anticancer drugs and radiotherapy. Hepatocellular carcinoma does not have a uniform geographical distribution: rather, very high incidences occur in Eastern and Southeastern Asia and in sub-Saharan Black Africans. In these regions and populations, the tumor shows a distinct shift in age distribution toward the younger ages, seen to greatest extent in sub-Saharan Black Africans. In all populations, males are more commonly affected. The most common risk factors for hepatocellular carcinoma in resource-poor populations with a high incidence of the tumor are chronic hepatitis B virus infection and dietary exposure to the fungal hepatocarcinogen aflatoxin B1. These two causative agents act either singly or synergistically. Both the viral infection and exposure to the fungus occur from early childhood, and the tumor typically presents at an early age. Chronic hepatitis C virus infection is an important cause of hepatocellular carcinoma in resource-rich countries with a low incidence of the tumor. The infection is acquired in adulthood and hepatocellular carcinoma occurs later than it does with hepatitis B virus-induced tumors. In recent years, obesity and the metabolic syndrome have increased markedly in incidence and importance as a cause of hepatocellular carcinoma in some resource-rich regions. Chronic alcohol abuse remains an important risk factor for malignant transformation of hepatocytes, frequently in association with alcohol-induced cirrhosis. Excessive iron

  17. Synchronous Fibrolamellar Hepatocellular Carcinoma and Auricular Myxoma

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    Yessica M. González-Cantú

    2015-01-01

    Full Text Available Synchronic occurrence of benign and malignant tumors is extremely rare. Fibrolamellar hepatocellular carcinoma represents 1% to 2% of all hepatocarcinomas, while myxomas represent about half of all the cases of primary tumors of the heart. We present the case of a 53-year-old woman with a left atrial myxoma that was surgically removed. Several weeks later, the patient returned to the hospital with abdominal pain. CT scan showed a mass in the left lobe of the liver that was resected and diagnosed as fibrolamellar hepatocellular carcinoma. As of this writing, the patient is healthy.

  18. Primary prevention of hepatocellular carcinoma.

    Science.gov (United States)

    Yu, S Z

    1995-01-01

    Hepatocellular carcinoma (HCC) is one of the major cancers in China. Accordingly, the mortality rates in 1990 (per 100,000) were 20.10 in certain cities and 24.32 in certain counties. More than 90% of HCC cases and 70% of controls were infected with the hepatitis B virus (HBV) (Odds Ratio (OR) = 10-50). In the same group of patients, 8-27% of those with HCC and 0-11% of the healthy controls were also infected with hepatitis C (HCV) (OR = 2.11-17.29). There appears to be some correlation between HBV markers and the OR. The government requires that 85% of infants be immunized with HBV vaccine. In 1992, there were 3 million infants inoculated with HB vaccines. Aflatoxins have been found as contaminants in food, particularly in corn, peanut oil, soya sauce and fermented soya beans. The intake of aflatoxin B1 (AFB1) by people of ten different villages correlated with HCC mortality rates (r = 0.55; P aflatoxins. These adducts are higher in hyperendemic HCC areas and cases. Most people have now changed their staple food and eat rice instead of corn. Six large epidemiological studies have confirmed that people who drink pond-ditch water experience higher HCC mortality rates than people who drink deep-well water. Recent research has found that the blue-green algal toxin microcystin (MCYST) was a contaminant of pond-ditch water. MCYST is a strong promoter of HCC and will induce severe intrahepatic haemorrhages and liver necrosis. More than 80% of people in Qidong County have already changed their sources of water from pond-ditches to deep wells. Therefore, a combined strategy of the prevention of hepatitis, control of crops and control of drinking water is advocated for the primary prevention of HCC in China.

  19. Decreased apoptosis in advanced-stage/high-grade hepatocellular carcinoma complicating chronic hepatitis C is mediated through the downregulation of p21 ras

    Institute of Scientific and Technical Information of China (English)

    Nahed Baddour; Ebtehal Farrag; Ahmed Zeid; Essam Bedewy; Yousry Taher

    2013-01-01

    Objective and background:Although p21 ras has been reported to be upregulated in hepatocellular carcinoma complicating chronic hepatitis C type Ⅰ,p21 ras has a different role in advanced stages,as it has been found to be downregulated.The goal of this study was to investigate the status of p21 ras in early-stage/low-grade and late-stage/high-grade hepatocellular carcinoma and its possible link to apoptosis.Material and methods:Thirty-five cases each of chronic HCV hepatitis type 4 (group Ⅰ) and cirrhosis with hepatocellular carcinoma (HCC) complicating chronic HCV hepatitis (groups Ⅱ and Ⅲ) were immunohistochemically evaluated using a p21 ras polyclonal antibody.The apoptotic index was determined in histologic sections using the terminal deoxynucleotidyl transferase-mediated d-UTP biotin nick end labeling (TUNEL) assay.Results:Significant differences (P=0.001) were detected in p21 ras protein expression between the three groups.A near 2-fold increase in p21 ras staining was observed in the cirrhotic cases compared to the hepatitis cases,and p21 ras expression was decreased in the HCC group.p21 ras expression correlated with stage (r=0.64,P=0.001) and grade (r=-0.65,P=0.001) in the HCC group and grade in the HCV group (r=0.44,P=0.008).Both p21 ras expression and TUNEL-LI were significantly lower in large HCCs compared to small HCCs (P=0.01 each).The TUNEL values were negatively correlated with stage in the HCC group (r=-0.85,P=0.001).The TUNEL values were also negatively correlated with grade in both the HCV and HCC groups (r=0.89,P=0.001 and r=-0.53,P=0.001,respectively).The p21 ras scores were significantly correlated with the TUNEL-LI values in the HCC group (r=0.63,P=0.001) and HCV group (r=0.88,P=0.001).Conclusions:p21 ras acts as an initiator in HCC complicating type 4 chronic HCV and is downregulated with HCC progression,which most likely promotes tumor cell survival because it facilitates the downregulation of apoptosis with tumor progression.

  20. A rare case report: Carcinoma pancreas with hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Vikas Yadav

    2014-01-01

    Full Text Available Synchronous double malignancies involving different organs are relatively rare and uncommon finding. We report an interesting case of double malignancy in which a patient exhibited synchronous two separate carcinomas, pancreatic and hepatocellular carcinoma (HCC. Patient was a 64-year-old male who presented primarily with symptoms pertaining to the biliary obstruction and ultrasound of abdomen revealing pancreatic head mass. HCC was detected incidentally during the investigations for carcinoma pancreas.

  1. Short-term and long-term efficacy of 7 targeted therapies for the treatment of advanced hepatocellular carcinoma: a network meta-analysis

    Science.gov (United States)

    Niu, Meng; Hong, Duo; Ma, Teng-Chuang; Chen, Xiao-Wei; Han, Jin-Hang; Sun, Jun; Xu, Ke

    2016-01-01

    Abstract Background: A variety of targeted drug therapies in clinical trials have been proven to be effective for the treatment of hepatocellular carcinoma (HCC). Our study aims to compare the short-term and long-term efficacies of different targeted drugs in advanced hepatocellular carcinoma (AHCC) treatment using a network meta-analysis approach. Methods: PubMed, Embase, Ovid, EBSCO, and Cochrane central register of controlled trials were searched for randomized controlled trials (RCTs) of different targeted therapies implemented to patients with AHCC. And the retrieval resulted in 7 targeted drugs, namely, sorafenib, ramucirumab, everolimus, brivanib, tivantinib, sunitinib, and sorafenib+erlotinib. Direct and indirect evidence were combined to evaluate stable disease (SD), progressive disease (PD), complete response (CR), partial response (PR), disease control rate (DCR), overall response ratio (ORR), overall survival (OS), and surface under the cumulative ranking curve (SUCRA) of patients with AHCC. Results: A total of 11 RCTs were incorporated into our analysis, including 6594 patients with AHCC, among which 1619 patients received placebo treatment and 4975 cases had targeted therapies. The results revealed that in comparison with placebo, sorafenib, and ramucirumab displayed better short-term efficacy in terms of PR and ORR, and brivanib was better in ORR. Regarding long-term efficacy, sorafenib and sorafenib+erlotinib treatments exhibited longer OS. The data of cluster analysis showed that ramucirumab or sorafenib+erlotinib presented relatively better short-term efficacy for the treatment of AHCC. Conclusion: This network meta-analysis shows that ramucirumab and sorafenib+erlotinib may be the better targeted drugs for AHCC patients, and sorafenib+erlotinib achieved a better long-term efficacy. PMID:27930578

  2. 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.)

  3. 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 limit

  4. 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 Mil

  5. Advancements in the surgical treatment of hepatocellular carcinoma%肝癌外科治疗的进展

    Institute of Scientific and Technical Information of China (English)

    樊嘉; 王征

    2011-01-01

    The incidence of hepatocellular carcinoma ( HCC ) has increased worldwide over the past two decades.Surgical resection and liver transplantation have been demonstrated as potentially curative treatment options, which could be considered in 30% to 40% of HCC patients.Recent advancements of surgical treatment have focused not only on the surgical techniques ,but also the hepatic functional reserve evaluation, resectability assessment and the effects of biological characteristics of tumor on prognosis.There is no single variable to evaluate hepatic functional reserve accurately.The combination of Child-Pugh classification, 15-minute retention rate?for? Indocyanine Green ( ICG15 ) ,portal vein pressure and remanent liver volume measurement is a reasonable strategy prior to ChildPugh classification alone for liver resection.Five-year survival rate after liver resection for HCC is about 50%.The results may be acceptable for some selected patients underwent tumor resection with thrombectomy,including HCC with portal vein tumor thrombus and bile duct thrombosis.The choice of local resection or regular hepatectomy is still controversial although the former is common in HCC with cirrhosis ,and the latter is in the setting without liver cirrhosis.The result of liver transplantation for HCC is better than that of liver resection,and Milan criteria is a generally accepted algorithm.Any attempts to expand the selection criteria should be cautious in the present setting of organ shortage.Salvage transplantation for intra-hepatic recurrence after liver resection may be a good choice in some resectable HCC.The recurrence and metastasis after surgical treatments are of the main obstacle to achieve better results.Identification of predictive factors could be helpful to develop prevention strategies.Due to the importance of biological characteristics in tumor recurrence and metastasis,a molecular classification to predict prognosis of HCC will lead to a more personalized

  6. Incorporating GSA-SPECT into CT-based dose-volume histograms for advanced hepatocellular carcinoma radiotherapy

    Institute of Scientific and Technical Information of China (English)

    Shintaro; Shirai; Morio; Sato; Yasutaka; Noda; Yoshitaka; Kumayama; Noritaka; Shimizu

    2014-01-01

    In single photon emission computed tomography-based three-dimensional radiotherapy(SPECT-B-3DCRT), im-ages of Tc-99 m galactosyl human serum albumin(GSA), which bind to receptors on functional liver cells, are merged with the computed tomography simulation im-ages. Functional liver is defined as the area of normal liver where GSA accumulation exceeds that of hepato-cellular carcinoma(HCC). In cirrhotic patients with a gigantic, proton-beam-untreatable HCC of ≥ 14 cm in diameter, the use of SPECT-B-3DCRT in combination with transcatheter arterial chemoembolization achieved a 2-year local tumor control rate of 78.6% and a 2-year survival rate of 33.3%. SPECT-B-3DCRT was applied to HCC to preserve as much functional liver as possible. Sixty-four patients with HCC, including 30 with Child B liver cirrhosis, received SPECT-B-3DCRT and none ex-perienced fatal radiation-induced liver disease(RILD). The Child-Pugh score deteriorated by 1 or 2 in > 20% of functional liver volume that was irradiated with ≥ 20 Gy. The deterioration in the Child-Pugh score decreased when the radiation plan was designed to irradiate ≤ 20% of the functional liver volume in patients givendoses of ≥ 20 Gy(FLV20Gy). Therefore, FLV20 Gy ≤ 20% may represent a safety index to prevent RILD during 3DCRT for HCC. To supplement FLV20 Gy as a qualitative index, we propose a quantitative indicator, F 20 Gy, which was calculated as F 20 Gy = 100% ×(the GSA count in the area irradiated with ≥ 20 Gy)/(the GSA count in the whole liver).

  7. Xanthohumol Inhibits Notch Signaling and Induces Apoptosis in Hepatocellular Carcinoma

    OpenAIRE

    Selvi Kunnimalaiyaan; Sokolowski, Kevin M.; Mariappan Balamurugan; T. Clark Gamblin; Muthusamy Kunnimalaiyaan

    2015-01-01

    Despite improvement in therapeutic strategies, median survival in advanced hepatocellular carcinoma (HCC) remains less than one year. Therefore, molecularly targeted compounds with less toxic profiles are needed. Xanthohumol (XN), a prenylated chalcone has been shown to have anti-proliferative effects in various cancers types in vitro. XN treatment in healthy mice and humans yielded favorable pharmacokinetics and bioavailability. Therefore, we determined to study the effects of XN and underst...

  8. Mammalian target of rapamycin inhibition in hepatocellular carcinoma

    OpenAIRE

    Ashworth, René E; Wu, Jennifer

    2014-01-01

    Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide. It is associated with a poor prognosis and has limited treatment options. Sorafenib, a multi-targeted kinase inhibitor, is the only available systemic agent for treatment of HCC that improves overall survival for patients with advanced stage disease; unfortunately, an effective second-line agent for the treatment of progressive or sorafenib-resistant HCC has yet to be identified. This review focuses...

  9. Rapid Regression of Advanced Hepatocellular Carcinoma Associated with Elevation of Des-Gamma-Carboxy Prothrombin after Short-Term Treatment with Sorafenib – A Report of Two Cases

    Directory of Open Access Journals (Sweden)

    Takahide Nakazawa

    2010-08-01

    Full Text Available Background: Sorafenib is the first molecular-targeted agent that is effective for advanced hepatocellular carcinoma (HCC, with prolongation of survival. However, a complete response is very rare, and rapid regression of HCC after short-term treatment with sorafenib has not been reported previously. Case Reports: We describe 2 patients with advanced multiple HCC who received sorafenib for short periods of 1 or 2 weeks, respectively. Longer treatment was precluded by the development of hepatic failure as an adverse event of sorafenib. Results: HCC rapidly regressed, and both patients had a partial response (PR, despite short-term treatment. Furthermore, an early elevation of des-gamma-carboxy prothrombin (DCP was temporarily seen in both patients, with no elevation of alpha-fetoprotein. Conclusions: Sorafenib can induce rapid regression of advanced HCC even after short-term treatment, and the initial response of HCC was identical in both patients. Since early elevation of DCP was observed in our patients with PR, DCP might be a predictive biomarker of anti-tumor response. Further studies are required to clarify the mechanisms underlying the effectiveness of sorafenib, including the alteration of DCP.

  10. Somatostatin receptor expression, tumour response, and quality of life in patients with advanced hepatocellular carcinoma treated with long-acting octreotide.

    Science.gov (United States)

    Cebon, J; Findlay, M; Hargreaves, C; Stockler, M; Thompson, P; Boyer, M; Roberts, S; Poon, A; Scott, A M; Kalff, V; Garas, G; Dowling, A; Crawford, D; Ring, J; Basser, R; Strickland, A; Macdonald, G; Green, M; Nowak, A; Dickman, B; Dhillon, H; Gebski, V

    2006-10-09

    Octreotide may extend survival in hepatocellular carcinoma (HCC). Forty-one per cent of HCCs have high-affinity somatostatin receptors. We aimed to determine the feasibility, safety, and activity of long-acting octreotide in advanced HCC; to identify the best method for assessing somatostatin receptor expression; to relate receptor expression to clinical outcomes; and to evaluate toxicity. Sixty-three patients with advanced HCC received intramuscular long-acting octreotide 20 mg monthly until progression or toxicity. Median age was 67 years (range 28-81 years), male 81%, Child-Pugh A 83%, and B 17%. The aetiologies of chronic liver disease were alcohol (22%), viral hepatitis (44%), and haemochromatosis (6%). Prior treatments for HCC included surgery (8%), chemotherapy (2%), local ablation (11%), and chemoembolisation (6%). One patient had an objective partial tumour response (2%, 95% CI 0-9%). Serum alpha-fetoprotein levels decreased more than 50% in four (6%). Median survival was 8 months. Thirty four of 61 patients (56%) had receptor expression detected by scintigraphy; no clear relationship with clinical outcomes was identified. There were few grade 3 or 4 toxicities: hyperglycaemia (8%), hypoglycaemia (2%), diarrhoea (5%), and anorexia (2%). Patients reported improvements in some symptoms, but no major changes in quality of life were detected. Long-acting octreotide is safe in advanced HCC. We found little evidence of anticancer activity. A definitive randomised trial would identify whether patients benefit from this treatment in other ways.

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  5. File list: His.Liv.05.AllAg.Carcinoma,_Hepatocellular [Chip-atlas[Archive

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  6. File list: His.Liv.50.AllAg.Carcinoma,_Hepatocellular [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  7. Transarterial Chemoembolization for the Treatment of Advanced Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis: Prognostic Factors in a Single-Center Study of 188 Patients

    Directory of Open Access Journals (Sweden)

    Lei Liu

    2014-01-01

    Full Text Available Transarterial chemoembolization (TACE could achieve a better survival benefit than conservative treatment for advanced hepatocellular carcinoma (HCC with portal vein tumor thrombosis (PVTT. In this retrospective study, all HCC patients with Child-Pugh score <7 and PVTT who were consecutively admitted to our center between January 2006 and June 2012 and underwent TACE were enrolled. The efficacy and safety of TACE were analyzed. Prognostic factors were determined by Cox regression analysis. Of the 188 patients included, 89% had hepatitis B virus infection, 100% were at Barcelona Clinic Liver Cancer stage C, and 81% (n=152 and 19% (n=36 were at Child-Pugh classes A and B, respectively. The incidence of procedure-related complications was 88%. No procedure-related death was found. The median overall survival was 6.1 months. Type of PVTT (hazard ratio [HR] = 2.806, number of tumor lesions (HR = 2.288, Child-Pugh class (HR = 2.981, and presence of metastasis (HR = 1.909 were the independent predictors of survival. In conclusion, TACE could be selectively used for the treatment of advanced HCC with PVTT. But a high rate of postoperative adverse events should not be undermined in spite of no procedure-related death. Preoperative type of PVTT, number of tumor lesions, Child-Pugh class, and metastasis could predict the prognosis of these patients.

  8. Retrospective comparison between a regular and a split-dose protocol of 5-fluorouracil, cisplatin, and mitoxantrone for the treatment of far advanced hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Pan Kuang-Tse

    2011-03-01

    Full Text Available Abstract Background In patients with advanced hepatocellular carcinoma (HCC, combination chemotherapy using 5- fluorouracil, cisplatin, and mitoxantrone (FMP could achieve a response rate > 20%, but the beneficial effect was compromised by formidable adverse events. Chemotherapy given in a split-dose manner was associated with reduced toxicities. In this retrospective study, we compared the efficacies and side effects between a regular and a split-dose FMP protocol approved in our medical center. Methods From 2005 to 2008, the clinical data of 84 patients with far advanced HCC, who had either main portal vein thrombosis and/or extrahepatic metastasis, were reviewed. Of them, 65 were treated by either regular (n = 27 or split-dose (n = 38 FMP and had completed at least one therapeutic course. The remaining 19 patients were untreated. Clinical parameters, therapeutic responses, survivals and adverse events were compared. Results The median overall survival was 6.0, 5.2, and 1.5 months, respectively, in patients receiving regular FMP, split-dose FMP, and no treatment (regular versus split-dose group, P = 0.447; regular or split-dose versus untreated group; P Conclusions Comparable overall survival was observed between patients receiving regular and split-dose FMP therapies. Patients receiving split-dose therapy had a significantly lower risk of grade 3/4 neutropenia. Positive anti-hepatitis C virus antibody, smaller tumor size, and absence of previous anti-cancer therapy were independent predictors for successful disease control.

  9. Comprehensive sequential interventional therapy for hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    ZHANG Liang; FAN Wei-jun; HUANG Jin-hua; LI Chuan-xing; ZHAO Ming; WANG Li-gang; TANG Tian

    2009-01-01

    Background Since the 1980s, various approaches to interventional therapy have been developed, with the development and achievement of medical imaging technology. This study aimed to evaluate the effectiveness of comprehensive sequential interventional therapy especially personal therapeutic plan in 53 radical cure patients with hepatocellular carcinoma (HCC).Methods From January 2003 to January 2005, a total of 203 patients with HCC received sequential interventional treatment in our hospital. Fifty-three patients achieved radical cure outcomes. Those patients were treated with transcatheter arterial chemoembolization (TACE), radiofrequency ablation (RFA), percutaneous ethanol injection (PEI), or high intensity focused ultrasound (HIFU), sequentially and in combination depending on their clinical and pathological features. PET-CT was used to evaluate, assess, and guide treatment.Results Based on the imaging and serological data, all the patients had a personal therapeutic plan. The longest follow-up time was 24 months, the shortest was 6 months, and mean survival time was 16.5 months.Conclusion Comprehensive sequential interventional therapy especially personal therapeutic plan for HCC play roles in interventional treatment of HCC in middle or advanced stage.

  10. Management of hepatocellular carcinoma in the elderly

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Mean age of hepatocellular carcinoma (HCC) patients hasbeen progressively increasing over the last decades andageing of these patients is becoming a real challenge inevery day clinical practice. Unfortunately, internationalguidelines on HCC management do not address thisproblem exhaustively and do not provide any specific recommendation. We carried out a literature search inMEDLINE database for studies reporting on epidemiology,clinical characteristics and treatment outcome of HCCin elderly patients. Available data seem to indicatethat in elderly patients the outcome of HCC is mostlyinfluenced by liver function and tumor stage rather thanby age and the latter should not influence treatmentallocation. Age is not a risk for resection and olderpatients with resectable HCC and good liver functioncould gain benefit from surgery. Mild comorbiditiesdo not seem a contraindication for surgery in agedpatients. Conversely, major resection in elderly, evenwhen performed in experienced high-volume centres,should be avoided. Both percutaneous ablation andtransarterial chemoembolization are not contraindicatedin aged patients and safety profile of these proceduresis acceptable. Sorafenib is a viable option for advancedHCC in elderly provided that a careful evaluation ofconcomitant comorbidities, particularly cardiovascularones, is taken into account. Available data seem tosuggest that in either elderly and younger, treatment isa main predictor of outcome. Consequently, a nihilisticattitude of physicians towards under- or no-treatment ofaged patients should not be longer justified.

  11. Status of hepatocellular carcinoma in Gulf region.

    Science.gov (United States)

    Rasul, Kakil Ibrahim; Al-Azawi, Safaa H; Chandra, Prem; Abou-Alfa, Ghassan K; Knuth, Alexander

    2013-12-01

    Hepatocellular carcinoma (HCC) has a unique geographic distribution that is likely to be determined by specific etiologic factors. There is a distinctive difference in sex and age related occurrence of disease. In the Gulf region, there are contradicting data on the prevalence and death rates due to HCC. In this review we highlight some aspects of HCC specific to the Gulf region. A retrospective analysis of 150 patient's data is presented, including demographic, epidemiological, aetiological disease status assessment with child Pugh criteria, modes of treatment and treatment related outcome. Hepatitis C virus (HCV) infection was the most common (45%) documented etiology, similar to Western European countries, followed by hepatitis B virus (HBV) infection in 27% of cases, alcoholic liver disease only in six patients (4%). Child-Pugh assessment was A in 33%, B in 37% and C in 30% of observed patients. Surgery (liver resection or transplantation) was performed in 12% and local ablation in 5% of cases. The others were treated by chemo-embolization in 17% and by systemic therapy with sorafenib in 13% of patients. Nearly half of the patients (53%) were in advanced stages and received palliative treatment. To improve the outcome of treatment in HCC patients in the Gulf region, an effective and strategic screening program must be implemented for early diagnosis and treatment to improve the outcome of this mostly fatal disease.

  12. Epidemiology of hepatocellular carcinoma (HCC) in hemophilia.

    Science.gov (United States)

    Shetty, Shrimati; Sharma, Nitika; Ghosh, Kanjaksha

    2016-03-01

    Hepatocellular carcinoma (HCC) is an important cause of increasing mortality in elderly hemophilia population. Majority of the patients treated with virus non-inactivated factor concentrates prepared from large plasma pools prior to 1985 have been found to be infected with hepatitis C virus (HCV), a major risk factor for HCC. A PubMed search of articles published until February 2015 was performed utilizing the keywords hemophilia, malignancy, neoplasm, cancer, mortality, ageing hemophilia, epidemiology, hepatocellular carcinoma and liver cancer and the relevant articles were included. Contradictory reports are available in literature on the incidence of cancers in general in hemophilia population. Almost all the studies where the incidence of HCC or mortality due to HCC have been analyzed in hemophilia population show that a vast majority of these patients are HCV infected. The incidence of HCC though higher in hemophilic population is related to the higher incidence of HCV infection and not due to the hemophilia phenotype.

  13. Hepatocellular carcinoma in the Malaysian Orang Asli.

    Science.gov (United States)

    Sumithran, E; Prathap, K

    1976-05-01

    Necropsies were performed on 285 consecutively unclaimed Orang Asli bodies from Gombak Orang Asli Hospital during an eight-year period from May 1967 to April 1975. Of the 25 malignant neoplasms, hepatocellular carcinoma was by far the commonest (36%). The nine patients with this neoplasm had coexistant macronodular cirrhosis. There were 20 cases of cirrhosis; 45% of these had coexistant hepatocellular carcinoma. The 53,000 Orang Aslis living in West Malaysia comprise three tribes, the Negrito, Senoi, and Melayu Asli (Proto Malays). The Sinoi appear to have a high predilection for liver cancer, all our nine cases occurring in this group. These aboriginal people live in the jungles where they practice shifting cultivation and maintain their own dietary and social customs. Detailed studies of their dietary habits may provide a clue to the etiology of liver cancer in these people.

  14. Radiotherapy for metastatic fibrolamellar hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Justin G. Peacock

    2013-07-01

    Full Text Available Fibrolamellar hepatocellular carcinoma (FLHCC is a rare variant of hepatocellular carcinoma (HCC that commonly affects young individuals without a prior history of liver disease. FLHCC commonly results in a better prognosis than HCC; however, the risk of recurrence and metastatic disease is high. FLHCC is typically treated by primary resection of the tumor with 50-75% cure rates. The use of radiation therapy in FLHCC has not been assessed on its own, and may show some success in a very few reported combination therapy cases. We report on the successful use of radiation therapy in a case of metastatic FLHCC to the lung following primary and secondary resections. Our treatment of the large, metastatic, pulmonary FLHCC tumor with 40 Gy in 10 fractions resulted in an 85.9% tumor volume decrease over six months. This suggests FLHCC may be a radiosensitive tumor and radiotherapy may be valuable in unresectable or metastatic tumors.

  15. Fibrolamellar Hepatocellular Carcinoma: A Case Report

    Directory of Open Access Journals (Sweden)

    "N. Ebrahimi Daryani

    2005-08-01

    Full Text Available Introduction & Background: Fibrolamellar hepatocel-lular carcinoma occurs in non-cirrhotic livers, most frequently in the adolescents or young adults without sex predominance, and the prognosis is more favor-able than that of the usual hepatocellular carcinoma. It is a rare condition; accounting for less than 1% of primary liver cancers. Case Presentation: This is a seventeen-year old male patient with history of right upper quadrant abdomi-nal pain, with no hepatomegaly. Liver function tests and serological markers for viral B, C hepatitis and tumor markers were normal. CT scan demonstrated a massive hyper- vascular lesion in the liver and the histological examination was reported as a typical fibrolamellar hepatocarcinoma. Intra-arterial chemo-therapy has been done for the patient about 6 months ago. Now he had none of the previous problems and his weight loss is reversed. Fibrolamellar hepatocellu-lar carcinoma should be kept in mind in young pa-tients with hypervascular liver masses and no history of hepatic diseases.

  16. Prognostic significance of catalase expression and its regulatory effects on hepatitis B virus X protein (HBx) in HBV-related advanced hepatocellular carcinomas.

    Science.gov (United States)

    Cho, Mi-Young; Cheong, Jae Youn; Lim, Wonchung; Jo, Sujin; Lee, Youngsoo; Wang, Hee-Jung; Han, Kyou-Hoon; Cho, Hyeseong

    2014-12-15

    Hepatitis B virus X protein (HBx) plays a role in liver cancer development. We previously showed that ROS increased HBx levels and here, we investigated the role of antioxidants in the regulation of HBx expression and their clinical relevance. We found that overexpression of catalase induced a significant loss in HBx levels. The cysteine null mutant of HBx (Cys-) showed a dramatic reduction in its protein stability. In clonogenic proliferation assays, Huh7-X cells produced a significant number of colonies whereas Huh7-Cys- cells failed to generate them. The Cys at position 69 of HBx was crucial to maintain its protein stability and transactivation function in response to ROS. Among 50 HBV-related hepatocellular carcinoma (HCC) specimens, 72% of HCCs showed lower catalase levels than those of surrounding non-tumor tissues. In advanced stage IV, catalase levels in non-tumor tissues were increased whereas those in tumors were further reduced. Accordingly, patients with a high T/N ratio for catalase showed significantly longer survival than those with a low T/N ratio. Together, catalase expression in HCC patients can be clinically useful for prediction of patient survival, and restoration of catalase expression in HCCs could be an important strategy for intervention in HBV-induced liver diseases.

  17. Bioinformatics Analysis Reveals Distinct Molecular Characteristics of Hepatitis B-Related Hepatocellular Carcinomas from Very Early to Advanced Barcelona Clinic Liver Cancer Stages.

    Directory of Open Access Journals (Sweden)

    Fan-Yun Kong

    Full Text Available Hepatocellular carcinoma (HCCis the fifth most common malignancy associated with high mortality. One of the risk factors for HCC is chronic hepatitis B virus (HBV infection. The treatment strategy for the disease is dependent on the stage of HCC, and the Barcelona clinic liver cancer (BCLC staging system is used in most HCC cases. However, the molecular characteristics of HBV-related HCC in different BCLC stages are still unknown. Using GSE14520 microarray data from HBV-related HCC cases with BCLC stages from 0 (very early stage to C (advanced stage in the gene expression omnibus (GEO database, differentially expressed genes (DEGs, including common DEGs and unique DEGs in different BCLC stages, were identified. These DEGs were located on different chromosomes. The molecular functions and biology pathways of DEGs were identified by gene ontology (GO analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG pathway analysis, and the interactome networks of DEGs were constructed using the NetVenn online tool. The results revealed that both common DEGs and stage-specific DEGs were associated with various molecular functions and were involved in special biological pathways. In addition, several hub genes were found in the interactome networks of DEGs. The identified DEGs and hub genes promote our understanding of the molecular mechanisms underlying the development of HBV-related HCC through the different BCLC stages, and might be used as staging biomarkers or molecular targets for the treatment of HCC with HBV infection.

  18. Bioinformatics Analysis Reveals Distinct Molecular Characteristics of Hepatitis B-Related Hepatocellular Carcinomas from Very Early to Advanced Barcelona Clinic Liver Cancer Stages

    Science.gov (United States)

    Hu, Wei; Kou, Yan-Bo; You, Hong-Juan; Liu, Xiao-Mei; Zheng, Kui-Yang; Tang, Ren-Xian

    2016-01-01

    Hepatocellular carcinoma (HCC)is the fifth most common malignancy associated with high mortality. One of the risk factors for HCC is chronic hepatitis B virus (HBV) infection. The treatment strategy for the disease is dependent on the stage of HCC, and the Barcelona clinic liver cancer (BCLC) staging system is used in most HCC cases. However, the molecular characteristics of HBV-related HCC in different BCLC stages are still unknown. Using GSE14520 microarray data from HBV-related HCC cases with BCLC stages from 0 (very early stage) to C (advanced stage) in the gene expression omnibus (GEO) database, differentially expressed genes (DEGs), including common DEGs and unique DEGs in different BCLC stages, were identified. These DEGs were located on different chromosomes. The molecular functions and biology pathways of DEGs were identified by gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and the interactome networks of DEGs were constructed using the NetVenn online tool. The results revealed that both common DEGs and stage-specific DEGs were associated with various molecular functions and were involved in special biological pathways. In addition, several hub genes were found in the interactome networks of DEGs. The identified DEGs and hub genes promote our understanding of the molecular mechanisms underlying the development of HBV-related HCC through the different BCLC stages, and might be used as staging biomarkers or molecular targets for the treatment of HCC with HBV infection. PMID:27454179

  19. Surgery for Intermediate and Advanced Hepatocellular Carcinoma: A Consensus Report from the 5th Asia-Pacific Primary Liver Cancer Expert Meeting (APPLE 2014)

    Science.gov (United States)

    Ho, Ming-Chih; Hasegawa, Kiyoshi; Chen, Xiao-Ping; Nagano, Hiroaki; Lee, Young-Joo; Chau, Gar-Yang; Zhou, Jian; Wang, Chih-Chi; Choi, Young Rok; Poon, Ronnie Tung-Ping; Kokudo, Norihiro

    2016-01-01

    Background The Barcelona Clinic Liver Cancer (BCLC) staging and treatment strategy does not recommended surgery for treating BCLC stage B and C hepatocellular carcinoma (HCC). However, numerous Asia-Pacific institutes still perform surgery for this patient group. This consensus report from the 5th Asia-Pacific Primary Liver Cancer Expert Meeting aimed to share opinions and experiences pertaining to liver resection for intermediate and advanced HCCs and to provide evidence to issue recommendations for surgery in this patient group. Summary Thirteen experts from five Asia-Pacific regions were invited to the meeting; 10 of them (Japan: 2, Taiwan: 3, South Korea: 2, Hong Kong: 1, and China: 2) voted for the final consensus. The discussion focused on evaluating the preoperative liver functional reserve and surgery for large tumors, multiple tumors, HCCs with vascular invasion, and HCCs with distant metastasis. The feasibility of future prospective randomized trials comparing surgery with transarterial chemoembolization for intermediate HCC and with sorafenib for advanced HCC was also discussed. The Child-Pugh score (9/10 experts) and indocyanine green retention rate at 15 min (8/10) were the most widely accepted methods for evaluating the preoperative liver functional reserve. All (10/10) experts agreed that portal hypertension, tumor size >5 cm, portal venous invasion, hepatic venous invasion, and extrahepatic metastasis are not absolute contraindications for the surgical resection of HCC. Furthermore, 9 of the 10 experts agreed that tumor resection may be performed for patients with >3 tumors. The limitations of surgery are associated with a poor liver functional reserve, incomplete tumor resection, and a high probability of recurrence. Key Messages Surgery provides significant survival benefits for Asian-Pacific patients with intermediate and advanced HCCs, particularly when the liver functional reserve is favorable. However, prospective randomized controlled trials

  20. 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....

  1. Fibrolamellar hepatocellular carcinoma with biliary tumor thrombus: an unreported association.

    Science.gov (United States)

    De Gaetano, Anna Maria; Nure, Erida; Grossi, Ugo; Frongillo, Francesco; Russo, Rosellina; Vecchio, Fabio Maria; Lirosi, Maria Carmen; Sganga, Gabriele; Felice, Carla; Bonomo, Lorenzo; Agnes, Salvatore

    2013-10-01

    Fibrolamellar hepatocellular carcinoma (FHCC) is a rare malignant tumor of hepatocyte origin occurring earlier in life than typical hepatocellular carcinoma (HCC). We describe a distinctive case of FHCC with biliary tumor thrombus (BTT) in a 25-year-old Caucasian patient, pointing out the imaging features supported by histopathology.

  2. Aflatoxins as a cause of hepatocellular carcinoma.

    Science.gov (United States)

    Kew, Michael C

    2013-09-01

    Aflatoxins, metabolites of the fungi Aspergillus flavus and Aspergillus parasiticus, are frequent contaminants of a number of staple foods, particularly maize and ground nuts, in subsistence farming communities in tropical and sub-tropical climates in sub-Saharan Africa, Eastern Asia and parts of South America. Contamination of foods occurs during growth and as a result of storage in deficient or inappropriate facilities. These toxins pose serious public health hazards, including the causation of hepatocellular carcinoma by aflatoxin B1. Exposure begins in utero and is life-long. The innocuous parent molecule of the fungus is converted by members of the cytochrome p450 family into mutagenic and carcinogenic intermediates. Aflatoxin-B1 is converted into aflatoxin B1-8,9 exo-epoxide, which is in turn converted into 8,9-dihydroxy-8-(N7) guanyl-9-hydroxy aflatoxin B1 adduct. This adduct is metabolized into aflatoxin B1 formaminopyrimidine adduct. These adducts are mutagenic and carcinogenic. In addition, an arginine to serine mutation at codon 249 of the p53 tumor suppressor gene is produced, abrogating the function of the tumor suppressor gene, and contributing to hepatocarcinogenesis. Aflatoxin B1 acts synergistically with hepatitis B virus in causing hepatocellular carcinoma. A number of interactions between the two carcinogens may be responsible for this action, including integration of hepatitis B virus x gene and its consequences, as well as interference with nucleotide excision repair, activation of p21waf1/cip1, generation of DNA mutations, and altered methylation of genes. But much remains to be learnt about the precise pathogenetic mechanisms responsible for aflatoxin B1-induced hepatocellular carcinoma as well as the interaction between the toxin and hepatitis B virus in causing the tumor.

  3. Non-viral causes of hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Wojciech; Blonski; David; S; Kotlyar; Kimberly; A; Forde

    2010-01-01

    Hepatocellular carcinoma(HCC) is the most common primary liver malignancy and represents an international public health concern as one of the most deadly cancers worldwide.The main etiology of HCC is chronic infection with hepatitis B and hepatitis C viruses.However,there are other important factors that contribute to the international burden of HCC.Among these are obesity,diabetes,non-alcoholic steatohepatitis and dietary exposures.Emerging evidence suggests that the etiology of many cases of HCC is in fac...

  4. Epigenetics of hepatocellular carcinoma: a new horizon

    Institute of Scientific and Technical Information of China (English)

    LIU Wei-ren; SHI Ying-hong; PENG Yuan-fei; FAN Jia

    2012-01-01

    Epigenetic changes refer to stable alterations in gene expression with no underlying modifications in the genetic sequence itself.It has become clear that not only gene variations but also epigenetic modifications may contribute to varied diseases,including cancer.This review will provide an overview of how epigenetic factors,including genomic DNA methylation,histone modifications,and miRNA regulation,contribute to hepatocellular carcinoma (HCC) dissemination,invasion,and metastasis.Additionally,the reversal of dysregulated epigenetic changes has emerged as a potential strategy for the treatment of HCC,and we will summarize the latest epigenetic therapies for HCC.

  5. Innovative surgical approaches for hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Riccardo; Memeo; Nicola; de’Angelis; Vito; de; Blasi; Zineb; Cherkaoui; Oronzo; Brunetti; Vito; Longo; Tullio; Piardi; Daniele; Sommacale; Jacques; Marescaux; Didier; Mutter; Patrick; Pessaux

    2016-01-01

    Hepatocellular carcinoma(HCC)is the sixth most common cancer worldwide,with an increasing diffusion in Europe and the United States.The management of such a cancer is continuously progressing and the objective of this paper is to evaluate innovation in the surgical treatment of HCC.In this review,we will analyze the modern concept of preoperative management,the role of laparoscopic and robotic surgery,the intraoperative use of three dimensional models and augmented reality,as well as the potential application of fluorescence.

  6. Microwave ablation of hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Although surgical resection is still the optimal treatmentoption for early-stage hepatocellular carcinoma(HCC) in patients with well compensated cirrhosis,thermal ablation techniques provide a valid nonsurgicaltreatment alternative, thanks to their minimalinvasiveness, excellent tolerability and safety profile,proven efficacy in local disease control, virtuallyunlimited repeatability and cost-effectiveness. Differentenergy sources are currently employed in clinics asphysical agents for percutaneous or intra-surgicalthermal ablation of HCC nodules. Among them, radiofrequency(RF) currents are the most used, whilemicrowave ablations (MWA) are becoming increasinglypopular. Starting from the 90s', RF ablation (RFA) rapidlybecame the standard of care in ablation, especially inthe treatment of small HCC nodules; however, RFAexhibits substantial performance limitations in thetreatment of large lesions and/or tumors located nearmajor heat sinks. MWA, first introduced in the FarEastern clinical practice in the 80s', showing promisingresults but also severe limitations in the controllabilityof the emitted field and in the high amount of poweremployed for the ablation of large tumors, resultingin a poor coagulative performance and a relativelyhigh complication rate, nowadays shows better resultsboth in terms of treatment controllability and of overallcoagulative performance, thanks to the improvementof technology. In this review we provide an extensiveand detailed overview of the key physical and technicalaspects of MWA and of the currently available systems,and we want to discuss the most relevant published dataon MWA treatments of HCC nodules in regard to clinicalresults and to the type and rate of complications, both inabsolute terms and in comparison with RFA.

  7. Advances in Research of Biotherapies for Primary Hepatocellular Carcinoma%肝癌生物治疗的研究进展

    Institute of Scientific and Technical Information of China (English)

    杨成芳

    2012-01-01

    生物治疗是治疗原发性肝癌的主要方法 之一.目前,在肝癌生物治疗的基础及临床研究中,分子靶向治疗、免疫治疗、基因治疗已经显示出了潜在的疗效及良好的发展前景.与肝癌三大传统治疗方法 相比,分子靶向治疗、基因治疗目标明确,对肿瘤细胞以外的正常细胞无影响,不良反应小.免疫治疗作用范围广泛,特别适用于多发病灶及有广泛转移的晚期肝癌.现就生物治疗在肝癌治疗中的研究和应用进行综述.%Biological therapy is one of the main treatments of primary hepatocellular carcinoma. At present, in the preclinical and clinical studies of biotherapy for liver cancer,molecular targeted therapy,immunotherapy and gene therapy have shown potential effects and great perspective. Compared with the three traditional treatments of liver cancer,molecular targeted therapy and gene therapy are featured with specific goal and no effect on the normal cells, and less side effects. Immunotherapy has an extensive range of therapeutic function, especially suitable for multiple lesions and the advanced liver cancer with wide metastasis. Here is to make a review on the research and application of biotherapy in the treatment of liver cancer.

  8. Advanced Hepatocellular Carcinoma: Early evaluation of response to targeted therapy and prognostic value of Perfusion CT and Dynamic Contrast Enhanced-Ultrasound. Preliminary results

    Energy Technology Data Exchange (ETDEWEB)

    Frampas, Eric, E-mail: eric.frampas@chu-nantes.fr [Central Department of Radiology and Medical Imaging, Hôtel-Dieu, 1 Place Alexis Ricordeau, 44093 Nantes Cedex 1 (France); Lassau, Nathalie, E-mail: Nathalie.LASSAU@igr.fr [IR4M UMR 8081, Université Paris Sud 11, Institut Gustave Roussy, 114 Av. Edouard Vaillant, 94805 Villejuif (France); Zappa, Magaly, E-mail: magaly.zappa@bjn.aphp.fr [Department of Radiology, APHP Assistance Publique-Hôpitaux de Paris, Hôpital Beaujon, 100 Bd du général Leclerc, 92110 Clichy (France); Vullierme, Marie-Pierre, E-mail: marie-pierre.vullierme@bjn.aphp.fr [Department of Radiology, APHP Assistance Publique-Hôpitaux de Paris, Hôpital Beaujon, 100 Bd du général Leclerc, 92110 Clichy (France); Koscielny, Serge, E-mail: serge.koscielny@igr.fr [Department of Biostatistics, Institut Gustave Roussy, 114 Av. Edouard Vaillant, 94805 Villejuif (France); Vilgrain, Valérie, E-mail: valerie.vilgrain@bjn.aphp.fr [Department of Radiology, APHP Assistance Publique-Hôpitaux de Paris, Hôpital Beaujon, 100 Bd du général Leclerc, 92110 Clichy (France); Université Paris Diderot, Sorbonne Paris Cité, INSERM CRB3 U773, 75018 Paris (France)

    2013-05-15

    Purpose: To investigate whether there is any correlation between standard endpoints and tumor perfusion measurements with Perfusion CT and Dynamic Contrast-Enhanced Ultrasonography (DCE-US) in patients with advanced Hepatocellular Carcinoma (HCC) treated with targeted therapy. Materials and methods: Nineteen patients were evaluated during targeted therapy (sorafenib n = 16, sunitinib n = 3). Changes in tumor perfusion measurements between baseline and month 1 were assessed and compared using RECIST progression criteria at month 2. Results: Median time to progression according to RECIST was 117 days and median time to death was 208 days. Perfusion CT values before treatment were significantly increased in HCC compared to the surrounding liver (n = 17, P < .02). Eleven patients received complete examinations with both techniques at baseline and month 1. A non-significant decrease was found in all Perfusion CT values between RECIST nonprogressors (n = 7) and progressors (n = 4): mean Blood Volume: −27.9 vs. −11.1% and mean Blood Flow: −25.0 vs. −11.7% respectively. With DCE-US, opposite changes were found (mean Area Under the Curve AUC: −38.3 vs. 436.3%). RECIST progression at month 2 was significantly correlated with a threshold 40% decrease in AUC (P = .015). None of the patients with a decrease in AUC ≥ 40% was a progressor at month 2. Conclusion: Despite perfusion changes with both Perfusion CT and DCE-US in patients receiving treatment, only DCE-US at month 1 (with a decrease in the AUC of more than 40%) predicted non-progression at month 2 and may be a potential surrogate marker of tumor response during targeted therapy.

  9. GPC-3 in hepatocellular carcinoma: current perspectives

    Directory of Open Access Journals (Sweden)

    Wu Y

    2016-11-01

    Full Text Available Yongle Wu,1 Hui Liu,2 Huiguo Ding1 1Department of Gastroenterology and Hepatology, 2Department of Pathology, Beijing You’an Hospital, Affiliated with Capital Medical University, Beijing, People’s Republic of China Abstract: Glypican-3 (GPC3, a member of heparan sulfate proteoglycans, attaches to the cell membrane and is frequently observed to be elevated in hepatocellular carcinoma (HCC. However, GPC3 is not detected in normal liver tissues and benign liver lesions. Consequently, GPC3 is currently being used as a diagnostic biomarker and HCC-specific positron emission computed tomography probe to identify HCCs in normal liver tissues and benign liver lesions. The overexpression of GPC-3 in serum or liver tissue also predicts poor prognosis for HCC patients. In addition, GPC3 promotes HCC growth and metastasis by activating the canonical Wnt and other signaling pathways. Targeting of GPC3, including GC33, HN3 and YP7, might offer new immunotherapeutic tools for HCC treatment. Keywords: glypican-3, hepatocellular carcinoma, diagnostics, prognosis, immunotherapy

  10. Primary hepatocellular carcinoma and metabolic syndrome:An update

    Institute of Scientific and Technical Information of China (English)

    Rubayat; Rahman; Ghassan; M; Hammoud; Ashraf; A; Al-mashhrawi; Khulood; T; Ahmed; Jamal; A; Ibdah

    2013-01-01

    Hepatocellular carcinoma(HCC) is the most common primary liver malignancy. The incidence of hepatocellular carcinoma has increased dramatically by 80% over the past two decades in the United States. Numerous basic science and clinical studies have documented a strong association between hepatocellular carcinoma and the metabolic syndrome. These studies have documented that, in most patients, non-alcoholic fatty liver disease is the hepatic manifestation of the metabolic syndrome, which may progress to hepatocellular carcinoma through the cirrhotic process. However, minority of patients with non-alcoholic fatty liver disease may progress to hepatocellular carcinoma without cirrhosis.This review summarizes the current literature of the link between hepatocellular carcinoma and metabolic syndrome with special emphasis on various components of the metabolic syndrome including risk of association with obesity, diabetes mellitus, hyperlipidemia,and hypertension. Current understanding of pathophysiology, clinical features, treatments, outcomes,and surveillance of hepatocellular carcinoma in the background of metabolic syndrome and non-alcoholic fatty liver disease is reviewed. With the current epidemic of metabolic syndrome, the number of patients with non-alcoholic fatty liver disease is increasing.Subsequently, it is expected that the incidence and prevalence of HCC will also increase. It is very important for the scientific community to shed more light on the pathogenesis of HCC with metabolic syndrome,both with and without cirrhosis. At the same time it is also important to quantify the risk of hepatocellular carcinoma associated with the metabolic syndrome in a prospective setting and develop surveillance recommendations for detection of hepatocellular carcinoma in patients with metabolic syndrome.

  11. Gingival metastasis from primary hepatocellular carcinoma. Report of a case.

    Science.gov (United States)

    Wedgwood, D; Rusen, D; Balk, S

    1979-03-01

    A case of primary hepatocellular carcinoma metastatic to the gingiva is described. Hepatocellular carcinoma is an uncommon malignancy, generally occurring in a cirrhotic liver, which rarely metastasizes to the maxillofacial area. Of eight such cases in the English-language literature, the present case is the fourth involving metastasis to the gingiva. Hepatocellular carcinoma would seem to metastasize with equal frequency to the gingiva and to the mandibular bone. In the case described, histologic examination of the gingival lesion definitively established the diagnosis following somewhat equivocal results of needle biopsy of the liver.

  12. Transar terial chemoembolization using degradable starch microspheres and iodized oil in the treatment of advanced hepatocellular carcinoma:evaluation of tumor response, toxicity, and survival

    Institute of Scientific and Technical Information of China (English)

    Timm D Kirchhoff; Tim F Greten; Stefan Kubicka; Michael P Manns; Michael Galanski; Joerg S Bleck; Arne Dettmer; Ajay Chavan; Herbert Rosenthal; Sonja Merkesdal; Bernd Frericks; Lars Zender; Nisar P Malek

    2007-01-01

    BACKGROUND:In a multidisciplinary conference patients with advanced non-resectable hepatocellular carcinoma (HCC) were stratiifed according to their clinical status and tumor extent to different regional modalities or to best supportive care. The present study evaluated all patients who were stratiifed to repeated transarterial chemoembolization (TACE) from 1999 until 2003 in terms of tumor response, toxicity, and survival. A moderate embolizing approach was chosen using a combination of degradable starch microspheres (DSM) and iodized oil (Lipiodol) in order to combine anti-tumoral efifciency and low toxicity. METHODS: Fourty-seven patients were followed up prospectively. TACE treatment consisted of cisplatin (50 mg/m2), doxorubicin (50 mg/m2), 450-900 mg DSM, and 5-30 ml Lipiodol. DSM and Lipiodol were administered according to tumor vascularization. Patient characteristics, toxicity, and complications were outlined. In multivariate regression analyses of pre-treatment variables from a prospective database, predictors for tumor response and survival after TACE were determined. RESULTS:112 TACE courses were performed (2.4±1.5 courses per patient). Mean maximum tumor size was 75 (± 43) mm, in 68%there was bilobar disease. Best response to TACE treatment was: progressive disease (PD) 9%, stable disease (SD) 55%, partial remission (PR) 36%, and complete remission (CR) 0%. Multivariate regression analyses identiifed tumor size ≤75 mm, tumor number≤5, and tumor hypervascularization as predictors for PR. The overall 1-, 2-, and 3-year-survival rates were 75%, 59%, and 41%, respectively, and the median survival was 26 months. Low α-fetoprotein levels (30 months, R2=36%). Grade 3 toxicity occurred in 7.1% (n=8), and grade 4 toxicity in 3.6%(n=4) of all courses in terms of reversible leukopenia and thrombocytopenia. The incidence of major complications was 5.4% (n=6). All complications were managed conservatively. The mortality within 6 weeks after TACE was 2

  13. 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.

  14. 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

  15. VEGF in hepatocellular carcinoma and surrounding cirrhotic liver tissues

    Institute of Scientific and Technical Information of China (English)

    Muriel Mathonnet; Bernard Descottes; Denis Valleix; Francois Labrousse; Yves Denizot

    2006-01-01

    @@ TO THE EDITOR We read with a great interest the recent work of Deli and colleagues.[1] in the World Journal of Gastroenterology reporting vascular endothelial growth factor (VEGF) expression in hepatocellular carcinoma (HCC) and cirrhotic liver tissues.

  16. Hepatocellular carcinoma : Dutch guideline for surveillance, diagnosis and therapy

    NARCIS (Netherlands)

    Eskens, F. A. L. M.; van Erpecum, K. J.; de Jong, K. P.; van Delden, O. M.; Klumpen, H. J.; Verhoef, C.; Jansen, P. L. M.; van den Bosch, M. A. A. J.; Romero, A. Mendez; Verheij, J.; Bloemena, E.; de Man, R. A.

    2014-01-01

    Hepatocellular carcinoma (HCC) is rare in the Netherlands, even though the incidence has increased quite sharply in recent years. Standard treatment options consist of surgery, orthotopic liver transplantation, radiofrequency ablation, transarterial chemoembolisation (TACE) and systemic therapy with

  17. Percutaneous local therapies for hepatocellular carcinoma impair gastric function

    Institute of Scientific and Technical Information of China (English)

    Fumihiko Kinekawa; Shigeki Kuriyama; Kazuya Matsuda; Tsutomu Masaki; Kazutaka Kurokohchi; Hirohito Yoneyama; Hideyuki Inoue; Hirohide Kurata; Yoshihito Uchida; Seishiro Watanabe

    2006-01-01

    @@ TO THE EDITOR Percutaneous local therapies, such as percutaneous ethanol injection (PEI), microwave coagulation and radiofrequency ablation (RFA), are frequently used worldwide for the treatment of hepatocellular carcinoma (HCC) because of their high effectiveness.

  18. Radiosensitivity of hepatocellular carcinoma; Radiosensibilite des cancers du foie

    Energy Technology Data Exchange (ETDEWEB)

    Hennequin, C.; Quero, L.; Rivera, S. [Service de cancerologie-radiotherapie, hopital Saint-Louis, 1, avenue Claude-Vellefeaux, 75475 Paris (France)

    2011-02-15

    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 {alpha}/{beta} 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)

  19. VESPRO: An Individual Patient Data Prospective Meta-Analysis of Selective Internal Radiation Therapy Versus Sorafenib for Advanced, Locally Advanced, or Recurrent Hepatocellular Carcinoma of the SARAH and SIRveNIB Trials

    Science.gov (United States)

    Gibbs, Emma; Gandhi, Mihir; Chatellier, Gilles; Dinut, Aurelia; Pereira, Helena; Chow, Pierce KH; Vilgrain, Valérie

    2017-01-01

    Background Untreated advanced hepatocellular carcinoma (HCC) has an overall poor prognosis. Currently there are 2 ongoing prospective randomized controlled trials that are evaluating the efficacy and safety of sorafenib and selective internal radiation therapy (SIRT) with yttrium-90 resin microspheres in patients with advanced HCC. The SorAfenib versus Radioembolisation in Advanced Hepatocellular carcinoma (SARAH; 459 patients) trial is being performed in Europe and the SIRt VErsus SorafeNIB (SIRveNIB; 360 patients) trial in the Asia Pacific region. Prospectively combining the results, these trials will not only allow for increased precision to estimate efficacy (in terms of survival), but will also provide increased statistical power for subgroup analyses. Objective To ensure the prospectivity and transparency of the meta-analysis. Methods The sirVEnib and SARAH merge PROject (VESPRO) is an individual, patient-data prospective meta-analysis of the SIRveNIB and SARAH randomized trials. The VESPRO protocol includes prespecified hypotheses, inclusion criteria, and outcome measures. The primary outcome measure is overall survival and secondary outcomes include tumor response rate, progression-free survival, progression in the liver as first event, and disease control in the liver. Pooling of toxicity results will allow for robust safety profiles to be established for both therapies, and provides increased statistical power to investigate treatment effects in key subgroups. Analyses will be performed in the intent-to-treat population stratified by trial. Results Both studies are expected to demonstrate a survival benefit for SIRT together with a better toxicity profile compared with sorafenib. It is also anticipated that liver progression as the first event would be longer in the intervention compared with the control. Conclusions As the results of the 2 trials are not yet known, the methodological strength is enhanced, as biases inherent in conventional meta

  20. Early steroid withdrawal after liver transplantation for hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To evaluate the impact of early steroid withdrawal on the incidence of rejection, tumor recurrence and complications after liver transplantation for advancedstage hepatocellular carcinoma.METHODS: Fifty-four patients underwent liver transplantation for advanced-stage hepatocellular carcinoma from April 2003 to June 2005. These cases were divided into a steroid-withdrawal group (group A, n = 28) and a steroid-maintenance group (group B,n = 26). In group A, steroid was withdrawn 3 mo after transplantation. In group B, steroid was continuously used postoperatively. The incidence of rejection, 6-mo and 1-year recurrence rate of carcinoma, 1-year survival rate, mean serum tacrolimus trough level, and liver and kidney function were compared between the two groups.RESULTS: In the two groups, no statistical difference was observed in the incidence of rejection (14.3 vs 11.5%, P > 0.05), mean serum tacrolimus trough levels (6.9 ± 1.4 vs 7.1 ± 1.1 μg/L, P > 0.05), liver and kidney function after 6 mo [alanine aminotransferase (ALT):533 ± 183 vs 617 ± 217 nka/L, P > 0.05; creatinine:66 ± 18 vs 71 ± 19 μmol/L, P > 0.05], 6-mo recurrence rate of carcinoma (25.0 vs 42.3%, P > 0.05), and 1-year survival rate (64.2 vs 46.1%, P > 0.05). The 1-year tumor recurrence rate (39.2 vs 69.2%, P < 0.05), serum cholesterol level (3.9 ± 1.8 vs 5.9 ± 2.6 mmol/L, P < 0.01)and fasting blood sugar (5.1 ± 2.1 vs 8.9 ± 3.6 mmol/L,P < 0.01) were significantly different. These were lower in the steroid-withdrawal group than in the steroidmaintenance group.CONCLUSION: Early steroid withdrawal was safe after liver transprantation in patients with advanced-stage hepatocellular carcinoma. When steroids were withdrawn 3 mo post-operation, the incidence of rejection did not increase, and there was no demand to maintain tacrolimus at a high level. In contrast, the tumor recurrence rate and the potential of adverse effects decreased significantly. This may have led to an

  1. Stem cell research in hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Chengyi SUN; Shi ZUO

    2008-01-01

    The traditional view that adult human liver tumors, mainly hepatocellular carcinoma (HCC), arise from mature cell types has been challenged in recent dec-ades. The results of several studies suggest that HCC can be derived from liver stem cells. There are four levels of cells in the liver stem cell lineage: hepatocytes, hepatic stem cells/oval cells, bone marrow stem cells and hepato-pancreas stem cells. However, whether HCC is resulted from the differentiation block of stem cells and, moreover, which liver stem cell lineage is the source cell of hepatocarcinogenesis remain controversial. In this review, we focus on the current status of liver stem cell research and their roles in carcinogenesis of HCC, in order to explore new approaches for stem cell therapy of HCC.

  2. Hepatocellular carcinoma (HCC biomarkers in Colombia

    Directory of Open Access Journals (Sweden)

    María Cristina Navas

    2007-02-01

    Full Text Available

    The hepatocellular carcinoma (HCC account for 70 to 85% of primary liver cancer worldwide. SouthEast Asia and sub-Saharan Africa represent the areas with the highest incidence; instead Europe and North America correspond to low incidence areas. The data available for Latin American countries show a low incidence (<3.3/100.000 inhabitants in most of the countries including Colombia. The rate of incidence is <5.6/100.000 in Central America, Peru and Argentina and <10/100.000 in Chile and Brazil.

  3. Combined interventional therapies of hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Jun Qian; Gan-Sheng Feng; Thomas Vogl

    2003-01-01

    Hepatocellular carcinoma (HCC) is one of the most commonmalignancies in the world, responsible for an estimated one million deaths annually. It has a poor prognosis due to its rapid infiltrating growth and complicating liver cirrhosis.Surgical resection, liver transplantation and cryosurgery are considered the best curative options, achieving a high rate of complete response, especially in patients with small HCC and good residual liver function. In nonsurgery, regional interventional therapies have led to a major breakthrough in the management of unresectable HCC, which include transarterial chemoembolization (TACE), percutaneous ethanol injection (PEI), radiofrequency ablation (RFA), microwave coagulation therapy (MCT), laser-induced thermotherapy (LITT), etc. As a result of the technical development of locoregional approaches for HCC during the recent decades,the range of combined interventional therapies has been continuously extended. Most combined multimodal interventional therapies reveal their enormous advantages as compared with any single therapeutic regimen alone,and play more important roles in treating unresectable HCC.

  4. Hepatocellular Carcinoma: The Role of Interventional Oncology

    Science.gov (United States)

    Donadon, Matteo; Solbiati, Luigi; Dawson, Laura; Barry, Aisling; Sapisochin, Gonzalo; Greig, Paul D; Shiina, Shuichiro; Fontana, Andrea; Torzilli, Guido

    2016-01-01

    Background Hepatocellular carcinoma (HCC) remains a major health issue because of its increasing incidence and because of the complexity of its management. In addition to the traditional potentially curative treatments, i.e., liver transplantation and surgical resection, other new and emerging local therapies have been applied with promising results. Summary Radiotherapy (RT) and interstitial treatments, such as radiofrequency ablation (RFA), microwave ablation (MWA), and irreversible electroporation (IRE), have recently opened new and interesting treatment scenarios for HCC and are associated with promising results in selected patients. Herein, we describe the emerging role of interventional oncology for the treatment of HCC and focus on the different Western and Eastern approaches. Key Messages Modern RT and modern interstitial therapies, such as RFA, MWA, and IRE, should be considered for inclusion in HCC therapy guidelines. PMID:27995086

  5. Yttrium-90 Selective Internal Radiation Therapy with Glass Microspheres for Hepatocellular Carcinoma: Current and Updated Literature Review

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Edward Wolfgang; Alanis, Lourdes [Division of Interventional Radiology, Department of Radiology, UCLA Medical Center, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095 (United States); Cho, Sung-Ki [Division of Interventional Radiology, Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351 (Korea, Republic of); Saab, Sammy [Division of Hepatology, Department of Medicine, Pfleger Liver Institute, University of California at Los Angeles, Los Angeles, CA 90024 (United States)

    2016-11-01

    Hepatocellular carcinoma is the most common primary liver cancer and it represents the majority of cancer-related deaths in the world. More than 70% of patients present at an advanced stage, beyond potentially curative options. Ytrrium-90 selective internal radiation therapy (Y90-SIRT) with glass microspheres is rapidly gaining acceptance as a potential therapy for intermediate and advanced stage primary hepatocellular carcinoma and liver metastases. The technique involves delivery of Y90 infused glass microspheres via the hepatic arterial blood flow to the appropriate tumor. The liver tumor receives a highly concentrated radiation dose while sparing the healthy liver parenchyma due to its preferential blood supply from portal venous blood. There are two commercially available devices: TheraSphere® and SIR-Spheres®. Although, Y90-SIRT with glass microspheres improves median survival in patients with intermediate and advanced hepatocellular carcinoma and has the potential to downstage hepatocellular carcinoma so that the selected candidates meet the transplantable criteria, it has not gained widespread acceptance due to the lack of large randomized controlled trials. Currently, there are various clinical trials investigating the use of Y90-SIRT with glass microspheres for treatment of hepatocellular carcinoma and the outcomes of these trials may result in the incorporation of Y90-SIRT with glass microspheres into the treatment guidelines as a standard therapy option for patients with intermediate and advanced stage hepatocellular carcinoma.

  6. Yttrium-90 selective internal radiation therapy with glass microspheres for hepatocellular carcinoma: Current and updated literature review

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Edward Wolfgang; Alanic, Lourdes [Div. of Interventional Radiology, Dept. of Radiology, UCLA Medical Center, David Geffen School of Medicine at UCLA, Los Angeles (United States); Cho, Sung Ki [Div. of Interventional Radiology, Dept. of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Saab, Sammy [Div. of Hepatology, Dept. of Medicine, Pfleger Liver Institute, University of California at Los Angeles, Los Angeles (United States)

    2016-07-15

    Hepatocellular carcinoma is the most common primary liver cancer and it represents the majority of cancer-related deaths in the world. More than 70% of patients present at an advanced stage, beyond potentially curative options. Ytrrium-90 selective internal radiation therapy (Y90-SIRT) with glass microspheres is rapidly gaining acceptance as a potential therapy for intermediate and advanced stage primary hepatocellular carcinoma and liver metastases. The technique involves delivery of Y90 infused glass microspheres via the hepatic arterial blood flow to the appropriate tumor. The liver tumor receives a highly concentrated radiation dose while sparing the healthy liver parenchyma due to its preferential blood supply from portal venous blood. There are two commercially available devices: TheraSphere® and SIR-Spheres®. Although, Y90-SIRT with glass microspheres improves median survival in patients with intermediate and advanced hepatocellular carcinoma and has the potential to downstage hepatocellular carcinoma so that the selected candidates meet the transplantable criteria, it has not gained widespread acceptance due to the lack of large randomized controlled trials. Currently, there are various clinical trials investigating the use of Y90-SIRT with glass microspheres for treatment of hepatocellular carcinoma and the outcomes of these trials may result in the incorporation of Y90-SIRT with glass microspheres into the treatment guidelines as a standard therapy option for patients with intermediate and advanced stage hepatocellular carcinoma.

  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. Regression of hepatocellular carcinoma during vitamin K administration

    Institute of Scientific and Technical Information of China (English)

    Kazuhiro Nouso; Nobuaki Okano; Masahiro Nakagawa; Motowo Mizuno; Yasuyuki Araki; Yasushi Shiratori; Shuji Uematsu; Kunihiro Shiraga; Ryoichi Okamoto; Ryo Harada; Shoko Takayama; Wakako Kawai; Shigeru Kimura; Toru Ueki

    2005-01-01

    An 85-year-old man with HCV infection and diabetes mellitus was diagnosed as having hepatocellular carcinoma (HCC, 13 cm in diameter) based on high serum alpha-fetoprotein (AFP),AFP-L3,and des-γ-carboxy prothrombin levels as well as typical enhancement pattern on contrast-enhanced CT. The patient did not receive any interventional treatments because of advanced age and the advanced stage of HCC.He chose to take vitamin K,which was reported to suppress the growth of HCC in vitro. Three months after starting vitamin K, all three tumor markers were normalized and HCC was markedly regressed, showing no enhancement in the early arterial phase on CT. Here we present the report describing the regression of HCC during the administration of vitamin K.

  9. Update on new approaches in the management of hepatocellular carcinoma.

    Science.gov (United States)

    Cabibbo, Giuseppe; Antonucci, Michela; Genco, Chiara

    2010-11-26

    Hepatocellular carcinoma (HCC) is a major health problem. It is currently the third cause of cancer-related death, it is highly prevalent in the Asia-Pacific region and Africa, and is increasing in Western countries. The natural history of HCC is very heterogeneous and prediction of survival in individual patients is not satisfactory because of the wide spectrum of the disease. During the past decade, major advances have been achieved in prevention, through better surveillance of patients at risk, and in therapy through better surgical and ablative therapies and multimodal treatment approaches. Moreover, the increasing knowledge of molecular hepatocarcinogenesis provides the opportunity for targeted therapies. In this setting, the impact of sorafenib on advanced-stage HCC is a landmark finding in the treatment of liver cancer. The role of sorafenib administration as adjuvant therapy after curative treatment is being evaluated in clinical studies. Future research should lead to a molecular classification of the disease and a more personalized treatment approach.

  10. Paraneoplastic alopecia associated with hepatocellular carcinoma in a cat.

    Science.gov (United States)

    Marconato, Laura; Albanese, Francesco; Viacava, Paolo; Marchetti, Veronica; Abramo, Francesca

    2007-08-01

    A 15-year-old spayed female domestic shorthair cat presented with alopecia associated with hepatocellular carcinoma. Clinical signs, which had commenced 6 months previously, included loss of appetite, loss of weight, and depression. As reported by the owner, the cat developed alopecia a week before referral. The hair loss was localized to the ventral aspect of the thorax and abdomen, medial aspect of front and hind limbs, and ventral aspect of the tail, and was associated with histological features consistent with paraneoplastic alopecia. At necropsy, multiple hepatic nodules were observed, and subsequent histopathological investigation showed cords and sheets of hepatocyte-like neoplastic cells positive for the hepatocyte marker (Hep Par 1), thereby demonstrating the hepatocellular origin of the tumour, which was diagnosed as a hepatocellular carcinoma. This is the first report of feline paraneoplastic alopecia associated with hepatocellular carcinoma confirmed by the Hep Par 1 marker.

  11. BRAIN METASTASIS FROM HEPATOCELLULAR CARCINOMA: A RARE CASE

    Directory of Open Access Journals (Sweden)

    A. Kh. Bekyashev

    2012-01-01

    Full Text Available Hepatocellular carcinoma ranks 5th in prevalence and 3rd in cancer mortality worldwide. The prognosis of this disease is very poor: the 5-year survival rate was not more than 3–5%. Metastases generally occur in the lung, in the lymph nodes of the abdomen, chest, and neck, in the vertebrae, kidneys, and adrenals. The cases of brain metastasis from hepatocellular cancer are very rare. Overall, the prognosis is very poor for patients with brain metastases from hepatocellular carcinoma. Nevertheless, solitary brain metastases and good hepatic function are favorable survival criteria; thus, the treatment of this group of patients may lead to their better survival. The paper describes a clinical case of brain metastasis from hepatocellular carcinoma in a patient receiving the combination treatment involving neurosurgical treatment and targeted therapy. 

  12. Sonic hedgehog通路与肝细胞癌的研究进展%The advance of researches on the Sonic hedgehog pathway and hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    谢晶日; 张亮; 李明; 刘小莲

    2011-01-01

    SHH通路与肿瘤的发生具有密切的关系,在由内胚层形成的组织器官肿瘤中常过度表达.最新研究表明,SHH通路与肝细胞癌(HCC)也存在密切联系,本文就SHH通路与HCC的研究进展作一综述.%Sonic hedgehog(SHH) pathway relates to the occurrence of cancer closely, which is overexpressed in endodermal organ of tumor. Recent research shows that SHH pathway is also closed with hepatocellular carcinoma(HCC). This paper reviews the research progress of SHH pathway and HCC.

  13. 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

  14. Role of Early Arterial Phase Multislice Helical CT Angiography in Evaluation of Hepatocellular Carcinoma

    Institute of Scientific and Technical Information of China (English)

    TANGBinghang; HEYaqi; LILiangcai; HUANGDecheng; WURenguo; YUYuanlong

    2005-01-01

    Objective: To investigate the clinical application of early arterial phase multislice CT angiography (MSCTA) of hepatic vessels in evaluation of middle or advanced stage hepatocellular carcinoma.Methods: Trigger Bolus program was used to carry out MSCTA in early and late arterial phases and portal vein phase with single breath holding. Hepatic vessels were reconstructed from the original images of early arterial phase by post processing. The blood supply of tumor and normal liver tissue and the appearances of venous thrombosis and arteriovenous shunts were analyzed. Results: The MSCTA with early arterial phase could perfectly display the origin, shape and amount of feeding vessels to normal liver tissue and tumor in middle or advanced stage hepatocellular carcinoma. It had the ability of displaying the arteriovenous shunts better than that in conventional dual phased liver scanning. Conclusion: MSCTA of hepatic vessels with early arterial phase acquisition using multislice helical CT in middle or advance stage hepatocellular carcinoma has favorable and promising application. It can be used as an imaging method for comprehensive assessment of the hepatocellular carcinoma before treatment.

  15. 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....

  16. Endobronchial metastasis from hepatocellular carcinoma – a case description with literature review

    OpenAIRE

    Szumera-Ciećkiewicz, Anna; Olszewski, Włodzimierz T.; Piech, Krzysztof; Głogowski, Maciej; Prochorec-Sobieszek, Monika

    2013-01-01

    Endobronchial metastases from hepatocellular carcinoma are very rare. Up to date, no more than 7 cases were reported. The authors present a case of 20-year old female with metastatic hepatocellular carcinoma to superior lobar bronchus. Examination of cytological and small biopsy specimens obtained from bronchoscopy revealed characteristic microscopic features and immunohistochemical profile of hepatocellular carcinoma.

  17. Endobronchial metastasis from hepatocellular carcinoma – a case description with literature review

    Science.gov (United States)

    Szumera-Ciećkiewicz, Anna; Olszewski, Włodzimierz T; Piech, Krzysztof; Głogowski, Maciej; Prochorec-Sobieszek, Monika

    2013-01-01

    Endobronchial metastases from hepatocellular carcinoma are very rare. Up to date, no more than 7 cases were reported. The authors present a case of 20-year old female with metastatic hepatocellular carcinoma to superior lobar bronchus. Examination of cytological and small biopsy specimens obtained from bronchoscopy revealed characteristic microscopic features and immunohistochemical profile of hepatocellular carcinoma. PMID:24040462

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  13. Hepatocellular carcinoma: natural history, current management, and emerging tools

    Directory of Open Access Journals (Sweden)

    Tinkle CL

    2012-07-01

    Full Text Available Christopher L Tinkle, Daphne Haas-KoganDepartment of Radiation Oncology, University of California, San Francisco, CA, USAAbstract: Hepatocellular carcinoma (HCC is the most common primary liver tumor and represents the third-leading cause of cancer-related death in the world. The incidence of HCC continues to increase worldwide, with a unique geographic, age, and sex distribution. The most important risk factor associated with HCC is liver cirrhosis, with the majority of cases caused by chronic infection with hepatitis B (HBV and C (HCV viruses and alcohol abuse, although nonalcoholic fatty liver disease is emerging as an increasingly important cause. Primary prevention in the form of HBV vaccination has led to a significant decrease in HBV-related HCC, and initiation of antiviral therapy appears to reduce the incidence of HCC in patients with chronic HBV or HCV infection. Additionally, the use of ultrasonography enables the early detection of small liver tumors and forms the backbone of recommended surveillance programs for patients at high risk for the development of HCC. Cross-sectional imaging studies, including computed tomography and magnetic resonance imaging, represent further noninvasive techniques that are increasingly employed to diagnose HCC in patients with cirrhosis. The mainstay of potentially curative therapy includes surgery – either resection or liver transplantation. However, most patients are ineligible for surgery, because of either advanced disease or underlying liver dysfunction, and are managed with locoregional and/or systemic therapies. Randomized controlled trials have demonstrated a survival benefit with both local therapies, either ablation or embolization, and systemic therapy in the form of the multikinase inhibitor sorafenib. Despite this, median survival remains poor and recurrence rates significant. Further advances in our understanding of the molecular pathogenesis of HCC hold promise in improving the

  14. Intra-atrial tumor thrombi secondary to hepatocellular carcinoma responding to chemotherapy

    Directory of Open Access Journals (Sweden)

    Ajay Vallakati

    2011-01-01

    Full Text Available Context : Hepatocellular carcinoma accounts for 1-2.5% of all cancer in America with extension to inferior vena cava and right atrium in 1-4% of the cases. Patients with advanced hepatocellular carcinoma invading the right heart are considered poor candidates for surgery. In the past, such patients had dismal prognosis due to complications like pulmonary embolism and sudden death. Case Report : Our patient was admitted with worsening jaundice, abdominal pain and significant weight loss. Abdominal ultrasound, elevated alfa feto-protein levels and computerized tomography pointed to the diagnosis of hepatocellular carcinoma. Transthoracic echocardiography demonstrated two masses in the right atrium with the base of masses extending from inferior vena cava into right atrium. The patient was diagnosed to have stage IV heptaocellular carcinoma. This is associated with dismal prognosis. But after being started on sorafenib, the tumor regressed considerably and was barely discernable on echocardiography performed a month later. Conclusion : Though aggressive surgical resection is the best therapeutic approach for hepatocellular carcinoma, it may not always be possible and in such cases combination of different therapeutic approaches such as chemotherapeutic agents, radiotherapy and chemoembolization may improve survival.

  15. Aflatoxins, hepatocellular carcinoma and public health.

    Science.gov (United States)

    Magnussen, Arvin; Parsi, Mansour A

    2013-03-14

    Hepatocellular carcinoma (HCC) is one of the leading causes of cancer deaths worldwide, primarily affecting populations in the developing countries. Aflatoxin, a food contaminant produced by the fungi Aspergillus flavus and Aspergillus parasiticus, is a known human carcinogen that has been shown to be a causative agent in the pathogenesis of HCC. Aflatoxin can affect a wide range of food commodities including corns, oilseeds, spices, and tree nuts as well as milk, meat, and dried fruit. Many factors affect the growth of Aspergillus fungi and the level of aflatoxin contamination in food. Drought stress is one of the factors that increase susceptibility of plants to Aspergillus and thus aflatoxin contamination. A recent drought is thought to be responsible for finding of trace amounts of aflatoxin in some of the corn harvested in the United States. Although it's too soon to know whether aflatoxin will be a significant problem, since United States is the world's largest corn producer and exporter, this has raised alarm bells. Strict regulations and testing of finished foods and feeds in the United States should prevent a major health scare, and prevent human exposure to deleterious levels of aflatoxin. Unfortunately, such regulations and testing are not in place in many countries. The purpose of this editorial is to summarize the current knowledge on association of aflatoxin and HCC, encourage future research and draw attention to this global public health issue.

  16. Tumor vaccine against recurrence of hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Bao-Gang Peng; Li-Jiang Liang; Qiang He; Ming Kuang; Jia-Ming Lia; Ming-De Lu; Jie-Fu Huang

    2005-01-01

    AIM: To investigate the effects of autologous tumor vaccine on recurrence of hepatocellular carcinoma (HCC).METHODS: Sixty patients with HCC who had undergone curative resection, were randomly divided into HCC vaccine group and control group. Three vaccinations at 2-wk intervals were performed after curative hepatic resection. Delayedtype- hypersensitivity (DTH) test was performed before and after vaccination. Primary endpoints were the time of recurrence.RESULTS: Four patients in control group and 6 patients in HCC vaccine group were withdrawn from the study. The vaccine containing human autologous HCC fragments showed no essential adverse effect in a phase Ⅱ clinical trial and 17 of 24 patients developed a DTH response against the fragments. Three of 17 DTH-positive response patients and 5 of 7 DTH- negative response patients had recurrences after curative resection. After the operation,1-, 2- and 3-year recurrence rates of HCC vaccine groupwere 16.7%, 29.2% and 33.3%, respectively. But, 1-, 2- and3-year recurrence rates of the control group were 30.8%,53.8% and 61.5%, respectively. The time before the first recurrence in the vaccinated patients was significantly longer than that in the control patients (P<0.05).CONCLUSION: Autologous tumor vaccine is of promise in decreasing recurrence of human HCC.

  17. Association between hepatitis C and hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Luis Jesuino de Oliveira Andrade

    2009-01-01

    Full Text Available Hepatocellular carcinoma (HCC is the fifth most common cancer, the third most common cause for cancer death in the world, a major cause of death in patients with chronic hepatitis C virus infection, and responsible for approximately one million deaths each year. Overwhelming lines of epidemiological evidence have indicated that persistent infection with hepatitis C virus (HCV is a major risk for the development of HCC. The incidence of HCC is expected to increase in the next two decades, largely due to hepatitis C infection and secondary cirrhosis, and detection of HCC at an early stage is critical for a favorable clinical outcome. Potential preventive strategies in the development of HCC are being recognized. The natural history of HCC is highly variable and the clinical management choices for HCC can be complex, hence patient assessment and treatment planning have to take the severity of the nonmalignant liver disease into account. This review summarizes the inter-relationship between HCV and liver carcinogenesis.

  18. Association Between Hepatitis C and Hepatocellular Carcinoma

    Science.gov (United States)

    de Oliveria Andrade, Luis Jesuino; D'Oliveira, Argemiro; Melo, Rosangela Carvalho; De Souza, Emmanuel Conrado; Costa Silva, Carolina Alves; Paraná, Raymundo

    2009-01-01

    Hepatocellular carcinoma (HCC) is the fifth most common cancer, the third most common cause for cancer death in the world, a major cause of death in patients with chronic hepatitis C virus infection, and responsible for approximately one million deaths each year. Overwhelming lines of epidemiological evidence have indicated that persistent infection with hepatitis C virus (HCV) is a major risk for the development of HCC. The incidence of HCC is expected to increase in the next two decades, largely due to hepatitis C infection and secondary cirrhosis, and detection of HCC at an early stage is critical for a favorable clinical outcome. Potential preventive strategies in the development of HCC are being recognized. The natural history of HCC is highly variable and the clinical management choices for HCC can be complex, hence patient assessment and treatment planning have to take the severity of the nonmalignant liver disease into account. This review summarizes the inter-relationship between HCV and liver carcinogenesis. PMID:20300384

  19. 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.

  20. Portal vein embolization for hepatocellular carcinoma.

    Science.gov (United States)

    Shindoh, Junichi; D Tzeng, Ching-Wei; Vauthey, Jean-Nicolas

    2012-11-01

    Portal vein embolization (PVE) improves the safety of major hepatectomy through hypertrophy of the future liver remnant (FLR), atrophy of the liver volume to be resected, and improvement in patient selection. Because most patients with hepatocellular carcinoma (HCC) have liver parenchymal injury due to underlying viral hepatitis or alcoholic liver fibrosis/cirrhosis, indication of PVE is relatively complex and sequential procedures, including transarterial chemoembolization, are required to maximize the effect of PVE as well as to minimize tumor progression due to increased arterial flow after PVE. PVE is currently indicated for patients with relatively well-preserved hepatic function [Child-Pugh A and indocyanine green tolerance test (ICG-R15) 40% is the minimal requirement for patients with chronic hepatitis or cirrhosis, and further strict criteria (FLR volume >50%) have been recommended for patients with marginal liver functional reserve (ICG-R15, 10-20%). Recent clinical results have suggested that PVE can be safely performed in patients with HCC and that it contributes to improved survival after major hepatectomy.

  1. Management of recurrent hepatocellular carcinoma afterliver transplant

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Hepatocellular carcinoma (HCC) is the leading cause ofdeaths in patients with hepatitis B or C, and its incidencehas increased considerably over the past decade and is stillon the rise. Liver transplantation (LT) provides the bestchance of cure for patients with HCC and liver cirrhosis.With the implementation of the MELD exception systemfor patients with HCC waitlisted for LT, the number ofrecipients of LT is increasing, so is the number of patientswho have recurrence of HCC after LT. Treatments forintrahepatic recurrence after transplantation and afterother kinds of surgery are more or less the same, butlong-term cure of posttransplant recurrence is rarelyseen as it is a "systemic" disease. Nonetheless, surgicalresection has been shown to be effective in prolongingpatient survival despite the technical difficulty in resectinggraft livers. Besides surgical resection, different kindsof treatment are also in use, including transarterialchemoembolization, radiofrequency ablation, highintensityfocused ultrasound ablation, and stereotacticbody radiation therapy. Targeted therapy and modulationof immunosuppressants are also adopted to treat thedeadly disease.

  2. Hepatocellular carcinoma in patients with autoimmune hepatitis

    Institute of Scientific and Technical Information of China (English)

    Andreas Teufel; Arndt Weinmann; Catherine Centner; Anja Piendl; Peter R Galle; Ansgar W Lohse; Stephan Kanzler

    2009-01-01

    AIM: To evaluate and confirm the low incidence of hepatocellular carcinoma (HCC) in patients with autoimmune hepatitis (AIH). At present only very few cases of HCC in patients with AIH and definite exclusion of chronic viral hepatitis have been published,suggesting that HCC due to AIH is rare. METHODS: In order to further investigate the incidence of HCC in patients with AIH, we reviewed our large cohort of 278 patients with AIH. RESULTS: Eighty-nine patients (32%) were diagnosed with liver cirrhosis, a preneoplastic condition for HCC. We studied a total of 431 patient years of cirrhosis in these patients, an average 4.8 years per patient. During this period none of the patients of our own study cohort developed HCC. However, three patients with HCC due to AIH associated liver cirrhosis were referred to our department for further treatment of HCC. In all three patients chronic viral hepatitis was excluded. CONCLUSION: We conclude that HCC may under rare circumstances develop due to chronic AIH dependent liver cirrhosis. Compared to other causes of liver cirrhosis such as chronic viral hepatitis, alcohol, or hemochromatosis, the incidence of HCC is significantly lower. Pathophysiological differences between AIH and chronic viral hepatitis responsible for differences in the incidence of HCC are yet to be further characterized and may lead to new therapeutic concepts in prevention and treatment of liver cancer.

  3. Activins and activin antagonists in hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Alev Deli; Emanuel Kreidl; Stefan Santifaller; Barbara Trotter; Katja Seir; Walter Berger; Rolf Schulte-Hermann; Chantal Rodgarkia-Dara; Michael Grusch

    2008-01-01

    In many parts of the world hepatocellular carcinoma (HCC) is among the leading causes of cancer-related mortality but the underlying molecular pathology is still insufficiently understood. There is increasing evidence that activins, which are members of the transforming growth factor β (TGFβ) superfamily of growth and differentiation factors, could play important roles in liver carcinogenesis. Activins are disulphide-linked homo-or heterodimers formed from four different β subunits termed βA, βB, βC, and βE, respectively. Activin A, the dimer of two βA subunits, is critically involved in the regulation of cell growth, apoptosis, and tissue architecture in the liver, while the hepatic function of other activins is largely unexplored so far. Negative regulators of activin signals include antagonists in the extracellular space like the binding proteins follistatin and FLRG, and at the cell membrane antagonistic co-receptors like Cripto or BAMBI. Additionally, in the intracellular space inhibitory Smads can modulate and control activin activity. Accumulating data suggest that deregulation of activin signals contributes to pathologic conditions such as chronic inflammation, fibrosis and development of cancer. The current article reviews the alterations in components of the activin signaling pathway that have been observed in HCC and discusses their potential significance for liver tumorigenesis.

  4. Protocol of Interventional Treatment for Hepatocellular Carcinoma

    Institute of Scientific and Technical Information of China (English)

    CHENXiaoming; LUOPengfei; LINHuahuan; SHAOPeijian; ZHOUZejian; FULi

    2005-01-01

    Objective: To establish a reasonable protocol for interventional treatment of hepatocellular carcinoma (HCC). Methods: The data of 1000 HCC patients treated by different kinds of interventional treatments were reviewed with their results of biochemistry, imaging, pathology and survival rate cvaluated.The values as well as the pros and cons of these various kinds of interventional treatments were compared in order to find an optimal protocol. Results: Segmental-transcatheter oil chemoembolization (S-TOCE) could more effectively eradicate the tumor yet inflicting less damage on the noncancerous hepatic tissue and giving much higher survival rate than the conventional transcatheter oil chemoembolization (C-TOCE).Precutaneous ethanol injection (PEI) in combination with chemoembolization could eliminate the residual tumor and significantly increase the survival rate without damaging the noncancerous hepatic tissue. The living quality or survival rate could be improved by choosing different ways of iuterventional treatments to cut down the complications. Conclusion: The selection of different interventional treatments should be done according to the size and type of HCC. Active management is indicated for different complications presenting along with HCC.

  5. Mast cells and human hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Fabio Grizzi; Barbara Franceschini; Maurizio Chiriva-Internati; Young Liu; Paul L. Hermonat; Nicola Dioguardi

    2003-01-01

    AIM: To investigate the density of mast cells (MCs) in human hepatocellular carcinoma (HCC), and to determine whether the MCs density has any correlations with histopathological grading, staging or some baseline patient characteristics.METHODS: Tissue sections of 22 primary HCCs were histochemically stained with toluidine blue, in order to be able to quantify the MCs in and around the neoplasm using a computer-assisted image analysis system. HCC was staged and graded by two independent pathologists. To identify the sinusoidal capillarisation of each specimen 3μm thick sections were histochemically stained with sirius red, and semi-quantitatively evaluated by two independent observers. The data were statistically analysed using Spearman′s correlation and Student′s t-test when appropriate.RESULTS: MCs density did not correlate with the age or sex of the patients, the serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels, or the stage or grade of the HCC. No significant differences were found between the MCs density of the patients with and without hepatitis C virus infection, but they were significantly higher in the specimens showing marked sinusoidal capillarisation.CONCLUSION: The lack of any significant correlation between MCs density and the stage or grade of the neoplastic lesions suggests that there is no causal relationship between MCs recruitment and HCC. However, as capillarisation proceeds concurrently with arterial blood supply during hepatocarcinogenesis, MCs may be considered of primary importance in the transition from sinusoidal to capillary-type endothelial cells and the HCC growth.

  6. The effect of sorafenib in advanced hepatocellular carcinoma patients%索拉非尼对中晚期肝细胞癌患者的影响

    Institute of Scientific and Technical Information of China (English)

    沈茜; 周益龙; 邵冰峰; 田思源; 徐爱兵

    2014-01-01

    目的:观察中晚期肝细胞癌患者索拉非尼治疗后药物相关性不良反应的发生率,并评价服药后6个月的疗效及对患者生活质量的影响。方法:对36例服用索拉非尼的肝细胞癌患者所发生的药物相关性不良反应进行分级、记录与统计分析。按照RECIST标准评价服药6个月后的疗效。EORTC QLQ-C30量表评估索拉非尼治疗前与治疗后6个月患者的生活质量。结果:患者服用索拉非尼后出现手足皮肤反应、腹泻、皮疹、高血压等不良反应。患者服药6个月后总反应率为75%。经索拉非尼治疗后患者在躯体、角色、认知、情绪及社会功能评分有所上升,有统计学差异( P<0.05)。除腹泻外其他症状评分均有下降,有统计学差异( P%Objective:To observe the incidence of sorafenib-related adverse drug reactions of patients with termi-nal-stage hepatocellular carcinoma after the treatment,and evaluate the effect and the influence on quality of life of patients six months after sorafenib treatment. Methods:Sorafenib-related adverse drug reactions in 36 hepatocellular carcinoma cases after treatment were graded,recorded and statistically analyzed. The effect of sorafenib treatment was evaluated according to RECIST criteria six months later. The quality of life of the patients were compared before and six months after treatment using EORTC QLQ-C30. Results:The adverse drug reactions were hand-foot skin reac-tion,diarrhea,rashes,high blood pressure and so on after sorafenib treatment. The overall response rate was 75% six months after treatment. The scores of physical,role,cognitive,emotion and social functioning were increased and the scores of symptom scales were decreased except diarrhea in patients after sorafenib treatment ,which had statistical difference( P <0 . 0 5 ). The global quality of life were much significantly improved than before the treatment( P<0. 05). Conclusion:Sorafenib as a

  7. Comparison of intra-arterial chemoembolization with and without radiotherapy for advanced hepatocellular carcinoma with portal vein tumor thrombosis: a meta-analysis

    Directory of Open Access Journals (Sweden)

    Zhao Q

    2016-12-01

    Full Text Available Qianqian Zhao,1,2 Kunli Zhu,2 Jinbo Yue,2 Zhonghua Qi,1,2 Shumei Jiang,2 Xiaoqing Xu,2 Rui Feng,2 Renben Wang2 1School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Sciences, 2Department of Radiation Oncology, Shandong Cancer Hospital affiliated to Shandong University, Jinan, People’s Republic of China Purpose: Numerous studies have tried to combine transarterial chemoembolization (TACE or hepatic arterial infusion chemotherapy (HAIC with radiotherapy (RT for the treatment of hepatocellular carcinoma (HCC patients with portal vein tumor thrombus (PVTT. However, the efficacy of TACE or HAIC combined with RT versus TACE or HAIC alone remains controversial. Thus, we performed a meta-analysis to compare the efficacy and safety of intra-arterial chemoembolization combined with RT versus intra-arterial chemoembolization alone for the treatment of HCC patients with PVTT.Methods: PubMed, Embase, and Cochrane Library databases were systematically searched for eligible studies. Two authors independently reviewed the abstracts, extracted relevant data and rated the quality of studies. The major end points were objective response rate (ORR, overall survival (OS, and adverse events.Results: Eight studies with a total of 1,760 patients were included in this meta-analysis. The pooled results showed that intra-arterial chemoembolization combined with RT significantly improved ORR of PVTT (OR, 4.22; 95% CI, 3.07–5.80; P<0.001 and OS (HR, 0.69; 95% CI, 0.57–0.83; P=0.001, but did not affect ORR of primary liver tumor (OR, 1.37; 95% CI, 0.67–2.79; P=0.390. The incidence of grade 3 or 4 leukopenia (OR, 5.80; 95% CI, 2.478–13.56; P<0.001 and thrombocytopenia (OR, 3.77; 95% CI, 1.06–13.43; P=0.041 was higher in the intra-arterial chemoembolization plus RT group than in the intra-arterial chemoembolization group.Conclusion: Combination therapy of intra-arterial chemoembolization and RT for HCC patients with PVTT could

  8. HGF, MET, and matrix-related proteases in hepatocellular carcinoma, fibrolamellar variant, cirrhotic and normal liver.

    Science.gov (United States)

    Schoedel, Karen E; Tyner, Valerie Zajac; Kim, Tae-Hyoung; Michalopoulos, George K; Mars, Wendy M

    2003-01-01

    Fibrolamellar variant is an uncommon subcategory of hepatocellular carcinoma with a better prognostic outcome. Proteinases and growth factors that are involved in the remodeling of extracellular matrix may influence the behavior of cancers. To determine whether these factors contribute to the distinct etiologies of fibrolamellar hepatocellular carcinoma and traditional hepatocellular carcinoma, we assayed hepatocyte growth factor, the hepatocyte growth factor receptor, and two hepatocyte growth factor activators, hepatocyte growth factor activator and urokinase-type plasminogen activator, in hepatocellular carcinoma, fibrolamellar hepatocellular carcinoma, cirrhotic liver and normal liver. In addition, we examined the urokinase-type plasminogen activator receptor, the type 1 plasminogen activator inhibitor, plasmin, fibrinogen, and the type IV matrix metalloproteinases. Eighteen hepatocellular carcinomas and 11 fibrolamellar hepatocellular carcinomas were obtained as paraffin embedded sections from the University of Pittsburgh Department of Pathology. Frozen tissues from a subset of cases (9 hepatocellular carcinomas, 4 fibrolamellar hepatocellular carcinomas, 12 cirrhotic livers and 2 normal livers) were also available for analysis. Antibodies against urokinase-type plasminogen activator, urokinase-type plasminogen activator receptor, hepatocyte growth factor and hepatocyte growth factor receptor were used to analyze immunoperoxidase stained slides from the paraffin blocks. Western blot analyses using antibodies against hepatocyte growth factor, hepatocyte growth factor receptor, phosphotyrosine, hepatocyte growth factor activator, urokinase-type plasminogen activator receptor, urokinase-type plasminogen activator, plasminogen activator inhibitor-1, fibrinogen and plasmin were performed on membrane-enriched fractions from the frozen tissue, as was collagen zymography for matrix metalloproteinase-2 and matrix metalloproteinase-9. The most notable findings are as

  9. Liver transplantation for hepatocellular carcinoma:an update

    Institute of Scientific and Technical Information of China (English)

    Ali Zarrinpar; Fady Kaldas; RonaldW Busuttil

    2011-01-01

    BACKGROUND: Hepatocellular carcinoma (HCC) is a heterogeneous malignancy with multiple etiologies, high incidence, and high mortality. The standard surgical management for patients with HCC consists of locoregional ablation, surgical resection, or liver transplantation, depending on the background state of the liver. Eighty percent of patients initially presenting with HCC are unresectable, either due to the extent of tumor or the level of underlying hepatic dysfunction. While in patients with no evidence of cirrhosis and good hepatic function resection has been the surgical treatment of choice, it is contraindicated in patients with moderate to severe cirrhosis. Liver transplantation is the optimal surgical treatment. DATA  SOURCES: PubMed search of recent articles (from January 2000 to March 2011) was performed looking for relevant articles about hepatocellular carcinoma and its treatment. Additional articles were identified by evaluating references from selected articles. RESULTS: Here we review criteria for transplantation, the types, indications, and role of locoregional therapy in treating the cancer and in downstaging for possible later transplantation. We also summarize the contribution of immunosuppression and adjuvant chemotherapy in the management and prevention of HCC recurrence. Finally we discuss recent advances in imaging, tumor biology, and genomics as we delineate the remaining challenges for the diagnosis and treatment of this disease. CONCLUSIONS: Much can be improved in the diagnosis and treatment of HCC. A great challenge will be to improve patient selection to criteria based on tumor biology. Another will be to incorporate systemic agents post-operatively in patients at high risk for recurrence, paying close attention to efficacy and safety. The future direction of the effort in treating HCC will be to stimulate prospective trials, develop molecular imaging of lymphovascular invasion, to improve recipient selection, and to investigate

  10. Helicobacter infection in hepatocellular carcinoma tissue

    Institute of Scientific and Technical Information of China (English)

    Shi-Ying Xuan; Ning Li; Xin Qiang; Rong-Rong Zhou; Yong-Xin Shi; Wen-Jie Jiang

    2006-01-01

    AIM: To investigate whether Helicobacter species (Helicobacter spp.) could be detected in hepatocellular carcinoma (HCC) tissue.METHODS: Liver samples from 28 patients with hepatocellular carcinoma (HCC) diagnosed by histopathology were studied. Twenty-two patients with other liver diseases (5 with liver trauma, 7 with cavernous liver hemangioma, 6 with liver cyst and 4 with hepatolithiasis), 25 patients with gastric cancer, 15 with colonic cancer and 15 with myoma of uterus served as controls. Two piceces of biopsy were obtained from each patient. One was cultured for Helicobacter spp. and extraction of DNA, the other was prepared for scanning electron microscopy (SEM) and in situ hybridization. The samples were cultured on Columbia agar plates with microaerobic techniques. Helicobacter spp. in biopsy from the studied subjects was detected by polymerase chain reaction (PCR) with Helicobacter spp. 16S rRNA primers. Amplified products were identified by Southern hybridization and sequenced further. Besides, other genes (vacA, cagA) specific for Helicobacter pylori (H pylori) were also detected by PCR. Helicobacter spp. in biopsies was observed by SEM. Transmission electron microscopy (TEM) was performed to identify the cultured positive Helicobacter spp. The presence of Helicobacter spp. was detected by in situ hybridization to confirm the type of Helicobacter.RESULTS: The positive rate of Helicobacter cultured in HCC and gastric cancer tissue was 10.7% (3/28) and 24%(6/25), respectively. Helicobacter microorganisms were identified further by typical appearance on Gram staining, positive urease test and characteristic colony morphology on TEM. The bacterium was observed in adjacent hepatocytes of the two HCC samples by SEM.The number of cocci was greater than that of bacilli. The bacterium was also found in four gastric cancer samples.PCR showed that the positive rate of HCC and gastric cancer samples was 60.7% and 72% respectively, while the controls were negative

  11. Stereotactic Body Radiotherapy for Primary Hepatocellular Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Andolino, David L., E-mail: dandolin@iupui.edu [Department of Radiation Oncology, Indiana University School of Medicine, Indianapolis, IN (United States); Johnson, Cynthia S. [Department of Biostatistics, Indiana University School of Medicine, Indianapolis, IN (United States); Maluccio, Mary [Department of Surgery, Indiana University School of Medicine, Indianapolis, IN (United States); Kwo, Paul [Department of Medicine, Indiana University School of Medicine, Indianapolis, IN (United States); Tector, A. Joseph [Department of Surgery, Indiana University School of Medicine, Indianapolis, IN (United States); Zook, Jennifer; Johnstone, Peter A.S.; Cardenes, Higinia R. [Department of Radiation Oncology, Indiana University School of Medicine, Indianapolis, IN (United States)

    2011-11-15

    Purpose: To evaluate the safety and efficacy of stereotactic body radiotherapy (SBRT) for the treatment of primary hepatocellular carcinoma (HCC). Methods and Materials: From 2005 to 2009, 60 patients with liver-confined HCC were treated with SBRT at the Indiana University Simon Cancer Center: 36 Child-Turcotte-Pugh (CTP) Class A and 24 CTP Class B. The median number of fractions, dose per fraction, and total dose, was 3, 14 Gy, and 44 Gy, respectively, for those with CTP Class A cirrhosis and 5, 8 Gy, and 40 Gy, respectively, for those with CTP Class B. Treatment was delivered via 6 to 12 beams and in nearly all cases was prescribed to the 80% isodose line. The records of all patients were reviewed, and treatment response was scored according to Response Evaluation Criteria in Solid Tumors v1.1. Toxicity was graded according to the Common Terminology Criteria for Adverse Events v4.0. Local control (LC), time to progression (TTP), progression-free survival (PFS), and overall survival (OS) were calculated according to the method of Kaplan and Meier. Results: The median follow-up time was 27 months, and the median tumor diameter was 3.2 cm. The 2-year LC, PFS, and OS were 90%, 48%, and 67%, respectively, with median TTP of 47.8 months. Subsequently, 23 patients underwent transplant, with a median time to transplant of 7 months. There were no {>=}Grade 3 nonhematologic toxicities. Thirteen percent of patients experienced an increase in hematologic/hepatic dysfunction greater than 1 grade, and 20% experienced progression in CTP class within 3 months of treatment. Conclusions: SBRT is a safe, effective, noninvasive option for patients with HCC {<=}6 cm. As such, SBRT should be considered when bridging to transplant or as definitive therapy for those ineligible for transplant.

  12. 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

  13. Targeting the insulin-like growth factor pathway in hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Mónica; Enguita-Germán; Puri; Fortes

    2014-01-01

    Hepatocellular carcinoma(HCC) is the third leading cause of cancer-related deaths worldwide. Only 30%-40% of the patients with HCC are eligible for curative treatments, which include surgical resection as the first option, liver transplantation and percutaneous ablation. Unfortunately, there is a high frequency of tumor recurrence after surgical resection and most HCC seem resistant to conventional chemotherapy and radiotherapy. Sorafenib, a multi-tyrosine kinase inhibitor, is the only chemotherapeutic option for patients with advanced hepatocellular carcinoma. Patients treated with Sorafenib have a significant increase in overall survival of about three months. Therefore, there is an urgent need to develop alternative treatments. Due to its role in cell growth and development, the insulin-like growth factor system is commonly deregulated in many cancers. Indeed, the insulin-like growth factor(IGF) axis has recently emerged as a potential target for hepatocellular carcinoma treatment. To this aim, several inhibitors of the pathway have been developed suchas monoclonal antibodies, small molecules, antisense oligonucleotides or small interfering RNAs. However recent studies suggest that, unlike most tumors, HCC development requires increased signaling through insulin growth factor Ⅱ rather than insulin growth factor Ⅰ. This may have great implications in the future treatment of HCC. This review summarizes the role of the IGF axis in liver carcinogenesis and the current status of the strategies designed to target the IGF-Ⅰ signaling pathway for hepatocellular carcinoma treatment.

  14. Loss of fragile histidine triad protein in human hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Po Zhao; Xin Song; Yuan-Yuan Nin; Ya-Li Lu; Xiang-Hong Li

    2003-01-01

    AIM: To investigate the expression of fragile histidine triad (FHIT) gene protein, Fhit, which is recently thought to be a candidate tumor suppressor. Abnormal expression of fragile histidine triad has been found in a variety of human cancers,but little is known about its expression in human hepatocellular carcinogenesis and evolution.METHODS: Sections of 83 primary human hepatocellular carcionoma with corresponding para-neoplastic liver tissue and 10 normal liver tissue were evaluated immunohistochemically for Fhit protein expression.RESULTS: All normal liver tissue and para-neoplastic liver tissue showed a strong expression of Fhit, whereas 50 of 83(65.0 %) carcinomas showed a marked loss or absence of Fhit expression. The differences of Fhit expression between carcinoma and normal or para-neoplastic liver tissue werehighly significant (P=0.000). The proportion of carcinomas with reduced Fhit expression showed an increasing trend (a) with decreasing differentiation or higher histological grade (P=0.219); (b) in tumors with higher clinical stage Ⅲ and ⅣV (91.3 %, P=0.000), compared with tumors with lower stage Ⅰ and Ⅱ (27.6 %); and (c) in cancers with bigger tumor size (>50 mm) (75.0 %, P=0.017), compared withsmaller tumor size (≤ 50 mm). CONCLUSION: FHIT inactivation seems to be both an earlyand a later event, associated with carcinogenesis andprogression to more aggressive hepatocellular carcinomas.Thus, evaluation of Fhit expression by immunohistochemistryin hepatocellular carcinoma may provide important diagnosticand prognostic information in clinical application.

  15. Inhibitory effects of xanthohumol from hops (Humulus lupulus L.) on human hepatocellular carcinoma cell lines.

    Science.gov (United States)

    Ho, Yi-Chien; Liu, Chi-Hsien; Chen, Chien-Nan; Duan, Kow-Jen; Lin, Ming-Tse

    2008-11-01

    Xanthohumol is one of the main flavonoids in hop extracts and in beer. Very few investigations of xanthohumol have studied hepatocellular carcinoma. In this study, the inhibitory effects of xanthohumol on human hepatocellular carcinoma cell lines were investigated. The IC(50) values of xanthohumol for two hepatocellular carcinoma cell lines and one normal hepatocyte cell line were 108, 166 and 211 microm, respectively. Normal murine hepatocyte cell line had more resistance to xanthohumol than hepatocellular carcinoma cell lines. Besides, the inhibitory effects of xanthohumol on human hepatocellular carcinoma cell lines were attributed to apoptosis as indicated in the results of flow cytometry, fluorescent nuclear staining and electrophoresis of oligonucleosomal DNA fragments. Hop xanthohumol was more efficient in the growth inhibition of hepatocellular carcinoma cell lines than the flavonoids silibinin and naringin from thistle and citrus. It was shown for the first time that xanthohumol from hops effectively inhibits proliferation of human hepatocellular carcinoma cells in vitro.

  16. Abnormal plasma prothrombin (PIVKA-II) levels in hepatocellular carcinoma.

    Science.gov (United States)

    Kawaguchi, Y

    1989-05-01

    The concentration of abnormal prothrombin, or the protein induced by vitamin K absence or antagonist II (PIVKA-II) in 102 patients with hepatic disorders was measured by an enzyme immunoassay method. The concentration of PIVKA-II in the plasma was elevated in 11 out of 18 patients with hepatocellular carcinoma and also in a patient with hepatoblastoma. There was no correlation between serum alpha-fetoprotein and plasma PIVKA-II levels. The PIVKA-II level was normal in 11 patients who had metastatic carcinoma or cholangiocellular carcinoma. Moreover, benign diseases of the liver did not cause an elevation in PIVKA-II. PIVKA-II might be an useful marker of hepatocellular carcinoma because, like alpha-fetoprotein, its level changes in close relation to the effects of treatment.

  17. Reduced expression of TANGO in colon and hepatocellular carcinomas.

    Science.gov (United States)

    Arndt, Stephanie; Bosserhoff, Anja K

    2007-10-01

    The TANGO gene was originally identified as a new family member of the MIA gene family. The gene codes for a 14-kDa protein of so far unknown function. Recently, we identified TANGO as a tumor suppressor in malignant melanoma. In this study we evaluated TANGO transcription in different colon and hepatocellular carcinoma cell lines and tissue samples, to analyze whether loss of TANGO expression is a more general process in tumor development. TANGO was down-regulated or lost in all hepatocellular and colon cell lines compared to primary human hepatocytes or normal colon epithelial cells, respectively, and in most of the tumor samples compared to non-tumorous tissue. These results were confirmed in situ by immunohistochemistry on paraffin-embedded sections of colon and hepatocellular tumors. Functional assays with exogenous TANGO treatment of colon and hepatoma cell lines revealed reduced motility and invasion capacity. Our studies present for the first time the down-regulation of TANGO in colon and hepatocellular carcinoma and provide the first indications for a tumor suppressor role of the TANGO gene in human colon and hepatocellular carcinoma. Thus, functional relevant loss of TANGO expression may contribute to general tumor development and progression, and may provide a new target for therapeutic strategies.

  18. Differentially expressed genes between solitary large hepatocellular carcinoma and nodular hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Lian-Yue Yang; Wei Wang; Ji-Xiang Peng; Jie-Quan Yang; Gen-Wen Huang

    2004-01-01

    AIM: To study the difference in gene expression between solitary large hepatocellular carcinoma (SLHCC) and nodular hepatocellular carcinoma (NHCC).METHODS: Polymerase chain reaction (PCR) products of 8464 human genes were spotted on a chip in array. DNAs were then fixed on a glass plate. Total RNA was isolated from freshly excised human SLHCC (n=7) and NHCC (n=15)tissues, and was reversely transcribed to cDNAs with the incorporation of fluorescent dUTP for preparation of hybridization probes. The mixed probes were then hybridized to the cDNA microarray. After highly stringent washing,cDNA microarray was scanned for the fluorescent signals to display the difference between the two kinds of HCC. In addition, the expression of RhoC and protocadherin LKC was also detected with the reverse transcriptase polymerase chain reaction (RT-PCR) method.RESULTS: Among the 8 464 human genes, 668 (7.89%)genes were expressed differentially at the mRNA levels between SLHCC and NHCC. Three hundred and fifty five (4.19%) genes, including protocadherin LKC, were upregulated, whereas 313 (3.70%) genes, including RhoC,were down-regulated. The mRNA expression levels of RhoC and protocadherin LKCwere confirmed by RT-PCR. Analysis of differentially expressed genes confirmed that our molecular data obtained by cDNA microarray were consistent with the published biochemical and clinical observations of SLHCC and NHCC.CONCLUSION: cDNA microarray is an effective technique in screening the difference in gene expression between SLHCC and NHCC. Many of these differentially expressed genes are involved in the invasion and metastasis of HCC.Further analysis of these genes will help to understand the different molecular mechanisms of SLHCC and NHCC.

  19. 肝动脉栓塞化疗联合肝复乐治疗晚期肝癌临床疗效观察%Efficacy of transcatheter arterial chemoembolization combined with ganfule on advanced hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Mingzhi Hao; Hailan Lin; Qizhong Chen; Yubin Hu; Dong Zhou; Ping Huang; YunBin Ye

    2013-01-01

    Objective: The aim of this study was to evaluate the efficacy of transcatheter arterial chemoembolization (TACE) combined with a Chinese compound preparation of ganfule on advanced hepatocellular carcinoma (HCC). Methods: The study population consisted of 132 advanced HCC patients with Child-pugh A/B. Tumor in all patients was involved with main trunk of portal vein and/or inferior vena cava, or local lymph node metastasis, or distant metastasis. TACE combined with ganfule were performed in 65 patients with advanced HCC (interventional treatment group), 67 patients were treated with traditional Chinese herbal drug alone (Chinese herb group). The prime end point was overall survival (OS), and prognostic factors were analyzed. Results: The median OS was 205 days [95% confidence interval (CI), 155-255 days] in interventional treatment group and 127 days (95% CI, 70-184 days) in Chinese herb group (P < 0.05). The 6-month, 1-year, and 2-year OS rates were 58.9%, 29.1%, 7.7% in interventional treatment group, and 33.3%, 12.3%, 1.8% in Chinese herb group, respectively. The portal vein thrombosis, ECOG performance status (PS) were independent prognostic factors for OS. Conclusion: Ttranscatheter arterial chemoembolization combined with a Chinese compound preparation of ganfule could greatly prolong the OS of advanced HCC patients. The portal vein thrombosis and ECOG PS were independent prognostic factors for OS.

  20. Hepatocellular carcinoma: perfusion quantification with dynamic contrast-enhanced MRI

    NARCIS (Netherlands)

    Taouli, B.; Johnson, R.S.; Hajdu, C.H.; Oei, M.T.H.; Merad, M.; Yee, H.; Rusinek, H.

    2013-01-01

    The objective of our study was to report our initial experience with dynamic contrast-enhanced MRI (DCE-MRI) for perfusion quantification of hepatocellular carcinoma (HCC) and surrounding liver.DCE-MRI of the liver was prospectively performed on 31 patients with HCC (male-female ratio, 26:5; mean ag

  1. The Correlation between Gene Polymorphism and Hepatocellular Carcinoma

    Institute of Scientific and Technical Information of China (English)

    Zhao-Chun Chi; Chang-Xin Geng; Quan-Jiang Dong

    2013-01-01

    The association of gene polymorphism and susceptibility to hepatocellular carcinoma (HCC) has been widely studied in recent years. Gene mutations are closely related to HCC. Understanding and measuring the gene mutations are useful to reduce the incidence of HCC and improve its prognosis.

  2. HCCNet: an integrated network database of hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Bing He; Xiaojie Qiu; Peng Li; Lishan Wang; QiLv; TieliuShi

    2010-01-01

    @@ Dear Editor, As a complex disease, the development and progression of hepatocellular carcinoma (HCC) involves the interactions of multiple proteins, genes and miRNAs in various biological pathways, and it has been extensively studied with different high-throughput techniques.

  3. Peanut butter consumption and hepatocellular carcinoma in Sudan

    NARCIS (Netherlands)

    El Hadi Omer, R.

    2001-01-01

    Hepatocellular carcinoma (HCC) is the sixth most common cancer in the world with 80% of cases occurring in developing countries in sub-Saharan regions in Africa, South-East Asia and China. The cancer is highly fatal and survival is generally less than 1 year from diagnosis. Clinical records suggest

  4. 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...

  5. Cerebral lipiodol embolism following transcatheter arterial chemoembolization for hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Cerebral lipiodol embolism (CLE) is an extremely rare complication of transcatheter arterial chemoembolization for hepatocellular carcinoma (HCC). The authors present a case of CLE that occurred after the second hepatic arterial chemoembolization for HCC, and attempt to introduce several plausible mechanisms of CLE, after reporting the clinical and radiological findings and reviewing the medical literature.

  6. 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 incomplet

  7. Correlation of exon 3 β-catenin mutations with glutamine synthetase staining patterns in hepatocellular adenoma and hepatocellular carcinoma.

    Science.gov (United States)

    Hale, Gillian; Liu, Xinxin; Hu, Junjie; Xu, Zhong; Che, Li; Solomon, David; Tsokos, Christos; Shafizadeh, Nafis; Chen, Xin; Gill, Ryan; Kakar, Sanjay

    2016-11-01

    The current clinical practice is based on the assumption of strong correlation between diffuse glutamine synthetase expression and β-catenin activation in hepatocellular adenoma and hepatocellular carcinoma. This high correlation is based on limited data and may represent an oversimplification as glutamine synthetase staining patterns show wide variability in clinical practice. Standardized criteria for interpreting diverse glutamine synthetase patterns, and the association between each pattern and β-catenin mutations is not clearly established. This study examines the correlation between glutamine synthetase staining patterns and β-catenin mutations in 15 typical hepatocellular adenomas, 5 atypical hepatocellular neoplasms and 60 hepatocellular carcinomas. Glutamine synthetase staining was classified into one of the three patterns: (a) diffuse homogeneous: moderate-to-strong cytoplasmic staining in >90% of lesional cells, without a map-like pattern, (b) diffuse heterogeneous: moderate-to-strong staining in 50-90% of lesional cells, without a map-like pattern, and (c) patchy: moderate-to-strong staining in glutamine synthetase staining (homogeneous or heterogeneous), an exon 3 β-catenin mutation was detected in 33% (2/6) of typical hepatocellular adenoma, 75% (3/4) of atypical hepatocellular neoplasm and 17% (8/47) of hepatocellular carcinomas. An exon 3 mutation was also observed in 15% (2/13) of hepatocellular carcinomas with patchy glutamine synthetase staining. The results show a modest correlation between diffuse glutamine synthetase immunostaining and exon 3 β-catenin mutations in hepatocellular adenoma and hepatocellular carcinoma with discrepancy rates >50% in both hepatocellular adenoma and hepatocellular carcinoma. The interpretation of β-catenin activation based on glutamine synthetase staining should be performed with caution, and the undetermined significance of various glutamine synthetase patterns should be highlighted in pathology reports.

  8. Application of Proteomics to the Study of Hepatocellular Carcinoma and Some Related Diseases

    Institute of Scientific and Technical Information of China (English)

    Yueguo Li; Xin Geng; Weiming Zhang

    2005-01-01

    Hepatocellular carcinoma is a malignant tumor causing one of the highest death rates in the world. Viral hepatitis, hepatic fibrosis and hepatocirrhosis etc. Are some of the most important causes of hepatocellular carcinoma. With the advent of the post-genomic age, studying carcinoma and some related diseases using the developing technology of proteomics has become a major focus of researchers. This article is a review of the application of proteomics to study hepatocellular carcinoma and some related diseases.

  9. 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

  10. Hepatocellular carcinoma in Asia: Prevention strategy andplanning

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    AIM To review all of epidemiological and etiologicalaspects of hepatocellular carcinoma (HCC) and examinedthe prevention of this disease in Asia.METHODS: We conducted a systematic reviewaccording to the PRISMA guidelines. We were chosenarticles that published previously, from PubMed(MEDLINE), the Cochrane database and Scopus. Thekey words used in this research were as follows: HCCin Asia and the way of prevention of this disease, withno language limitations. We selected those paperspublished before 2014 that we considered to be mostimportant and appropriate. All relevant articles wereaccessed in full text and all relevant materials wasevaluated and reviewed.RESULTS: More than 70% of all new cases of livercancer were diagnosed in Asia, a region that 75% of allthose chronically infected with hepatitis B virus (HBV)in the world. Chronic HBV infection is the main causeof HCC in Asia, where the virus is endemic and verticaltransmissionis common. Japan, Saudi Arabia, Egyptand Pakistan are exception because of high prevalenceof HCV infection in these regions. The prevalence of thiscancer is high in Eastern and South-Eastern Asia, ButMiddle Eastern countries are characterized as moderateprevalence rate of HCC region and Central Asia andsome part of Middle Eastern countries are known as lowprevalence rate of HCC. In addition of HBV and HCVthe other factors such as aflatoxin, alcohol, obesity,diabetes and non-alcoholic fatty liver disease (NAFLD)might be responsible for a low prevalence of HCC inAsian countries. Currently available HCC therapies,chemotherapy, surgical are inefficient, mainly due tousually late diagnosis and high recurrence rates aftersurgical resection, and usually end with treatmentfailure. Liver transplantation also remains as a difficultstrategy in patients with HCC. Thus prevention of HCCby treating and prevention HBV and HCV infection,the major causative agents of HCC, and the other risk factors such as aflatoxin, alcohol, obesity

  11. Design and rationale of the HCC BRIDGE study in China: a longitudinal, multicenter cohort trial in hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Qiao You-Lin

    2011-05-01

    Full Text Available Abstract Background More than 50% of the worldwide cases of hepatocellular carcinoma occur in China, and this malignancy currently represents the country's second leading cause of cancer death in cities and the leading cause in rural areas. Despite recent advances in the control and management of hepatocellular carcinoma within China, this disease remains a major health care issue. The global HCC BRIDGE study, designed to assess patterns of hepatocellular carcinoma therapy use and associated outcomes across real-world clinical practice, has recently been expanded as a national study in China, allowing a detailed analysis of hepatocellular carcinoma in this important country. Methods/Design The global HCC BRIDGE study is a multiregional longitudinal cohort trial including patients newly diagnosed with hepatocellular carcinoma between January 1, 2005, and June 30, 2011, who are receiving treatment for hepatocellular carcinoma via sites in the Asia-Pacific, European, and North American regions. The HCC BRIDGE China national study comprises the portion of the global HCC BRIDGE study conducted within mainland China. Patients will be followed from time of diagnosis of hepatocellular carcinoma (post-January 1, 2005 to time of death or December 31, 2011, whichever comes first. Data will be collected on demographic/clinical characteristics, relevant laboratory values, hepatocellular carcinoma/underlying liver disease treatment, tumor response, adverse events, hospitalizations, and overall survival. The primary study end point is overall survival; secondary end points are disease progression, treatment-limiting adverse events, and treatment failure. Results At the time of writing, 15 sites have selected for participation across all 7 traditional regions of China (North, North-East, East, South, South-West, North-West, and Central. The anticipated study population from the China national study is approximately 9000 patients. Discussion Findings from the

  12. Risk Analysis of Hepatocellular Carcinoma in Northeast China

    Institute of Scientific and Technical Information of China (English)

    Zhi-fang Jia; Meng Su; Miao He; Zhi-hua Yin; Wei Wu; Xue-lian Li; Peng Guan; Bao-sen Zhou

    2009-01-01

    Objective: It is known that chronic hepatitis B virus (HBV) infection is a main risk factor for hepatocellular carcinoma (HCC). To assess the effect of HBV infection and its interaction with other factors on the risk for HCC, a hospital-based case-control study was carried out in Northeast China. Methods: A total of 384 cases with hepatocellular carcinoma and 432 controls without evidence of liver diseases were enrolled in the study. Blood samples were collected to detect the serum markers of hepatitis B virus (HBV) and hepatitis C virus (HCV) and questionnaires about lifestyle and family tumor history were performed in all subjects. Results: The total infection rate of HBV in hepatocellular carcinoma cases was 70.8% and 10.0% in non-liver disease controls. There was a statistically significant difference (P<0.0001) between cases and controls (OR= 22.0; 95%CI:15.0-32.3). Interaction analysis indicated that in HBV chronic carriers with HCV infection or alcohol consumption or family HCC history, the risk for HCC increased (OR=41.1, 95%CI: 20.2-83.9, OR=125.0, 95%CI: 66.5-235.2; OR=56.9, 95%CI: 27.2-119.3 respectively). In addition, hepatitis B history, HCV infection, hepatic cirrhosis and family history of HCC were also potential HCC independent risk factors. Conclusion: We confirmed that HBV is a chief risk factor for hepatocellular carcinoma and accounts for 67.7% of all hepatocellular carcinoma in Northeast China. HCV infection, alcohol intake and family history could enhance the risk for HCC in chronic HBV carriers.

  13. Serum tumor markers for detection of hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Lin Zhou; Jia Liu; Feng Luo

    2006-01-01

    Hepatocellular carcinoma (HCC) is one of the most frequent malignant tumors and is the second most common cause of cancer death in China. Therefore, it is very important to detect this disease and the recurrence at its earlier period. Serum tumor markers, as the effective method for detecting hepatocellular carcinoma for a long time, could be divided into 4 categories:oncofetal antigens and glycoprotein antigens; enzymes and isoenzymes; genes; and cytokines. Serum alpha fetoprotein (AFP) is the most widely used tumor marker in detecting patients with hepatocellular carcinoma, and has been proven to have capability of prefiguring the prognosis. However, it has been indicated that AFP-L3and DCP excel AFP in differentiating hepatocellular carcinoma from nonmalignant hepatopathy and detecting small hepatocellular carcinoma. Some tumor markers, such as human cervical cancer oncogene and human telomerase reverse transcriptase mRNA, have also been indicated to have higher accuracies than AFP. Furthermore, some other tumor markers, such as glypican-3, gamma-glutamyl transferase Ⅱ, alpha-Ⅰ-fucosidase, transforming growth factor-beta1, tumor-specific growth factor, have been indicated to be available supplementaries to AFP in the detection. AFP mRNA has been shown to correlate with the metastasis and recurrence of HCC, and it may be the most useful marker to prefigure the prognosis. Some other markers,such as gamma-glutamyl transferase mRNA, vascular endothelial growth factor, and interleukin-8, could also be used as available prognostic indicators, and the simultaneous determination of AFP and these markers may detect the recurrence of HCC at its earlier period.

  14. Increased nociceptin/orphanin FQ plasma levels in hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Ferenc Szalay; Mónika B Hantos; Andrea Horvath; Peter L. Lakatos; Aniko Folhoffer; Kinga Dunkel; Dalma Hegedus; Kornélia Tekes

    2004-01-01

    AIM: The heptadecapeptide nociceptin alias orphanin FQ is the endogenous agonist of opioid receptor-like1 receptor.It is involved in modulation of pain and cognition. High blood level was reported in patients with acute and chronic pain,and in Wilson disease. An accidental observation led us to investigate nociceptin in hepatocellular carcinoma.METHODS: Plasma nociceptin level was measured by radioimmunoassay, aprotinin was used as protease inhibitor.Hepatocellular carcinoma was diagnosed by laboratory,ultrasound, other imaging, and confirmed by fine needle biopsy. Results were compared to healthy controls and patients with other chronic liver diseases.RESULTS: Although nociceptin levels were elevated in patients with Wilson disease (14.0±2.7 pg/mL, n=26),primary biliary cirrhosis (12.1±3.2 pg/mL, n=21) and liver cirrhosis (12.8±4.0 pg/mL, n=15) compared to the healthy controls (9.2±1.8 pg/mL, n=29, P<0.001 for each), in patients with hepatocellular carcinoma a ten-fold increase was found (105.9±14.4 pg/mL, n=29, P<0.0001). High plasma levels were found in each hepatocellular carcinoma patient including those with normal alpha fetoprotein and those with pain (104.9±14.9 pg/mL, n=12) and without (107.7±14.5pg/mL, n=6).CONCLUSION: A very high nociceptin plasma level seems to be an indicator for hepatocellular carcinoma. Further research is needed to clarify the mechanism and clinical significance of this novel finding.

  15. Protein arginine N-methyltransferase 1 promotes the proliferation and metastasis of hepatocellular carcinoma cells.

    Science.gov (United States)

    Gou, Qing; He, ShuJiao; Zhou, ZeJian

    2017-02-01

    Hepatocellular carcinoma is the most common subtype of liver cancer. Protein arginine N-methyltransferase 1 was shown to be upregulated in various cancers. However, the role of protein arginine N-methyltransferase 1 in hepatocellular carcinoma progression remains incompletely understood. We investigated the clinical and functional significance of protein arginine N-methyltransferase 1 in a series of clinical hepatocellular carcinoma samples and a panel of hepatocellular carcinoma cell lines. We performed suppression analysis of protein arginine N-methyltransferase 1 using small interfering RNA to determine the biological roles of protein arginine N-methyltransferase 1 in hepatocellular carcinoma. In addition, the expression of epithelial-mesenchymal transition indicators was verified by western blotting in hepatocellular carcinoma cell lines after small interfering RNA treatment. Protein arginine N-methyltransferase 1 expression was found to be significantly upregulated in hepatocellular carcinoma cell lines and clinical tissues. Moreover, downregulation of protein arginine N-methyltransferase 1 in hepatocellular carcinoma cells by small interfering RNA could inhibit cell proliferation, migration, and invasion in vitro. These results indicate that protein arginine N-methyltransferase 1 may contribute to hepatocellular carcinoma progression and serves as a promising target for the treatment of hepatocellular carcinoma patients.

  16. Update in management of hepatocellular carcinoma inEastern population

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Hepatocellular carcinoma (HCC) is one of the commonestmalignant tumours in the East. Although themanagement of HCC in the West is mainly basedon the Barcelona Clinic for Liver Cancer staging, it isconsidered too conservative by Asian countries wherethe number of HCC patients is huge. Scientific andclinical advances were made in aspects of diagnosis,staging, and treatment of HCC. HCC is well known to be associated with cirrhosis and the treatment of HCC musttake into account the presence and stage of chronicliver disease. The major treatment modalities of HCCinclude: (1) surgical resection; (2) liver transplantation;(3) local ablation therapy; (4) transarterial locoregionaltreatment; and (5) systemic treatment. Among these,resection, liver transplantation and ablation therapy forsmall HCC are considered as curative treatment. Portalvein embolisation and the associating liver partitionwith portal vein ligation for staged hepatectomy mayreduce dropout in patients with marginally resectabledisease but the midterm and long-term results are stillto be confirmed. Patient selection for the best treatmentmodality is the key to success of treatment of HCC. Thepurpose of current review is to provide a descriptionof the current advances in diagnosis, staging, preoperativeliver function assessment and treatmentoptions for patients with HCC in the east.

  17. Hepatocellular carcinoma (Letter to the editor)

    DEFF Research Database (Denmark)

    Békássy, Albert N.; Garwicz, Stanislaw; Jensen, O.A.

    1994-01-01

    Øjenpatologi, Alagill's syndrome, hepatic carcinoma, biliary atresia, histopathology, liver, child, liver cirrhosis, autopsy, eyes, AFP......Øjenpatologi, Alagill's syndrome, hepatic carcinoma, biliary atresia, histopathology, liver, child, liver cirrhosis, autopsy, eyes, AFP...

  18. 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.

  19. Comparison of intra-arterial chemoembolization with and without radiotherapy for advanced hepatocellular carcinoma with portal vein tumor thrombosis: a meta-analysis

    Science.gov (United States)

    Zhao, Qianqian; Zhu, Kunli; Yue, Jinbo; Qi, Zhonghua; Jiang, Shumei; Xu, Xiaoqing; Feng, Rui; Wang, Renben

    2017-01-01

    Purpose Numerous studies have tried to combine transarterial chemoembolization (TACE) or hepatic arterial infusion chemotherapy (HAIC) with radiotherapy (RT) for the treatment of hepatocellular carcinoma (HCC) patients with portal vein tumor thrombus (PVTT). However, the efficacy of TACE or HAIC combined with RT versus TACE or HAIC alone remains controversial. Thus, we performed a meta-analysis to compare the efficacy and safety of intra-arterial chemoembolization combined with RT versus intra-arterial chemoembolization alone for the treatment of HCC patients with PVTT. Methods PubMed, Embase, and Cochrane Library databases were systematically searched for eligible studies. Two authors independently reviewed the abstracts, extracted relevant data and rated the quality of studies. The major end points were objective response rate (ORR), overall survival (OS), and adverse events. Results Eight studies with a total of 1,760 patients were included in this meta-analysis. The pooled results showed that intra-arterial chemoembolization combined with RT significantly improved ORR of PVTT (OR, 4.22; 95% CI, 3.07–5.80; P<0.001) and OS (HR, 0.69; 95% CI, 0.57–0.83; P=0.001), but did not affect ORR of primary liver tumor (OR, 1.37; 95% CI, 0.67–2.79; P=0.390). The incidence of grade 3 or 4 leukopenia (OR, 5.80; 95% CI, 2.478–13.56; P<0.001) and thrombocytopenia (OR, 3.77; 95% CI, 1.06–13.43; P=0.041) was higher in the intra-arterial chemoembolization plus RT group than in the intra-arterial chemoembolization group. Conclusion Combination therapy of intra-arterial chemoembolization and RT for HCC patients with PVTT could bring higher ORR of PVTT and better survival benefits. This combination therapy was also associated with a significantly increased risk of adverse events. However, they were mostly mild to moderate and successfully treated with conservative treatment. PMID:28053537

  20. Immunosupression in liver transplant for hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Juan Carlos Restrepo Restrepo

    2007-02-01

    Full Text Available

    The hepatocellular carcinoma (HCC has turned into a frequent indication for liver transplant. The reports of different series indicate that it represents at least 12% of all liver transplants in Europe. But what kind of inmunosuppression is better in these patients is an unanswered question. Our intension with this review is to give basic information to define which would be the best immunosuppression alternative. There is enough information on the relationship between immunosuppression and cancer, as it is seen in states of primary immunodeficiency or infection with the Human Immunodeficiency virus (HIV. The immune system offers a state of permanent guard to avoid the arousal of neoplasic diseases in immunocompetent patients and from this point of view it has been seen that in immunosuppressed patients there is an association with this condition and the development of lymphoproliferative disorders, which can range from reversible diseases (polyclonal proliferation of B type lymphocytes to the development of a lymphoma and other types of tumors, like the ones observed in skin, genital region or oropharynx. Colon tumors and breast tumors have not been associated with immunosuppression. Immunosuppressive medication takes part in a different manner in the development of tumors, it has been said that steroids that are associated with some tumors, especially those regarding skin, paradoxically have a protective role in the development of lymph tissue tumors.

    It has been said about Azathioprine and Mycophenolate mofetil (MMF that its immunosuppressive effect is an antiproliferative type of immunosuppression, inhibiting the synthesis of purinic nucleotides, especially in lymphocytes. Azathioprine has been involved in the development of hepatic tumors, especially in the era previous

  1. The Combination of Periostin Overexpression and Microvascular Invasion Is Related to a Poor Prognosis for Hepatocellular Carcinoma

    Science.gov (United States)

    Jang, Se Young; Park, Soo Young; Lee, Hye Won; Choi, Yeon-Kyung; Park, Keun-Gyu; Yoon, Ghil Suk; Tak, Won Young; Kweon, Young Oh; Hur, Keun; Lee, Won Kee

    2016-01-01

    Background/Aims Periostin is an extracellular matrix protein and is known to be related to the metastatic potential and prognosis of cancer. However, few studies have investigated the expression level of periostin and its association with prognoses in hepatocellular carcinoma. Therefore, we analyzed periostin overexpression in hepatocellular carcinoma and its implication for prognoses. Methods We evaluated 149 patients who underwent surgical resection between 2006 and 2010. Tissue microarrays were constructed from hepatocellular carcinoma tissue and adjacent nontumor tissue, and immunohistochemistry was performed. Results A high periostin level was observed more frequently in cases of multiple tumors (odds ratio [OR], 2.826; 95% confidence interval [CI], 1.224 to 6.527; p=0.013), positive microvascular invasion (OR, 2.974; 95% CI, 1.431 to 6.181; p=0.003), and advanced stage disease (OR, 3.032; 95% CI, 1.424 to 6.452; p=0.003). Patients with high periostin expression had significantly (p=0.002) lower overall survival rates than those with low periostin expression (90.3%, 66.1%, and 56.2% vs 97.7%, 85.1%, and 77.5% at 1, 3, and 5 years). Conclusions We found that a combination of periostin overexpression and microvascular invasion in hepatocellular carcinoma was correlated with a poor prognosis and can be a good prognostic marker for hepatocellular carcinoma. PMID:27458178

  2. Emerging role of Hpo signaling and YAP in hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Valero V III

    2015-06-01

    exhibit YAP overexpression, and YAP serves as an independent prognostic marker for disease-free survival and overall survival in patients with HCC. Recently, the small molecule inhibitor, verteporfin has been shown to attenuate YAP activity in murine models, perhaps offering a novel therapeutic approach for patients with advanced HCC.Keywords: hepatocellular carcinoma, yes-associated-protein, Hippo signaling, liver cancer, hepatic malignancy

  3. Prevenção do carcinoma hepatocelular Prevention of hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Francine Papaiordanou

    2009-06-01

    responsible for nearly two thirds of deaths caused by cancer. METHOD: Review of the national and international literature in the last 12 years (1997-2009, of 25 articles researched through the electronic databases MedLine, Scielo and Lilacs. CONCLUSION: Despite of the medical advances and the implementation of precocious measures to detect the hepatocellular carcinoma in patients considered as within risk groups, there was no improvement on the afterlife over the last three decades. The cause that can explain this reality is the absence of symptoms during the early stages of the disease, and by the time the patient looks for medical help, the tumor has frequently reached an advanced stage and the therapeutical options are already too few.

  4. Simultaneous Resection of Disseminated Hepatocellular Carcinoma and Colon Cancer

    Directory of Open Access Journals (Sweden)

    Yuki Haga

    2013-01-01

    Full Text Available A 75-year-old woman with abdominal pain and vomiting was admitted to our hospital. Colonoscopy showed an advanced colon cancer that encompassed the entire circumference of the descending colon’s lumen. The patient was diagnosed with occlusive ileus associated with the colon cancer. She had been watched for liver cirrhosis due to the hepatitis C virus and received radiofrequency ablation therapy for hepatocellular carcinoma (HCC 6 years previously. Although she exhibited a gradual increase in serum levels of α-fetoprotein and PIVKA-II starting 2 years before admission, no tumors were detected in the liver by abdominal ultrasonography and computed tomography. On admission, contrast-enhanced computed tomography revealed not only the colon cancer but also a tumor adjacent to the cecum. Both tumors were successfully removed by surgery and a pathological analysis revealed that the cecum tumor was poorly-differentiated HCC. The serum levels of α-fetoprotein and PIVKA-II declined markedly after the operation and no masses considered as peritoneal metastasis have been detected to date. This is the first report of the simultaneous resection of disseminated HCC and colon cancer.

  5. Preoperative portal vein embolization for hepatocellular carcinoma: consensus and controversy

    Institute of Scientific and Technical Information of China (English)

    Taku; Aoki; Keiichi; Kubota

    2016-01-01

    Thirty years have passed since the first report of portal vein embolization(PVE),and this procedure is widely adopted as a preoperative treatment procedure for patients with a small future liver remnant(FLR).PVE has been shown to be useful in patients with hepatocellular carcinoma(HCC)and chronic liver disease.However,special caution is needed when PVE is applied prior to subsequent major hepatic resection in cases with cirrhotic livers,and volumetric analysis of the liver segments in addition to evaluation of the liver functional reserve before PVE is mandatory in such cases.Advances in the embolic material and selection of the treatment approach,and combined use of PVE and transcatheter arterial embolization/chemoembolization have yielded improved outcomes after PVE and major hepatic resections.A novel procedure termed the associating liver partition and portal vein ligation for staged hepatectomy has been gaining attention because of the rapid hypertrophy of the FLR observed in patients undergoing this procedure,however,application of this technique in HCC patients requires special caution,as it has been shown to be associated with a high morbidity and mortality even in cases with essentially healthy livers.

  6. 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

  7. Non-surgical management of hepatocellular carcinoma; Prise en charge non chirurgicale du carcinome hepatocellulaire

    Energy Technology Data Exchange (ETDEWEB)

    Merle, P. [Service d' hepato-gastroenterologie, hopital de l' Hotel-Dieu, 69 - Lyon (France); Inserm U871 -Oncogenese hepatique et hepatites virales-, 69 - Lyon (France); IFR62 Lyon-Est, universite Lyon 1, 69 - Lyon (France); Mornex, F. [Departement de radiotherapie-oncologie, centre hospitalier Lyon-Sud, 69 - Pierre-Benite (France)

    2010-10-15

    Most of patients with hepatocellular carcinoma (HCC) cannot benefit from surgical therapies. Among non-surgical options, only radiofrequency can challenge surgery for small size tumours. Conformal radiotherapy is likely highly efficient on solitary tumours, but controlled studies are warranted to conclude. Other options are purely palliative. Trans-arterial hepatic chemo-embolization is the goal-standard for multifocal hepatocellular carcinoma and Sorafenib for hepatocellular carcinoma with portal vein invasion, leading to modest but significant benefit on survival rates. Yttrium-90 radio-embolization is under evaluation through controlled studies, and could be of major interest for multifocal hepatocellular carcinoma with or without portal venous invasion. (authors)

  8. Mammalian target of rapamycin inhibition in hepatocellular carcinoma

    Science.gov (United States)

    Ashworth, René E; Wu, Jennifer

    2014-01-01

    Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide. It is associated with a poor prognosis and has limited treatment options. Sorafenib, a multi-targeted kinase inhibitor, is the only available systemic agent for treatment of HCC that improves overall survival for patients with advanced stage disease; unfortunately, an effective second-line agent for the treatment of progressive or sorafenib-resistant HCC has yet to be identified. This review focuses on components of the mammalian target of rapamycin (mTOR) pathway, its role in HCC pathogenesis, and dual mTOR inhibition as a therapeutic option with potential efficacy in advanced HCC. There are several important upstream and downstream signals in the mTOR pathway, and alternative tumor-promoting pathways are known to exist beyond mTORC1 inhibition in HCC. This review analyzes the relationships of the upstream and downstream regulators of mTORC1 and mTORC2 signaling; it also provides a comprehensive global picture of the interaction between mTORC1 and mTORC2 which demonstrates the pre-clinical relevance of the mTOR pathway in HCC pathogenesis and progression. Finally, it provides scientific rationale for dual mTORC1 and mTORC2 inhibition in the treatment of HCC. Clinical trials utilizing mTORC1 inhibitors and dual mTOR inhibitors in HCC are discussed as well. The mTOR pathway is comprised of two main components, mTORC1 and mTORC2; each has a unique role in the pathogenesis and progression of HCC. In phase III studies, mTORC1 inhibitors demonstrate anti-tumor activity in advanced HCC, but dual mTOR (mTORC1 and mTORC2) inhibition has greater therapeutic potential in HCC treatment which warrants further clinical investigation. PMID:25429315

  9. Mechanisms and signiifcance of lipoprotein(a) in hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Jing-Ting Jiang; Chang-Ping Wu; Ning Xu; Xue-Guang Zhang

    2009-01-01

    BACKGROUND: The liver plays a key role in the metabolism of plasma apolipoproteins, endogenous lipids and lipoproteins. Hepatocellular carcinoma is one of the most common fatal malignant tumors in China and in other Southeast Asian countries. It has been demonstrated that plasma lipid proifles are changed in liver cancer. DATA SOURCES: A MEDLINE database search was performed to identify relevant articles using the keywords "hepatocellular carcinoma" and "lipoprotein(a)". The search was conducted and research articles were reviewed from 1960 to 2008. RESULTS: Production and homeostasis of lipids, apo-lipoproteins and lipoproteins depend on the integrity of hepatocellular functions, which ensures normal lipid and lipoprotein metabolismin vivo. When hepatocellular injury or liver cancer occurs these processes can be impaired. It has been suggested that plasma levels of apolipoprotein(a) (apo(a)) and/or lipoprotein(a) (Lp(a)) may be considered as sensitive markers of hepatic impairment. CONCLUSIONS: Plasma levels of apo(a) and Lp(a) display signiifcant correlations with hepatic status. Most studies demonstrated that the plasma levels of apo(a) and Lp(a) can be considered as an additional clinical index of liver function.

  10. 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. In princ......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...... and treatment of liver cancer and offers a walkthrough from the MNPs imaging applicability to further therapeutic options, including their potential flaws. The MNP unique physical and biochemical properties will be mentioned in close relationship to their subsequent effects on the human body, and, also......, their toxic potential will be noted. A presentation of what barriers the MNPs should overcome to be more successful will conclude this review....

  11. Cytogenetic and molecular genetic alterations in hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Sze-hang LAU; Xin-yuan GUAN

    2005-01-01

    Specific chromosome aberrations are frequently detected during the development of hepatocellular carcinoma. Molecular cytogenetic approaches such as comparative genomic hybridization and loss of heterozygosity analyses have provided fruitful information on changes in HCC cases at the genomic level. Mapping of chromosome gains and losses have frequently resulted in the identification of oncogenes and tumor suppressors, respectively. In this review, we summarize some frequently detected chromosomal aberrations reported for hepatocellular carcinoma cases using comparative genomic hybridization and loss of heterozygosity studies. Focus will be on gains of 1q, 8q, and 20q, and losses of 4q,8p, 13q, 16q, and 17p. We then examine the candidate oncogenes and tumor suppressors located within these regions, and explore their possible functions in hepatocarcinogenesis. Finally, the impact of microarray-based screening platforms will be discussed.

  12. 晚期肝癌患者主要照顾者需求及其影响因素研究%Needs of Major Caregivers of Patients with Advanced Hepatocellular Carcinoma and Its Influence Factors

    Institute of Scientific and Technical Information of China (English)

    刘维; 周新民; 付菊芳; 胡雪慧; 王丹; 温佳; 王安辉; 于方方; 刘俊; 宋汉歌

    2015-01-01

    Objective To understand the needs of major caregivers of patients with advanced hepatocellular carcinoma and to explore its influence factors. Methods A total of 220 pairs of patients with advanced hepatocellular carcinoma and their major caregivers were investigated with a self-designed general information questionnaire, KPS scale and needs of caregivers of patients with advanced cancer questionnaire from February to October in 2014. Results The total score of needs of major caregivers of patients with advanced hepatocellular carcinoma was 131.23 ±26.17 and the total mean score of needs was 3.65 ±0.73. Generally, the needs of caregivers remained in a mediate or above level. The highest score of needs from the domain of disease knowledge information was 4.53±0.78 , followed by related behaviors of doctors was 4.43±0.64 and nurses and symptom control was 3.88±1.18, and the lowest score of funeral support needs was 2.94 ±1.12. The KPS score, gender and caring experience were entered into the regression equation of needs (P<0.05). Conclusion The major caregivers of patients with advanced hepatocellular carcinoma have unmet supportive care needs in various domains which were affected by multiple factors and there are different factors influencing the needs of different domains. Medical staff should pay more attention to strengthening training and education to the caregivers on related knowledge of disease and care skills so to improve the quality of life of patients and their caregivers.%目的:评估晚期肝癌患者主要照顾者的需求及其影响因素。方法采用自行设计的一般资料调查表、患者身体功能状态评分量表(Karnofsky Performance Status, KPS)及晚期癌症患者照顾者需求调查表,对2014年2-10月西安市某三级甲等医院消化科220对晚期肝癌患者及其主要照顾者进行问卷调查。结果晚期肝癌患者主要照顾者需求总分为(131.23±26.17)分,需求总均分为(3.65±0

  13. Dose response relationship in local radiotherapy for hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Park, Hee Chul; Seong, Jin Sil; Han, Kwang Hyub; Chon, Chae Yoon; Moon, Young Myoung; Song, Jae Seok; Suh, Chang Ok [College of Medicine, Yonsei Univ., Seoul (Korea, Republic of)

    2001-06-01

    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

  14. Hepatocellular carcinoma and liver metastases: Diagnosis and treatment

    Energy Technology Data Exchange (ETDEWEB)

    Hoogewoud, H.M.

    1993-12-31

    The state of the art concerning hepatocellular carcinoma and liver metastases is given in this review of the literature. The results of the author`s analysis are frequently summarized in tables that are easy to understand. The book covers the broad range of possible diagnostic and management techniques: pathology, imaging, surgery, radiotherapy and chemotherapy. The gamut of indications, contra-indications, results and complications is discussed. Emphasis is placed particularly on catheter techniques. (orig.). 41 figs., 21 tabs.

  15. Hepatocellular carcinoma HBsAg positive in pregnancy.

    Science.gov (United States)

    Gonçalves, C S; Pereira, F E; de Vargas, P R; Ferreira, L S

    1984-01-01

    The authors present a case of hepatocellular carcinoma diagnosed in a pregnant woman (four months pregnancy). The clinical evolution was complicated because of a severe hypoglicemia and the patient died 12 weeks after admission. The fetus died before a tentative of surgical delivery. The patient was HBsAg positive and five out of eight sons (inclusively the fetus), were HBsAg positive. There was not indication that the pregnancy had enhanced the tumor evolution.

  16. Surgical spacer placement and proton radiotherapy for unresectable hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Shohei; Komatsu; Yuichi; Hori; Takumi; Fukumoto; Masao; Murakami; Yoshio; Hishikawa; Yonson; Ku

    2010-01-01

    Few potentially curative treatment options exist apart from hepatic resection for patients with huge hepatocellular carcinoma (HCC). Proton radiotherapy is a promising new modality which has an inherent antitumor effect against HCC. However, the application of proton radiotherapy for tumors adjacent to the gastrointestinal tract is restricted because the tolerance dose of the intestine is extremely low. A novel two-step treatment was developed with surgical spacer placement and subsequent proton radiotherap...

  17. Decreased PCSK9 expression in human hepatocellular carcinoma

    OpenAIRE

    2015-01-01

    Background The management of hepatocellular carcinoma (HCC) is limited by the lack of adequate screening biomarkers and chemotherapy. In response, there has been much interest in tumor metabolism as a therapeutic target. PCSK9 stimulates internalization of the LDL-receptor, decreases cholesterol uptake into hepatocytes and affects liver regeneration. Thus, we investigated whether PCSK9 expression is altered in HCC, influencing its ability to harness cholesterol metabolism. Methods Thirty-nine...

  18. Hepatic artery pseudoaneurysms arising from within a hepatocellular carcinoma

    Science.gov (United States)

    Chingkoe, C M; Chang, S D; Legiehn, G M; Weiss, A

    2010-01-01

    We report a case of a 70-year-old man with a large hepatocellular carcinoma (HCC) containing two pseudoaneurysms measuring up to 2 cm in diameter. The pseudoaneurysms and part of the HCC were supplied by branches from the middle colic artery, which arises from the superior mesenteric artery. This complex arterial vasculature was visualised on CT and confirmed with conventional angiography. PMID:21088082

  19. Targeting FGFR4 Inhibits Hepatocellular Carcinoma in Preclinical Mouse Models

    OpenAIRE

    French, Dorothy M.; Benjamin C Lin; Manping Wang; Camellia Adams; Theresa Shek; Kathy Hötzel; Brad Bolon; Ronald Ferrando; Craig Blackmore; Kurt Schroeder; Rodriguez, Luis A.; Maria Hristopoulos; Rayna Venook; Avi Ashkenazi; Desnoyers, Luc R.

    2012-01-01

    The fibroblast growth factor (FGF)-FGF receptor (FGFR) signaling system plays critical roles in a variety of normal developmental and physiological processes. It is also well documented that dysregulation of FGF-FGFR signaling may have important roles in tumor development and progression. The FGFR4-FGF19 signaling axis has been implicated in the development of hepatocellular carcinomas (HCCs) in mice, and potentially in humans. In this study, we demonstrate that FGFR4 is required for hepatoca...

  20. A case report of hepatocellular carcinoma in common hepatic duct

    Energy Technology Data Exchange (ETDEWEB)

    Song, Chi Sung; Park, In Ae; Choi, Sang Woon; Chung, Jung Kee [YongDeungPo City Hospital, Seoul (Korea, Republic of)

    1989-08-15

    We experienced a rare case of intraductal (common hepatic duct) hepatocellular carcinoma. Review of the literature disclosed 30 cases or less in which common duct involvement was a predominant clinical feature. Well demarcated, ovoid filling defect mass in CHD without parenchymal tumor mass was noted in ultrasound, PTC and CT study. The liver was cirrhotic, but {alpha}-fetoprotein level was normal. Differential diagnosis especially with Klatskin tumor is important and thought to be possible.

  1. Surgical treatment of hepatocellular carcinoma with severe intratumoral arterioportal shunt

    Institute of Scientific and Technical Information of China (English)

    Hiromichi; Ishii; Teruhisa; Sonoyama; Shingo; Nakashima; Hiroyuki; Nagata; Atsushi; Shiozaki; Yoshiaki; Kuriu; Hisashi; Ikoma; Masayoshi; Nakanishi; Daisuke; Ichikawa; Hitoshi; Fujiwara; Kazuma; Okamoto; Toshiya; Ochiai; Yukihito; Kokuba; Chohei; Sakakura; Eigo; Otsuji

    2010-01-01

    We report a case of hepatocellular carcinoma (HCC) that caused a severe arterioportal shunt (APS). A 49-year-old man was admitted to hospital due to esophagogastric variceal hemorrhage and HCC, and underwent endoscopic variceal ligation (EVL) and endoscopic injection sclerotherapy (EIS). He was then referred to our hospital. Abdominal computed tomography revealed a lowdensity lesion in the posterior segment of the liver and an intratumoral APS, which caused portal hypertension. Although the patient underwen...

  2. Right ventricular exclusion for hepatocellular carcinoma metastatic to the heart

    Directory of Open Access Journals (Sweden)

    Fan Shou-Zen

    2010-10-01

    Full Text Available Abstract We used for the first time a right ventricular exclusion procedure for the treatment of hepatocellular carcinoma metastatic to the right ventricle. Our case report shows that this surgical option can be effective as rescue therapy for right ventricular outflow tract obstruction secondary to myocardial metastasis in critically ill patients. Most notably, this technique can prevent inadvertent dislodgement of tumor cells.

  3. Heparanase and hepatocellular carcinoma:Promoter or inhibitor?

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Heparan sulphate proteoglycans (HSPGs) consist of a core protein and several heparan sulphate (HS) side chains covalently linked. HS also binds a great deal of growth factors, chemokines, cytokines and enzymes to the extracellular matrix and cell surface. Heparanase can specially cleave HS side chains from HSPGs. There are a lot of conflicting reports about the role of heparanase in hepatocellular carcinoma (HCC). Heparanase is involved in hepatitis B virus infection and hepatitis C virus infection, the act...

  4. Hepatocellular carcinoma occurring in a Crohn’s disease patient

    Institute of Scientific and Technical Information of China (English)

    Mitsuaki; Ishida; Shigeyuki; Naka; Hisanori; Shiomi; Tomoyuki; Tsujikawa; Akira; Andoh; Tamio; Nakahara; Yasuharu; Saito; Yoshi-hide; Fujiyama; Mikiko; Takikita-Suzuki; Fumiyoshi; Kojima; Machiko; Hotta; Tohru; Tani; Yoshimasa; Kurumi; Hidetoshi; Okabe

    2010-01-01

    We report a case of hepatocellular carcinoma (HCC) occurring in a patient with Crohn’s disease (CD) without chronic hepatitis or liver cirrhosis, and review the clinicopathological features of HCC in CD patients. A 37-year-old Japanese man with an 8-year history of CD and a medication history of azathioprine underwent resection of a liver tumor. The histopathology of the liver tumor was pseudoglandular type HCC. In the nonneoplastic liver, focal hepatocyte glycogenosis (FHG) was observed, however, there was...

  5. Investigating the biochemical progression of liver disease through fibrosis, cirrhosis, dysplasia, and hepatocellular carcinoma using Fourier transform infrared spectroscopic imaging

    Science.gov (United States)

    Sreedhar, Hari; Pant, Mamta; Ronquillo, Nemencio R.; Davidson, Bennett; Nguyen, Peter; Chennuri, Rohini; Choi, Jacqueline; Herrera, Joaquin A.; Hinojosa, Ana C.; Jin, Ming; Kajdacsy-Balla, Andre; Guzman, Grace; Walsh, Michael J.

    2014-03-01

    Hepatocellular carcinoma (HCC) is the most common form of primary hepatic carcinoma. HCC ranks the fourth most prevalent malignant tumor and the third leading cause of cancer related death in the world. Hepatocellular carcinoma develops in the context of chronic liver disease and its evolution is characterized by progression through intermediate stages to advanced disease and possibly even death. The primary sequence of hepatocarcinogenesis includes the development of cirrhosis, followed by dysplasia, and hepatocellular carcinoma.1 We addressed the utility of Fourier Transform Infrared (FT-IR) spectroscopic imaging, both as a diagnostic tool of the different stages of the disease and to gain insight into the biochemical process associated with disease progression. Tissue microarrays were obtained from the University of Illinois at Chicago tissue bank consisting of liver explants from 12 transplant patients. Tissue core biopsies were obtained from each explant targeting regions of normal, liver cell dysplasia including large cell change and small cell change, and hepatocellular carcinoma. We obtained FT-IR images of these tissues using a modified FT-IR system with high definition capabilities. Firstly, a supervised spectral classifier was built to discriminate between normal and cancerous hepatocytes. Secondly, an expanded classifier was built to discriminate small cell and large cell changes in liver disease. With the emerging advances in FT-IR instrumentation and computation there is a strong drive to develop this technology as a powerful adjunct to current histopathology approaches to improve disease diagnosis and prognosis.

  6. Hepatocellular carcinoma in situs inversus totalis-a case report

    Directory of Open Access Journals (Sweden)

    Thuingaren Sareo

    2014-03-01

    Full Text Available A 43-year old male presented with persistent discomfort and pain upper abdomen (epigastrium more on left side associated with fever on and off, along with fatigue and loss of appetite for the last four months. Physical examination revealed mass on left hypochondrium extending to epigastrium with mild distension of the abdomen. Imaging studies of the patient showed dextrocardia on chest x-ray  postero-anterior (PA view, thoracic and abdominal CT scan showed situs inversus totalis with multiple SOL (space occupying lesion in right lobe of liver with largest measuring 8x6 cm2 in the 4th segment. USG-guided FNAC of the mass showed features of hepatocellular carcinoma. Thereupon, hepatocellular carcinoma in situs inversus totalis was diagosed to this patient and was clinically staged as T3aN0M0. He was given sorafenib 400 mg orally twice daily with an advice to come for regular assessment every 4 week.Keywords: hepatocellular carcinoma, situs inversus totalis, case report

  7. Hepatectomy for Hepatocellular Carcinoma Complicated by Vasculitis Flare

    Directory of Open Access Journals (Sweden)

    Zeinab Abdi

    2010-01-01

    Full Text Available Background. The hepatitis C virus is a major cause of hepatocellular carcinoma. Extrahepatic manifestations of hepatitis C include mixed cryoglobulinemia which can result in ischemic damage to multiple organs. The management of these sequelae in posthepatectomy patients is unclear. Case Report. A 49-year-old male with hepatitis C was found to have a 4 cm hepatocellular carcinoma on surveillance imaging. He underwent portal vein embolization followed by hepatectomy. His postoperative course was complicated by the development of splenic infarcts, small bowel ischemia, skin lesions, and liver damage. Findings of elevated cryocrit and elevated rheumatoid factor suggested the diagnosis of cryoglobulin-related vasculitis. The patient improved on supportive care. Conclusion. Cryoglobulinemia is associated with hepatitis C and may complicate the care of this patient population. The treatment of cryoglobulinemia posthepatectomy patients is complicated by concerns over how medications may affect the regenerating liver. Steroids should be used with caution in this setting. Summary. Brief report of hepatectomy complicated by vasculitis in the context of hepatocellular carcinoma secondary to hepatitis C addresses the management of mixed cryoglobulinemia in post-hepatectomy patients.

  8. WJH 6th Anniversary Special Issues(2): Hepatocellular carcinoma Mammalian target of rapamycin inhibition in hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    René; E; Ashworth; Jennifer; Wu

    2014-01-01

    Hepatocellular carcinoma(HCC) is one of the leading causes of cancer-related death worldwide. It is associated with a poor prognosis and has limited treatment options. Sorafenib, a multi-targeted kinase inhibitor, is the only available systemic agent for treatment of HCC that improves overall survival for patients with advanced stage disease; unfortunately, an effective second-line agent for the treatment of progressive or sorafenib-resistant HCC has yet to be identified. This review focuses on components of the mammalian target of rapamycin(mTOR) pathway, its role in HCC pathogenesis, and dual mTOR inhibition as a therapeutic option with potential efficacy in advanced HCC. There are several important upstream and downstream signals in the mTOR pathway, and alternative tumor-promoting pathways are known to exist beyond mTORC1 inhibition in HCC. This review analyzes the relationships of the upstream and downstream regulators of mTORC1 and mTORC2 signaling; it also provides a comprehensive global picture of the interaction between mTORC1 and mTORC2 which demonstrates the pre-clinical relevance of the mTOR pathway in HCC pathogenesis and progression. Finally, it provides scientific rationale for dual mTORC1 and mTORC2 inhibition in the treatment of HCC. Clinical trials utilizing mTORC1 inhibitors and dual mTOR inhibitors in HCC are discussed as well. The mTOR pathway is comprised of two main components, mTORC1 and mTORC2; each has a unique role in the pathogenesis and progression of HCC. In phase Ⅲ studies, mTORC1 inhibitors demonstrate anti-tumor ac-tivity in advanced HCC, but dual mTOR(mTORC1 and mTORC2) inhibition has greater therapeutic potential in HCC treatment which warrants further clinical investigation.

  9. 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

  10. Impact of PIVKA-II in diagnosis of hepatocellular carcinoma

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    Nadia I. Zakhary

    2013-11-01

    Full Text Available Liver cancer grows silently with mild or no symptoms until advanced. In the absence of an effective treatment for advanced stage of hepatic cancer hope lies in early detection, and screening for high-risk population. Among Egyptians viral hepatitis is the most common risk factor for hepatocellular carcinoma (HCC. The current work was designed to determine the level of prothrombin induced by vitamin K absence-II (PIVKA-II in sera of patients suffering from HCC and hepatitis C virus (HCV patients being the most common predisposing factor for HCC. Our ultimate goal is diagnosis of HCC at its early stage. The current study was carried out on 83 individuals within three groups; Normal control, HCV and HCC groups. Patients were subdivided into cirrhotic and non-cirrhotic. Complete clinicopathological examination was carried out for each individual to confirm diagnosis. Individuals’ sera were subjected to quantitative determination of alpha-fetoprotein (AFP, PIVKA-II and other parameters. PIVKA-II proved to be superior to AFP for early detection of HCC patients being highly sensitive and specific. Furthermore it has the ability to discriminate between different histopathological grades of HCC and It has a powerful diagnostic validity to evaluate the thrombosis of portal vein and to differentiate between early and late stages of HCC. The direct relation between the level of PIVKA-II and the size of tumor makes it an attractive tool for early HCC diagnosis and surveillance. Using the best cut-off value of AFP (>28, showed a sensitivity of (44% and specificity of (73.3%. While cut-off value of PIVKA-II (>53.7 showed 100% sensitivity and specificity.

  11. Impact of PIVKA-II in diagnosis of hepatocellular carcinoma.

    Science.gov (United States)

    Zakhary, Nadia I; Khodeer, Sherif M; Shafik, Hanan E; Abdel Malak, Camelia A

    2013-11-01

    Liver cancer grows silently with mild or no symptoms until advanced. In the absence of an effective treatment for advanced stage of hepatic cancer hope lies in early detection, and screening for high-risk population. Among Egyptians viral hepatitis is the most common risk factor for hepatocellular carcinoma (HCC). The current work was designed to determine the level of prothrombin induced by vitamin K absence-II (PIVKA-II) in sera of patients suffering from HCC and hepatitis C virus (HCV) patients being the most common predisposing factor for HCC. Our ultimate goal is diagnosis of HCC at its early stage. The current study was carried out on 83 individuals within three groups; Normal control, HCV and HCC groups. Patients were subdivided into cirrhotic and non-cirrhotic. Complete clinicopathological examination was carried out for each individual to confirm diagnosis. Individuals' sera were subjected to quantitative determination of alpha-fetoprotein (AFP), PIVKA-II and other parameters. PIVKA-II proved to be superior to AFP for early detection of HCC patients being highly sensitive and specific. Furthermore it has the ability to discriminate between different histopathological grades of HCC and It has a powerful diagnostic validity to evaluate the thrombosis of portal vein and to differentiate between early and late stages of HCC. The direct relation between the level of PIVKA-II and the size of tumor makes it an attractive tool for early HCC diagnosis and surveillance. Using the best cut-off value of AFP (>28), showed a sensitivity of (44%) and specificity of (73.3%). While cut-off value of PIVKA-II (>53.7) showed 100% sensitivity and specificity.

  12. Multimodal imaging of a humanized orthotopic model of hepatocellular carcinoma in immunodeficient mice

    Science.gov (United States)

    Wu, Tao; Heuillard, Emilie; Lindner, Véronique; Bou About, Ghina; Ignat, Mihaela; Dillenseger, Jean-Philippe; Anton, Nicolas; Dalimier, Eugénie; Gossé, Francine; Fouré, Gael; Blindauer, Franck; Giraudeau, Céline; El-Saghire, Hussein; Bouhadjar, Mourad; Calligaro, Cynthia; Sorg, Tania; Choquet, Philippe; Vandamme, Thierry; Ferrand, Christophe; Marescaux, Jacques; Baumert, Thomas F.; Diana, Michele; Pessaux, Patrick; Robinet, Eric

    2016-01-01

    The development of multimodal strategies for the treatment of hepatocellular carcinoma requires tractable animal models allowing for advanced in vivo imaging. Here, we characterize an orthotopic hepatocellular carcinoma model based on the injection of luciferase-expressing human hepatoma Huh-7 (Huh-7-Luc) cells in immunodeficient mice. Luciferase allows for an easy repeated monitoring of tumor growth by in vivo bioluminescence. The intrahepatic injection was more efficient than intrasplenic or intraportal injection in terms of survival, rate of orthotopic engraftment, and easiness. A positive correlation between luciferase activity and tumor size, evaluated by Magnetic Resonance Imaging, allowed to define the endpoint value for animal experimentation with this model. Response to standard of care, sorafenib or doxorubicin, were similar to those previously reported in the literature, with however a strong toxicity of doxorubicin. Tumor vascularization was visible by histology seven days after Huh-7-Luc transplantation and robustly developed at day 14 and day 21. The model was used to explore different imaging modalities, including microtomography, probe-based confocal laser endomicroscopy, full-field optical coherence tomography, and ultrasound imaging. Tumor engraftment was similar after echo-guided intrahepatic injection as after laparotomy. Collectively, this orthotopic hepatocellular carcinoma model enables the in vivo evaluation of chemotherapeutic and surgical approaches using multimodal imaging. PMID:27739457

  13. Brazilian society of hepatology recommendations for the diagnosis and treatment of hepatocellular carcinoma.

    Science.gov (United States)

    Carrillo, Flair J; Mattos, Angelo Alves de; Vianey, Alex F; Vezozzo, Denise Cerqueira P; Marinho, Fábio; Souto, Francisco J; Cotrim, Helma P; Coelho, Henrique Sergio M; Silva, Ivonete; Garcia, José Huygens P; Kikuchi, Luciana; Lofego, Patricia; Andraus, Wellington; Strauss, Edna; Silva, Giovanni; Altikes, Isaac; Medeiros, Jose Eymard; Bittencourt, Paulo L; Parise, Edison R

    2015-12-01

    Hepatocellular carcinoma is a malignancy of global importance and is associated with a high rate of mortality. Recent advances in the diagnosis and treatment of this disease make it imperative to update the recommendations on the management of the disease. In order to draw evidence-based recommendations concering the diagnosis and management of hepatocellular carcinoma, the Brazilian Society of Hepatology has sponsored a single-topic meeting in João Pessoa (PB). All the invited pannelists were asked to make a systematic review of the literature and to present topics related to the risk factors for its development, methods of screening, radiological diagnosis, staging systems, curative and palliative treatments and hepatocellular carcinoma in noncirrhotic liver. After the meeting, all panelists gathered together for the discussion of the topics and the elaboration of those recommendations. The text was subsequently submitted for suggestions and approval of all members of the Brazilian Society of Hepatology through its homepage. The present paper is the final version of the reviewed manuscript containing the recommendations of the Brazilian Society of Hepatology.

  14. Emerging role of microRNAs in the treatment of hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Callegari E

    2015-05-01

    Full Text Available Elisa Callegari,1 Marco Domenicali,2 Laura Gramantieri,3 Massimo Negrini,1 Silvia Sabbioni4 1Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, Ferrara, 2Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, 3Center for Applied Biomedical Research, S Orsola-Malpighi University Hospital, Bologna, 4Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy Abstract: Hepatocellular carcinoma is the third leading cause of cancer deaths worldwide. Currently available curative options, such as surgery and transplantation, are not available to patients with advanced stages of disease. Among the potential new treatments being investigated are microRNA (miRNA-based therapies. A number of preclinical studies have reported antitumor activities of miRNA mimics or anti-miRNA molecules. Optimal in vivo delivery of miRNA molecules is crucial to their action. To this end, significant progress has been made in the development of nanoparticles for in vivo delivery of miRNA molecules. Delivery of these molecules, alone or in combination with other drugs, promises to open new possibilities for therapeutic approaches to hepatocellular carcinoma. Keywords: hepatocellular carcinoma, microRNA, nanocarriers, therapy 

  15. Treatments of Hepatocellular Carcinoma Patients with Hepatitis B Virus Infection: Treat HBV-related HCC

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    Charing Ching-Ning Chong

    2016-03-01

    Full Text Available There have been major advances recently on the therapeutic approaches of hepatitis B virus (HBV-related hepatocellular carcinoma (HCC. Surgical treatments are the key curative treatments of HCC, whereas local ablative treatments may also achieve clinical remission in selected cases. Trans-arterial locoregional therapies are regarded as palliative but still lead to improved survival. There have been major breakthroughs in the systemic therapies for HCC. The first marketed targeted therapy, sorafenib, was shown to improve survival in patients with advanced HCC. Studies on other targeted therapies also showed promising results. Suppressing HBV with effective antiviral treatment would also benefit HCC patients by reducing recurrence and improving liver function.

  16. Primary study of leptin and human hepatocellular carcinoma in vitro

    Institute of Scientific and Technical Information of China (English)

    Jing Zhou; Wei Lei; Lei Shen; He-Sheng Luo; Zhi-Xiang Shen

    2008-01-01

    AIM: To investigate the expression level and effects of leptin in human hepatocellular carcinoma cells in vitro and to explore the correlation between them.METHODS: Human hepatocellular carcinoma cell line HepG2 was cultured in vitro, and (the expression level)mRNA of leptin and leptin receptors in HepG2 were assessed using reverse transcription polymerase chain reaction (RT-PCR). Effects of different concentrations of leptin (50 ng/mL, 100 ng/mL, 200 ng/mL) on HepG2 were detected with colorimetric assay by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) after incubation periods of 24 h, 48 h,and 72 h. Flow cytometry was performed to assess cell cycle progression of different concentrations of leptin as stated above after each 24 h incubation period.RESULTS: mRNA of leptin and leptin receptors (including short and long isoforms) were expressed in HepG2.The 72 h incubation of leptin at different concentrations (50 ng/mL, 100 ng/mL, 200 ng/mL) promoted proliferation of HepG2 in a concentration- and timedependent manner. The experimental group shows significant statistical differences when compared to the controlled group which contained 0 ng/mL of leptin. As the concentration of leptin increases, significant fewer cells were detected in G0-G1 phase and more cells in S and G2-M phases.CONCLUSION: Leptin and leptin receptor are simultaneously expressed in human hepatocellular carcinoma cell line HepG2. Addition of leptin (O ng/mL200 ng/mL) in 72 h periods indicated there is a concentration- and time-dependent correlation in the stimulation of HepG2 cell proliferation. The effect of proliferation by leptin is due to promotion of DNA synthesis and enhancement of mitotic activity. The relationship between leptin and human hepatocellular carcinoma cells might indicate that adipokine could be associated with the progression of human hepatocellular carcinoma.

  17. 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.

    2015-01-01

    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 alpha

  18. Is human hepatocellular carcinoma a hormone-responsive tumor?

    Institute of Scientific and Technical Information of China (English)

    Massimo Di Maio; Bruno Daniele; Sandra Pignata; Ciro Gallo; Ermelinda De Maio; Alessandro Morabito; Maria Carmela Piccirillo; Francesco Perrone

    2008-01-01

    Before the positive results recently obtained with multitarget tyrosine kinase inhibitor sorafenib, there was no standard systemic treatment for patients with advanced hepatocellular carcinoma (HCC). Sex hormones receptors are expressed in a significant proportion of HCC samples. Following preclinical and epidemiological studies supporting a relationship between sex hormones and HCC tumorigenesis, several randomized controlled trials (RCTs) tested the efficacy of the anti-estrogen tamoxifen as systemic treatment. Largest among these trials showed no survival advantage from the administration of tamoxifen, and the recent Cochrane systematic review produced a completely negative result. This questions the relevance of estrogen receptor-mediated pathways in HCC. However, a possible explanation for these disappointing results is the lack of proper patients selection according to sex hormones receptors expression, but unfortunately the interaction between this expression and efficacy of tamoxifen has not been studied adequately. It has been also proposed that negative results might be explained if tamoxifen acts in HCC via an estrogen receptor-independent pathway, that requires higher doses than those usually administered, but an Asian RCT conducted to assess dose-response effect was completely negative. Interesting, preliminaryresults have been obtained when hormonal treatment (tamoxifen or megestrol) has been selected according to the presence of wild-type or variant estrogen receptors respectively, but no large RCTs are available to support this strategy. Negative results have been obtained also with anti-androgen therapy. In conclusion, there is no robust evidence to consider HCC a hormone-responsive tumor. Hormonal treatments should not be part of the current management of HCC.

  19. Progress in surgical and nonsurgical approaches for hepatocellular carcinoma treatment

    Institute of Scientific and Technical Information of China (English)

    Ender Gunes Yegin; Erkan Oymaci; Emrah Karatay; Ahmet Coker

    2016-01-01

    BACKGROUND: Hepatocellular carcinoma (HCC) is a com-plex and heterogeneous malignancy, frequently occurs in the setting of a chronically diseased organ, with multiple con-founding factors making its management challenging. HCC represents one of the leading causes of cancer-related mortal-ity globally with a rising trend of incidence in some of the de-veloped countries, which indicates the need for better surgical and nonsurgical management strategies. DATA SOURCES: PubMed database was searched for relevant articles in English on the issue of HCC management. RESULTS: Surgical resection represents a potentially cura-tive option for appropriate candidates with tumors detected at earlier stages and with well-preserved liver function. The long-term outcome of surgery is impaired by a high rate of recurrence. Surgical approaches are being challenged by local ablative therapies such as radiofrequency ablation and micro-wave ablation in selected patients. Liver transplantation offers potential cure for HCC and also correction of underlying liver disease, and minimizes the risk of recurrence, but is reserved for patients within a set of criteria proposed for a prudent allocation in the shortage of donor organs. Transcatheter locoregional therapies have become the palliative standard allowing local control for intermediate stage patients with noninvasive multinodular or large HCC who are beyond the potentially curative options. The signiifcant survival beneift with the multikinase inhibitor sorafenib for advanced HCC has shifted the direction of research regarding systemic treat-ment toward molecular therapies targeting the disregulated pathways of hepatocarcinogenesis. Potential beneift is sug-gested from simultaneous or sequential multimodal therapies, and optimal combinations are being investigated. Despite the striking progress in preclinical studies of HCC immuno-therapy and gene therapy, extensive clinical trials are required to achieve successful clinical applications

  20. Progress in surgical and nonsurgical approaches for hepatocellular carcinoma treatment

    Institute of Scientific and Technical Information of China (English)

    Ender Gunes Yegin; Erkan Oymaci; Emrah Karatay; Ahmet Coker

    2015-01-01

    BACKGROUND: Hepatocellular carcinoma (HCC) is a com-plex and heterogeneous malignancy, frequently occurs in the setting of a chronically diseased organ, with multiple con-founding factors making its management challenging. HCC represents one of the leading causes of cancer-related mortal-ity globally with a rising trend of incidence in some of the de-veloped countries, which indicates the need for better surgical and nonsurgical management strategies. DATA SOURCES: PubMed database was searched for relevant articles in English on the issue of HCC management. RESULTS: Surgical resection represents a potentially cura-tive option for appropriate candidates with tumors detected at earlier stages and with well-preserved liver function. The long-term outcome of surgery is impaired by a high rate of recurrence. Surgical approaches are being challenged by local ablative therapies such as radiofrequency ablation and micro-wave ablation in selected patients. Liver transplantation offers potential cure for HCC and also correction of underlying liver disease, and minimizes the risk of recurrence, but is reserved for patients within a set of criteria proposed for a prudent allocation in the shortage of donor organs. Transcatheter locoregional therapies have become the palliative standard allowing local control for intermediate stage patients with noninvasive multinodular or large HCC who are beyond the potentially curative options. The signiifcant survival beneift with the multikinase inhibitor sorafenib for advanced HCC has shifted the direction of research regarding systemic treat-ment toward molecular therapies targeting the disregulated pathways of hepatocarcinogenesis. Potential beneift is sug-gested from simultaneous or sequential multimodal therapies, and optimal combinations are being investigated. Despite the striking progress in preclinical studies of HCC immuno-therapy and gene therapy, extensive clinical trials are required to achieve successful clinical applications

  1. Serological Biomarkers of Hepatocellular Carcinoma in Egyptian Patients

    Directory of Open Access Journals (Sweden)

    Sarmad F. El-Tayeh

    2012-01-01

    Full Text Available Hepatocellular carcinoma (HCC is one of the most aggressive cancers worldwide. In Egypt, the disease is usually detected in an advanced stage at which no treatment may be effective including surgery. Early detection of the disease is thus an important goal allowing the patient to be treated before the enlargement of the tumor or its metastasis to distant organs. Tumor markers are serological agents which serum level may be useful in predicting the presence of the tumor at early stages. Alpha fetoprotein (AFP which is the golden marker for HCC is of low sensitivity, therefore, additional markers such as alpha-L-fucosidase (AFU, transforming growth factors alpha and beta (TGF-α and TGF-β and interleukin-8 (IL-8 are suggested to be simultaneously evaluated in order to enhance the detection of HCC. A total of 96 patients with different liver diseases such as HCC, hepatitis C virus (HCV, hepatitis B virus (HBV and cirrhotic patients are included in this study. Sixteen healthy volunteers are used as a control group. In patients with HCC each of AFP, AFU, TGF-α and TGF-β recorded significantly higher levels than the other patient groups and controls. HCC patients recorded significantly lower level of IL-8 compared to the other patient groups but significantly higher than the control. For AFP, AFU, TGF-α, TGF-β and IL-8, at the optimal cut-off values (obtained from the receiver operating characteristic (ROC curves, the calculated sensitivities are 46%, 72.97%, 67.56%, 54.05% and 83.8%, respectively. The simultaneous evaluation using all of the suggested markers resulted in increasing the sensitivity up to 100%. It thus recommended that, if patients with cirrhosis, as high risk patients, are subjected to regular examination using these markers in addition to AFP, HCC may be detected by 100% sensitivity in an early stage and as a consequence an effective treatment can be achieved.

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

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    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.

  3. Xanthohumol inhibits Notch signaling and induces apoptosis in hepatocellular carcinoma.

    Directory of Open Access Journals (Sweden)

    Selvi Kunnimalaiyaan

    Full Text Available Despite improvement in therapeutic strategies, median survival in advanced hepatocellular carcinoma (HCC remains less than one year. Therefore, molecularly targeted compounds with less toxic profiles are needed. Xanthohumol (XN, a prenylated chalcone has been shown to have anti-proliferative effects in various cancers types in vitro. XN treatment in healthy mice and humans yielded favorable pharmacokinetics and bioavailability. Therefore, we determined to study the effects of XN and understand the mechanism of its action in HCC. The effects of XN on a panel of HCC cell lines were assessed for cell viability, colony forming ability, and cellular proliferation. Cell lysates were analyzed for pro-apoptotic (c-PARP and cleaved caspase-3 and anti-apoptotic markers (survivin, cyclin D1, and Mcl-1. XN concentrations of 5 μM and above significantly reduced the cell viability, colony forming ability and also confluency of all four HCC cell lines studied. Furthermore, growth suppression due to apoptosis was evidenced by increased expression of pro-apoptotic and reduced expression of anti-apoptotic proteins. Importantly, XN treatment inhibited the Notch signaling pathway as evidenced by the decrease in the expression of Notch1 and HES-1 proteins. Ectopic expression of Notch1 in HCC cells reverses the anti-proliferative effect of XN as evidenced by reduced growth suppression compared to control. Taken together these results suggested that XN mediated growth suppression is appeared to be mediated by the inhibition of the Notch signaling pathway. Therefore, our findings warrants further studies on XN as a potential agent for the treatment for HCC.

  4. Xanthohumol inhibits Notch signaling and induces apoptosis in hepatocellular carcinoma.

    Science.gov (United States)

    Kunnimalaiyaan, Selvi; Sokolowski, Kevin M; Balamurugan, Mariappan; Gamblin, T Clark; Kunnimalaiyaan, Muthusamy

    2015-01-01

    Despite improvement in therapeutic strategies, median survival in advanced hepatocellular carcinoma (HCC) remains less than one year. Therefore, molecularly targeted compounds with less toxic profiles are needed. Xanthohumol (XN), a prenylated chalcone has been shown to have anti-proliferative effects in various cancers types in vitro. XN treatment in healthy mice and humans yielded favorable pharmacokinetics and bioavailability. Therefore, we determined to study the effects of XN and understand the mechanism of its action in HCC. The effects of XN on a panel of HCC cell lines were assessed for cell viability, colony forming ability, and cellular proliferation. Cell lysates were analyzed for pro-apoptotic (c-PARP and cleaved caspase-3) and anti-apoptotic markers (survivin, cyclin D1, and Mcl-1). XN concentrations of 5 μM and above significantly reduced the cell viability, colony forming ability and also confluency of all four HCC cell lines studied. Furthermore, growth suppression due to apoptosis was evidenced by increased expression of pro-apoptotic and reduced expression of anti-apoptotic proteins. Importantly, XN treatment inhibited the Notch signaling pathway as evidenced by the decrease in the expression of Notch1 and HES-1 proteins. Ectopic expression of Notch1 in HCC cells reverses the anti-proliferative effect of XN as evidenced by reduced growth suppression compared to control. Taken together these results suggested that XN mediated growth suppression is appeared to be mediated by the inhibition of the Notch signaling pathway. Therefore, our findings warrants further studies on XN as a potential agent for the treatment for HCC.

  5. INVESTIGATION OF THE THERAPEUTIC EFFECT OF EXPRESSION OF TRAIL IN VIVO ON MOUSE HEPATOCELLULAR CARCINOMA

    Institute of Scientific and Technical Information of China (English)

    张桂梅; 薛胜利; 张慧; 黎培员; 李东; 冯作化

    2003-01-01

    Objective: To construct an eukaryotic expressing plasmid of mouse TRAIL (mTRAIL), and investigate its ability to induce the apoptosis of hepatocellular carcinoma cells in vitro and in vivo, its inhibitory effect on the growth of hepatocellular carcinoma, and its synergism with pCH510, an eukaryotic expressing plasmid of recombinant human FN polypeptide. Methods: The eukaryotic expressing plasmid of mTRAIL was constructed by RT-PCR and DNA recombination techniques. Gene transfection was performed in vitro and in vivo. The apoptosis rate of hepatocellular carcinoma cells was measured by Flow Cytometry. The apoptosis of hepatocellular carcinoma cells was detected by TdT-mediated dUTP nick end labeling (TUNEL) and histochemistry techniques. The inhibitory effect of gene transfection on solid tumor was observed in mice. Results: The cDNA of mTRAIL was amplified by RT-PCR from the RNA of mouse spleen cells, and cloned into the eukaryotic expressing vector pcDNA3.1. The recombinant plasmid was designated as pX1. The BHK cells transfected with plasmid pX1 could attack H22 hepatocellular carcinoma cells and induce the apoptosis of them. The transfection of plasmid pX1 through injection into mouse muscles could inhibit the growth of hepatocellular carcinoma by inducing the apoptosis of tumor cells. Plasmid pX1 and pCH510 had a synergistic inhibitory effect on the hepatocellular carcinoma growth. Conclusion: Plamid pX1 could be expressed in cells and in vivo in mouse. The expression of pX1 in vivo and in vitro could induce the apoptosis of hepatocellular carcinoma cells and inhibit the growth of hepatocellular carcinoma. Plasmid pX1 and pCH510 had a synergistic inhibitory effect on the hepatocellular carcinoma growth.

  6. Detection of the inferred interaction network in hepatocellular carcinoma from EHCO (Encyclopedia of Hepatocellular Carcinoma genes Online

    Directory of Open Access Journals (Sweden)

    Chen Chang-Han

    2007-02-01

    Full Text Available Abstract Background The significant advances in microarray and proteomics analyses have resulted in an exponential increase in potential new targets and have promised to shed light on the identification of disease markers and cellular pathways. We aim to collect and decipher the HCC-related genes at the systems level. Results Here, we build an integrative platform, the Encyclopedia of Hepatocellular Carcinoma genes Online, dubbed EHCO http://ehco.iis.sinica.edu.tw, to systematically collect, organize and compare the pileup of unsorted HCC-related studies by using natural language processing and softbots. Among the eight gene set collections, ranging across PubMed, SAGE, microarray, and proteomics data, there are 2,906 genes in total; however, more than 77% genes are only included once, suggesting that tremendous efforts need to be exerted to characterize the relationship between HCC and these genes. Of these HCC inventories, protein binding represents the largest proportion (~25% from Gene Ontology analysis. In fact, many differentially expressed gene sets in EHCO could form interaction networks (e.g. HBV-associated HCC network by using available human protein-protein interaction datasets. To further highlight the potential new targets in the inferred network from EHCO, we combine comparative genomics and interactomics approaches to analyze 120 evolutionary conserved and overexpressed genes in HCC. 47 out of 120 queries can form a highly interactive network with 18 queries serving as hubs. Conclusion This architectural map may represent the first step toward the attempt to decipher the hepatocarcinogenesis at the systems level. Targeting hubs and/or disruption of the network formation might reveal novel strategy for HCC treatment.

  7. Lengthening and shortening of plasma DNA in hepatocellular carcinoma patients

    Science.gov (United States)

    Jiang, Peiyong; Chan, Carol W. M.; Chan, K. C. Allen; Cheng, Suk Hang; Wong, John; Wong, Vincent Wai-Sun; Wong, Grace L. H.; Chan, Stephen L.; Mok, Tony S. K.; Chan, Henry L. Y.; Lai, Paul B. S.; Chiu, Rossa W. K.; Lo, Y. M. Dennis

    2015-01-01

    The analysis of tumor-derived circulating cell-free DNA opens up new possibilities for performing liquid biopsies for the assessment of solid tumors. Although its clinical potential has been increasingly recognized, many aspects of the biological characteristics of tumor-derived cell-free DNA remain unclear. With respect to the size profile of such plasma DNA molecules, a number of studies reported the finding of increased integrity of tumor-derived plasma DNA, whereas others found evidence to suggest that plasma DNA molecules released by tumors might be shorter. Here, we performed a detailed analysis of the size profiles of plasma DNA in 90 patients with hepatocellular carcinoma, 67 with chronic hepatitis B, 36 with hepatitis B-associated cirrhosis, and 32 healthy controls. We used massively parallel sequencing to achieve plasma DNA size measurement at single-base resolution and in a genome-wide manner. Tumor-derived plasma DNA molecules were further identified with the use of chromosome arm-level z-score analysis (CAZA), which facilitated the studying of their specific size profiles. We showed that populations of aberrantly short and long DNA molecules existed in the plasma of patients with hepatocellular carcinoma. The short ones preferentially carried the tumor-associated copy number aberrations. We further showed that there were elevated amounts of plasma mitochondrial DNA in the plasma of hepatocellular carcinoma patients. Such molecules were much shorter than the nuclear DNA in plasma. These results have improved our understanding of the size profile of tumor-derived circulating cell-free DNA and might further enhance our ability to use plasma DNA as a molecular diagnostic tool. PMID:25646427

  8. Hepatocellular carcinoma and the risk of occupational exposure

    Science.gov (United States)

    Rapisarda, Venerando; Loreto, Carla; Malaguarnera, Michele; Ardiri, Annalisa; Proiti, Maria; Rigano, Giuseppe; Frazzetto, Evelise; Ruggeri, Maria Irene; Malaguarnera, Giulia; Bertino, Nicoletta; Malaguarnera, Mariano; Catania, Vito Emanuele; Di Carlo, Isidoro; Toro, Adriana; Bertino, Emanuele; Mangano, Dario; Bertino, Gaetano

    2016-01-01

    Hepatocellular carcinoma (HCC) is the most common type of liver cancer. The main risk factors for HCC are alcoholism, hepatitis B virus, hepatitis C virus, nonalcoholic steatohepatitis, obesity, type 2 diabetes, cirrhosis, aflatoxin, hemochromatosis, Wilson’s disease and hemophilia. Occupational exposure to chemicals is another risk factor for HCC. Often the relationship between occupational risk and HCC is unclear and the reports are fragmented and inconsistent. This review aims to summarize the current knowledge regarding the association of infective and non-infective occupational risk exposure and HCC in order to encourage further research and draw attention to this global occupational public health problem. PMID:27168870

  9. Usefulness of MRI in diagnosis of hepatocellular carcinoma (HCC)

    Energy Technology Data Exchange (ETDEWEB)

    Usuki, Noriaki; Kawabe, Jouji; Nishikawa, Minori; Fukuda, Haruyuki; Saiwai, Shigeo; Nakajima, Hideyuki; Miyamoto, Takeshi; Kudoh, Masatoshi (Kobe General City Hospital (Japan))

    1992-06-01

    Sixty-six cases of histologically proven hepatocellular carcinomas (HCC) were studied by MRI. Detectability was better by MRI than by CT, especially in the tumor under 2 cm in diameter. The capsule was detected in all cases of HCC over 3 cm in diameter. The capsule was able to be diagnosed only by dynamic MRI study in some cases. High intensity on the T1-weighted image and iso or low intensity on the T2-weighted image suggested that the nodule was adenomatous hyperplasi (AH) or well differentiated HCC. MRI is concluded to be an essential modality in the diagnosis of HCC. (author).

  10. Resection of a giant hepatocellular carcinoma weighing over ten kilograms

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    The authors report a giant hepatocellular carcinoma(HCC)with a diameter over 30 cm and weight over 10 kg that was resected completely.A 62-year-old man was admitted because of continuous abdominal uplift.A computed tomography scan demonstrated that the entire abdomen was filled with a giant tumor containing both cystic and solid components with a size of 29 cm×22 cm.The huge tumor was successfully resected without any complication,such as massive hemorrhage or visceral injuries.The size and weight of the tu...

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

    Science.gov (United States)

    Santangelo, Laura; Battistelli, Cecilia; Montaldo, Claudia; Citarella, Franca; Strippoli, Raffaele; Cicchini, Carla

    2017-01-01

    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.

  13. Dysregulated serum response factor triggers formation of hepatocellular carcinoma.

    OpenAIRE

    Ohrnberger, Stefan; Thavamani, Abhishek; Braeuning, Albert; Daniel B. Lipka; Kirilov, Milen; Geffers, Robert; Authenrieth, Stella E; Römer, Michael; Zell, Andreas; Bonin, Michael; Schwarz, Michael; Schütz, Günther; Schirmacher, Peter; Plass, Christoph; Longerich, Thomas

    2015-01-01

    The ubiquitously expressed transcriptional regulator serum response factor (SRF) is controlled by both Ras/MAPK (mitogen-activated protein kinase) and Rho/actin signaling pathways, which are frequently activated in hepatocellular carcinoma (HCC). We generated SRF-VP16iHep mice, which conditionally express constitutively active SRF-VP16 in hepatocytes, thereby controlling subsets of both Ras/MAPK- and Rho/actin-stimulated target genes. All SRF-VP16iHep mice develop hyperproliferative liver nod...

  14. Laser ablation of hepatocellular carcinoma-A review

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    A wide range of local thermal ablative therapies have been developed in the treatment of non resectable hepatocellular carcinoma (HCC) in the last decade. Laser ablation (LA) and radiofrequency ablation (RFA) are the two most widely used of these. This article provides an up to date overview of the role of laser ablation in the local treatment of HCC. General principles, technique, image guidance and patient selection are discussed. A review of published data on treatment efficacy, long term outcome and complication rates of laser ablation is included and comparison with RFA made. The role of laser ablation in combination with transcatheter arterial chemoembolisation is also discussed.

  15. The role of cyclin E1 in hepatocellular carcinoma

    OpenAIRE

    Chan, Yan-yan; 陳茵茵

    2014-01-01

    Hepatocellular carcinoma (HCC) accounts for 70-85% of liver cancer, which is the sixth most common cancer in the world. Prognosis of HCC is dismal with little chance of complete recovery after diagnosis. It is of essence to discover the key molecules involved in the tumor progression. This could help earlier detection of HCC and establish targeted molecular therapies. Cyclin E1 (CCNE1) is a cyclin molecule responsible for the transition from G1 to S phase of the cell cycle and is often dysreg...

  16. Local recurrence of hepatocellular carcinoma after radiofrequency ablation

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    A 51-year-old Chinese male with a 20-year history of hepatitis B was diagnosed with hepatocellular carcinoma in the right anterior portion of the liver, sized 3.5 cm × 3.2 cm, and was treated with radiofrequency ablation (RFA) on December 18, 2001. The patient did not receive antiviral therapy for hepatitis B virus after RFA. The treated lesion reduced gradually and reached its minimum size of 1.7 cm × 1.5 cm seven years later on November 18, 2008. However computed tomography findings revealed that a recurr...

  17. Sustained treatment response of metastatic hepatocellular carcinoma with bevacizumab and sorafenib

    Institute of Scientific and Technical Information of China (English)

    Christina; Wich; Abbas; Agaimy; Deike; Strobel; Thaddaus; Till; Wissniowski; Arndt; Hartmann; Matthias; Ocker

    2010-01-01

    The overall survival for patients with advanced hepatocellular carcinoma(HCC)is still limited.Although the multi-kinase inhibitor sorafenib has recently been approved for this disease,response rates are still low and patients often face dose-limiting toxicities which lead to a reduction in prognosis and treatment success.We here report a patient with metastasized HCC who shows a sustained response for more than 30 mo to sorafenib therapy after failure of a first line therapy with gemcitabine,oxaliplatin and...

  18. Locoregional treatment for hepatocellular carcinoma:The best is yet to come

    Institute of Scientific and Technical Information of China (English)

    Naveen; Kalra; Pankaj; Gupta; Yogesh; Chawla; Niranjan; Khandelwal

    2015-01-01

    Hepatocellular carcinoma(HCC) is the sixth-most common type of cancer worldwide. The only definitive treatment modalities capable of achieving a cure are hepatic resection and hepatic transplantation. However, most patients are not candidates for these therapies. Overall, treatment options are driven by the stage of HCC. Early-stage disease is treated with ablative therapies, with radiofrequency ablation the ablative therapy of choice. Microwave ablation and irreversible electroporation are the other upcoming alternatives. Intermediate-stage disease is managed with transarterial chemoembolization(TACE), while advanced-stage disease is managed by sorafenib, with TACE and radioembolization as other alternatives.

  19. Anatomic pathology of hepatocellular carcinoma: histopathology using classic and new diagnostic tools.

    Science.gov (United States)

    Pittman, Meredith E; Brunt, Elizabeth M

    2015-05-01

    Hepatocellular carcinoma can be diagnosed on a needle biopsy of the liver; however, uncertainty may arise because of the inherent complexity of liver histology. This article aims to provide practicing pathologists with tools for the approach to mass-directed liver biopsies clinically concerning for hepatocellular carcinoma. The examination of routine hematoxylin-eosin stains and the use of ancillary histochemical and immunohistochemical stains are discussed. Sections reviewing liver carcinoma with biphenotypic differentiation and the challenge of dysplastic nodules are included.

  20. Spontaneous rupture of multifocal hepatocellular carcinoma: case report

    Directory of Open Access Journals (Sweden)

    Özen Ö

    2015-08-01

    Full Text Available Özkan Özen, Alptekin Tosun, Çiğdem Akgül Department of Radiology, Faculty of Medicine, Giresun University, Giresun, Turkey Abstract: Hemoperitoneum due to nontraumatic liver rupture is rare. The most common cause of nontraumatic rupture of the liver is hepatocellular carcinoma (HCC. The other causes of nontraumatic liver ruptures are peliosis hepatis, polyarteritis nodosa, systemic lupus erythematosus, preeclampsia, metastatic carcinoma, and other primary liver tumors. In this report, we present the computed tomography findings of spontaneous liver rupture in a 52-year-old male patient due to multifocal HCC, with the diagnosis proven by surgical specimen. Keywords: computed tomography, hemoperitoneum, liver, nontraumatic liver rupture

  1. Sorafenib combined with radiofrequency ablation in the treatment of a patient with renal cell carcinoma plus primary hepatocellular carcinoma.

    Science.gov (United States)

    Gang, Guo; Hongkai, Yu; Xu, Zhang

    2015-01-01

    The combination of renal cell carcinoma (RCC) and hepatocellular carcinoma (HCC) is extremely rare, and the prognosis for patients with these two cancers is poor. In the past decade, molecular targeted therapy and radiofrequency ablation (RFA) have emerged and these treatments are now playing an increasingly important role in the management of patients with advanced primary RCC and HCC. In this case report, a 72-year-old male patient diagnosed as having RCC invading the renal vein and grade I-II HCC was treated with RFA and sorafenib (400 mg twice daily). After 3 months of this combination treatment, an evaluation of his target lesions showed stable disease (SD), and progression-free survival (PFS) times were 28 months weeks for RCC and 16 months weeks for HCC. Overall survival (OS) was 40 weeks.

  2. 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.

  3. Infrequent microsatellite instability mutator phenotype in Chinese hepatocellular carcinomas

    Institute of Scientific and Technical Information of China (English)

    方丽; 房殿春; 汪荣泉; 杨仕明; 吴凯

    2003-01-01

    Objective:In order to elucidate the molecular mechanisms that might be responsible for hepatocarcinogenesis,we examined microsatellite instability(MSI),mismatch repair gene hMLH1 mutation and methylation in hepatocellular carcinoma.Methods:Fifty-two cases of surgically resected sporadic hepatocellular carcinoma(HCC)were studied.hMLH1 mutation was examined by two-dimensional electrophoresis and DNA sequencing; hMLH1 methylation was determined by methylation-specific PCR(MSP); and MSI at BAT26 was analyzed by PCR-based methods.Results:MSI at BAT26 was found in 3 of 52 cases(5.8%)of the tumors analyzed.No hMLH1 mutation or hypermethylation was found in these 52 cancerous tissues.No correlation existed between MSI and clinico-pathological characteristics of the patients.Conclusion:Our results suggest that MSI at BAT26 is rarely associated with carcinogenesis of chinese HCC.The genesis of sporadic HCC may occur in an alternative pathway that is probably different from MSI pathway.

  4. Targeting FGFR4 inhibits hepatocellular carcinoma in preclinical mouse models.

    Directory of Open Access Journals (Sweden)

    Dorothy M French

    Full Text Available The fibroblast growth factor (FGF-FGF receptor (FGFR signaling system plays critical roles in a variety of normal developmental and physiological processes. It is also well documented that dysregulation of FGF-FGFR signaling may have important roles in tumor development and progression. The FGFR4-FGF19 signaling axis has been implicated in the development of hepatocellular carcinomas (HCCs in mice, and potentially in humans. In this study, we demonstrate that FGFR4 is required for hepatocarcinogenesis; the progeny of FGF19 transgenic mice, which have previously been shown to develop HCCs, bred with FGFR4 knockout mice fail to develop liver tumors. To further test the importance of FGFR4 in HCC, we developed a blocking anti-FGFR4 monoclonal antibody (LD1. LD1 inhibited: 1 FGF1 and FGF19 binding to FGFR4, 2 FGFR4-mediated signaling, colony formation, and proliferation in vitro, and 3 tumor growth in a preclinical model of liver cancer in vivo. Finally, we show that FGFR4 expression is elevated in several types of cancer, including liver cancer, as compared to normal tissues. These findings suggest a modulatory role for FGFR4 in the development and progression of hepatocellular carcinoma and that FGFR4 may be an important and novel therapeutic target in treating this disease.

  5. Diphenyl difluoroketone: a potent chemotherapy candidate for human hepatocellular carcinoma.

    Directory of Open Access Journals (Sweden)

    Yingjian Liang

    Full Text Available Diphenyl difluoroketone (EF24, a molecule having structural similarity to curcumin, was recently reported to inhibit proliferation of various cancer cells significantly. Here we try to determine the effect and mechanism of EF24 on hepatocellular carcinoma. 2 µM EF24 was found to inhibit the proliferation of PLC/PRF/5, Hep3B, HepG2, SK-HEP-1 and Huh 7 cell lines. However, even 8 µM EF24 treatment did not affect the proliferation of normal liver LO2 cells. Accordingly, 20 mg/kg/d EF24 inhibited the growth of the tumor xenografts conspicuously while causing no apparent change in liver, spleen or body weight. In addition, significant apoptosis and G(2/M phase cell cycle arrest were found using flow cytometry. Besides, caspases and PARP activation and features typical of apoptosis including fragmented nuclei with condensed chromatin were also observed. Furthermore, the mechanism was targeted at the reduction of nuclear factor kappa b (NF-κB pathway and the NF-κB-regulated gene products Bcl-2, COX-2, Cyclin B1. Our study has offered a strategy that EF24 being a therapeutic agent for hepatocellular carcinoma.

  6. Hepatitis B virus infection and the risk of hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Ya-Jun Tan

    2011-01-01

    Epidemiological studies have provided overwhelming evidence for a causal role of chronic hepatitis B virus (HBV) infection in the development of hepatocellular carcinoma (HCC). However, the pathogenesis of HBV infection and carcinogenesis of HBV-associated HCC are still elusive. This review will summarize the current knowledge on the mechanisms involved in HBV-related liver carcinogenesis. The role of HBV in tumor formation appears to be complex, and may involve both direct and indirect mechanisms. Integration of HBV DNA into the host genome occurs at early steps of clonal tumor expansion, and it has been shown to enhance the host chromosomal instability, leading to large inverted duplications, deletions and chromosomal translocations. It has been shown that the rate of chromosomal alterations is increased significantly in HBV-related tumors. Prolonged expression of the viral regulatory HBV x protein may contribute to regulating cellular transcription, protein degradation, proliferation, and apoptotic signaling pathways, and it plays a critical role in the development of hepatocellular carcinoma.

  7. Targeting FGFR4 inhibits hepatocellular carcinoma in preclinical mouse models.

    Science.gov (United States)

    French, Dorothy M; Lin, Benjamin C; Wang, Manping; Adams, Camellia; Shek, Theresa; Hötzel, Kathy; Bolon, Brad; Ferrando, Ronald; Blackmore, Craig; Schroeder, Kurt; Rodriguez, Luis A; Hristopoulos, Maria; Venook, Rayna; Ashkenazi, Avi; Desnoyers, Luc R

    2012-01-01

    The fibroblast growth factor (FGF)-FGF receptor (FGFR) signaling system plays critical roles in a variety of normal developmental and physiological processes. It is also well documented that dysregulation of FGF-FGFR signaling may have important roles in tumor development and progression. The FGFR4-FGF19 signaling axis has been implicated in the development of hepatocellular carcinomas (HCCs) in mice, and potentially in humans. In this study, we demonstrate that FGFR4 is required for hepatocarcinogenesis; the progeny of FGF19 transgenic mice, which have previously been shown to develop HCCs, bred with FGFR4 knockout mice fail to develop liver tumors. To further test the importance of FGFR4 in HCC, we developed a blocking anti-FGFR4 monoclonal antibody (LD1). LD1 inhibited: 1) FGF1 and FGF19 binding to FGFR4, 2) FGFR4-mediated signaling, colony formation, and proliferation in vitro, and 3) tumor growth in a preclinical model of liver cancer in vivo. Finally, we show that FGFR4 expression is elevated in several types of cancer, including liver cancer, as compared to normal tissues. These findings suggest a modulatory role for FGFR4 in the development and progression of hepatocellular carcinoma and that FGFR4 may be an important and novel therapeutic target in treating this disease.

  8. 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.

  9. Histone deacetylase inhibitors for treatment of hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Danila CORADINI; Annalisa SPERANZA

    2005-01-01

    Hepatocellular carcinoma (HCC) is one of the most common cancers in the world.Surgical resection has been considered the optimal treatment approach, but only a small proportion of patients are suitable candidates for surgery, and the relapse rate is high. Approaches to prevent recurrence, including chemoemboliza-tion before and adjuvant therapy after surgery, have proven to have a limited benefit;liver transplantation is successful in treating limited-stage HCC because only a minority of patients qualify for transplantation. Therefore, new therapeutic strategies are urgently needed. Because in addition to the classical genetic mechanisms of deletion or inactivating point mutations, epigenetic alterations, such as hyperacetylation of the chromatin-associated histones (responsible for gene silencing), are believed to be involved in the development and progression of HCC, novel compounds endowed with a histone deacetylase (HDAC) inhibitory activity are an attractive therapeutic approach. In particular, pre-clinical results obtained using HA-But, an HDAC inhibitor in which butyric acid residues are esterified to a hyaluronic acid backbone and characterized by a high affinity for the membrane receptor CD44, indicated that this class of compounds may represent a promising approach for hepatocellular carcinoma treatment.

  10. Telomerase-specific oncolytic virotherapy for human hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    AIM: To evaluate the therapeutic efficiency of replicative adenovirus CNHK300 targeted in telomerase-positive hepatocellular carcinoma. METHODS: CNHK300, ONYX-015 (55 kDa protein deleted adenovirus) and wtAd5 (wild type adenovirus 5) were compared, and virus proliferation assay, cell viability assay, Western blot and fluorescence microscopy were used to evaluate the proliferation and cytolysis selectivity of CNHK300.RESULTS:The replicative multiples in Hep3B and HepG after 48 h of CNHK300 proliferation were 40625and 65326 fold, respectively, similar to that of wtAd5..However, CNHK300 exhibited attenuated replicative ability in normal fibroblast cell line BJ.CNHK300 could lyse hepatocellular carcinoma cells at a low multiplicity of infection (MOI),but could not affect growth of normal cells even at a high MOI.CONCLUSION:CNHK300 is a cancer-selective replication-competent adenovirus which can cause oncolysis of liver cancer cells as well as wtAd5 (wild type adenovirus 5),but had severely attenuated replicative and cytolytic ability in normal cells. This novel strategy of cancer treatment offers a promising treatment platform.

  11. Nuclear and mitochondrial DNA microsatellite instability in hepatocellular carcinoma in Chinese

    Institute of Scientific and Technical Information of China (English)

    Dian-Chun Fang; Li Fang; Rong-Quan Wang; Shi-Ming Yang

    2004-01-01

    AIM: To study the nuclear microsatellite instability (nMSI)at BAT26 and mitochondral microsalellite instability (mtMSI)in the occurrence and development of hepatocellular carcinoma and the relationship between nMSI and mtMSI.METHODS: nMSI was observed with PCR and mtMSI with PCR-SSCP in 52 cases of hepatocellular carcinoma.RESULTS: mtMSI was detected in 11 out of the 52 cases of hepatocellular carcinoma (21.2%). Among the 11 cases of hepatocellular carcinoma with mtMSI, 7 occured in one locus and 4 in 2 loci. The frequency of mtMSI in the 52 cases of hepatocellular careinoma showed no correlation to sex, age,infection of hepatitis B, liver cirrhosis as well as positive AFP of the patients (P>0.05). In addition, nMSI was detected in 3 out of 52 cases of hepatocellular carcinoma (5.8%) and there was no correlation of the incidence of mtMSI to that CONCLUSION: mtMSI may be involved in the coccurrence and development of hepatocellular carcinoma and it is independent of nMSI.

  12. WJH 6th Anniversary Special Issues(1): Management of hepatocellular carcinoma Management of “very early” hepatocellular carcinoma on cirrhotic patients

    Institute of Scientific and Technical Information of China (English)

    Gonzalo; Sapisochin; Elena; Fernandez; de; Sevilla; Juan; Echeverri; Ramón; Charco

    2014-01-01

    Due to the advances in screening of cirrhotic patients, hepatocellular carcinoma(HCC) is being diagnosed in earlier stages. For this reason the number of patients diagnosed of very early HCC(single tumors ≤ 2 cm) is continuously increasing. Once a patient has been diagnosed with this condition, treatment strategies include liver resection, local therapies or liver transplantation. The decision on which therapy should the patient undergo depends on the general patients performance status and liver disease. Anyway, even in patients with similar conditions, the best treatment offer is debatable. In this review we analyze the state of the art on the management of very early HCC on cirrhotic patients to address the best treatment strategy for this patient population.

  13. Nal-IRI With 5-fluorouracil (5-FU) and Leucovorin or Gemcitabine Plus Cisplatin in Advanced Biliary-tract Cancer

    Science.gov (United States)

    2017-02-03

    Adenocarcinoma Metastatic; Biliary Tract Cancer; Adenocarcinoma of the Biliary Tract; Adenocarinoma Locally Advanced; Non-Resectable Hepatocellular Carcinoma; Intrahepatic Bile Duct Carcinoma; Extrahepatic Bile Duct Carcinoma

  14. Combined hepatocellular and cholangiocellular carcinoma presenting with radiological characteristics of focal nodular hyperplasia

    Institute of Scientific and Technical Information of China (English)

    Inneke Willekens; Anne Hoorens; Caroline Geers; Bart Op de Beeck; Frederik Vandenbroucke; Johan de Mey

    2009-01-01

    Combined hepatocellular and cholangiocellular carcinoma (cHCC-CC) is a rare tumor type containing unequivocal elements of both hepatocellular carcinoma and cholangiocarcinoma that are intimately mixed.Although these tumors are usually considered to be more related to hepatocellular carcinoma than to cholangiocarcinoma, they sometimes, in contrast to hepatocellular carcinoma, contain a significant amount of fibrous stroma. This might in some cases explain atypical radiological features. We report a case of a cHCC-CC in a 47-year-old female that resembled focal nodular hyperplasia on Magnetic Resonance Imaging.Correlation of imaging and serum levels of α-fetoprotein and CA19.9 can help to make the correct diagnosis preoperatively.

  15. Hemodynamic study of hepatocellular car-cinoma nodules by multi-slice spiral computed tomographic perfusion

    Institute of Scientific and Technical Information of China (English)

    马国林

    2013-01-01

    Objective To analyze the 64-slice computed tomographic(CT) perfusion parameters of hepatocellular carcinoma(HCC) nodule so as to assess the diagnostic value of hemodynamic changes of HCC nodule by this perfusion

  16. Expression and survival prediction of microRNA-155 in hepatocellular carcinoma after liver transplantation

    Institute of Scientific and Technical Information of China (English)

    韩中博

    2013-01-01

    Objective To explore the expression of microRNA-155in hepatocellular carcinoma(HCC)and its contribution to recurrence and prognosis of HCC after liver transplantation(LT).Methods The expression levels

  17. Expression and survival prediction of microRNA-155 in hepatocellular carcinoma after liver transplantation

    Institute of Scientific and Technical Information of China (English)

    韩中博

    2013-01-01

    Objective To explore the expression of microRNA-155in hepatocellular carcinoma(HCC)and its contribution to recurrence and prognosis of HCC after liver transplantation(LT).Methods The expression levels of

  18. Cure is Possible with Salvage Surgery following Downstaging of Hepatocellular Carcinoma

    Institute of Scientific and Technical Information of China (English)

    LauW.Y.

    2004-01-01

    Combined modality non-surgical treatment can effectively downstage unresectable hepatocellular carcinoma in some patients to become resectable. Salvage surgery following tumour-downstaging can be curative in these patients.

  19. Interaction of DNA repair gene polymorphisms and aflatoxin B1 in the risk of hepatocellular carcinoma

    OpenAIRE

    2014-01-01

    Aflatoxin B1 (AFB1) is an important environmental carcinogen and can induce DNA damage and involve in the carcinogenesis of hepatocellular carcinoma (HCC). The deficiency of DNA repair capacity related to the polymorphisms of DNA repair genes might play a central role in the process of HCC tumorigenesis. However, the interaction of DNA repair gene polymorphisms and AFB1 in the risk of hepatocellular carcinoma has not been elucidated. In this study, we investigated whether six polymorphisms (i...

  20. A case of spontaneous regression of hepatocellular carcinoma after ultrasound guided liver biopsy

    Energy Technology Data Exchange (ETDEWEB)

    Jo, Jeong Hyun [Dept. of Radiology, Dong A University Hospital, Dong A University College of Medicine, Busan (Korea, Republic of)

    2014-10-15

    Spontaneous regression of hepatocellular carcinoma after liver biopsy has not been reported in the English literature. Herein, we present a case of partial spontaneous regression of hepatocellular carcinoma after ultrasound guided liver biopsy in a 64-year-old female. During 28 months, the tumor, which had been shrinking, showed no interval change. However, after 28 months, tumor showed regrowth, which led to a segmentectomy.

  1. Nonlinear tumor evolution from dysplastic nodules to hepatocellular carcinoma.

    Science.gov (United States)

    Joung, Je-Gun; Ha, Sang Yun; Bae, Joon Seol; Nam, Jae-Yong; Gwak, Geum-Youn; Lee, Hae-Ock; Son, Dae-Soon; Park, Cheol-Keun; Park, Woong-Yang

    2017-01-10

    Dysplastic nodules are premalignant neoplastic nodules found in explanted livers with cirrhosis. Genetic signatures of premalignant dysplastic nodules (DNs) with concurrent hepatocellular carcinoma (HCC) may provide an insight in the molecular evolution of hepatocellular carcinogenesis. We analyzed four patients with multifocal nodular lesions and cirrhotic background by whole-exome sequencing (WES). The genomic profiles of somatic single nucleotide variations (SNV) and copy number variations (CNV) in DNs were compared to those of HCCs. The number and variant allele frequency of somatic SNVs of DNs and HCCs in each patient was identical along the progression of pathological grade. The somatic SNVs in DNs showed little conservation in HCC. Additionally, CNVs showed no conservation. Phylogenetic analysis based on SNVs and copy number profiles indicated a nonlinear segregation pattern, implying independent development of DNs and HCC in each patient. Thus, somatic mutations in DNs may be developed separately from other malignant nodules in the same liver, suggesting a nonlinear model for hepatocarcinogenesis from DNs to HCC.

  2. Surgical Intervention for Hepatocellular Carcinoma with Bile Buct Thrombi

    Institute of Scientific and Technical Information of China (English)

    PENGShuyou; LIUYingbin; WANGJianwei; CAIXiujun; MOUYiping; WUYulian; FangHeqing; LIJiangtao; WANGXinbao; XUBin; LIHaijun

    2003-01-01

    Objective: To summarize the experience of surgical intervention for hepatocellular carcinoma(HCC) with bile duct thrombi (BDT), and to evaluate the influence on prognosis. Methods: From 1994 to 2002, 15 patients with HCC and BDT who underwent surgical intervention were retrospectively analyzed.Results: The operative procedures included hepatectomy with removel of BDT (n=7), hepatectomy com-bined with extrahepatic bile duct resection (n=4), thrombectomy through choledochotomy (n=3), piggy back orthotopic liver transplantation (n=1). The 1-and 3-year survival rates were 73.3% and 40%, respec-tively. Two patients survived over 5 years. Conclusion: Surgical intervention was effective for patients with HCC and BDT. Operation for recurrent lesion can prolong survival period. Liver transplantation is a new treatment worthy of further investigation.

  3. 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.

  4. Radioembolization for hepatocellular carcinoma using TheraSphere®

    Directory of Open Access Journals (Sweden)

    Safiyya Mohamed Ali

    2011-01-01

    Full Text Available Background/Aim: 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. Results: 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. Conclusions: 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.

  5. Improving outcomes for patients receiving transarterial chemoembolization for hepatocellular carcinoma.

    Science.gov (United States)

    McCurdy, Heather M

    2013-01-01

    Hepatocellular carcinoma is a cancer with increasing incidence in the veteran population. This type of cancer can be treated with transarterial chemoembolization, an invasive procedure performed by specially trained interventional radiologists. The most common serious complications are liver failure, sepsis secondary to ischemic cholecystitis or liver abscess, gastrointestinal bleeding, and death. However, nursing staff and physicians often have little or no experience in caring for patients in the hospital who have had this procedure. Patient safety can be threatened by this lack of knowledge. Sources of threat to patient safety are described by the Institute of Medicine as falling into 4 categories: management, workforce, work processes, and organizational culture. To promote patient safety, defenses need to be deployed to address each category. In this article, the author provides a case example, describes threats to the patient's safety, and describes a plan to improve the care of all patients undergoing this procedure.

  6. Next big threat for Pakistan Hepatocellular Carcinoma (HCC).

    Science.gov (United States)

    Parkash, Om; Hamid, Saeed

    2016-06-01

    In our country, world hepatitis day (28th May 2013) was observed as a liver cancer day to draw global attention on the global health menace caused by Hepatocellular carcinoma (HCC). This is the right time to write a review article to apprise the nation of this growing burden of HCC caused most commonly by viruses in our country. Pakistan is also recognized as one of the countries of the world where hepatitis C virus (HCV) is endemic. Recent large national surveys suggest an overall HCV prevalence of 4.8% and that of HBV as 2.5%. There are however communities where the sero-prevalence of HCV can be as high as 23%. No wonder that chronic liver disease is the fifth most common reason for morbidity and mortality in the country and Pakistan has been perhaps accurately called a "cirrhotic state". Hence majority of such patients are at risk of developing HCC.

  7. Epigenetic Regulation in Hepatocellular Carcinoma Requires Long Noncoding RNAs

    Directory of Open Access Journals (Sweden)

    Laura Amicone

    2015-01-01

    Full Text Available Recent evidence has proven the relevance of epigenetic changes in the development of hepatocellular carcinoma (HCC, the major adult liver malignancy. Moreover, HCC onset and progression correlate with the deregulation of several long noncoding RNAs (lncRNAs, exhibiting great biological significance. As discussed in this review, many of these transcripts are able to specifically act as tumor suppressors or oncogenes by means of their role as molecular platforms. Indeed, these lncRNAs are able to bind and recruit epigenetic modifiers on specific genomic loci, ultimately resulting in regulation of the gene expression relevant in cancer development. The evidence presented in this review highlights that lncRNAs-mediated epigenetic regulation should be taken into account for potential targeted therapeutic approaches.

  8. Malignant fibrous histiocytoma presenting as hemoperitoneum mimicking hepatocellular carcinoma rupture

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Malignant fibrous histiocytoma (MFH) is a pleomorphic mesenchynal sarcoma. It is uncommonly arises primarily from the intra-peritoneal cavity. Primary peritoneal MFH with tumor bleeding and rupture is rare. We describe the imaging features of a 70-year-old patient presenting with ruptured hemorrhagic peritoneal MFH at subhepatic area, accompanied by massive hemoperitoneum,mimicking a ruptured pedunculated hepatocellular carcinoma. Computed tomography (CT) revealed a large heterogeneous enhanced subhepatic mass with adjacent liver, gallbladder and colon invasion. Tumor hemorrhage and rupture complicated with peritoneal seeding and massive bloody ascites were also detected.Angiography showed a hypervascular tumor fed by enlarged right hepatic arteries, cystic artery and omental branches of gastroepiploic artery. The patient underwent laparotomy for tumor resection, but the tumor recurred one month after operation. To our knowledge, the CT appearance of ruptured intraperitoneal MFH complicated by hemoperitoneum has not been previously described.

  9. 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.

  10. Strategies to increase the resectability of hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Wong; Hoi; She; Kenneth; SH; Chok

    2015-01-01

    Hepatocellular carcinoma(HCC) is best treated by liver transplantation, but the applicability of transplantation is greatly limited. Tumor resection in partial hepatectomy is hence resorted to. However, in most parts of the world, only 20%-30% of HCCs are resectable. The main reason for such a low resectability is a future liver remnant too small to be sufficient for the patient. To allow more HCC patients to undergo curative hepatectomy, a variety of ways have been developed to increase the resectability of HCC, mainly ways to increase the future liver remnants in patients through hypertrophy. They include portal vein embolization, sequential transarterial chemoembolization and portal vein embolization, staged hepatectomy, two-staged hepatectomy with portal vein ligation, and Associating Liver Partition and Portal Vein Ligation in Staged Hepatectomy. Herein we review, describe and evaluate these different ways, ways that can be life-saving.

  11. 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.

  12. MRI Features of Hepatocellular Carcinoma Related to Biologic Behavior

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    Cho, Eun-Suk [Department of Radiology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul 135-720 (Korea, Republic of); Choi, Jin-Young [Department of Radiology, Severance Hospital, Yonsei University College of Medicine, Seoul 120-752 (Korea, Republic of)

    2015-11-01

    Imaging studies including magnetic resonance imaging (MRI) play a crucial role in the diagnosis and staging of hepatocellular carcinoma (HCC). Several recent studies reveal a large number of MRI features related to the prognosis of HCC. In this review, we discuss various MRI features of HCC and their implications for the diagnosis and prognosis as imaging biomarkers. As a whole, the favorable MRI findings of HCC are small size, encapsulation, intralesional fat, high apparent diffusion coefficient (ADC) value, and smooth margins or hyperintensity on the hepatobiliary phase of gadoxetic acid-enhanced MRI. Unfavorable findings include large size, multifocality, low ADC value, non-smooth margins or hypointensity on hepatobiliary phase images. MRI findings are potential imaging biomarkers in patients with HCC.

  13. 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.

  14. Metastatic hepatocellular carcinoma of the external auditory canal

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    This report describes a rare case of metastatic hepatocellular carcinoma (HCC) presenting a huge mass in the left external auditory canal (EAC). The patient was a 55-year-old man with hepatitis B virus-related HCC.He presented to our department with a three-month history of increasing left otalgia, and hearing loss with recent fresh aural bleeding. Histopathologic examination indicated that the tumor was secondary to HCC. Although external irradiation was not effective, the tumor was treated with surgical debulking and high dose rate 192 Ir remote afterloading system (RALS) for postoperative intracavitary irradiation. A review of the literature revealed only five other cases of HCC metastasis to the temporal bone, all of which mainly metastasteed in the internal acoustic meatus. The present case is the first report of HCC metastasis to the EAC.

  15. Detection of epigenetic aberrations in the development of hepatocellular carcinoma.

    Science.gov (United States)

    Zhang, Yujing

    2015-01-01

    Hepatocellular carcinoma (HCC) is the third most common cause of cancer death worldwide. Hepatocarcinogenesis is a complex, multistep process. It is now recognized that HCC is a both genetic and epigenetic disease; genetic and epigenetic components cooperate at all stages of hepatocarcinogenesis. Epigenetic changes involve aberrant DNA methylation, posttranslational histone modifications and aberrant expression of microRNAs all of which can affect the expression of oncogenes, tumor suppressor genes and other tumor-related genes and alter the pathways in cancer development. Several risk factors for HCC, including hepatitis B and C virus infections and exposure to the chemical carcinogen aflatoxin B1 have been found to influence epigenetic changes. Their interactions could play an important role in the initiation and progression of HCC. Discovery and detection of biomarkers for epigenetic changes is a promising area for early diagnosis and risk prediction of HCC.

  16. Interplay of genetic and epigenetic alterations in hepatocellular carcinoma.

    Science.gov (United States)

    Lee, Sun-Min; Kim-Ha, Jeongsil; Choi, Won-Young; Lee, Jungwoo; Kim, Dawon; Lee, Jinyoung; Choi, Eunji; Kim, Young-Joon

    2016-07-01

    Genetic and epigenetic alterations play prominent roles in hepatocarcinogenesis and their appearance varies depending on etiological factors, race and tumor progression. Intriguingly, distinct patterns of these genetic and epigenetic mutations are coupled not only to affect each other, but to trigger different types of tumorigenesis. The patterns and frequencies of somatic variations vary depending on the nature of the surrounding chromatin. On the other hand, epigenetic alterations often induce genomic instability prone to mutation. Therefore, genetic mutations and epigenetic alterations in hepatocellular carcinoma appear to be inseparable factors that accelerate tumorigenesis synergistically. We have summarized recent findings on genetic and epigenetic modifications, their influences on each other's alterations and putative roles in liver tumorigenesis.

  17. Towards the optimization of management of hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Xi Feng; Madhava Pai; Malkhaz Mizandari; Tinatin Chikovani; Duncan Spalding; Long Jiao; Nagy Habib

    2011-01-01

    Hepatocellular carcinoma (HCC) is the fifth most common neoplasm in the world,closely correlated with viral hepatitis and liver cirrhosis.The vast majority of HCC patients present at a late stage and are unsuitable for surgery due to limited liver functional reserve.Tumors can involve major vessels or hilar structures,necessitating major liver resection and/or rendering liver resection unfeasible.A series of new technologies have been developed to optimise HCC management.Stem cell therapy improves impaired liver functional reserve prior to liver resection,Intravascular radiofrequency ablation recanalises the portal vein invaded by tumour thrombus and endobiliary radiofrequency ablation restores and extends biliary patency of the bile duct invaded by malignancy.Laparoscopic radiofrequency assisted liver resection minimizes blood loss and avoids liver warm ischemia,while increasing parenchymal sparing.These benefits combined maximize the safety of liver resection.

  18. Autoantibodies against tumor-associated antigens fordetection of hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Hepatocellular carcinoma (HCC) is one of the mostcommon tumors worldwide. The survival rate after theonset of symptoms is generally less than one year forthe late presentation of HCC, and reliable tools for earlydiagnosis are lacking. Therefore, novel biomarkers forthe early detection of HCC are urgently required. Recentstudies show that the abnormal release of proteins bytumor cells can elicit humoral immune responses toself-antigens called tumor-associated antigens (TAAs).The corresponding autoantibodies can be detectedbefore the clinical diagnosis of cancer. Therefore, thereis growing interest in using serum autoantibodies ascancer biomarkers. In this review, we focus on theadvances in research on autoantibodies against TAAs asserum biomarker for detection of HCC, the mechanismof the production of TAAs, and the association ofautoantibodies with patients' clinical characteristics.

  19. Proteomics for the early diagnosis and treatment of hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Autor OJS

    2007-02-01

    Full Text Available

    The incidence of primary cancer has been increasing globally and now-a-days it constitutes the 5th most frequent cancer of humans representing around 5% of all cancers worldwide. Chronic HBV infection assumes greater significance because of its reported association with cirrhosis, and more ominously hepatocellular carcinoma or HCC. Hepatitis B infection constitutes a major global problem with nearly 400 million infected individuals. It contributes to a significant degree of morbidity on account of the associated chronicity that develops in 5-10% of infected adults and more than 90% of infected neonates. Globally, around one million people suffering from HBVrelated chronic heptatitis and HCC die per year. Despite the availability of an effective prophylactic vaccine against hepatitis B for over 20 years, effective treatment of the chronic disease and associated HCC remains elusive. Therefore, identification of the cellular mediators and effectors of HCC is an important medical objective for developing new diagnostic tools and therapeutic strategies against it. Molecular biomarkers hold great promise for refining our ability to establish early diagnosis and prognosis for HCC, and to predict response to therapy. Proteomics is a rapidly expanding discipline that is expected to change the way in which disease can be diagnosed, treated and monitored in the near future. The proteomic analysis of serum and tumors should allow accurate prediction of what is happening at the protein level in a cancer cell or a body fluid proteome. It is the hope that, by deciphering the alterations in serum and liver proteome, biomarkers and patterns of biomarkers will be found that should be helpful in improving early detection, diagnosis and treatment monitoring of HCC. In the last few years, HCC has been extensively investigated using different proteomic approaches on HCC cell lines

  20. The new research on tumor suppressor gene in hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    JI Yu-bin; YANG Hai-fan; YU Lei; PANG lin-lin; LI Hai-jiao; LIU Guang-da

    2008-01-01

    Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death in the world. The carcinogenesis of HCC is multifactorial, multifunctional and multistage. Tumor suppressor gene therapy is one of the strategies, it is mainly used to make use of tumor suppressor gene groups which can inhibit the cell growth, to prevent the expression of oncogenes or to resume the function of anti-oncogenes. But so far, there is not a particular gene to be a main tumor suppressor gene in HCC. Therefore, it is necessary to study on the new anti-oncogenes to explain pathogenesis of liver cancer and seek for the newly effective target to carry on liver cancer gene therapy. PTEN (phosphatase and tensin homolog deleted on chromosome ten) was discovered as a tumor suppressor gene. It functions as a protein tyrosine phosphatase and as a lipid phosphatase. As a lipid phosphatase, PTEN antagonizes PI3K/Akt signaling by dephosphorylating the D3 position of the inositol ring of phosphatidylinositol 3, 4, 5-trisphosphate(PIP3), to generate phosphatidylinositol-4, 5,- biphosphate(PIP2). On the other hand, as a protein tyrosine phosphatase, PTEN can dephosphorylate itself, focal adhesion kinase (FAK) and the platelet derived growth factor receptor, involves in the migration, adhension of cells. Many researches have been testified that there is a higher frequency of negative expression of PTEN protein in hepatocellular carcinoma, the negative correlation between expression of PTEN gene and differential grade, clinic stage of HCC indicated that in activation of PTEN gene maybe a late incidence in the development of hepatocellular carcinoma and may play an important role in the genesis and development of some hepatocellular carcinoma. KLF6, a member of Krupple-like gene family, a ubiquitously expressed zinc finger transcription factor, has an important role in regulating cell growth and differentiation. Several experiments have been proved that the genetic events of tumor

  1. Management before hepatectomy for hepatocellular carcinoma with cirrhosis

    Institute of Scientific and Technical Information of China (English)

    Hisashi; Nakayama; Tadatoshi; Takayama

    2015-01-01

    The global distribution of hepatocellular carcinoma(HCC) varies markedly among regions, and patients in East Asia and Central Africa account for about 80% of all cases. The risk factors are hepatitis B, hepatitis C, alcohol, and etc. The risk of carcinogenesis further increases with progression to hepatic cirrhosis in all liver disorders. Radical treatment of HCC by liver resection without causing liver failure has been established as a safe approach through selection of an appropriate range of resection of the damaged liver. This background indicates that both evaluation of hepatic functional reserve and measures against concomitant diseases such as thrombocytopenia accompanying portal hypertension, prevention of rupture of esophageal varices, reliable control of ascites, and improvement of hypoalbuminemia are important issues in liver resection in patients with hepatic cirrhosis. We review the latest information on perioperative management of liver resection in HCC patients with hepatic cirrhosis.

  2. Radiotherapy for multiple brain metastases from hepatocellular carcinomas

    Institute of Scientific and Technical Information of China (English)

    Nobuyuki Toshikuni; Kazuhiko Morii; Michinori Yamamoto

    2007-01-01

    A 78-year-old man with liver cirrhosis was found to have multiple hepatocellular carcinomas (HCCs)and underwent 3 sessions of transcatheter arterial chemoembolization. Fourteen months after diagnosis,the patient presented with left hemiparesis. Contrastenhanced magnetic resonance imaging showed multiple metastases with ring-shaped enhancement in the cerebrum and cerebellum. There were no metastases to other organs. The metastatic lesions almost completely disappeared after whole-brain radiotherapy with a total dose of 50 Gy. Neurologic symptoms decreased,and the patient's quality of life improved. The patient underwent 2 more sessions of transcatheter arterial chemoembolization. Twelve months after the diagnosis of brain metastasis, the patient remains alive. The present case indicates that radiotherapy can improve quality of life and prolong survival in some patients with brain metastases from HCCs.

  3. Dermatomyositis associated with hepatitis B virus-related hepatocellular carcinoma.

    Science.gov (United States)

    Yang, Suh Yoon; Cha, Bong Ki; Kim, Gihyeon; Lee, Hyun Woong; Kim, Jae Gyu; Chang, Sae Kyung; Kim, Hyung Joon

    2014-03-01

    Dermatomyositis is an idiopathic inflammatory myopathy with typical cutaneous manifestations. It has been proposed that dermatomyositis may be caused by autoimmune responses to viral infections. Previous studies have shown an association between dermatomyositis and malignant tumors such as ovarian cancer, lung cancer, and colorectal cancer. However, a chronic hepatitis B virus (HBV) infection associated with dermatomyositis and hepatocellular carcinoma (HCC) has been very rarely reported. Here, we report a rare case of dermatomyositis coinciding with HBV-associated HCC. A 55-year-old male was confirmed to have HCC and dermatomyositis based on proximal muscle weakness, typical skin manifestations, elevated muscle enzyme levels, and muscle biopsy findings. This case suggests that HCC and/or a chronic HBV infection may be factors in the pathogenesis of dermatomyositis through a paraneoplastic mechanism.

  4. Worse or better?-Cirrhosis with hepatocellular carcinoma.

    Science.gov (United States)

    Xue, Ran; Meng, Qinghua; Li, Juan; Feng, Jiliang; Shi, Hanping

    2016-12-01

    Hepatocellular carcinoma (HCC) accounts for about 90% of all malignant tumors of liver, ranking fifth in the worldwide incidence of malignant tumors and the third in fatality. More and more evidences suggest that cancer is a metabolic-related disease. From the analysis of recent clinical research data, we found that as the severity of the cirrhosis aggravated, patients with HCC and end-stage liver cirrhosis had a flat energy metabolism which was better than it in patients with simple end-stage liver cirrhosis. Based on these clinical phenomenon, the major aim of this study is to present a new hypothesis: "compensated liver function mechanism" for patients with HCC and liver cirrhosis, cancer cells may play a role to compensate liver function. In this study, we elaborated relevant content about this novel standpoint combined with tumor energy metabolism reprogramming mechanism and tumor cell origin as well as cell exchange mechanism.

  5. 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

  6. Rapid progression of hepatocellular carcinoma after Radiofrequency Ablation

    Institute of Scientific and Technical Information of China (English)

    Andrea Ruzzenente; Giovanni de Manzoni; Matteo Molfetta; Silvia Pachera; Bruno Genco; Matteo Donataccio; Alfredo Guglielmi

    2004-01-01

    AIM: To report the results of radiofrequency ablation (RFA)of hepatocellular carcinoma (HCC) in cirrhotic patients and to describe the treatment related complications (mainly the rapid intrahepatic neoplastic progression).METHODS: Eighty-seven consecutive cirrhotic patients with 104 HCC (mean diameter 3.9 cm, 1.3 SD) were submitted to RFA between January 1998 and June 2003. In all cases RFA was performed with percutaneous approach under ultrasound guidance using expandable electrode needles.Treatment efficacy (necrosis and recurrence) was estimated with dual phase computed tomography (CT) and alphafetoprotein (AFP) level.RESULTS: Complete necrosis rate after single or multiple treatment was 100%, 87.7% and 57.1% in HCC smaller than 3 cm, between 3 and 5 cm and larger than 5 cm respectively (P=0.02). Seventeen lesions of 88(19.3%)developed local recurrence after complete necrosis during a mean follow up of 19.2 mo. There were no treatment-related deaths in 130 procedures and major complications occurred in 8 patients (6.1%). In 4 patients, although complete local necrosis was achieved, we observed rapid intrahepatic neoplastic progression after treatment. Risk factors for rapid neoplastic progression were high preoperative AFP values and location of the tumor near segmental portal branches.CONCLUSION: RFA is an effective treatment for hepatocellular carcinoma smaller than 5 cm with complete necrosis in more than 80% of lesions. Patients with elevated AFP levels and tumors located near the main portal branch are at risk for rapid neoplastic progression after RFA. Further studies are necessary to evaluate the incidence and pathogenesis of this underestimated complication.

  7. 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

  8. 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.

  9. Sorafenib and radiotherapy association for hepatocellular carcinoma; Sorafenib et radiotherapie dans le carcinome hepatocellulaire

    Energy Technology Data Exchange (ETDEWEB)

    Girard, N. [Service de pneumologie, hopital Louis-Pradel, hospices Civils de Lyon, 28, avenue du Doyen-Jean-Lepine, 69500 Bron (France); UMR 754, universite Claude-Bernard Lyon 1, 43, boulevard du 11-novembre-1918, 69622 Villeurbanne cedex (France); Mornex, F. [UMR 754, universite Claude-Bernard Lyon 1, 43, boulevard du 11-novembre-1918, 69622 Villeurbanne cedex (France); Departement de radiotherapie-oncologie, centre hospitalier Lyon Sud, 165, chemin du Grand-Revoyet, 69495 Pierre-Benite cedex (France)

    2011-02-15

    Conformal radiotherapy is a promising therapeutic strategy for hepatocellular carcinoma (HCC), producing local control rates above 90% within the radiation beam. However, survival after radiotherapy remains limited by the high frequency of intra- and extra-hepatic recurrences, which occurs in 40-50 and 20-30% of cases, respectively. Sorafenib (BAY43-9006, Nexavar; Bayer, West Haven, CT) is a small molecule inhibitor that demonstrated potent activity to target v-raf murine sarcoma oncogene homologue B1 (BRAF) and VEGFR tyrosine kinases. Sorafenib is the only drug that demonstrated effectiveness to increase overall survival in advanced or metastatic hepatocellular carcinoma. The rationale to combine radiotherapy with sorafenib is the following: (1) targeting RAS-RAF-MAPK and VEGFR signaling pathways, which are specifically activated after exposure to radiation, and responsible for radio-resistance phenomenon; (2) enhancing the oxygen effect through normalization of the surviving tumor vasculature; and (3) synchronization of the cell cycle. Sorafenib and radiotherapy represent complementary strategies, as radiotherapy may be useful to prolong the effect of sorafenib through control of the macroscopic disease, when sorafenib may target latent microscopic disease. Sorafenib and radiotherapy associations are thus based on a relevant biological and clinical rationale and are being evaluated in ongoing phase I-II trials. (authors)

  10. Venom from Cuban Blue Scorpion has tumor activating effect in hepatocellular carcinoma

    Science.gov (United States)

    Giovannini, Catia; Baglioni, Michele; Baron Toaldo, Marco; Cescon, Matteo; Bolondi, Luigi; Gramantieri, Laura

    2017-01-01

    Complementary and alternative medicine (CAM) is the term used to describe many kinds of products, practices, and systems that are not part of conventional medicine. Cancer patients usually do everything they can to combat the disease, manage its symptoms, and cope with the side effects of treatment. Unfortunately, patients who use CAM underestimate the risk of interaction with cancer therapy or worse they omit conventional therapy thus reducing the possibility of cancer remission. Herein we analyzed the effects of Vidatox 30 CH (venom extracted from the Junceus Rhopalurus scorpion) on hepatocellular carcinoma (HCC), the second leading cause of cancer-related deaths. We found out that Vidatox increases HCC proliferation and invasion whereas it does not seem to interact with sorafenib, the orally active multikinase inhibitor approved for the treatment of advanced hepatocellular carcinoma. Our results suggest that the concentration of Vidatox used in the present study has not anti-neoplastic effects and care must be taken in hiring Vidatox in patients with HCC. PMID:28322221

  11. Role of endoscopic ultrasound in diagnosis and management of hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Koduru P

    2015-10-01

    Full Text Available Pramoda Koduru,1 Rei Suzuki,2 Sundeep Lakhtakia,3 Mohan Ramchandani,3 Dadang Makmun,4 Manoop S Bhutani,1 1Department of Gastroenterology, Hepatology and Nutrition, University of Texas MD Anderson Cancer Center, Houston, TX, USA; 2Department of Gastroenterology and Rheumatology, Fukushima University School of Medicine, Fukushima, Japan; 3Asian Institute of Gastroenterology, Hyderabad, India; 4University of Indonesia/Cipto Mangunkusumo Hospital, Jakarta, Indonesia Abstract: Hepatocellular carcinoma (HCC is an aggressive tumor and a leading cause of cancer-related deaths globally. The mortality rate remains high despite many advances in treatment. HCC is frequently diagnosed late in its course due to lack of classical symptoms at earlier stages. Endoscopic ultrasound (EUS has emerged as an important diagnostic tool for the diagnostic evaluation, staging, and treatment of gastrointestinal tract disorders. EUS-guided fine needle aspiration has been a valuable addition to EUS by being able to obtain tissue under direct visualization. Here, we review the potential role of EUS in the diagnosis and management of HCC. EUS seems to be a safe and reliable alternative method for obtaining tissue for diagnosis of liver cancer, especially for lesions that are inaccessible by traditional methods. EUS could play an important role in the diagnosis and management of HCC. Keywords: endoscopic ultrasound, fine needle aspiration, hepatocellular carcinoma, hepatoma

  12. 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

  13. Antiviral therapy for hepatitis B virus-related hepatocellular carcinoma after surgery: A comment for moving forward

    Institute of Scientific and Technical Information of China (English)

    Jian-Hong; Zhong; Tian; Yang; Bang-De; Xiang; Le-Qun; Li; Liang; Ma

    2016-01-01

    Recurrence rate of hepatocellular carcinoma remains quite high even after surgery,and no postoperative therapies have been definitively shown to prevent hepatocellular carcinoma recurrence.A previous study showed that therapy with nucleos(t)ide analogues given to such patients after surgery significantly improved survival.However,many questions still exist about the usage of nucleos(t)ide analogues for patients with hepatocellular carcinoma after surgery.

  14. Therapeutic potential of small interfering RNAs/micro interfering RNA in hepatocellular carcinoma.

    Science.gov (United States)

    Farra, Rossella; Grassi, Mario; Grassi, Gabriele; Dapas, Barbara

    2015-08-14

    Hepatocellular carcinoma (HCC) is the predominant form of primary liver cancer and represents the third leading cause of cancer-related death worldwide. Current available therapeutic approaches are poorly effective, especially for the advanced forms of the disease. In the last year, short double stranded RNA molecules termed small interfering RNAs (siRNAs) and micro interfering RNAs (miRNA), emerged as interesting molecules with potential therapeutic value for HCC. The practical use of these molecules is however limited by the identification of optimal molecular targets and especially by the lack of effective and targeted HCC delivery systems. Here we focus our discussion on the most recent advances in the identification of siRNAs/miRNAs molecular targets and on the development of suitable siRNA/miRNAs delivery systems.

  15. Epigenetic inactivation of SLIT2 in human hepatocellular carcinomas.

    Science.gov (United States)

    Jin, Jie; You, Haiyan; Yu, Bin; Deng, Yun; Tang, Ning; Yao, Genfu; Shu, Huiqun; Yang, Shengli; Qin, Wenxin

    2009-01-30

    Recent findings have shown that SLIT2 appears to function as a novel tumor suppressor gene. In addition, hypermethylation of its promoter region has been detected in various cancers, including breast and lung cancer, colorectal carcinoma, and gliomas. Here, we report for the first time that there is epigenetic silencing of SLIT2 in human hepatocellular carcinoma (HCC). Downregulation of SLIT2 was detected in 6 of 8 (75%) HCC cell lines by quantitative real-time RT-PCR (qRT-PCR), and the downregulation of SLIT2 was generally dependent on the degree of methylation at the promoter region. Furthermore, expression of SLIT2 was restored in relatively low-expressing cell lines after treatment with 5-aza-2-deoxycytidine (5-Aza-dC). Downregulation of SLIT2 expression was also detected in 45 of 54 primary HCC samples (83.3%), and the decrease in expression was significantly correlated with CpG island hypermethylation. This decrease of SLIT2 expression was also associated with lymph node metastasis in HCC. Moreover, overexpression of SLIT2 in SMMC-7721 cells induced by recombinant adenovirus suppressed cell growth, migration, and invasion, These results suggest that epigenetic inactivation of SLIT2 in HCC may be important in the development and progression of HCC. Thus, SLIT2 may be useful as a therapeutic target in the treatment of HCC.

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

    Institute of Scientific and Technical Information of China (English)

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

    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.

  17. Research Advancement of NF-κB in HBV Infection Related Hepatocellular Carcinoma%核因子κB在HBV相关性肝癌中的研究进展

    Institute of Scientific and Technical Information of China (English)

    杨春霞

    2011-01-01

    It has been proved that hepatitis B virus infection is the main factor causing hepatocellular carcinoma( HCC ). The discovery of NF-κB set up a bridge between inflammation and tumor. NF-κB is activated by hepatitis B virus directly or indirectly,which then results in cancer by acting on carcinogens. The interaction is a negative feedback which is cascade amplified rather than unidirectional. Not only did NF-κB take part in the development in cancer,but also primary drug resistance. NF-κB plays a rather important role in HBV infection related hepatocellular carcinoma. The HBV-NF-κB-HCC clues will be reviewed in this article.%目前大量的研究证明,HBV感染是引起原发性肝癌的主要原因.核因子κB(NF-κB)的发现,在炎症和肿瘤之间搭起了一座桥梁.HBV通过自身直接或者间接引起NF-κB的激活,NF-κB又作用于致癌因子,从而引发肿瘤.但这种相互作用不是单向的,而是级联放大的负反馈.NF-κB不仅参与肝癌的发生、发展,还与化疗药物耐药有关,NF-κB在HBV感染引起的肝癌中的作用至关重要.

  18. The relationship between the hepatitis B virus base core and precore/core promoter mutations and the development of cirrhotic hepatocellular carcinoma and noncirrhotic hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    徐尧江

    2013-01-01

    Objective To investigate the mutations of basal core promoter(BCP) and precore(PreC) region of hepatitis B virus(HBV) and the association with the development of hepatocellular carcinoma in patients with chronic HBV infection. Methods Totally 381 untreated HBV patients were recruited from the Department of Infectious

  19. Rapid induction of orthotopic hepatocellular carcinoma in immune-competent rats by non-invasive ultrasound-guided cells implantation

    Directory of Open Access Journals (Sweden)

    Pan Huay-Ben

    2010-07-01

    Full Text Available Abstract Background The fact that prognoses remain poor in patients with advanced hepatocellular carcinoma highlights the demand for suitable animal models to facilitate the development of anti-cancer medications. This study employed a relatively non-invasive approach to establish an orthotopic hepatocellular carcinoma model in immune-competent rats. This was done by ultrasound-guided implantation of cancer cells and the model was used to evaluate the therapeutic efficacy of short-term and low-dose epirubicin chemotherapy. Methods Rat Novikoff hepatoma cells were injected percutaneously into the liver lobes of Sprague-Dawley rats under the guidance of high resolution ultrasound. The implantation rate and the correlation between dissected and ultrasound-measured tumor sizes were evaluated. A similar induction procedure was performed by means of laparotomy in a different group of rats. Pairs of tumor measurement were compared by ultrasound and computerized tomography scan. Rats with a successful establishment of the tumor were divided into the treatment (7-day low-dose epirubicin group and the control group. The tumor sizes were non-invasively monitored by the same ultrasound machine. Blood and tumor tissues from tumor-bearing rats were examined by biochemical and histological analysis respectively. Results Ultrasound-guided implantation of Novikoff hepatoma cells led to the formation of orthotopic hepatocellular carcinoma in 60.4% (55/91 of the Sprague-Dawley rats. Moreover, tumor sizes measured by ultrasound significantly correlated with those measured by calipers after sacrificing the animals (P Conclusions Ultrasound-guided implantation of Novikoff hepatoma cells is an effective means of establishing orthotopic hepatocellular carcinoma in Sprague-Dawley rats. Short-term and low-dose epirubicin chemotherapy had perturbed tumor progression by inducing apoptosis and neovascularization blockade.

  20. 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

  1. 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

  2. A patient with spinal metastasis from hepatocellular carcinoma discovered from neurological findings

    Institute of Scientific and Technical Information of China (English)

    Katsuyoshi Tamaki; Ichiro Shimizu; Mari Urata; Nao Kohno; Hiroshi Fukuno; Susumu Ito; Nobuya Sano

    2007-01-01

    Although spinal tumors are uncommon, they may reduce survival or cause serious functional disorders in the extremities. Metastatic spinal tumors from malignant tumors can induce symptoms of spinal cord compression, such as paraplegia, quadriplegia, and vesicorectal disturbance, which are aggravated with progression of the diseases and time. We report a patient with hepatocellular carcinoma (HCC) who was suspected of having spinal lesions based on neurological findings, and a metastatic spinal tumor was found by imaging examination. Assuming that metastasis had occurred at the time lumbar pain developed, the patient reached the level of gAlt disturbance within only 4 mo, showing a rapid advancement of symptoms. If early diagnosis had been possible, treatment could be performed before acute myelopathy progressed to complete paralysis. We speculate that the terminal stage of HCC is not only liver fAllure associated with intrahepatic lesions but also metastasis to other regions, treatment for individual pathologies therefore, will be needed, which constitutes an important issue.

  3. Chemoembolic Hepatopulmonary Shunt Reduction to Allow Safe Yttrium-90 Radioembolization Lobectomy of Hepatocellular Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Gaba, Ron C., E-mail: rgaba@uic.edu [University of Illinois Medical Center at Chicago, Department of Radiology, Section in Interventional Radiology (United States); VanMiddlesworth, Kyle A. [Midwestern University School of Medicine (United States)

    2012-12-15

    Yttrium-90 ({sup 90}Y) radioembolization represents an emerging transcatheter treatment option for the management of hepatocellular carcinoma (HCC). Elevation of the hepatopulmonary shunt fraction risks nontarget radiation to the lungs and may limit the use of {sup 90}Y therapy in patients with locally advanced disease with vascular invasion, who often demonstrate increased shunting. We present two cases in which patients with HCC and portal vein invasion resulting in elevated hepatopulmonary shunt fractions underwent chemoembolic shunt closure to allow safe {sup 90}Y radioembolization. Both patients demonstrated excellent tumor response and patient survival. On this basis, we propose a role for chemoembolic reduction of the lung shunt fraction before {sup 90}Y radioembolization in patients with extensive tumor-related hepatopulmonary shunting.

  4. Splenic infarction associated with sorafenib use in a hepatocellular carcinoma patient

    Institute of Scientific and Technical Information of China (English)

    Sang Ock Kim; Sang Young Han; Yang Hyun Baek; Sung Wook Lee; Ji Sun Han; Byung Geun Kim; Jin Han Cho; Kyung Jin Nam

    2011-01-01

    Sorafenib, a multitargeted tyrosine kinase inhibitor, has been shown to improve survival in patients with advanced hepatocellular carcinoma (HCC). As the clinical use of sorafenib increases, many adverse effects have been reported, such as hand-foot skin reaction, diarrhea,anorexia, asthenia, alopecia, weight loss, hypertension and arterial thromboembolism. However, there are no prior reports of splenic infarction as an adverse effect of sorafenib. Here, a case of splenic infarction in a patient with HCC who was treated with sorafenib is reported.The patient had no other predisposing factors to explain the splenic infarction except for the administration of sorafenib. The splenic infarction improved after sorafenib was discontinued; however, the HCC progressed.

  5. 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...... growth in cancer cell lines and in vivo. The vitamin D receptor is expressed in hepatocytes and more abundantly in HCC cells. In total, 56 patients with inoperable advanced HCC were included in an uncontrolled study of oral Seocalcitol treatment for up to 1 year (with possible extension for responders...... for 29 and at least 36 months (patient still in remission when data censored). Seocalcitol was well tolerated; the most frequent toxicity was hypercalcaemia and related symptoms. Most patients tolerated a daily dose of 10 micro g of Seocalcitol. This is the first study showing activity, by reduction...

  6. Low hemoglobin level is associated with the development of delirium after hepatectomy for hepatocellular carcinoma patients.

    Directory of Open Access Journals (Sweden)

    Yao-Li Chen

    Full Text Available Hepatocellular carcinoma (HCC is one of the most common malignant tumors worldwide and liver resection is the only potential curative treatment option for those patients. Postoperative complications specific to elderly surgical patients such as delirium will be increasingly relevant in the coming decades. Herein, we aimed to investigate the risk factors for postoperative delirium in patients who have received hepatectomy for HCC.This is a single medical center observational study and the study subjects comprised 401 individuals who underwent liver resection for hepatocellular carcinoma during January 2009 to October 2013. Multivariate analysis was used to examine whether preoperative, intra-operative, or postoperative variables were associated with the development of delirium.Of the 401 patients who underwent hepatectomy, 34 developed postoperative delirium (8.4%. In the majority of those patients, symptoms and signs of the syndrome occurred on postoperative day 2 and the mean duration of symptoms was 3.61 ± 3.71 days. Multivariate analysis revealed that advanced age (>71 years [odds ratio (OR = 1.133, 95% confidence interval (CI: 1.071-1.200, p190 minutes (OR = 1.009, 95% CI: 1.000-1.017, p = 0.038, a decreased postoperative hemoglobin level (< 10.16 g/dL (OR = 0.777, 95% CI: 0.613-0.983, p = 0.036, and history of hypnotic drug use (OR = 3.074, 95% CI: 1.045-9.039, p = 0.041 were independent risk factors for the development of postoperative delirium after hepatectomy.Although the mechanism of postoperative delirium is not well understood, numbers of studies have shown that patients with postoperative delirium tend to have prolonged hospital stay, worse postoperative outcome and an increased risk of short- and long-term mortality. In this study, we found that advanced age, prolonged operative time, postoperative low hemoglobin level and history of hypnotic drug use are independent risk factors for postoperative delirium.

  7. Portal vein thrombosis and arterioportal shunts: Effects on tumor response after chemoembolization of hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Thomas J Vogl; Nour-Eldin Nour-Eldin; Sally Emad-Eldin; Nagy NN Naguib; Joerg Trojan; Hans Ackermann; Omar Abdelaziz

    2011-01-01

    AIM: To evaluate the effect of portal vein thrombosis and arterioportal shunts on local tumor response in advanced cases of unresectable hepatocellular carcinoma treated by transarterial chemoembolization. METHODS: A retrospective study included 39 patients (mean age: 66.4 years, range: 45-79 years, SD: 7) with unresectable hepatocellular carcinoma (HCC) who were treated with repetitive transarterial chemoembolization (TACE) in the period between March 2006 and October 2009. The effect of portal vein thrombosis (PVT) (in 19 out of 39 patients), the presence of arterioportal shunt (APS) (in 7 out of 39), the underlying liver pathology, Child-Pugh score, initial tumor volume, number of tumors and tumor margin definition on imaging were correlated with the local tumor response after TACE. The initial and end therapy local tumor responses were evaluated according to the response evaluation criteria in solid tumors (RECIST) and magnetic resonance imaging volumetric measurements. RESULTS: The treatment protocols were well tolerated by all patients with no major complications. Local tumor response for all patients according to RECIST criteria were partial response in one patient (2.6%), stable disease in 34 patients (87.1%), and progressive disease in 4 patients (10.2%). The MR volumetric measurements showed that the PVT, APS, underlying liver pathology and tumor margin definition were statistically significant prognostic factors for the local tumor response (P = 0.018, P = 0.008, P = 0.034 and P = 0.001, respectively). The overall 6-, 12- and 18-mo survival rates from the initial TACE were 79.5%, 37.5% and 21%, respectively. CONCLUSION: TACE may be exploited safely for palliative tumor control in patients with advanced unresectable HCC; however, tumor response is significantly affected by the presence or absence of PVT and APS.

  8. Novel Altered Region for Biomarker Discovery in Hepatocellular Carcinoma (HCC Using Whole Genome SNP Array

    Directory of Open Access Journals (Sweden)

    Esraa M. Hashem

    2016-04-01

    Full Text Available cancer represents one of the greatest medical causes of mortality. The majority of Hepatocellular carcinoma arises from the accumulation of genetic abnormalities, and possibly induced by exterior etiological factors especially HCV and HBV infections. There is a need for new tools to analysis the large sum of data to present relevant genetic changes that may be critical for both understanding how cancers develop and determining how they could ultimately be treated. Gene expression profiling may lead to new biomarkers that may help develop diagnostic accuracy for detecting Hepatocellular carcinoma. In this work, statistical technique (discrete stationary wavelet transform for detection of copy number alternations to analysis high-density single-nucleotide polymorphism array of 30 cell lines on specific chromosomes, which are frequently detected in Hepatocellular carcinoma have been proposed. The results demonstrate the feasibility of whole-genome fine mapping of copy number alternations via high-density single-nucleotide polymorphism genotyping, Results revealed that a novel altered chromosomal region is discovered; region amplification (4q22.1 have been detected in 22 out of 30-Hepatocellular carcinoma cell lines (73%. This region strike, AFF1 and DSPP, tumor suppressor genes. This finding has not previously reported to be involved in liver carcinogenesis; it can be used to discover a new HCC biomarker, which helps in a better understanding of hepatocellular carcinoma.

  9. 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.

  10. Bacoside A downregulates matrix metalloproteinases 2 and 9 in DEN-induced hepatocellular carcinoma.

    Science.gov (United States)

    Janani, Panneerselvam; Sivakumari, Kanakarajan; Geetha, Arumugam; Yuvaraj, Sambandam; Parthasarathy, Chandrakesan

    2010-03-01

    Cancer metastasis is a complex multi-step process, responsible for a majority of cancer-related deaths by affecting the critical organs and causing complications in therapies. Hepatocellular carcinoma is a multi-factorial disease and is the third most common cause of cancer related mortality worldwide. Clinical and experimental studies have shown that MMP-2 and MMP-9 are involved in tumor invasion and metastases and their elevated expression has been associated with poor prognosis. Our recent studies showed a strong anti-oxidant and hepatoprotective effects of bacoside A (BA) against carcinogen. Nevertheless the effect of BA on the activities and expression of MMP-2 and MMP-9 during hepatocellular carcinoma is not yet recognized. Therefore, the present study was designed to assess the same. Results of gelatin zymography study showed that BA co-treatment significantly decreased the activities of MMP-2 and MMP-9, which is increased during hepatocellular carcinoma. Further immunoblot analysis showed decreased expression of MMP-2 and MMP-9 in rats co-treated with BA compared to DEN-induced hepatocellular carcinoma. Our results reveal that BA exerts its anti-metastatic effect against DEN-induced hepatocellular carcinoma by inhibiting the activities and expressions of MMP-2 and MMP-9.

  11. Transarterial RAdioembolization versus ChemoEmbolization for the treatment of hepatocellular carcinoma (TRACE: study protocol for a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Seinstra Beatrijs A

    2012-08-01

    Full Text Available Abstract Background Hepatocellular carcinoma is a primary malignant tumor of the liver that accounts for an important health problem worldwide. Only 10 to 15% of hepatocellular carcinoma patients are suitable candidates for treatment with curative intent, such as hepatic resection and liver transplantation. A majority of patients have locally advanced, liver restricted disease (Barcelona Clinic Liver Cancer (BCLC staging system intermediate stage. Transarterial loco regional treatment modalities offer palliative treatment options for these patients; transarterial chemoembolization (TACE is the current standard treatment. During TACE, a catheter is advanced into the branches of the hepatic artery supplying the tumor, and a combination of embolic material and chemotherapeutics is delivered through the catheter directly into the tumor. Yttrium-90 radioembolization (90Y-RE involves the transarterial administration of minimally embolic microspheres loaded with Yttrium-90, a β-emitting isotope, delivering selective internal radiation to the tumor. 90Y-RE is increasingly used in clinical practice for treatment of intermediate stage hepatocellular carcinoma, but its efficacy has never been prospectively compared to that of the standard treatment (TACE. In this study, we describe the protocol of a multicenter randomized controlled trial aimed at comparing the effectiveness of TACE and 90Y-RE for treatment of patients with unresectable (BCLC intermediate stage hepatocellular carcinoma. Methods/design In this pragmatic randomized controlled trial, 140 patients with unresectable (BCLC intermediate stage hepatocellular carcinoma, with Eastern Cooperative Oncology Group performance status 0 to 1 and Child-Pugh A to B will be randomly assigned to either 90Y-RE or TACE with drug eluting beads. Patients assigned to 90Y-RE will first receive a diagnostic angiography, followed by the actual transarterial treatment, which can be divided into two sessions in case

  12. Effect of PTPRD rs2279776 gene and interaction with hepatitis B virus mutations on the risk of hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    邓阳

    2014-01-01

    Objective To investigate the effect of rs2279776 at the PTPRD and its interactions on hepatitis B virus(HBV)mutations as well as related risk on hepatocellular carcinoma(HCC).Methods A total of 3023 individ-uals,including 1012 healthy controls,990 HCC-free HBV-infected subjects,and 1021 HBV-caused hepatocellular carcinoma patients(HCC)

  13. Advantage of autologous blood transfusion in surgery for hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Yoshito Tomimaru; Hiroaki Nagano; Hidetoshi Eguchi; Shigeru Marubashi; Hiroshi Wada; Shogo Kobayashi; Masahiro Tanemura; Koji Umeshita; Yuichiro Doki; Masaki Mori

    2011-01-01

    AIM: To evaluate the significance of autologous blood transfusion (AT) in reducing homologous blood trans-fusion (HT) in surgery for hepatocellular carcinoma (HCC).METHODS: The proportion of patients who received HT was compared between two groups determined by the time of AT introduction; period A (1991-1994, n = 93) and period B (1995-2000, n = 201). Multivariate logistic regression analysis was performed in order to identify independent significant predictors of the need for HT. We also investigated the impact of AT and HT on long-term postoperative outcome after curative sur-gery for HCC.RESULTS: The proportion of patients with HT was significantly lower in period B than period A (18.9% vs 60.2%, P < 0.0001). Multivariate logistic regression analysis identified AT administration as a significant independent predictor of the need for HT (P < 0.0001). Disease-free survival in patients with AT was com-parable to that without any transfusion. Multivariate analysis identified HT administration as an independent significant factor for poorer disease-free survival (P = 0.0380).CONCLUSION: AT administration significantly de-creased the need for HT. Considering the postoperative survival disadvantage of HT, AT administration could improve the long-term outcome of HCC patients.

  14. Role of hepatectomy for recurrent or initially unresectable hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Yoji; Kishi; Kazuaki; Shimada; Satoshi; Nara; Minoru; Esaki; Tomoo; Kosuge

    2014-01-01

    As a result of donor shortage and high postoperative morbidity and mortality after liver transplantation,hepatectomy is the most widely applicable and reliable option for curative treatment of hepatocellular carcinoma(HCC).Because intrahepatic tumor recurrence is frequent after loco-regional therapy,repeated treatments are advocated provided background liver function is maintained.Among treatments including local ablation and transarterial chemoembolization,hepatectomy provides the best long-term outcomes,but studies comparing hepatectomy with other nonsurgical treatments require careful review for selection bias.In patients with initially unresectable HCC,transarterial chemo-or radio-embolization,and/or systemic chemotherapy can down-stage the tumor and conversion to resectable HCC is achieved in approximately 20%of patients.However,complete response is rare,and salvage hepatectomy is essential to help prolong patients’survival.To counter the short recurrence-free survival,excellent overall survival is obtained by combining and repeating different treatments.It is important to recognize hepatectomy as a complement,rather than a contraindication,to other nonsurgical treatments in a mul-tidisciplinary approach for patients with HCC,including recurrent or unresectable tumors.

  15. Aided Diagnosis of Hepatocellular Carcinoma Using Serum Fucosylated Haptoglobin Ratios

    Science.gov (United States)

    Shang, Shuxin; Li, Wei; Qin, Xue; Zhang, Shu; Liu, Yinkun

    2017-01-01

    Aberrant fucosylation plays a functional role in regulating ontogeny and celluar differentiation and are differentially regulated in cancerous condition, which could provide hallmarks for cancer diagnostics and surveillance. We previously developed a magnetic beads-based lectin ELISA system to measure fucosylated haptoglobin (Hp), which has been reported to be a cancer biomarker through a series of glycoproteomic analysis. In this study, serum fucosylated Hp ratios were measured using our ELISA kit in a separate cohort of 260 patients independently, including 130 healthy controls and 130 patients with hepatocellular carcinoma (HCC). Fucosylated Hp /Hp ratio (levels of fucosylated Hp /levels of protein Hp) and ELISA Index (OD value of fucosylated Hp /OD value of protein Hp) were calculated respectively to reflect Hp fucosylation level on its protein level. Our data showed that fucosylated Hp /Hp ratio (AUC=0.8449) and ELISA Index (AUC=0.8581) had better performance in distinguishing HCC from controls, which indicated that fucosylated Hp ratios could improve the diagnosis and prediction of HCC even with a low level of alpha-fetoprotein (AFP). Additionally, the combination analysis of AFP and fucosylated Hp ratios increased the AUC value for HCC diagnosis. PMID:28382152

  16. Diagnostic and therapeutic application of noncoding RNAsfor hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Chikako Shibata; Motoyuki Otsuka; Takahiro Kishikawa; Motoko Ohno; Takeshi Yoshikawa; Akemi Takata; Kazuhiko Koike

    2015-01-01

    MicroRNAs (miRNAs) are small, noncoding RNA moleculesthat regulate gene expression posttranscriptionally,targeting thousands of messenger RNAs. Long noncodingRNAs (lncRNAs), another class of noncodingRNAs, have been determined to be also involved intranscription regulation and translation of target genes.Since deregulated expression levels or functions ofmiRNAs and lncRNAs in hepatocellular carcinoma (HCC)are frequently observed, clinical use of noncodingRNAs for novel diagnostic and therapeutic applicationsin the management of HCCs is highly and emergentlyexpected. Here, we summarize recent findingsregarding deregulated miRNAs and lncRNAs for theirpotential clinical use as diagnostic and prognosticbiomarkers of HCC. Specifically, we emphasize thederegulated expression levels of such noncoding RNAsin patients' sera as noninvasive biomarkers, a field thatrequires urgent improvement in the clinical surveillanceof HCC. Since nucleotide-based strategies are beingapplied to clinical therapeutics, we further summarizeclinical and preclinical trials using oligonucleotidesinvolving the use of miRNAs and small interfering RNAsagainst HCC as novel therapeutics. Finally, we discusscurrent open questions, which must be clarified in thenear future for realistic clinical applications of thesenew strategies.

  17. Liver regeneration microenvironment of hepatocellular carcinoma for prevention and therapy

    Science.gov (United States)

    Li, Hanmin; Zhang, Lisheng

    2017-01-01

    Research on liver cancer prevention and treatment has mainly focused on the liver cancer cells themselves. Currently, liver cancers are no longer viewed as only collections of genetically altered cells but as aberrant organs with a plastic stroma, matrix, and vasculature. Improving the microenvironment of the liver to promote liver regeneration and repair by affecting immune function, inflammation and vasculature can regulate the dynamic imbalance between normal liver regeneration and repair and abnormal liver regeneration, thus improving the microenvironment of liver regeneration for the prevention and treatment of liver cancer. This review addresses the basic theory of the liver regeneration microenvironment, including the latest findings on immunity, inflammation and vasculature. Attention is given to the potential design of molecular targets in the microenvironment of hepatocellular carcinoma (HCC). In an effort to improve the liver regeneration microenvironment of HCC, researchers have extensively utilized the enhancement of immunity, anti-inflammation and the vasculature niche, which are discussed in detail in this review. In addition, the authors summarize the latest pro-fibrotic transition characteristics of the vascular niche and review potential cell therapies for liver disease. PMID:27655683

  18. 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.

  19. MicroRNA-429 Modulates Hepatocellular Carcinoma Prognosis and Tumorigenesis

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    Xiao-Ying Huang

    2013-01-01

    Full Text Available MicroRNA-429 (miR-429 may modify the development and progression of cancers; however, the role of this microRNA in the hepatocellular carcinoma (HCC has not been well elaborated. Here, we tested miR-429 expression in 138 pathology-diagnosed HCC cases and SMMC-7721 cells. We found that miR-429 was upregulated in HCC tumor tissues and that the high expression of miR-429 was significantly correlated with larger tumor size (odd ratio (OR, 2.70; 95% confidence interval (CI, 1.28–5.56 and higher aflatoxin B1-DNA adducts (OR = 3.13, 95% CI = 1.47–6.67. Furthermore, this microRNA overexpression modified the recurrence-free survival and overall survival of HCC patients. Functionally, miR-429 overexpression progressed tumor cells proliferation and inhibited cell apoptosis. These results indicate for the first time that miR-429 may modify HCC prognosis and tumorigenesis and may be a potential tumor therapeutic target.

  20. Natural history of hepatitis-related hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    David Yiu-Kuen But; Ching-Lung Lai; Man-Fung Yuen

    2008-01-01

    Hepatocellular carcinoma (HCC) is an important cause of cancer death in the world. It has great regional differences in the pathology and epidemiology. The variation is greatly influenced by the aetiologies of the disease. Hepatitis B and C infection are the most important risk factors. HCC incidence rates are higher but in decreasing trend in developing countries. However, the figures in the developed countries are contrary. Successful hepatitis B virus (HBV) vaccination programs, better food hygiene, increased global hepatitis C virus (HCV) prevalence and population migration are the possible explanations. A number of clinical and pathogenic differences exist between HBV- and HCV-related HCC. HBV infection leads to the development of HCC through direct and indirect pathways as it has the ability to integrate into the host genome affecting cellular signaling and growth control. HCV causes HCC mainly through indirect pathways: chronic inflammation, cell deaths and proliferation. As a result, HCC is almost exclusively found in cirrhotic HCV patients while HCC is sometimes found in HBV patients without significant liver cirrhosis. Due to the different severities of liver cirrhosis and HCC extent, therapeutic strategies from resection, liver transplantation to symptoms palliation are available. Poorly differentiated histology, lack of fibrous capsule, large tumour size, early vascular invasion and elevated serum levels of alpha fetoprotein (AFP) are the features for more aggressive disease. Combined with markers of liver reserve and performance status, accurate scoring systems and models have been developed to predict patients' survival and match best treatment option.

  1. Risk factors for residual tumor after resection of hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Xiao-Hong Chen; Bo-Heng Zhang; Yin Xin; Zheng-Gang Ren; Jia Fan; Shuang-Jian Qiu; Jian Zhou

    2011-01-01

    AIM: To identify the clinicopathological risk factors correlated with residual tumor in hepatocellular carcinoma (HCC) patients after resection.METHODS: From January 2001 to April 2007, 766 HCC patients who had undergone resection were included in this research.Lipiodol angiography was performed within 2 mo after surgery and followed by post-Lipiodol computed tomography (CT) 4 wk later for all 766 patients to monitor tumor in the remnant liver.Tumor detected within the first 3-mo postoperative period was defined as residual tumor.Patients were divided into 2 groups: disease or disease-free within the first 3 mo after surgery.Risk factors for residual tumor were investigated among various clinicopathological variables.RESULTS: A total of 63 (8.22%) patients were found to have residual tumor after surgery.Three independent factors associated with residual tumor were identified by multivariate analysis: preoperative serum α -fetoprotein (AFP) level [odds ratio (OR) = 1.68 (95% confidence interval (CI): 1.20-2.36)], tumor size [OR = 1.73 (95% CI: 1.29-2.31)] and microvascular invasion [OR = 1.91 (95% CI: 1.12-3.24)].CONCLUSION: Residual tumor is related to AFP level, tumor size and microvascular invasion.Patients at high risk should undergo closer follow-up and could be candidates for multimodality therapy.

  2. Improving clinical trial design for hepatocellular carcinoma treatments

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    Garrett Hisatake

    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.

  3. MicroRNAs: Emerging Novel Clinical Biomarkers for Hepatocellular Carcinomas

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    Sumadi Lukman Anwar

    2015-08-01

    Full Text Available The discovery of small non-coding RNAs known as microRNAs has refined our view of the complexity of gene expression regulation. In hepatocellular carcinoma (HCC, the fifth most frequent cancer and the third leading cause of cancer death worldwide, dysregulation of microRNAs has been implicated in all aspects of hepatocarcinogenesis. In addition, alterations of microRNA expression have also been reported in non-cancerous liver diseases including chronic hepatitis and liver cirrhosis. MicroRNAs have been proposed as clinically useful diagnostic biomarkers to differentiate HCC from different liver pathologies and healthy controls. Unique patterns of microRNA expression have also been implicated as biomarkers for prognosis as well as to predict and monitor therapeutic responses in HCC. Since dysregulation has been detected in various specimens including primary liver cancer tissues, serum, plasma, and urine, microRNAs represent novel non-invasive markers for HCC screening and predicting therapeutic responses. However, despite a significant number of studies, a consensus on which microRNA panels, sample types, and methodologies for microRNA expression analysis have to be used has not yet been established. This review focuses on potential values, benefits, and limitations of microRNAs as new clinical markers for diagnosis, prognosis, prediction, and therapeutic monitoring in HCC.

  4. Laparoscopic liver resection for hepatocellular carcinoma in patients with cirrhosis

    Institute of Scientific and Technical Information of China (English)

    Jai Young Cho; Ho-Seong Han

    2016-01-01

    Hepatocellular carcinoma (HCC) is a common malignant tumor and many cases occur in patients with liver cirrhosis. Although liver transplantation is the most effective treatment option, hepatectomy is still the ifrst curative treatment option because liver transplantation is limited by the donors and high cost. In recent years, laparoscopic liver resection (LLR) has increasingly been performed in patients with liver cirrhosis, and has several advantages over open liver resection. Besides less pain and shorter hospital stay, LLR in patients with liver cirrhosis is also associated with lower incidences of postoperative liver failure and ascites because of greater preservation of collateral veins and less liver manipulation. With increasing experience, LLR for HCC located in segments 7 or 8 is now feasible, and anatomic LLR could be performed in patients with cirrhosis. Many comparative studies have shown that LLR is better than open liver resection in patients with liver cirrhosis in terms of a lower incidence of postoperative liver failure and similar patient survival. In conclusion, LLR is a promising treatment modality for HCC in patients with liver cirrhosis.

  5. Pulmonary complications of transcatheter arterial chemoembolization for hepatocellular carcinoma

    Science.gov (United States)

    Nhu, Quan M; Knowles, Harry; Pockros, Paul J; Frenette, Catherine T

    2016-01-01

    Transarterial chemoembolization (TACE) is an effective palliative intervention that is widely accepted for the management of hepatocellular carcinoma (HCC). Post-TACE pulmonary complications resulting in acute lung injury (ALI) or acute respiratory distress syndrome (ARDS) are rare events. Pulmonary complications after TACE are thought to be related to chemical injury subsequent to the migration of the infused ethiodized oil or chemotherapeutic agent to the lung vasculature, facilitated by arteriovenous (AV) shunts within the hyper-vascular HCC. We review herein the literature on pulmonary complications related to TACE for HCC. Post-TACE pulmonary complications have included pulmonary oil embolism, interstitial pneumonitis, chemical pneumonitis, ALI, ARDS, lipoid pneumonia, acute eosinophilic and neutrophilic pneumonia, bilious pleuritis, pulmonary abscess, pulmonary tumor embolism, and possibly pulmonary metastasis with HCC. The risk factors associated with post-TACE pulmonary complications identified in the literature include large hyper-vascular HCC with AV shunts, large-volume Lipiodol infusion, and embolization via the right inferior phrenic artery. However, the absence of known risk factors is not a guarantee against serious complications. An astute awareness of the potential post-TACE pulmonary complications should expedite appropriate therapeutic interventions and increase potential for early recovery. PMID:27904836

  6. Platelet-activating factor in cirrhotic liver and hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Muriel Mathonnet; Bernard Descottes; Denis Valleix; Véronique Truffinet; Francois Labrousse; Yves Denizot

    2006-01-01

    AIM: Platelet-activating factor (PAF) is a pro-inflammatory and angiogenic lipid mediator. Here we aimed to investigate levels of PAF, lyso-PAF (the PAF precursor),phospholipase A2 (PLA2, the enzymatic activity generating lyso-PAF), acetylhydrolase activity (AHA, the PAF degrading enzyme) and PAF receptor (PAF-R) transcripts in cirrhotic liver and hepatocellular carcinoma (HCC).METHODS: Twenty-nine patients with HCC were ehrolled in this study. Cirrhosis was present in fourteen patients and seven had no liver disease. Tissue PAF levels were investigated by a platelet-aggregation assay. LysoPAF was assessed after its chemical acetylation into PAF.AHA was determined by degradation of [3H]-PAF. PLA2 levels were assessed by EIA. PAF-R transcripts were investigated using RT-PCR.RESULTS: Elevated amounts of PAF and PAF-R transcripts 1 (leukocyte-type) were found in cirrhotic tissues as compared with non-cirrhotic ones. Higher amounts of PAF and PAF-R transcripts 1 and 2 (tissue-type) were found in HCC tissues as compared with non-tumor tissues. PLA2, lyso-PAF and AHA levels were not changed in cirrhotic tissues and HCC.CONCLUSION: While the role of PAF is currently unknown in liver physiology, this study suggests its potential involvement in the inflammatory network found in the cirrhotic liver and in the angiogenic response during HCC.

  7. De-regulation of common housekeeping genes in hepatocellular carcinoma

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    Wurmbach Elisa

    2007-07-01

    Full Text Available Abstract Background Tumorigenesis is associated with changes in gene expression and involves many pathways. Dysregulated genes include "housekeeping" genes that are often used for normalization for quantitative real-time RT-PCR (qPCR, which may lead to unreliable results. This study assessed eight stages of hepatitis C virus (HCV induced hepatocellular carcinoma (HCC to search for appropriate genes for normalization. Results Gene expression profiles using microarrays revealed differential expression of most "housekeeping" genes during the course of HCV-HCC, including glyceraldehyde-3-phosphate dehydrogenase (GAPDH and beta-actin (ACTB, genes frequently used for normalization. QPCR reactions confirmed the regulation of these genes. Using them for normalization had strong effects on the extent of differential expressed genes, leading to misinterpretation of the results. Conclusion As shown here in the case of HCV-induced HCC, the most constantly expressed gene is the arginine/serine-rich splicing factor 4 (SFRS4. The utilization of at least two genes for normalization is robust and advantageous, because they can compensate for slight differences of their expression when not co-regulated. The combination of ribosomal protein large 41 (RPL41 and SFRS4 used for normalization led to very similar results as SFRS4 alone and is a very good choice for reference in this disease as shown on four differentially expressed genes.

  8. Small hepatocellular carcinomas in chronic liver disease: Detection with SPECT

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    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%.

  9. Scirrhous hepatocellular carcinoma displaying atypical findings on imaging studies

    Institute of Scientific and Technical Information of China (English)

    Soo Ryang Kim; Susumu Imoto; Taisuke Nakajima; Kenji Ando; Keiji Mita; Katsumi Fukuda; Ryo Nishikawa; Yu-ichiro Koma; Toshiyuki Matsuoka; Masatoshi Kudo; Yoshitake Hayashi

    2009-01-01

    We describe a 15-mm scirrhous hepatocellular carcinoma (HCC) in a 60-year-old man with B-type cirrhosis. Ultrasound disclosed a 15-mm hypoechoic nodule in segment 7. Contrast-enhanced US revealed heterogeneous, not diffuse, hypervascularity in the early phase and a defect in the Kupffer phase. Contrast-enhanced computed tomography (CT) revealed a heterogeneous hypervascular nodule in the early phase and a low-density area in the late phase. Magnetic resonance imaging (MRI) revealed iso- to hypointensity at T1 and high intensity at T2-weighted sequences. Contrast-enhanced MRI also revealed a heterogeneous hypervascular nodule in the early phase and washout in the late phase. Super-paramagnetic iron oxide-MRI revealed a hyperintense nodule. CT during hepatic arteriography and CT during arterial portography revealed heterogeneous hyperattenuation and a perfusion defect, respectively. Based on these imaging findings the nodule was diagnosed as a mixed well-differentiated and moderately-differentiated HCC. Histologically, the nodule was moderately-differentiated HCC characterized by typical cytological and structural atypia with dense fibrosis. Immunohistochemically, the nodule was positive for heterochromatin protein 1 and alpha-smooth muscle actin, and negative for cytokeratin 19. From the above findings, the nodule was diagnosed as scirrhous HCC. Clinicians engaged in hepatology should exercise caution with suspected scirrhous HCC when imaging studies reveal atypical findings, as shown in our case on the basis of chronic liver disease.

  10. Bioinformatics analysis of metastasis-related proteins in hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Pei-Ming Song; Yang Zhang; Yu-Fei He; Hui-Min Bao; Jian-Hua Luo; Yin-Kun Liu; Peng-Yuan Yang; Xian Chen

    2008-01-01

    AIM: To analyze the metastasis-related proteins in hepatocellular carcinoma (HCC) and discover the biomark-er candidates for diagnosis and therapeutic intervention of HCC metastasis with bioinformatics tools.METHODS: Metastasis-related proteins were determined by stable isotope labeling and MS analysis and analyzed with bioinformatics resources, including Phobius, Kyoto encyclopedia of genes and genomes (KEGG), online mendelian inheritance in man (OHIH) and human protein reference database (HPRD).RESULTS: All the metastasis-related proteins were linked to 83 pathways in KEGG, including MAPK and p53 signal pathways. Protein-protein interaction network showed that all the metastasis-related proteins were categorized into 19 function groups, including cell cycle, apoptosis and signal transcluction. OMIM analysis linked these proteins to 186 OMIM entries.CONCLUSION: Metastasis-related proteins provide HCC cells with biological advantages in cell proliferation, migration and angiogenesis, and facilitate metastasis of HCC cells. The bird's eye view can reveal a global charac-teristic of metastasis-related proteins and many differen-tially expressed proteins can be identified as candidates for diagnosis and treatment of HCC.

  11. Study on MXR7 methylation in hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    GUO Ting-ting; ZENG Jin-zhang; WANG Hong-yang

    2005-01-01

    Objective:To obtain information at the molecular level on the possible mechanism of MXR7 gene overexpressed in hepatocellular carcinoma (HCC) and also to provide a clue for further study. Methods:Genomic DNA was isolated from 20 samples of hepatoma and paired non-HCC liver tissues, 2 cases of blood tumor and two types of cells (HepG2, MCF-7) and digested with two kinds of endonucleases (EcoR Ⅰ and EagⅠwhich is methylation sensitive endonuclease). And the condition of MXR7 gene methylation was examined and analyzed by Southern blot. Results: MXR7 was unmethylated neither in tested tumorous liver samples nor in paired non-HCC liver tissues. In addition, the same result was found in 2 blood tumor samples and HepG2. Only two paired samples had different methylation outcome, one was unmethylated and the other was partly methylated. Conclusion: MXR7 is unmethylated in HHC, suggesting methylation of MXR7 may have no relation with its expression and regulation.

  12. Occult HBV infection among Egyptian hepatocellular carcinoma patients

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    Mansor Tarek M

    2011-03-01

    Full Text Available Abstract Background Occult HBV infection accelerates the progression of liver fibrosis, cirrhosis, and finally leading to hepatocellular carcinoma (HCC. This study analyzed the occult HBV-genotypes in HCC patients. Methods To achieve our objective, matched serum and tissue samples were collected from 40 HCC patients. Three sets of primers were used for the HBV-DNA detection by nested-PCR, which cover the HBV-genome; Core, Surface and X genes. Genotyping system based on PCR using type-specific primers was applied on HBV-DNA positive samples. Results Intrahepatic occult HBV-DNA was detected in 62.5%, whereas; Serum occult HBV-DNA were detected in only 22.5% of HCC patients. In patients' positive for both anti-HBs and anti-HBc, 10% had occult HBV in serum. In serologically negative HCV patients, 63% had intrahepatic HBV-DNA, and 21% had HBV-DNA in serum samples. HBV-genotype D (32% and B (24% attributed predominantly to intrahepatic HBV infections in HCC patients, whereas HBV-genotype A (4% and C (8% infections were the least observed. Conclusion This is the first study to show the genotypes of occult HBV infection in HCC Patients. We suggest that B or D may influence the outcome of HBV infection which may lead to the development of HCC.

  13. Chemokine expression in hepatocellular carcinoma versus colorectal liver metastases

    Institute of Scientific and Technical Information of China (English)

    Claudia Rubie; Vilma Oliveira Frick; Mathias Wagner; Christina Weber; Bianca Kruse; Katja Kempf; Jochen K(o)nig; Bettina Rau; Martin Schilling

    2006-01-01

    AIM: To evaluate and compare the expression profiles of CXCL12 (SDF-1), CCL19 (MIP-3β), CCL20 (MIP-3α) and CCL21 (6Ckine, Exodus2) and their receptors on RNA and protein levels in hepatocellular carcinoma (HCC) versus colorectal liver metastases (CRLM) and to elucidate their impact on the carcinogenesis and progression of malignant liver diseases.METHODS: Chemokine expression was analyzed by RT-PCR and ELISA in 11 cases of HCC specimens and in 23 cases of CRLM and corresponding adjacent nontumorous liver tissues, respectively. Expressions of their receptors CXCR4, CCR6 and CCR7 were analyzed by RTPCR and Western blot analysis in the same cases of HCC and CRLM.RESULTS: Significant up-regulation for CCL20/CCR6 was detected in both cancer types. Moreover, CCL20demonstrated significant overexpression in CRLM in relation to the HCC tissues. Being significantly upregulated only in CRLM, CXCR4 displayed an aberrant expression pattern with respect to the HCC tissues.CONCLUSION: Correlation of CXCR4 expression with CRLM suggests CXCR4 as a potential predictive factor for CRLM. High level expression of CCL20 and its receptor CCR6 in HCC and CRLM with marked upregulation of CCL20 in CRLM in relation to HCC tissues indicates involvement of the CCL20/CCR6 ligand-receptor pair in the carcinogenesis and progression of hepatic malignancies.

  14. Significant biomarkers for the management of hepatocellular carcinoma.

    Science.gov (United States)

    Kondo, Yasuteru; Kimura, Osamu; Shimosegawa, Tooru

    2015-06-01

    Surveillance of hepatocellular carcinoma (HCC) is important for early detection. Imaging tests including computed tomography, magnetic resonance imaging and ultrasonography with or without various kinds of contrast medium are important options for detecting HCC. In addition to the imaging tests, various kinds of biomarkers including alpha-fetoprotein (AFP), lectin-bound AFP (AFP-L3) and protein induced by vitamin K absence or antagonist II (PIVKA-II) have been widely used to detect HCC and analyze treatment response. Recently, various kinds of novel biomarkers (proteins and miRNA) have been found to predict the malignancy potential of HCC and treatment response to specific therapies. Moreover, various combinations of well-established biomarkers and novel biomarkers have been tested to improve sensitivity and specificity. In practical terms, biomarkers that can be analyzed using peripheral blood samples might be more useful than immunohistochemical techniques. It has been reported that quantification of cytokines in peripheral blood and the analysis of peripheral immune subsets could be good biomarkers for managing HCC. Here, we describe the usefulness of and update well-established and novel biomarkers for the management of HCC.

  15. Intratumoral sampling variability in hepatocellular carcinoma: A case report

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The differential diagnosis between hepatocellular carcinoma (HCC) and regenerative liver nodules and other primary liver tumors may be very difficult,particularly when performed on liver biopsies. Difficulties in histological typing may be often minimized by immunohistochemistry. Among the numerous markers proposed, CK18, Hep Par1 and glypican 3 (GPC3) are considered the most useful in HCC diagnosis. Here we report a case of HCC in a 72-year-old male with HBV-related chronic liver disease, characterized by a marked morphological and immunohistochemical intratumoral variability. In this case, tumor grading ranged from areas extremely well differentiated, similar to regenerative nodule, to undifferentiated regions, with large atypical multinucleated cells. While almost all sub nodules were immunostained by Hep Par 1, immunoreactivity for glypican 3 and for Ck18 was patchy, with negative tumor region adjacent to the highly immunoreactive areas. Our case stresses the relevance of sampling variability in the diagnosis of HCC, and indicates that caution should be taken in grading an HCC and in the interpretation of immunohistochemical stains when only small core biopsies from liver nodules are available.

  16. Prognostic factors affecting postoperative survival ofpatients withsolitary small hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    MuYanCai; FengWeiWang; ChangPengLi; LiXuYan; JieWeiChen; RongZhenLuo; JingPingYun; YiXinZeng; DanXie

    2016-01-01

    Background:Small hepatocellular carcinoma (sHCC) is a unique variant of HCC that is characterized by small tumor size (maximum tumor diameter≤3cm) and favorable long‑term outcomes. The present study aimed to deifne clin‑icopathologic factors that predict survival in patients with sHCC. Methods:The study population consisted of 335 patients who underwent hepatectomy for solitary sHCC between December 1998 and 2010. Prognostic factors were evaluated using Kaplan–Meier curves and Cox proportional hazard models. Results:The 5‑year overall survival (OS) and recurrence‑free survival (RFS) rates were 77.7% and 59.9%, respectively. Kaplan–Meier curves showed that tumor size and vascular invasion had prognostic signiifcance within this relatively selected cohort (P Conclusions:Tumor size and vascular invasion are feasible and useful prognostic factors for sHCC. The proposed prognostic model, based on tumor size and vascular invasion, is informative in predicting survival in sHCC patients undergoing hepatectomy.

  17. Mechanical Stress Promotes Cisplatin-Induced Hepatocellular Carcinoma Cell Death

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    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.

  18. Complete hepatocellular carcinoma necrosis following sequential porto-arterial embolization

    Institute of Scientific and Technical Information of China (English)

    Stéphane Zalinski; Olivier Scatton; Bruto Randone; Olivier Vignaux; Bertrand Dousset

    2008-01-01

    Most patients with hepatocellular carcinoma (HCC) are not eligible for curative treatment, which is resection or transplantation. Two recent series have emphasized the potential benefits of preoperative arterio-portal embolization prior to surgical resection of such tumours. This preoperative strategy offers a better disease free survival rate and a higher rate of total tumor necrosis. In case of non resectable HCC it is now widely accepted that transarterial chemoembolization (TACE) leads to a better survival when compared to conservative treatment. Thus, the question remains whether combined portal vein embolization (PVE) may enhance the proven efficiency of TACE in patients with unresectable HCC. We herein report the case of a 56-year-old cirrhotic woman with a voluminous HCC unsuitable for surgical resection. Yet, complete tumour necrosis and prolonged survival could be achieved after a combined porto-arterial embolization. This case emphasizes the potential synergistic effect of a combined arterio-portal embolization and the hypothetical survival benefit of such a procedure, in selected patients, with HCC not suitable for surgery or local ablative therapy.

  19. Adrenal metastasis as first presentation of hepatocellular carcinoma

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    Zacharakis Evangelos

    2005-07-01

    Full Text Available Abstract Background Metastases from hepatocellular carcinoma (HCC can be found in the lung and adrenal gland. We report case of a patient who presented with adrenal metastasis as the first clinical manifestation of HCC. Case presentation A patient was referred for surgical treatment for a tumor in retro-peritoneal space. The computerized tomography (CT scan revealed a mass originating from the left adrenal gland. The patient underwent left adrenalectomy and the exploration of abdominal cavity did not reveal any other palpable lesions. Histologically, the resected lesion was a poorly differentiated metastatic tumor from HCC. Seven months later patient was readmitted complaining of cachexia, icterus, and significant weight loss. CT scan revealed hyperdense lesions of the liver Conclusion HCC may have atypical presentations like in present case. Fine needle aspiration/tru-cut® biopsy might be useful in the investigation of an accidentally discovered adrenal mass regardless of the size and can lead to the detection of a primary tumor.

  20. Clinical studies of hepatocellular carcinoma with liver cirrhosis and ascites.

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    Yuasa,Shiro

    1984-06-01

    Full Text Available A comparison was made of the clinical findings of 59 patients with liver cirrhosis (LC accompanied with hepatocellular carcinoma (HCC (of which 35 had ascites and 24 did not at the time of admission and 164 patients with LC, but without HCC (of which 39 had ascites and 125 did not. HCC patients were older and more often had hepatomegaly, vascular spider and pleural effusion than LC patients. Ascites was more frequently observed in HCC than in LC patients when the serum albumin level and the indocyanine green disappearance rate were relatively well maintained and when peripheral edema was absent. There was no difference in the ascitic protein concentration between LC and HCC patients. Malignant cells were detected in ascites only in 14% of the HCC patients. These facts indicate the presence of ascites-inducing factors in HCC patients which have no direct relation to serum colloid osmotic pressure and effective hepatic blood flow. Almost all of the HCC patients with ascites (96% died with ascites, whereas 54% of the LC patients with ascites recovered from the ascitic condition.

  1. Current status of laparoscopic liver resection for hepatocellular carcinoma.

    Science.gov (United States)

    Guro, Hanisah; Cho, Jai Young; Han, Ho-Seong; Yoon, Yoo-Seok; Choi, YoungRok; Periyasamy, Mohan

    2016-06-01

    Laparoscopic liver resection (LLR) is becoming widely accepted for the treatment of hepatocellular carcinoma (HCC). Laparoscopic left lateral sectionectomy and minor laparoscopic liver resection are now considered standard approaches, especially for tumors located in the anterolateral segments of the liver. Laparoscopic left lateral sectionectomy in adult donors is also gaining acceptance for child liver transplantation in many centers. Major LLRs, including left hepatectomy and right hepatectomy, have been recently attempted. Laparoscopic donor hepatectomy is becoming more popular owing to increasing demand from young living donors who appreciate its minimal invasiveness and excellent cosmetic outcomes. Several centers have performed total laparoscopic donor right hepatectomy in adult-to-adult living donor liver transplantation. Many meta-analyses have shown that LLR is better than open liver resection in terms of short-term outcomes, principally cosmetic outcomes. Although no randomized control trials have compared LLR with open liver resection, the long-term oncologic outcomes were similar for both procedures in recent case-matched studies.

  2. Tumor information extraction in radiology reports for hepatocellular carcinoma patients

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    Yim, Wen-wai; Denman, Tyler; Kwan, Sharon W.; Yetisgen, Meliha

    2016-01-01

    Hepatocellular carcinoma (HCC) is a deadly disease affecting the liver for which there are many available therapies. Targeting treatments towards specific patient groups necessitates defining patients by stage of disease. Criteria for such stagings include information on tumor number, size, and anatomic location, typically only found in narrative clinical text in the electronic medical record (EMR). Natural language processing (NLP) offers an automatic and scale-able means to extract this information, which can further evidence-based research. In this paper, we created a corpus of 101 radiology reports annotated for tumor information. Afterwards we applied machine learning algorithms to extract tumor information. Our inter-annotator partial match agreement scored at 0.93 and 0.90 F1 for entities and relations, respectively. Based on the annotated corpus, our sequential labeling entity extraction achieved 0.87 F1 partial match, and our maximum entropy classification relation extraction achieved scores 0.89 and 0. 74 F1 with gold and system entities, respectively. PMID:27570686

  3. Stratification of Hepatocellular Carcinoma Patients Based on Acetate Utilization

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    Elias Björnson

    2015-12-01

    Full Text Available Hepatocellular carcinoma (HCC is a deadly form of liver cancer that is increasingly prevalent. We analyzed global gene expression profiling of 361 HCC tumors and 49 adjacent noncancerous liver samples by means of combinatorial network-based analysis. We investigated the correlation between transcriptome and proteome of HCC and reconstructed a functional genome-scale metabolic model (GEM for HCC. We identified fundamental metabolic processes required for cell proliferation using the network centric view provided by the GEM. Our analysis revealed tight regulation of fatty acid biosynthesis (FAB and highly significant deregulation of fatty acid oxidation in HCC. We predicted mitochondrial acetate as an emerging substrate for FAB through upregulation of mitochondrial acetyl-CoA synthetase (ACSS1 in HCC. We analyzed heterogeneous expression of ACSS1 and ACSS2 between HCC patients stratified by high and low ACSS1 and ACSS2 expression and revealed that ACSS1 is associated with tumor growth and malignancy under hypoxic conditions in human HCC.

  4. Aberrant regulation of Wnt signaling in hepatocellular carcinoma

    Science.gov (United States)

    Liu, Li-Juan; Xie, Shui-Xiang; Chen, Ya-Tang; Xue, Jing-Ling; Zhang, Chuan-Jie; Zhu, Fan

    2016-01-01

    Hepatocellular carcinoma (HCC) is one of the most lethal malignancies in the world. Several signaling pathways, including the wingless/int-1 (Wnt) signaling pathway, have been shown to be commonly activated in HCC. The Wnt signaling pathway can be triggered via both catenin β1 (CTNNB1)-dependent (also known as “canonical”) and CTNNB1-independent (often referred to as “non-canonical”) pathways. Specifically, the canonical Wnt pathway is one of those most frequently reported in HCC. Aberrant regulation from three complexes (the cell-surface receptor complex, the cytoplasmic destruction complex and the nuclear CTNNB1/T-cell-specific transcription factor/lymphoid enhancer binding factor transcriptional complex) are all involved in HCC. Although the non-canonical Wnt pathway is rarely reported, two main non-canonical pathways, Wnt/planar cell polarity pathway and Wnt/Ca2+ pathway, participate in the regulation of hepatocarcinogenesis. Interestingly, the canonical Wnt pathway is antagonized by non-canonical Wnt signaling in HCC. Moreover, other signaling cascades have also been demonstrated to regulate the Wnt pathway through crosstalk in HCC pathogenesis. This review provides a perspective on the emerging evidence that the aberrant regulation of Wnt signaling is a critical mechanism for the development of HCC. Furthermore, crosstalk between different signaling pathways might be conducive to the development of novel molecular targets of HCC. PMID:27672271

  5. Family history influences the early onset of hepatocellular carcinoma

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    Park, Chung-Hwa; Jeong, Seung-Hee; Yim, Hyeon-Woo; Kim, Jin Dong; Bae, Si Hyun; Choi, Jong Young; Yoon, Seung Kew

    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. PMID:22690075

  6. Liver Surgery for Hepatocellular Carcinoma: Laparoscopic versus Open Approach

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    C. G. Ker

    2011-01-01

    Full Text Available In this study, we try to compare the benefit of laparoscopic versus open operative procedures. Patients and Methods. One hundred and sixteen patients underwent laparoscopic liver resection (LR and another 208 patients went for open liver resection (OR for hepatocellular carcinoma (HCC. Patients' selection for open or laparoscopic approach was not randomized. Results. The CLIP score for LR and OR was 0.59 ± 0.75 and 0.86 ± 1.04, respectively, (=.016. The operation time was 156.3 ± 308.2 and 190.9 ± 79.2 min for LR and OR groups, respectively. The necessity for blood transfusion was found in 8 patients (6.9% and 106 patients (50.9% for LR and OR groups. Patients resumed full diet on the 2nd and 3rd postoperative day, and the average length of hospital stay was 6 days and 12 days for LR and OR groups. The complication rate and mortality rate were 0% and 6.0%, 2.9% and 30.2% for LR and OR groups, respectively. The 1-yr, 3-yr, and 5-yr survival rate was 87.0%, 70.4%, 62.2% and 83.2%, 76.0%, 71.8% for LR and OR group, respectively, of non-significant difference. From these results, HCC patients accepted laparoscopic or open approach were of no significant differences between their survival rates.

  7. Multiple Ectopic Hepatocellular Carcinomas Arising in the Abdominal Cavity

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    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.

  8. Hepatitis B and alcohol affect survival of hepatocellular carcinoma patients

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    Linda L. Wong; Whitney M. Limm; Naoky Tsai; Richard Severino

    2005-01-01

    AIM: In the USA, Hawaii has the highest incidence of hepatocellular carcinoma (HCC) and a diverse population.It is an ideal place to characterize HCC in the context of ethnicity/risk factors.METHODS: A total of 262 cases of HCC (1992-2003) were retrospectively reviewed for demographics, ethnicity, birthplace, viral hepatitis, alcohol use, diabetes, smoking and risk factors for viral hepatitis such as intravenous drug abuse (IVDA), transfusions, tattoos and vertical transmission. Tumor stage, Child's class, Cancer of the Liver Italian Program (CLIP) score, α-fetoprotein level, treatment and survival were recorded.RESULTS: Gender, age, viral hepatitis, alcohol, IVDA, and diabetes differed significantly in Asians, non-Asians and Pacific Islanders. There were also specific differences within Asian subgroups. Alpha-fetoprotein, smoking, transfusions, stage and resectability did not differ between groups. Asians were more likely to have hepatitis B, while non-Asians were more likely to have hepatitis C. Factors that decreased survival included hepatitis B, alcohol, elevated alpha-fetoprotein, CLIP >2 and increased Child's class. When Asians were combined with Pacific Islanders, median survival (1.52 years vs 3.54 years), 1- and 3-year survival was significantly worse than those for non-Asians. After Cox regression analysis for hepatitis B and alcohol, there was no difference in survival by ethnicity.CONCLUSION: Various ethnicities have different risk factors for HCC. Hepatitis B, alcohol, and α-fetoprotein are more important factors for survival than ethnicity.

  9. Prevention of hepatocellular carcinoma in patients with chronic hepatitis B

    Institute of Scientific and Technical Information of China (English)

    Conrado; M; Fernández-Rodríguez; María; Luisa; Gutiérrez-García

    2014-01-01

    Patients with chronic hepatitis B are at significant risk for hepatocellular carcinoma(HCC). Globally,over half a million people each year are diagnosed with HCC,with marked geographical variations. Despite overwhelming evidence for a causal role of hepatitis B virus(HBV) infection in the development of HCC and a well-established relationship between high baseline hepatitis B viral load and cumulative risk of HCC,the molecular basis for this association has not been fully elucidated. In addition,a beneficial role for antiviral therapy in preventing the development of HCC has been difficult to establish. This review examines the biological and molecular mechanisms of HBV-related hepatocarcinogenesis,recent results on the effect of modern nucleos(t)ides on the rate of HCC development in high risk HBV cohorts and the potential mechanisms by which long-term antiviral therapy with potent inhibitors of HBV replication might reduce the risk of HCC in patients with chronic hepatitis B. Although evidence from randomized controlled trials shows the favourable effects of antiviral agentsin achieving profound and durable suppression of HBV DNA levels while improving liver function and histology,robust evidence of other long-term clinical outcomes,such as prevention of HCC,are limited.

  10. An Analysis of Immunoreactive Signatures in Early Stage Hepatocellular Carcinoma

    Science.gov (United States)

    Hong, Yu; Long, Jiang; Li, Hai; Chen, Shuhong; Liu, Qiqi; Zhang, Bei; He, Xiaomin; Wang, Yan; Li, Hongyi; Li, Yimei; Zhang, Tao; Lu, Chenzhen; Yan, Hao; Zhang, Minli; Li, Qing; Cao, Bangwei; Bai, Zhigang; Wang, Jin; Zhang, Zhongtao; Zhu, Shengtao; Zheng, Jiasheng; Ou, Xiaojuan; Ma, Hong; Jia, Jidong; You, Hong; Wang, Shengqi; Huang, Jian

    2015-01-01

    Background Hepatocellular carcinoma (HCC) is prevalent worldwide and early diagnosis of HCC is critical for effective treatment and optimal prognosis. Methods Serum was screened first by immunoproteomic analysis for HCC-related tumor associated antigens (TAAs). Selected TAAs were clinically evaluated retrospectively in patients with HCC, liver cirrhosis, chronic hepatitis and healthy controls. Levels of autoantibody to the selected TAAs were measured by protein microarrays containing protein antigens of the candidate TAAs. Analyses were done by using receiver operating characteristics (ROC) to calculate diagnostic accuracy. Findings Twenty-two candidate TAAs were assessed by protein microarray analysis in 914 participants with serum α-fetoprotein (AFP) available. Twelve candidate TAAs were statistically different in signal intensity between HCC and controls. Among them, CENPF, HSP60 and IMP-2 showed AUC (area under the curve) values of 0.826, 0.764 and 0.796 respectively for early HCC. The highest prevalence of autoantibody positivity was observed in HCC cases with BCLC tumor stage A, well-differentiated histology and Child-Pugh grade C. Specifically, 73.6% or 79.3% cases of early HCC with negative AFP were positive for autoantibody to CENPF or HSP60. Interpretation Tumor-associated autoimmune reactions may be triggered by early stage HCCs. Measurement of serum autoantibody to TAAs may be complementary to AFP measurements and improve diagnosis of early HCC. PMID:26137588

  11. Recurrently deregulated lncRNAs in hepatocellular carcinoma

    Science.gov (United States)

    Yang, Yang; Chen, Lei; Gu, Jin; Zhang, Hanshuo; Yuan, Jiapei; Lian, Qiuyu; Lv, Guishuai; Wang, Siqi; Wu, Yang; Yang, Yu-Cheng T.; Wang, Dongfang; Liu, Yang; Tang, Jing; Luo, Guijuan; Li, Yang; Hu, Long; Sun, Xinbao; Wang, Dong; Guo, Mingzhou; Xi, Qiaoran; Xi, Jianzhong; Wang, Hongyang; Zhang, Michael Q.; Lu, Zhi John

    2017-01-01

    Hepatocellular carcinoma (HCC) cells often invade the portal venous system and subsequently develop into portal vein tumour thrombosis (PVTT). Long noncoding RNAs (lncRNAs) have been associated with HCC, but a comprehensive analysis of their specific association with HCC metastasis has not been conducted. Here, by analysing 60 clinical samples' RNA-seq data from 20 HCC patients, we have identified and characterized 8,603 candidate lncRNAs. The expression patterns of 917 recurrently deregulated lncRNAs are correlated with clinical data in a TCGA cohort and published liver cancer data. Matched array data from the 60 samples show that copy number variations (CNVs) and alterations in DNA methylation contribute to the observed recurrent deregulation of 235 lncRNAs. Many recurrently deregulated lncRNAs are enriched in co-expressed clusters of genes related to cell adhesion, immune response and metabolic processes. Candidate lncRNAs related to metastasis, such as HAND2-AS1, were further validated using RNAi-based loss-of-function assays. Thus, we provide a valuable resource of functional lncRNAs and biomarkers associated with HCC tumorigenesis and metastasis. PMID:28194035

  12. Hong Kong Consensus Recommendations on the Management of Hepatocellular Carcinoma

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    Poon, Ronnie Tung-Ping; Cheung, Tom Tan-To; Kwok, Philip Chong-Hei; Lee, Ann-Shing; Li, Tat-Wing; Loke, Kwok-Loon; Chan, Stephen Lam; Cheung, Moon-Tong; Lai, Tak-Wing; Cheung, Chin-Cheung; Cheung, Foon-Yiu; Loo, Ching-Kong; But, Yiu-Kuen; Hsu, Shing-Jih; Yu, Simon Chun-Ho; Yau, Thomas

    2015-01-01

    Background Hepatocellular carcinoma (HCC) is particularly prevalent in Hong Kong because of the high prevalence of chronic hepatitis B (CHB) infection; HCC is the fourth commonest cancer in men and the seventh commonest in women, and it is the third leading cause of cancer death in Hong Kong. The full spectrum of treatment modalities for HCC is available locally; however, there is currently no local consensus document detailing how these modalities should be used. Summary In a series of meetings held between May and October 2013, a multidisciplinary group of Hong Kong clinicians − liver surgeons, medical oncologists, clinical oncologists, hepatologists, and interventional radiologists − convened to formulate local recommendations on HCC management. These recommendations consolidate the most current evidence pertaining to HCC treatment modalities, together with the latest thinking of practicing clinicians engaged in HCC management, and give detailed guidance on how to deploy these modalities effectively for patients in various disease stages. Key messages Distinct from other regional guidelines, these recommendations provide guidance on the use of antiviral therapy to reduce the incidence of HCC in CHB patients with cirrhosis and to reduce recurrence of CHB-related HCC. PMID:26020029

  13. Radiofrequency Ablation of Hepatocellular Carcinoma: A Literature Review

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    Yasunori Minami

    2011-01-01

    Full Text Available Radiofrequency ablation (RFA of liver cancers can be performed safely using percutaneous, laparoscopic, or open surgical techniques, and much of the impetus for the use of RFA has come from cohort series that have provided an evidence base for this technique. Here, we give an overview of the current status of radiofrequency ablation (RFA for hepatocellular carcinoma (HCC, including its physical properties, to assess the characteristics that make this technique applicable in clinical practice. We review the technical development of probe design and summarize current indications and outcomes of reported clinical use. An accurate evaluation of treatment response is very important to secure successful RFA therapy since a sufficient safety margin (at least 0.5 cm can prevent local tumor recurrences. We also provide a profile of side effects and information on the integration of this technique into the general management of patients with HCC. To minimize complications of RFA, physicians should be familiar with each feature of complication. Appropriate management of complications is essential for successful RFA treatment. Moreover, adjuvant therapy, such as molecular targeted therapies following curative therapy, is expected to further improve survival after RFA.

  14. An overview of loco-regional treatments in patients and mouse models for hepatocellular carcinoma.

    Science.gov (United States)

    Bimonte, Sabrina; Barbieri, Antonio; Palaia, Raffaele; Leongito, Maddalena; Albino, Vittorio; Piccirillo, Mauro; Arra, Claudio; Izzo, Francesco

    2015-01-01

    Hepatocellular carcinoma is a highly aggressive malignancy and is the third leading cause of cancer-related deaths worldwide. Although surgery is currently considered the most effective curative treatment for this type of cancer, it is note that most of patients have a poor prognosis due to chemioresistence and tumor recurrence. Loco-regional therapies, including radiofrequency ablation, surgical resection and transcatheter arterial chemoembolization play a major role in the clinical management of hepatocellular carcinoma. In order to improve the treatment outcome of patients diagnosed with this disease, several in vivo studies by using different techniques on cancer mouse models have been performed. This review will focus on the latest papers on the efficacy of loco-regional therapy and combined treatments in patients and mouse models of hepatocellular carcinoma.

  15. Budd-Chiari syndrome as an initial presentation of hepatocellular carcinoma: a case report.

    Science.gov (United States)

    Bălăceanu, Lavinia Alice; Diaconu, Camelia Cristina; Aron, Gheorghiţa

    2014-06-01

    We report the case of a 84-year-old admitted with symptoms of congestive heart failure. Ultrasonography revealed a hyperechoic nodule in the left lobe of the liver, with a peripheral hypoechoic rim, multiple irregular hypoechoic nodules in both hepatic lobes, portal vein, inferior vena cava, and right atrium thrombosis. On ultrasonographic and alpha-fetoprotein criteria the case was interpreted as hepatocellular carcinoma with Budd-Chiari syndrome. The particularity of the case is the initial presentation of the hepatocellular carcinoma as Budd-Chiari syndrome. The inferior vena cava and right atrium thrombosis, as a cause of secondary Budd-Chiari syndrome in a patient with hepatocellular carcinoma, has been rarely reported.

  16. WJH 6th Anniversary Special Issues(2): Hepatocellular carcinoma Problem of hepatocellular carcinoma in West Africa

    Institute of Scientific and Technical Information of China (English)

    Nimzing; G; Ladep; Olufunmilayo; A; Lesi; Pantong; Mark; Maud; Lemoine; Charles; Onyekwere; Mary; Afihene; Mary; ME; Crossey; Simon; D; Taylor-Robinson

    2014-01-01

    The incidence of hepatocellular carcinoma(HCC) isknown to be high in West Africa with an approximateyearly mortality rate of 200000. Several factors are responsible for this. Early acquisition of risk factors; with vertical or horizontal transmission of hepatitis B(HBV), environmental food contaminants(aflatoxins), poor management of predisposing risk factors and poorlymanaged strategies for health delivery. There has been a low uptake of childhood immunisation for hepatitis B in many West African countries. Owing to late presentations, most sufferers of HCC die within weeks of their diagnosis. Highlighted reasons for the specific disease pattern of HCC in West Africa include:(1) high rate of risk factors;(2) failure to identify at risk populations;(3) lack of effective treatment; and(4) scarce resources for timely diagnosis. This is contrasted to the developed world, which generally has sufficient resources to detect cases early for curative treatment. Provision of palliative care for HCC patients is limited by availability and affordability of potent analgesics. Regional efforts, as well as collaborative networking activities hold promise that could change the epidemiology of HCC in West Africa.

  17. Recent advances in multidisciplinary management ofhepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Asmaa I Gomaa; Imam Waked

    2015-01-01

    The incidence of hepatocellular carcinoma (HCC)is increasing, and it is currently the second leadingcause of cancer-related death worldwide. Potentiallycurative treatment options for HCC include resection,transplantation, and percutaneous ablation, whereaspalliative treatments include trans-arterial chemoembolization(TACE), radioembolization, and systemictreatments. Due to the diversity of available treatmentoptions 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 moleculartargeted 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.

  18. Des-gamma-carboxy prothrombin as an important prognostic indicator in patients with small hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Kenichi Hakamada; Norihisa Kimura; Takuya Miura; Hajime Morohashi; Keinosuke Ishido; Masaki Nara; Yoshikazu Toyoki; Shunji Narumi; Mutsuo Sasaki

    2008-01-01

    AIM:To clarify the effect of a high des-gamma-carboxy prothrombin (DCP) level on the invasiveness and prognosis of small hepatocellular carcinoma.METHODS:Among 142 consecutive patients with known DCP levels,who underwent hepatectomy because of hepatocellular carcinoma,85 patients met the criteria for small hepatocellular carcinoma,i.e.one≤5 cm sized single tumor or no more than three≤3 cm sized tumors.RESULTS:The overall survival rate of the 142 patients was 92.1% for 1 year,69.6% for 3 years,and 56.9% for 5 years.Multivariate analysis showed that microscopic vascular invasion (P = 0.03) and serum DCP≥400mAU/mL (P = 0.02) were independent prognostic factors.In the group of patients who met the criteria for small hepatocellular carcinoma,DCP≥400 mAU/mL was found to be an independent prognostic factor for recurrence-free (P = 0.02) and overall survival (P = 0.0005).In patients who did not meet the criteria,the presence of vascular invasion was an independent factor for recurrence-free (P = 0.02) and overall survivals (P = 0.01).In 75% of patients with small hepatocellular carcinoma and high DCP levels,recurrence occurred extrahepatically.CONCLUSION:For small hepatocellular carcinoma,a high preoperative DCP level appears indicative for tumor recurrence.Because many patients with a high preoperative DCP level develop extrahepatic recurrence,it is necessary to screen the whole body.

  19. 中药对肝癌细胞信号转导通路影响的研究进展%Advances in research on Chinese medicines that can induce apoptosis of hepatocellular carcinoma cells by the signal transduction pathway

    Institute of Scientific and Technical Information of China (English)

    濮忠建; 华海清

    2011-01-01

    As the research on the signal transduction pathway of tumor is developing, people has become more aware of the confusion of the signal transduction mechanisms on the tumor cells and their effects on tumor growth, apoptosis, and metastasis. Currently, the research that Chinese medicine and its extract inducing apoptosis and angiogenesis of hepatocellular carcinoma by acting on the signal transduction pathway has made gratifying progress. In this article, we will provide an overview of recent literature about this.%随着对肿瘤信号转导通路研究的不断深入,人们对肿瘤细胞内部复杂的信号转导机制以及它们对肿瘤生长、凋亡和转移等的影响越来越了解.目前,中药及其提取物通过作用于信号转导通路诱导肝癌细胞凋亡、影响肝癌血管生成的研究已取得可喜进步.现对近年来有关文献进行回顾,就此进展作一综述.

  20. Major liver resection for hepatocellular carcinoma in the morbidly obese: A proposed strategy to improve outcome

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    Ozaki Claire F

    2008-09-01

    Full Text Available Abstract Background Morbid obesity strongly predicts morbidity and mortality in surgical patients. However, obesity's impact on outcome after major liver resection is unknown. Case presentation We describe the management of a large hepatocellular carcinoma in a morbidly obese patient (body mass index >50 kg/m2. Additionally, we propose a strategy for reducing postoperative complications and improving outcome after major liver resection. Conclusion To our knowledge, this is the first report of major liver resection in a morbidly obese patient with hepatocellular carcinoma. The approach we used could make this operation nearly as safe in obese patients as it is in their normal-weight counterparts.

  1. Enhancement of antitumor vaccine in ablated hepatocellular carcinoma by high-intensity focused ultrasound

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    AIM:To investigate whether tumor debris created by high-intensity focused ultrasound(HIFU)could trigger antitumor immunity in a mouse hepatocellular carcinoma model. METHODS:Twenty C57BL/6J mice bearing H22 hepatocellular carcinoma were used to generate antitumor vaccines.Ten mice underwent HIFU ablation,and the remaining 10 mice received a sham-HIFU procedure with no ultrasound irradiation.Sixty normal mice were randomly divided into HIFU vaccine,tumor vaccine and control groups.These mice were immunized w...

  2. Chronic renal disease in a captive two-toed sloth (Choloepus didactylus) with concurrent hepatocellular carcinoma.

    Science.gov (United States)

    Salas, Elisa; Wolf, Tiffany; Harris, Seth

    2014-06-01

    A 13-yr-old female two-toed sloth (Choloepus didactylus) with a prolonged history of worsening azotemia was necropsied shortly after euthanasia. On necropsy, the sloth had poor body condition, bilaterally shrunken kidneys, and a large neoplastic mass replacing the right liver lobe. Histologic examination demonstrated chronic renal disease with metastatic mineralization as the cause of morbidity. The liver mass was not associated with any known clinical signs and was diagnosed as a solitary and well-differentiated hepatocellular carcinoma. To the authors' knowledge, this is the first report of hepatocellular carcinoma diagnosed in a sloth and the first detailed description of chronic renal disease in this species.

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

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    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

  4. Hepatocellular carcinoma surgery outcomes in the developing world: A 20-year retrospective cohort study at the National Cancer Institute of Peru

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    Eloy Ruiz

    2016-01-01

    Full Text Available In the developing world, most patients with hepatocellular carcinoma present with advanced-stage disease, considered to be incurable based on current therapeutic algorithms. Here, we demonstrate that curative liver resection is achievable in a portion of Peruvian patients not addressed by these treatment algorithms. We conducted a retrospective cohort study of 253 hepatocellular carcinoma patients that underwent a curative hepatectomy between 1991 and 2011 at the National Cancer Institute of Peru. The median age of the cohort was 36 years, and merely 15.4% of the patients displayed cirrhosis. The average tumor size was over 14 cm in diameter, resulting in 76.3% of major hepatectomies performed. The 5- and 10-year survival probability estimates were 37.5% and 26.2%, respectively. Age (>44 vs. ≤44 years old; P = 0.005, tumor size (>10 cm vs. ≤10 cm in diameter; P = 0.009, cirrhosis (P < 0.001, satellite lesions (P < 0.001, macroscopic vascular invasion (P < 0.001, allogeneic blood transfusion (P = 0.011, and spontaneous rupture of the tumor (P = 0.006 were independent predictive factors for prognosis. Hepatocellular carcinomas in Peru are characterized by a distinct clinical presentation with notable features compared with those typically described throughout relevant literature. Despite a large number of advanced-stage hepatocellular carcinomas, the outcomes of liver resection observed in the present study were in good standing with the results previously described in other series. It thus appears that staging systems and associated therapeutic algorithms designed for use in the developed world remain inadequate in certain populations, especially in the context of Peruvian patients. Our findings suggest that clinicians in the developing world should reconsider management guidelines pertaining to hepatocellular carcinoma. Indeed, we hypothesize that, in developing countries, a strict adherence to these therapeutic algorithms might create a

  5. Solitary Large Hepatocellular Carcinoma: Staging and Treatment Strategy.

    Directory of Open Access Journals (Sweden)

    Po-Hong Liu

    Full Text Available Controversies exist on staging and management of solitary large (>5 cm hepatocellular carcinoma (HCC. This study aims to evaluate the impact of tumor size on Barcelona Clinic Liver Cancer (BCLC staging and treatment strategy.BCLC stage A and B patients were included and re-classified as single tumor 2-5 cm or up to 3 tumors ≤3 cm (group A; n = 657, single tumor >5 cm (group SL; n = 224, and multiple tumors >3 cm (group B; n = 351. Alternatively, 240 and 229 patients with solitary large HCC regardless of tumor stage received surgical resection (SR and transarterial chemoembolization (TACE, respectively. The propensity score analysis identified 156 pairs of patients from each treatment arm for survival comparison.The survival was significantly higher for group A but was comparable between group SL and group B patients. Of patients with solitary large HCC, the 1-, 3- and 5-year survival rates were 88% versus 74%, 76% versus 44%, and 63% versus 35% between SR and TACE group, respectively (p<0.001. When baseline demographics were adjusted in the propensity model, the respective 1-, 3- and 5-year survival rates were 87% versus 79%, 76% versus 46%, and 61% versus 36% (p<0.001. The Cox proportional hazards model identified TACE with a 2.765-fold increased risk of mortality compared with SR (95% confidence interval: 1.853-4.127, p<0.001.Patients with solitary large HCC should be classified at least as intermediate stage HCC. SR provides significantly better survival than TACE for solitary large HCC regardless of tumor stage. Further amendment to the BCLC classification is mandatory.

  6. Intermediate hepatocellular carcinoma: How to choose the best treatment modality?

    Science.gov (United States)

    Di Costanzo, Giovan Giuseppe; Tortora, Raffaella

    2015-05-28

    Intermediate stage, or stage B according to Barcelona Clinic Liver Cancer classification, of hepatocellular carcinoma (HCC) comprises a heterogeneous population with different tumor burden and liver function. This heterogeneity is confirmed by the large variability of treatment choice and disease-relate survival. The aim of this review was to highlight the existing evidences regarding this specific topic. In a multidisciplinary evaluation, patients with large (> 5 cm) solitary HCC should be firstly considered for liver resection (LR). When LR is unfeasible, locoregional treatments are evaluable therapeutic options, being transarterial chemoembolization (TACE), the most used procedure. Percutaneous ablation can be an evaluable treatment for large HCC. However, the efficacy of all ablative procedures decrease as tumor size increases over 3 cm. In clinical practice, a combination treatment strategy [TACE or transarterial radioembolization (TARE)-plus percutaneous ablation] is "a priori" preferred in a relevant percentage of these patients. On the other hands, sorafenib is the treatment of choice in patients who are unsuitable to surgery and/or with a contraindication to locoregional treatments. In multifocal HCC, TACE is the first-line treatment. The role of TARE is still undefined. Surgery may have also a role in the treatment of multifocal HCC in selected cases (patients with up to three nodules, multifocal HCC involving 2-3 adjacent liver segments). In some patients with bilobar disease the combination of LR and ablative treatment may be a valuable option. The choice of the best treatment in the patient with intermediate stage HCC should be "patient-tailored" and made by a multidisciplinary team.

  7. 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.

  8. HLA class I expression in primary hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Jian Huang; Mei-Ying Cai; Da-Peng Wei

    2002-01-01

    AIM: To investigate whether CTL vaccine therapy issuitable for primary hepatocellular carcinoma (HCC)from the viewpoint of HLA class I antigens expression.METHODS: The immunocytochemistry, image analysis,flow cytometry, and labeled streptavidin biotin (LSAB)method of immunohistochemistry were appliedrespectively to study 4 HCC cell lines (e.g. Alexander,HepG2, SMMC-7721, and QGY-7703) cultured in vitroand 6 frozen tissue specimens of HCC. RESULTS: The positive control cell line Raji had verystrong positive staining. Most mitotic and nonmitoticcells of the 4 HCC cell lines had various intensity ofHLA class Ⅰ antigens expression. The negative controlcell K562 and the control slides of all the cell lines hadno positive staining. In the 6 HCC specimensimmunohistochemically studied, histological normalhepatocytes had no or very weak positive staining andthe liver sinus had very strong positive staining. MostHCC cells in the sections from the 6 HCC specimenshad strong positive HLA class Ⅰ antigens staining. Thepositive staining was located in the cytoplasm, theperinuclear area, and at the cell membrane of the livercancer cells. Flow cytometry also revealed that Raji andthose 4 HCC cell lines had strong HLA class Ⅰ antigensexpression, which was confirmed quantitatively by theimage analysis. Tt showed that the objective grayscalevalues of Raji and those 4 HCC cell lines weresignificantly different from that of K562 (Raji 124.04+10.94, Alexander 165.97+5.35, HepG2 167.02+12.60,QGY-7703 161.46+7.13, SMMC-7721 165.93+5.21,K562 244.89+4.60, P<0.01). Significant differenceswere also found between Raji and the 4 HCC cell lines.CONCLUSION: HCC cells express HLA class I antigensstrongly. From this point of view, the active specificimmunotherapy of CTL vaccine is suitable andpracticable for HCC.

  9. Tumour seeding after percutaneous cryoablation for hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Chun-Ping Wang; Hong Wang; Jian-Hui Qu; Yin-Ying Lu; Wen-Lin Bai; Zheng Dong; Xu-Dong Gao

    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.

  10. The importance of a multidisciplinary approach to hepatocellular carcinoma

    Science.gov (United States)

    Siddique, Osama; Yoo, Eric R; Perumpail, Ryan B; Perumpail, Brandon J; Liu, Andy; Cholankeril, George; Ahmed, Aijaz

    2017-01-01

    Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide. The rising incidence, genetic heterogeneity, multiple etiologies, and concurrent chronic liver diseases make diagnosis, staging, and selection of treatment options challenging in patients with HCC. The best approach to optimize the management of HCC is one that utilizes a core multidisciplinary liver tumor board, consisting of hepatologists, pathologists, interventional radiologists, oncologists, hepatobiliary and transplant surgeons, nurses, and general practitioners. In most cases, HCC is diagnosed by abdominal imaging studies, preferably with a triphasic computed tomography scan of the abdomen or magnetic resonance imaging of the abdomen. Histopathological diagnosis using a guided liver biopsy may be needed in noncirrhotic patients or when radiological diagnostic criteria are not fulfilled in the setting of cirrhosis. The Barcelona Clinic Liver Cancer staging system facilitates a standardized therapeutic strategy based on the tumor burden, extent of metastasis, severity of hepatic decompensation, comorbid medical illnesses, functional status of patient, HCC-related symptoms, and preference of the patient. Treatment options include curative surgery (hepatic resection and liver transplantation) and palliative measures (radiofrequency ablation, transarterial chemoembolization, and chemotherapy with sorafenib). The role of the multidisciplinary team is crucial in promptly reconfirming the diagnosis, staging the HCC, and formulating an individualized treatment plan. In potential liver transplant candidates, timely liver transplant evaluation and coordinating bridging/downsizing treatment modalities, such as radiofrequency ablation and transarterial chemoembolization, can be time-consuming. In summary, a multidisciplinary team approach provides a timely, individualized treatment plan, which can vary from curative surgery in patients with early-stage HCC to palliative

  11. 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

  12. Surgical treatment of hepatocellular carcinoma:Evidence-based outcomes

    Institute of Scientific and Technical Information of China (English)

    Shintaro Yamazaki; Tadatoshi Takayama

    2008-01-01

    Surgeons may be severely criticized from the perspective of evidence-based medicine because the majority of surgical publications appear not to be convincing.In the top nine surgical journals in 1996,half of the 175publications refer to pilot studies lacking a control group,18% to animal experiments,and only 5% to randomized controlled trials (RCT).There are five levels of clinical evidence:level 1 (randomized controlled trial),level 2 (prospective concurrent cohort study),level 3 (retrospective historical cohort study),level 4(pre-post study),and level 5 (case report).Recently,a Japanese evidence-based guideline for the surgical treatment of hepatocellular carcinoma (HCC) was made by a committee (Chairman,Professor Makuuchi and five members).We searched the literature using the Medline Dialog System with four keywords:HCC,surgery,English papers,in the last 20 years.A total of 915 publications were identified systematically reviewed.At the first selection (in which surgery-dominant papers were Selected),478 papers survived.In the second selection (clearly concluded papers),181 papers survived.In the final selection (clinically significant papers),100 papers survived.The evidence level of the 100 surviving papers is shown here:level-1 papers (13%),level-2 papers (11%),level-3 papers (52%),and level-4 papers (24%);therefore,there were 24% prospective papers and 76%retrospective papers.Here,we present a part of the guideline on the five main surgical issues:indication to operation,operative procedure,peri-operative care,prognostic factor,and post-operative adjuvant therapy.

  13. Hepatitis B virus genotypes and hepatocellular carcinoma in Thailand

    Institute of Scientific and Technical Information of China (English)

    Pisit Tangkijvanich; Varocha Mahachai; Piyawat Komolmit; Juthatip Fongsaru; Apiradee Theamboonlers; Yong Poovorawan

    2005-01-01

    AIM: The role of hepatitis B virus (HBV) genotypes on the clinical features and prognosis of patients with hepatocellular carcinoma (HCC) is currently unknown. The aim of the present study was to evaluate the distribution of HBV genotypes and their clinical relevance in Thai patients.METHODS: HBV genotypes were determined by PCR-RFLP in stored sera of 93 asymptomatic carriers, 103 patients with chronic hepatitis, 60 patients with cirrhosis and 76patients with HCC. The clinical data were analyzed in relation to the HBV genotype.RESULTS: HBV genotypes C and B were predominant in Thailand, accounting for 73% and 21%, respectively. The distributions of genotypes B and C were similar in HCC patients compared to the other groups. Genotype C was significantly more common in HCC patients who were under 40 years old than genotype B (18% vs 0%, P= 0.03), but was significantly less common in patients older than 60 years (26% vs 56.5%, P= 0.01). The positive rate of hepatitis B e antigen (HBeAg) in patients with genotype C was significantly higher than that in patients with genotype B (71.6% vs 44.4%, P = 0.03 in chronic hepatitis; 56.8% vs 11.1%,P = 0.01 in cirrhosis). There were no differences between HCC patients with genotypes B and C regarding tumor staging by CLIP criteria and the overall median survival. Multivariate analyses showed that HBV genotype was not an independent prognostic factor of survival in HCC patients.CONCLUSION: Patients with genotype C had a higher positive rate of HBeAg and exhibited earlier progression of cirrhosis and HCC than those with genotype B. However,there were no differences in the risk of developing HCC and its prognosis between patients with these genotypes.

  14. 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.

  15. Intermediate hepatocellular carcinoma: How to choose the best treatment modality?

    Science.gov (United States)

    Di Costanzo, Giovan Giuseppe; Tortora, Raffaella

    2015-01-01

    Intermediate stage, or stage B according to Barcelona Clinic Liver Cancer classification, of hepatocellular carcinoma (HCC) comprises a heterogeneous population with different tumor burden and liver function. This heterogeneity is confirmed by the large variability of treatment choice and disease-relate survival. The aim of this review was to highlight the existing evidences regarding this specific topic. In a multidisciplinary evaluation, patients with large (> 5 cm) solitary HCC should be firstly considered for liver resection (LR). When LR is unfeasible, locoregional treatments are evaluable therapeutic options, being transarterial chemoembolization (TACE), the most used procedure. Percutaneous ablation can be an evaluable treatment for large HCC. However, the efficacy of all ablative procedures decrease as tumor size increases over 3 cm. In clinical practice, a combination treatment strategy [TACE or transarterial radioembolization (TARE)-plus percutaneous ablation] is “a priori” preferred in a relevant percentage of these patients. On the other hands, sorafenib is the treatment of choice in patients who are unsuitable to surgery and/or with a contraindication to locoregional treatments. In multifocal HCC, TACE is the first-line treatment. The role of TARE is still undefined. Surgery may have also a role in the treatment of multifocal HCC in selected cases (patients with up to three nodules, multifocal HCC involving 2-3 adjacent liver segments). In some patients with bilobar disease the combination of LR and ablative treatment may be a valuable option. The choice of the best treatment in the patient with intermediate stage HCC should be “patient-tailored” and made by a multidisciplinary team. PMID:26019734

  16. Increased HCMV seroprevalence in patients with hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Lepiller Quentin

    2011-10-01

    Full Text Available Abstract Background Hepatocellular carcinoma (HCC is the most common primary liver cancer, usually arising after years of chronic liver inflammation that could result from viral infections such as hepatitis B virus (HBV and hepatitic C virus (HCV infections. Human cytomegalovirus (HCMV infects primary human hepatocytes and remains an important cause of morbidity in immunocompromised persons where it may manifest as symptomatic end-organ disease including hepatitis. The goal of the present study was to determine a potential correlation between HCMV infection and the appearance of HCC. Methods First, we analyzed the seroprevalence of HCMV in a cohort of 11,318 patients hospitalized between 2003 and 2009 in different departments of a French University Hospital. Second, we studied HCMV seroprevalence in a cohort of 190 subjects who were stratified on the basis of age, gender, HCC, cirrhosis (Cir, and the exposition to hepatotropic viruses (HCV, HBV. We further determined whether HCMV DNA was present specifically in tumour area in liver biopsies from HCC-positive patients by using nested PCR. Results We found that the HCMV seroprevalence was high in the Hepatology department. The HCMV seroprevalence was significantly higher in patients infected with HCV and/or HBV than in patients who were not infected by those later viruses (76.2% versus 56.5%, p Conclusions Our results indicate that HCMV seroprevalence in patients with HCC is significantly higher than in patients without HCC, is positively correlated with serum IL-6 levels in cirrhotic patients, and is positively associated with the presence of other hepatotropic viruses such as HCV and HBV.

  17. Thrombocytosis:A paraneoplastic syndrome in patients with hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Shinn-Jang Hwang; Chun-Chung Lee; Full-Young Chang; Shou-Dong Lee; Jiing-Chyuan Luo; Chung-Pin Li; Cheng-Wei Chu; Jaw-Ching Wu; Chiung-Ru Lai; Jen-Huei Chiang; Gar-Yang Chau; Wing-Yiu Lui

    2004-01-01

    AIM: Hepatocellular carcinoma (HCC) patients manifest a variety of paraneoplastic syndromes. Thrombocytosis was reported in children with hepatoblastoma. The aims of this study were to evaluate the prevalence and dinical significance of thrombocytosis in HCC patients and its relationships with serum thrombopoietin (TPO).METHODS: We retrospectively reviewed clinical, biochemical and image data of 1 154 HCC patients. In addition, we measured platelet count and serum TPO in HCC patients with and without thrombocytosis, in patients with cirrhosis,chronic hepatitis and healthy subjects in a cross-sectional study.RESULTS: Thirty-one (2.7%) of 1 154 HCC patients had thrombocytosis (platelet count ≥400 K/mm3). HCC patients with thrombocytosis were significantly younger, had a higher serum α-fetoprotein, higher rate of main portal vein thrombosis, larger tumor volume, shorter survival, and were less likely to receive therapy than HCC patients without thrombocytosis. Multivariate logistic regression analyses showed that tumor volumes ≥30% and serum α-fetoprotein ≥ 140 000 ng/mL could significantly predict thrombocytosis.HCC patients with thrombocytosis had a significantly higher mean serum TPO than those without, as well as patients with cirrhosis, chronic hepatitis and healthy subjects.Platelet count and serum TPO dropped significantly after tumor resection in HCC patients with thrombocytosis and re-elevated after tumor recurred. Furthermore, the expression of TPO mRNA was found to be more in tumor tissues than in non-tumor tissues of liver in an HCC patient with thrombocytosis.CONCLUSION: Thrombocytosis is a paraneoplastic syndrome of HCC patients due to the overproduction of TPO by HCC.It is frequently associated with a large tumor volume and high serum α-fetoprotein.

  18. Expression of β-catenin in hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Liem Thanh Tien; Masahiro Ito; Mikiko Nakao; Daisuke Niino; Meirmanov Serik; Masahiro Nakashima; Chun-Yang Wen; Hiroshi Yatsuhashi; Hiromi Ishibashi

    2005-01-01

    AIM: The β-catenin has been recognized as a critical member of the Wnt signaling pathway and plays an important role in the generation/differentiation of many tissues. Inappropriate activation of this pathway has been implicated in carcinogenesis. The mechanism underlying the development as well as its prognosis of hepatocellular carcinoma (HCC) has remained unclear. The purpose of this study is to analyze the expression of β-catenin in HCC in relation to histological grades and viral hepatitis backgrounds.METHODS: Thirty-two sections were selected at random from autopsy and surgical cases of HCC. Immuohistologically,the location and positivity of β-catenin expression in HCC was examined.RESULTS: Normal hepatocytes did not express β-catenin.In 78% of HCC β-catenin was expressed at the membrane of the cells, with or without cytoplasmic and/or nuclear expression. The tumor cells with well- and moderatelydifferentiated grades expressed frequently at the membrane and cytoplasm compared with poorly-differentiated type.Nuclear expression of β-catenin was prone to occur in the tumor cells of poorly-differentiated grade. There were 15% of hepatitis C virus (HCV) backgrounds with nuclear expression. In contrast, there was 38% with nuclear expression in hepatitis B virus (HBV) backgrounds. In nonBnonC hepatitis, no case expressed nuclear β-catenin.CONCLUSION: The β-catenin expression in HCC cells was heterogenous among types of hepatitis viral infection.Wnt signaling pathway might be deeply involved in less-differentiated HCC and HBV background.

  19. Glycylproline dipeptidyl aminopeptidase isoenzyme in diagnosis of primary hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Run-Zhou Ni; Jie-Fei Huang; Ming-Bing Xiao; Mei Li; Xian-Yong Meng

    2003-01-01

    AIM: To investigate the role of glycylproline dipeptidyl aminopeptidase (GPDA) isoenzyme in the diagnosis of primary hepatocellular carcinoma (PHC), especially in patients with negative alpha-fetoprotein (AFP).METHODS: A stage gradient polyacrylamide gel discontinuous electrophoresis system was developed to separate serum GPDA isoenzymes, which were determined in 102 patients with PHC, 45 cases with liver cirrhosis, 24cases with chronic hepatitis, 35 cases with benign liver spaceoccupying lesions, 20 cases with metastatic liver cancer and 50 cases with extra-hepatic cancer, as well as 80 healthy subjects. The relationships between GPDA isoenzymes and AFP, the sizes of tumors, as well as alanine aminotransferase (ALT) were also analyzed.RESULTS: Serum GPDA was separated into two isoenzymes,GPDA-S and GPDA-F. The former was positive in all subjects,while the latter was found mainly in majority of PHC (85.3 %)and a few cases with liver cirrhosis (11.1%), chronic hepatitis (33.3 %), metastatic liver cancer (15.0 %) and non-hepatic cancer (16.0 %). GPDA-F was negative in all healthy subjects and patients with benign liver space-occupying lesions,including abscess, cysts and angioma. There was no correlation between GPDA-F and AFP concentration or tumor size. GPDA-F was consistently positive and not correlated with ALT in PHC, but GPDA-F often converted to negative as decline of ALT in benign liver diseases. The electrophoretic migration of GPDA-F became sluggish after the treatment of neuraminidase.CONCLUSION: GPDA-F is a new useful serum marker for PHC. Measurement of serum GPDA-F is helpful in diagnosis of PHC, especially in patients with negative AFP. GPDA-F is one kind of glycoproteins rich in sialic acid.

  20. Surgical outcomes of hepatocellular carcinoma invading hepatocaval conlfuence

    Institute of Scientific and Technical Information of China (English)

    Wei Li; Hong Wu; Jun Han

    2016-01-01

    BACKGROUND: Combined liver and inferior vena cava (IVC) resection followed by IVC and/or hepatic vein reconstruc-tion (HVR) is a curative operation for selected patients with hepatocellular carcinoma (HCC) invading the hepatocaval conlfuence. The present study aimed to elucidate the prog-nostic factors for patients with HCC invading the hepatocaval conlfuence. METHODS: Forty-two consecutive patients underwent hepa-tectomy, 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 in-vaded the hepatocaval conlfuence 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 conlfuence were inifltrated, and the hepatic vein remnant was re-implanted onto the side of the tube graft. The patient characteristics, intra- and postopera-tive results, and long-term overall survival were compared among the three groups. The survival-related factors were analyzed by univariate and multivariate analysis. RESULTS: The group 1 had higher preoperative alpha-fetopro-tein level (P CONCLUSIONS: Patients with reconstructing hepatic vein with patches locally (group 2) or to the artiifcial graft (group 3) had worse long-term survival than those without HVR (group 1). HVR was one of the unfavorable prognostic factors of overall survival.

  1. Pivotal Role of mTOR Signaling in Hepatocellular Carcinoma

    Science.gov (United States)

    Villanueva, Augusto; Chiang, Derek Y.; Newell, Pippa; Peix, Judit; Thung, Swan; Alsinet, Clara; Tovar, Victoria; Roayaie, Sasan; Minguez, Beatriz; Sole, Manel; Battiston, Carlo; van Laarhoven, Stijn; Fiel, Maria I; Di Feo, Analisa; Hoshida, Yujin; Yea, Steven; Toffanin, Sara; Ramos, Alex; Martignetti, John A.; Mazzaferro, Vincenzo; Bruix, Jordi; Waxman, Samuel; Schwartz, Myron; Meyerson, Matthew; Friedman, Scott L.; Llovet, Josep M.

    2008-01-01

    BACKGROUND The advent of targeted therapies in hepatocellular carcinoma (HCC) has underscored the importance of pathway characterization to identify novel molecular targets for treatment. Based on its role in cell growth and differentiation, we evaluated mTOR signaling activation in human HCC, as well as the anti-tumoral effect of a dual-level blockade of the mTOR pathway. METHODS The mTOR pathway was assessed using integrated data from mutation analysis (direct sequencing), DNA copy number changes (SNP-array), mRNA levels (qRT-PCR and gene expression microarray), and protein activation (immunostaining) in 351 human samples, including HCC (n=314), and non-tumoral tissue (n=37). Effects of dual blockade of mTOR signaling using a rapamycin analog (everolimus) and an EGFR/VEGFR inhibitor (AEE788) were evaluated in liver cancer cell lines, and in a tumor xenograft model. RESULTS Aberrant mTOR signaling (phosphorylated-RPS6) was present in half of the cases, associated with IGF pathway activation, EGF upregulation, and PTEN dysregulation. PTEN and PI3KCA-B mutations were rare events. Chromosomal gains in RICTOR (25% of patients) and positive pRPS6 staining correlated with recurrence. RICTOR-specific siRNA downregulation reduced tumor cell viability in vitro. Blockage of mTOR signaling with everolimus in vitro and in a xenograft model decelerated tumor growth and increased survival. This effect was enhanced in vivo after EGFR blockade. CONCLUSIONS MTOR signaling has a critical role in the pathogenesis of HCC, with evidence for the role of RICTOR in tumor oncogenesis. MTOR blockade with everolimus is effective in vivo. These findings establish a rationale for targeting mTOR pathway in clinical trials in HCC. PMID:18929564

  2. Probiotics modulated gut microbiota suppresses hepatocellular carcinoma growth in mice.

    Science.gov (United States)

    Li, Jun; Sung, Cecilia Ying Ju; Lee, Nikki; Ni, Yueqiong; Pihlajamäki, Jussi; Panagiotou, Gianni; El-Nezami, Hani

    2016-03-01

    The beneficial roles of probiotics in lowering the gastrointestinal inflammation and preventing colorectal cancer have been frequently demonstrated, but their immunomodulatory effects and mechanism in suppressing the growth of extraintestinal tumors remain unexplored. Here, we adopted a mouse model and metagenome sequencing to investigate the efficacy of probiotic feeding in controlling s.c. hepatocellular carcinoma (HCC) and the underlying mechanism suppressing the tumor progression. Our result demonstrated that Prohep, a novel probiotic mixture, slows down the tumor growth significantly and reduces the tumor size and weight by 40% compared with the control. From a mechanistic point of view the down-regulated IL-17 cytokine and its major producer Th17 cells, whose levels decreased drastically, played critical roles in tumor reduction upon probiotics feeding. Cell staining illustrated that the reduced Th17 cells in the tumor of the probiotic-treated group is mainly caused by the reduced frequency of migratory Th17 cells from the intestine and peripheral blood. In addition, shotgun-metagenome sequencing revealed the crosstalk between gut microbial metabolites and the HCC development. Probiotics shifted the gut microbial community toward certain beneficial bacteria, including Prevotella and Oscillibacter, that are known producers of antiinflammatory metabolites, which subsequently reduced the Th17 polarization and promoted the differentiation of antiinflammatory Treg/Tr1 cells in the gut. Overall, our study offers novel insights into the mechanism by which probiotic treatment modulates the microbiota and influences the regulation of the T-cell differentiation in the gut, which in turn alters the level of the proinflammatory cytokines in the extraintestinal tumor microenvironment.

  3. 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.

  4. NEK2 serves as a prognostic biomarker for hepatocellular carcinoma

    Science.gov (United States)

    Li, Gang; Zhong, Yanping; Shen, Qingrong; Zhou, Yi; Deng, Xiaofang; Li, Cuiping; Chen, Jiagui; Zhou, Ying; He, Min

    2017-01-01

    Never in mitosis gene A (NIMA)-related kinase 2 (NEK2) is a microtubule-associated protein that regulates spindle assembly in human cells and is overexpressed in various malignancies. However, the role of NEK2 in hepatocellular carcinoma (HCC) remains undetermined. We performed RNA-seq of the HCC cell line SMMC-7721 and the normal liver cell line HL-7702 using the Ion Proton System. NEK2 expression was detected using quantitative reverse transcription polymerase chain reaction in two cell lines and 5 matched HCC and adjacent non-tumorous liver tissues. The correlation between survival and NEK2 expression was analyzed in 359 patients with HCC using RNASeqV2 data available from The Cancer Genome Atlas (TCGA) website (https://tcga-data.nci.nih.gov/tcga/). The expression of NEK2, phospho-AKT and MMP-2 was evaluated by immunohistochemistry in 63 cases of HCC and matched adjacent non-tumorous liver tissues. Relationships between protein expression and clinicopathological parameters were assessed, and the correlations between NEK2 with phospho-AKT and MMP-2 expressions were evaluated. A total of 610 differentially expressed genes (DEGs) were revealed in the transcriptome comparison, 297 of which were upregulated and 313 were downregulated in HCC. NEK2, as the most obviously different DEG in cells and tissues from the RNA-seq data, was listed as an HCC candidate biomarker for further verification. NEK2 was overexpressed in HCC cells and tissues (P=0.002, P=0.013) and HCC patients with a high expression of NEK2 had a poor prognosis (P=0.0145). Clinical analysis indicated that the overexpression of NEK2 in HCC was significantly correlated with diolame complete (PMMP-2 (r=0.781, PMMP-2 expression. PMID:28101574

  5. Chemoembolization for Hepatocellular Carcinoma Supplied by a Lumbar Artery

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Han Myun, E-mail: seoul49@naver.com [Hallym University College of Medicine, Department of Radiology, Kangnam Sacred Heart Hospital (Korea, Republic of); Kim, Hyo-Cheol, E-mail: angiointervention@gmail.com; Woo, Sungmin, E-mail: j-crew7@hotmail.com [Seoul National University College of Medicine, Institute of Radiation Medicine, Seoul National University Medical Research Center, and Clinical Research Institute, Seoul National University Hospital, Department of Radiology (Korea, Republic of); Son, Kyu Ri, E-mail: kyurad@gmail.com [Korea University College of Medicine, Department of Radiology, Korea University Medical Center (Korea, Republic of); Cho, Seong Whi, E-mail: chosw@kangwon.ac.kr [Kangwon National University College of Medicine, Department of Radiology, Kangwon National University Hospital (Korea, Republic of); Chung, Jin Wook, E-mail: chungjw@snu.ac.kr [Seoul National University College of Medicine, Institute of Radiation Medicine, Seoul National University Medical Research Center, and Clinical Research Institute, Seoul National University Hospital, Department of Radiology (Korea, Republic of)

    2015-02-15

    PurposeTo describe the radiologic findings and imaging response of hepatocellular carcinoma (HCC) supplied by the lumbar artery.MethodsBetween April 2004 and December 2012, we encountered HCC supplied by a lumbar artery in 21 patients. Two investigators retrospectively reviewed clinical and radiological findings of HCC supplied by the lumbar artery using computed tomography (CT) scans and digital subtraction angiograms.ResultsPatients had received 1–27 sessions of previous chemoembolization procedures (mean 7.7 sessions, median 4 sessions). Mean tumor size was 5.3 cm. The locations of HCC supplied by lumbar artery were the bare area (n = 14, 67 %) and segment VI (n = 7, 33 %). Tumor-feeding arteries arose from the main lumbar artery (n = 7), proximal anterior division (n = 4), and distal anterior division (n = 14). In 20 patients, selective chemoembolization through the tumor-feeding arteries of the lumbar artery was achieved. In 1 patient, nonselective embolization at the main lumbar artery was performed. There was no complication such as skin necrosis or paralysis. On the first follow-up enhanced CT scan, target tumors fed by the lumbar artery showed complete response (n = 6), partial response (n = 4), stable disease (n = 3), and progressive disease (n = 8), but overall tumor response was partial response (n = 1) and progressive disease (n = 20).ConclusionWhen HCC is located in the inferior tip or bare area of the liver, a lumbar artery may supply the tumor. Although selective chemoembolization via the tumor-feeding vessel of the lumbar artery can be achieved in most cases, overall tumor response is commonly unfavorable.

  6. Hepatocellular Carcinoma with Foamy Histiocyte-Like Appearance: A Deceptively Clear Cell Carcinoma Appearing Variant

    Directory of Open Access Journals (Sweden)

    Takuji Noro

    2010-08-01

    Full Text Available Hepatocellular carcinoma (HCC shows many pathological features, and it varies architecturally and cytologically. There have been many reports and discussions of the morphological features of HCC. A 63-year-old man was found to have a solitary tumor in liver segment 7 that was diagnosed as HCC. A partial resection of liver segment 7 was performed. Microscopically, the tumor lesion showed a moderately differentiated HCC. There was also a lesion with foamy histiocyte-like cells corresponding to the white lesion in the face of the cut tumor. Immunohistochemical staining showed that they were negative for CD68, S-100, vimentin, and HMB-45. The cytoplasm itself was negative on periodic acid Schiff (PAS and Sudan staining. Without immunohistological analysis, it is difficult to distinguish this HCC variant from clear cell carcinoma or metastases of renal cell carcinoma. It is important to recognize this type as a specific cytological variant of HCC that requires confirmation by immunohistochemistry. This report describes the case of a patient with a morphologically distinctive pattern of HCC with prominent cell cytoplasm that had a foamy histiocyte-like appearance. To the best of our knowledge, this is the first report of this HCC variant.

  7. Function of oval cells in hepatocellular carcinoma in rats

    Institute of Scientific and Technical Information of China (English)

    Chi-Hua Fang; Jia-Qing Gong; Wei Zhang

    2004-01-01

    AIM: To study oval cells' pathological characteristics and relationship with the occurrence of hepatocellular carcinoma (HCC); to observe the form and structural characteristics of oval cells; to explore the expression characteristics of C-kit, PCNA mRNA and c-myc gene during the occurrence and development of HCC and the effect of ulinastatin (UTI) on C-kit and PCNA expression.METHODS: One hundred and twenty-five SD rats fed on 3,3'-diaminobenzidine (DAB) to construct HCC models were divided into control group, cancer-inducing group and UTI intervention group. In each group, rat liver samples were collected at weeks 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22 and 24 respectively to study pathological distribution characteristics of oval cells in the process of carcinogenesis under optical microscope. Oval cells were separated by the methods of improved density gradient centrifugation and their structural characteristics were observed under optical microscope and electronic microscope respectively; the oval cells expressing C-kit and PCNA in the collected samples were observed by the methods of immunohistochemistry and image analysis and the expression of c-myc mRNA was also detected by reverse transcription polymerase chain reaction (RT-PCR).RESULTS: Oval cells proliferated firstly in the portal area then gradually migrated into hepatic parenchyma in the inducing group and intervention group. The oval cells distributed inside and outside the carcinoma nodes. The oval cells presented the characteristics of undifferentiated cells: a high ratio of nucleolus and cellular plasm and obvious nucleoli, rare organelle in plasm. Only a few mitochondria and endoplasmic reticulum and some villuslike apophysis on surface of cells could be seen. Cells stained with C-kit and PCNA antibody were mainly oval cells distributed in the portal area. The expression of cmyc mRNA increased with the progression of HCC.However, in the intervention group, UTI could retard its i n c rea se

  8. Systems biology analysis of hepatitis C virus infection reveals the role of copy number increases in regions of chromosome 1q in hepatocellular carcinoma metabolism

    DEFF Research Database (Denmark)

    Elsemman, Ibrahim; Mardinoglu, Adil; Shoaie, Saeed;

    2016-01-01

    on hepatocellular metabolism. Here, we integrated HCV assembly reactions with a genome-scale hepatocyte metabolic model to identify metabolic targets for HCV assembly and metabolic alterations that occur between different HCV progression states (cirrhosis, dysplastic nodule, and early and advanced hepatocellular...... carcinoma (HCC)) and healthy liver tissue. We found that diacylglycerolipids were essential for HCV assembly. In addition, the metabolism of keratan sulfate and chondroitin sulfate was significantly changed in the cirrhosis stage, whereas the metabolism of acyl-carnitine was significantly changed...

  9. Expression of fragile histidine triad in primary hepatocellular carcinoma and its relation with cell proliferation and apoptosis

    Institute of Scientific and Technical Information of China (English)

    Ke-Jun Nan; Zhi-Ping Ruan; Zhao Jing; Hai-Xia Qin; Hong-Yan Wang; Hui Guo; Rui Xu

    2005-01-01

    AIM: To evaluate the expression of fragile histidine triad (FHIT) gene protein, product of a candidate tumor suppressor,and to investigate the relationship between FHIT, cell apoptosis and proliferation, and pathological features of primary hepatocellular carcinoma (HCC).METHODS: Forty-seven HCC and ten normal liver specimens were collected during surgical operation between 2001and 2003. FHIT and proliferating cell nuclear antigen (PCNA)expression were detected by immunohistochemistry, and apoptotic level was evaluated by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay on the tissue sections.RESULTS: All normal liver tissues showed a strong expression of FHIT, whereas 28 of 47 (59.6%) carcinomas showed a significant loss or absence of FHIT expression (P = 0.001).The proportion of reduced FHIT expression in those carcinomas at stages Ⅲ-Ⅳ (70.6%) and in those with extrahepatic metastasis (86.7%) showed an increasing trend compared with those at stages Ⅰ-Ⅱ (30.8%, P= 0.013) and those without metastasis (46.9%, P = 0.010) respectively. Apoptotic incidence in advanced TNM stage carcinoma and those with positive FHIT expression was higher than that in early stage carcinoma (P = 0.030) and in those with negative FHIT expression (P = 0.044) respectively. The proliferating potential of hepatocellular carcinoma was associated with FHIT expression (P = 0.016) and the aggressive feature (P = 0.019). Kaplan-Meier analysis demonstrated that the survival time of these 47 patients correlated with TNM stage,FHIT expression and metastasis.CONCLUSION: There is marked loss or absence of FHIT expression, as well as abnormal apoptosis-proliferation balance in HCC. FHIT may play an important role in carcinogenesis and development of HCC.

  10. The effect of surgical excision combined with radioactive particles interstitial brachytherapy on serum indexes of patients with hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Zhi-Gang Dong; Li-Li Ma; Ya-Juan Li; Zhan-Hong Zhang

    2015-01-01

    Objective:To study the effect of surgical excision combined with radioactive particles interstitial brachytherapy on serum indexes of patients with hepatocellular carcinoma.Methods: 120 cases of patients with hepatocellular carcinoma received surgical treatment in our hospital were chosen and divided into combined treatment group and simple surgery group. Serum was collected after treatment and contents of miRNAs, hepatocellular carcinoma markers and Wnt signal molecules were detected.Results:(1) miRNAs: compared with serum miRNAs contents of simple surgery group, serum miR-1, miR-10a and miR-451 contents of combined treatment group were higher; miR-106b and miR-224 contents were lower; (2) hepatocellular carcinoma markers: compared with serum hepatocellular carcinoma marker contents of simple surgery group, serum AFP-L3, GP73, sB7-H3, AFU and Cat S contents of combined treatment group were all lower; (3) Wnt signal molecules: compared with serum Wnt signal molecule contents of simple surgery group, serum mRNA contents of Wnt,β-catenin, CyclinD1, c-myc, CD44v6 and VEGF of combined treatment group were lower.Conclusion:Surgical excision combined with radioactive particles interstitial brachytherapy is helpful to regulate miRNAs contents, reduce hepatocellular carcinoma marker contents and inhibit Wnt signal pathway function; it’s an ideal method in the treatment of hepatocellular carcinoma.

  11. 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.

  12. Risk factors for the recurrence of hepatocellular carcinoma after radiofrequency ablation of hepatocellular carcinoma in patients with hepatitis C

    Institute of Scientific and Technical Information of China (English)

    Yutaka Yamanaka; Atsuhiro Nakatsuka; Koichiro Yamakado; Kan Takeda; Katsuya Shiraki; Kazumi Miyashita; Tomoko Inoue; Tomoyuki Kawakita; Yumi Yamaguchi; Yukiko Saitou; Norihiko Yamamoto; Takeshi Nakano

    2005-01-01

    AIM: To analyze the risk factors of hepatocellular carcinoma (HCC) recurrence after radiofrequency ablation (RFA) treatment with HCV-associated hepatitis. METHODS: Twenty-six patients with HCV-associated HCC who were followed-up for more than 12 mo were selected for this study. Risk factors for distant intrahepatic recurrences of HCC were evaluated for patients in whom complete coagulation was achieved without recurrence in the same subsegment as the primary nodule. Twelve clinical and tumoral factors were examined: Age, gender, nodule diameter, number of primary HCC nodule, Child-Pugh classification, serum platelet, serum albumin, serum AST, post RFA AST, serum ALT, post RFA ALT, post RFA treatment.RESULTS: Distant recurrences of HCC in remnant liver after RFA were observed in 14 cases and in the number of primary HCC nodules (P = 0.047), and the serum platelets (P = 0.030), the clear difference came out by the recurrence group and the non-recurrence group. The cumulative recurrence rates after 1 and 2 years were30.8% and 86.8%, respectively for primary multinodular HCC, and 15.4% and 29.5% respectively, for primary uninodular HCC. In addition the 1-year recurrence rates for patients with serum albumin more than 3.4 g/dL and less than 3.4 g/dL were 23.1% for both, but the 2-years recurrence rates were 89.0% and 23.1%, respectively. The number of primary HCC nodules (relative risk, 6.970; P = 0.016) were found to be a statistically significant predictor for poor distant intrahepatic recurrence by univariate analysis.CONCLUSION: Patients who have multiple HCC nodules, low serum platelets and low serum albumin accompanied by HCV infection, should be carefully followed because of the high incidence of new HCC lesions in the remnant liver, even if coagulation RFA is complete.

  13. Examestane in advanced or recurrent endometrial carcinoma

    DEFF Research Database (Denmark)

    Lindemann, Kristina; Malander, Susanne; Christensen, René dePont;

    2014-01-01

    We evaluated the efficacy and safety of the aromatase inhibitor exemestane in patients with advanced, persistent or recurrent endometrial carcinoma.......We evaluated the efficacy and safety of the aromatase inhibitor exemestane in patients with advanced, persistent or recurrent endometrial carcinoma....

  14. Immunohistochemical expression of SALL4 in hepatocellular carcinoma, a potential pitfall in the differential diagnosis of yolk sac tumors.

    Science.gov (United States)

    Gonzalez-Roibon, Nilda; Katz, Betina; Chaux, Alcides; Sharma, Rajni; Munari, Enrico; Faraj, Sheila F; Illei, Peter B; Torbenson, Michael; Netto, George J

    2013-07-01

    SALL4 is a transcription factor that serves as a marker of yolk sac tumor. Yolk sac tumor and hepatocellular carcinoma share histologic, serologic, and immunohistochemical features. Previous studies have shown lack of SALL4 expression in hepatocellular carcinoma, suggesting utility in this differential diagnosis. Sixty-nine samples of hepatocellular carcinoma were retrieved from surgical pathology archives and used to construct 9 tissue microarrays. A germ cell tumor tissue microarray containing 10 yolk sac tumors was used for comparison. Extent, intensity, and pattern of nuclear SALL4 expression were assessed in each spot. Mean percentage of expression was calculated for each tumor and used during analysis. Optimal discriminatory extent of expression cutoff was determined by receiver operating characteristic curve analysis. Other potential discriminatory markers including Hep Par1 were also evaluated. Forty-six percent (32/69) of hepatocellular carcinoma and all yolk sac tumors revealed at least focal expression of SALL4. A unique punctuate/clumped pattern of nuclear staining was present in 94% (30/32) of hepatocellular carcinoma, whereas all yolk sac tumors displayed a diffuse finely granular nuclear staining pattern. A 25% extent of SALL4 expression cutoff was found to be optimal for the distinction of yolk sac tumor from hepatocellular carcinoma yielding a sensitivity of 100%, specificity of 92.8%, and a positive predictive value of 66.6% for yolk sac tumor diagnosis. The addition of Hep Par1 increased the specificity (99%) and positive predictive value (90%). This is the first report of SALL4 expression in hepatocellular carcinoma. Our finding should be taken into consideration in the differential diagnosis of hepatocellular carcinoma and yolk sac tumor. The unique punctuate/clumped pattern seen in hepatocellular carcinoma cases could be of further discriminatory value.

  15. Relationships among hepatitis C virus, hepatocellular carcinoma, and diffuse large B cell lymphoma: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Byun, Hyuk Jun; Kim, Seong Hoon [Dept. of Radiology, Daegu Fatima Hospital, Daegu (Korea, Republic of)

    2015-07-15

    Hepatitis C virus (HCV) is one of the main causes of hepatocellular carcinoma (HCC). Recent studies have reported various associations between HCV and the incidence of non-Hodgkin's lymphoma. We report the radiologic findings in a rare case of simultaneous occurrence of HCC and diffuse large B cell lymphoma in a HCV carrier.

  16. Preoperative Alpha-Fetoprotein Slope is Predictive of Hepatocellular Carcinoma Recurrence after Liver Transplantation

    Directory of Open Access Journals (Sweden)

    Kathy Han

    2007-01-01

    Full Text Available BACKGROUND: Liver transplantation (LT offers a possible cure for patients with hepatocellular carcinoma (HCC and cirrhosis. However, tumour progression while on the waiting list and tumour recurrence after LT are common. The prognostic significance of various pre- and postoperative variables were investigated in regard to tumour recurrence, with an emphasis on the slope of preoperative serum alpha-fetoprotein (AFP levels.

  17. The role of interventional radiology in the treatment of hepatocellular carcinoma.

    NARCIS (Netherlands)

    Steiner, K.; Papadopoulou, A.; Yu, D.

    2013-01-01

    The incidence of hepatocellular carcinoma (HCC) in the UK is increasing. The role of interventional radiology in the treatment of HCC is well established. We discuss the minimally invasive treatment options that are available. It is important that procedures are undertaken in and postprocedure imagi

  18. Immunotherapy of hepatocellular carcinoma: is there a place for regulatory T-lymphocyte depletion?

    NARCIS (Netherlands)

    Cany, J.S.; Tran, L.; Gauttier, V.; Judor, J.P.; Vassaux, G.; Ferry, N.; Conchon, S.

    2011-01-01

    Immunotherapy represents a potential therapeutic option for patients with hepatocellular carcinoma (HCC), especially as secondary treatment to prevent recurrence. It has been shown that a patient's survival is directly correlated to the type and number of tumor-infiltrating immune cells, indicating

  19. Liver transplantation for unresectable hepatocellular carcinoma in patients without liver cirrhosis

    NARCIS (Netherlands)

    Mergental, Hynek; Porte, Robert J.

    2010-01-01

    P>Hepatocellular carcinoma (HCC) arising in noncirrhotic and nonfibrotic liver (NC-HCC) is a rare type of malignancy frequently found in healthy young individuals. Partial liver resection is the treatment of choice with expected 5-year survival rates between 40% and 70%. As a result of absence of an

  20. RNAI-based gene therapy of hepatocellular carcinoma: targeting ABC transporters

    NARCIS (Netherlands)

    Borel, F.

    2012-01-01

    Hepatocellular carcinoma (HCC) is a primary cancer of the liver, and HCC patients have an average survival of only 5% at 5-year post-diagnosis. This low survival has several identified causes, among which multidrug resistance i.e. resistance to chemotherapeutic treatment. These issues need be addres

  1. Role of cell adhesion signal molecules in hepatocellular carcinoma cell apoptosis

    Institute of Scientific and Technical Information of China (English)

    Jian-Min Su; Li-Ying Wang; Yu-Long Liang; Xi-Liang Zha

    2005-01-01

    AIM: Cell adhesion molecules and their signal molecules play a very important role in carcinogenesis. The aim of this study is to elucidate the role of these molecules and the signal molecules of integrins and E-cadherins, such as (focal adhesion kinase) FAK, (integrin linked kinase)ILK, and β-catenin in hepatocellular carcinoma cell apoptosis.METHODS: We first synthesized the small molecular compound, S-(1,2-dichlorovinyl)-L-cysteine (DCVC), and identified it, by element analysis and 1H NMR. To establish the apoptosis model of the SMMC-7721 hepatocellular carcinoma cell, we treated cells with DCVC in EBSS for different concentrations or for various length times in the presence of 20 μmol/L N,N-diphenyl-p-phenylenediamine,which blocks necrotic cell death and identified this model by flow cytometry and DNA ladder. Then we studied the changes of FAK, ILK, β-catenin, and PKB in this apoptotic model by Western blot.RESULTS: We found that the loss or decrease of cell adhesion signal molecules is an important reason in apoptosis of SMMC-7721 hepatocellular carcinoma cell and the apoptosis of SMMC-7721 cell was preceded by the loss or decrease of FAK, ILK, PKB, and β-catenin or the damage of cell-matrix and cell-cell adhesion.CONCLUSION: Our results suggested that the decrease of adhesion signal molecules, FAK, ILK, PKB, and β-catenin,could induce hepatocellular carcinoma cell apoptosis.

  2. Dietary fat, fat subtypes and hepatocellular carcinoma in a large European cohort

    NARCIS (Netherlands)

    Duarte-Salles, Talita; Fedirko, Veronika; Stepien, Magdalena; Aleksandrova, Krasimira; Bamia, Christina; Lagiou, Pagona; Laursen, Anne Sofie Dam; Hansen, Louise; Overvad, Kim; Tjønneland, Anne; Boutron-Ruault, Marie Christine; Fagherazzi, Guy; His, Mathilde; Boeing, Heiner; Katzke, Verena; Kühn, Tilman; Trichopoulou, Antonia; Valanou, Elissavet; Kritikou, Maria; Masala, Giovanna; Panico, Salvatore; Sieri, Sabina; Ricceri, Fulvio; Tumino, Rosario; Bueno-De-Mesquita, H. B.; Peeters, Petra H.; Skeie, Guri; Weiderpass, Elisabete; Ardanaz, Eva; Bonet, Catalina; Chirlaque, Maria Dolores; Dorronsoro, Miren; Quirõs, J. Ramõn; Johansson, Ingegerd; Ohlsson, Bodil; Sjöberg, Klas; Wennberg, Maria; Khaw, Kay Tee; Travis, Ruth C.; Wareham, Nick; Ferrari, Pietro; Freisling, Heinz; Romieu, Isabelle; Cross, Amanda J.; Gunter, Marc; Lu, Yunxia; Jenab, Mazda

    2015-01-01

    The role of amount and type of dietary fat consumption in the etiology of hepatocellular carcinoma (HCC) is poorly understood, despite suggestive biological plausibility. The associations of total fat, fat subtypes and fat sources with HCC incidence were investigated in the European Prospective Inve

  3. Antiviral therapy for prevention of hepatocellular carcinoma and mortality in chronic hepatitis B

    DEFF Research Database (Denmark)

    Thiele, Maja; Gluud, Lise Lotte; Dahl, Emilie K;

    2013-01-01

    The effect of antiviral therapy on clinical outcomes in chronic hepatitis B virus (HBV) is not established. We aimed to assess the effects of interferon and/or nucleos(t)ide analogues versus placebo or no intervention on prevention of hepatocellular carcinoma (HCC) and mortality in chronic HBV....

  4. Late retroperitoneal recurrence of hepatocellular carcinoma 12 years after initial diagnosis

    Institute of Scientific and Technical Information of China (English)

    Tiffany; Cho-Lam; Wong; Ka-Fai; To; Simon; See-Ming; Hou; Sidney; Kam-Hung; Yip; Chi-Fai; Ng

    2010-01-01

    Hepatocellular carcinoma (HCC) is an aggressive tumor with poor long-term prognosis.Here,we present an unusual patient with a solitary recurrence of HCC in the right kidney 12 years after the initial diagnosis.This illustrates the importance of considering late recurrence in patients with a history of HCC and the management of these metastases.

  5. Hepatocellular carcinoma: low risk of HCC in patients who have PSC and cirrhosis.

    Science.gov (United States)

    Gossard, Andrea A; Lindor, Keith D

    2014-05-01

    Primary sclerosing cholangitis (PSC) is understood to be associated with an increased risk of malignancy in the bile ducts, gallbladder and colon. The risk of hepatocellular carcinoma in the setting of PSC, however, is not well defined. Zenouzi et al. provide an analysis of their experience in a recent article.

  6. Hepatocellular carcinoma in noncirrhotic livers is associated with steatosis rather than steatohepatitis: potential implications for pathogenesis

    NARCIS (Netherlands)

    van Meer, S; van Erpecum, KJ; Sprengers, Dave; Klümpen, Heinz-Josef; Jansen, P.L.M.; Ijzermans, Jan N. M.; Siersema, PD; de Man, R.A.

    2016-01-01

    Objective: The risk of hepatocellular carcinoma (HCC) is increased in patients with metabolic syndrome (MS), possibly related to nonalcoholic fatty liver disease (NAFLD). As histological features of NAFLD may regress in cirrhosis, we compared steatosis versus steatohepatitis in the nontumoral liver

  7. Moving toward an understanding of the metastatic process in hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    W. Michael Korn

    2001-01-01

    @@INTRODUCTION Clinical factors contributing to the therapeutic challenge of hepatocellular carcinoma (HCC) are manifold :tumors arise often in patients with compromised liver function ,therefore limiting therapeutic options ;symptoms develop only at later stages of tumor progression ,and tumors tend to invade normal stuctures or occur in multiple locations simultaneously.

  8. A case of hepatocellular carcinoma arising within large focal nodular hyperplasia with review of the literature

    Institute of Scientific and Technical Information of China (English)

    Theodoros Petsas; Athanassios Tsamandas; Irene Tsota; Dionisios Karavias; Chrysoula Karatza; Vassilios Vassiliou; Dimitrios Kardamakis

    2006-01-01

    Focal nodular hyperplasia (FNH) is a relatively rare benign hepatic tumor, usually presenting as a solitary lesion; however, multiple localizations have also been described. The association of FNH with other hepatic lesions, such as adenomas and haemangiomas has been reported by various authors. We herein report a case of a hepatocellular carcinoma arising within a large focal nodular hyperplasia, in a young female patient.

  9. Hepatitis C impairs survival following liver transplantation irrespective of concomitant hepatocellular carcinoma

    DEFF Research Database (Denmark)

    Melum, Espen; Friman, Styrbjörn; Bjøro, Kristian;

    2007-01-01

    BACKGROUND/AIMS: Liver transplantation (LTX) is the only curative treatment for end-stage liver disease caused by hepatitis C (HCV). Hepatocellular carcinoma (HCC) is common in patients with HCV cirrhosis. METHODS: Two hundred and eighty-two HCV patients listed for LTX in the Nordic countries...

  10. Risk factors for immediate post-operative fatal recurrence after curative resection of hepatocellular carcinoma

    OpenAIRE

    Kim, Bong-Wan; Kim, Young-Bae; Wang, Hee-Jung; Kim, Myung-Wook

    2006-01-01

    AIM: To investigate the clinicopathological risk factors for immediate post-operative fatal recurrence of hepatocellular carcinoma (HCC), which may have practical implication and contribute to establishing high risk patients for pre- or post-operative preventive measures against HCC recurrence.

  11. Genome-wide survey of recurrent HBV integration in hepatocellular carcinoma

    DEFF Research Database (Denmark)

    Sung, Wing-Kin; Zheng, Hancheng; Li, Shuyu;

    2012-01-01

    To survey hepatitis B virus (HBV) integration in liver cancer genomes, we conducted massively parallel sequencing of 81 HBV-positive and 7 HBV-negative hepatocellular carcinomas (HCCs) and adjacent normal tissues. We found that HBV integration is observed more frequently in the tumors (86.4%) tha...

  12. Rho signaling inhibitor,Y-27632,inhibits invasiveness of metastastic hepatocellular carcinoma in a mouse model

    Institute of Scientific and Technical Information of China (English)

    XUE Feng; ZHANG Jian-jun; QIU Feng; ZHANG Ming; CHEN Xiao-song; LI Qi-gen; HAN Long-zhi; XI Zhi-feng; XIA Qiang

    2007-01-01

    @@ Hepatocellular carcinoma(HCC)is among the most common tumors worldwide.Despite extensive exploration of novel therapies,the prognosis of HCC patients with intrahepatic metastasis is still poor,and no treatment is effective against metastases.Therefore,more effective therapeutic strategies for treatment of metastasis are urgently needed.

  13. Drug Development for Hepatocellular Carcinoma: Knowing the Past Helps to Understand the Future

    OpenAIRE

    2014-01-01

    Hepatocellular carcinoma (HCC) is a highly complicated disease characterized by comorbid cirrhosis and disease heterogeneity. Given multiple failures in the past, we need to learn from previous experiences and generate novel ideas to increase the chance of success. More effort and patience should be exercised in the selection of a homogeneous patient population and identification of predictive markers during drug development for HCC.

  14. Ethanol injection is highly effective for hepatocellular carcinoma smaller than 2 cm

    Institute of Scientific and Technical Information of China (English)

    Maurizio Pompili; Gian Ludovico Rapaccini; Erica Nicolardi; Valeria Abbate; Luca Miele; Laura Riccardi; Marcello Covino; Nicoletta De Matthaeis; Antonio Grieco; Raffaele Landolfi

    2011-01-01

    AIM: To analyze the long-term prognosis in a cohort of western cirrhotic patients with single hepatocellular carcinoma treated with ethanol injection. METHODS: One-hundred forty-eight patients with solitary hepatocellular carcinoma were enrolled. The tumor diameter was lower than 2 cm in 47 patients but larger in the remaining 101 patients. The impact of some pretreatment clinical and laboratory parameters and of tumor recurrence on patients' survival was assessed. RESULTS: Among the pre-treatment parameters, only a tumor diameter of less than 2 cm was an independent prognostic factor of survival. The occurrence of new nodules in other liver segments and the neoplastic portal invasion were linked to a poorer prognosis at univariate analysis. Patients with a single hepatocellular carcinoma smaller than 2 cm showed a better 5-year cumulative survival (73.0% vs 47.9%) (P = 0.009), 3-year local recurrence rate (29.1% vs 51.5%) (P = 0.011), and 5-year distant intrahepatic recurrence rate (52.9% vs 62.8%) (P = 0.054) compared to patients with a larger tumor. CONCLUSION: The 5-year survival rate of patients with single hepatocellular carcinoma < 2 cm undergoing ethanol injection is excellent and comparable to that achieved using radiofrequency ablation.

  15. Embolization of an unusual metastatic site of hepatocellular carcinoma in the humerus

    Institute of Scientific and Technical Information of China (English)

    Andreas Hansch; Rotraud Neumann; Alexander Pfeil; Ivan Marintchev; Stefan Pfleiderer; Mieczyslaw Gajda; Werner A Kaiser

    2009-01-01

    Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world. This case documents an unusual metastatic presentation of HCC in the humerus. Preoperative palliative arterial embolization of the tumor was performed to arrest severe tumor bleeding caused by the biopsy. Embolization turned out to be useful also in limiting/preventing potential uncontrolled bleeding during subsequent amputation.

  16. Tumor Implantation into the Intrahepatic Bile Duct after Percutaneous Ethanol Injection Therapy for Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Shogo Tanaka

    2009-11-01

    Full Text Available A 74-year-old man who had undergone transcatheter arterial embolization for hepatitis C virus-related hepatocellular carcinoma (Couinaud’s segment III/IV in April 2003 and percutaneous ethanol injection for recurrence at the same site in February 2006 was found to have dilation of the intrahepatic bile duct by computed tomography in October 2008. Contrast-enhanced computed tomography and magnetic resonance cholangiopancreatography showed a thrombosis occupying the left hepatic duct to the lateral branches with peripheral bile duct dilation. Serum concentration of alpha-fetoprotein was elevated. We performed a left hepatectomy under a preoperative diagnosis of hepatocellular carcinoma with bile duct invasion. The cut surface of the resected specimen showed a tumor thrombosis occupying the region between the left hepatic duct and lateral branches, but no tumor in the liver parenchyma. Histologic examination showed that the thrombosis in the intrahepatic bile duct was hepatocellular carcinoma. Since part of the hepatocellular carcinoma in the region treated with percutaneous ethanol injection was adjacent to the tumor thrombosis in the intrahepatic bile duct in diagnostic imaging, we diagnosed implantation into the intrahepatic bile duct due to percutaneous ethanol injection. The postoperative course was uneventful and the patient is doing well without recurrence 8 months after the operation.

  17. ShRNA-targeted COMMD7 suppresses hepatocellular carcinoma growth.

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    Lu Zheng

    Full Text Available BACKGROUND: COMMD7 is a newly identified gene overexpressed in hepatocellular carcinoma (HCC and associated with tumor invasion and poor prognosis. We aim to examine the biological function of COMMD7 in HCC by shRNA silencing. METHODS: COMMD7 expressions were examined in human HCC cell lines HepG2, Huh7, Hep3B, HLE, HLF, SK-Hep-1 and PLC/PRF/5 cells. Recombinant pGenesil-COMMD7-shRNA was transfected into COMMD7-abundant HepG2 cells to silence COMMD7 expression. The effects of COMMD7 silencing on HepG2 cell proliferation in vitro and xenograft tumor growth in vivo were evaluated. Flow cytometry profiling was used to detect the presence of apoptosis in COMMD7-silenced HepG2 cells and to differentiate cell cycle distribution. Electrophoretic mobility shift assay and luciferase reporter assays to examine the activities of nuclear factor-kappaB (NF-κB signaling pathways in response to tumor necrosis factor (TNF-α in COMMD7-silenced HepG2 cells. RESULTS: COMMD7 expression level was abundance in HepG2 and SK-Hep-1 cells. COMMD7 was aberrantly overexpressed in HepG2 cells, whilst pGenesil-COMMD7-shRNA exhibited a maximal inhibition rate of 75%. COMMD7 silencing significantly reduced HepG2 cell proliferation and colony formation. The knockdown of COMMD7 resulted in an increased apoptosis and cell cycle arrest at S-phase. COMMD7 knockdown also exhibited an antineoplastic effect in vivo, which manifested as tumor xenograft growth retardation. COMMD7 silencing also suppressed the responsiveness of NF-κB signaling pathway to the stimulation with TNF-α in vitro. Moreover, the similar suppressive effects of COMMD7 silence on SK-Hep-1 cells were also observed. CONCLUSIONS: COMMD7 contributes to HCC progression by reducing cell apoptosis and overcoming cell cycle arrest. The proliferative and antiapoptotic effects of COMMD7 may be mediated by NF-κB signaling pathway.

  18. Efficacy and safety of thalidomide in patients with hepatocellular carcinoma

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    Hsueh-Erh Chiou; Tsang-En Wang; Ying-Yue Wang; Hui-Wen Liu

    2006-01-01

    AIM: To evaluate which patients with hepatocellular carcinoma (HCC) are most likely to respond to thalidomide treatment.METHODS: From July 2002 to July 2004, patients enrolled. We extracted relevant data from the patients' medical records, including history and type of hepatitis,comorbidity, serum α-fetoprotein (α-FP) level, volumetric changes in tumor, length of survival, and the dose,duration, side effects of thalidomide treatment. The tumor response was evaluated. On the basis of these data, the patients were divided into two groups: those with either partial response or stable disease (PR + SD group) and those with progressive disease (PD group).RESULTS: Two of 42 (5%) patients had a partial tumor response after treatment with thalidomide, 200 mg/d,and 9 (21%) had stable disease. Patients in the PR +SD group all had cirrhosis. Comparing patients with and without cirrhosis, the former were more likely to respond to thalidomide therapy (PR + SD: 100% vs PD:64.5%, P = 0.041 < 0.05). Thalidomide was significantly more likely to be effective in tumors smaller than 5 cm (PR + SD: 63.6% vs PD: 25.8%, P = 0.034 < 0.05).Compared with patients with progressive disease (PD),patients in the PR + SD group had a higher total dose of thalidomide (13669.4 ± 8446.0 mg vs 22022.7 ±11461.4 mg, P = 0.023 < 0.05) and a longer survival (181.0 ± 107.1 d vs 304.4 ± 167.1 d, P = 0.047 < 0.05).Patients with comorbid disease had a significantly greater incidence of adverse reactions than those without (93.8%vs 60.0%, P = 0.021 < 0.05). The average number of adverse reactions in each person with a comorbid condition was twice as high as in those without other diseases (2.2 ± 1.3 vs 1.1 ± 1.2; P = 0.022 < 0.05).CONCLUSION: Thalidomide therapy is most likely to be effective in patients with early stage small HCC, especially in those with other underlying diseases. A low dose (200 mg/d) of thalidomide is recommended to continue the treatment long enough to make it more

  19. FADD and TRADD expression and apoptosis in primary hepatocellular carcinoma

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    Bao Hua Sun; Xi Ping Zhao; Bao Ju Wang; Dong Liang Yang; Lian Jie Hao

    2000-01-01

    AIM To investigate the clinical features of FADD and TRADD expressions in primary hepatocellular carcinoma ( HCC ) and to determine their relationship with hepatic apoptosis. METHODS FADD and TRADD expressions were detected by immunohistochemistry and hepatic apoptosis were determined by in situ endlabeling ( ISEL). RESULTS Ten (25.6%) cases of HCC were detected to express FADD protein. The positive rate in HCC is lower than that in non-cancerous adjacent liver tissues (62.5%) (P<0.05). In those of grade Ⅰ - Ⅱ, 8 (38.1%) cases were FADD positive, while only 2/18 (11. 1%) cases of grade Ⅲ - Ⅳ had detectable FADD protein (P<0.05). No relationship was found between FADD expression and other clinical features,such as gender, age, tumor size, differentiation or metastasis. ISEL positive cells can be seen in all cases of HCC. The hepatic apoptosis was associated with FADD expression as more apoptotic cells were detected in those cases which had moderately to strongly positive FADD, as compared with negative or weak positive FADD cases (P< 0.05). No relationship was found between FADD expression and hepatic apoptosis in non-cancerous adjacent liver tissues. Fifteen of 39 (38.5%) cases of HCC were found positive for TRADD protein, and similar positive rate (37.5%) in non-cancerous adjacent liver tissues (P >0.05). The expression of TRADD is correlated with HCC differentiation,as only 22.2% of moderately to highly differentiated HCC showed positive TRADD protein, while as high as 52.4% of poorly differentiated HCC had TRADD (P<0.05). No relationship was found between TRADD expression and gender, age, tumor size or grade or metastasis, although 42.9% of HCC of grade Ⅰ/Ⅱ showed positive TRADD which was slightly higher than that of grade Ⅲ/Ⅳ (33.3%,P > 0.05). Hepatic apoptosis was not related to TRADD expression in HCC or non-cancerous adjacent liver tissues. CONCLUSION Loss of FADD expression plays an important role in HCC carcinogenesis, and

  20. Antitumor Effects of Soluble TRAIL in Human Hepatocellular Carcinoma

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    HE Songqing; CHEN Yan; CHEN Xiaoping; ZHAO Yongzhong; WANG Haiping; ZHANG Wanguang; WANG Shaofa

    2005-01-01

    The therapeutic potential of soluble TRAIL (sTRAIL) in hepatocellular carcinoma(HCC) was studied. The expression of TRAIL receptors was detected in 60 HCC tissues, 20 normal liver samples and 2 HCC cell lines (HepG2 and SMMC-7721) by in situ hybridization. Before and after HepG2 and SMMC-7721 were treated with sTRAIL protein with various concentrations,the apoptosis rate was observed by using flow cytometry and in situ terminal deoxynucleotidyl tranferase (TdT) labeling. The results showed death receptor 4 (DR4) and DR5 were expressed in 60 HCC tissues and 20 normal liver samples, while the expression intensity of DR in HCC tissues was stronger than in normal liver samples. DcR1and DcR2 were not detectable in 54 (90 %) and 25 (41.7 %)HCC tissues, while in 20 normalliver samples, DcR was detectable. The high expressionof DR and low expression of DcR in HCC tissues were significantly differed from the low expression and high expression in normal liver samples. The expression of DR5, DR4 and DcR2 in both HCC cell lines was detectable, but the expression of DcR1 was not detectable. The expression of DR in HCC tissues was related to the differentiation and grades of HCC. In the poor differentiated HCC, the expression of DR was decreased (P<0.01). The expression of DR in Ⅲ/Ⅳ grades was significantly lower than that in Ⅰ / Ⅱ grades (P<0.05). The expression of DR was not related to gender, age, HBsAg, AFP, tumor sizeand metastasis. The expression of DR in the HCC drugresistant lines was decreased. After treatment with TRAIL (100 ng/ml) for 24 h, the apoptosis rate of HCC cells, Jurkat cells and human cholangiocarcinoma cell line QBC939 was 10 %, 70 %,50 % respectively. It was suggested that the TRAILR expression is prevalent in HCC with different expression patterns of different receptor types. HCC is resistant to TRAIL-mediated apoptosis.The treatment of TRAIL alone has a limited effect on inducing apoptosis of HepG2 and SMMC-7721.

  1. Recurrence of hepatocellular carcinoma with rapid growth after spontaneous regression

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    Tomoki Nakajima; Michihisa Moriguchi; Tadashi Watanabe; Masao Noda; Nobuaki Fuji; Masahito Minami; Yoshito Itoh; Takeshi Okanoue

    2004-01-01

    We report an 80-year-old man who presented with spontaneous regression of hepatocellular carcinoma (HCC). He complained of sudden right flank pain and low-grade fever.The level of protein induced by vitamin K antagonist (PIVKA)-Ⅱ was 1 137 mAU/mL. A computed tomography scan in November 2000 demonstrated a low-density mass located in liver S4 with marginal enhancement and a cystic mass of 68 mmx55 mm in liver S6, with slightly high density content and without marginal enhancement. Angiography revealed that the tumor in S4 with a size of 25 mm×20 mm was a typical hypervascular HCC, and transarterial chemoembolization was performed. However, the tumor in S6 was hypovascular and atypical of HCC, and thus no therapy was given. In December 2000, the cystic mass regressed spontaneously to 57 mmx44 mm, and aspiration cytology revealed bloody fluid, and the mass was diagnosed cytologically as class Ⅰ.The tumor in S4 was treated successfully with a 5 mm margin of safety around it. The PⅣKA-Ⅱ level normalized in February2001. In July 2001, the tumor regressed further but presented with an enhanced area at the posterior margin. In November2001, the enhanced area extended, and a biopsy revealed well-differentiated HCC, although the previous tumor in S4 disappeared. Angiography demonstrated two tumor stains, one was in S6, which was previously hypovascular,and the other was in S8. Subsequently, the PⅣKA-Ⅱ level started to rise with the doubling time of 2-3 wk, and the tumor grew rapidly despite repeated transarterial embolization with gel foam. In February 2003, the patient died of bleeding into the peritoneal cavity from the tumor that occupied almost the entire right lobe. Considering the acute onset of the symptoms, we speculate that local ischemia possibly due to rapid tumor growth, resulted in intratumoral bleeding and/or hemorrhagic necrosis, and finally spontaneous regression of the initial tumor in S6.

  2. Does surgical resection of hepatocellular carcinoma accelerate cancer dissemination?

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    I-Shyan Sheen; Yi-Chun Tsai; Tsu-Yen Wu; Kuo-Shyang Jeng; Shou-Chuan Shih; Po-Chuan Wang; Wen-Hsiung Chang; Horng-Yuan Wang; Li-Rung Shyung; Shee-Chan Lin; Chin-Roa Kao

    2004-01-01

    AIM: This study was to investigate whether surgery could increase cancer dissemination and postoperative recurrence in patients with hepatocellular carcinoma (HCC) by detection of human α-fetoprotein messenger RNA (hAFP mRNA), hAFP mRNA in the peripheral blood of patients with HCC has been considered as a surrogate marker for circulating tumor cells.METHODS: Eighty-one consecutive patients who underwent curative resection for HCC entered this prospective cohort study. We examined hAFP mRNA from the peripheral blood obtained preoperatively, perioperatively, and postoperatively to correlate the prognosis after curative resections from HCC patients and from the control subjects. Detection of hAFP mRNA by reverse transcriptase and polymerase chain reaction amplification (RT-PCR) was performed with primers specifically. The relations between the clinical variables (age,sex, associated liver cirrhosis, hepatitis B virus infection,hepatitis C virus infection, serum α-fetoprotein and ChildPugh class), the histological variables (size, capsule, vascular permeation, grade of differentiation, and daughter nodules),hAFP mRNA in peripheral blood of 3 different sessions, and postoperative course (recurrence, and recurrence related death) were analysed.RESULTS: No hAFP mRNA was detected in control group subjects. Twenty-two (27%), 24 (30%) and 19 (23%) of 81 HCC patients had hAFP mRNA positivity in the preoperative,perioperative and postoperative peripheral blood. The preoperative presence did not influence the risk of HCC recurrence (55% vs41%, P=0.280). In contrast, patients with postoperative presence had a significantly higher recurrence (90% vs 31%, P<0.001; odds ratio 19.2; 95% confidence interval: 4.0-91.7). In the multivariate analysis by COX proportional hazards model, postoperative positivity had a significant influence on recurrence (P=0.067) and recurrence related mortality (P=0.017). Whereas, the perioperative positivity of hAFP mRNA did not increase HCC

  3. Hepatocellular carcinoma: cost-effectiveness of screening. A systematic review

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    Ruggeri M

    2012-06-01

    Full Text Available Matteo RuggeriFacoltà di Economia, Università Cattolica del Sacro Cuore – sede di Roma, Rome, ItalyAbstract: Hepatocellular carcinoma (HCC is one of the most common tumors worldwide. HCC is a potential target for cancer surveillance (or screening as it occurs in well-defined, at-risk populations. Curative therapy is possible only for small tumors and screening strategy has been recommended by the US, Italian, and other international liver societies and is practiced widely, but its benefits are not clearly established. The objective of this study was to review the available evidence with respect to the cost-effectiveness of key technologies in the prevention HCC. The literature search was conducted with the support of PubMed. Firstly we selected articles by reading the abstracts. Secondly, we read the articles and the revision was further restricted, with the following as inclusion criteria: (1 full economic evaluation of HCC screening programs; (2 comparison between HCC techniques; (3 outcome measures expressed in terms of quality adjusted life years (QALY; (4 full text availability. The initial review of the literature yielded 346 articles. Of those, 288 were excluded at the first stage. Of those excluded, 108 did not meet the target, 106 did not present the cost analysis, 33 did not analyze the treatment of the disease, and in 41 the abstract was not available. Of the 58 included in the first step, seven examined the cost-effectiveness of different HCC screening techniques, seven investigated the cost-effectiveness of HCC screening versus no screening, and one looked at the cost-effectiveness of timing for HCC surveillance and monitoring, while 43 were about HBV vaccination and screening. We included only the seven articles examining the cost-effectiveness of different HCC screening techniques. In general, incidence is the key parameter which determines the cost-effectiveness of HCC screening. Discrepancies in the results exist when

  4. Hepatocellular carcinoma with obstructive jaundice:diagnosis,treatment and prognosis

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    Lun-Xiu Qin; Zhao-You Tang

    2003-01-01

    Obstructive jaundice as the main clinical feature is uncommon in patients with hepatocellular carcinoma (HCC). Only 1-12 %of HCC patients manifest obstructive jaundice as the initial complaint. Such cases are clinically classified as "icteric type hepatoma", or "cholestatic type of HCC". Identification of this group of patients is important, because surgical treatment may be beneficial. HCC may involve the biliary tract in several different ways: tumor thrombosis, hemobilia,tumor compression, and diffuse tumor infiltration. Bile duct thrombosis (BDT) is one of the main causes for obstructive jaundice, and the previously reported incidence is 1.2-9 %.BDT might be benign, malignant, or a combination of both.Benign thrombi could be blood clots, pus, or sludge.Malignant thrombi could be primary intrabiliary malignant tumors, HCC with invasion to bile ducts, or metastatic cancer with bile duct invasion. The common clinical features of this type of HCC include: high level of serum AFP; history of cholangitis with dilation of intrahepatic bile duct; aggravating jaundice and rapidly developing into liver dysfunction. It is usually difficult to make diagnosis before operation, because of the low incidence rate, ignorant of this disease, and the difficulty for the imaging diagnosis to find the BDT preoperatively. Despite recent remarkable improvements in the imaging tools for diagnosis of HCC, such cases are still incorrectly diagnosed as cholangiocarcinoma or choledocholithiases. Ultrasonography (US) and CT are helpful in showing hepatic tumors and dilated intrahepatic and/or extrahepatic ducts containing dense material corresponding to tumor debris. Direct cholangiography including percutaneous transhepatic cholangiography (PTC) and endoscopic retrograde cholangiopancreatography (ERCP)remains the standard procedure to delineate the presence and level of biliary obstruction. Magnetic resonance cholangiopancreatography (MRCP) is superior to ERCP in interpreting the cause and

  5. Squamous cell carcinoma antigen in hepatocellular carcinoma: Ready for the prime time?

    Science.gov (United States)

    Montagnana, Martina; Danese, Elisa; Lippi, Giuseppe

    2015-05-20

    Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer and the third cause of cancer deaths. The leading predisposing condition is represented by an underlying viral hepatitis, mainly sustained by hepatitis B and C viruses. Since the cumulative risk of developing HCC can be as high as 30-fold in patients with infectious cirrhosis, a timely diagnosis is necessary for establishing an appropriate treatment in these patients. The armamentarium of diagnostic and prognostic biomarkers in patients with HCC currently entails alpha-fetoprotein (AFP) and a limited number of innovative biomarkers, among which squamous cell carcinoma antigen (SCCA) and its immune complexes are among the most widely investigated. The clinical data published so far and reviewed in this article seemingly suggest that neither total serum SSCA or its isoform 1 (i.e., SCCA1) may be ready for the prime time for management of patients with HCC. More interesting evidence has emerged from studies investigating the serum values of SCCA-IgM, since the diagnostic performance of this biomarker was found to be frequently superior to that of AFP and, even more importantly, the combination of SCCA-IgM and AFP was characterized by a much better sensitivity than either biomarker alone, with only a modest decrease of specificity. Larger studies are needed before these preliminary findings can be generalized, but the combined use of AFP and SCCA-IgM represents an appealing perspective in diagnosis and prognostication of HCC.

  6. Prevention of hepatocellular carcinoma by correction ofmetabolic abnormalities: Role of statins and metformin

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Hepatocellular carcinoma is the third leading causeof cancer-related deaths in the world. It is associatedwith an important mortality rate and the incidenceis increasing. Patients showing metabolic syndromeseem to have higher incidence and mortality ratesfrom hepatocellular carcinoma than healthy subjects,especially those with type 2 diabetes mellitus and obesity.Thus, metformin and statins, both to treat features ofmetabolic syndrome, have been proposed to decreasethe risk of hepatocellular carcinoma. Otherwise, livercancer is the result of a complex process which impairsseveral signaling cascades, such as RAS/RAF/mitogenactivatedprotein kinase kinase (MEK)/extracellularsignal-regulated kinase (ERK), phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/AKT/mammalian targetof rapamycin (mTOR) and Wnt/β-catenin signaling.Metformin (through 5′-adenosine monophosphateactivatedprotein kinase pathway activation) andstatins (through 3?hydroxy?3-methylglutaryl coenzymeA inhibition) show anti-tumoral properties modifyingseveral steps of RAS/RAF/MEK/ERK, PI3K/AKT/mTORand Wnt/β-catenin signaling cascades. On the otherhand, metformin and statins have been found toreduce the risk of hepatocellular carcinoma up to 50%and 60%, respectively. Furthermore, both drugs haveshown a dose-dependent protective effect. However,information about chemopreventive role of metforminand statins is mainly obtained of observational studies,which could not take into account some bias. Inconclusion, given the rising of incidence of hepatocellularcarcinoma and the important morbidity andmortality rates associated with this cancer, lookingfor chemopreventive strategies is an essential task.Randomized controlled trials are needed to determinethe definite role of metformin and statins on theprevention of hepatocellular carcinoma.

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

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    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.

  8. 肝动脉化疗栓塞联合索拉非尼治疗中晚期肝细胞癌的临床分析%Clinical analysis of the treatment:transcatheter arterial chemoembolization combined with sorafenib in advanced hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    李勇; 黄建文; 陆骊工; 邵培坚; 胡宝山; 黄国敏; 魏照光; 张磊

    2010-01-01

    Objective To provide more evidence sources to the standard treatment for patients with advanced hepatocellular carcinoma,the writer analyze patients' time to progression (TTP) and overall survival (OS) after patients receiving transcatheter arterial chemoembolization (TACE) combined with sorafenib as a treatment of advanced hepatocellular carcinoma (HCC);observe the healing effect embolization combined with anti-angiogenic treatment for advanced hepatocellular carcinoma;and also analyze treatment of security.MethodsThere are 36 patients,33 male and 3 female had been Pathologically or clinical diagnosis.After receiving Transcatheter Arterial Chemoembolization (TACE)therapy,in the following 3 to 7 days,this group of patients continuously take sorafenib ( brand name:Nexavar) ( per tablet 200 mg),2 tablets each time,2 times a day.Every 4 to 8 weeks is called as one period of treatment.Referring to RECIST Evaluation,the writers mainly observe patients' tumor progression (TTP) and overall survival (OS),record adverse events.Using life table method to analyze survival rate,using Kaplan-Meier method to analyze all the survival curves.Results Till March,2010,14 of 36evaluable patients died and 22 survive;the median time to tumor progression (mTTP) to 8.62 months (95%CI:6.51-10.24 months);the median survival time (mOS) of 12.41 months (95% CI:9.57-14.80months).The overall survival rate to observation period is 61.1%;36 patients had been studied,22survive.Among the survivals,there is no CR cases,and 1 case PR,15 patients SD,6 patients PD;disease control rate (DCR) (CR + PR + SD) is 44.4%.The side effects of taking Sorafenib mainly are hand-foot skin reaction,diarrhea,fatigue and loss of appetite.These side effects can be markedly eased after symptomatic treatment.Conclusion Combined with sorafenib treatment may give patients with advanced hepatocellular carcinoma a longer longevity and keep the disease in a steady state.This therapy can be added into the treatments to

  9. Tumor markers for early diagnosis for brain metastasis of hepatocellular carcinoma: A case series and literature review for effective loco-regional treatment.

    Science.gov (United States)

    Kamimura, Kenya; Kobayashi, Yuji; Takahashi, Yoshifumi; Abe, Hiroyuki; Kumaki, Daisuke; Yokoo, Takeshi; Kamimura, Hiroteru; Sakai, Norihiro; Sakamaki, Akira; Abe, Satoshi; Takamura, Masaaki; Kawai, Hirokazu; Yamagiwa, Satoshi; Terai, Shuji

    2017-02-01

    Intrahepatic lesions of hepatocellular carcinoma (HCC) have been controlled by significant advances in treatment using loco-regional therapies, including, surgery, ablative therapy, catheter-based chemotherapy, and embolization. Consequently, the number of patients with extrahepatic metastatic lesions has increased. Their prognosis remains poor with approximately loco-regional treatment, including surgical resection and radiation therapy should be performed for better prognosis by preventing re-bleeding from the tumors.

  10. Hepatocellular carcinoma: current trends in worldwide epidemiology, risk factors, diagnosis, and therapeutics

    Directory of Open Access Journals (Sweden)

    Dhanasekaran R

    2012-05-01

    Full Text Available Renumathy Dhanasekaran, Alpna Limaye, Roniel CabreraDivision of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Florida, Gainesville, FL, USAAbstract: Hepatocellular carcinoma (HCC is a common malignancy in developing countries and its incidence is on the rise in the developing world. The epidemiology of this cancer is unique since its risk factors, including hepatitis C and B, have been clearly established. The current trends in the shifting incidence of HCC in different regions of the world can be explained partly by the changing prevalence of hepatitis. Early detection offers the only hope for curative treatment for patients with HCC, hence effective screening strategies for high-risk patients is of utmost importance. Liver transplantation and surgical resection remains the cornerstone of curative treatment. But major advances in locoregional therapies and molecular-targeted therapies for the treatment of advanced HCC have occurred recently. In this review, current trends in the worldwide epidemiology, surveillance, diagnosis, standard treatments, and the emerging therapies for HCC are discussed.Keywords: liver cancer, sorafenib, hepatitis C, TACE

  11. Perspectives of TGF-β inhibition in pancreatic and hepatocellular carcinomas

    Science.gov (United States)

    Tijeras-Raballand, Annemilaï; de Mestier, Louis; Cros, Jérome; Faivre, Sandrine; Raymond, Eric

    2014-01-01

    Advanced pancreatic ductal adenocarcinoma (PDAC) and hepatocellular carcinoma (HCC) are non-curable diseases with a particularly poor prognosis. Over the last decade, research has increasingly focused on the microenvironment surrounding cancer cells, and its role in tumour development and progression. PDAC and HCC differ markedly regarding their pathological features: PDAC are typically stromal-predominant, desmoplastic, poorly vascularized tumours, whereas HCC are cellular and highly vascularized. Despite these very different settings, PDAC and HCC share transforming growth factor-β (TGF-β) as a common key-signalling mediator, involved in epithelial-to-mesenchymal transition, invasion, and stroma-tumour dialogue. Recently, novel drugs blocking the TGF-β pathway have entered clinical evaluation demonstrating activity in patients with advanced PDAC and HCC. TGF-β signalling is complex and mediates both pro- and anti-tumoural activities in cancer cells depending on their context, in space and time, and their microenvironment. In this review we provide a comprehensive overview of the role of the TGF-β pathway and its deregulation in PDAC and HCC development and progression at the cellular and microenvironment levels. We also summarize key preclinical and clinical data on the role of TGF-β as a target for therapeutic intervention in PDAC and HCC, and explore perspectives to optimize TGF-β inhibition therapy PMID:24393789

  12. Sarcopenia predicts early dose-limiting toxicities and pharmacokinetics of sorafenib in patients with hepatocellular carcinoma.

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    Olivier Mir

    Full Text Available BACKGROUND: Sorafenib induces frequent dose limiting toxicities (DLT in patients with advanced hepatocellular carcinoma (HCC. Sarcopenia has been associated with poor performance status and shortened survival in cancer patients. PATIENTS AND METHODS: The characteristics of Child Pugh A cirrhotic patients with HCC receiving sorafenib in our institution were retrospectively analyzed. Sorafenib plasma concentrations were determined at each visit. Toxicities were recorded during the first month of treatment, and sarcopenia was determined from baseline CT-scans. RESULTS: Forty patients (30 males were included. Eleven (27.5% were sarcopenic. Eighteen patients (45% experienced a DLT during the first month of treatment. Sarcopenic patients experienced significantly more DLTs than non-sarcopenic patients did (82% versus 31%, p = 0.005. Grade 3 diarrhea was significantly more frequent in sarcopenic patients than in non-sarcopenic patients (45.5% versus 6.9%, p = 0.01, but not grade 3 hand foot syndrome reaction (9% versus 17.2%, p = 1. On day 28, median sorafenib AUC (n = 17 was significantly higher in sarcopenic patients (102.4 mg/l.h versus 53.7 mg/l.h, p = 0.013. CONCLUSIONS: Among cirrhotic Child Pugh A patients with advanced HCC, sarcopenia predicts sorafenib exposure and the occurrence of DLT within the first month of treatment.

  13. Yttrium-90 resin microspheres as an adjunct to sorafenib in patients with unresectable hepatocellular carcinoma

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    Mahvash A

    2016-02-01

    Full Text Available Armeen Mahvash,1 Ravi Murthy,1 Bruno C Odisio,1 Kanwal Pratap Raghav,2 Lauren Girard,2 Sheree Cheung,1 Van Nguyen,3 Joe Ensor,4 Sameer Gadani,5 Khaled M Elsayes,6 Reham Abdel-Wahab,1,7 Manal Hassan,1 Ahmed S Shalaby,1 James C Yao,1 Michael J Wallace,1 Ahmed O Kaseb2 1Department of Interventional Radiology, 2Department of Gastrointestinal Medical Oncology, 3Department of Pharmacy, 4Department of Statistics, The University of Texas MD Anderson Cancer Center, Houston, TX, 5Department of Radiology, Saint Louis University Hospital, St Louis, MO, 6Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; 7Department of Clinical Oncology, Assiut University Hospital, Assiut, Egypt Purpose: The safety and efficacy of the combined use of sorafenib and yttrium-90 resin microspheres (Y90 RMS to treat advanced hepatocellular carcinoma (HCC is not well established. We determined the incidence of adverse events with this combination therapy in patients with advanced HCC at our institution and analyzed the treatment and survival outcomes. Materials and methods: We reviewed the records of 19 patients with Barcelona Clinic Liver Cancer class B or C HCC who underwent treatment with Y90 RMS (for 21 sessions while receiving full or reduced doses of sorafenib between January 2008 and May 2010. Therapy response was evaluated using Response Evaluation Criteria in Solid Tumors. We evaluated median overall survival (OS and progression-free survival (PFS as well as hepatic and extrahepatic disease PFS and incidence of adverse events. Results: The median patient age was 67 years, and portal or hepatic venous invasion was present in eight patients (42%. Ten patients received reduced doses of sorafenib. The median Y90 radiation activity delivered was 41.2 mCi. The partial response of Response Evaluation Criteria in Solid Tumors was observed in four patients (19%. The median hepatic disease PFS was 7.82 months, extrahepatic

  14. Glycogenotic hepatocellular carcinoma with glycogen-ground-glass hepatocytes: A heuristically highly relevant phenotype

    Institute of Scientific and Technical Information of China (English)

    Peter Bannasch

    2012-01-01

    Glycogenotic hepatocellular carcinoma (HCC) with glycogen-ground-glass hepatocytes has recently been described as an allegedly "novel variant" of HCC,but neither the historical background nor the heuristic relevance of this observation were put in perspective.In the present contribution,the most important findings in animal models and human beings related to the emergence and further evolution of excessively glycogen storing (glycogenotic) hepatocytes with and without ground glass features during neoplastic development have been summarized.Glycogenotic HCCs with glycogen-ground-glass hepatocytes represent highly differentiated neoplasms which contain subpopulations of cells phenotypically resembling those of certain types of preneoplastic hepatic foci and benign hepatocellular neoplasms.It is questionable whether the occurrence of glycogen-ground-glass hepatocytes in a glycogenotic HCC justifies its classification as a specific entity.The typical appearance of ground-glass hepatocytes is due to a hypertrophy of the smooth endoplasmic reticulum,which is usually associated with an excessive storage of glycogen and frequently also with an expression of the hepatitis B surface antigen.Sequential studies in animal models and observations in humans indicate that glycogen-ground-glass hepatocytes are a facultative,integral part of a characteristic cellular sequence commencing with focal hepatic glycogenosis potentially progressing to benign and malignant neoplasms.During this process highly differentiated glycogenotic cells including ground-glass hepatocytes are gradually transformed via various intermediate stages into poorly differentiated glycogen-poor,basophilic (ribosome-rich) cancer cells.Histochemical,microbiochemical,and molecular biochemical studies on focal hepatic glycogenosis and advanced preneoplastic and neoplastic lesions in tissue sections and laser-dissected specimens in rat and mouse models have provided compelling evidence for an early insulinomimetic

  15. Astrocyte Elevated Gene-1 (AEG-1) Contributes to Non-thyroidal Illness Syndrome (NTIS) Associated with Hepatocellular Carcinoma (HCC)*

    OpenAIRE

    Srivastava, Jyoti; Robertson, Chadia L.; Gredler, Rachel; Siddiq, Ayesha; Rajasekaran, Devaraja; Akiel, Maaged A; Emdad, Luni; Mas, Valeria; Mukhopadhyay, Nitai D.; FISHER, PAUL B.; Sarkar, Devanand

    2015-01-01

    Background: Astrocyte elevated gene-1 (AEG-1) inhibits retinoid X receptor (RXR) function and is overexpressed in human hepatocellular carcinoma (HCC), which is associated with non-thyroidal illness syndrome (NTIS).

  16. DISTRIBUTION PATTERNS OF EXTRACELLULAR MATRICES IN HEPATOCELLULAR CARCINOMA AND THEIR CLINICAL SIGNIFICANCE

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective: In order to find out the distribution patterns of extracellular matrix (ECM) in hepatocellular carcinoma (HCC) and explore the relationshi between distribution patterns and hepatocellular caricnoma malignancy. Methods: Forty cases of HCC were studied by immunohitochemistry with 5 antibodies of anti-ECM. Results; Four types of distribution patterns were found: 1. continuous peritrabecular or periacinar type; 2. discontinuous peritrabecular or periacinar type; 3. vascular stroma type; 4. membrane and cytoplasmic type. The former 3 types were correlated closely with the growth pattern, cell differntiation and proliferation of tumor. Conclusions: ECM were useful marker for valution of malignant degree in HCC.

  17. MCM3AP,a Novel HBV Integration Site in Hepatocellular Carcinoma and Its Implication in Hepatocarcinogenesis

    Institute of Scientific and Technical Information of China (English)

    王晶; 林菊生; 常莹; 黎培元; 杨玉珍

    2010-01-01

    A novel HBV integration site involved in hepatocarcinogenesis was investigated. The HBV DNA integration sites were detected by Alu-PCR in hepatocellular carcinoma tissues, matched surrounding liver tissues in 30 patients with hepatitis B-related hepatocellular carcinoma (HCC) and 3 cases of normal liver tissues. The integration sites and flanking sequences in human genome were sequenced and blasted, and the expression of integrated HBV genes was determined by reverse transcriptase-polymerase chain reaction ...

  18. Post-Transplant Recurrence of Hepatocellular Carcinoma and Elevated NLR

    Science.gov (United States)

    Rustagi, Tarun

    2010-01-01

    Background: Hepatocellular carcinoma (HCC) is the third most common cause of cancer death worldwide. Approximately 80% of patients with HCC have cirrhosis, making liver transplantation (LT) the ideal treatment modality, as it provides a cure for the underlying liver disease as well as complete neoplastic clearance of tumor. Many criteria have been developed for HCC patient selection for LT, although the use of current criteria does not completely eliminate the risk of recurrence. Approximately 15% to 20% of patients who are within the criteria still develop recurrent disease, leading to an extensive search for surrogate markers of HCC aggressiveness. Methods: A prospectively collected database of all patients undergoing LT at our institution between January 1990 and January 2006 with a diagnosis of HCC was retrospectively analyzed. Patients undergoing LT had neutrophil and lymphocyte counts measured preoperatively on the day before surgery. The neutrophil to lymphocyte ratio (NLR) was calculated by dividing the neutrophil measurement by the lymphocyte measurement. An NLR ≥ 5 was considered elevated. Incidence of elevated NLR was compared in LT patients with and without HCC recurrence. Results: Total of 47 patients who underwent LT for HCC were identified. Patients were followed for mean duration of 6 years (range, 8 months – 15 years). Eight (8) patients had recurrence of HCC during the follow-up period. The mean duration between LT and diagnosis of HCC recurrence was 667 days (range, 306 – 1424 days). Twice the number of patients (16) were randomly selected from the remaining 39 patients who had no recurrence. Only 2/8 patients with recurrence and 3/16 patients without recurrence were found to have an elevated NLR. There was no statistical difference in incidence of elevated NLR between patients with and without recurrence (25% vs. 18.75%; P > .05). Conclusions: The effect of inflammation on carcinogenesis has been widely investigated, with recent increased

  19. The utility of hepatocyte paraffin 1 antibody in the immunohistological distinction of hepatocellular carcinoma from cholangiocarcinoma and metastatic carcinoma.

    Science.gov (United States)

    Shiran, M S; Isa, M R; Sherina, M S; Rampal, L; Hairuszah, I; Sabariah, A R

    2006-12-01

    Hepatocellular carcinoma (HCC) is the most common primary liver cancer and its diagnosis on routine stains is usually straightforward, except in some cases where there may be difficulty in distinguishing HCCs from metastatic carcinomas (MC) and cholangiocarcinomas (CC). Hepatocyte Paraffin 1 antibody (Hep Par 1) is a new monoclonal antibody which reacts with normal and neoplastic hepatocytes, and this study aims to determine its specificity and sensitivity in distinguishing hepatocellular carcinoma (HCC) from cholangiocarcinoma (CC) and metastatic carcinomas (MC). Hep Par 1 antibody was applied to 28 cases of HCC, 22 cases of MC from varying sites and 8 CCs, and produced a strong, diffuse, granular, cytoplasmic staining of all benign hepatocytes. 23