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Sample records for advanced orthotopic hepatocellular

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

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    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

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

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    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

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

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    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.

  4. Using PEGylated iron oxide nanoparticles with ultrahigh relaxivity for MR imaging of an orthotopic model of human hepatocellular carcinoma

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    Wang, Ruizhi; Hu, Yong; Yang, Yuchan; Xu, Wei; Yao, Mingrong; Gao, Dongmei; Zhao, Yan; Zhan, Songhua; Shi, Xiangyang; Wang, Xiaolin

    2017-02-01

    Hepatocellular carcinoma (HCC) is the most common type of liver malignant tumor, which is often diagnosed in advanced stages, resulting in low survival rate. The sensitive diagnosis of early HCC presents a great interest. Herein, a novel superparamagnetic contrast agent composed of iron oxide nanoparticles is reported. Firstly, polyethyleneimine-coated iron oxide (Fe3O4@PEI) nanoparticles (NPs) were synthesized via a mild reduction route, followed by their modification of polyethylene glycol monomethyl ether ( mPEG-COOH) via 1-ethyl-3-(3-(dimethylamino)propyl) carbodiimide hydrochloride coupling chemistry. After acetylation of the remaining PEI amines, the PEGylated Fe3O4 (Fe3O4@PEI.Ac- mPEG-COOH) NPs were successively characterized via different techniques. The Fe3O4@PEI.Ac- mPEG-COOH probes with an Fe3O4 NP size of 9 nm are water dispersible and cytocompatible within the given concentration range. The percentages of PEI and m-PEG-COOH on the particles surface are calculated to be 15.5 and 7.2%, respectively. Prior to the administration of Fe3O4@PEI.Ac- mPEG-COOH NPs of ultrahigh r 2 relaxivity (461.29 mM-1 s-1) via tail intravenous injection for MR imaging of HCC, the orthotopic model of HCC was established in the nude mice by surgical transplantation with HCCLM3 cells. The analysis of MR signal intensity (SI) in the orthotopic tumor model demonstrated that the developed Fe3O4@PEI.Ac- mPEG-COOH NPs were able to infiltrate into the tumor area through the enhanced permeability and retention (EPR) effect reaching the bottom at 2 h postinjection. The developed Fe3O4@PEI.Ac- mPEG-COOH NPs may be further applied for theranostics of different diseases through combing various therapeutic agents.

  5. Development of a High-Throughput Molecular Imaging-Based Orthotopic Hepatocellular Carcinoma Model.

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    Hwang, Gloria L; van den Bosch, Maurice A; Kim, Young I; Katzenberg, Regina; Willmann, Juergen K; Paulmurugan, Ramasamy; Gambhir, Sanjiv S; Hofmann, Lawrence

    2015-06-01

    We have developed a novel orthotopic rat hepatocellular (HCC) model and have assessed the ability to use bioluminescence imaging (BLI), positron emission tomography (PET), and ultrasound for early tumor detection and monitoring of disease progression.  Briefly, rat HCC cells were stably transfected with click beetle red as a reporter gene for BLI. Tumor cells were injected under direct visualization into the left or middle lobe of the liver in 37 rats. In six animals, serial PET, BLI, and ultrasound imaging were performed at 10-time points in 28 days. The remainder of the animals underwent PET imaging at 14 days. Tumor implantation was successful in 34 of 37 animals (91.9%). In the six animals that underwent serial imaging, tumor formation was first detected with BLI on Day 4 with continued increase through Day 21, and hypermetabolic activity on PET was first noted on Days 14-15 with continued increase through Day 28. PET activity was seen on Day 14 in the 28 other animals that demonstrated tumor development. Anatomic tumor formation was detected with ultrasound at Days 10-12 with continued growth through Day 28. The first metastases were detected by PET after Day 24.        We have successfully developed and validated a novel orthotopic HCC small animal model that permits longitudinal assessment of change in tumor size using molecular imaging techniques. BLI is the most sensitive imaging method for detection of early tumor formation and growth. This model permits high-throughput in vivo evaluation of image-guided therapies.

  6. New advances in hepatocellular carcinoma

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    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.

  7. Asparagus polysaccharide and gum with hepatic artery embolization induces tumor growth and inhibits angiogenesis in an orthotopic hepatocellular carcinoma model.

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    Weng, Ling-Ling; Xiang, Jian-Feng; Lin, Jin-Bo; Yi, Shang-Hui; Yang, Li-Tao; Li, Yi-Sheng; Zeng, Hao-Tao; Lin, Sheng-Ming; Xin, Dong-Wei; Zhao, Hai-Liang; Qiu, Shu-Qi; Chen, Tao; Zhang, Min-Guang

    2014-01-01

    Liver cancer is one of leading digestive malignancies with high morbidity and mortality. There is an urgent need for the development of novel therapies for this deadly disease. It has been proven that asparagus polysaccharide, one of the most active derivates from the traditional medicine asparagus, possesses notable antitumor properties. However, little is known about the efficacy of asparagus polysaccharide as an adjuvant for liver cancer chemotherapy. Herein, we reported that asparagus polysaccharide and its embolic agent form, asparagus gum, significantly inhibited liver tumor growth with transcatheter arterial chemoembolization (TACE) therapy in an orthotopic hepatocellular carcinoma (HCC) tumor model, while significantly inhibiting angiogenesis and promoting tumor cell apoptosis. Moreover, asparagine gelatinous possessed immunomodulatory functions and showed little toxicity to the host. These results highlight the chemotherapeutic potential of asparagus polysaccharide and warrant a future focus on development as novel chemotherapeutic agent for liver cancer TACE therapy.

  8. 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 ...

  9. Simple Risk Score for Prediction of Early Recurrence of Hepatocellular Carcinoma within the Milan Criteria after Orthotopic Liver Transplantation

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    Feng, Jiliang; Wu, Jushan; Zhu, Ruidong; Feng, Dezhao; Yu, Lu; Zhang, Yan; Bu, Dayu; Li, Chenlei; Zhou, Yuyan; Si, Lianghao; Liu, Yuhan; Liang, Ziwei; Xu, Jianing; Wu, Tianjun

    2017-01-01

    Ten to twenty percent of the hepatocellular carcinoma (HCC) patients fulfilling the Milan criteria (MC) recurred within three years after orthotopic liver transplantation (OLT). We therefore utilize a training cohort to develop an improved prognostic model for predicting the recurrence in these patients. By univariate and multivariate analysis, AFP level [cut-off value: 321 ng/mL, area under the curve (AUC) = 0.724, 95% confidence interval (CI) = 0.604–0.843, P < 0.001] and cytokeratin-19 (CK19) and glypican-3 (GPC3) expression pattern from nine putative prognostic factors were entered in risk factor scoring model to conjecture the tumor recurrence. In the training cohort, the AUC value of the model was 0.767 (95% CI = 0.645–0.890, P < 0.001), which was the highest among all the elements. The model’s performance was then assessed using a validation cohort. In the validation cohort, the AUC value of the model was 0.843 (95% CI = 0.720−0.966, P < 0.001) which was higher than any other elements. The results indicated that model had high performance with good discrimination ability and significantly improved the predictive capacity for the recurrence of HCC patients within MC after OLT. PMID:28276470

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

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    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.

  11. Anti-tumor effects of polybutylcyanoacrylate nanoparticles of diallyl trisulfide on orthotopic transplantation tumor model of hepatocellular carcinoma in BALB/c nude mice

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    ZHANG Zhi-mian; YANG Xiao-yun; DENG Shu-hai; XU Wei; GAO Hai-qing

    2007-01-01

    Background Hepatocellular carcinoma (HCC) ranked the second among the causes of cancer mortality in China since the 1990s. Up to now, medication still plays an important role in the treatment of HCC. The therapies based on the allicin as a potential chemopreventive analog although is in its infancy at the present time, may have a significant role in the future management of HCC. Diallyl trisulfide (DATS) is a natural compound derived from garlic. In this study, we investigated the inhibitory effects of hepatic targeted polybutylcyanoacrylate nanoparticles of diallyl trisulfide(DATS-PBCA-NP) on orthotopic transplanted HepG2 hepatocellular carcinoma in nude mice.Methods DATS-PBCA-NP were detected by transmission electron microscope (TEM) and high-performance liquid chromatography (HPLC). The orthotopic transplantation HCC models were established by implanting HCC HepG2 xenograft bits under the envelope of the mice liver. Successful models (n=29) were divided into 4 groups: normal saline(NS), empty nanoparticles (EN), DATS and DATS-PBCA-NP were intravenously administered to the mice respectively for 2 weeks. In vivo antitumor efficacy was evaluated by the measurement of tumor volume. Terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) assay and protein levels of apoptosis and cell proliferation proteins by immunoblotting in tumor tissues were performed to elucidate the possible mechanism.Results DATS-PBCA-NP possessed smooth and round appearance, dispersed well, and released in vitro in accord with double phase kinetics model. DATS-PBCA-NP changed the tissue/organ distribution of DATS in vivo. The successful rate of tumor implantation was 100%. Intravenous administration of DATS-PBCA-NP significantly retarded the growth of orthotopically transplanted hepatoma in BALB/c nude mice (compared with the other three groups, all P<0.05) without causing weight loss (P>0.05). TUNEL staining showed that the tumors from DATS-PBCA-NP treated mice

  12. Making an Orthotopic Tumor Model of Hepatocellular Carcinoma for ICR Mice by Direct Injection%直接注射法制作ICR小鼠肝癌原位移植瘤模型

    Institute of Scientific and Technical Information of China (English)

    张建民; 施晓雷; 陶科; 潘军平; 吴亚夫

    2011-01-01

    目的:培养鼠肝癌H22细胞,直接注射法制作ICR小鼠肝癌原位移植瘤,为后续实验奠定基础.方法:鼠肝癌H22细胞体外培养,将调整好的对数生长期的肝癌细胞直接注射小鼠肝脏,2周后解剖观察,并进行组织HE染色.结果:所有实验小鼠均可见肿瘤生长,HE染色示肝细胞肝癌.结论:直接注射法制作ICR小鼠肝癌原位移植瘤模型简便易行,值得推广应用.%Objective: To cultivate H22 cell line and making an orthotopic tumor model of hepatocellular carcinoma on ICR mouse using direct injection method to lay the foundation for subsequent experiment. Methods: Cultivate H22 cell line in vitro and an orthotopic xenograft tumor model of hepatocellular carcinoma was created by injection of H22 cells in logarithmic growth phase directly into the liver parenchyma of ICR mice. Two weeks later, hepatocellular carcinoma specimens of animals were observed and stained with hematoxylin/eosin. Results: Tumor growth happened on all the experimental mice and was showed as hepatocellular carcinoma by hematoxylin-eosin staining. Conclusion: It is convenient of direct injection method on making an orthotopic tumor model of hepatocellular carcinoma and should be reported and used widely.

  13. MicroRNA-regulated non-viral vectors with improved tumor specificity in an orthotopic rat model of hepatocellular carcinoma

    DEFF Research Database (Denmark)

    Ronald, J A; Katzenberg, R; Nielsen, Carsten Haagen

    2013-01-01

    In hepatocellular carcinoma (HCC), tumor specificity of gene therapy is of utmost importance to preserve liver function. MicroRNAs (miRNAs) are powerful negative regulators of gene expression and many are downregulated in human HCC. We identified seven miRNAs that are also downregulated in tumors...... in a rat hepatoma model (P...

  14. Evolution of systemic therapy of advanced hepatocellular carcinoma

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    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.

  15. 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.

  16. Development of a locally advanced orthotopic prostate tumor model in rats for assessment of combined modality therapy.

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    Tumati, Vasu; Mathur, Sanjeev; Song, Kwang; Hsieh, Jer-Tsong; Zhao, Dawen; Takahashi, Masaya; Dobin, Timothy; Gandee, Leah; Solberg, Timothy D; Habib, Amyn A; Saha, Debabrata

    2013-05-01

    The purpose of this study was to develop an aggressive locally advanced orthotopic prostate cancer model for assessing high-dose image-guided radiation therapy combined with biological agents. For this study, we used a modified human prostate cancer (PCa) cell line, PC3, in which we knocked down a tumor suppressor protein, DAB2IP (PC3‑KD). These prostate cancer cells were implanted into the prostate of nude or Copenhagen rats using either open surgical implantation or a minimally invasive procedure under ultrasound guidance. We report that: i) these DAB2IP-deficient PCa cells form a single focus of locally advanced aggressive tumors in both nude and Copenhagen rats; ii) the resulting tumors are highly aggressive and are poorly controlled after treatment with radiation alone; iii) ultrasound-guided tumor cell implantation can be used successfully for tumor development in the rat prostate; iv) precise measurement of the tumor volume and the treatment planning for radiation therapy can be obtained from ultrasound and MRI, respectively; and v) the use of a fiducial marker for enhanced radiotherapy localization in the rat orthotopic tumor. This model recapitulates radiation-resistant prostate cancers which can be used to demonstrate and quantify therapeutic response to combined modality treatments.

  17. Hepatocellular carcinoma:current management and recent advances

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    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.

  18. Therapeutic options for intermediate-advanced hepatocellular carcinoma

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    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.

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

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    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.

  20. 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.

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

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    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.

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

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    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.

  3. 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

  4. 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.

  5. Hepatocellular Carcinoma Metastasis to the Orbit in a Coinfected HIV+ HBV+ Patient Previously Treated with Orthotopic Liver Transplantation: A Case Report

    Directory of Open Access Journals (Sweden)

    S. Guerriero

    2011-01-01

    Full Text Available Hepatocellular carcinoma rarely metastasizes to the orbit. We report a 45-year-old male, HBV+, HIV+, with a past history of a liver transplant for ELSD (end-stage liver disease with hepatocellular carcinoma and recurrent HCC, who presented with proptosis and diplopia of the left eye. CT scans of the head revealed a large, irregular mass in the left orbit causing superior and lateral destruction of the orbital bone. Biopsy specimens of the orbital tumor showed features of metastatic foci of hepatocellular carcinoma. Only 16 other cases of HCC metastasis to the orbit have been described in literature, and this is the first case in a previously transplanted HIV+, HBV+ patient.

  6. 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...

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 抗VEGFR-2嵌合Fab抗体对裸鼠肝癌原位移植瘤的治疗作用%Therapeutical effect of chimeric anti-VEGFR-2 Fab antibody on orthotopic xenograft of hepatocellular carcinoma in BALB/c nude mice

    Institute of Scientific and Technical Information of China (English)

    李倩君; 潘峰; 王丙剑; 朱进; 张建民; 吴亚夫; 周传文

    2013-01-01

    目的 检测抗血管内皮生长因子受体2 (VEGFR-2)嵌合Fab抗体对裸鼠肝癌原位移植瘤的治疗作用.方法 40只4周龄雄性BALB/c裸鼠建立肝癌H22细胞移植瘤模型后随机均分为Fab抗体(A)组和生理盐水对照(B)组.比较两组裸鼠生存时间、移植瘤病理变化及微血管密度(MVD).结果 成功建立裸鼠H22肝癌原位移植瘤模型,HE染色显示肝细胞肝癌.A组裸鼠中位数生存时间明显长于B组(20.0 d vs.14.0 d)(P<0.01);A组肝脏实体瘤内MVD较B组显著减少(8.65±1.79 vs.25.64±1.53)(P<0.05).结论 抗VEGFR-2嵌合Fab抗体对裸鼠肝癌原位移植瘤有治疗作用.%Objective To investigate the therapeutical effect of chimeric anti-vascular endothelial growth factor receptor(VEGFR)-2 Fab antibody on orthotopic xenograft in BALB/c nude mice. Methods The orthotopic xenograft model of hepatocellular carcinoma H22 cells was established in 40 nude mice, which were equally randomized into two groups of A (treated with chimeric anti-VEGFR-2 Fab antibody) and B(treated with normal saline). The survival time, pathological changes and microvessel density(MVD) in H22 xenografts were compared between two groups. Results An orthotopic xenograft model of hepatocellular carcinoma was successfully created in nude mice, which was confermed as hepatocellular carcinoma by hematoxylin-eosin staining. The mean survival time was longer in group A than that in group B(20. 0 d vs. 14. 0 d) (P<0. 05). MVD in the xenografts was less in group A than that in group B(8. 65±1. 79 vs. 25. 64±1. 53) (P<0. 05). Conclusion The chimeric anti-VEGFR-2 Fab antibody has some therapeutical effect on an orthotopic xenografts in nude mice.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. An autologous in situ tumor vaccination approach for hepatocellular carcinoma. 2. Tumor-specific immunity and cure after radio-inducible suicide gene therapy and systemic CD40-ligand and Flt3-ligand gene therapy in an orthotopic tumor model.

    Science.gov (United States)

    Kawashita, Yujo; Deb, Niloy J; Garg, Madhur K; Kabarriti, Rafi; Fan, Zuoheng; Alfieri, Alan A; Roy-Chowdhury, Jayanta; Guha, Chandan

    2014-08-01

    Diffuse hepatocellular carcinoma (HCC) is a lethal disease that radiation therapy (RT) currently has a limited role in treating because of the potential for developing fatal radiation-induced liver disease. However, recently diffuse HCC, "radio-inducible suicide gene therapy" has been shown to enhance local tumor control and residual microscopic disease within the liver for diffuse HCC, by using a combination of chemoactivation and molecular radiosensitization. We have demonstrated that the addition of recombinant adenovirus-expressing human Flt3 ligand (Adeno-Flt3L) after radio-inducible suicide gene therapy induced a Th1-biased, immune response and enhanced tumor control in an ectopic model of HCC. We hypothesized that sequential administration of recombinant adenovirus-expressing CD40L (Adeno-CD40L) could further potentiate the efficacy of our trimodal therapy with RT + HSV-TK + Adeno-Flt3L. We examined our hypothesis in an orthotopic model of diffuse HCC using BNL1ME A.7R.1 (BNL) cells in Balb/c mice. BNL murine hepatoma cells (5 × 10(4)) transfected with an expression vector of HSV-TK under the control of a radiation-inducible promoter were injected intraportally into BALB/cJ mice. Fourteen days after the HCC injection, mice were treated with a 25 Gy dose of radiation to the whole liver, followed by ganciclovir (GCV) treatment and systemic adenoviral cytokine gene therapy (Flt3L or CD40L or both). Untreated mice died in 27 ± 4 days. Radiation therapy alone had a marginal effect on survival (median = 35 ± 7 days) and the addition of HSV-TK/GCV gene therapy improved the median survival to 47 ± 6 days. However, the addition of Adeno-Flt3L to radiation therapy and HSV-TK/GCV therapy significantly (P = 0.0005) increased survival to a median of 63 ± 20 days with 44% (7/16) of the animals still alive 116 days after tumor implantation. The curative effect of Flt3L was completely abolished when using immunodeficient nude mice or mice depleted for CD4, CD8 and

  20. 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.

  1. 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

  2. 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

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

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Hepatocellular carcinoma (HCC) remains a common andlethal malignancy worldwide and arises in the setting ofa host of diseases. The incidence continues to increasedespite multiple vaccines and therapies for viruses suchas the hepatitis B and C viruses. In addition, due to thegrowing incidence of obesity in Western society, thereis anticipation that there will be a growing populationwith HCC due to non-alcoholic fatty liver disease. Dueto the growing frequency of this disease, screening isrecommended using ultrasound with further imagingusing magnetic resonance imaging and multi-detectorcomputed tomography used for further characterizationof masses. Great advances have been made to help withthe early diagnosis of small lesions leading to potentialcurative resection or transplantation. Resection andtransplantation maybe used in a variety of patients thatare carefully selected based on underlying liver disease.Using certain guidelines and clinical acumen patientsmay have good outcomes with either resection ortransplantation however many patients are inoperableat time of presentation. Fortunately, the use of newlocoregional therapies has made down staging patientsa potential option making them potential surgicalcandidates. Despite a growing population with HCC,new advances in viral therapies, chemotherapeutics,and an expanding population of surgical and transplantcandidates might all contribute to improved long-termsurvival of these patients.

  4. 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.

  5. [Our technique in orthotopic neobladder].

    Science.gov (United States)

    Del Boca, C; Colloi, D; Guardamagna, A; Giuberti, A C; Ferrari, C

    1995-09-01

    The strive in the field of orthotopic neobladders derives from the need to improve their morphofunctional aspects and to simplify the surgical procedures. The Authors propose their experience on a new method of orthotopic neobladder in 8 patients submitted to radical cystectomy for advanced bladder neoplasia from march 91 until june 93. The surgical technique was to prepare a reservoir with a simile Camey 2 type procedure modified by them using 50 cm of ileus, 30 of which detubularized and reconfigured into a simile spheric shape with Polygia 75 staplers. The remaining length was left intact for the ureteral anastomosis performing the Wallace 1 type procedure. The advantages of this technique are that: the neobladder is prepared rapidly using staplers, thus reducing operating time the presence of an isoperistaltic segment of ileus for ureteral anastomosis permits an reduced ureteral mobilization with a low probability of reflux a simple reconversion in ileal conduit in case of reservoir failure or neoplastic urethral recurrence is possible. The criteria for selecting the patients are reported and the diagnostic algorithm regarding the follow-up presented. The latter is done with biochemical, echographic, radiological and pressure studies, every 4-6 or 12 months. Particular attention has been focused on the quality of life in relation to the diurnal/nocturnal continence and micturation interval. They conclude that this technique is surgically simple and rapid with satisfactory clinical and urodynamic results.

  6. 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.

  7. 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.

  8. 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.

  9. 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

  10. 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

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. Hepatocellular carcinoma in patients undergoing orthotopic liver transplantation: radiological findings with anatomopathological correlation in Brazil Carcinoma hepatocelular em pacientes submetidos a transplante hepático: achados radiológicos com correlação anatomopatológica no Brasil

    Directory of Open Access Journals (Sweden)

    Antônio Carlos Maciel

    2006-03-01

    Full Text Available BACKGROUND: Hepatocellular carcinoma is one of the most common malignant tumors worldwide. Imaging techniques, specially computed tomography and ultrasound, are among the most useful diagnostic tools, although the accuracy of these methods may have a significant variability. AIMS: To determine the prevalence of hepatocellular carcinoma in cirrhotic patients undergoing orthotopic liver transplantation at "Santa Casa de Misericórdia" of Porto Alegre, RS, Brazil; to estimate the sensitivity of computed tomography and ultrasound in pretransplantation detection of hepatocellular carcinoma in this population; to correlate the radiological characteristics with anatomopathological findings. MATERIALS AND METHODS: Retrospective prevalence study. Population: adult, cirrhotic patients undergoing orthotopic liver transplantation from January 1990 to July 2003. Among the 292 transplanted patients, 31 cases of hepatocellular carcinoma were diagnosed, of which 29 were included in the study. Tumor characteristics in both ultrasound and computed tomography were compared to those observed in anatomopathological examination. RESULTS: Prevalence of hepatitis C virus infection among patients with diagnosis of hepatocellular carcinoma was 93.5%, and the prevalence of hepatocellular carcinoma among transplanted patients was 10.6%. The overall sensitivity of the imaging techniques was 70.3% for computed tomography and 72% for ultrasound. CONCLUSION: The prevalence of hepatocellular carcinoma at our institution, as well as the sensitivity of both ultrasound and computed tomography to detect such tumors at pretransplantation screening were similar to those found by other authors, while the prevalence of hepatitis C virus infection, the most common etiological agent for liver disease in our patients, is one of the highest ever reported in literature. Factors influencing hepatocellular carcinoma detection rates were: time from examination to liver transplantation

  16. Development of a preclinical orthotopic xenograft model of ewing sarcoma and other human malignant bone disease using advanced in vivo imaging.

    Directory of Open Access Journals (Sweden)

    Britta Vormoor

    Full Text Available Ewing sarcoma and osteosarcoma represent the two most common primary bone tumours in childhood and adolescence, with bone metastases being the most adverse prognostic factor. In prostate cancer, osseous metastasis poses a major clinical challenge. We developed a preclinical orthotopic model of Ewing sarcoma, reflecting the biology of the tumour-bone interactions in human disease and allowing in vivo monitoring of disease progression, and compared this with models of osteosarcoma and prostate carcinoma. Human tumour cell lines were transplanted into non-obese diabetic/severe combined immunodeficient (NSG and Rag2(-/-/γc(-/- mice by intrafemoral injection. For Ewing sarcoma, minimal cell numbers (1000-5000 injected in small volumes were able to induce orthotopic tumour growth. Tumour progression was studied using positron emission tomography, computed tomography, magnetic resonance imaging and bioluminescent imaging. Tumours and their interactions with bones were examined by histology. Each tumour induced bone destruction and outgrowth of extramedullary tumour masses, together with characteristic changes in bone that were well visualised by computed tomography, which correlated with post-mortem histology. Ewing sarcoma and, to a lesser extent, osteosarcoma cells induced prominent reactive new bone formation. Osteosarcoma cells produced osteoid and mineralised "malignant" bone within the tumour mass itself. Injection of prostate carcinoma cells led to osteoclast-driven osteolytic lesions. Bioluminescent imaging of Ewing sarcoma xenografts allowed easy and rapid monitoring of tumour growth and detection of tumour dissemination to lungs, liver and bone. Magnetic resonance imaging proved useful for monitoring soft tissue tumour growth and volume. Positron emission tomography proved to be of limited use in this model. Overall, we have developed an orthotopic in vivo model for Ewing sarcoma and other primary and secondary human bone malignancies, which

  17. 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.

  18. 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.

  19. 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

  20. 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

  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. Aspergillus Mediastinitis after Orthotopic Heart Transplantation: A Case Report.

    Science.gov (United States)

    El-Sayed Ahmed, Magdy M; Almanfi, Abdelkader; Aftab, Muhammad; Singh, Steve K; Mallidi, Hari R; Frazier, O H

    2015-10-01

    A 55-year-old woman was admitted for orthotopic heart transplantation. Her medical history was notable for multiple cardiovascular problems, including ischemic cardiomyopathy that necessitated circulatory support with a left ventricular assist device. Five weeks after undergoing orthotopic heart transplantation, she developed Aspergillus calidoustus mediastinitis, for which she underwent a prolonged course of antifungal treatment that comprised (in sequence) posaconazole for 11 days, voriconazole for 10 days, and amphotericin B for 42 days. During this period, she also underwent repeated mediastinal drainage and sternal débridement, followed by sternal wiring and coverage with bilateral pectoralis advancement flaps. Four months postoperatively, she was discharged from the hospital with a successfully controlled infection and a healed sternum. To our knowledge, only 3 previous cases of Aspergillus mediastinitis after orthotopic heart transplantation have been reported in the literature, none of which was Aspergillus calidoustus.

  3. 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.

  4. 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.

  5. 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.

  6. 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

  7. 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.

  8. 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.

  9. 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.

  10. Complications of Radical Cystectomy and Orthotopic Reconstruction

    Directory of Open Access Journals (Sweden)

    Wei Shen Tan

    2015-01-01

    Full Text Available Radical cystectomy and orthotopic reconstruction significant morbidity and mortality despite advances in minimal invasive and robotic technology. In this review, we will discuss early and late complications, as well as describe efforts to minimize morbidity and mortality, with a focus on ileal orthotopic bladder substitute (OBS. We summarise efforts to minimize morbidity and mortality including enhanced recovery as well as early and late complications seen after radical cystectomy and OBS. Centralisation of complex cancer services in the UK has led to a fall in mortality and high volume institutions have a significantly lower rate of 30-day mortality compared to low volume institutions. Enhanced recovery pathways have resulted in shorter length of hospital stay and potentially a reduction in morbidity. Early complications of radical cystectomy occur as a direct result of the surgery itself while late complications, which can occur even after 10 years after surgery, are due to urinary diversion. OBS represents the ideal urinary diversion for patients without contraindications. However, all patients with OBS should have regular long term follow-up for oncological surveillance and to identify complications should they arise.

  11. Long acting octreotide in the treatment of advanced hepatocellular cancer and overexpression of somatostatin receptors: Randomized placebo-controlled trial

    Institute of Scientific and Technical Information of China (English)

    D Dimitroulopoulos; D Daskalopoulou; E Paraskevas; D Xinopoulos; K Tsamakidis; A Zisimopoulos; E Andriotis; D Panagiotakos; A Fotopoulou; C Chrysohoou; A Bazinis

    2007-01-01

    AIM: To estimate if and to what extent long acting octreotide (LAR) improves survival and quality of life in patients with advanced hepatocellular carcinoma (HCC).METHODS: A total of 127 cirrhotics, stages A-B, due to chronic viral infections and with advanced HCC, were enrolled in the study. Scintigraphy with 111Indium labeled octreotide was performed in all cases. The patients with increased accumulation of radionuclear compound were randomized to receive either oral placebo only or octreotide/octreotide LAR only as follows: octreotide 0.5mg s.c. Every 8 h for 6 wk, at the end of wk 4-8 octreotide LAR 20 mg I.m. And at the end of wk 12 and every 4 wk octreotide LAR 30mg I.m.. Follow-up was worked out monthly as well as the estimation of quality of life (QLQ-C30 questionnaire). Patients with negative somatostatin receptors (SSTR) detection were followed up in the same manner.RESULTS: Scintigraphy demonstrated SSTR in 61 patients. Thirty were randomized to receive only placebo and 31 only octreotide. A significantly higher survival time was observed for the octreotide group (49±6 wk)as compared to the control group (28±1 wk) and to the SSTR negative group (28±2 wk), LR=20.39, df=2,P<0.01. The octreotide group presented 68.5% lower hazard ratio [95% CI (47.4%-81.2%)]. During the first year, a 22%, 39% and 43% decrease in the QLQ-C30 score was observed in each group respectively.CONCLUSION: The proposed therapeutic approach has shown to improve the survival and quality of life in SSTR positive patients with advanced HCC.

  12. Galactosylated Chitosan/5-fluorouracil Nanoparticles Inhibit Hepatocellular Carcinoma in the Orthotopic Transplant Mouse Model%半乳糖基壳聚糖/5-氟尿嘧啶纳米粒抑制小鼠原位肝癌移植模型的实验研究

    Institute of Scientific and Technical Information of China (English)

    李清; 庄婵娟; 程明荣; 何秉; 韩江

    2012-01-01

    目的:观察半乳糖基壳聚糖(GC)/5-氟尿嘧啶(5-FU)纳米粒抑制小鼠原位肝癌移植模型的疗效及机制.方法:合成GC/5-FU纳米粒,建立小鼠原位肝癌移植模型,通过动物实验观察GC/5-FU纳米粒治疗小鼠原位肝癌移植模型的疗效,通过原位末端标记法(TUNEL法)检测肝癌的凋亡.结果:GC/5-FU纳米粒成功合成,呈规则的球形,表面光滑,大小均匀,纳米粒间无粘连.实验结束时,小鼠的肝癌组织称重,进行方差分析发现GC/5-Fu的瘤重为(0.4361±0.1153)g,5-Fu组为(0.7932±0.1283)g,GC为(1.3989±0.2125)g,和对照组为(1.5801±0.2821)g,4组瘤重之间差异有显著的统计学意义(P<0.01).GC/5-FU组和5-FU组的瘤重明显小于GC组及对照组,差异有统学意义(P<0.01);GC/5-FU的瘤重又显著小于5-Fu组(P<0.01).观察各组小鼠的生存期发现对照组的中位生存时间为12d,GC组为13d,5-FU为17d,而GC/5-FU组最高为30d.GC/5-FU组的生存时间最长.通过TUNEL法观察肝癌细胞的凋亡发现GC/5-FU组的平均凋亡指数(AI)为21.34%较5-FU组的14.74%明显增高(P<0.05),均较GC组和对照组明显增高,而GC组和对照组间的AI无明显差异(P>0.05).结论:GC/5-FU纳米粒在体内对小鼠原位肝癌具有明显抑制作用,较5-FU明显增强.其机理可能与GC能通过细胞膜将5-FU从细胞外转移到细胞内,增强5-FU对肝癌细胞的凋亡.%Objective: To observe the efficacy and mechanism of hepatocellular carcinoma in the orthotopic transplant mouse model with galactosylated chitosan (GC) / 5-fluorouracil (5-FU) nanoparticles. Methods: The GC/5-FU nanoparticles were prepared, the hepatocellular carcinoma in the orthotopic transplant mouse model were established, the apoptosis in liver cancer by TdT-mediated dUTP nick end labeling (TUNEL) were detected. Results: GC/5-FU nanoparticles were successfully synthesized in spherical, smooth surface, uniform size, no adhesion between the nanoparticles. At the end of

  13. 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.

  14. 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.

  15. 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.

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  18. 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.

  19. 七例八次背驮式原位肝移植%Piggyback orthotopic liver transplantation in 4 patients with Wilson disease and 3 with advanced liver diseases

    Institute of Scientific and Technical Information of China (English)

    叶启发; 陈知水; 陈实; 曾凡军; 刘敦贵; 周平; 夏穗生; 襄法祖

    1998-01-01

    对4例Wilson病及3例晚期肝病患者施行了8次背驮式原位肝移植术,其中1例为减体积性背驮式原位肝移植.3例已分别存活2年、9个月、6个月,4例死于术后并发症.认为代谢性疾病是原位肝移植的最佳适应证,其次是肝硬变;术后感染、急性和慢性排斥、肺部并发症及胆道并发症是影响患者存活的重要因素;背驮式原位肝移植对全身血流动力学的影响较小.%Piggyback orthotopic liver transplantation(OLT)(8 times)was performed in 4 patients with Wilson disease and 3 with advanced liver diseases.Of 7 patients,6 cases(7 times) received piggyback OLT with whole liver,1 piggyback OLT with reduced-size grafts of right hepatic lobe.Three cases have survived 2 years, 9 months and 4 months,respectively.Four cases died of postoperative complications.It was considered that metabolic disease was the best indications for OLT,then the hepatic cirrhosis.The key factors influencing the survival of the patients include postoperative infection,acute and chronic rejection,pulmonary complications and bile duct complications.Piggyback OLT has little effect on the haemodynamics of whole bodv.

  20. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

  3. Establishment of a high metastatic potential human hepatocellular carcinoma orthotopic transplantation model with palliative liver resection in nude mice%高转移MHCC97H细胞裸鼠原位移植瘤姑息性肝癌切除模型的建立

    Institute of Scientific and Technical Information of China (English)

    黄修燕; 黄自丽; 许永华; 黄新余; 周俭; 叶胜龙; 樊嘉; 汤钊猷; 郑起

    2013-01-01

    Objective To construct a high metastatic potential human hepatocellular carcinoma (HCC)orthotopic transplantation model with palliative liver resection in nude mice.Methods A human HCC orthotopic nude mice model was established by administering a single inoculation of the highly metastatic MHCC97H tumor tissue (size 2 mm × 2 mm × 2 mm) into the left liver lobe.At day 14 post-inoculation,a random group of the mice received palliative liver resection; the unresected mice served as controls.Changes in expression levels of 113 genes with metastasis-related functions were evaluated in the residual HCC tissues.At day 35 post-resection,a random group of the mice were sacrificed by cervical dislocation and a comprehensive metastases examination was performed.The remaining mice were used to observe life span.All statistical analyses were performed by the SPSS v17.0 software,and significance was defined as P < 0.05.Results The nude mouse model of highly metastatic HCC with palliative liver resection was successfully established.Incidences of intrahepatic and abdominal metastases were higher in the palliative resected group (vs.unresected group:11.7 ± 4.7 vs.6.3 ± 2.8,t =-2.412,P < 0.05 and 9.8 ± 3.4 vs.5.2 ± 2.6,t =-2.641,P < 0.05respectively).In addition,the palliative resected group showed significantly enhanced pulmonary metastasis (vs.unresected group:14.3 ± 4.7 vs.8.7 ± 4.7,t =-2.348,P < 0.05).Differential gene expression levels were found for MTSS1,TGFβ1,SMAD2,IL-1β,and MMP7,and were situated in the central position of gene function net of residual HCC.The life-span of the palliative resected group was significantly longer than that of the unresected group (60.8 ± 2.7 vs.51.3 ± 1.4days,x2=12.850,P<0.01).Conclusion The highly metastatic human HCC nude mouse model with palliative liver resection that was successfully constructed in this study represents a useful investigational tool to assess the biological characteristics of residual cancer and to

  4. 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

  5. The prognostic value of combined analysis of KLF4 expression and the Milan criteria in hepatocellular carcinoma patients after orthotopic liver transplantation%KLF4表达联合米兰标准在肝癌肝移植受者预后分析中的价值

    Institute of Scientific and Technical Information of China (English)

    孙红成; 彭志海

    2014-01-01

    Objective To evaluate the prognostic value of combined analysis of the biomarker Krüppel-like factor 4 (KLF4) and the Milan criteria in hepatocellular carcinoma (HCC) patients treated by orthotopic liver transplantation (OLT).Method The clinicopathological data and outcome of the recruited 105 HCC patients undergoing OLT from October 2001 to April 2009 were retrospectively analyzed.KLF4 expression in HCC and paired non-tumor tissue was detected by immonohistochemistry and confirmed by Western blotting analysis.Five-year overall survival (OS) and recurrence-free survival (RFS) rate and survival curves of the grouped patients were calculated and plotted by Kaplan-Meier method.Result The level of KLF4 expression was lower in HCC than that in paired non-tumor tissue (P<0.05).KLF4 expression was significantly lower in poorly differentiated HCC than that in well-moderately differentiated HCC (P =0.008).Loss of KLF4 was an independent risk factor for predicting tumor recurrence and survival of HCC after OLT (HR =0.459 and 5.42,respectively,P<0.001).The level of KLF4 expression could not differentiate the OS and RFS rate in the patients with tumors meeting the Milan criteria,whereas the OS and RFS rate in the patients with tumors exceeding the Milan criteria differentiated according to KLF4 expression.The patients with tumors beyond the Milan criteria and exhibiting moderate to high KLF4 expression had unexpectedly favorable 5-year OS (91.7%) and RFS (70.5%) rate.Conclusion KLF4 is a useful biomarker for prognostication of HCC patients undergoing OLT.Integrated use of KLF4 biomarker and the Milan criteria improves accurate prediction of survival and tumor recurrence for HCC patients after OLT.%目的 探讨转录因子Krüppel样因子4(KLF4)作为分子标志物联合米兰标准预测肝癌患者肝移植预后的价值.方法 回顾性分析2001年至2009年间接受肝移植的105例肝细胞肝癌患者的病例资料,应用免疫组织化学、蛋白质印

  6. [A new case of hepatic adenomatosis treated with orthotopic liver transplantation].

    Science.gov (United States)

    Yunta, P J; Moya, A; San-Juan, F; López-Andújar, R; De Juan, M; Orbis, F; Mir, J

    2001-09-01

    Hepatic adenomatosis is a rare disease with multiple hepatic adenomas (10 or more), not associated with an history of oral contraceptive use or anabolic steroids use or with glycogen storage disease. A new case is reported in a 23 year-old woman who consulted for an abdominal mass and who had more than 50 adenomas of the liver. The suspicion of malignant transformation by the elevation of the alpha-foetoprotein, and the diffuse affectation of the liver, with minimum free parenchyma, suggested to carry out an orthotopic liver transplantation. The definitive histological examination of the surgical specimen confirmed the existence of local areas of hepatocellular carcinoma.

  7. 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.

  8. 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.

  9. 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

  10. 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.

  11. 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

  12. Hepatocellular calcification

    DEFF Research Database (Denmark)

    Ladefoged, Claus; Frifelt, J J

    1987-01-01

    Autopsy of a twenty year old girl dying from complications of renal and cardiac failure demonstrated severe hepatocellular calcification, a rare finding. The pathogenesis is thought to be a combination of dystrophic calcification caused by severe centrilobular necrosis and metastatic calcification...

  13. Ethyl pyruvate inhibits proliferation and induces apoptosis of hepatocellular carcinoma via regulation of the HMGB1–RAGE and AKT pathways

    Energy Technology Data Exchange (ETDEWEB)

    Cheng, Ping; Dai, Weiqi; Wang, Fan; Lu, Jie; Shen, Miao; Chen, Kan; Li, Jingjing; Zhang, Yan; Wang, Chengfen; Yang, Jing; Zhu, Rong; Zhang, Huawei; Zheng, Yuanyuan; Guo, Chuan-Yong, E-mail: guochuanyong@hotmail.com; Xu, Ling, E-mail: xuling606@sina.com

    2014-01-24

    Highlights: • Ethyl pyruvate inhibits liver cancer. • Promotes apoptosis. • Decreased the expression of HMGB1, p-Akt. - Abstract: Ethyl pyruvate (EP) was recently identified as a stable lipophilic derivative of pyruvic acid with significant antineoplastic activities. The high mobility group box-B1 (HMGB1)–receptor for advanced glycation end-products (RAGE) and the protein kinase B (Akt) pathways play a crucial role in tumorigenesis and development of many malignant tumors. We tried to observe the effects of ethyl pyruvate on liver cancer growth and explored its effects in hepatocellular carcinoma model. In this study, three hepatocellular carcinoma cell lines were treated with ethyl pyruvate. An MTT colorimetric assay was used to assess the effects of EP on cell proliferation. Flow cytometry and TUNEL assays were used to analyze apoptosis. Real-time PCR, Western blotting and immunofluorescence demonstrated ethyl pyruvate reduced the HMGB1–RAGE and AKT pathways. The results of hepatoma orthotopic tumor model verified the antitumor effects of ethyl pyruvate in vivo. EP could induce apoptosis and slow the growth of liver cancer. Moreover, EP decreased the expression of HMGB1, RAGE, p-AKT and matrix metallopeptidase-9 (MMP9) and increased the Bax/Bcl-2 ratio. In conclusion, this study demonstrates that ethyl pyruvate induces apoptosis and cell-cycle arrest in G phase in hepatocellular carcinoma cells, plays a critical role in the treatment of cancer.

  14. Endoscopic Treatment of Studer's Orthotopic Neobladder Lithiasis

    Science.gov (United States)

    Gil-Sousa, Diogo; Oliveira-Reis, Daniel; Cavadas, Vitor; Oliveira, Manuel; Soares, José; Fraga, Avelino

    2015-01-01

    Studer's neobladder lithiasis is a rare but important long term complication of this orthotopic bladder substitute technique. We report a case of a 45 year-old male patient, submitted to a radical cystoprostatectomy with a Studer's orthotopic neobladder 4 years before, presenting bad compliance to recommended urinary habits, increased production of mucus and high post voiding residue. CT scan and urethrocystography showed a distended pouch with 2 major sacculations with narrow communication and a stone in each sacculation. A minimally invasive endoscopic technique was successfully used in the treatment of the 2 small calculus. PMID:26793507

  15. Endoscopic Treatment of Studer's Orthotopic Neobladder Lithiasis

    Directory of Open Access Journals (Sweden)

    Diogo Gil-Sousa

    2015-05-01

    Full Text Available Studer's neobladder lithiasis is a rare but important long term complication of this orthotopic bladder substitute technique. We report a case of a 45 year-old male patient, submitted to a radical cystoprostatectomy with a Studer's orthotopic neobladder 4 years before, presenting bad compliance to recommended urinary habits, increased production of mucus and high post voiding residue. CT scan and urethrocystography showed a distended pouch with 2 major sacculations with narrow communication and a stone in each sacculation. A minimally invasive endoscopic technique was successfully used in the treatment of the 2 small calculus.

  16. 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.

  17. 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.

  18. 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

  19. 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).

  20. 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.

  1. 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.

  2. 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

  3. 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

  4. 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.

  5. 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.

  6. Establishment of a mdrl Multidrug Resistant Model of Orthotopic Transplantation of Liver Carcinoma on Nude Mice

    Institute of Scientific and Technical Information of China (English)

    HANYu; CHENXiaoping

    2005-01-01

    Objective: To develop a new method of inducing mdrl multidrug resistance by establishing a nude mice model of orthotopic transplantation of liver carcinoma by sporadic abdominal chemotherapy at intervals. Methods: Hepatocellular carcinoma HepG2 cell was cultured and injected subcutaneously to form the tumor-supplying mice. The tumor bits from the tumor-supplying mice were implanted under the envelope of the mice liver and induced by abdominal chemotherapy with Pharmorubicin. Physical examination, ultrasonography, spiral CT and operative inspection were used to examine tumor progression. RT-PCR and immunohistochemistry were adopted to detect the expression of mdrl-mRNA and its encoded protein P-gp protein (P-gp). Results: There was no operative dead, the rate of implanting tumor successfully was 88% (22/25), the rate of implanting secondly successfully was 100% (3/3), and the rate of inducing successfully was 80% (16/20). The expression of mdrl-mRNA and the P-gp in the inducing group was 23 folds and 13 folds in the control group respectively. Conclusion: We have established an in vivo model of mdr using nude mice transplanted with orthotopic liver neoplasm coupled to chemotherapy.

  7. 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

  8. Orthotopic nonauxiliary allotransplantation of part of the liver in dogs

    NARCIS (Netherlands)

    N.M.A. Bax (Klaas)

    1984-01-01

    textabstractAt present, end-stage hepatic disease can only be cured by orthotopic liver transplantation. As a pediatric surgeon the writer of this thesis was interested in the problems that hamper the development of pediatric orthotopic liver transplantation and particularly in the problem of the sh

  9. SIRT1 facilitates hepatocellular carcinoma metastasis by promoting PGC-1α-mediated mitochondrial biogenesis.

    Science.gov (United States)

    Li, Yuming; Xu, Shangcheng; Li, Jing; Zheng, Lu; Feng, Min; Wang, Xiaoya; Han, Keqiang; Pi, Huifeng; Li, Min; Huang, Xiaobing; You, Nan; Tian, Yewang; Zuo, Guohua; Li, Hongyan; Zhao, Hongzhi; Deng, Ping; Yu, Zhengping; Zhou, Zhou; Liang, Ping

    2016-05-17

    SIRT1 is a multifaceted NAD+-dependent protein deacetylase known to act as a tumor promoter or suppressor in different cancers. Here, we describe a novel mechanism of SIRT1-induced hepatocellular carcinoma (HCC) metastasis. SIRT1 overexpression was frequently detected in human HCC specimens and was associated with microvascular invasion (P = 0.0039), advanced tumor node metastasis (TNM) stages (P = 0.0016), HCC recurrence (P = 0.021) and poor outcomes (P = 0.039). Lentivirus-mediated knockdown of SIRT1 in MHCC97H cells reduced invasion and metastasis in vitro and in vivo. SIRT1 depletion attenuated mitochondrial biogenesis and adenosine triphosphate (ATP) production but did not affect epithelial-mesenchymal transition. Elevated SIRT1 expression strongly correlated with the upregulation of PGC-1α in HCC specimens, and ectopic expression of SIRT1 increased PGC-1α levels. In cell assays and an orthotopic transplantation model, PGC-1α overexpression reversed the inhibitory effects of SIRT1 depletion on invasion and metastasis by enhancing mitochondrial biogenesis. These findings reveal the involvement of SIRT1 in HCC metastasis and provide a rationale for exploring therapeutic targets against the SIRT1/PGC-1α axis.

  10. 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.

  11. Cryopreservation and orthotopic transplantation of rat ovaries.

    Science.gov (United States)

    Dorsch, Martina; Wedekind, Dirk

    2010-01-01

    The number of rat strains increased considerably in the last decade and will increase continuously during the next years. This requires enough space for maintaining vital strains and techniques for cryobanking, which can be applied not only in specialised rat resource centres but also in regular animal houses. Here we describe an easy and fast method for the cryopreservation and transplantation of frozen-thawed ovaries of the rat. With dimethyl sulfoxide as cryoprotectant rat ovaries can be stored at -196 degrees C for unlimited time. For revitalisation thawed ovaries have to be orthotopically transplanted into appropriate ovarectomised recipients. Reestablishment of the reproductive cycle in the recipients can be confirmed by vaginal cytology shortly after transplantation. The recipients are able to produce 2-3 litters after mating with males of an appropriate strain. Cyropreservation of ovaries thus can be considered a reliable method to preserve scientifically and economically important stocks and strains of rats that are currently not required.

  12. Orthotopic Liver Transplantation for Alcoholic Cirrhosis

    Science.gov (United States)

    Starzl, Thomas E.; Van Thiel, David; Tzakis, Andreas G.; Iwatsuki, Shunzaburo; Todo, Satoru; Marsh, J. Wallis; Koneru, Babu; Staschak, Sandee; Stieber, Andrei; Gordon, Robert D.

    2010-01-01

    Fifteen patients with Laennec's cirrhosis underwent orthotopic liver transplantation between 1963 and the end of 1979. The first eight patients died perioperatively or within two months, but four of the next seven patients had long survival; three are still alive after 11 to 14 years. After the introduction of cyclosporine therapy, 41 more patients with alcoholic cirrhosis were treated with liver transplantation from 1980 to June 1987. The one-year survival is 73.2%, and, after one to three years, 28 (68%) of the recipients are living. Of the 35 patients in the combined old and new series who lived for six months or longer, only two returned to alcohol abuse. Social and vocational rehabilitation has been the rule in these recipients who were selected primarily because of urgency of need, because they or their families insisted on treatment, and because they and their families thereby committed themselves to long-standing programs of alcoholism care. PMID:3050180

  13. 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.

  14. [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

  15. 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.

  16. Portal venous perfusion steal causing graft dysfunction after orthotopic liver transplantation: serial imaging findings in a successfully treated patient

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Min Su; Chung, Yong Eun; Choi, Jin Young; Park, Mi Suk; Lim, Joon Seok; Kim, Myeong Jin; Kim, Hon Soul [Dept. of Radiology, Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of); Kim, Sang Kyun [Dept. of Pathology, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2016-01-15

    A 53-year-old male with hepatocellular carcinoma underwent orthotopic liver transplantation. Preoperative computed tomography revealed main portal vein luminal narrowing by flat thrombi and the development of cavernous transformation. On post-transplantation day 1, thrombotic portal venous occlusion occurred, and emergency thrombectomy was performed. Subsequent Doppler ultrasonography and contrast-enhanced ultrasonography confirmed the restoration of normal portal venous flow. The next day, however, decreased portal venous velocity was observed via Doppler ultrasonography, and serum liver enzymes and bilirubin levels remained persistently elevated. Direct portography identified massive perfusion steal through prominent splenorenal collateral veins. Stent insertion and balloon angioplasty of the portal vein were performed, and subsequent Doppler ultrasonography demonstrated normalized portal flow parameters. Afterwards, the serum liver enzymes and bilirubin levels rapidly normalized.

  17. 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.

  18. 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.

  19. Successful Orthotopic Heart Transplantation and Immunosuppressive Management in 2 Human Immunodeficiency Virus-Seropositive Patients.

    Science.gov (United States)

    Conte, Antonio Hernandez; Kittleson, Michelle M; Dilibero, Deanna; Hardy, W David; Kobashigawa, Jon A; Esmailian, Fardad

    2016-02-01

    Few orthotopic heart transplantations have been performed in patients infected with the human immunodeficiency virus since the first such case was reported in 2001. Since that time, advances in highly active antiretroviral therapy have resulted in potent and durable suppression of the causative human immunodeficiency virus-accompanied by robust immune reconstitution, reversal of previous immunodeficiency, a marked decrease in opportunistic and other infections, and near-normal long-term survival. Although human immunodeficiency virus infection is not an absolute contraindication, few centers in the United States and Canada have performed heart transplantations in this patient population; these patients have been de facto excluded from this procedure in North America. Re-evaluation of the reasons for excluding these patients from cardiac transplantation is warranted in light of such significant advances in antiretroviral therapy. This case report documents successful orthotopic heart transplantation in 2 patients infected with human immunodeficiency virus, and we describe their antiretroviral therapy and immunosuppressive management challenges. Both patients were doing well without sequelae 43 and 38 months after transplantation.

  20. 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 ...

  1. Evaluation of IGL-1 preservation solution using an orthotopic liver transplantation model

    Institute of Scientific and Technical Information of China (English)

    Hassen Ben Abdennebi; Ziad Elrassi; Jean-Yves Scoazec; Jean-Paul Steghens; Silvina Ramella-Virieux; Olivier Boillot

    2006-01-01

    AIM: To compare, in a pig liver transplantation model,the protective effect of UW with that of IGL-1, a highsodium preservation solution containing polyethylene glycol (PEG) as an oncotic supply.METHODS: All livers were harvested and grafted orthotopically according to standard techniques. The livers were washed out and preserved for 7 h in IGL-1 (n = 6) or in UW solution (n = 7) at 4℃. In a sham group (n = 4), the livers underwent a 60-min warm ischemia at 37℃. The hepatocellular injury was assessed in organ preservation solution washed out from the graft at the end of ischemic storage (before revascularization), and in serum 2 h after reperfusion and daily for up to 6 d.RESULTS: Livers preserved in IGL-1 solution released markedly less AST than that preserved in the UW solution before and after revascularization (P < 0.05).Besides, the activity of creatine kinase-BB, a marker of sinusoidal lining cells injury, was higher in the UW group than in the IGL-1 group (P < 0.05). Histological results showed less necrotic regions in livers preserved in IGL-1 solution; however, no difference was observed for inflammation.CONCLUSION: IGL-1 liquid effectively protects parenchymal and non-parenchymal cells against preservation-reperfusion injuries.

  2. 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

  3. 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

  4. 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.

  5. Sequential and simultaneous revascularization in adult orthotopic piggyback liver transplantation

    NARCIS (Netherlands)

    Polak, WG; Miyamoto, S; Nemes, BA; Peeters, PMJG; de Jong, KP; Porte, RJ; Slooff, MJH

    2005-01-01

    The aim of the study was to assess whether there is a difference in outcome after sequential or simultaneous revascularization during orthotopic liver transplantation (OLT) in terms of patient and graft survival, mortality, morbidity, and liver function. The study population consisted of 102 adult p

  6. INFERIOR VENA-CAVA OBSTRUCTION AFTER ORTHOTOPIC LIVER-TRANSPLANTATION

    NARCIS (Netherlands)

    BROUWERS, MAM; DEJONG, KP; PEETERS, PMJG; BIJLEVELD, CMA; KLOMPMAKER, IJ; SLOOFF, MJH

    1994-01-01

    Post-operative inferior vena cava (IVC) obstruction is reported as an uncommon complication after orthotopic liver transplantation (OLT). We report 6 cases after 245 OLT's in the period between March '79 and December '92. Compression or torsion of the IVC or a technical problem were underlying cause

  7. Conversion to sirolimus immunosuppression in liver transplantation recipients with hepatocellular carcinoma: Report of an initial experience

    Institute of Scientific and Technical Information of China (English)

    Jian Zhou; Yi-Feng He; Yu-Qi Wang; Zhao-You Tang; Jia Fan; Zheng Wang; Zhi-Quan Wu; Shuang-Jian Qiu; Xiao-Wu Huang; Yao Yu; Jian Sun; Yong-Sheng Xiao

    2006-01-01

    AIM: To report a retrospective analysis of preliminary results of 36 patients who received sirolimus (SRL, Rapamune(R), rapamycin) in a consecutive cohort of 248 liver allograft recipients.METHODS: Thirty-six liver transplant patients with hepatocellular carcinoma (HCC) who were switched to SRL-based immunosuppression therapy from tacrolimus were enrolled in this study. The patients who were diagnosed as advanced HCC before orthotopic liver transplantation (OLT) were divided into group A (n = 11), those who were found to have HCC recurrence and/or metastasis after OLT were assigned to group B (n = 18), and those who developed renal insufficiency caused by calcineurin inhibitor (CNI) were assigned to group C (n = 7) after OLT.RESULTS: The patients were followed up for a median of 10.4 mo (range, 3.8-19.1 mo) after conversion to SRL therapy and 12.3 mo (range, 5.1-34.4 mo) after OLT.Three patients developed mild acute cellular rejection 2 wk after initiating SRL therapy, which was fully reversed after prednisolone pulse therapy. In group A, only 1 patient was found to have HCC recurrence and metastasis 12 mo after OLT. In group B, 66.7% (12/18) patients (2 with progressive tumor, 7 with stable tumor and 3 without tumor) were still alive due to conversing to SRL and/or resection for HCC recurrence at the end of a median follow-up of 6.8 mo post conversion and 10.7 mo posttransplant. In group C, no HCC recurrence was demonstrated in 7 patients, and renal function became normal after SRL therapy. Thrombocytopenia (n = 2), anemia (n = 8), and oral aphthous ulcers (n = 7) found in our cohort were easily manageable.CONCLUSION: The conversion to SRL-based immunosuppression may inhibit the recurrence and metastasis of HCC and improve CNI-induced renal insufficiency in OLT patients with HCC.

  8. 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

  9. 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.

  10. Gastric Metastasis of Hepatocellular Carcinoma With Gastrointestinal Bleeding After Liver Transplant: A Case Report.

    Science.gov (United States)

    Li, L; Zhang, W H; Meng, F P; Ma, X M; Shen, L J; Jin, B; Li, H W; Han, J; Zhou, G D; Liu, S H

    2015-10-01

    Gastrointestinal (GI) metastasis of hepatocellular carcinoma is very rare. This is the first report of post-transplantation gastric metastasis. A 43-year-old man with a history of hepatitis B-related hepatocellular carcinoma (HCC) in the right anterior segment of the liver received an orthotopic liver transplant. Three months after the transplantation, pulmonary metastasis was found by chest computed tomography, and he received 1 course of gamma knife treatment. He complained of melena with anemia 17 months post liver transplantation. Abdominal CT scan showed new occupying lesions in the liver and a mass in the stomach and around the spleen with embolus in the splenic vein. Endoscopy revealed a large irregular cauliflower-like mass in fundus with ulceration and bleeding on the surface. He received symptomatic treatment, but died of cancer-related bleeding 4 months later. GI bleeding may due to gastric metastasis after liver transplantation.

  11. 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

  12. Acidic pH-Triggered Drug-Eluting Nanocomposites for Magnetic Resonance Imaging-Monitored Intra-arterial Drug Delivery to Hepatocellular Carcinoma.

    Science.gov (United States)

    Park, Wooram; Chen, Jeane; Cho, Soojeong; Park, Sin-Jung; Larson, Andrew C; Na, Kun; Kim, Dong-Hyun

    2016-05-25

    Transcatheter hepatic intra-arterial (IA) injection has been considered as an effective targeted delivery technique for hepatocellular carcinoma (HCC). Recently, drug-eluting beads (DEB) were developed for transcatheter IA delivery to HCC. However, the conventional DEB has offered relatively modest survival benefits. It can be difficult to control drug loading/release from DEB and to monitor selective delivery to the targeted tumors. Embolized DEBs in hepatic arteries frequently induce hypoxic and low pH conditions, promoting cancer cell growth. In this study, an acidic pH-triggered drug-eluting nanocomposite (pH-DEN) including superparamagnetic iron oxide nanocubes and pH-responsive synthetic peptides with lipid tails [octadecylamine-p(API-l-Asp)10] was developed for magnetic resonance imaging (MRI)-monitored transcatheter delivery of sorafenib (the only FDA-approved systemic therapy for liver cancer) to HCC. The synthesized sorafenib-loaded pH-DENs exhibited distinct pH-triggered drug release behavior at acidic pH levels and highly sensitive MR contrast effects. In an orthotopic HCC rat model, successful hepatic IA delivery and distribution of sorafenib-loaded pH-DEN was confirmed with MRI. IA-delivered sorafenib-loaded pH-DENs elicited significant tumor growth inhibition in a rodent HCC model. These results indicate that the sorafenib-pH-DENs platform has the potential to be used as an advanced tool for liver-directed IA treatment of unresectable HCC.

  13. 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

  14. [Orthotopic ileal neobladder: urodynamic and metabolic aspects. Our experience].

    Science.gov (United States)

    Mangiarotti, B; Ceresoli, A; Del Nero, A; Parravicini, M; Prati, G; Currò, A; Zanetti, G P; Trinchieri, A; Pisani, E

    1996-12-01

    We subjected to a functional and metabolic evaluation (urodynamic examination + cystography) 10 patients underwent to radical cystectomy with a ileal orthotopic reservoir (VIP) for bladder cancer. At the moment patients have a minimum 3-years follow-up and they are out of disease. The medium capacity of the reservoir is about 447 ml, with a low pressure flow, a medium pressure of ureteral closing of 62.5 cm of H2O. At the cystography neither ureteral reflux nor post miction residuum have been proved. All the patients are continent, with the exception of one patient suffering from episodes of nocturnal enuresis. The metabolic evaluation hasn't proved substantial changes except the presence of hypocitraturia in the only patient in metabolic acidosis. In conclusion the ileal orthotopic reservoir showed a good long-term functionality without considerable complication of metabolism.

  15. Pre-clinical Orthotopic Murine Model of Human Prostate Cancer.

    Science.gov (United States)

    Shahryari, Varahram; Nip, Hannah; Saini, Sharanjot; Dar, Altaf A; Yamamura, Soichiro; Mitsui, Yozo; Colden, Melissa; Bucay, Nathan; Tabatabai, Laura Z; Greene, Kirsten; Deng, Guoren; Tanaka, Yuichiro; Dahiya, Rajvir; Majid, Shahana

    2016-08-29

    To study the multifaceted biology of prostate cancer, pre-clinical in vivo models offer a range of options to uncover critical biological information about this disease. The human orthotopic prostate cancer xenograft mouse model provides a useful alternative approach for understanding the specific interactions between genetically and molecularly altered tumor cells, their organ microenvironment, and for evaluation of efficacy of therapeutic regimens. This is a well characterized model designed to study the molecular events of primary tumor development and it recapitulates the early events in the metastatic cascade prior to embolism and entry of tumor cells into the circulation. Thus it allows elucidation of molecular mechanisms underlying the initial phase of metastatic disease. In addition, this model can annotate drug targets of clinical relevance and is a valuable tool to study prostate cancer progression. In this manuscript we describe a detailed procedure to establish a human orthotopic prostate cancer xenograft mouse model.

  16. 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.

  17. Progressive pulmonary calcification in a child after orthotopic liver transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Weaver, Olena O.; Stazzone, Madelyn M.; Bhalla, Sanjeev [Washington University School of Medicine, Department of Radiology, 660 S. Euclid Ave., Campus Box 8131, St. Louis, MO (United States)

    2006-06-15

    We present a case of progressive pulmonary calcification associated with prolonged respiratory insufficiency in a 2-year-old boy with a history of orthotopic liver transplantation. This case demonstrates the potentially progressive nature of pulmonary calcification and that it can present with respiratory insufficiency at a later period after transplantation than previously thought. We describe radiological findings and discuss established as well as plausible pathological mechanisms contributing to the development of calcifications in these patients. (orig.)

  18. Gut perforation after orthotopic liver transplantation in adults

    Institute of Scientific and Technical Information of China (English)

    Jun Xiong; Shen You; Xiao-Shun He

    2007-01-01

    AIM: To describe cases of gut perforation after orthotopic liver transplantation.METHODS: Data were colleted from our center database and medical records. Six of 187 patients (3.2%)who underwent orthotopic liver transplantation from January to December 2005 developed gut perforation.All patients were male with an average age of 46 years.Modified piggyback liver transplantation was performed at the Organ Transplantation Center, First Affiliated Hospital, Sun Yat-Sen University.RESULTS: Previous operation, steroid therapy, and prolonged portal venous cross clamp time, poor nutritional status and iatrogenic injury were found to be its ecological factors. The patients with gut perforation were found to have fever, increased leukocytes, mild abdominal pain and tenderness. The median portal venous clamp time was 63 min (range 45-72 min),median cold ischaemia time was 11.3 h (range 7-15 h).Median intraoperative blood loss was 500 mL (range 100-1200 mL) and median operation time was 8.8 h (range 6-12 h). None of the six patients developed acute cellular rejection. White cell count was above 18 × 109/L in five patients (neutrophilic leukocytes were above 90%) and 1.5 × 109/L in one patient. Bacterial culture in drainage liquid revealed enterococci in five patients. Of the 6 patients undergoing orthotopic liver transplantation, 3 survived and 3 died after modified piggyback liver transplantation.CONCLUSION: Gut perforation occurs after orthotopic liver transplantation in adults. A careful and minimal dissection during OLT, longer retention of the stomach tube, and reducing the portal clamp time and steroid dose should be taken into consideration. If gut perforation is not prevented, then early diagnosis,preferably through detection of enterococci may ensure better survival.

  19. Cystectomy with orthotopic reconstruction following radical retropubic prostatectomy

    Directory of Open Access Journals (Sweden)

    Ari Miotto Jr

    2004-04-01

    Full Text Available The development of infiltrative bladder carcinoma in patients previously treated with radical prostatectomy due to prostate adenocarcinoma represents a challenging perspective. Radical cystectomy remains the best option for invasive bladder cancer, however, there are few reports about the best approach to such individuals. Nevertheless, despite possible technical difficulties found during surgery, the orthotopic urinary shunt is a reasonable option in selected cases.

  20. Experimental modified orthotopic piggy-back liver autotransplantation

    Energy Technology Data Exchange (ETDEWEB)

    Roveda, L. [Oncologic Surgery, Cancer Center of Excellence Fond. ' T.Campanella' , Europa Avenue, Catanzaro CZ-88100 (Italy)], E-mail: roveda.l@libero.it; Zonta, A. [Department of Surgery, University of Pavia, PV 27100 (Italy); Staffieri, F. [Veterinary Surgery Unit, Department of Emergencies and Organs Transplantation, Faculty of Veterinary Medicine, SP per Casamassima km 3, Valenzano, BA 70010 (Italy); Timurian, D.; DiVenere, B. [Surgery ' Madonna delle Grazie' Hospital, Contrada Cattedra Ambulante, Matera, MT 75100 (Italy); Bakeine, G.J. [Laboratorio Nazionale di Tecnologie Avanzate e Nanoscienza (TASC), Basovizza, TR (Italy); Crovace, A. [Veterinary Surgery Unit, Department of Emergencies and Organs Transplantation, Faculty of Veterinary Medicine, SP per Casamassima km 3, Valenzano, BA 70010 (Italy); Prati, U. [Oncologic Surgery, Cancer Center of Excellence Fond. ' T.Campanella' , Europa Avenue, Catanzaro CZ-88100 (Italy)

    2009-07-15

    The classical orthotopic liver autotransplantation is a very challenging and time wasting technique; it includes the division of major hepatic vessels and choledocus, and subsequent reconnection by end to end anastomoses. The caval end to end anastomoses are the most difficult to be performed and the interposition of a prosthesis can be required. We adopted the classical orthotopic liver autotransplantation technique in 2 patients affected with diffused liver metastases from colorectal cancer, for extracorporeal neutron capture therapy (BNCT). The procedure required very long operating times and the extracorporeal circulation (ECC) set up; furthermore the vena cava reconstruction was performed by the interposition of a goretex-prosthesis. We propose a 'modified orthotopic piggy-back technique' to simplify liver reconnection and shorten the operating time. Materials and methods: The technique was developed in the swine (25 kg body weight), under general anaesthesia. We performed the resection of the retro-hepatic vena cava with preservation of the caval flow during the anhepatic phase, by interposing a goretex-prosthesis. The reconstruction of the vena cava was then performed by a side-to-side cava-prosthesis anastomosis with lateral clamping of the prosthesis. The procedure was then completed according to the classical technique of liver transplantation. Results: The mean time for VC reconstruction was 56 ({+-}10) min. and the mean time for side-to-side VC-prosthesis anastomosis was 13 ({+-}4) min. Conclusions: The 'modified orthotopic piggy-back technique' can simplify the reimplant of the liver during autotransplantation and shorten the operating time. Furthermore also the time of total extracorporeal circulation is reduced, as during the anhepatic phase and during the side-to-side cava-prosthesis anastomosis the flow in the inferior vena cava is uninterrupted.

  1. New Natural Pigment Fraction Isolated from Saw Palmetto: Potential for Adjuvant Therapy of Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Hor-Yue Tan

    2016-08-01

    Full Text Available For the first time, we discovered a small proportion of aqueous fraction from Saw Palmetto apart from the fatty acid-rich fraction exhibited pharmacological activity. Therefore, this study aims to explore the anti-tumor potential of red pigmented aqueous fraction of Saw Palmetto, NYG on human hepatocellular carcinoma and its possible targets. Subcutaneous xenograft and orthotopic implantation models of HCC were used to evaluate the tumor inhibitory effect of NYG. Human hepatocellular carcinoma (HCC cell lines and human umbilical vein endothelial cells (HUVEC were used as in vitro model. The mRNA expression was conducted by qPCR. Protein expression was monitored by immunoblotting and immunohistochemistry. Cell migration and blood vessel formation were determined by chamber assay and tube formation assay, respectively. Significant tumor inhibition of NYG in dose-dependent manner was observed on subcutaneous xenograft and orthotopic HCC model. NYG has no direct action on cell viability or VEGF secretion of HCC cells. However, NYG reduced in vitro migration and vessel formation activities of HUVEC cells, as well as in vivo intratumoral neovascularization. NYG attenuated extracellular signal-regulated kinases (ERK activation in endothelial cells, which may be associated with the suppression of migration and tube formation of HUVEC. NYG suppressed tumor expansion of HCC via inhibiting neovascularization, and may be potential adjuvant treatment for HCC.

  2. Gastrointestinal function and metabolic control after construction of an orthotopic ileal neobladder in bladder cancer

    DEFF Research Database (Denmark)

    Thorstenson, Andreas; Jacobsson, Hans; Onelöv, Erik

    2007-01-01

    OBJECTIVE: To investigate the effects of ileum resection in orthotopic neobladder construction on gastrointestinal function and metabolic control. MATERIAL AND METHODS: We included 28 patients who underwent radical cystectomy and construction of an orthotopic neobladder or continent ileal reservoir...... were unchanged. CONCLUSIONS: Using the distal ileum for orthotopic neobladder construction causes bowel disorders in a quarter of cystectomy patients. Diarrhoea and faecal urgency are probably caused by decreased reabsorption of bile and are not due to changes in gastrointestinal hormones. A sizeable...

  3. It’s a Man’s World: Does Orthotopic Liver Transplantation in the Elderly Male Confer an Additional Risk on Survival?

    Directory of Open Access Journals (Sweden)

    Eoin Slattery

    2012-01-01

    Full Text Available BACKGROUND: Orthotopic liver transplantation (OLT in a well-selected population is a highly successful procedure, with one-year survival rates reported to be as high as 90%. Advanced age is considered to be a contraindication. Survival rates in patients >60 years of age appear to be comparable with those of younger patients. However, little objective data exist on the outcomes of patients >65 years of age undergoing OLT.

  4. 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.

  5. Nude mice multi-drug resistance model of orthotopic transplantation of liver neoplasm and Tc-99m MIBI SPECT on p-glycoprotein

    Institute of Scientific and Technical Information of China (English)

    Yu Han; Xiao-Ping Chen; Zhi-Yong Huang; Hong Zhu

    2005-01-01

    AIM: To establish a model of drug-resistant neoplasms using a nude mice model, orthotopic transplantation of liver neoplasm and sporadic abdominal chemotherapy.METHODS: Hepatocellular carcinoma cells HepG2 were cultured and injected subdermally to form the tumorsupplying mice. The orthotopic drug-resistant tumors were formed by implanting the tumor bits under the envelope of the mice liver and induced by abdominal chemotherapy with Pharmorubicin. Physical examination, ultrasonography, spiral CT and visual inspection were used to examine tumor progression. RT-PCR and immunohistochemistry wereused to detect expression of mdr1 mRNA and its encodedprotein p-glycoprotein (p-gp). Tc-99m sestamibi scintigraphy was performed by obtaining planar abdominal images at 20 min after injection, and the liver/heart ratios werecalculated.RESULTS: Post-implantation mortality was 0% (0/25),tumor implantation success was 90% (22/25), and the rate of implanting successfully for the second time was 100% (3/3). Tumor induction using Pharmorubicin was 80% (16/20). The mdr1 mRNA expression of the induced group was 23 times higher than that of the control group, and p-gp protein expression was 13-fold higher compared to the control group. The liver/heart ratio (as assessed in vivo, using Tc-99m radiography) was decreased significantly in the induced group as compared to the control group. CONCLUSION: We have established an in vivo model of mdr1 in nude mice by orthotopic transplantation of liver neoplasm coupled to chemotherapy. We propose that identification of drug resistance as characterized by decreased 99mTc-ppm radiography due to enhanced clearance by p-gp may be useful in detecting in vivo drug resistance, as well as a useful tool in designing more effective therapies.

  6. 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...

  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. Beneath the Copper-Pediatric Wilson's Disease Cirrhosis and Hepatocellular Carcinoma: A Case Report with Literature Review.

    Science.gov (United States)

    Rosencrantz, Richard A; LeCompte, Lesli; Yusuf, Yasmin

    2015-11-01

    Primary hepatic malignancies are uncommon in pediatrics. Tumors such as hepatocellular carcinoma (HCC) develop typically in the setting of chronic liver disease. The incidence of HCC in Wilson's disease-related cirrhosis is disproportionately lower than in many other forms of end-stage liver disease. A preadolescent girl presented with Wilson's disease cirrhosis and a HCC requiring orthotopic liver transplantation. This case highlights the need to consider hepatic malignancies even in young Wilson's disease patients. Pediatric Wilson's disease and the hepatic tumor literature are reviewed.

  9. Recombinant factor Vlla in orthotopic liver transplantation : influence on parameters of coagulation and fibrinolysis

    NARCIS (Netherlands)

    Meijer, K; Hendriks, HGD; de Wolf, JTM; Klompmaker, IJ; Lisman, T; Hagenaars, AAM; Slooff, MJH; Porte, RJ; van der Meer, J

    2003-01-01

    The effect of recombinant factor Vila (rFVIIa) on blood loss was evaluated in cirrhotic patients undergoing orthotopic liver transplantation. In the present study, we explored the effect of rFVIIa on coagulation and fibrinolysis during orthotopic liver transplantation. Coagulation factors, parameter

  10. 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

  11. Hepatitis C Virus and Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Masao Omata

    2013-01-01

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

  12. Large orthotopic reservoir stone burden: Role of open surgery

    Directory of Open Access Journals (Sweden)

    Madbouly Khaled

    2010-01-01

    Full Text Available Purpose: To present our experience in open poucholithotomy as a primary management of large orthotopic reservoir stone burden and discuss different management options. Materials and Methods: Records of men underwent radical cystectomy and orthotopic urinary diversion were retrospectively reviewed as regards pouch stone formation. Patients with large reservoir stone burden managed by open poucholithotomy were further selected. Results: Large reservoir stone burden was encountered in 12 post radical cystectomy men. All underwent open poucholithotomy as a primary management of their reservoir stones. Median age at cystectomy was 46 (range: 32-55 years with a median total follow up period of 214.15 (range: 147-257 months and a median interval to stone detection of 99 (range: 63-132 months. The median stone burden was 5260 (range: 3179-20410 mm 2 . All patients were continent during the day while 5 showed nocturnal enuresis; 2 of them became continent after removal of the stones. Post poucholithotomy, all patients had sterile urine cultures except one who showed occasional colonization. None of the 12 patients showed stone recurrence after poucholithotomy. Two patients underwent revision of a dessuscepted nipple valve in association with stone removal. Conclusions: Open poucholithotomy for large reservoir stone burden is a feasible and safe option. It saves the reservoir mesentery and adjacent bowel. It allows complete removal of the stone(s leaving no residual fragments. Furthermore, it permits correction of concomitant reservoir abnormalities.

  13. [Orthotopic liver transplant in rats. Surgical technique, complications and treatment].

    Science.gov (United States)

    Lausada, Natalia R; Gondolesi, G E; Ortiz, E; Dreizzen, E; Raimondi, J C

    2002-01-01

    The orthotopic rat liver transplant model is a widely used technique in transplantation research. It has many advantages over other animal transplant models because of its availability and low cost. However, it must be emphasized that success with the rat model requires thorough training. The aim of this paper is to describe the microsurgical technique involved in 60 rat liver transplants and to discuss the complications and their treatments. Forty-nine liver transplants were performed at the Experimental Laboratory of the University Hospital, Ontario, Canada (ELUH) and 11 were performed at the Laboratorio de Trasplante de Organos de la Facultad de Ciencias Médicas de La Plata, Buenos Aires. Argentina (LTO). Among the transplants performed at the ELUH, the observed complications were haemorrhage (n = 4), pneumothorax (n = 1), anastomotic failure (n = 15), bile leak (n = 3), and bile duct necrosis (n = 9). The remaining 17 rats at the ELUH were healthy at day 7 after surgery. Animal survival immediately postop, at 24 hours postop and at 7 days postop was achieved with the 9th, 20th and 21st transplants respectively. At the LTO, 3 rats died as a result of anaesthetic complications. Seven-day animal survival was achieved with the 11th transplant. We beleive that the description of the orthotopic rat liver transplantation technique, as well as the discussion regarding complications and their management, can be useful for researchers interested in performing liver transplantation in rats.

  14. 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.

  15. Severe Acute Hyperkalemia during Pre-Anhepatic Stage in Cadaveric Orthotopic Liver Transplantation

    Directory of Open Access Journals (Sweden)

    Mohammad Ali Sahmeddini

    2012-09-01

    Full Text Available A serious hazard to patients during orthotopic liver transplantation is hyperkalemia. Although the most frequent and hazardous hyperkalemia occurs immediately after reperfusion of the newly transplanted liver, morbid hyperkalemia could happen in the other phases during orthotopic liver transplantation. However, pre-anhepatic hyperkalemia during orthotopic liver transplantation is rare. This report describes one such patient, who without transfusion, developed severe hyperkalemia during pre-anhepatic phase. The variations in serum potassium concentration of the present case indicate that it is necessary to take care of the changes of serum potassium concentration not only during reperfusion but also during the other phases of the liver transplantation.

  16. 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.

  17. Metastatic Hepatocellular Carcinoma Responsive to Pembrolizumab.

    Science.gov (United States)

    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.

  18. 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).

  19. 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.

  20. 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

  1. Aprotinin and transfusion requirements in orthotopic liver transplantation : a multicentre randomised double-blind study

    NARCIS (Netherlands)

    Porte, RJ; Molenaar, IQ; Begliomini, B; Groenland, THN; Januszkiewicz, A; Lindgren, L; Palareti, G; Hermans, J; Terpstra, OT

    2000-01-01

    Background Intraoperative hyperfibrinolysis contributes to bleeding during adult orthotopic liver transplantation. We aimed to find out whether aprotinin, a potent antifibrinolytic agent, reduces blood loss and transfusion requirements. Methods We did a randomised, double-blind placebo-controlled tr

  2. Biliary complications following orthotopic liver transplantation: May contrast-enhanced MR Cholangiography provide additional information?

    Directory of Open Access Journals (Sweden)

    Piero Boraschi

    2016-01-01

    Conclusions: Contrast-enhanced T1-weighted MR Cholangiography may improve the level of diagnostic confidence provided by conventional T2-weighted MR Cholangiography in the evaluation of biliary complications after orthotopic liver transplantation.

  3. Long term complications after radical cystoprostatectomy with orthotopic diversion in male patients: Preliminary experience

    Directory of Open Access Journals (Sweden)

    A. Shelbaia

    2013-06-01

    Conclusion: Long term follow-up for patients with radical cystectomy and orthotopic diversion is associated with high complication rate. Long term follow up for those patients is needed to verify the causes of complications and how to prevent them.

  4. Cancer stem cells from human breast tumors are involved in spontaneous metastases in orthotopic mouse models

    Science.gov (United States)

    Liu, Huiping; Patel, Manishkumar R.; Prescher, Jennifer A.; Patsialou, Antonia; Qian, Dalong; Lin, Jiahui; Wen, Susanna; Chang, Ya-Fang; Bachmann, Michael H.; Shimono, Yohei; Dalerba, Piero; Adorno, Maddalena; Lobo, Neethan; Bueno, Janet; Dirbas, Frederick M.; Goswami, Sumanta; Somlo, George; Condeelis, John; Contag, Christopher H.; Gambhir, Sanjiv Sam; Clarke, Michael F.

    2010-01-01

    To examine the role of breast cancer stem cells (BCSCs) in metastasis, we generated human-in-mouse breast cancer orthotopic models using patient tumor specimens, labeled with optical reporter fusion genes. These models recapitulate human cancer features not captured with previous models, including spontaneous metastasis in particular, and provide a useful platform for studies of breast tumor initiation and progression. With noninvasive imaging approaches, as few as 10 cells of stably labeled BCSCs could be tracked in vivo, enabling studies of early tumor growth and spontaneous metastasis. These advances in BCSC imaging revealed that CD44+ cells from both primary tumors and lung metastases are highly enriched for tumor-initiating cells. Our metastatic cancer models, combined with noninvasive imaging techniques, constitute an integrated approach that could be applied to dissect the molecular mechanisms underlying the dissemination of metastatic CSCs (MCSCs) and to explore therapeutic strategies targeting MCSCs in general or to evaluate individual patient tumor cells and predict response to therapy. PMID:20921380

  5. Current update on combined hepatocellular-cholangiocarcinoma

    Directory of Open Access Journals (Sweden)

    Suresh Maximin

    2014-01-01

    Combined hepatocellular cholangiocarcinoma tends to present with an more aggressive behavior and a poorer prognosis than either hepatocellular carcinoma or cholangiocarcinoma. An accurate preoperative diagnosis and aggressive treatment planning can play crucial roles in appropriate patient management.

  6. 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...

  7. 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...

  8. Combination radiotherapy in an orthotopic mouse brain tumor model.

    Science.gov (United States)

    Kramp, Tamalee R; Camphausen, Kevin

    2012-03-06

    Glioblastoma multiforme (GBM) are the most common and aggressive adult primary brain tumors. In recent years there has been substantial progress in the understanding of the mechanics of tumor invasion, and direct intracerebral inoculation of tumor provides the opportunity of observing the invasive process in a physiologically appropriate environment. As far as human brain tumors are concerned, the orthotopic models currently available are established either by stereotaxic injection of cell suspensions or implantation of a solid piece of tumor through a complicated craniotomy procedure. In our technique we harvest cells from tissue culture to create a cell suspension used to implant directly into the brain. The duration of the surgery is approximately 30 minutes, and as the mouse needs to be in a constant surgical plane, an injectable anesthetic is used. The mouse is placed in a stereotaxic jig made by Stoetling (figure 1). After the surgical area is cleaned and prepared, an incision is made; and the bregma is located to determine the location of the craniotomy. The location of the craniotomy is 2 mm to the right and 1 mm rostral to the bregma. The depth is 3 mm from the surface of the skull, and cells are injected at a rate of 2 μl every 2 minutes. The skin is sutured with 5-0 PDS, and the mouse is allowed to wake up on a heating pad. From our experience, depending on the cell line, treatment can take place from 7-10 days after surgery. Drug delivery is dependent on the drug composition. For radiation treatment the mice are anesthetized, and put into a custom made jig. Lead covers the mouse's body and exposes only the brain of the mouse. The study of tumorigenesis and the evaluation of new therapies for GBM require accurate and reproducible brain tumor animal models. Thus we use this orthotopic brain model to study the interaction of the microenvironment of the brain and the tumor, to test the effectiveness of different therapeutic agents with and without

  9. 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.

  10. Tricuspid Valve Regurgitation after Orthotopic Heart Transplantation: Prevalence and Etiology

    Directory of Open Access Journals (Sweden)

    Yaniv Berger

    2012-01-01

    Full Text Available Background. Tricuspid valve regurgitation (TR after orthotopic heart transplantation (OHT is common. The aims of this study were to determine the prevalence of TR after OHT, to examine the correlation between its development and various variables, and to determine its outcomes. Methods. All 163 OHT patients who were followed up between 1988 and 2009 for a minimal period of 12 months were divided into those with no TR/mild TR and those with at least mild-moderate TR, as assessed by doppler echocardiography. These groups were compared regarding preoperative hemodynamic variables, surgical technique employed, number of endomyocardial biopsies, number of acute cellular rejections, incidence of graft vasculopathy, and clinical outcomes. Results. At the end of the followup (average 8.2 years significant TR was evident in 14.1% of the patients. The development of late TR was found by univariate, but not multivariate, analysis to be significantly correlated with the biatrial surgical technique ( and the presence of graft vasculopathy (. TR development was found to be correlated with the need for tricuspid valve surgery but not with an increased mortality. Conclusions. The development of TR after OHT may be related to the biatrial anastomosis technique and to graft vasculopathy.

  11. Dynamic Quantitative T1 Mapping in Orthotopic Brain Tumor Xenografts

    Directory of Open Access Journals (Sweden)

    Kelsey Herrmann

    2016-04-01

    Full Text Available Human brain tumors such as glioblastomas are typically detected using conventional, nonquantitative magnetic resonance imaging (MRI techniques, such as T2-weighted and contrast enhanced T1-weighted MRI. In this manuscript, we tested whether dynamic quantitative T1 mapping by MRI can localize orthotopic glioma tumors in an objective manner. Quantitative T1 mapping was performed by MRI over multiple time points using the conventional contrast agent Optimark. We compared signal differences to determine the gadolinium concentration in tissues over time. The T1 parametric maps made it easy to identify the regions of contrast enhancement and thus tumor location. Doubling the typical human dose of contrast agent resulted in a clearer demarcation of these tumors. Therefore, T1 mapping of brain tumors is gadolinium dose dependent and improves detection of tumors by MRI. The use of T1 maps provides a quantitative means to evaluate tumor detection by gadolinium-based contrast agents over time. This dynamic quantitative T1 mapping technique will also enable future quantitative evaluation of various targeted MRI contrast agents.

  12. Monitoring of Acute Rejection after Orthotopic Heart Tranplantation

    Institute of Scientific and Technical Information of China (English)

    Meng chun ying; Huang ke li; Luo bin; Wen ding guo

    2006-01-01

    Objectives To study the monitoring of rejection after orthotopic heart thansplantation.Methods From 1998 to 2005, 10 othotopic heart thansplans were performed, and acute rejection was monitored by endomyocardial biopsy as well as by clinical features, ECG, ultrasonocardiography and blood serum determination of Tropin I, and by the combination of these methods, we analysed the monitoring of acute rejection after the heart transplantation. Results With the combination of clinical features, ECG, ultrasonocardiography and blood serum test, 5 occurences of acute rejection were judged in the postoperative course, which were comfirmed by endomyocardial biopsy to be 2 acute rejections in Ⅰ b degree, 3 acute rejections in Ⅲ a degree. Endomyocardial biopsy were routinely performed 21 times postoperatively in which there were 1 acute rejection in Ⅰ a degree and 5 acute rejections in Ⅰ b degree. Conclusions Acute rejection is an important factor influencing the postoperative course of heart transplantation, so it is imperative to have an intime, effective and planned monitoring procedure for acute rejection. Endomyocardial biopsy is a sensitive and reliable method in diagnosis of acute rejection, but it is invasive and probable for some complications. The noninvasive method such as clinical features, ECG,ultrasonocardiography and blood serum test can be used as additive means in the diagnosis of acute rejection.Endomyocardial biopsy should be combined with some noninvasive methods in monitoring acute rejection after the heart transplantation.

  13. Inorganic Nanovehicle Targets Tumor in an Orthotopic Breast Cancer Model

    Science.gov (United States)

    Choi, Goeun; Kwon, Oh-Joon; Oh, Yeonji; Yun, Chae-Ok; Choy, Jin-Ho

    2014-03-01

    The clinical efficacy of conventional chemotherapeutic agent, methotrexate (MTX), can be limited by its very short plasma half-life, the drug resistance, and the high dosage required for cancer cell suppression. In this study, a new drug delivery system is proposed to overcome such limitations. To realize such a system, MTX was intercalated into layered double hydroxides (LDHs), inorganic drug delivery vehicle, through a co-precipitation route to produce a MTX-LDH nanohybrid with an average particle size of approximately 130 nm. Biodistribution studies in mice bearing orthotopic human breast tumors revealed that the tumor-to-liver ratio of MTX in the MTX-LDH-treated-group was 6-fold higher than that of MTX-treated-one after drug treatment for 2 hr. Moreover, MTX-LDH exhibited superior targeting effect resulting in high antitumor efficacy inducing a 74.3% reduction in tumor volume compared to MTX alone, and as a consequence, significant survival benefits. Annexin-V and propidium iodine dual staining and TUNEL analysis showed that MTX-LDH induced a greater degree of apoptosis than free MTX. Taken together, our data demonstrate that a new MTX-LDH nanohybrid exhibits a superior efficacy profile and improved distribution compared to MTX alone and has the potential to enhance therapeutic efficacy via inhibition of tumor proliferation and induction of apoptosis.

  14. Cerebrovascular complications after orthotopic liver transplantation: a clinicopathologic study.

    Science.gov (United States)

    Estol, C J; Pessin, M S; Martinez, A J

    1991-06-01

    We analyzed 55 autopsy cases in 1,357 patients undergoing orthotopic liver transplantation at the University of Pittsburgh and found that 13 (23.6%) patients had intracranial bleeding, and five (9%) had infarcts. Eight patients had bleeding localized to one intracranial compartment: intracerebral hemorrhage (three patients); subarachnoid hemorrhage (three patients); and subdural hematoma (two patients). Five patients had combinations of multiple sites of bleeding: three with subarachnoid hemorrhage-intracerebral hemorrhage, one with subarachnoid hemorrhage-intracerebral hemorrhage-subdural hematoma, and one with subdural hematoma-intracerebral hemorrhage. Coexistent CNS infections (fungal or bacterial) were associated with hemorrhagic infarcts and intracerebral hemorrhage in four patients. Cerebral embolism and hemorrhagic infarction from bacterial endocarditis occurred in one patient. Five patients died of intracranial bleeding. Severe coagulopathy was the major cause of intracranial bleeding and was associated with systemic bleeding in 12 patients. Significant systemic or metabolic complications were present in all patients and masked the focal signs of the intracranial process in more than one half.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  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. Synergistically killing activity of aspirin and histone deacetylase inhibitor valproic acid (VPA) on hepatocellular cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Li, Xiaofei; Zhu, Yanshuang [Department of Infectious Diseases, Yiwu Central Hospita, 519 Nan men Street, Yiwu, Jinhua, Zhejing 322000 (China); He, Huabin [Department of Orthopedics, Yiwu Central Hospita, 519 Nan men Street, Yiwu, Jinhua, Zhejing 322000 (China); Lou, Lianqing; Ye, Weiwei; Chen, Yongxin [Department of Infectious Diseases, Yiwu Central Hospita, 519 Nan men Street, Yiwu, Jinhua, Zhejing 322000 (China); Wang, Jinghe, E-mail: Xiaofeili2000@163.com [Department of Infectious Diseases, Yiwu Central Hospita, 519 Nan men Street, Yiwu, Jinhua, Zhejing 322000 (China)

    2013-06-28

    Highlights: •Novel combination therapy using aspirin and valproic acid (VPA). •Combination of aspirin and VPA elicits synergistic cytotoxic effects. •Combination of aspirin and VPA significantly reduces the drug dosage required alone. •Combination of aspirin and VPA significantly inhibit tumor growth. •Lower dose of aspirin in combination therapy will minimize side effects of aspirin. -- Abstract: Aspirin and valproic acid (VPA) have been extensively studied for inducing various malignancies growth inhibition respectively, despite their severe side effects. Here, we developed a novel combination by aspirin and VPA on hepatocellular cancer cells (HCCs). The viability of HCC lines were analyzed by MTT assay, apoptotic analysis of HepG2 and SMMC-7721 cell was performed. Real time-PCR and Western blotting were performed to determine the expression of apoptosis related genes and proteins such as Survivin, Bcl-2/Bax, Cyclin D1 and p15. Moreover, orthotopic xenograft tumors were challenged in nude mice to establish murine model, and then therapeutic effect was analyzed after drug combination therapy. The viability of HCC lines’ significantly decreased after drug combination treatment, and cancer cell apoptosis in combination group increasingly induced compared with single drug use. Therapeutic effect was significantly enhanced by combination therapy in tumor volume and tumor weight decrease. From the data shown here, aspirin and VPA combination have a synergistic killing effect on hepatocellular cancers cells proliferation and apoptosis.

  2. Orthotopic neobladder reconstrution: postoperative CT appearance, complications and potential pitfalls

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Su Lim; Jung, Seung Eun; Im, Yeon Soo; Lee, Jae Mun; Lee, Ji Youl; Yoon, Moon Soo; Hahn, Seong Tai [The Catholic University of Korea College of Medicine, Seoul (Korea, Republic of)

    2003-08-01

    To evaluate the postoperative CT appearance, complications and potential pitfalls of radical cystectomy with orthotopic neobladder reconstruction. We examined 46 patients [43 men and 3 women aged 34-72 (mean, 56.7) years] who had undergone neobladder reconstruction (ileocolic neobladder in 25 patients and ileal-W neobladder in 21). The CT scans were assessed in terms of their depiction of normal anatomy, namely the shape, location and internal architecture of the neobladder, the location of bladder bases, and the ureteral course. Early and late complications were also assessed. The characteristics of ileocolic neobadder were a right-side location, a lobulated outer margin, interal projections due to haustra or plication, a base in the retropubis, and right-side insertion of both ureters. In contrast, the characteristics of an ileal-W neobladder were a central location, an ovoid shape, nodular thickening at the ureteral insertion site, internal projections due to plication, and a retropubic bladder base. Early complications included hematoma with abscess formation (n=2), and postoperative peritonitis (n=1), while late complications were hydronephrosis due to stricture ar the ureteral anastomotic site (n=16), tumor recurrence at this site (n=1), distal ureteral stone (n=1), mucus urinary retention (n=1), incisional hernia (n=2), tumor recurrence in the pelvic side wall (n=1), carcinomatosis peritonei (n=1), and liver metastasis (n=2). A knowledge of normal anatomic changes is essential for the accurate interpretation of CT scans. CT is a useful modality of the evaluation of postoperative change and the complications occurring in patients who have undergone radial cystectomy with othotopic neobladder reconstruction.

  3. 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.

  4. ASP5878, a Novel Inhibitor of FGFR1, 2, 3, and 4, Inhibits the Growth of FGF19-Expressing Hepatocellular Carcinoma.

    Science.gov (United States)

    Futami, Takashi; Okada, Hidetsugu; Kihara, Rumi; Kawase, Tatsuya; Nakayama, Ayako; Suzuki, Tomoyuki; Kameda, Minoru; Shindoh, Nobuaki; Terasaka, Tadashi; Hirano, Masaaki; Kuromitsu, Sadao

    2017-01-01

    Hepatocellular carcinoma is an aggressive cancer with poor prognosis. Fibroblast growth factor 19, a member of the fibroblast growth factor family, is a ligand for fibroblast growth factor receptor 4. Moreover, it plays a crucial role in the progression of hepatocellular carcinoma. ASP5878 is a novel inhibitor of fibroblast growth factor receptors 1, 2, 3, and 4 that is under development. It inhibits fibroblast growth factor receptor 4 kinase activity with an IC50 of 3.5 nmol/L. ASP5878 potently suppressed the growth of the fibroblast growth factor 19-expressing hepatocellular carcinoma cell lines Hep3B2.1-7, HuH-7, and JHH-7. In the Hep3B2.1-7 cell line, ASP5878 inhibited the phosphorylation of fibroblast growth factor receptor 4 and its downstream signaling molecules as well as induced apoptosis. Oral administration of ASP5878 at 3 mg/kg induced sustained tumor regression in a subcutaneous xenograft mouse model using Hep3B2.1-7. In HuH-7, an orthotopic xenograft mouse model, ASP5878 induced complete tumor regression and dramatically extended the survival of the mice. These results suggest that ASP5878 is a potentially effective therapeutic agent for hepatocellular carcinoma patients with tumors expressing fibroblast growth factor 19. Mol Cancer Ther; 16(1); 68-75. ©2016 AACR.

  5. 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

  6. Glioblastoma Eradication Following Immune Checkpoint Blockade in an Orthotopic, Immunocompetent Model.

    Science.gov (United States)

    Reardon, David A; Gokhale, Prafulla C; Klein, Sarah R; Ligon, Keith L; Rodig, Scott J; Ramkissoon, Shakti H; Jones, Kristen L; Conway, Amy Saur; Liao, Xiaoyun; Zhou, Jun; Wen, Patrick Y; Van Den Abbeele, Annick D; Hodi, F Stephen; Qin, Lei; Kohl, Nancy E; Sharpe, Arlene H; Dranoff, Glenn; Freeman, Gordon J

    2016-02-01

    Inhibition of immune checkpoints, including cytotoxic T-lymphocyte antigen-4 (CTLA-4), programmed death-1 (PD-1), and its ligand PD-L1, has demonstrated exciting and durable remissions across a spectrum of malignancies. Combinatorial regimens blocking complementary immune checkpoints further enhance the therapeutic benefit. The activity of these agents for patients with glioblastoma, a generally lethal primary brain tumor associated with significant systemic and microenvironmental immunosuppression, is not known. We therefore systematically evaluated the antitumor efficacy of murine antibodies targeting a broad panel of immune checkpoint molecules, including CTLA-4, PD-1, PD-L1, and PD-L2 when administered as single-agent therapy and in combinatorial regimens against an orthotopic, immunocompetent murine glioblastoma model. In these experiments, we observed long-term tumor-free survival following single-agent anti-PD-1, anti-PD-L1, or anti-CTLA-4 therapy in 50%, 20%, and 15% of treated animals, respectively. Combination therapy of anti-CTLA-4 plus anti-PD-1 cured 75% of the animals, even against advanced, later-stage tumors. In long-term survivors, tumor growth was not seen upon intracranial tumor rechallenge, suggesting that tumor-specific immune memory responses were generated. Inhibitory immune checkpoint blockade quantitatively increased activated CD8(+) and natural killer cells and decreased suppressive immune cells in the tumor microenvironment and draining cervical lymph nodes. Our results support prioritizing the clinical evaluation of PD-1, PD-L1, and CTLA-4 single-agent targeted therapy as well as combination therapy of CTLA-4 plus PD-1 blockade for patients with glioblastoma.

  7. 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

  8. Establishment of Orthotopic Xuanwei Lung Cancer SCID Mouse Model 
and Analysis of Biological Properties

    Directory of Open Access Journals (Sweden)

    Yongchun ZHOU

    2012-08-01

    Full Text Available Background and objective The incidence of Xuanwei lung cancer ranks first in China, and its pathogenesis requires in-depth investigation. This study aims to establish an orthotopic Xuanwei lung cancer severe combined immunodeficiency (SCID mouse model and to provide a basic experimental platform for further study. Methods The Xuanwei lung cancer cell line XWLC-05 was inoculated into the lung tissue of SCID mice in high and low doses. The tumor formation rates, tumor characteristics, spontaneous metastases, and survival times of the mice were observed, taking a subcutaneously transplanted tumor as control. Results The tumor formation rates of the orthotopic transplantation of lung cancer cells in high and low doses were 81% and 83%, respectively, among which mice in the high-dose group appeared cachectic on day 13. Extensive invasion and adhesion were observed in the contralateral lung and thoracic cavity, but no distant metastasis was exhibited. Mice with low-dose cells in the orthotopic transplantation group appeared cachectic and distant metastasis occurred on day 25. The tumor formation rates in the subcutaneous inoculation group by the high and low doses of cells were 100% and 94.5%, respectively, and no distant metastasis was observed. The rate of metastasis within the orthotopic transplantation group and between the orthotopic and subcutaneous inoculation groups showed a significant difference (P<0.05. A significant difference was indicated by the survival rate within and between the groups (P<0.001. Conclusion We successfully established an orthotopic XWLC SCID mouse model, which lays the foundation for a more in-depth study.

  9. 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.

  10. Orthotopic heart transplant versus left ventricular assist device: A national comparison of cost and survival

    Science.gov (United States)

    Mulloy, Daniel P.; Bhamidipati, Castigliano M.; Stone, Matthew L.; Ailawadi, Gorav; Kron, Irving L.; Kern, John A.

    2012-01-01

    Objectives Orthotopic heart transplantation is the standard of care for end-stage heart disease. Left ventricular assist device implantation offers an alternative treatment approach. Left ventricular assist device practice has changed dramatically since the 2008 Food and Drug Administration approval of the HeartMate II (Thoratec, Pleasanton, Calif), but at what societal cost? The present study examined the cost and efficacy of both treatments over time. Methods All patients who underwent either orthotopic heart transplantation (n = 9369) or placement of an implantable left ventricular assist device (n = 6414) from 2005 to 2009 in the Nationwide Inpatient Sample were selected. The trends in treatment use, mortality, and cost were analyzed. Results The incidence of orthotopic heart transplantation increased marginally within a 5-year period. In contrast, the annual left ventricular assist device implantation rates nearly tripled. In-hospital mortality from left ventricular assist device implantation decreased precipitously, from 42% to 17%. In-hospital mortality for orthotopic heart transplantation remained relatively stable (range, 3.8%–6.5%). The mean cost per patient increased for both orthotopic heart transplantation and left ventricular assist device placement (40% and 17%, respectively). With the observed increase in both device usage and cost per patient, the cumulative Left ventricular assist device cost increased 232% within 5 years (from $143 million to $479 million). By 2009, Medicare and Medicaid were the primary payers for nearly one half of all patients (orthotopic heart transplantation, 45%; left ventricular assist device, 51%). Conclusions Since Food and Drug Administration approval of the HeartMate II, mortality after left ventricular assist device implantation has decreased rapidly, yet has remained greater than that after orthotopic heart transplantation. The left ventricular assist device costs have continued to increase and have been

  11. Orthotopic ureterocele masquerading as a bladder tumor in a woman with pelvic pain

    Directory of Open Access Journals (Sweden)

    David D. Thiel

    2005-12-01

    Full Text Available Single system orthotopic ureteroceles often present in adulthood are associated with characteristic radiographic findings. We present the case of a 54 year old woman with 8 months of urgency/frequency and pelvic pain that has the cystoscopic appearance of a bladder tumor. Cystoscopic images, radiographs and intraoperative photos demonstrate the work-up, evaluation, and treatment of this unique single system orthotopic ureterocele containing a calculus. This patient demonstrates the need for cystoscopy accompanied by upper tract imaging in patients with new onset pelvic pain, urgency/frequency, and frequent urinary tract infections.

  12. 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

  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. Gene mutations in hepatocellular adenomas

    DEFF Research Database (Denmark)

    Raft, Marie B; Jørgensen, Ernö N; Vainer, Ben

    2015-01-01

    is associated with bi-allelic mutations in the TCF1 gene and morphologically has marked steatosis. β-catenin activating HCA has increased activity of the Wnt/β-catenin pathway and is associated with possible malignant transformation. Inflammatory HCA is characterized by an oncogene-induced inflammation due....... This review offers an overview of the reported gene mutations associated with hepatocellular adenomas together with a discussion of the diagnostic and prognostic value....

  15. 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.

  16. Aprotinin in orthotopic liver transplantation : Evidence for a prohemostatic, but not a prothrombotic, effect

    NARCIS (Netherlands)

    Molenaar, IQ; Legnani, C; Groenland, THN; Palareti, G; Begliomini, B; Terpstra, OT; Porte, RJ

    2001-01-01

    Aprotinin reduces blood transfusion requirements in orthotopic liver transplantation (OLT). Concern has been voiced about the potential risk for thrombotic complications when aprotinin is used. The aim of this study is to evaluate the effects of aprotinin on the two components of the hemostatic syst

  17. 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.

  18. Risk Factors for Fatal Recurrence of Liver Transplant Recipients with Hepatocellular Carcinoma in the First Year

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective: To investigate the clinicopathological risk factors for fatal recurrence of hepatocellular carcinoma (HCC) in orthotopic liver transplant recipients in the first year. Methods: From April 2002 to October 2005, 303 recipients who received orthotopic liver transplantation for HCC were reviewed. Of These patients, those who demonstrated diffuse intra-hepatic or multiple systemic recurrent lesions and died within 1 y after surgery were investigated (fatal recurrence group, 48 cases). The remaining patients were designated as the control group, and the two groups were compared for clinicopathologic risk factors by logistic regression analysis. Results: Among the 303 patients reviewed, 48 patients were enrolled in the fatal recurrence group (15.84%). Multivariate analysis between the fatal recurrence group and control group showed that the presence of vascular invasion, tumor size greater than 6.5 cm, and pre-operative serum alpha-fetoprotein (AFP) level greater than 1000 μg/L were the risk factors in the fatal recurrence group. 85.71% of the patients who had all the three risk factors, 37.84% of those who had two risk factors, 13.64% of those who had one risk factors, and 6.71% of those who had none risk factors died because of recurrence within 1 y after transplantation. Conclusion: Three distinct risk factors attributed to fatal recurrence of liver transplant recipients for HCC are vascular invasion, tumor size ≥6.5 cm, and pre-operative serum AFP level ≥1000 μg/L. The high risk HCC patients with two or more risk factors should not to be the candidates for liver transplantation.

  19. Notch1-Snail1-E-cadherin pathway in metastatic hepatocellular carcinoma.

    Science.gov (United States)

    Wang, Xiao Qi; Zhang, Wu; Lui, Eric L H; Zhu, Yongqiang; Lu, Ping; Yu, Xiaoming; Sun, Jisan; Yang, Sitian; Poon, Ronnie T P; Fan, Sheung Tat

    2012-08-01

    Notch signaling, a critical pathway for tissue development, also contributes to tumorigenesis in many cancers, but its pathological function in liver cancer is not well defined. In our study, Notch1 expression and its clinicopathological parameters were evaluated in 82 human hepatocellular carcinoma (HCC) patients. Plasmid-based siNotch1 shRNA was transiently or stably transfected into metastatic HCC cells and subsequently evaluated for the effects on orthotopic liver tumor metastasis in a mouse model as well as the effects on downstream pathways. Aberrant high expression of Notch1 was significantly associated with metastatic disease parameters in HCC patients, such as tumor-node-metastasis Stages III-IV and tumor venous invasion. Knocking-down Notch1 reduced cell motility in vitro and orthotopic tumor metastasis from the liver to the lung in vivo in a mouse model. In metastatic HCC cells, abnormal expression of Notch1 was associated with increased expression of Snail1 and repressed expression of E-cadherin; the Notch1-Snail1-E-cadherin association can also be found in HCC patient tumors. Inhibition of Notch1 by shRNA abolished Snail1 expression, which further resulted in the re-establishment of repressed E-cadherin in metastatic HCC cells. Thus, abnormal Notch1 expression was strongly associated with HCC metastatic disease, which might be mediated through the Notch1-Snail1-E-cadherin pathway. Knock-down of Notch1 reversed HCC tumor metastasis in a mouse model. Therefore, these data suggest that effective targeting of Notch signaling might also inhibit tumor metastasis.

  20. Radiosensitizing Effect of a Phenylbutyrate-Derived Histone Deacetylase Inhibitor in Hepatocellular Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Lu, Yen-Shen [Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan (China); Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan (China); Cancer Research Center, National Taiwan University College of Medicine, Taipei, Taiwan (China); Chou, Chia-Hung [Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan (China); Tzen, Kai-Yuan [Department of Nuclear Medicine, National Taiwan University Hospital, Taipei, Taiwan (China); Gao, Ming [Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan (China); Cheng, Ann-Lii [Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan (China); Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan (China); Cancer Research Center, National Taiwan University College of Medicine, Taipei, Taiwan (China); Graduate Institutes of Oncology, National Taiwan University College of Medicine, Taipei, Taiwan (China); Kulp, Samuel K. [Division of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, The Ohio State University, Columbus, OH (United States); Cheng, Jason Chia-Hsien, E-mail: jasoncheng@ntu.edu.tw [Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan (China); Cancer Research Center, National Taiwan University College of Medicine, Taipei, Taiwan (China); Graduate Institutes of Oncology, National Taiwan University College of Medicine, Taipei, Taiwan (China)

    2012-06-01

    Purpose: Radiotherapy is integrated into the multimodal treatment of localized hepatocellular carcinoma (HCC) refractory to conventional treatment. Tumor control remains unsatisfactory and the sublethal effect associates with secondary spread. The use of an effective molecularly targeted agent in combination with radiotherapy is a potential therapeutic approach. Our aim was to assess the effect of combining a phenylbutyrate-derived histone deacetylase (HDAC) inhibitor, AR-42, with radiotherapy in in vitro and in vivo models of human HCC. Methods and Materials: Human HCC cell lines (Huh-7 and PLC-5) were used to evaluate the in vitro synergism of combining AR-42 with irradiation. Flow cytometry analyzed the cell cycle changes, whereas Western blot investigated the protein expressions after the combined treatment. Severe combined immunodeficient (SCID) mice bearing ectopic and orthotopic HCC xenografts were treated with AR-42 and/or radiotherapy for the in vivo response. Results: AR-42 significantly enhanced radiation-induced cell death by the inhibition of the DNA end-binding activity of Ku70, a highly versatile regulatory protein for DNA repair, telomere maintenance, and apoptosis. In ectopic xenografts of Huh-7 and PLC-5, pretreatment with AR-42 significantly enhanced the tumor-suppressive effect of radiotherapy by 48% and 66%, respectively. A similar combinatorial effect of AR-42 (10 and 25 mg/kg) and radiotherapy was observed in Huh-7 orthotopic model of tumor growth by 52% and 82%, respectively. This tumor suppression was associated with inhibition of intratumoral Ku70 activity as well as reductions in markers of HDAC activity and proliferation, and increased apoptosis. Conclusion: AR-42 is a potent, orally bioavailable inhibitor of HDAC with therapeutic value as a radiosensitizer of HCC.

  1. Genetic alteration in hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    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).

  2. 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.

  3. Diagnosis and treatment of hepatocellular carcinoma: Anupdate

    Institute of Scientific and Technical Information of China (English)

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

    2015-01-01

    Hepatocellular carcinoma (HCC) is one of the mostcommon malignancies leading to high mortality ratesin the general population; in cirrhotic patients, it isthe primary cause of death. The diagnosis is usuallydelayed in spite of at-risk population screening recommendations,i.e., patients infected with hepatitis B or Cvirus. Hepatocarcinogenesis hinges on a great numberof genetic and molecular abnormalities that lead totumor angiogenesis and foster their disseminationpotential. The diagnosis is mainly based on imagingstudies such as computed tomography and magneticresonance, in which lesions present a characteristicclassical pattern of early arterial enhancement followedby contrast medium "washout" in late venous phase.On occasion, when imaging studies are not conclusive,biopsy of the lesion must be performed to establish thediagnosis. The Barcelona Clinic Liver Cancer stagingmethod is the most frequently used worldwide andrecommended by the international guidelines of HCCmanagement. Currently available treatments includetumor resection, liver transplant, sorafenib and locoregionaltherapies (alcoholization, radiofrequencyablation, chemoembolization). The prognosis of hepatocarcinomais determined according to the lesion's stageand in cirrhotic patients, on residual liver function.Curative treatments, such as liver transplant, aresought in patients diagnosed in early stages; patients inmore advanced stages, were not greatly benefitted bychemotherapy in terms of survival until the advent oftarget molecules such as sorafenib.

  4. 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.

  5. 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.

  6. 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.

  7. 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

  8. Surgical Treatment for Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    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.

  9. 同种异体半相合细胞因子诱导的杀伤细胞治疗晚期肝癌的疗效及安全性评估%Curative effect and safety of haploidentical allogeneic cytokine-induced killer in treatment of advanced hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    杨帆; 郑小芳; 刘畅; 陈文捷; 程锦涛; 阳莉; 卢建溪; 张琪

    2015-01-01

    Objective To investigate the curative effect and safety of haploidentical allogeneic cytokine-induced killer (CIK)in treatment of advanced hepatocellular carcinoma.Methods The peripheral blood mononuclear cell (PBMC) of the healthy immediate family members of 21 patients with advanced hepatocellular carcinoma (HCC) were collected,induced into haploidentical allogeneic CIK in vitro and transfused to the patients for 4 cycles.The curative effect and safety were assessed.Results The 21 patients were followed up for half a year.The survival rate was 81 % (1 7 /21 ).Among the 21 patients,1 1 cases were with stable disease and 1 0 cases were with progressive disease (including 4 dead cases).Six patients developed fever of different degrees during the treatment and one patient developed rash.The platelet counts of the patients at the fourth cycle after the treatment decreased compared with that before the treatment ,with significance difference (P 0.05 ).Conclusions Haploidentical allogeneic CIK in treatment of advanced HCC may effectively improve the quality of life and the adverse reactions are tolerable,which is a relatively safe therapy.%目的:探讨同种异体半相合细胞因子诱导的杀伤(CIK)细胞治疗晚期肝癌的疗效及安全性。方法采集21例晚期肝细胞癌(肝癌)患者健康一级直系亲属的外周血单个核细胞,在体外诱导成异体半相合 CIK 细胞后回输给患者,回输4个周期。评估治疗效果和安全性。结果随访半年,21例患者的存活率为81%(17/21),疾病稳定患者11例,疾病进展患者10例(含4例死亡病例)。6例患者治疗期间出现不同程度的发热,1例出现皮疹。与治疗前相比,患者治疗后第4周期的血小板数量降低,差异有统计学意义(P <0.05),而患者治疗后第1、4周期的白细胞、中性粒细胞、淋巴细胞、血红蛋白,肝、肾功能差异均无统计学意义(均为 P >0.05)。

  10. 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.

  11. Evidenced-based clinical practice of interventional therapy for advanced hepatocellular carcinoma:2-year follow-up results in 59 cases%中晚期肝细胞肝癌介入治疗的循证临床实践二年随访观察

    Institute of Scientific and Technical Information of China (English)

    李保国; 温浩; 郭志; 王海涛

    2010-01-01

    目的 探讨借助循证医学方法为中晚期肝细胞肝癌患者确定介入治疗目标以及治疗方案的效果.方法 在充分评价肝癌介入治疗现状后,提出临床问题,从EBSCO、Cochrane图书馆(2007年第1期)、Medline(1990年1月至2007年1月)、ACP Journal Club(1991年1月至2007年1月)和http://sumsearch.uthsea. Edu/searchform4.htm上进行检索,检索主题词:肝细胞肝癌、介入治疗、系统评价、荟萃分析等.对检索获得的循证医学证据进行分析评价并制定合理的循证介入治疗方案后,纳入患者实施治疗;与同期收治的纳入标准一致但按照传统方式进行介入治疗的患者进行比较,观察该方案的有效性及两组病例的治疗获益差别.统计处理采用SPSS 16.0统计软件,用Kaplan-Meier法绘制生存曲线,运用时序检验Log-rank进行统计学显著性分析,组间率的比较采用x2检验.结果 共检索出与不同问题相关的随机对照试验9篇,系统评价和荟萃分析3篇.总共纳入了119例患者,59例实施循证介入治疗,60例接受传统方式的介入治疗.连续随访2年证实,循证介入治疗方案更适合本组患者,1、2年生存率分别为79.7%、50.8%,而非循证介入治疗组分别为68.3%、31.7%,两组比较差异具有统计学意义(P<0.05).结论 运用循证治疗的方法为中晚期肝癌患者确定合理的治疗方案,有助于提高介入治疗的疗效、增加患者的生存获益.%Objective To explore the methods of evidence-based medicine to determine objectives and evaluate the efficacy of interventional therapy for advanced hepatocellular carcinoma. Methods Clinical questions were raised after a thorough evaluation of the status of interventional therapy. The term of evidence based medicine methods was searched in EBSCO, Cochrane library, Medline (January 1990 -January 2007 ), ACP Journal Club (January 1991 -January 2007 ) and Sumsearch. The searching subjects were hepatocellular carcinoma

  12. Listeria monocytogenes following orthotopic liver transplantation: Central nervous system involvement and review of the literature

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Listeria monocytogene is a well-recognized cause of bacteremia in immunocompromised individuals, including solid organ transplant recipients, but has been rarely reported following orthotopic liver transplantation. We describe a case of listeria meningitis that occurred within a week after liver transplantation. The patient developed a severe headache that mimicked tacrolimus encephalopathy, and was subsequently diagnosed with listeria meningitis by cerebrospinal fluid culture. The infection was successfully treated with three-week course of intravenous ampicillin. Recurrent hepatitis C followed and was successfully treated with interferon alfa and ribavirin. Fourteen cases of listeriosis after orthotopic liver transplantation have been reported in the English literature. Most reported cases were successfully treated with intravenous ampicillin. There were four cases of listeria meningitis, and the mortality of them was 50%.Early detection and treatment of listeria meningitis are the key to obtaining a better prognosis.

  13. Intraoperative blood loss in orthotopic liver transplantation:The predictive factors

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Liver transplantation has been associated with massiveblood loss and considerable transfusion requirements.Bleeding in orthotopic liver transplantation is multifactorial.Technical difficulties inherent to this complex surgicalprocedure and pre operative derangements of the primaryand secondary coagulation system are thought tobe the principal causes of perioperative hemorrhage.Intraoperative practices such as massive fluid resuscitationand resulting hypothermia and hypocalcemia secondaryto citrate toxicity further aggravate the preexistingcoagulopathy and worsen the perioperative bleeding.Excessive blood loss and transfusion during orthotopicliver transplant are correlated with diminished graftsurvival and increased septic episodes and prolongedICU stay. With improvements in surgical skills, anesthetictechnique, graft preservation, use of intraoperative cellsavers and overall perioperative management, orthotopicliver transplant is now associated with decreased intraoperative blood losses. The purpose of this review isto discuss the risk factors predictive of increased intraoperative bleeding in patients undergoing orthotopic livertransplant.

  14. Sacrocolpopexy with Polypropylene Tape as Valuable Surgical Modification during Cystectomy with Orthotopic Ileal Bladder: Functional Results

    Directory of Open Access Journals (Sweden)

    Marcin Życzkowski

    2015-01-01

    Full Text Available Introduction. Urinary diversion is very often associated with urinary retention and urinary incontinence. In this study, a surgical modification during cystectomy with orthotopic ileal neobladder is presented. Material and Methods. Female patients enrolled in the study (n-24 were subjected to sacrocolpopexy during the operation. Apart from oncological control, the follow-up consisted of 1-hour inlay test and questionnaires (UDI-6 and IIQ-7 in the 3rd, 6th, and 12th month after the operation. In the 12th month after the surgery, the urodynamic pressure-flow test was performed. Outcomes were compared with the control group (n-18 in which sacrocolpopexy was not implemented. Results. The study group was characterised by reduced urinary retention and improved continence. Conclusion. Sacrocolpopexy during cystectomy with orthotopic ileal bladder is a valuable surgical method which provides patients with a better quality of life.

  15. Radiofrequency ablation of recurrent cholangiocarcinoma after orthotopic liver transplantation - a case report

    Institute of Scientific and Technical Information of China (English)

    Rakesh Rai; Derek Manas; John Rose

    2005-01-01

    AIM: To report the use of radiofrequency ablation in the treatment of recurrenct cholangiocarcinoma in the transplanted liver.METHODS: A lady who underwent orthotopic liver transplantation (OLT) for intrahepatic cholangiocarcinoma recurrence of tumour 13 mo after tralsplantation inspite of adjuvant chemotherapy. Her recurrent tumour was treated with radiofrequency ablation.RESULTS: She survived for 18 mo following the recurrence of her tumour.CONCLUSION: Radiofrequency ablation can be used safely in the transplanted liver to treat recurrent tumour.

  16. Placement of removable metal biliary stent in post-orthotopic liver transplantation anastomotic stricture

    Institute of Scientific and Technical Information of China (English)

    Hoi-Poh; Tee; Martin; W; James; Arthur; J; Kaffes

    2010-01-01

    Postoperative biliary strictures are the most common cause of benign biliary stricture in Western countries, secondary to either operative injury or bile duct anastomotic stricture following orthotopic liver transplantation(OLT).Surgery or endoscopic interventions are the mainstay of treatment for benign biliary strictures.We aim to report the outcome of 2 patients with refractory anastomotic biliary stricture post-OLT,who had successful temporary placement of a prototype removable covered self-expandable m...

  17. Influence of preoperative diastolic dysfunction on hemodynamics and outcomes of patients undergoing orthotopic liver transplantation

    OpenAIRE

    2013-01-01

    Objective: Left ventricular diastolic dysfunction is receiving more attention in patients with end-stage liver diseases. The importance of diastolic dysfunction observed before orthotopic liver transplantation (OLT) and its adverse effects on hemodynamics and outcomes of OLT patients, have not been fully explored. We carried a retrospective study to investigate the influence of diastolic dysfunction on OLT patients. Methods: Included in this retrospective study were 330 consecutive patients s...

  18. Radiography Monitoring of Osteoconduction and Osteoinduction of Orthotopic Allograft Autoclaved Covered With Propolis

    OpenAIRE

    BOUDRA Abdellatif; Hamdi, Mohamed; AMARA Karim; BOUKNINE Asma

    2014-01-01

    The veterinarian orthopedic surgeon is often faced to the loss of bone substance in diaphyseal region of long bones. Our study is based on a biological approach to the filling of segmental bone loss by implanting an autoclaved orthotopic allograft of one centimeter length covered and uncovered with propolis in the femoral diaphysis under general anesthesia and sterile condition. The experiment involved eight adult dogs, from local breed and different sex; split into two groups. An autoclaved ...

  19. Pulmonary artery rupture in a patient receiving an orthotopic heart transplant after total artificial heart explant.

    Science.gov (United States)

    Nomoto, Koichi; Weiner, Menachem M; Evans, Adam

    2014-02-01

    Our case illustrates a patient who suffered a pulmonary artery rupture despite previous total artificial heart implantation and replacement with orthotopic heart transplant. Pulmonary artery rupture during or following cardiac surgery has been reported to occur due to both pulmonary artery catheter use and surgical technique. Our case is the first to demonstrate the occurrence of this complication in the total artificial heart patient population.

  20. 前列腺素E1对移植肝的保护作用%Experiment study on the relationship between the protective effect of prostaglandin E1 and the lysosome in orthotopic liver transplantation in rats

    Institute of Scientific and Technical Information of China (English)

    阚彤; 杨甲梅; 严以群; 陈汉; 吴孟超

    2001-01-01

    Objective To study the protective effect of prostaglandin E1 (PGE1) on the liver in orthotopic liver transplantation rats. Methods PGE1 was infused intravenously during orthotopic liver transplantation in recipient rats. Sham-operated and normal saline groups served as control groups. One-week survival rate and ultrastructure pathological changes in liver were observed. Results The survival rate in the PGE1-treated group was obviously increased as compared with that in the control group. Electron microscopic examination revealed a dramatic elevation of hepatocellular lysosome number in the control groups, and bleb and rupture of lysosome membrane were also observed in the PGE1-trated group. Conclusions PGE1 treatment during recipient operation could increase one-week survival rate, which might be related with its stabilizing effect on lysosome membrane.%目的探讨术中应用前列腺素E1(PGE1)对移植肝脏的保护作用。方法大鼠原位肝移植术中经颈内静脉灌注PGE1,设盐水和空白对照,观察术后1周存活率和肝脏超微结构变化。结果 PGE1治疗组术后1周存活率较对照组明显提高,电镜证实PGE1治疗组肝细胞内溶酶体膜无鼓泡和破溃现象。结论术中应用PGE1能显著提高大鼠肝移植后的1周存活率,其机制可能与PGE1稳定溶酶体膜的作用有关。

  1. Establishment of orthotopic impact/metastasis model of human ovary cancer in nude mice

    Institute of Scientific and Technical Information of China (English)

    侯向华; 辛晓燕; 杨红; 王德堂; 郭慧玲

    2003-01-01

    Objective:To establish a patient-like human ovary carcinoma/spontaneous metastasis model using orthotopic transplanation of histologically intact tumor tissue.Methods:An highly metastatic ovarian tumor line(HO8910PM:Human serum carcinoma of the ovary)previously grown substaneously was transplanted into the ovicapsule using microsurgery technique .Histologically intact human ovary tumor pieces gained from implantation site were passaged between ovicapsules for four generations.Results:All mice developed ovary tumors and the metastatic rates were about 75%.The tumors only metastasized to liver but no other organs.The earliest appearance of metastasis was 14 d and the average survival period was 20.7 ± 4.89 d.The microscopic appearance of the metastases was similar to the tumor observed in the substaneous xenografts and orthotopically transplanted.Chromosomes analysis exhibited the feature of human carcinoma and retained genetic stability during the processes of passage.Conclusion:Orthotopic implanation provides a suitable micro-enviroment in which ovarian cancer can express its intrinsic clinically-relevant properties.This approach is relevant to the spontaneous development of ovarian cancer and is thought to be a useful model for studies of metastatic mechanism and therapy for ovary cancer.

  2. Clinical and pathological analysis of acute rejection following orthotopic liver transplantation

    Institute of Scientific and Technical Information of China (English)

    MA Yi; WANG Guo-dong; HE Xiao-shun; LI Jun-liang; ZHU Xiao-feng; HU Rui-de

    2009-01-01

    Background Acute rejection is one of the most important factors for prognosis following liver transplantation. With the use of potent immunosuppressants, acute rejection does not always present typical manifestations. Moreover, other complications often occur concomitantly after liver transplantation, which makes early diagnosis of acute rejection more difficult. Acute rejection is best diagnosed by liver biopsy. Differentiation of clinical manifestations and pathological features plays an important role in achieving individualized immunosuppressive treatment and prolonging long term survival of patients given orthotopic liver transplants.Methods From January 2004 to December 2006, 516 orthotopic liver transplantations were performed at the First Affiliated Hospital, Sun Yat-sen University. For patients who suffered acute rejection, clinical manifestations, histopathological features, diagnosis and anti-rejection treatment were summarized and analyzed. Results In 86 cases (16.7%), of the 516 recipients, 106 episodes of acute rejection occurred, which included 9 with histopathological borderline changes, 36 Banff Ⅰ rejections, 48 Banff Ⅱ and 13 Banff Ⅲ. Among these, 36 were cured by adjusting the dose of immunosuppressant and 65 were reversed by methylprednisolone pulse treatment. Five were methylprednisolone resistant, 3 of whom were given OKT3 treatment and 2 underwent liver retransplantation. Conclusions Due to potent immunosuppressive agents, acute rejection following an orthotopic liver transplantation lacks typical clinical manifestations and pathological features. Acute rejection is best diagnosed by liver biopsy. Designing rational individualized immunosuppressive regimen based on clinical and pathological features of acute rejection plays an important role in prolonging long term survival of patients.

  3. Screening of the residual normal ovarian tissue adjacent to orthotopic epithelial ovarian carcinomas in nude mice.

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    Zhu, G H; Wang, S T; Yao, M Z; Cai, J H; Chen, C Y; Yang, Z X; Hong, L; Yang, S Y

    2014-04-16

    The objective of this study was to explore the feasibility and methods of screening the residual normal ovarian tissue adjacent to orthotopic ovarian carcinomas in nude mice. Human epithelial ovarian cancer cells (OVCAR3) were subcutaneously implanted for a tumor source and ovarian orthotopic transplantation. The cancer tissue, proximal paraneoplastic tissue, middle paraneoplastic tissue, remote paraneoplastic tissue, and normal ovarian tissue were removed. CK-7, CA125, p53, survivin, MMP-2, and TIMP-2 expression was detected by reverse transcription polymerase chain reaction. We obtained 35 paraneoplastic residual ovarian tissues with normal biopsies from 40 cases of an orthotopic epithelial ovarian carcinoma model (87.5%). CK-7, CA125, p53, survivin, MMP-2, and TIMP-2 expression was lower in proximal paraneoplastic tissue than in cancer tissue (P tissue (P tissue as well as among residual normal ovarian tissues with different severity (P > 0.05). In ovarian tissues of 20 normal nude mice, the expression of CK- 7, CA125, p53, survivin, MMP-2, and TIMP-2 was negative. Overall, the expression levels of CK-7, CA125, p53, survivin, MMP-2, TIMP-2, and other molecular markers showed a decreasing trend in the non-cancer tissue direction. The expression levels can be used as standards to screen residual normal ovarian tissue. We can obtain relatively safe normal ovarian tissues adjacent to epithelial ovarian cancer.

  4. 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.

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

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    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.

  6. 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.

  7. Interstitial fluid pressure, vascularity and metastasis in ectopic, orthotopic and spontaneous tumours

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    Brown Allison

    2008-01-01

    Full Text Available Abstract Background High tumour interstitial fluid pressure (IFP has been adversely linked to poor drug uptake in patients, and to treatment response following radiotherapy in cervix cancer patients. In this study we measured IFP values in a selection of murine and xenograft models, spontaneously arising or transplanted either intramuscularly (i/m or orthotopically and analysed their relationship to tumour vascularity and metastatic spread. Methods KHT-C murine fibrosarcoma, ME180 and SiHa human cervix carcinoma were grown either intramuscularly (i/m, sub-cutaneously (s/c or orthotopically. Polyoma middle-T (MMTV-PyMT transgenic spontaneous mammary tumours were studied either as spontaneous tumours or following orthotopic or i/m transplantation. IFP was measured in all tumours using the wick-in-needle method. Spontaneous metastasis formation in the lungs or lymph nodes was assessed in all models. An immunohistochemical analysis of tumour hypoxia, vascular density, lymphatic vascular density and proliferation was carried out in ME180 tumours grown both i/m and orthotopically. Blood flow was also assessed in the ME180 model using high-frequency micro-ultrasound functional imaging. Results Tumour IFP was heterogeneous in all the models irrespective of growth site: KHT-C i/m: 2–42 mmHg, s/c: 1–14 mmHg, ME180: i/m 5–68 mmHg, cervix 4–21 mmHg, SiHa: i/m 20–56 mmHg, cervix 2–26 mmHg, MMTV-PyMT: i/m: 13–45 mmHg, spontaneous 2–20 mmHg and transplanted 2–22 mmHg. Additionally, there was significant variation between individual tumours growing in the same mouse, and there was no correlation between donor and recipient tumour IFP values. Metastatic dissemination to the lungs or lymph nodes demonstrated no correlation with tumour IFP. Tumour hypoxia, proliferation, and lymphatic or blood vessel density also showed no relationship with tumour IFP. Speckle variance analysis of ultrasound images showed no differences in vascular perfusion

  8. Hepatic Artery Chemoembolization for Hepatocellular Carcinoma Recurrence Confined to the Transplanted Liver

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    Brian I. Carr

    2012-09-01

    Full Text Available Background: Careful hepatocellular carcinoma (HCC case selection permits orthotopic liver transplantation with the expectation of around 70% plus 5-year survival. However, many patients have tumor recurrences and there is little literature guidance in the management of these patients. Aims: A retrospective examination of patients transplanted with HCC who subsequently developed liver recurrence. Methods: A case cohort series of patients was prospectively followed who had liver-only multifocal tumor recurrence of HCC after liver transplant and were then treated with chemoembolization. Results: All 6 patients had recurrent HCC. 2 had no response, 1 had stable disease, 2 had partial response (PR and 1 had complete disappearance (CR of disease. Their survival (in months was: 13 (no response, 18 (no response, 12 (stable disease, 19 (PR, 30 (PR and 50 (CR. There were no liver toxicities. Conclusions: Chemoembolization for tumor recurrence in the transplanted liver is as safe as or safer than in the pre-transplant liver, due to the absence of cirrhosis. In this series, there were 3 of 6 responses with some long survivors.

  9. Percutaneous microwave ablation vs radiofrequencyablation in the treatment of hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Hepatocellular cancer ranks fifth among cancers andis related to chronic viral hepatitis, alcohol abuse,steatohepatitis and liver autoimmunity. Surgical resectionand orthotopic liver transplantation have curativepotential, but fewer than 20% of patients are suitablecandidates. Interventional treatments are offered to thevast majority of patients. Radiofrequency (RFA) andmicrowave ablation (MWA) are among the therapeuticmodalities, with similar indications which include thepresence of up to three lesions, smaller than 3 cm in size,and the absence of extrahepatic disease. The therapeuticeffect of both methods relies on thermal injury, but MWAuses an electromagnetic field as opposed to electricalcurrent used in RFA. Unlike MWA, the effect of RFA ispartially limited by the heat-sink effect and increasedimpedance of the ablated tissue. Compared with RFA,MWA attains a more predictable ablation zone, permitssimultaneous treatment of multiple lesions, and achieveslarger coagulation volumes in a shorter procedural time.Major complications of both methods are comparableand infrequent (approximately 2%-3%), and theyinclude haemorrhage, infection/abscess, visceral organinjury, liver failure, and pneumothorax. RFA may incurthe additional complication of skin burns. Nevertheless,there is no compelling evidence for differences in clinicaloutcomes, including local recurrence rates and survival.

  10. Orthotopic transplantation of cryopreserved mouse ovaries and gonadotrophin releasing hormone analogues in the restoration of function following chemotherapy-induced ovarian damage.

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    Qing Li

    Full Text Available Therapy advances are constantly improving survival rates of cancer patients, however the toxic effects of chemotherapy drugs can seriously affect patients' quality of life. In women, fertility and premature ovarian endocrine dysfunction are of particular concern. It is urgently we find methods to preserve or reconstruct ovarian function for these women. This study compares GnRHa treatment with ovarian tissue cryopreservation and orthotopic transplantation in a chemotherapy-induced ovarian damage murine model. 56 inbred Lewis rats were divided into 4 treatment groups: Saline control (group I; cyclophosphamide only (group II; cyclophosphamide plus GnRHa (group III; cyclophosphamide and grafting of thawed cryopreserved ovaries (group IV. Body weight, estrous cycle recovery time, ovarian weight, morphology and follicle count, as well as breeding and fertility were compared among groups. Only group IV was able to restore to normal body weight by the end of the observation period and resumed normal estrous cycles in a shorter time compared to other treatment groups. There was a decrease in primordial follicles in all treatment groups, but group III had the greatest reduction. Although, there was no difference in pregnancy, only one animal littered normal pups in group II, none littered in group III and four littered in group IV. Thus, cryopreservation and orthotopic transplantation of ovarian tissue can restore the fertility of rats subjected to chemotherapy in a manner that is superior to GnRHa treatment. We also observed increased rates of hepatic, splenic and pulmonary haemorrhage in group III, suggesting there may be synergistic toxicity of GnRHa and cyclophosphamide.

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

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    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.

  12. 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.

  13. Hypoxia-targeted 131I therapy of hepatocellular cancer after systemic mesenchymal stem cell-mediated sodium iodide symporter gene delivery.

    Science.gov (United States)

    Müller, Andrea M; Schmohl, Kathrin A; Knoop, Kerstin; Schug, Christina; Urnauer, Sarah; Hagenhoff, Anna; Clevert, Dirk-André; Ingrisch, Michael; Niess, Hanno; Carlsen, Janette; Zach, Christian; Wagner, Ernst; Bartenstein, Peter; Nelson, Peter J; Spitzweg, Christine

    2016-08-23

    Adoptively transferred mesenchymal stem cells (MSCs) home to solid tumors. Biologic features within the tumor environment can be used to selectively activate transgenes in engineered MSCs after tumor invasion. One of the characteristic features of solid tumors is hypoxia. We evaluated a hypoxia-based imaging and therapy strategy to target expression of the sodium iodide symporter (NIS) gene to experimental hepatocellular carcinoma (HCC) delivered by MSCs.MSCs engineered to express transgenes driven by a hypoxia-responsive promoter showed robust transgene induction under hypoxia as demonstrated by mCherry expression in tumor cell spheroid models, or radioiodide uptake using NIS. Subcutaneous and orthotopic HCC xenograft mouse models revealed significant levels of perchlorate-sensitive NIS-mediated tumoral radioiodide accumulation by tumor-recruited MSCs using 123I-scintigraphy or 124I-positron emission tomography. Functional NIS expression was further confirmed by ex vivo 123I-biodistribution analysis. Administration of a therapeutic dose of 131I in mice treated with NIS-transfected MSCs resulted in delayed tumor growth and reduced tumor perfusion, as shown by contrast-enhanced sonography, and significantly prolonged survival of mice bearing orthotopic HCC tumors. Interestingly, radioiodide uptake into subcutaneous tumors was not sufficient to induce therapeutic effects. Our results demonstrate the potential of using tumor hypoxia-based approaches to drive radioiodide therapy in non-thyroidal tumors.

  14. 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.

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

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    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

  16. Surgical management of spontaneous ruptured hepatocellular adenoma

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    Marcelo Augusto Fontenelle Ribeiro Junior

    2009-01-01

    Full Text Available AIMS: Spontaneous ruptured hepatocellular adenoma (SRHA is a rare life-threatening condition that may require surgical treatment to control hemorrhaging and also stabilize the patient. We report a series of emergency surgeries performed at our institution for this condition. METHODS: We reviewed medical records and radiology files of 28 patients (from 1989 to 2006 with a proven diagnosis of hepatocellular adenoma (HA. Three (10.7% of 28 patients had spontaneous ruptured hepatocellular adenoma, two of which were associated with intrahepatic hemorrhage while one had intraperitoneal bleeding. Two patients were female and one was male. Both female patients had a background history of oral contraceptive use. Sudden abdominal pain associated with hemodynamic instability occurred in all patients who suffered from spontaneous ruptured hepatocellular adenoma. The mean age was 41.6 years old. The preoperative assessment included liver function tests, ultrasonography and computed tomography. RESULTS: The surgical approaches were as follows: right hemihepatectomy for controlling intraperitoneal bleeding, and right extended hepatectomy and non-anatomic resection of the liver for intrahepatic hemorrhage. There were no deaths, and the postoperative complications were bile leakage and wound infection (re-operation, as well as intraperitoneal abscess (re-operation and pleural effusion. CONCLUSION: Spontaneous ruptured hepatocellular adenoma may be treated by surgery for controlling hemorrhages and stabilizing the patient, and the decision to operate depends upon both the patient's condition and the expertise of the surgical team.

  17. The impact of prior prostatic surgery on urinary continence in patients undergoing orthotopic ileal neobladder

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    Homero O. de Arruda

    2003-12-01

    Full Text Available OBJECTIVE: To establish if previous surgery for benign prostatic hyperplasia (transurethral resection of the prostate or open prostatectomy, age, and preservation of prostatic apex can influence postoperative urinary continence in patients submitted to radical cystectomy and orthotopic ileal neobladder. PATIENTS AND METHODS: We analyzed 62 patients with bladder cancer who were treated with radical cystectomy and orthotopic ileal neobladder between 1987 and 1998 and had been followed for at least 24 months. The average age and median follow up were 61 years and 53 months, respectively. Postoperative urinary continence was correlated with 3 factors: patient age, preservation of prostatic apex during surgical excision and prior prostatic surgery for benign disease. Patients were defined as incontinent when they had to use more than 1 protective pad at the daytime. RESULTS: The overall incidence of urinary incontinence was 12.9% (8 out of 62 patients. The only statistically significant factor that impacted upon urinary continence was previous prostatic surgery, with respectively 33% versus 7% rate of incontinence for patients previously operated on and for those without previous operation (p = 0.023 odds ratio = 6.5, 95% confidence interval. Preservation of prostatic apex did not reach difference, 12% versus 13%, for those with and without preservation, and age also did not influence the postoperative continence rate. CONCLUSIONS: Prior prostatic surgery for benign prostatic hyperplasia probably can increases the risk for postcystectomy incontinence and preservation of prostate apex did not affect the continence rate. This issue deserves to be considered by the surgeon and must be discussed previously with the patients when planning an orthotopic bladder replacement.

  18. Effects of different mitogens on intrasplenic liver tissue transplants in comparison to orthotopic liver.

    Science.gov (United States)

    Lupp, Amelie; Lucas, Norma; Tralls, Manuela; Fuchs, Udo; Danz, Manfred

    2003-06-01

    Ectopic liver cell transplants, when compared to orthotopic liver, can serve as a tool to study topic influences on liver cell differentiation, multiplication, function and responsiveness to xenobiotics. The aim of the present study was to evaluate, if characteristic effects of mitogens are exerted in both liver and intrasplenic liver cell transplants in a similar manner. Fetal liver tissue suspensions were transplanted into the spleens of adult male syngenic rats. Four months later, transplant recipients and controls were treated with fluorene (FEN), fluorenone (FON), 2-acetylaminofluorene (AAF), N-nitrosodibenzylamine (NDBA) or the solvent 48 hours before sacrifice. The following parameters were assessed within livers and spleens: mitotic activity of hepatocytes, glycogen content, cytochrome P450 (P450) isoforms expression, P450 mediated monooxygenase functions, tissue content of lipid peroxides (LPO) and of reduced and oxidized glutathione (GSH; GSSG). In both orthotopic livers and intrasplenic transplants FEN, FON or NDBA administration increased the mitotic activity of the hepatocytes. Treatment with the mitogens caused a distinct and characteristic induction of the P450 isoforms expression and of the respective monooxygenase functions in the livers and (with certain differences) also in the transplants. FEN and FON slightly increased, AAF and NDBA reduced liver glycogen content. The latter effect was also seen in the transplants. NDBA administration caused a slight increase in tissue LPO content in livers, but not in spleens. Additionally, AAF or NDBA treatment led to an elevation of liver (but not of spleen) GSH and GSSG concentrations. The results of the present investigation show that characteristic effects of mitogens on orthotopic liver occur with certain differences also in ectopic liver cell transplants.

  19. Detection of rejection of canine orthotopic cardiac allografts with indium-111 lymphocytes and gamma scintigraphy

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    Eisen, H.J.; Rosenbloom, M.; Laschinger, J.C.; Saffitz, J.E.; Cox, J.L.; Sobel, B.E.; Bolman, R.M. III; Bergmann, S.R.

    1988-07-01

    Previous studies have demonstrated the feasibility of detecting canine heterotopic cardiac allograft rejection scintigraphically after administration of 111In lymphocytes. To determine whether the approach is capable of detecting rejection in orthotopic cardiac transplants in which labeled lymphocytes circulating in the blood pool may reduce sensitivity, the present study was performed in which canine orthotopic cardiac transplants were evaluated in vivo. Immunosuppression was maintained with cyclosporine A (10-20 mg/kg/day) and prednisone (1 mg/kg/day) for 2 wk after transplantation. Subsequently, therapy was tapered. Five successful allografts were evaluated scintigraphically every 3 days after administration of 100-350 microCi 111In autologous lymphocytes. Correction for labeled lymphocytes circulating in the blood pool, but not actively sequestered in the allografts was accomplished by administering 3-6 mCi 99mTc autologous erythrocytes and employing a previously validated blood-pool activity correction technique. Cardiac infiltration of labeled lymphocytes was quantified as percent indium excess (%IE), scintigraphically detectable 111In in the transplant compared with that in blood, and results were compared with those of concomitantly performed endomyocardial biopsy. Scintigraphic %IE for hearts not undergoing rejection manifest histologically was 0.7 +/- 0.4. Percent IE for rejecting hearts was 6.8 +/- 4.0 (p less than 0.05). Scintigraphy detected each episode of rejection detected by biopsy. Scintigraphic criteria for rejection (%IE greater than 2 s.d. above normal) were not manifest in any study in which biopsies did not show rejection. Since scintigraphic results with 111In-labeled lymphocytes were concordant with biopsy results in orthotopic cardiac transplants, noninvasive detection of graft rejection in patients should be attainable with the approach developed.

  20. Welfare Assessment following Heterotopic or Orthotopic Inoculation of Bladder Cancer in C57BL/6 Mice.

    Science.gov (United States)

    Miller, Amy; Burson, Hannah; Söling, Ariane; Roughan, Johnny

    2016-01-01

    Few studies have assessed whether mice used as cancer models experience pain. Despite this possibility, the usual practice is to withhold analgesics as these are generally viewed as confounding. However, pain also alters cancer progression, so preventing it might not only be beneficial to welfare but also to study validity. Establishing the extent to which different cancer models result in pain is an important first step towards their refinement. We used conditioned place preference (CPP) testing and body-weight and behaviour analyses to evaluate the assumption that heterotopically implanted tumours result in less pain and fewer welfare concerns than those implanted orthotopically. C57Bl/6 mice received MB49Luc luciferase expressing bladder cancer cells or saline implanted subcutaneously or into the bladder. These tumour-bearing or control groups underwent 2 daily 45 minute conditioning trials to saline or morphine (2mg/kg) and then a 15 minute drug-free preference test on day 3 of a 3 day cycle, continuing until the study ended. Tumours were imaged and behaviour data obtained following preference tests. Development of preference for the morphine-paired chamber (morphine-seeking) was determined over time. Heterotopic tumour development had no effect on morphine-seeking, and although the restraint used for heterotopic inoculation caused greater initial weight losses than anaesthesia, these mice steadily gained weight and behaved comparatively normally throughout the study. Orthotopic tumour inoculation caused no initial weight losses, but over the final 7 days these mice became less active and lost more body weight than cancer-free controls. This indicated orthotopic implantation probably caused a more negative impact on welfare or conceivably pain; but only according to the current test methods. Pain could not be confirmed because morphine-seeking in the tumour-bearing groups was similar to that seen in controls. Imaging was not found to be an effective method of

  1. Monitoring Prostate Tumor Growth in an Orthotopic Mouse Model Using Three-Dimensional Ultrasound Imaging Technique

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    Jie Ni

    2016-02-01

    Full Text Available Prostate cancer (CaP is the most commonly diagnosed and the second leading cause of death from cancer in males in USA. Prostate orthotopic mouse model has been widely used to study human CaP in preclinical settings. Measurement of changes in tumor size obtained from noninvasive diagnostic images is a standard method for monitoring responses to anticancer modalities. This article reports for the first time the usage of a three-dimensional (3D ultrasound system equipped with photoacoustic (PA imaging in monitoring longitudinal prostate tumor growth in a PC-3 orthotopic NODSCID mouse model (n = 8. Two-dimensional and 3D modes of ultrasound show great ability in accurately depicting the size and shape of prostate tumors. PA function on two-dimensional and 3D images showed average oxygen saturation and average hemoglobin concentration of the tumor. Results showed a good fit in representative exponential tumor growth curves (n = 3; r2 = 0.948, 0.955, and 0.953, respectively and a good correlation of tumor volume measurements performed in vivo with autopsy (n = 8, r = 0.95, P < .001. The application of 3D ultrasound imaging proved to be a useful imaging modality in monitoring tumor growth in an orthotopic mouse model, with advantages such as high contrast, uncomplicated protocols, economical equipment, and nonharmfulness to animals. PA mode also enabled display of blood oxygenation surrounding the tumor and tumor vasculature and angiogenesis, making 3D ultrasound imaging an ideal tool for preclinical cancer research.

  2. Welfare Assessment following Heterotopic or Orthotopic Inoculation of Bladder Cancer in C57BL/6 Mice.

    Directory of Open Access Journals (Sweden)

    Amy Miller

    Full Text Available Few studies have assessed whether mice used as cancer models experience pain. Despite this possibility, the usual practice is to withhold analgesics as these are generally viewed as confounding. However, pain also alters cancer progression, so preventing it might not only be beneficial to welfare but also to study validity. Establishing the extent to which different cancer models result in pain is an important first step towards their refinement. We used conditioned place preference (CPP testing and body-weight and behaviour analyses to evaluate the assumption that heterotopically implanted tumours result in less pain and fewer welfare concerns than those implanted orthotopically. C57Bl/6 mice received MB49Luc luciferase expressing bladder cancer cells or saline implanted subcutaneously or into the bladder. These tumour-bearing or control groups underwent 2 daily 45 minute conditioning trials to saline or morphine (2mg/kg and then a 15 minute drug-free preference test on day 3 of a 3 day cycle, continuing until the study ended. Tumours were imaged and behaviour data obtained following preference tests. Development of preference for the morphine-paired chamber (morphine-seeking was determined over time. Heterotopic tumour development had no effect on morphine-seeking, and although the restraint used for heterotopic inoculation caused greater initial weight losses than anaesthesia, these mice steadily gained weight and behaved comparatively normally throughout the study. Orthotopic tumour inoculation caused no initial weight losses, but over the final 7 days these mice became less active and lost more body weight than cancer-free controls. This indicated orthotopic implantation probably caused a more negative impact on welfare or conceivably pain; but only according to the current test methods. Pain could not be confirmed because morphine-seeking in the tumour-bearing groups was similar to that seen in controls. Imaging was not found to be an

  3. Successful Treatment of Recurrent Primary Sclerosing Cholangitis after Orthotopic Liver Transplantation with Oral Vancomycin

    Directory of Open Access Journals (Sweden)

    Yinka K. Davies

    2013-01-01

    Full Text Available Primary sclerosing cholangitis (PSC is a progressive, cholestatic disease of the liver that is marked by inflammation of the bile ducts and damage to the hepatic biliary tree. Approximately 60–70% of patients also have inflammatory bowel disease and progression of PSC can lead to ulcerative colitis and cirrhosis of the liver. Due to limited understanding of the etiology and mechanism of PSC, the only existing treatment option is orthotopic liver transplantation (OLT; however, recurrence of PSC, after OLT is estimated to be between 5% and 35%. We discuss the successful treatment of a pediatric patient, with recurrent PSC, after OLT with oral Vancomycin.

  4. Improvements of Surgical Technique in Establishment of Rat Orthotopic Pulmonary Transplantation Model Using Cuffs

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    In order to establish more simple and effective rat orthotopic lung transplantation models, 20 rats were divided into donor and recipient groups. Rat lung transplantation models were established by using improved cuff technique. All the 10 operations were accomplished successfully.The mean operative time of recipients was 45±4 min. The survival time was over 30 days after lung transplantation. The checks of X-ray were almost ncrmal. There was no significant difference in the blood gas analysis before and after clipping the right hilum (P>. 05). This method is more simple,applicable and requires less time.

  5. 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.

  6. Giant hepatocellular adenoma; case report

    Energy Technology Data Exchange (ETDEWEB)

    Pitella, F.A.; Coutinho, A.M.N.; Coura Filho, G.B.; Costa, P.L.A.; Ono, C.R.; Watanabe, T.; Sapienza, M.T.; Hironaka, F.; Cerri, G.G.; Buchpiguel, C.A. [Universidade de Sao Paulo (FM/USP), SP (Brazil). Inst. de Radiologia. Servico de Medicina Nuclear

    2008-07-01

    Full text: Introduction: Hepatocellular adenoma is a benign hepatic tumor identified mainly in women during fertility age, with estimated incidence of 4/1000 inhabitants. It is usually unique, well circumscribed, with or without a capsule, size varying from 1 to 30 cm, with possible central areas of necrosis and hemorrhage. Case Report: A 37-year-old female patient presenting with no comorbities, use of hormonal birth control pills for 18 years, a condition of reduction in the consistency of feces, increase in number of daily defecations, abdominal cramps, and a stuffed sensation after meals for two years. A palpable abdominal mass extending from the right hypochondriac to the right iliac fossa was noticed four months ago. A computerized tomography (CT) showed an extensive hepatic mass on the right which was considered, within the diagnostic hypotheses, hepatic adenomatosis, without ruling out secondary lesions. A hepatic scintillography with {sup 99m}Tc-DISIDA showed an extensive exophytic area from segment V to the right iliac fossa with arterialized blood flow and hepatocytic activity, as well as a hepatic nodule in segment VII with hepatocytic activity consistent with the hepatic adenomas hypothesis. The biopsy confirmed the hepatic adenoma diagnosis and the patient was submitted to a partial hepatectomy and cholecystectomy with good clinical evolution. Conclusion: Nuclear Medicine may supplement the assessment of hepatic nodules, including giant masses, thus suggesting new hypotheses and direction to therapeutic conduct. (author)

  7. Interventional treatments for hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    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.

  8. Term Effect of Arsenic Trioxide Treatment of Advanced Hepatocellular Carcinoma%三氧化二砷治疗中晚期原发性肝癌的近期疗效

    Institute of Scientific and Technical Information of China (English)

    林志宇; 马闻; 付榆; 乔青; 宿向东

    2014-01-01

    Objective To study the clinical therapeutic effects and the side effects of arsenic trioxide(As2O3)when used to treat middle or advanced primary hepatocellular carcinoma by interventional ways. Methods 33 cases with single agent arsenic trioxide 10 mg/d and saline infusion for 14 d for 1 cycles, 2 weeks intermittent, at least 2 cycles. Results All the 4 patients with PR, 22 cases of NC, 7 cases of PD, the efifciency of 12%. Clinical beneift rate:78.8%;pain relief rate was 82.7%, the quality of life of patients with 81.8% increase; adverse reaction of the treatment mainly Ⅰ to Ⅱ gastrointestinal reaction and hematologic toxicity, liver function impairment mild. Conclusion Arsenic trioxide in the treatment of middle or advanced primary hepatocellular carcinoma have the good curative effect, less adverse reaction, is a good choice for l hepatocellular carcinoma treatment, worthy of clinical application.%目的:观察三氧化二砷治疗中晚期原发性肝癌的近期疗效及不良反应。方法对33例采用单药三氧化二砷10mg/d加入生理盐水静脉滴注连续14d为1个周期,间歇2周,至少使用2个周期。结果全组4例PR,22例NC,7例PD,客观有效率12%。临床受益率:78.8%;疼痛缓解率为82.7%,81.8%患者生存质量提高;该治疗方案不良反应主要表现为Ⅰ~Ⅱ度胃肠道反应和血液学毒性,轻度的肝功能损害。结论三氧化二砷治疗中晚期原发性肝癌有较好疗效,不良反应较小,是肝癌治疗用药的较佳选择,值得临床推广。

  9. 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...

  10. 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

  11. Hepatocellular carcinoma: epidemiology and risk factors

    Directory of Open Access Journals (Sweden)

    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

  12. 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.

  13. 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

  14. 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

  15. Monitoring Prostate Tumor Growth in an Orthotopic Mouse Model Using Three-Dimensional Ultrasound Imaging Technique.

    Science.gov (United States)

    Ni, Jie; Cozzi, Paul; Hung, Tzong-Tyng; Hao, Jingli; Graham, Peter; Li, Yong

    2016-02-01

    Prostate cancer (CaP) is the most commonly diagnosed and the second leading cause of death from cancer in males in USA. Prostate orthotopic mouse model has been widely used to study human CaP in preclinical settings. Measurement of changes in tumor size obtained from noninvasive diagnostic images is a standard method for monitoring responses to anticancer modalities. This article reports for the first time the usage of a three-dimensional (3D) ultrasound system equipped with photoacoustic (PA) imaging in monitoring longitudinal prostate tumor growth in a PC-3 orthotopic NODSCID mouse model (n = 8). Two-dimensional and 3D modes of ultrasound show great ability in accurately depicting the size and shape of prostate tumors. PA function on two-dimensional and 3D images showed average oxygen saturation and average hemoglobin concentration of the tumor. Results showed a good fit in representative exponential tumor growth curves (n = 3; r(2) = 0.948, 0.955, and 0.953, respectively) and a good correlation of tumor volume measurements performed in vivo with autopsy (n = 8, r = 0.95, P model, with advantages such as high contrast, uncomplicated protocols, economical equipment, and nonharmfulness to animals. PA mode also enabled display of blood oxygenation surrounding the tumor and tumor vasculature and angiogenesis, making 3D ultrasound imaging an ideal tool for preclinical cancer research.

  16. Longterm outcomes of auxiliary partial orthotopic liver transplantation in preadolescent children with fulminant hepatic failure.

    Science.gov (United States)

    Weiner, Joshua; Griesemer, Adam; Island, Eddie; Lobritto, Steven; Martinez, Mercedes; Selvaggi, Gennaro; Lefkowitch, Jay; Velasco, Monica; Tryphonopoulos, Panagiotis; Emond, Jean; Tzakis, Andreas; Kato, Tomoaki

    2016-04-01

    By preserving part of the native liver, auxiliary partial orthotopic liver transplantation (APOLT) provides the advantage of potential immunosuppression (ISP) withdrawal if the native liver recovers but has had limited acceptance, especially in the United States, due to technical complications and low rates of native liver regeneration. No previous study has evaluated APOLT specifically for preadolescent children with fulminant hepatic failure (FHF). This population might benefit especially based on greater capacity for liver regeneration. Data from 13 preadolescent children who underwent APOLT were compared to 13 matched controls who underwent orthotopic liver transplantation (OLT) for FHF from 1996 to 2013. There were no significant differences in patient demographics or survival between the 2 groups. However, all surviving OLT recipients (10/13) remain on ISP, while all but 1 surviving APOLT recipient (12/13) showed native liver regeneration, and the first 10 recipients (76.9%) are currently off ISP with 2 additional patients currently weaning. In our experience, APOLT produced excellent survival and high rates of native liver regeneration in preadolescent children with FHF. This represents the largest series to date to report such outcomes. Liberating these children from lifelong ISP without the downside of increased surgical morbidity makes APOLT an attractive alternative. In conclusion, we therefore propose that, with the availability of technical expertise and with the technical modifications above, APOLT for FHF should be strongly considered for preteenage children with FHF.

  17. Pseudomyxoma peritonei – two novel orthotopic mouse models portray the PMCA-I histopathologic subtype

    Directory of Open Access Journals (Sweden)

    Wiig Johan N

    2007-06-01

    Full Text Available Abstract Background Pseudomyxoma peritonei (PMP is a rare malignant disease, most commonly originating from appendiceal lesions and characterized by accumulation of mucinous tumor tissue in the peritoneal cavity. Since the disease is infrequent, the task of carrying out studies of treatment efficacy and disease biology in the clinical setting is challenging, warranting the development of relevant in vitro and in vivo PMP models. Methods Human tumor tissue was implanted in the peritoneal cavity of nude mice to establish two orthotopic models exhibiting noninvasive intraperitoneal growth without metastasis development. Results Xenograft tissues have retained essential properties of the original human tumors, such as macro- and microscopic growth patterns, mucin production as well as expression of carcinoembryonal antigen, cytokeratins 20 and 7 and the proliferation marker pKi67. Upon microscopic examination, the human tumors were categorized as the PMCA-I (peritoneal mucinous carcinomatosis of intermediate features subtype, which was conserved through 14 examined passages in mice, for the first time modeling this particular histopathologic category. Conclusion In conclusion, two novel orthotopic models of human PMP have been established that consistently portray a distinct histopathologic subtype and reflect essential human tumor properties. Xenografts can easily and reproducibly be transferred to new generations of mice with acceptable passage periods, rendering the models as attractive tools for further studies of PMP biology and treatment.

  18. MUC1 selectively targets human pancreatic cancer in orthotopic nude mouse models.

    Directory of Open Access Journals (Sweden)

    Jeong Youp Park

    Full Text Available The goal of this study was to determine whether MUC1 antibody conjugated with a fluorophore could be used to visualize pancreatic cancer. Anti-MUC1 (CT2 antibody was conjugated with 550 nm or 650 nm fluorophores. Nude mouse were used to make subcutaneous and orthotopic models of pancreatic cancer. Western blot and flow cytometric analysis confirmed the expression of MUC1 in human pancreatic cancer cell lines including BxPC-3 and Panc-1. Immunocytochemistry with fluorophore conjugated anti-MUC1 antibody demonstrated fluorescent areas on the membrane of Panc-1 cancer cells. After injecting the conjugated anti-MUC1 antibodies via the tail vein, subcutaneously transplanted Panc-1 and BxPC-3 tumors emitted strong fluorescent signals. In the subcutaneous tumor models, the fluorescent signal from the conjugated anti-MUC1 antibody was noted around the margin of the tumor and space between the cells. The conjugated anti-MUC1 antibody bound the tumor in orthotopically-transplanted Panc-1 and BxPC-3 models enabling the tumors to be imaged. This study showed that fluorophore conjugated anti-MUC1 antibodies could visualize pancreatic tumors in vitro and in vivo and may help to improve the diagnosis and treatment of pancreatic cancer.

  19. Dose requirements of continuous infusion of rocuronium and atracurium throughout orthotopic liver transplantation in humans

    Institute of Scientific and Technical Information of China (English)

    WENG Xiao-chuan; ZHOU Liang; FU Yin-yan; ZHU Sheng-mei; HE Hui-liang; WU Jian

    2005-01-01

    Objective: To compare the dose requirements of continuous infusion of rocuronium and atracurium throughout orthotopic liver transplantation (OLT) in humans. Methods: Twenty male patients undergoing liver transplantation were randomly assigned to two comparable groups of 10 patients each to receive a continuous infusion of rocuronium or atracurium under itravenous balanced anesthesia. The response of adductor pollicis to train-of-four (TOF) stimulation of unlar nerve was monitored.The infusion rates of rocuronium and atracurium were adjusted to maintain T1/Tc ratio of 2%~10%. The total dose of each drug given during each of the three phases of OLT was recorded. Results: Rocuronium requirement, which were (0.468±0.167)unchanged during orthotopic liver transplantation. Conclusions: This study showed that the exclusion of the liver from the circulation results in the significantly reduced requirement of rocuronium while the requirement of atracurium was not changed,which suggests that the liver is of major importance in the clearance of rocuronium. A continuous infusion of atracurium with constant rate can provide stable neuromuscular blockade during the three stages of OLT.

  20. Neuroblastoma patient-derived orthotopic xenografts retain metastatic patterns and geno- and phenotypes of patient tumours.

    Science.gov (United States)

    Braekeveldt, Noémie; Wigerup, Caroline; Gisselsson, David; Mohlin, Sofie; Merselius, My; Beckman, Siv; Jonson, Tord; Börjesson, Anna; Backman, Torbjörn; Tadeo, Irene; Berbegall, Ana P; Ora, Ingrid; Navarro, Samuel; Noguera, Rosa; Påhlman, Sven; Bexell, Daniel

    2015-03-01

    Neuroblastoma is a childhood tumour with heterogeneous characteristics and children with metastatic disease often have a poor outcome. Here we describe the establishment of neuroblastoma patient-derived xenografts (PDXs) by orthotopic implantation of viably cryopreserved or fresh tumour explants of patients with high risk neuroblastoma into immunodeficient mice. In vivo tumour growth was monitored by magnetic resonance imaging and fluorodeoxyglucose-positron emission tomography. Neuroblastoma PDXs retained the undifferentiated histology and proliferative capacity of their corresponding patient tumours. The PDXs expressed neuroblastoma markers neural cell adhesion molecule, chromogranin A, synaptophysin and tyrosine hydroxylase. Whole genome genotyping array analyses demonstrated that PDXs retained patient-specific chromosomal aberrations such as MYCN amplification, deletion of 1p and gain of chromosome 17q. Thus, neuroblastoma PDXs recapitulate the hallmarks of high-risk neuroblastoma in patients. PDX-derived cells were cultured in serum-free medium where they formed free-floating neurospheres, expressed neuroblastoma gene markers MYCN, CHGA, TH, SYP and NPY, and retained tumour-initiating and metastatic capacity in vivo. PDXs showed much higher degree of infiltrative growth and distant metastasis as compared to neuroblastoma SK-N-BE(2)c cell line-derived orthotopic tumours. Importantly, the PDXs presented with bone marrow involvement, a clinical feature of aggressive neuroblastoma. Thus, neuroblastoma PDXs serve as clinically relevant models for studying and targeting high-risk metastatic neuroblastoma.

  1. Neuroblastoma patient-derived orthotopic xenografts reflect the microenvironmental hallmarks of aggressive patient tumours.

    Science.gov (United States)

    Braekeveldt, Noémie; Wigerup, Caroline; Tadeo, Irene; Beckman, Siv; Sandén, Caroline; Jönsson, Jimmie; Erjefält, Jonas S; Berbegall, Ana P; Börjesson, Anna; Backman, Torbjörn; Øra, Ingrid; Navarro, Samuel; Noguera, Rosa; Gisselsson, David; Påhlman, Sven; Bexell, Daniel

    2016-06-01

    Treatment of high-risk childhood neuroblastoma is a clinical challenge which has been hampered by a lack of reliable neuroblastoma mouse models for preclinical drug testing. We have previously established invasive and metastasising patient-derived orthotopic xenografts (PDXs) from high-risk neuroblastomas that retained the genotypes and phenotypes of patient tumours. Given the important role of the tumour microenvironment in tumour progression, metastasis, and treatment responses, here we analysed the tumour microenvironment of five neuroblastoma PDXs in detail. The PDXs resembled their parent tumours and retained important stromal hallmarks of aggressive lesions including rich blood and lymphatic vascularisation, pericyte coverage, high numbers of cancer-associated fibroblasts, tumour-associated macrophages, and extracellular matrix components. Patient-derived tumour endothelial cells occasionally formed blood vessels in PDXs; however, tumour stroma was, overall, of murine origin. Lymphoid cells and lymphatic endothelial cells were found in athymic nude mice but not in NSG mice; thus, the choice of mouse strain dictates tumour microenvironmental components. The murine tumour microenvironment of orthotopic neuroblastoma PDXs reflects important hallmarks of aggressive and metastatic clinical neuroblastomas. Neuroblastoma PDXs are clinically relevant models for preclinical drug testing.

  2. Orthotopic ileal neobladder reconstruction for bladder cancer: is adjuvant chemotherapy safe?

    Directory of Open Access Journals (Sweden)

    Murugesan Manoharan

    2006-10-01

    Full Text Available OBJECTIVE: We examined our database of patients undergoing radical cystectomy (RC with orthotopic neobladder (NB to determine whether adjuvant chemotherapy in this group is safe. MATERIALS AND METHODS: We performed a retrospective analysis of patients who underwent radical cystectomy and urinary diversion between 1992 and 2004. Relevant clinical and therapeutic data were entered into a database. High-risk bladder cancer patients who underwent NB were identified. They were stratified into 2 groups, those who received adjuvant chemotherapy and those who did not. The incidence of complications between the 2 groups was analyzed and compared. RESULTS: Over the 12-year period, 136 patients underwent RC and NB construction for bladder cancer. Of these, 83 patients were at high risk for recurrence. Nineteen patients received adjuvant chemotherapy and 64 did not. The complication rate in the adjuvant chemotherapy group was 53% and it was 23% in those who did not receive chemotherapy. There were no perioperative or treatment related death. There were 2 patients with grade 4 toxicity in the adjuvant chemotherapy group. There was a statistical difference between these two groups with regard to the incidence of complications. However, none of these complications was life-threatening, required only conservative treatment and caused no long-term disability. CONCLUSIONS: Adjuvant chemotherapy is a safe treatment for patients undergoing RC and NB substitution. Hence, the option of orthotopic NB should not be denied in selected bladder cancer patients with high risk for recurrent disease.

  3. An improved intrafemoral injection with minimized leakage as an orthotopic mouse model of osteosarcoma

    Science.gov (United States)

    Sasaki, Hiromi; Iyer, Swathi V.; Sasaki, Ken; Tawfik, Ossama W.; Iwakuma, Tomoo

    2015-01-01

    Osteosarcoma, the most common type of primary bone cancer, is the second highest cause of cancer-related death in pediatric patients. To understand the mechanisms behind osteosarcoma progression and to discover novel therapeutic strategies for this disease, a reliable and appropriate mouse model is essential. For this purpose, osteosarcoma cells need to be injected into the bone marrow. Previously, the intratibial and intrafemoral injection methods were reported; however, the major drawback of these methods is the potential leakage of tumor cells from the injection site during or after these procedures. To overcome this, we have established an improved method to minimize leakage in an orthotopic mouse model of osteosarcoma. By taking advantage of the anatomical benefits of the femur with less bowing and larger medullary cavity than those of the tibia, osteosarcoma cells are injected directly into the femoral cavity following reaming of its intramedullary space. To prevent potential leakage of tumor cells during and after the surgery, the injection site is sealed with bone wax. This method requires a minor surgery of approximately 15 minutes under anesthesia. Our established orthotopic osteosarcoma model could serve as a valuable and reliable tool for examining tumor progression of various types of bone tumors. PMID:26142221

  4. 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.

  5. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  7. 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.)

  8. Genotype phenotype classification of hepatocellular adenoma

    Institute of Scientific and Technical Information of China (English)

    Paulette Bioulac-Sage; Jean Frédéric Blanc; Sandra Rebouissou; Charles Balabaud; Jessica Zucman-Rossi

    2007-01-01

    Studies that compare tumor genotype with phenotype have provided the basis of a new histological/molecular classification of hepatocellular adenomas. Based on two molecular criteria (presence of a TCF1/HNF1α or β-catenin mutation), and an additional histological criterion (presence or absence of an inflammatory infiltrate), subgroups of hepatocellular adenoma can be defined and distinguished from focal nodular hyperplasia. Analysis of 96 hepatocellular adenomas performed by a French collaborative network showed that they can be divided into four broad subgroups: the first one is defined by the presence of mutations in TCF1 gene inactivating the hepatocyte nuclear factor 1 (HNF1α); the second by the presence of β-catenin activating mutations; the category without mutations of HNF1α or β-catenin is further divided into 2 subgroups depending on the presence or absence of inflammation. Therefore, the approach to the diagnosis of problematic benign hepatocytic nodules may be entering a new era directed by new molecular information. It is hoped that immunohistological tools will improve significantly diagnosis of liver biopsy in our ability to distinguish hepatocellular adenoma from focal nodular hyperplasia (FNH), and to delineate clinically meaningful entities within each group to define the best clinical management. The optimal care of patients with a liver nodule will benefit from the recent knowledge coming from molecular biology and the combined expertise of hepatologists, pathologists, radiologists, and surgeons.

  9. 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

  10. 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

  11. Inhibition of tumor growth and metastasis with antisense oligonucleotides(Cantide) targeting hTERT in an in situ human hepatocellular carcinoma model

    Institute of Scientific and Technical Information of China (English)

    Ru-xian LIN; Chao-wei TUO; Qiu-jun L(u); Wei ZHANG; Sheng-qi WANG

    2005-01-01

    Aim: To evaluate the in vivo antitumor effects of Cantide and the combined effect with 5-fluorouracil. Methods: An in situ human hepatocellular carcinoma model was established in mice livers orthotopically. Drugs were administered intravenously and tumor sizes were monitored with calipers. Plasma alpha-fetoprotein (AFP) were detected by radiation immunoassay. Morphology of tumors was evaluated by hematoxylin-eosin (H&E) staining of histological sections. Human telomerase reverse transcriptase (hTERT) protein levels were detected by Western blotting. Results: Cantide significantly inhibit in situ human hepatocellular compared to the saline group in a dose-dependent manner, which included injectthe tumor in liver. Cantide was also found to prevent tumor recurrence in the liver and metastasis in the lung, showing a dose-dependent response. When Cantide was administered by iv combined with 5-fluorouracil, it resulted in a significant reduction in tumor growth compared to either agent alone treatment group. After the treatment with Cantide alone or combined with 5-fluorouracil, plasma AFP concentration decreased in a dose-dependent manner. Conclusion: These results demonstrated that Cantide was an effective antitumor antisense oligonucleotide in vivo and has the potential to be developed into a clinical anti-cancer drug.

  12. 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.

  13. The orthotopic Fischer/AY-27 rat bladder urothelial cell carcinoma model to test the efficacy of different apaziquone formulations.

    NARCIS (Netherlands)

    Arentsen, H.C.; Hendricksen, K.; Hulsbergen- van de Kaa, C.A.; Reddy, G.; Oosterwijk, E.; Alfred Witjes, J.

    2012-01-01

    OBJECTIVES: Apaziquone used intravesically showed significant activity in phase I and II marker lesion studies in non-muscle-invasive bladder cancer. The objective of this study was to assess antitumor activity and safety of 3 different formulations of intravesical apaziquone in an orthotopic rat bl

  14. The influence of surgical technique on early posttransplant atrial fibrillation – comparison of biatrial, bicaval, and total orthotopic heart transplantation

    Science.gov (United States)

    Rivinius, Rasmus; Helmschrott, Matthias; Ruhparwar, Arjang; Erbel, Christian; Gleissner, Christian A; Darche, Fabrice F; Thomas, Dierk; Bruckner, Tom; Katus, Hugo A; Doesch, Andreas O

    2017-01-01

    Purpose Early posttransplant atrial fibrillation (AF) has been associated with worse clinical outcomes after heart transplantation (HTX). The type of surgical technique may constitute a relevant risk factor for AF. Patients and methods This retrospective single-center study included 530 adult patients. Patients were stratified by surgical technique (biatrial, bicaval, or total orthotopic HTX) and early posttransplant heart rhythm (AF or sinus rhythm). Univariate and multivariate analyses were performed to evaluate risk factors for AF. Results A total of 161 patients received biatrial HTX (30.4%), 115 bicaval HTX (21.7%), and 254 total orthotopic HTX (47.9%). Sixty-one of 530 patients developed early posttransplant AF (11.5%). Patients with AF showed a statistically inferior 5-year survival compared to those with sinus rhythm (Pvalvular heart disease (P=0.0372), posttransplant enlarged left atrium (P=0.0066), posttransplant mitral regurgitation (P=0.0370), and non-total orthotopic HTX (P=0.0112) as risk factors for AF. Conclusion Early posttransplant AF was associated with increased mortality (P<0.0001). Total orthotopic HTX showed the lowest rate of AF compared to biatrial or bicaval HTX (P=0.0012). PMID:28331331

  15. Expression of vascular endothelial growth factor and basic fibroblast growth factor in acute rejection reaction following rat orthotopic liver transplantation.

    Science.gov (United States)

    Zhang, Changsong; Yang, Guangshun; Lu, Dewen; Ling, Yang; Chen, Guihua; Zhou, Tianbao

    2014-08-01

    The aim of the present study was to investigate the expression levels of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in acute rejection reaction (ARR) following orthotopic liver transplantation in a rat model. Serum VEGF and bFGF levels were detected using ELISA, and their expression levels in liver and spleen tissues were determined using immunohistochemistry. The mRNA expression levels of VEGF and bFGF were detected by conducting a quantitative polymerase chain reaction during the ARR following orthotopic liver transplantation. The expression levels of VEGF and bFGF in the serum 3 days following liver transplantation were significantly higher compared with those in the other groups (1 and 7 days following transplantation; Pliver tissue that were shown to be positive for the expression VEGF and bFGF using immunohistochemistry were significantly higher 3 days following transplantation than at the other time points (Pspleen detected 3 days following the transplantation surgery were also significantly higher compared with those at the other time points (Pchanged dynamically, by peaking and then declining, in ARR following orthotopic liver transplantation. These changes may have an important impact on angiogenesis and the inflammatory reaction, and the identification of these changes increases the current understanding of ARR following orthotopic liver transplantation.

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

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  12. Study of orthotopic transplantation model of human gastrointestinal cancerand detection of micrometastases

    Institute of Scientific and Technical Information of China (English)

    Jun Hui Cui; Uwe Krueger; Doris Henne-Bruns; Bernd Kremer; Holger Kalthoff

    2000-01-01

    AIM To establish a relevant animal model of human gastrointestinal cancer, which can be used forrepetitive investigations and may improve our understanding of carcinogenesis and cancer metastasis.METHODS Intact tissue of human colorectal and pancreatic cancers was transplanted in nude mice. Thebiological characteristics of the original and corresponding transplanted tumors were investigated by HEstaining, PAS staining and immunostaining. The metastases in livers and lungs of the nude mice wereinvestigated by immunostaining with biotinylated mab KL-1 and by RT-PCR using CK20 specific primers.RESULTS Nine of 16 surgical specimens grew in the nude mice subcutaneously and/or orthotopically (4 of6 colorectal and 5 of 10 pancreatic cancer). Tumor cell content of the specimens and freezing of tissuespecimens are important factors influencing the growth of transplanted tumor. In the group of fresh tumortissues with greater than 50% tumor cell content, transplantation rate was 100% (3 cases of pancreatic cancerand 3 cases of colorectal cancer). The orthotopically transplanted tumors resembled the original tumormorphologically and biologically, including TAA expression such as CEA by immunohistochemistry, andCEA level in the serum of mice. Ki-67 labeling index and the expression of TAA especially K-ras, 17-1A and RA-96, were associated with the potential of tumor growth in nude mice. Micrometastases in the lungs andlivers of tumor bearing mice could be detected by immunostaining with biotinylated mab KL-1 and CK20-sepcific RT-PCR.CONCLUSION An orthotopic transplantation model for human colon and pancreatic cancer in nude micehas been established. The sensitive detection methods with CK-immunohistochemistry and CK20-RT-PCRwere also established to study xenotransplanted human cancer and its metastatic cancer cells in the liver andlung of nude mice. This study may be helpful in understanding the mechanism of cancer metastasis and indeveloping new diagnostic methods and

  13. 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.

  14. Expansion of endothelial surface by an increase of vessel diameter during tumor angiogenesis in experimental hepatocellular and pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Eduard Ryschich; Eduard Schmidt; Sasa-Marcel Maksan; Ernst Klar; Jan Schmidt

    2004-01-01

    AIM: A low vessel density is a common feature of malignant tumors. We suggested that the expansion of vessel diameter might reconstitute the oxygen and nutritient's supply in this situation. The aim of the present study was to compare the number and diameter of blood vessels in pancreatic and liver carcinoma with normal tissue.METHODS: Tumor induction of pancreatic (DSL6A) or hepatocellular (Morris-hepatoma) carcinoma was performed in male Lewis (pancreatic cancer) and ACI (hepatoma) rats by an orthotopic inoculation of solid tumor fragments (pancreatic cancer) or tumor cells (hepatoma). Six weeks (pancreatic cancer) or 12 d (hepatoma) after tumor implantation, the tumor microvasculature as well as normal pancreatic or liver blood vessels were investigated by intravital microscopy. The number of perfused blood vessels in tumor and healthy tissue was assessed by computer-assisted image analysis.RESULTS: The vessel density in healthy pancreas (565±89n/mm2) was significantly higher compared to pancreatic cancer (116±36 n/mm2) (P<0.001). Healthy liver showed also a significantly higher vessel density (689±36 n/mm2) compared to liver carcinoma (286±32 n/mm2) (P<0.01). The comparison of diameter frequency showed a significant increase of vessel diameter in both malignant tumors compared to normal tissue (P<0.05).CONCLUSION: The expansion of endothelial cells during tumor angiogenesis is accompanied to a large extent by an increase of vessel diameter rather than by formation of new blood vessels. This may be a possible adaptive mechanism by which experimental pancreatic and hepatocellular cancers expand their endothelial diffusion surface of endothelium to compensate for inadequate neoangiogenesis.

  15. 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

  16. Perioperative changes of ventricular function and three indicators of myocardial injury during orthotopic liver transplantation

    Institute of Scientific and Technical Information of China (English)

    HEI Zi-qing; LIU De-zhao; LUO Chen-fang; LI Shang-rong; MA Wu-hua; LUO Gang-jian

    2006-01-01

    @@ Patients undergoing orthotopic liver transplantation may develop significant haemodynamic instability, especially during anhepatic phase and immediately after reperfusion of the graft. The haemodynamic instability may be caused directly by myocardial depression due to pathogenic substances released from the liver, or by acute blood loss.1 Creatine kinase(CK) and its MB fraction (CK-MB) are sensitive and specific indicators to reflect myocardial damage.2 Cardiac troponin I (cTnl) is a specific and sensitive marker of myocardial necrosis.3 This study assessed perioperative cardiac function using three indicators (CK,CK-MB,and CTnl) to evaluate perioperative myocardial damage.$4This study was supported by grants from the National Natural Science Foundation of China (No. 30271254) and Guangdong Medical Development Foundation (No. 2004B35001005).

  17. DOXORUBICIN-LOADED BORON-RICH POLYMER NANOPARTICLES FOR ORTHOTOPICALLY IMPLANTED LIVER TUMOR TREATMENT

    Institute of Scientific and Technical Information of China (English)

    Lu-zhong Zhang; Ya-jun Zhang; Wei Wu; Xi-qun Jiang

    2013-01-01

    The in vivo behaviors of doxorubicin (DOX)-loaded dextran-poly(3-acrylamidophenylboronic acid) (DextranPAPBA) nanoparticles (NPs) were studied.The DOX-loaded NPs had a narrowly distributed diameter of ca.74 nm and mainly accumulated in liver of tumor-bearing mice after intravenous injection as demonstrated by in vivo real-time near infrared fluorescent imaging.The DOX contents in various tissues were quantified and consisted well with the results of fluorescent imaging.The biodistribution pattern of DOX-loaded NPs encourages us to investigate their liver tumor treatment by using an orthotopically implanted liver tumor model,revealing that the DOX-loaded NPs formulation had better antitumor effect than free DOX.

  18. Life-Threatening Cardiac Tamponade Secondary to Chylopericardium Following Orthotopic Heart Transplantation-A Case Report.

    Science.gov (United States)

    Wierzbicki, Karol; Mazur, Piotr; Węgrzyn, Piotr; Kapelak, Bogusław

    2016-08-23

    Chylopericardium is a rare complication in cardiac surgery, and an extremely rare occurrence in patients following orthotopic heart transplantation (OHT), which, however, can lead to cardiac tamponade. Here we present a case of a 59-year-old man who underwent OHT and suffered from chylopericardium resulting in cardiac tamponade late in the postoperative course, despite the initially uneventful early postoperative period (decreasing blood drainage was observed directly after the procedure, and the drains were safely removed). After the diagnosis of chylopericardium was made, the conservative treatment was initiated, which turned out to be insufficient, and eventually invasive approach for the recurrence of tamponade secondary to chylopericardium was required. We discuss the available therapeutic options for chylopericardium and demonstrate the successful invasive therapeutic approach with use of the absorbable fibrin sealant patch.

  19. Orthotopic transplantation model of human gastrointestinal cancer and detection of micrometastases

    Institute of Scientific and Technical Information of China (English)

    Jun Hui Cui; Uwe Krueger; Doris Henne-Bruns; Bernd Kremer; Holger Kalthoff

    2001-01-01

    AIM To establish a relevant animal model ofhuman gastrointestinal cancer, which can beused for repetitive investigations, so as toimprove our understanding and management ofcarcinogenesis and cancer metastasis.METHODS Intact tissues of human colorectaland pancreatic cancers were transplanted innude mice. The biological characteristics of theoriginal and the corresponding transplantedtumors were investigated by HE staining, PASstaining and immunostaining. The metastases inthe livers and lungs of nude mice wereinvestigated by immunostaining withbiotinylated mab KL-1 and by RT-PCR using CK20specific primers.RESULTS There were totally 9 of 16 surgicalspecimens growing in nude mice subcutaneouslyand/.or orthotopically (4 of 6 colorectal and 5 of10 pancreatic cancer). Tumor cell content of thespecimens and freezing of tissue specimens areimportant factors influencing the growth oftransplanted tumor. In the group of fresh tumortissues with greater than 50% tumor cellcontent, the success rate of the transplantationwas 100% (3 cases of pancreatic cancer and 3cases of colorectal cancer). The orthotopicallytransplanted tumors resemble the original tumormorphologically and biologically, including TAAexpression such as CEA byimmunohistochemistry, and CEA level in theserum of mice. Ki-67 labeling index and theexpression of TAA especially K-ras, 17-lA andRA-96, are associated with the potential of tumorgrowth in nude mice. Micrometastases in thelungs and livers of tumor bearing mice can bedetected by immunostaining with biotinylatedmab KL-1 and CK20-specific RT-PCR.CONCLUSION An orthotopic transplantationmodel for human colon and pancreatic cancer innude mice has been set up. We have alsoestablished sensitive detection methods withCK-immunohistochemistry and CK20-RT-PCR tostudy xenotransplanted human cancer and itsmetastatic cancer cells in the liver and lung ofnude mice. This study may be helpful inunderstanding the mechanism of cancermetastasis and in developing new

  20. RNAi-mediated stathmin suppression reduces lung metastasis in an orthotopic neuroblastoma mouse model.

    Science.gov (United States)

    Byrne, F L; Yang, L; Phillips, P A; Hansford, L M; Fletcher, J I; Ormandy, C J; McCarroll, J A; Kavallaris, M

    2014-02-13

    Metastatic neuroblastoma is an aggressive childhood cancer of neural crest origin. Stathmin, a microtubule destabilizing protein, is highly expressed in neuroblastoma although its functional role in this malignancy has not been addressed. Herein, we investigate stathmin's contribution to neuroblastoma tumor growth and metastasis. Small interfering RNA (siRNA)-mediated stathmin suppression in two independent neuroblastoma cell lines, BE(2)-C and SH-SY5Y, did not markedly influence cell proliferation, viability or anchorage-independent growth. In contrast, stathmin suppression significantly reduced cell migration and invasion in both the neuroblastoma cell lines. Stathmin suppression altered neuroblastoma cell morphology and this was associated with changes in the cytoskeleton, including increased tubulin polymer levels. Stathmin suppression also modulated phosphorylation of the actin-regulatory proteins, cofilin and myosin light chain (MLC). Treatment of stathmin-suppressed neuroblastoma cells with the ROCKI and ROCKII inhibitor, Y-27632, ablated MLC phosphorylation and returned the level of cofilin phosphorylation and cell invasion back to that of untreated control cells. ROCKII inhibition (H-1152) and siRNA suppression also reduced cofilin phosphorylation in stathmin-suppressed cells, indicating that ROCKII mediates stathmin's regulation of cofilin phosphorylation. This data demonstrates a link between stathmin and the regulation of cofilin and MLC phosphorylation via ROCK. To examine stathmin's role in neuroblastoma metastasis, stathmin short hairpin RNA (shRNA)\\luciferase-expressing neuroblastoma cells were injected orthotopically into severe combined immunodeficiency-Beige mice, and tumor growth monitored by bioluminescent imaging. Stathmin suppression did not influence neuroblastoma cell engraftment or tumor growth. In contrast, stathmin suppression significantly reduced neuroblastoma lung metastases by 71% (Pstathmin in hematogenous spread using a clinically

  1. 中药加味一贯煎提高原发性肝癌晚期患者生存率的临床研究%Clinical Study on Jiawei Yiguanjian for Improvement of the Survival Rate in Advanced Hepatocellular Carcinoma Patients

    Institute of Scientific and Technical Information of China (English)

    杨云柯; 仇冬则; 王国骅; 顾喜喜; 范越; 唐辰龙

    2011-01-01

    Objective:To evaluate the effect of Jiawei Yiguanjian on improving survival time and life quality in advanced hepato-cellular carcinoma( HCC) patients. Methods: A total of 100 patients (males 84,females 16) with advanced HCC of Zhongshan Hospital,Fudan university were randomized into two groups: The TCM therapy group and the control group. The control group received ordinary therapy while the treatment group received extra Jiawei Yiguanjian. The half-year survival rate,median survival time,quality of life score (Karnofsky),score of Eastern Cooperative Oncology Group(ECOG) and score of traditionnal chi-nese medical syndrome were compared between the two groups. Results: The half year survival rate with TCM therapy was 35. 80% and the median survival time was 114 days, and 21. 21% ,71days of the control group respectively. The difference was significant between the two groups(F<0. 05). There were much apparent differences in score of traditionnal Chinese medical syndrome, quality of life score (Karnofsky) and score of ECOG (P<0. 05). The TCM therapy group was better than control group at improving symptom,life quality and physical strength. Meanwhile, the mortality risk of advanced HCC patients was related to ECOG score and Child-Pugh score. The mortality increased significanT1y with the rise of the ECOG score and Child-Pugh score, the mortality rate increased 1. 8 times by adding one ECOG score and 1. 24 times by adding one Child-Pugh score. Conclusions; Using Jiawei Yiguanjian can increase the half-year survival rate and median survival time, improve the life quality and physical status of advanced HCC patients and reduce the score of traditionnal Chinese medical syndrome.%目的:探讨中药加味一贯煎在提高晚期肝癌患者生存期及改善生活质量方面的疗效.方法:将复旦大学附属中山医院的原发性肝癌患者100例(男性84例,女性16例)随机分成中药组和对照组,2组均进行常规保肝及对症治疗,中药

  2. Advances in understanding clinical significance of circulating tumor cells and cell-free DNA methylation in patients with hepatocellular carcinoma%循环肿瘤细胞及游离DNA甲基化在肝细胞癌患者中的研究进展

    Institute of Scientific and Technical Information of China (English)

    邱必军; 薛峰; 余坚; 夏强

    2012-01-01

    During the early formation and growth of a primary tumor, tumor cells can be detached from the primary tumor and circulate through the bloodstream to form circulating tumor cells (CTCs). Also during the early stage of tumor development, apoptotic and necrotic tumor cells can release DNA into the bloodstream to form circulating cell-free DNA. Therefore, analysis of CTCs and circulating cell-free DNA is considered as a real-time "liquid biopsy" for cancer patients. CTCs are very heterogeneous and can be enriched and detected using different technologies based on their physical and biological properties. The use of modern molecular biological techniques to extract the cell-free DNA in circulating blood and detect aberrant genetic and epigenetic alterations can provide valuable information for the early diagnosis, prediction of response to therapy, recurrence monitoring and prognosis evaluation in cancer patients. In this paper, we will give a review of recent advances in understanding the clinical significance of CTCs and cell-free DNA in patients with hepatocellular carcinoma.%随着对肿瘤认识的不断深入,人们发现在原发肿瘤形成和生长的早期阶段,肿瘤细胞即可以脱离原发肿瘤组织释放到外周血形成循环肿瘤细胞,同样在肿瘤形成的早期阶段就会出现肿瘤细胞的坏死和凋亡,这些凋亡或坏死的肿瘤细胞也可以释放其DNA入外周血形成血浆或血清游离的DNA,因此对肿瘤患者循环肿瘤细胞及游离DNA的分析被认为是实时的“液相活检”,肿瘤患者中的循环肿瘤细胞具有非常强的异质性,我们可以根据其物理和生物学性质采用不同的技术对其进行富集和检测;可以借助现代分子生物学手段对循环游离DNA进行提取,并对其遗传学和表观遗传学的异常改变进行分析,这可为肿瘤的早期诊断、疗效评估、复发监测及预后判断提供重要的信息.本文结合本课题组的研究重点,就循环肿

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. Liver transplantation for patients with hepatocellular carcinoma at the Liver Cancer Institute of Fudan University, China

    Institute of Scientific and Technical Information of China (English)

    ZHOU Jian; HE Yi-feng; YANG Guo-huan; SONG Kang; YUAN Zhou; WANG Yu-qi; TANG Zhao-you; FAN Jia; WU Zhi-quan; QIU Shuang-jian; HUANG Xiao-wu; YU Yao; WANG Zheng; SUN Jian; XIAO Yong-sheng

    2005-01-01

    Background Selection of patients with hepatocellular carcinoma (HCC) for orthotopic liver transplantation (OLT) remains controversial. Since there is a trend to expand the transplant criteria for HCC patients, we reviewed the data of patients with HCC who had received OLT at our institute to determine their survival and prognostic factors.Methods A total of 67 patients with HCC who had undergone OLT from April 2001 through December 2003 were reviewed retrospectively. Selection OLT candidates with HCC was dependent on the anatomical characteristics and/or the severity of underlying liver cirrhosis. The 67 patients were followed up for more than 6 months after transplantation. Their survival rate was calculated by the Kaplan-Meier method. Univariate and multivariate analyses using the Cox proportional hazards regression model were performed to reveal the factors affecting the survival rate.Results No perioperative death occurred in this series. The 1- and 2-year cumulative survival rates were 90.0% and 65.6%, and the disease-free survival (DFS) rates were 77.5% and 62.5% respectively. Univariate analysis revealed the tumor size, portal vein tumor thrombus (PVTT), serum alpha-fetoprotein level, bilobular distribution of tumors, pTNM stage and histological differentiation were statistically significant factors affecting the DFS (P<0.05). Multivariate analysis showed tumor size and PVTT were independent and statistically significant factors affecting the DFS (P=0.005 and 0.010, respectively). In this series, all but 2 received systemic chemotherapy, among them 13 had tumor recurrence within 8 months after OLT.Conclusions OLT is indicated for patients with HCC, even for some patients with end-stage liver disease who may survive longer without tumor recurrence. Adjuvant chemotherapy may decrease the recurrence of HCC after OLT.

  8. A single center experience: post-transplantation adjuvant chemotherapy impacts the prognosis of hepatocellular carcinoma patients

    Institute of Scientific and Technical Information of China (English)

    Wu Junyi; Sun Hongcheng; Han Zhongbo; Peng Zhihai

    2014-01-01

    Background The aim of this research was to investigate the impact of post-transplantation adjuvant chemotherapy in the prevention of tumor recurrence and metastasis for hepatocellular carcinoma (HCC) exceeding Milan criteria after liver transplantation.Methods A total of 117 patients with HCC exceeding the Milan criteria who had undergone orthotopic liver transplantation (OLT) from August 2002 to February 2009 were enrolled and retrospectively analyzed.The patients were divided into four groups according to chemotherapy regimens and the impact of different chemotherapy regimens on survival,disease-free survival,and adverse effects were compared.Results One year survival rates for the gemicitabine,conventional chemotherapy,oxaliplatin plus capecitabine and the best supportive care (BSC) group were 87.5%,84.2%,81.6%,and 67.5%.The 3-year survival rates were 48.1%,25.9%,31.6%,and 33.7%,respectively for the four groups.One year disease free survival rates for the four groups were 69.8%,47.4%,53.8%,and 45.7% respectively.And 3-year disease free survival rates were 43.2%,23.7%,23.6%,and 25.1% for the four groups.Stratification analysis showed that the gemcitabine regimen and conventional chemotherapy could significantly improve the survival rate and disease free survival rate for HCC patients who had major vascular invasion and/or microvascular invasion after liver transplantation compared with BSC group.Conclusions For HCC patients beyond Milan criteria,especially who had vascular invasion and/or micorvascular invasion,post-transplantation adjuvant chemotherapy can significantly improve survival.Gemcitabine is a proper regimen for postoperative adjuvant chemotherapy.Conventional chemotherapy can also benefit patients,but the adverse effects are not satisfactory.

  9. Expanded criteria for liver transplantation in patients with cirrhosis and hepatocellular carcinoma.

    Science.gov (United States)

    Silva, Mauricio; Moya, Angel; Berenguer, Marina; Sanjuan, Fernando; López-Andujar, Rafael; Pareja, Eugenia; Torres-Quevedo, Rodrigo; Aguilera, Victoria; Montalva, Eva; De Juan, Manuel; Mattos, Angelo; Prieto, Martín; Mir, José

    2008-10-01

    Orthotopic liver transplantation (OLT) selection for patients with hepatocellular carcinoma (HCC) is a matter of debate. The Milan criteria (MC) have been largely adopted by the international community. The main aim of this study was to evaluate the survival rates and recurrence probabilities of a new proposal for criteria (up to 3 tumors, each no larger than 5 cm, and a cumulative tumor burden

  10. Sorafenib inhibits growth and metastasis of hepatocellular carcinoma by blocking STAT3

    Institute of Scientific and Technical Information of China (English)

    Fang-Ming Gu; Quan-Lin Li; Qiang Gao; Jia-Hao Jiang; Xiao-Yong Huang; Jin-Feng Pan; Jia Fan; Jian Zhou

    2011-01-01

    AIM: To investigate the inhibitory role and the underlying mechanisms of sorafenib on signal transducer and activator of transcription 3 (STAT3) activity in hepatocellular carcinoma (HCC). METHODS: Human and rat HCC cell lines were treated with sorafenib. Proliferation and STAT3 dephosphorylation were assessed. Potential molecular mechanisms of STAT3 pathway inhibition by sorafenib were evaluated. In vivo antitumor action and STAT3 inhibition were investigated in an immunocompetent orthotopic rat HCC model. RESULTS: Sorafenib decreased STAT3 phosphorylation at the tyrosine and serine residues (Y705 and S727), but did not affect Janus kinase 2 (JAK2) and phospha-tase shatterproof 2 (SHP2), which is associated with growth inhibition in HCC cells. Dephosphorylation of S727 was associated with attenuated extracellular signal-regulated kinase (ERK) phosphorylation, similar to the effects of a mitogen-activated protein kinase (MEK) inhibitor U0126, suggesting that sorafenib induced S727 dephosphorylation by inhibiting MEK/ERK signaling. Meanwhile, sorafenib could also inhibit Akt phosphorylation, and both the phosphatidylinositol-3-kinase (PI3K) inhibitor LY294002 and Akt knockdown resulted in Y705 dephosphorylation, indicating that Y705 dephosphorylation by sorafenib was mediated by inhibiting the PI3K/Akt pathway. Finally, in the rat HCC model, sorafenib significantly inhibited STAT3 activity, reducing tumor growth and metastasis. CONCLUSION: Sorafenib inhibits growth and metastasis of HCC in part by blocking the MEK/ERK/STAT3 and PI3K/Akt/STAT3 signaling pathways, but independent of JAK2 and SHP2 activation.

  11. Asialoglycoprotein receptor-magnetic dual targeting nanoparticles for delivery of RASSF1A to hepatocellular carcinoma

    Science.gov (United States)

    Xue, Wan-Jiang; Feng, Ying; Wang, Fei; Guo, Yi-Bing; Li, Peng; Wang, Lei; Liu, Yi-Fei; Wang, Zhi-Wei; Yang, Yu-Min; Mao, Qin-Sheng

    2016-02-01

    We developed a nanovector with double targeting properties for efficiently delivering the tumor suppressor gene RASSF1A specifically into hepatocellular carcinoma (HCC) cells by preparing galactosylated-carboxymethyl chitosan-magnetic iron oxide nanoparticles (Gal-CMCS-Fe3O4-NPs). After conjugating galactose and CMCS to the surface of Fe3O4-NPs, we observed that Gal-CMCS-Fe3O4-NPs were round with a relatively stable zeta potential of +6.5 mV and an mean hydrodynamic size of 40.1 ± 5.3 nm. Gal-CMCS-Fe3O4-NPs had strong DNA condensing power in pH 7 solution and were largely nontoxic. In vitro experiments demonstrated that Gal-CMCS-Fe3O4-NPs were highly selective for HCC cells and liver cells. In vivo experiments showed the specific accumulation of Gal-CMCS-Fe3O4-NPs in HCC tissue, especially with the aid of an external magnetic field. Nude mice with orthotopically transplanted HCC received an intravenous injection of the Gal-CMCS-Fe3O4-NPs/pcDNA3.1(+)RASSF1A compound and intraperitoneal injection of mitomycin and had an external magnetic field applied to the tumor area. These mice had the smallest tumors, largest percentage of TUNEL-positive cells, and highest caspase-3 expression levels in tumor tissue compared to other groups of treated mice. These results suggest the potential application of Gal-CMCS-Fe3O4-NPs for RASSF1A gene delivery for the treatment of HCC.

  12. 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.

  13. 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 

  14. miR-592/WSB1/HIF-1α axis inhibits glycolytic metabolism to decrease hepatocellular carcinoma growth

    Science.gov (United States)

    Song, Ying; Liu, Mei-You; Yang, Xiao-Juan; Xue, Yan; Wen, Ai-Dong; Shi, Lei

    2016-01-01

    Hepatocellular carcinoma (HCC) cells rapidly switch their energy source from oxidative phosphorylation to glycolytic metabolism in order to efficiently proliferate. However, the molecular mechanisms responsible for this switch remain unclear. In this study, we found that miR-592 was frequently downregulated in human HCC tissues and cell lines, and its downregulation was closely correlated with aggressive clinicopathological features and poor prognosis of HCC patients. Overexpression of miR-592 inhibited aerobic glycolysis and proliferation in HCC cells in vitro. Conversely, knockdown of miR-592 promoted HCC growth in both subcutaneous injection and orthotopic liver tumor implantation models in vivo. Mechanistically, miR-592 downregulation in human HCCs was correlated with an upregulation of WD repeat and SOCS box containing 1 (WSB1). We further showed that miR-592 directly binds to the 3′-UTR of the WSB1 gene, thus disrupting hypoxia inducible factor-1α (HIF-1α) protein stabilization. In turn, overexpression of WSB1 in HCC cells rescued decreased HIF-1α expression, glucose uptake, and HCC growth induced by miR-592. Collectively, our clinical data and functional studies suggest that miR-592 is a new robust inhibitor of the Warburg effect and a promising therapeutic target for HCC treatment. PMID:27153552

  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. Orthotopic liver transplantation after successful treatment with anti-CD20 monoclonal antibody (rituximab) for severe steroid-resistant autoimmune hemolytic anemia: a case report.

    Science.gov (United States)

    Annicchiarico, B E; Siciliano, M; Avolio, A W; Agnes, S; Bombardieri, G

    2009-05-01

    Chronic hepatitis C virus (HCV) infection has been associated with a wide number of immunologic disorders, ranging from clinically silent laboratory abnormalities (eg, autoantibody positivity) to severe systemic diseases (eg, cryoglobulinemic vasculitis). Autoimmune hemolytic anemia (AIHA), due to the production of antibodies against erythrocyte membrane antigens, is an uncommon extrahepatic manifestation in the setting of chronic hepatitis C. Herein we have reported the case of a 57-year-old woman with decompensated HCV-related cirrhosis awaiting orthotopic liver transplantation (OLT) who experienced severe AIHA. After 1 month of treatment with prednisone (1 mg/kg body weight/d), there was no significant amelioration of anemia. Rituximab, an anti-CD20 monoclonal antibody that depletes B-lymphocytes reducing serum immunoglobulins, was initiated (375 mg/m(2) IV, weekly for 4 weeks) with a prompt, sustained increase in hemoglobin. The drug was well tolerated; it did not interfere with the course of the liver disease. Thirty-one months after rituximab therapy with resolution of AIHA, the patient successfully underwent OLT using immunosuppression with tacrolimus and low-dose steroids. The patient was discharged on postoperative day 36. No infectious event occurred in the postoperative period. At 18 months follow-up after OLT, there has been no infectious or hematological event. Our experience supported the safety of rituximab use in patients with advanced HCV-related liver disease before OLT.

  17. Gas gangrene caused by clostridium perfringens involving the liver, spleen, and heart in a man 20 years after an orthotopic liver transplant: a case report.

    Science.gov (United States)

    Kitterer, Daniel; Braun, Niko; Jehs, Margit C; Schulte, Bernhard; Alscher, M Dominik; Latus, Joerg

    2014-04-01

    Despite advances in immunosuppression and liver transplant in the past, mortality and morbidity caused by infections remain major problems. We present a 71-year-old man who was admitted to our internal intensive care unit with septicemia. Upon admission, he had poorly localized epigastric pain and fever of 2 days ' duration. Twenty years earlier, he had undergone an orthotopic liver transplant. Testing revealed a high C-reactive protein level, elevated liver enzymes, and an acute kidney injury. A computer tomography scan showed 2 circular, non--rim-enhancing, totally emphysematous intrahepatic lesions. Additionally, gas could be seen in the portal veins mainly, as well as in the biliary system, in the right auricle, and the splenic veins. To the best of our knowledge, he showed no malignant lesion or predisposing trauma. Empirically, treatment with broad-spectrum antibiotics was begun, and the patient was transferred to the operating suite. When surgery began, blood cultures revealed the presence of gram-positive bacilli, which were identified as Clostridium perfringens. Seven hours after the surgery, the patient developed asystole and died. In septic patients presenting with severe hemolysis, Clostridium perfringens infection must be considered in the absence of a malignant lesion or a predisposing trauma; a previous episode of gastroenteritis might be a predisposing trauma by impairing the barrier of the intestinal flora, leading to Clostridium perfringens infection.

  18. Five-year update on the mouse model of orthotopic lung transplantation: Scientific uses, tricks of the trade, and tips for success

    Science.gov (United States)

    Lin, Xue; Li, Wenjun; Lai, Jiaming; Okazaki, Mikio; Sugimoto, Seiichiro; Yamamoto, Sumiharu; Wang, Xingan; Gelman, Andrew E.; Kreisel, Daniel

    2012-01-01

    It has been 5 years since our team reported the first successful model of orthotopic single lung transplantation in the mouse. There has been great demand for this technique due to the obvious experimental advantages the mouse offers over other large and small animal models of lung transplantation. These include the availability of mouse-specific reagents as well as knockout and transgenic technology. Our laboratory has utilized this mouse model to study both immunological and non-immunological mechanisms of lung transplant physiology while others have focused on models of chronic rejection. It is surprising that despite our initial publication in 2007 only few other laboratories have published data using this model. This is likely due to the technical complexity of the surgical technique and perioperative complications, which can limit recipient survival. As two of the authors (XL and WL) have a combined experience of over 2500 left and right single lung transplants, this review will summarize their experience and delineate tips and tricks necessary for successful transplantation. We will also describe technical advances made since the original description of the model. PMID:22754663

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-04-15

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

  20. Effects of radiotherapy combined with transcatheter arterial chemoembolization on patients with advanced unresectable primary hepatocellular carcinoma%肝动脉栓塞化疗联合放疗治疗不能手术的原发性肝癌的临床观察

    Institute of Scientific and Technical Information of China (English)

    古金耀; 熊雪峰; 李道生

    2011-01-01

    目的 观察肝动脉栓塞化疗(TACE)联合直线加速器或全身伽玛刀治疗不能手术的原发性肝癌(PHC)的疗效及毒副反应.方法 2005年7月至2008年6月,108例不能手术的PHC患者中50例行TACE联合直线加速器放疗(加速器组),58例行TACE联合全身伽玛刀放疗(伽玛刀组).TACE灌注化疗药物包括丝裂霉素(MMC)10~20mg、氟尿嘧啶(5-FU)1000~1500mg、表阿霉素(E-ADM)30~50mg,栓塞剂为40%超液态碘化油5~20ml.直线加速器治疗用6MV-X,95%等剂量线包绕PTV,40~60Gy/15~25f,3~5f/周;伽玛刀治疗用月亮神立体定向伽玛射线旋转聚焦全身放射治疗系统(LUNATM-260),40%~60%等剂量线包绕PTV,单次剂量3~6Gy,3~5f/周,照射总量30~50Gy.联合应用TACE为1~3个疗程.结果 加速器组及伽玛刀组的中位生存期分别为14个月和16个月,中位肿瘤进展时间(TTP)分别为7.6个月和8.1个月;2年局部控制率分别为45.4%和43.6%(X2=0.020,P=0.887),3年局部控制率分别为36.5%和37.9%(X2=0.040,P=0.841);2年生存率分别为41.1%和39.6%(X2=0.021,P=0.885),3年生存率分别为34.3%和30.2%(X2=0.368,P=0.544).加速器组中出现1例放射诱发的肝病,伽玛刀组未见相关病例.结论 直线加速器和伽玛刀联合TACE治疗PHC均安全可靠,疗效相当.%Objective To evaluate the effects of transcatheter arterial chemoembolization (TACE) combined with radiation therapy on patients with advanced unresectable primary hepatocellular carcinoma ( PHC ). Methods From July 2005 to June 2008,108 patients with advanced unresectable PHC were divided into 2 groups. Fifty patients were treated with linear accelerator combined with TACE(accelerator group) , and 58 patients were treated with body gamma knife combined with TACE( gamma knife group). For accelerator group, 6MV-X ray was used, ≥95% isodose included PTV, and the total treatment dosage was 40-60Cy with 3-5 times per week. For gamma knife

  1. 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...

  2. 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

  3. Imaging exosome transfer from breast cancer cells to stroma at metastatic sites in orthotopic nude-mouse models.

    Science.gov (United States)

    Suetsugu, Atsushi; Honma, Kimi; Saji, Shigetoyo; Moriwaki, Hisataka; Ochiya, Takahiro; Hoffman, Robert M

    2013-03-01

    Exosomes play an important role in cell-to-cell communication to promote tumor metastasis. In order to image the fate of cancer-cell-derived exosomes in orthotopic nude mouse models of breast cancer, we used green fluorescent protein (GFP)-tagged CD63, which is a general marker of exosomes. Breast cancer cells transferred their own exosomes to other cancer cells and normal lung tissue cells in culture. In orthotopic nude-mouse models, breast cancer cells secreted exosomes into the tumor microenvironment. Tumor-derived exosomes were incorporated into tumor-associated cells as well as circulating in the blood of mice with breast cancer metastases. These results suggest that tumor-derived exosomes may contribute to forming a niche to promote tumor growth and metastasis. Our results demonstrate the usefulness of GFP imaging to investigate the role of exosomes in cancer metastasis.

  4. Overexpression of vascular endothelial growth factor C increases growth and alters the metastatic pattern of orthotopic PC-3 prostate tumors

    Directory of Open Access Journals (Sweden)

    Väänänen H Kalervo

    2009-10-01

    Full Text Available Abstract Background Prostate cancer metastasizes to regional lymph nodes and distant sites but the roles of lymphatic and hematogenous pathways in metastasis are not fully understood. Methods We studied the roles of VEGF-C and VEGFR3 in prostate cancer metastasis by blocking VEGFR3 using intravenous adenovirus-delivered VEGFR3-Ig fusion protein (VEGFR3-Ig and by ectopic expression of VEGF-C in PC-3 prostate tumors in nude mice. Results VEGFR3-Ig decreased the density of lymphatic capillaries in orthotopic PC-3 tumors (p p p p Conclusion The data suggest that even though VEGF-C/VEGFR3 pathway is primarily required for lymphangiogenesis and lymphatic metastasis, an increased level of VEGF-C can also stimulate angiogenesis, which is associated with growth of orthotopic prostate tumors and a switch from a primary pattern of lymph node metastasis to an increased proportion of metastases at distant sites.

  5. 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....

  6. Calvarial Mass Confused With Trichilemmal Cyst: Hepatocellular Cancer Metastasis.

    Science.gov (United States)

    Polat, Gökhan; Sade, Recep

    2017-03-01

    The hepatocellular cancer calvarial metastasis is a rare condition that commonly presents cranial swelling. Therefore, calvarial swelling may confuse with frequent lesions of the scalp. The authors' patient was operated as trichilemmal cyst. But, intracranial extension was seen in operation. Calvarial metastasis of hepatocellular cancer was observed by examination of the patient.

  7. 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.

  8. Carbon Monoxide Induces Cytoprotection in Rat Orthotopic Lung Transplantation via Anti-Inflammatory and Anti-Apoptotic Effects

    OpenAIRE

    Song, Ruiping; KUBO, Masatoshi; Morse, Danielle; Zhou, Zhihong; Zhang, Xuchen; Dauber, James H.; Fabisiak, James; Alber, Sean M.; Watkins, Simon C.; Zuckerbraun, Brian S.; Otterbein, Leo E.; Ning, Wen; Oury, Tim D; Patty J. Lee; McCurry, Kenneth R.

    2003-01-01

    Successful lung transplantation has been limited by the high incidence of acute graft rejection. There is mounting evidence that the stress response gene heme oxygenase-1 (HO-1) and/or its catalytic by-product carbon monoxide (CO) confers cytoprotection against tissue and cellular injury. This led us to hypothesize that CO may protect against lung transplant rejection via its anti-inflammatory and antiapoptotic effects. Orthotopic left lung transplantation was performed in Lewis rat recipient...

  9. Acute lower gastrointestinal bleeding from a dieulafoy lesion proximal to the anorectal junction post-orthotopic liver transplant

    Institute of Scientific and Technical Information of China (English)

    Wichian Apiratpracha; Jin Kee Ho; James J Powell; Eric M Yoshida

    2006-01-01

    A 67-year-old woman underwent an orthotopic liver transplantation for end stage liver disease secondary to chronic autoimmune hepatitis. She developed sudden massive hematochezia on post-operative day 23 with hemodynamic compromise. The source of hemorrhage was found at colonoscopy after careful irrigation and inspection to be a dieulafoy lesion situated just proximal to the anorectal junction. Hemostasis was achieved with epinephrine injection and thermal coagulation.

  10. 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...

  11. 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.

  12. 活体荧光成像对裸鼠肝癌细胞系MHCC97-H原位移植模型的动态量化分析%Dynamic and Quantitative Analysis of Orthotopically Transplanted Nude Mouse Model with MHCC97-H Cells using Bioluminescent Imaging Technology

    Institute of Scientific and Technical Information of China (English)

    曹阳; 韩炜; 刘洋; 张勇; 郭欣; 陈勇

    2013-01-01

    目的:利用生物自发光的裸鼠肝癌原位移植模型,以活体荧光成像技术对肝癌的生长和转移情况进行动态、量化分析.方法:将稳定转染了荧光素酶(luciferase)基因的人肝癌细胞株MHCC97-H-LUC细胞,移植至裸鼠肝脏包膜下,每周利用活体荧光成像系统对裸鼠体内移植瘤的生长部位和范围进行成像,测量肿瘤细胞生物发光量,动态观察肝癌细胞在裸鼠体内的肿瘤数量、生长速度和转移情况.结果:建立可稳定表达荧光素酶的人肝癌细胞株MHCC97-H-LUC并用于进行生物自发光的裸鼠原位移植模型;利用活体荧光成像系统对裸鼠体内的移植瘤成像,见发光部位由肝脏向腹腔扩散,发光量随时间呈指数级增长;病理学观察证实肿瘤细胞长.结论:利用活体荧光成像技术的动态量化分析可灵敏、准确地监测裸鼠肝癌原位移植模型中肿瘤细胞的生长及转移情况,为肿瘤发生、生长、转移机制及对抗肿瘤生长和转移的体内研究提供了科学的量化手段.%Objective: To investigate the growth and metastasis of hepatocellular carcinoma (HCC) dynamically and quantitatively in orthotopically transplanted nude mouse model for HCC by the mean of bioluminescent imaging technology. Method: Human hepatocellular carcinoma cell line MHCC97-H was stably transfected with luciferase gene and transplanted under the capsule of nude mice liver. The location and extent of transplanted tumors in nude mice was detected by using bioluminescent imaging system, and total photon flux emitting from tumor cells was measured weekly. The growth and metastasis of transplanted tumor in nude mice was detected dynamically and quantitatively. Results: Hepatocellular carcinoma cell line MHCC97-H-LUC, stably expressing luciferase, was established and it was used to build an orthotopically transplanted nude mouse model for HCC. By bioluminescent imaging, it was found that the lighting area spread

  13. Successful orthotopic liver transplantation in an adult patient with sickle cell disease and review of the literature

    Directory of Open Access Journals (Sweden)

    Morey Blinder

    2013-05-01

    Full Text Available Sickle cell disease can lead to hepatic complications ranging from acute hepatic crises to chronic liver disease including intrahepatic cholestasis, and iron overload. Although uncommon, intrahepatic cholestasis may be severe and medical treatment of this complication is often ineffective. We report a case of a 37 year-old male patient with sickle cell anemia, who developed liver failure and underwent successful orthotopic liver transplantation. Both pre and post-operatively, he was maintained on red cell transfusions. He remains stable with improved liver function 42 months post transplant. The role for orthotopic liver transplantation is not well defined in patients with sickle cell disease, and the experience remains limited. Although considerable challenges of post-transplant graft complications remain, orthotopic liver transplantation should be considered as a treatment option for sickle cell disease patients with end-stage liver disease who have progressed despite conventional medical therapy. An extended period of red cell transfusion support may lessen the post-operative complications.

  14. Efficacy of dietary antioxidants combined with a chemotherapeutic agent on human colon cancer progression in a fluorescent orthotopic mouse model.

    Science.gov (United States)

    Ma, Huaiyu; Das, Tapas; Pereira, Suzette; Yang, Zhijian; Zhao, Ming; Mukerji, Pradip; Hoffman, Robert M

    2009-07-01

    We report here the efficacy of dietary antioxidants in combination with chemotherapy on tumor growth in the orthotopic COLO-205-green fluorescent protein (GFP) human colon cancer mouse model. The orthotopically-transplanted nude mice used for the study were randomly divided into 5 groups (A-E) after surgical orthotopic implantation (SOI) of tumor tissue. The following diets were given: Diet A, modified AIN-93M mature rodent diet with 4% fish oil; Diet B, modified AIN-93M which contains added antioxidants vitamin A, vitamin E, and selenium at levels present in the standard AIN-93M diet; Diet C, Diet A without added antioxidants vitamin A, vitamin E, or selenium; Diet D, Diet A with 5 times the amount of added antioxidants vitamin A, vitamin E, and selenium present in Diet B. Cisplatin, 7 mg/kg, was administered intraperitoneally on day 16 after SOI. Throughout the course of treatment, noninvasive whole-body imaging, based on the GFP expression of the tumor, permitted visualization of tumor progression. At sacrifice, the mean tumor weights showed significant statistical differences in all of the treated groups compared to the negative control (no cisplatin treatment) (p cisplatin efficacy by high-dose antioxidants in combination with fish oil for colon cancer progression and suggests the design of clinical trials for this regimen.

  15. Reduced-size orthotopic liver transplantation with different grade steatotic grafts in rats

    Institute of Scientific and Technical Information of China (English)

    叶晟; 韩本立; 董家鸿

    2003-01-01

    Objective To explore the survival time, pathological change and liver regeneration in different kinds of reduced-size liver transplantation in rats using steatotic grafts. Methods Macrovesicular and microvesicular steatotic rat liver models were established by feeding rats with a diet consisting of 79% standard chow, 20% lard and 1% cholesterol for different time periods. With modified two cuff vascular anastomoses and end-to-end sutures on the bile duct, reduced-size orthotopic rat liver transplantations were performed in an attempt to explore the ratio of graft weight to recipient body weight, recipient original liver weight and histological and electron-microscopic findings in comparison with whole rat liver transplantations. Results A one-week survival rates for the rats undergoing whole liver transplantation, and those in the 70% reduced-size orthotopic liver transplantation (ROLT) group, the 60%ROLT group and the 50%ROLT group (grade Ⅰ macrosteatotic grafts) were 91.67%, 75%, 75% and 25%. A 2-week survival rate was 83.33%, 75%, 58.33% and 0 respectively. And their graft recipient body weight (GRBW) values SD were 3.56%±0.36%, 2.53%±0.15%, 2.28%±0.12% and 1.83%±0.16%, respectively. In grade Ⅱ macrosteatotic grafts, the one-week survival rate for those undergoiong whole liver transplantation and those in the 70% ROLT group was 83.33% and 25%. In the microsteatosis grafts for whole liver transplantation, 70% ROLT, 60% ROLT and 50% ROLT, the one-week survival rate was 83.33%, 75%, 75% and 33.33%; and the 2-week survival rate was 75%, 66.67%, 66.67% and 0, respectively. The survival rate of the 50% ROLT group using grade Ⅰ macrosteatotic grafts or grafts mainly with microsteatosis was significantly different from that of other groups. While using macrosteatotic grafts in grade Ⅱ, the 1-week survival rate of the 70% ROLT group was very poor. Pathological findings after operation included liver regeneration and portal space with mild lymphocyte

  16. Laparoscopic radical cystectomy with orthotopic ileal neobladder: report of 33 cases

    Institute of Scientific and Technical Information of China (English)

    HUANG Jian; XU Ke-wei; YAO You-sheng; GUO Zheng-hui; XIE Wen-lian; JIANG Chun; HAN Jin-li; LI Si-yao

    2005-01-01

    Background The laparoscopic radical cystectomy (LRC) with orthotopic ileal neobladder is now applied to treat invasive bladder cancer, however, it has not been well codified and illustrated. We describe in this paper a technique step by step that we have developed in 33 patients and achieved excellent results.Methods The surgical procedure can be divided into eight steps: laparoscopic pelvic lymphadenectomy and mobilization of the distal ureters; exposing Denonvillier's space and the posterior aspect of prostate; exposing retropubic space and anterior surface of the bladder; dividing the lateral pedicles of the bladder and the prostate; dividing the apex of the prostate; extracorporeal formation of the ileal pouch; extracorporeal implantation of the ureters; and laparoscopic urethra-neobladder anastomosis. This operation was performed in 33 patients, 29 males and 4 females, with muscle invasive bladder cancer between December 2002 and September 2004.Results The operating time was 5.5-8.5 hours with an average of 6.5 hours; the estimated blood loss was 200-1000 ml with an average of 460 ml. The surgical margins of the bladder specimen were negative in all patients. There was no evidence of local recurrence at follow-up of 1-21 months in all the patients. However lymph node metastases were found in one case at 9 months postoperatively. Most of patients achieved urine control 1 to 3 months after surgery. The daytime continence rate was 94% (31 cases) and nighttime continence rate was 88% (29 cases). Urodynamic evaluation was performed between 3 and 6 months postoperatively for all cases. The mean value of neobladder capacity was (296±37) ml. The mean value of maximum flow rate was (18.7±7.1) ml/s. The mean residual urine volume was (32±19) ml. In all cases, excretory urography at 1 to 2 months postoperatively demonstrated slightly dilated upper urinary tracts without ureteral obstruction, which resolved at follow up. Cystography showed neobladders being similar in

  17. The efficacy of transarterial chemoembolization plus Sorafenib for advanced hepatocellular carcinoma:a systematic review%肝动脉化疗栓塞联合索拉非尼治疗中晚期肝细胞癌疗效的系统评价

    Institute of Scientific and Technical Information of China (English)

    王洪良; 钟鉴宏; 马良; 游雪梅; 向邦德; 黎乐群

    2012-01-01

    Objective To evaluate the efficacy of transarterial chemoembolization(TACE)plus Sorafenib for patients with advanced hepatocellular carcinoma( HCC). Methods Electric databases, such as Cochrane library, MEDLINE,etc, were systematically searched until May 2012. Meta-analysis of randomized clinical trials( RCTs) and cohort studies was performed to estimate the effects of the TACE plus Sorafenib on overall survival( OS) . Risk ratios (RR) and 95% confidence intervals ( 95% CI) were calculated. Results A total of 2 RCTs and 3 cohort studies involving 307 patients were included. TACE combined with Sorafenib significantly improved the 6-months OS, with RR of 1. 13(95% CI 1. 03-1. 25). The 1-year OS and CBR were also increased, with RR of 1. 44(95% CI 1. 15-1.71), and 1.40(95% CI 1. 15-1. 71 ), respectively. The most common adverse reactions followed by sorafenib therapy were hand-foot skin reaction, hypertension, nausea, rash, diarrhea, anorexia, and alopecia. Conclusions TACE plus Sorafenib improve the short-term OS and clinical benefit rate for advanced HCC patients. However,this conclusions should be interpreted with caution. More extensive studies with larger sample sizes and longer follow-up are needed.%目的 评价肝动脉化疗栓塞(TACE)联合索拉非尼治疗中晚期肝癌的疗效.方法 计算机检索Cochrane图书馆临床对照试验资料库、MEDLINE、中国生物医学文献数据库(CBM)、中文科技期刊全文数据库(CNKI)和中国期刊全文数据库(VIP),截止到2012年5月.收集公开发表的关于TACE联合索拉非尼与TACE单一治疗或索拉非尼单药治疗的对照试验,对纳入的文献进行资料提取和质量评价,采用Revman 5.0软件进行统计分析.结果 5个研究共307例患者.TACE联合索拉非尼为试验组的半年生存率高于用TACE做单一治疗的对照组,差异有统计学意义(RR=1.13,95% CI 1.03~1.25,P=0.01).TACE联合索拉非尼为试验组的一年生存率高于用TACE做单一治疗的

  18. McMaster模式家庭干预对中晚期肝癌患者自我效能、心理及生活状态的调节作用%Regulation of McMaster model of family intervention on self-efficacy, psychological status and life quality in patients with advanced hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    刘娟; 苏美霞; 王丹; 杜晓娅

    2016-01-01

    Objective To analyze the regulation of McMaster model of family intervention on self-efficacy, psychological and living conditions in patients with advanced hepatocellular carcinoma (HCC). Methods A total of 106 patients with HCC in West China Hospital of Sichuan University from Jul. 2012 to Jul. 2014 were chosen as study subjects, which were divided into observation group and control group based on different interventions, each with 53 pa-tients. The control group applied routine clinical intervention, and the observation group used McMaster model of family in-tervention. General Self-efficacy Scale (GSES), Patient Activation Measure (PAM), Communication and Attitudinal Self-Ef-ficacy scale for cancer (CASE-cancer), Self-rated Abilities for Health Practices Scale (SRAHP) were used to evaluate the patients' self-efficacy, psychological status and life quality after intervention. Results (1) GSES score, PAM score, CASE-cancer score, SRAHP in the observation group after intervention were significantly higher than those in the con-trol group (P<0.05); (2) The somatic score, obsessive-compulsive symptoms score, interpersonal sensitivity score, de-pression score, anxiety score, hostility score, terror score, paranoid score, psychotic score in the observation group after intervention were significantly lower than those in the control group (P<0.05);(3) The physical activity score, physical function score, body pain score, general health status score, energy score, social function score, emotional function score, spiritual to establish score in the observation group after intervention were significantly higher than those in the control group (P<0.05). Conclusion McMaster model of family intervention applied in patients with advanced HCC can en-hance their self-efficacy, and optimize psychological status and the quality of life, which has a positive significance.%目的:分析McMaster模式家庭干预对中晚期肝癌患者自我效能、心理及生活状态

  19. 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

  20. 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.

  1. 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.

  2. Experimental models of small intestinal transplantation in rats: orthotopic versus heterotopic model.

    Directory of Open Access Journals (Sweden)

    Nakao A

    2002-04-01

    Full Text Available Two kinds of surgical models of small intestinal transplantation (SITx in rats, namely heterotopic (HIT and orthotopic transplantion (OIT, have been reviewed. In OIT, the small intestine of the recipient is removed and the transplanted intestine replaces it in continuity. On the other hand, in the HIT model, the small intestinal grafts are rendered dysfunctional without alimentary tract continuity. Histological evidence showed that acute rejection appeared earlier in HIT as compared to OIT. Hyperplasia and hypertrophy of the muscularis externa produced in the chronic rejection process were more pronounced in HIT allografts. The HIT grafts showed severe mucosal atrophy due to the lack of intraluminal trophic factors, because oral feedings can stimulate tropic hormones for mucosal growth, and provide nutrients for enterocytes. Intestinal permeability was consistently higher after HIT than after OIT. The HIT grafts demonstrated less contractility and less response to chemical stimulation than did OIT grafts. The OIT models are advantageous in studies of intraluminal nutrients, and intestinal secretions in these models might modulate the intestinal immune status and possibly delay rejection. The superior intestinal barrier function and the delayed onset of rejection in OIT rats suggest that nutrients and other factors in the succus entericus are important for the maintenance of intestinal graft function.

  3. A novel mucosal orthotopic murine model of human papillomavirus-associated genital cancers.

    Science.gov (United States)

    Decrausaz, Loane; Gonçalves, Ana-Rita; Domingos-Pereira, Sonia; Pythoud, Christelle; Stehle, Jean-Christophe; Schiller, John; Jichlinski, Patrice; Nardelli-Haefliger, Denise

    2011-05-01

    Cervical cancer results from infection with high-risk type human papillomaviruses (HPV). Therapeutic vaccines aiming at controlling existing genital HPV infections and associated lesions are usually tested in mice with HPV-expressing tumor cells subcutaneously implanted into their flank. However, effective vaccine-induced regression of these ectopic tumors strongly contrasts with the poor clinical results of these vaccines produced in patients with HPV-associated genital neoplasia. To assess HPV therapeutic vaccines in a more relevant setting, we have, here, established an orthotopic mouse model where tumors in the genital mucosa (GM) develop after an intravaginal instillation of HPV16 E6/E7-expressing tumor cells transduced with a luciferase-encoding lentiviral vector for in vivo imaging of tumor growth. Tumor take was 80-90% after nonoxynol-9 induced damage of the epithelium. Tumors remained localized in the genital tract, and histological analysis showed that most tumors grew within the squamous epithelium of the vaginal wall. Those tumors induced (i) E7-specific CD8 T cells restricted to the GM and draining lymph nodes, in agreement with their mucosal location and (ii) high Foxp3+ CD4+ infiltrates, similarly to those found in natural non-regressing HPV lesions. This novel genital HPV-tumor model by requiring GM homing of vaccine-induced immune responses able to overcome local immuno-suppression may be more representative of the situation occurring in patients upon therapeutic vaccination.

  4. Preliminary results of orthotopic en bloc uterus and ovary transplantation in the laboratory rat.

    Science.gov (United States)

    Motoc, A; Jiga, L; Ionac, M; Raica, M; Motoc, M; Chiovschi, S

    2003-01-01

    A new experimental model of whole uterus and ovary transplantation in the laboratory rat was achieved. The main goals of this study were concerned with developing and standardizing the microsurgical technique of uterus transplantation in rats and observing the particular cellular patterns of acute allograft rejection at the level of the transplanted graft. Thirty-five orthotopic uterus transplantations were performed. An additional 20 female rats were used for dissection training sessions. Recipients were euthanasied at 24 hours, 48 hours and 72 hours. Immediate postoperative survival was 100%. Patency of the microsurgical anastomoses, checked at 24 hours, was 100%. At 72 hours thrombosis occurred in all anastomoses. The explanted uterine grafts were fixed in formaline and analyzed under light microscopy and specific imunohistochemical analysis. The acute allograft rejection has a particular cellular reaction pattern, probably due to the unique diversity of the tissues that compose it. Inflammatory cells like LTCD8+, LBCD20+ and mastocytes tend to agglomerate in the vicinity of nervous and vascular structures, showing no signs of lymphoid tissue disposition like in typical acute rejection. Uterus transplantation in rats has proven to be a valid experiment that allows us to express hope that by further research on transplantation of the uterus gynecologists will be able to introduce an adapted technique in the treatment of specific cases of human female infertility.

  5. Preoperative risk factor analysis in orthotopic liver transplantation with pretransplant artificial liver support therapy

    Institute of Scientific and Technical Information of China (English)

    Jin-Zhong Yuan; Qi-Fa Ye; Ling-Ling Zhao; Ying-Zi Ming; Hong Sun; Shai-Hong Zhu; Zu-Fa Huang; Min-Min Wang

    2006-01-01

    AIM: To assess the value of pre-transplant artificial liver support in reducing the pre-operative risk factors relating to early mortality after orthotopic liver transplantation (OLT).METHODS: Fifty adult patients with various stages and various etiologies undergoing OLT procedures were treated with molecular adsorbent recycling system (MARS) as preoperative liver support therapy. The study included two parts, the first one is to evaluate the medical effectiveness of single MARS treatment with some clinical and laboratory parameters, which were supposed to be the therapeutical pre-transplant risk factors, the second part is to study the patients undergoing OLT using the regression analysis on preoperative risk factors relating to early mortality (30 d)after OLT.RESULTS: In the 50 patients, the statistically significant improvement in the biochemical parameters was observed (pre-treatment and post-treatment). Eight patients avoided the scheduled Ltx due to significant relief of clinical condition or recovery of failing liver function, 8 patients died, 34 patients were successfully bridged to Ltx, the immediate outcome of this 34patients within 30d observation was: 28 kept alive and 6patients died.CONCLUSION: Pre-operative SOFA, level of creatinine,INR, TNF-α, IL-10 are the main preoperative risk factors that cause early death after operation, MARS treatment before transplantion can relieve these factors significantly.

  6. Multi-factor analysis of initial poor graft function after orthotopic liver transplantation

    Institute of Scientific and Technical Information of China (English)

    Hao Chen; Cheng-Hong Peng; Bai-Yong Shen; Xia-Xing Deng; Chuan Shen; Jun-Jie Xie; Wei Dong; Hong-Wei Li

    2007-01-01

    BACKGROUND: In the early period of orthotopic liver transplantation (OLT), initial poor graft function (IPGF) is one of the complications which leads to primary graft non-function (PGNF) in serious cases. This study set out to establish the clinical risk factors resulting in IPGF after OLT. METHODS: Eighty cases of OLT were analyzed. The IPGF group consisted of patients with alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) above 1500 IU/L within 72 hours after OLT, while those in the non-IPGF group had values below 1500 IU/L. Recipient-associated factors before OLT analyzed were age, sex, primary liver disease and Child-Pugh classiifcation;factors analyzed within the peri-operative period were non-heart beating time (NHBT), cold ischemia time (CIT), rewarming ischemic time (RWIT), liver biopsy at the end of cold ischemia;and factors analyzed within 72 hours after OLT were ALT and/or AST values. A logistic regression model was applied to iflter the possible factors resulting in IPGF. RESULTS:Donor NHBT, CIT and RWIT were signiifcantly longer in the IPGF group than in the non-IPGF group;in the logistic regression model, NHBT was the risk factor leading to IPGF (P CONCLUSIONS:Longer NHBT is an important risk factor leading to IPGF, while serious steatosis in the donor liver, CIT and RWIT are potential risk factors.

  7. Internal jugular versus subclavian vein catheterization for central venous catheterization in orthotopic liver transplantation.

    Science.gov (United States)

    Torgay, A; Pirat, A; Candan, S; Zeyneloglu, P; Arslan, G; Haberal, M

    2005-09-01

    The aim of this study was to compare incidence rates of mechanical and infectious complications associated with central venous catheterization via the internal jugular vein (IJV) versus the subclavian vein (SV) among 45 consecutive patients undergoing orthotopic liver transplantation (OLT) between January 2000 and June 2004. The subjects were divided into two groups according to the site of central venous catheterization (IJV or SV). We recorded each patient's physical characteristics, international normalized ratio (INR), partial thromboplastin time, platelet levels, number of puncture attempts, success/failure of central venous catheterization, duration of catheter placement, occurrence of catheter tip misplacement, arterial puncture, incidence of hematoma or pneumothorax, catheter-related infection, or bacterial colonization of the catheter. Senior staff anesthesiologists performed 22 SV and 23 IJV catheterizations for the 45 OLT procedures. The SV and IVJ groups both had minor coagulation abnormalities with slightly increased INR values at the time of catheterization. There were no significant differences between the groups with respect to success of central venous catheterization (100% for both), numbers of attempted punctures, duration of catheter placement, and incidence rates of mechanical and infectious complications. Both groups showed high frequencies of catheter tip misplacement, with right atrium as the site of misplacement in all cases. Two patients in the IJV group (8.7%) developed hematomas after accidental carotid artery puncture. The results suggest that, when performed by experienced anesthesiologists, central venous catheterization via the SV is an acceptable alternative to IJV catheterization for patients undergoing OLT.

  8. Curcumin Inhibits Tumor Growth and Angiogenesis in an Orthotopic Mouse Model of Human Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Sabrina Bimonte

    2013-01-01

    Full Text Available Pancreatic cancer is a malignant neoplasm originating from transformed cells arising in tissues forming the pancreas. The best chemotherapeutic agent used to treat pancreatic cancer is the gemcitabine. However, gemcitabine treatment is associated with many side effects. Thus novel strategies involving less toxic agents for treatment of pancreatic cancer are necessary. Curcumin is one such agent that inhibits the proliferation and angiogenesis of a wide variety of tumor cells, through the modulation of many cell signalling pathways. In this study, we investigated whether curcumin plays antitumor effects in MIA PaCa-2 cells. In vitro studies showed that curcumin inhibits the proliferation and enhances apoptosis of MIA PaCa-2 cells. To test whether the antitumor activity of curcumin is also observed in vivo, we generated an orthotopic mouse model of pancreatic cancer by injection of MIA PaCa-2 cells in nude mice. We placed mice on diet containing curcumin at 0.6% for 6 weeks. In these treated mice tumors were smaller with respect to controls and showed a downregulation of the transcription nuclear factor NF-κB and NF-κB-regulated gene products. Overall, our data indicate that curcumin has a great potential in treatment of human pancreatic cancer through the modulation of NF-κB pathway.

  9. Liver biochemistry profile, significance and endoscopic management of biliary tract complications post orthotopic liver transplantation

    Institute of Scientific and Technical Information of China (English)

    Yogesh M Shastri; Nicolas M Hoepffner; Bora Akoglu; Christina Zapletal; Wolf O Bechstein; Wolfgang F Caspary; Dominik Faust

    2007-01-01

    AIA:To correlate the significance of liver biochemical tests in diagnosing post orthotopic liver transplantation (OLT) biliary complications and to study their profile before and after endoscopic therapy.METHODS: Patients who developed biliary complications were analysed in detail for the clinical information,laboratory tests, treatment offered, response to it,follow up and outcomes. The profile of liver enzymes was determined. The safety, efficacy and outcomes of endoscopic retrograde cholangiography (ERC) were also analysed.RESULTS: 40 patients required ERC for 70 biliary complications. GGT was found to be > 3 times (388.1± 70.9 U/mL vs 168.5 ± 34.2 U/L, P = 0.007) and SAP > 2 times (345.1 ± 59.1 U/L vs152.7 ± 21.4 U/L, P =0.003) the immediate post OLT values. Most frequent complication was isolated anastomotic strictures in 28 (40%).Sustained success was achieved in 26 (81%) patients.CONCLUSION: Biliary complications still remain an important problem post OLT. SAP and GGT can be used as early, non-invasive markers for diagnosis and also to assess the adequacy of therapy. Endoscopic management is usually effective in treating the majority of these biliary complications.

  10. Orthotopic Osteogenecity Enhanced by a Porous Gelatin Sponge in a Critical-Sized Rat Calvaria Defect.

    Science.gov (United States)

    Kanda, Naofumi; Anada, Takahisa; Handa, Takuto; Kobayashi, Kazuhito; Ezoe, Yushi; Takahashi, Tetsu; Suzuki, Osamu

    2015-12-01

    The gelatin (Gel) powders, derived from acidic and basic extractions of porcine dermis (referred to as AE and BE), were processed for the porous sponge preparation. The disks, which were less than or greater than 500 μm in diameter [small (S) and large (L) pores, respectively] in both extractions and had an interconnected structure respectively, were implanted in critical-sized defects (CSD) of rat calvaria for 4 and 8 weeks to analyze the bone repair capability. Only the AE-S disk induced bone formation (over 60%) histomorphometrically in the CSD after 8 weeks, although the collagen orientation of the regenerated bone was still immature. Osteoblastic cell culture until 14 days did not substantiate marked superiority of AE-S disk regarding the proliferation and the differentiation, although the initial attachment was enhanced on AE-S disk than BE-L disk. The results provide the findings that a Gel sponge with a specific porous structure is capable of inducing orthotopic bone formation in vivo environment.

  11. Uptake of verteporfin by orthotopic xenograft pancreas models with different levels of aggression

    Science.gov (United States)

    O'Hara, Julia; Samkoe, Kimberley S.; Chen, Alina; Hoopes, P. Jack; Rizvi, Imran; Hasan, Tayyaba; Pogue, Brian W.

    2009-06-01

    Pancreatic cancer is an aggressive disease with a poor prognosis, usually treated with chemoradiation therapy. Interstitial photodynamic therapy is a potentially effective adjuvant treatment that is under development. In the current study, two orthotopic pancreatic cancer models (AsPC-1 and Panc-1), have been characterized with respect to growth rates, morphology and liposomal drug (Verteporfin) uptake and distribution in SCID mice. Fluorescence of Verteporfin was measured in liver and tumor in vivo using a PDT fluorescence dosimeter with measurements taken before and up to one hour after tail vein injection. Fluorescence reached a plateau by about 15 minutes and did not decrease over the first hour. At time points from 15 minutes to 24 hrs, the internal organs (kidney, spleen, pancreas, tumor, muscle, lung, liver, and skin were excised and scanned on a Typhoon imager. The ratio of fluorescence in tumor versus normal tissues was analyzed with image processing, calculated at each time point and compared to in vivo results. Tissue distribution of Verteporfin in relation to functional vasculature marked by DiOc7 was carried out on frozen sections. Final analysis will result in determination of the ideal time point to administer light to achieve maximum tumor destruction while preserving normal tissue.

  12. Orthotopic urinary diversion after radical cystectomy in treatment of muscle invasive bladder cancer.

    Science.gov (United States)

    Jovan, Hadži-Djokić; Vladan, Andrejević; Tomislav, Pejčić; Miodrag, Aćimović; Uroš, Babić; Miodrag, Stanić; Zoran, Džamić

    2014-01-01

    Surgical treatment of invasive carcinoma of the bladder in males includes total cystectomy removal of the prostate, seminal vesicles, and the distal parts of the urethers and the pelvic lymph node dissection as well. At this moment it is not possible to recommend a particular type of urinary diversion, but today in clinical practice commonly used derivative are ileal orthotopic neobladder as the continent one and ileal conduit as non-continent urinary diversion. Continent urinary diversion after radical cystectomy are the result of the application of technological innovation in surgery, but also knowledge, imagination and skill of well trained urologist. This type of operation significantly improves the quality of life in patients who underwent radical cystectomy, and the proposal is to operate whenever there is a possibility for this type of procedure. Also it is very important, during surgery to respect oncological principles, of complete removal of tumorous tissue and that the functional principle of ensur- ing that the patients have daytime and also nighttime continence later on after the surgery.

  13. 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...

  14. Hepatocellular carcinoma: From diagnosis to treatment

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Hepatocellular carcinoma (HCC) is the sixth mostprevalent malignancy worldwide and is a rising causeof cancer related mortality. Risk factors for HCC arewell documented and effective surveillance and earlydiagnosis allow for curative therapies. The majority ofHCC appears to be caused by cirrhosis from chronichepatitis B and hepatitis C virus. Preventive strategiesinclude vaccination programs and anti-viral treatments.Surveillance with ultrasonography detects early stagedisease and improves survival rates. Many treatmentoptions exist for individuals with HCC and are determinedby stage of presentation. Liver transplantation is offeredto patients who are within the Milan criteria and arenot candidates for hepatic resection. In patients withadvanced stage disease, sorafenib shows some survivalbenefit.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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

  20. Hepatocellular Tumors: Immunohistochemical Analyses for Classification and Prognostication

    Institute of Scientific and Technical Information of China (English)

    Regina Cheuk-Lam Lo; Irene Oi-Lin Ng

    2011-01-01

    Following the classification of hepatocellular nodules by the International Working Party in 1995 and further elaboration by the International Consensus Group for Hepatocellular Neoplasia in 2009,entities under the spectrum of hepatocellular nodules have been better characterized.Research work hence has been done to answer questions such as distinguishing high-grade dysplastic nodules from early hepatocellular carcinoma (HCC),delineating the tumor cell origin of HCC,identifying its prognostic markers,and subtyping hepatocellular adenomas.As a result,a copious amount of data at immunohistochemical and molecular levels has emerged.A panel of immunohistochemical markers including glypican-3,heat shock protein 70 and glutamine synthetase has been found to be of use in the diagnosis of small,well differentiated hepatocellular tumors and particularly of HCC.The use of liver fatty acid binding protein (L-FABP),β-catenin,glutamine synthetase,serum amyloid protein and C-reactive protein is found to be helpful in the subtyping of hepatocellular adenomas.The role of tissue biomarkers for prognostication in HCC and the use of biomarkers in subclassifying HCC based on tumor cell origin are also discussed.

  1. 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

  2. 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.

  3. GPC-3 in hepatocellular carcinoma: current perspectives

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    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

  4. Recombinant VP1, an Akt inhibitor, suppresses progression of hepatocellular carcinoma by inducing apoptosis and modulation of CCL2 production.

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    Tai-An Chen

    Full Text Available BACKGROUND: The application of viral elements in tumor therapy is one facet of cancer research. Recombinant capsid protein VP1 (rVP1 of foot-and-mouth disease virus has previously been demonstrated to induce apoptosis in cancer cell lines. Here, we aim to further investigate its apoptotic mechanism and possible anti-metastatic effect in murine models of hepatocellular carcinoma (HCC, one of the most common human cancers worldwide. METHODOLOGY/PRINCIPAL FINDINGS: Treatment with rVP1 inhibited cell proliferation in two murine HCC cell lines, BNL and Hepa1-6, with IC₅₀ values in the range of 0.1-0.2 µM. rVP1 also induced apoptosis in these cells, which was mediated by Akt deactivation and dissociation of Ku70-Bax, and resulted in conformational changes and mitochondrial translocation of Bax, leading to the activation of caspases-9, -3 and -7. Treatment with 0.025 µM rVP1, which did not affect the viability of normal hepatocytes, suppressed cell migration and invasion via attenuating CCL2 production. The production of CCL2 was modulated by Akt-dependent NF-κB activation that was decreased after rVP1 treatment. The in vivo antitumor effects of rVP1 were assessed in both subcutaneous and orthotopic mouse models of HCC in immune-competent BALB/c mice. Intratumoral delivery of rVP1 inhibited subcutaneous tumor growth as a result of increased apoptosis. Intravenous administration of rVP1 in an orthotopic HCC model suppressed tumor growth, inhibited intra-hepatic metastasis, and prolonged survival. Furthermore, a decrease in the serum level of CCL2 was observed in rVP1-treated mice. CONCLUSIONS/SIGNIFICANCE: The data presented herein suggest that, via inhibiting Akt phosphorylation, rVP1 suppresses the growth, migration, and invasion of murine HCC cells by inducing apoptosis and attenuating CCL2 production both in vitro and in vivo. Recombinant protein VP1 thus has the potential to be developed as a new therapeutic agent for HCC.

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

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    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.

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

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    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

  7. 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.

  8. 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.

  9. 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

  10. Symptomatic osteonecrosis of the femoral head after adult orthotopic liver transplantation

    Institute of Scientific and Technical Information of China (English)

    LI Hua; CHEN Gui-hua; ZHANG Jian; HE Ji-wen; WANG Kun; WANG Gen-shu; JIANG Nan; FU Bin-sheng; WANG Guo-ying; YANG Yang

    2012-01-01

    Background With the increase of survival in liver transplantation recipients,more patients are at a high risk of developing osteonecrosis,especially in the femoral head,due to immunosuppressive treatment.The purpose of this study was to report the incidence,possible risk factors,and outcome of symptomatic osteonecrosis of the femoral head (ONFH) in adult patients with current immunosuppressive agents and individual protocol after liver transplantation in China.Methods A ratrospective analysis was performed on 226 adult patients who underwent orthotopic liver transplantation (OLT) at a single liver transplantation institution between January 2004 and December 2008.The posttransplant survival time (or pre-retransplantation survival time) of all the patients were more than 24 months.The possible pre- and post-transplantation risk factors of symptomatic ONFH were investigated and the curative effects of the treatment were also reported.Results The incidence of ONFH was 1.33% in patients after OLT.ONFH occurred at a mean of (14±6) months (range,10-21 months) after transplantation.Male patients more often presented with osteonecrosis as a complication than female patients.The patients with lower pre-transplantation total bilirubin and direct bilirubin levels (P <0.05).There was no difference in the cumulative dose of corticosteroids or tacrolimus between the patients with or without symptomatic ONFH.Patients were treated either pharmacologically or surgically.All patients showed a nice curative effect without major complications during the 18-63 months post-treatment follow up.Conclusions The symptomatic ONFH does not occur commonly after adult OLT in the current individual immunosuppressive protocol in China.

  11. Evaluation of pleth variability index as a predictor of fluid responsiveness during orthotopic liver transplantation.

    Science.gov (United States)

    Konur, Huseyin; Erdogan Kayhan, Gulay; Toprak, Huseyin Ilksen; Bucak, Nizamettin; Aydogan, Mustafa Said; Yologlu, Saim; Durmus, Mahmut; Yılmaz, Sezai

    2016-07-01

    Fluid management is challenging and still remains controversial in orthotopic liver transplantation (OLT). The pleth variability index (PVI) has been shown to be a reliable predictor of fluid responsiveness of perioperative and critically ill patients; however, it has not been evaluated in OLT. This study was designed to examine whether the PVI can reliably predict fluid responsiveness in OLT and to compare PVI with other hemodynamic indexes that are measured using the PiCCO2 monitoring system. Twenty-five patients were enrolled in this study. Each patient was monitored using the noninvasive Masimo and PiCCO2 monitoring system. PVI was obtained with a Masimo pulse oximeter. Cardiac index was obtained using a transpulmonary thermodilution technique (CITPTD). Stroke volume variation (SVV), pulse pressure variation, and systemic vascular resistance index were measured using the PiCCO2 system. Fluid loading (10 mL/kg colloid) was performed at two different phases during the operation, and fluid responsiveness was defined as an increase in CITPTD ≥ 15%. During the dissection phase and the anhepatic phase, respectively, 14 patients (56%) and 18 patients (75%) were classified as responders. There were no differences between the baseline values of the PVI of responders and nonresponders. Area under the curve for PVI was 0.56 (sensitivity 35%, specificity 90%, p = 0.58) at dissection phase, and was 0.55 (sensitivity 55%, specificity 66%, p = 0.58) at anhepatic phase. Of the parameters, a higher area under the curve value was found for SVV. We conclude that PVI was unable to predict fluid responsiveness with sufficient accuracy in patients undergoing OLT, but the SVV parameter was reliable.

  12. Characterization of gastric cancer models from different cell lines orthotopically constructed using improved implantation techniques

    Institute of Scientific and Technical Information of China (English)

    Yan Li; Bo Li; Chun-Ping Xiang; Yu Zhang; Yuan-Yuan Li; Xiao-Ling Wu

    2012-01-01

    AIM: To develop orthotopic gastric cancer mouse models from different cell lines and characterize the tumor features to assist further in preclinical trials and clinical treatment strategies. METHODS: Human gastric cancer SGC-7901 and BGC- 823 cell suspensions were injected subcutaneously into nude mice to develop solid tumors, and tumor tissue pieces were then implanted under the serous coat of the stomach. An autopsy was performed on all animals of the SGC-7901 and BGC-823 models to observe the primary tumor growth and metastases using pathological and immunohistochemical methods. RESULTS: Both models showed large tumors in situ resulting in pressure and infiltration of the adjacent organs. The gastric cavity became smaller, along with stenosis of the cardia or pylorus. There were biological and statistical differences between the two models. The metastasis rate in involved organs (lymph nodes, kidney, spleen, testis) was significantly higher in the BGC-823 model compared to the SGC-7901 model (P < 0.05 or P < 0.01). The median survival of the BGC-823 model was shorter than that of SGC-7901 (23 d vs 84 d, P < 0.05). Histopathologically, the primary tumor and metastatic lesions of the two models showed obvious atypia and mucus in the cytoplasm. Compared with the SGC-7901 model, BGC-823 appeared more poorly differentiated (absence of adenoid structure), had a smaller volume, and richer capillary structure. Immunohistochemical staining revealed cytokeratin 20 and epithelial membrane antigen expression was positive in the SGC-7901 tumors, while negative in BGC-823 ones. CONCLUSION: Models using the SGC-7901 and BGC-823 cell lines were established which could function in gastric cancer research on carcinogenesis mechanism and drug discovery. The two models showed different tumor behavior and the latter was more malignant than the former.

  13. Resveratrol inhibits growth of orthotopic pancreatic tumors through activation of FOXO transcription factors.

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    Sanjit K Roy

    Full Text Available BACKGROUND: The forkhead transcription factors of the O class (FOXO play a direct role in cellular proliferation, oxidative stress response, and tumorigenesis. The objectives of this study were to examine whether FOXOs regulate antitumor activities of resveratrol in pancreatic cancer cells in vitro and in vivo. METHODOLOGY/PRINCIPAL FINDINGS: Pancreatic cancer cell lines were treated with resveratrol. Cell viability, colony formation, apoptosis and cell cycle were measured by XTT, soft agar, TUNEL and flow cytometry assays, respectively. FOXO nuclear translocation, DNA binding and transcriptional activities were measured by fluorescence technique, gelshift and luciferase assay, respectively. Mice were orthotopically implanted with PANC1 cells and orally gavaged with resveratrol. The components of PI3K and ERK pathways, FOXOs and their target gene expressions were measured by the Western blot analysis. Resveratrol inhibited cell viability and colony formations, and induced apoptosis through caspase-3 activation in four pancreatic cancer cell lines (PANC-1, MIA PaCa-2, Hs766T, and AsPC-1. Resveratrol induced cell cycle arrest by up-regulating the expression of p21/CIP1, p27/KIP1 and inhibiting the expression of cyclin D1. Resveratrol induced apoptosis by up-regulating Bim and activating caspase-3. Resveratrol inhibited phosphorylation of FOXOs, and enhanced their nuclear translocation, FOXO-DNA binding and transcriptional activities. The inhibition of PI3K/AKT and MEK/ERK pathways induced FOXO transcriptional activity and apoptosis. Furthermore, deletion of FOXO genes abrogated resveratrol-induced cell cycle arrest and apoptosis. Finally, resveratrol-treated mice showed significant inhibition in tumor growth which was associated with reduced phosphorylation of ERK, PI3K, AKT, FOXO1 and FOXO3a, and induction of apoptosis and FOXO target genes. CONCLUSIONS: These data suggest that inhibition of ERK and AKT pathways act together to activate FOXO

  14. Prognostic features for quality of life after radical cystectomy and orthotopic neobladder

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    Alexander Kretschmer

    Full Text Available ABSTRACT Purpose: To analyse prognostic features on quality of life (QoL following radical cystectomy and urinary diversion via orthotopic neobladder in a single-centre patient cohort. Materials and Methods: Postoperative QoL of 152 patients was assessed retrospectively using the validated QLQ-C30 questionnaire. Potential associations of patient's quality of life including pre-and intraoperative characteristics, surgeon experience, postoperative time course, adjuvant therapies, and functional outcome were defined a priori and evaluated. Mann-Whitney-U-, Kruskal-Wallis-, Spearman correlation and post hoc-testing were used. A multivariate analysis using a multiple logistic regression model was performed. A p value 100 previous cystectomies, p=0.007, and nerve-sparing surgery (p=0.001. Patients who underwent secondary chemotherapy or radiotherapy had significant lower QLQ-C30 scores (p=0.04, p=0.02 respectively. Patients who were asymptomatic had a significantly higher quality of life (p<0.001. A significant impact of severity of incontinence based on ICIQ-SF score (p<0.001 and daily pad usage (p<0.001, existence of daytime incontinence (p<0.001, existence of urgency symptoms (p=0.007, and IIEF-5 score (p<0.001 could be observed. In multivariate analysis, independent prognostic relevance could be confirmed for preoperative ECOG performance status of 0 (p=0.020 vs. ECOG 1, p=0.047 vs. ECOG 2, experience of the respective surgeon (≥100 vs. <100 previous cystectomies, p=0.021, and daytime continence (p=0.032. Conclusion: In the present study, we report health-related QoL outcomes in a contemporary patient cohort and confirm preoperative ECOG status, surgeon experience and daytime incontinence as independent prognostic features for a good postoperative QoL.

  15. Cardiac Troponin Elevation Predicts Mortality in Patients Undergoing Orthotopic Liver Transplantation

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    David Snipelisky

    2013-01-01

    Full Text Available Introduction. While patients undergoing orthotopic liver transplantation (OLT have high cardiovascular event rates, preoperative risk stratification may not necessarily predict those susceptible patients. Troponin T (TnT may help predict patients at risk for cardiovascular complications. Methods. Consecutive patients undergoing OLT at Mayo Clinic in Florida between 1998 and 2010 who had TnT obtained within 10 days following surgery were included. Three groups were compared based on TnT level: (1 normal (TnT ≤0.01 ng/mL, (2 intermediate (TnT 0.02–0.11 ng/mL, and (3 elevated (TnT >0.11 ng/mL. Overall and cardiovascular mortality was assessed. Results. Of the 78 patients included, there was no difference in age, gender, severity of liver disease, and echocardiographic findings. Patients in the normal and intermediate TnT groups had a lower overall mortality rate (14.3% and 0%, resp. when compared with those with elevated TnT (50%; P=0.001. Patients in the elevated TnT group had a cardiovascular mortality rate of 37.5% compared with 1.4% in the other groups combined (P<0.01. The elevated TnT group had a much higher mortality rate when compared with those in the intermediate group (P<0.0001. Conclusion. TnT may accurately help risk stratify patients in the early postoperative setting to better predict cardiovascular complications.

  16. Intraductal delivery of adenoviruses targets pancreatic tumors in transgenic Ela-myc mice and orthotopic xenografts.

    Science.gov (United States)

    José, Anabel; Sobrevals, Luciano; Miguel Camacho-Sánchez, Juan; Huch, Meritxell; Andreu, Núria; Ayuso, Eduard; Navarro, Pilar; Alemany, Ramon; Fillat, Cristina

    2013-01-01

    Gene-based anticancer therapies delivered by adenoviruses are limited by the poor viral distribution into the tumor. In the current work we have explored the feasibility of targeting pancreatic tumors through a loco-regional route. We have taken advantage of the ductal network in the pancreas to retrogradelly inject adenoviruses through the common bile duct in two different mouse models of pancreatic carcinogenesis: The transgenic Ela-myc mice that develop mixed neoplasms displaying both acinar-like and duct-like neoplastic cells affecting the whole pancreas; and mice bearing PANC-1 and BxPC-3 orthotopic xenografts that constitute a model of localized human neoplastic tumors. We studied tumor targeting and the anticancer effects of newly thymidine kinase-engineered adenoviruses both in vitro and in vivo, and conducted comparative studies between intraductal or intravenous administration. Our data indicate that the intraductal delivery of adenovirus efficiently targets pancreatic tumors in the two mouse models. The in vivo application of AduPARTKT plus ganciclovir (GCV) treatment induced tumor regression in Ela-myc mice. Moreover, the intraductal injection of ICOVIR15-TKT oncolytic adenoviruses significantly improved mean survival of mice bearing PANC-1 and BxPC-3 pancreatic xenografts from 30 to 52 days and from 20 to 68 days respectively (p less than 0.0001) when combined with GCV. Of notice, both AduPARTKT and ICOVIR15-TKT antitumoral responses were stronger by ductal viral application than intravenously, in line with the 38-fold increase in pancreas transduction observed upon ductal administration. In summary our data show that cytotoxic adenoviruses retrogradelly injected to the pancreas can be a feasible approach to treat localized pancreatic tumors.

  17. The scoring system for patients with severe sepsis after orthotopic liver transplantation

    Institute of Scientific and Technical Information of China (English)

    Shun-Wei Huang; Xiang-Dong Guan; Xiao-Shun He; Juan Chen; Bin Ouyang

    2006-01-01

    BACKGROUND:Because of the complicated pathological features after liver transplantation, severe sepsis is dififcult to treat and often leads to death. This study was undertaken to analyze the role of orthotopic liver transplantation (OLT) in patients with severe sepsis and to evaluate the effect of the scoring system. METHODS:Fifty-six patients conformed to the inclusion criteria. They were divided into two groups: non-OLT group (group A) and OLT group (group B). Besides the general data of the patients, the surveillance of blood lactate, the number of failed organs, acute physiology and chronic health evaluationⅡ(APACHEⅡ) and mutiple organ dysfunction score (MODS) were evaluated at the 1st, 3rd and 7th day after OLT. RESULTS:The mortality during hospitalization was 30%in the non-OLT group and 57.6%in the other group. The level of blood lactate at the 1st day of OLT increased more signiifcantly in the OLT group than in the non-OLT group (P CONCLUSIONS: The persistently higher level of blood lactate during 7 days may be a dependent risk factor. Immunosuppression may be another risk factor for OLT patients. The mortality of OLT in patients with severe sepsis in 28 days is almost double that in non-OLT patients. The MODS score is better than the APACHEⅡscore in the assessment of organ failure in OLT patients with severe sepsis. The standard scoring system could be improved or a new scoring system that includes the blood lactate score should be established for liver transplantation.

  18. Sensitivity of MRI tumor biomarkers to VEGFR inhibitor therapy in an orthotopic mouse glioma model.

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    Christian T Farrar

    Full Text Available MRI biomarkers of tumor edema, vascular permeability, blood volume, and average vessel caliber are increasingly being employed to assess the efficacy of tumor therapies. However, the dependence of these biomarkers on a number of physiological factors can compromise their sensitivity and complicate the assessment of therapeutic efficacy. Here we examine the response of these MRI tumor biomarkers to cediranib, a potent vascular endothelial growth factor receptor (VEGFR inhibitor, in an orthotopic mouse glioma model. A significant increase in the tumor volume and relative vessel caliber index (rVCI and a slight decrease in the water apparent diffusion coefficient (ADC were observed for both control and cediranib treated animals. This contrasts with a clinical study that observed a significant decrease in tumor rVCI, ADC and volume with cediranib therapy. While the lack of a difference between control and cediranib treated animals in these biomarker responses might suggest that cediranib has no therapeutic benefit, cediranib treated mice had a significantly increased survival. The increased survival benefit of cediranib treated animals is consistent with the significant decrease observed for cediranib treated animals in the relative cerebral blood volume (rCBV, relative microvascular blood volume (rMBV, transverse relaxation time (T2, blood vessel permeability (K(trans, and extravascular-extracellular space (ν(e. The differential response of pre-clinical and clinical tumors to cediranib therapy, along with the lack of a positive response for some biomarkers, indicates the importance of evaluating the whole spectrum of different tumor biomarkers to properly assess the therapeutic response and identify and interpret the therapy-induced changes in the tumor physiology.

  19. Study of morbidity in orthotopic small intestine transplantation with Wistar rats: experimental study

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    LEE André Dong Won

    2002-01-01

    Full Text Available Background - Transplantation of the small intestine is a surgical procedure currently under investigation for its possible application in the treatment of patients with short bowel syndrome, aiming at the reintroduction of an oral diet. Aim - To define the morbidity and mortality of intestinal transplantation in small animals using microsurgery. Intra and postoperative morbidity and mortality were studied in Wistar rats submitted to orthotopic intestinal allotransplantation. Material and Method - The animals were divided into three groups: group A (37 donor animals, group B (37 recipient animals, and group C (10 control animals. Group B was divided into three subgroups according to survival time. Subgroup TI consisted of animals that died during surgery or due to causes directly related to surgical intervention, subgroup T2 consisted of animals that died between the 4th and 29th postoperative day, and subgroup T3 consisted of animals that survived after 30 days. Transplanted animals were evaluated in terms of surgical technique used (vascular and intestinal anastomosis, graft quality, surgical time, and clinical parameters. The animals that died by the 29th postoperative day were submitted to autopsy and the remaining ones were sacrificed after 30 days. Result - There was a high rate of complication of a surgical nature. Early mortality rate, i.e., mortality up to the third postoperative day, was 54% with vascular anastomosis being the major cause of death. Surgical time was evaluated in a restricted and homogeneous group and showed a strong prognostic value in terms of successful transplantation. Clinical parameters such as weight loss, reduction of ingestion, reduction of motor activity and diarrhea were directly correlated with acute rejection. Conclusion - The experimented intestinal transplant is a procedure companied by considerable morbidity and mortality due to surgical complications in postoperative period, vascular anastomosis and

  20. Establishment of a new pig model for auxiliary partial orthotopic liver transplantation

    Institute of Scientific and Technical Information of China (English)

    Cheng-Hong Peng; Liu-Bin Shi; Hong-Wei Zhang; Shu-You Peng; Guang-Wen Zhou; Hong-Wei Li

    2005-01-01

    AIM: To establish a new pig model for auxiliary partial orthotopic liver transplantation (APOLT).METHODS: The liver of the donor was removed from its body. The left lobe of the liver was resected in vivo and the right lobe was used as a graft. After the left lateral lobe of the recipient was resected, end-to-side anastomoses of suprahepatic inferior vena cava and portal vein were performed between the donor and recipient livers,respectively. End-to-end anastomoses were made between hepatic artery of graft and splenic artery of the host.Outside drainage was placed in donor common bile duct.RESULTS: Models of APOLT were established in 5 pigs with a success rate of 80%. Color ultrasound examination showed an increase of blood flow of graft on 5th d compared to the first day after operation. When animals were killed on the 5th d after operation, thrombosis of hepatic vein (HV) and portal vein (PV) were not found. Histopathological examination of liver samples revealed evidence of damage with mild steatosis and sporadic necrotic hepatocytes and focal hepatic lobules structure disorganized in graft. Infiltration of inflammatory cells was mild in portal or central vein area. Hematologic laboratory values and blood chemical findings revealed that compared with group A (before transplantation), mean arterial pressure (MAP), central venous pressure (CVP), buffer base (BB), standard bicarbonate (SB) and K+ in group B (after portal vein was clamped) decreased (P<0.01). After reperfusion of the graft, MAP, CVP and K+ restored gradually.CONCLUSION: Significant decrease of congestion in portal vein and shortened blocking time were obtained because of the application of in vitro veno-venous bypass during complete vascular clamping. This new procedure,with such advantages as simple vessel processing, quality anastomosis, less postoperative hemorrhage and higher success rate, effectively prevents ischemia reperfusion injury of the host liver and deserves to be spread.

  1. Evaluation of orthotopic liver transplantation with no veno-venous bypass

    Institute of Scientific and Technical Information of China (English)

    黄东胜; 郑树森; 吴健; 梁廷波; 王伟林; 沈岩; 张珉

    2002-01-01

    To assess the feasibility and outcome of orthotopic liver transplantation(OLT) with no veno-venous bypass(v-v hypass)in adult patients.Methods:Between 1999 and 2001 ,43 adult patients underwent OLT with v-v bypass,33 with no v-v bypass.The operation time,anhepatic time,amount of blood loss,amount of blood transfusion,ICU stay days of the two groups were compared.renal function and gastrointestinal function in the two groups were examined.Results:There was no significant difference in mean serum creatinine on day 3 and gas discharge time in patients with v-v bypass or not.With no v-v hypass,the average operation time was 5.7±1.3 hours,anhepatic time was 64±13 minutes,median amount of blood loss in operation was 4000±820mL,median amount of blood transfused intracperatively was 4650±910mL,median ICU stay was 5.7 days;all those were lower or shorter than those with v-v hypass.and these differences betweent the two groups had statistical significances.Conclusion:OLT with no v-v bypass is safe and can be performed in the majority of adult patients.The practice of liver transplantation with no v-v hypass is associated with shorter total operation time.shorter anhepatic time,lower blood product ussege,and shorter ICU stay compared with standard technique of OLT with routine use of v-v bypass.

  2. Changes in systemic and splanchnic hemodynamics after orthotopic liver transplantation in cirrhotic rats

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective To investigate early changes in systemic and splanchnic hemodynamics after orthotopic liver transplantation (OLT) in normal and cirrhotic rats. Methods Male Sprague-Dawley rats were divided into 4 groups:normal controls (NL,n=10),intrahepatic portal hypertension (IHPH, n=10) induced by injection of CCl4, normal rats with OLT (NL-OLT,n=9) and IHPH rats with OLT (IHPH-OLT,n=16). IHPH-OLT rots were divided into 2 subgroups: 3 days (Group A, n=9) and 7 days (Group B, n=7) after OLT. OLT was pedormed in rats using cuffs for the anastomosis of the suprahepatic inferior vena cava,infrahepatic vena cava and portal vein. Two weeks after production of IHPH rots, 7 days after NL-OLT rats, 3 days and 7 days after IHPH-OLT rats, radicective microspheres were used in a hemodynamic study. Results There were no significant differences in hemodynamic changes between NL-OLT and NL rets, except mean arterial blood pressure (MAP).The characteristies of systemic and splanchnic hyperdynamic circulatory slate,including increased cardiac output and splanchnic blood flow, decreased mean acterial blood pressure, total peripheral vascular resistance and splanchnic vascular resistance were ibserved in IHPH, IHPH-OLT A, and IHPH-OLT B rats,The magnitude of hyperhemodynamics was in the order of IHPH>IHPH-OLT A>IHPH-OLT B rats. Moreover, the derangement of splanchnic hyper hemodynamice was more significant than that of systemic hyperhemodynamics. Conclusioos The present study demonstrates that the persistence of early systemic and splanchnic hyperkinetic circulation after OLT may be the consequence of factors which maintain hyperhemo dynamics in liver cirrhosis, where portal hypertension is not completely eliminated. Hyperhemodynamics is not induced by OLT per se.

  3. An Improved Syngeneic Orthotopic Murine Model of Human Breast Cancer Progression

    Science.gov (United States)

    Rashid, Omar M.; Nagahashi, Masayuki; Ramachandran, Suburamaniam; Dumur, Catherine; Schaum, Julia; Yamada, Akimitsu; Terracina, Krista P.; Milstien, Sheldon; Spiegel, Sarah; Takabe, Kazuaki

    2014-01-01

    Purpose Breast cancer drug development costs nearly $610 million and 37 months in preclinical mouse model trials with minimal success rates. Despite these inefficiencies, there are still no consensus breast cancer preclinical models. Methods Murine mammary adenocarcinoma 4T1-luc2 cells were implanted subcutaneous (SQ) or orthotopically percutaneous injection in the area of the nipple (OP), or surgically into the chest 2nd mammary fat pad under direct vision (ODV) in Balb/c immunocompetent mice. Tumor progression was followed by in vivo bioluminescence and direct measurements, pathology and survival determined, and tumor gene expression analyzed by genome-wide microarrays. Results ODV produced less variable sized tumors and was a reliable method of implantation. ODV implantation into the chest 2nd mammary pad rather than into the abdominal 4th mammary pad, the most common implantation site, better mimicked human breast cancer progression pattern, which correlated with bioluminescent tumor burden and survival. Compared to SQ, ODV produced tumors that differentially expressed genes whose interaction networks are of importance in cancer research. qPCR validation of 10 specific target genes of interest in ongoing clinical trials demonstrated significant differences in expression. Conclusions ODV implantation into the chest 2nd mammary pad provides the most reliable model that mimics human breast cancer compared from subcutaneous implantation that produces tumors with different genome expression profiles of clinical significance. Increased understanding of the limitations of the different preclinical models in use will help guide new investigations and may improve the efficiency of breast cancer drug development. PMID:25200444

  4. Histologic differences between orthotopic xenograft pancreas models affect Verteporfin uptake measured by fluorescence microscopy and spectroscopy

    Science.gov (United States)

    O'Hara, Julia A.; Samkoe, Kimberley S.; Chen, Alina; Isabelle, Martin; Hoopes, P. J.; Hasan, Tayyaba; Pogue, Brian W.

    2012-02-01

    Photodynamic therapy (PDT) that uses the second generation photosensitizer, verteporfin (VP), is a developing therapy for pancreatic cancer. The optimal timing of light delivery related to VP uptake and distribution in pancreatic tumors will be important information to obtain to improve treatment for this intractable disease. In this work we examined uptake and distribution of VP in two orthotopic pancreatic tumors with different histological structure. ASPC-1 (fast-growing) and Panc-1 (slower growing) tumors were implanted in SCID mice and studied when tumors were approximately 100mm3. In a pilot study, these tumors had been shown to differ in uptake of VP using lightinduced fluorescence spectroscopy (LIFS) in vivo and fluorescence imaging ex vivo and that work is extended here. In vivo fluorescence mean readings of tumor and liver increased rapidly up to 15 minutes after photosensitizer injection for both tumor types, and then continued to increase up to 60 minutes post injection to a higher level in ASPC-1 than in Panc-1. There was variability among animals with the same tumor type, in both liver and tumor uptake and no selectivity of tumor over liver. In this work we further examined VP uptake at multiple time points in relation to microvascular density and perfusion, using DiOC7 (to mark blood vessels) and VP fluorescence in the same tissue slices. Analysis of DiOC7 fluorescence indicates that AsPC-1 and Panc-1 have different vascular densities but AsPC-1 vasculature is more perfusive. Analysis of colocalized DiOC7 and VP fluorescence showed ASPC-1 with higher accumulation of VP 3 hrs after injection and more VP at a distance from blood vessels compared to Panc-1. This work shows the need for techniques to analyze photosensitizer distribution in order to optimize photodynamic therapy as an effective treatment for pancreatic tumors.

  5. Evaluation of orthotopic liver transplantation with no veno-venous bypass

    Institute of Scientific and Technical Information of China (English)

    黄东胜; 郑树森; 吴健; 梁廷波; 王伟林; 沈岩; 张珉

    2002-01-01

    Objective: To assess the feasibility and o utcome of orthotopic liver transplantation(OLT) with no veno-venous bypass(v-v bypass) in adult patien ts . Methods: Between 1999 and 2001, 43 adult patients underwent OLT with v-v bypa s s, 33 with no v-v bypass. The operation time, anhepatic time, amount of blood l o ss, amount of blood transfusion, ICU stay days of the two groups were compared; renal function and gastrointestinal function in the two groups were examined. R esults: There was no significant difference in mean serum creatinine on day 3 an d gas discharge time in patients with v-v bypass or not. With no v-v bypass , th e average operation time was 5.7±1.3 hours, anhepatic time was 64±13 minutes, median amount of blood loss in operation was 4000±820 mL, median amount of blood trans fused intraoperatively was 4650±910 mL, median ICU stay was 5.7 days; all thos e were lower or shorter than those with v-v bypass; and these differences betw e en the two groups had statistical significances. Conclusion: OLT with no v-v b y pass is safe and can be performed in the majority of adult patients. The practic e of liver transplantation with no v-v bypass is associated with shorter total o peration time, shorter anhepatic time, lower blood product usage, and shorter IC U stay compared with standard technique of OLT with routine use of v-v bypass.

  6. 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.

  7. Hepatocellular transport proteins and their role in liver disease

    Institute of Scientific and Technical Information of China (English)

    Carmen Stanca; Diana Jung; Peter J. Meier; Gerd A. Kullak-Ublick

    2001-01-01

    @@MOLECULAR PHYSIOLLGY OF HEPATOCELLULAR TRANSPORT PROTEINS Basolaferal transport systems Na+-dependent bile salt uptake Uptake of bile salts into the liver was first isolated perfused rat liver[1],isolated hepatocyte cultures and basolateral plasma membrane vesicles [2,4].

  8. 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.

  9. 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.

  10. 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)

  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. Pictures of focal nodular hyperplasia and hepatocellular adenomas

    Institute of Scientific and Technical Information of China (English)

    Christine; Sempoux; Charles; Balabaud; Paulette; Bioulac-Sage

    2014-01-01

    This practical atlas aims to help liver and non liver pa-thologists to recognize benign hepatocellular nodules on resected specimen. Macroscopic and microscopic views together with immunohistochemical stains illustrate typical and atypical aspects of focal nodular hyperplasia and of hepatocellular adenoma, including hepatocel-lular adenomas subtypes with references to clinical and imaging data. Each step is important to make a correct diagnosis. The specimen including the nodule and the non-tumoral liver should be sliced, photographed and all different looking areas adequately sampled for par-affin inclusion. Routine histology includes HE, trichrome and cytokeratin 7. Immunohistochemistry includes glu-tamine synthase and according to the above results ad-ditional markers such as liver fatty acid binding protein, C reactive protein and beta catenin may be realized to differentiate focal nodular hyperplasia from hepatocel-lular adenoma subtypes. Clues for differential diagnosis and pitfalls are explained and illustrated.

  13. Porphyrin lipid nanoparticles for enhanced photothermal therapy in a patient-derived orthotopic pancreas xenograft cancer model

    Science.gov (United States)

    MacLaughlin, Christina M.; Ding, Lili; Jin, Cheng; Cao, Pingjiang; Siddiqui, Iram; Hwang, David M.; Chen, Juan; Wilson, Brian C.; Zheng, Gang; Hedley, David W.

    2016-03-01

    Local disease control is a major problem in the treatment of pancreatic cancer, because curative-intent surgery is only possible in a minority of patients, and radiotherapy cannot be delivered in curative doses. Despite the promise of photothermal therapy (PTT) for ablation of pancreatic tumors, this approach remains under investigated. Using photothermal sensitizers in combination with laser light for PTT can result in more efficient conversion of light energy to heat, and confinement of thermal destruction to the tumor, thus sparing adjacent organs and vasculature. Porphyrins have been previously employed as photosensitizers for PDT and PTT, however their incorporation in to "porphysomes", lipid-based nanoparticles each containing ~80,000 porphyrins through conjugation of pyropheophorbide to phospholipids, carries two distinct advantages: 1) high-density porphyrin packing imparts the nanoparticles with enhanced photonic properties for imaging and phototherapy; 2) the enhanced permeability and retention effect may be exploited for optimal delivery of porphysomes to the tumor region thus high payload porphyrin delivery. The feasibility of porphysome-enhanced PTT for pancreatic cancer treatment was investigated using a patient-derived orthotopic pancreas xenograft tumor model. Uptake of porphysomes at the orthotopic tumor site was validated using ex vivo fluorescence imaging of intact organs of interest. The accumulation of porphysomes in orthotopic tumor microstructure was also confirmed by fluorescence imaging of excised tissue slices. PTT progress was monitored as changes in tumor surface temperature using IR optical imaging. Histological analyses were conducted to examine microstructure changes in tissue morphology, and the viability of remaining tumor tissues following exposure to heat. These studies may also provide insight as to the contribution of heat sink in application of thermal therapies to highly vascularized pancreatic tumors.

  14. Glucose metabolism via the pentose phosphate pathway, glycolysis and Krebs cycle in an orthotopic mouse model of human brain tumors.

    Science.gov (United States)

    Marin-Valencia, Isaac; Cho, Steve K; Rakheja, Dinesh; Hatanpaa, Kimmo J; Kapur, Payal; Mashimo, Tomoyuki; Jindal, Ashish; Vemireddy, Vamsidhara; Good, Levi B; Raisanen, Jack; Sun, Xiankai; Mickey, Bruce; Choi, Changho; Takahashi, Masaya; Togao, Osamu; Pascual, Juan M; Deberardinis, Ralph J; Maher, Elizabeth A; Malloy, Craig R; Bachoo, Robert M

    2012-10-01

    It has been hypothesized that increased flux through the pentose phosphate pathway (PPP) is required to support the metabolic demands of rapid malignant cell growth. Using orthotopic mouse models of human glioblastoma (GBM) and renal cell carcinoma metastatic to brain, we estimated the activity of the PPP relative to glycolysis by infusing [1,2-(13) C(2) ]glucose. The [3-(13) C]lactate/[2,3-(13) C(2) ]lactate ratio was similar for both the GBM and brain metastasis and their respective surrounding brains (GBM, 0.197 ± 0.011 and 0.195 ± 0.033, respectively (p = 1); metastasis: 0.126 and 0.119 ± 0.033, respectively). This suggests that the rate of glycolysis is significantly greater than the PPP flux in these tumors, and that the PPP flux into the lactate pool is similar in both tumors. Remarkably, (13) C-(13) C coupling was observed in molecules derived from Krebs cycle intermediates in both tumor types, denoting glucose oxidation. In the renal cell carcinoma, in contrast with GBM, (13) C multiplets of γ-aminobutyric acid (GABA) differed from its precursor glutamate, suggesting that GABA did not derive from a common glutamate precursor pool. In addition, the orthotopic renal tumor, the patient's primary renal mass and brain metastasis were all strongly immunopositive for the 67-kDa isoform of glutamate decarboxylase, as were 84% of tumors on a renal cell carcinoma tissue microarray of the same histology, suggesting that GABA synthesis is cell autonomous in at least a subset of renal cell carcinomas. Taken together, these data demonstrate that (13) C-labeled glucose can be used in orthotopic mouse models to study tumor metabolism in vivo and to ascertain new metabolic targets for cancer diagnosis and therapy.

  15. Glucose Metabolism via the Pentose Phosphate Pathway, Glycolysis and Krebs Cycle in an Orthotopic Mouse Model of Human Brain Tumors

    Science.gov (United States)

    Marin-Valencia, Isaac; Cho, Steve K.; Rakheja, Dinesh; Hatanpaa, Kimmo J.; Kapur, Payal; Mashimo, Tomoyuki; Jindal, Ashish; Vemireddy, Vamsidhara; Good, Levi B.; Raisanen, Jack; Sun, Xiankai; Mickey, Bruce; Choi, Changho; Takahashi, Masaya; Togao, Osamu; Pascual, Juan M.; DeBerardinis, Ralph J.; Maher, Elizabeth A.; Malloy, Craig R.; Bachoo, Robert M.

    2013-01-01

    It has been hypothesized that increased flux through the pentose phosphate pathway (PPP) is required to support the metabolic demands of rapid malignant cell growth. Using an orthotopic mouse model of primary human glioblastoma (GBM) and a brain metastatic renal tumor of clear cell renal cell carcinoma (CCRCC) histology, we estimated the activity of the PPP relative to glycolysis by infusing [1,2-13C2]glucose. The [3-13C]lactate/[2,3-13C2]lactate ratio was similar for both the GBM and renal tumor and their respective surrounding brains (GBM: 0.197 ± 0.011 and 0.195 ± 0.033 (p=1); CCRCC: 0.126 and 0.119 ± 0.033, respectively). This suggests that the rate of glycolysis is significantly greater than PPP flux in these tumors, and that PPP flux into the lactate pool was similar in both tissues. Remarkably, 13C-13C coupling was observed in molecules derived from Krebs cycle intermediates in both tumors, denoting glucose oxidation. In the renal tumor, in contrast to GBM and surrounding brain, 13C multiplets of GABA differed from its precursor glutamate, suggesting that GABA did not derive from a common glutamate precursor pool. Additionally, the orthotopic renal tumor, the patient’s primary renal mass and brain metastasis were all strongly immunopositive for the 67-kDa isoform of glutamate decarboxylase, as were 84% of tumors on a CCRCC tissue microarray suggesting that GABA synthesis is cell-autonomous in at least a subset of renal tumors. Taken together, these data demonstrate that 13C-labeled glucose can be used in orthotopic mouse models to study tumor metabolism in vivo and to ascertain new metabolic targets for cancer diagnosis and therapy. PMID:22383401

  16. 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.

  17. CD24 expression identifies teratogen-sensitive fetal neural stem cell subpopulations: evidence from developmental ethanol exposure and orthotopic cell transfer models.

    Directory of Open Access Journals (Sweden)

    Joseph D Tingling

    Full Text Available BACKGROUND: Ethanol is a potent teratogen. Its adverse neural effects are partly mediated by disrupting fetal neurogenesis. The teratogenic process is poorly understood, and vulnerable neurogenic stages have not been identified. Identifying these is a prerequisite for therapeutic interventions to mitigate effects of teratogen exposures. METHODS: We used flow cytometry and qRT-PCR to screen fetal mouse-derived neurosphere cultures for ethanol-sensitive neural stem cell (NSC subpopulations, to study NSC renewal and differentiation. The identity of vulnerable NSC populations was validated in vivo, using a maternal ethanol exposure model. Finally, the effect of ethanol exposure on the ability of vulnerable NSC subpopulations to integrate into the fetal neurogenic environment was assessed following ultrasound guided, adoptive transfer. RESULTS: Ethanol decreased NSC mRNAs for c-kit, Musashi-1and GFAP. The CD24(+ NSC population, specifically the CD24(+CD15(+ double-positive subpopulation, was selectively decreased by ethanol. Maternal ethanol exposure also resulted in decreased fetal forebrain CD24 expression. Ethanol pre-exposed CD24(+ cells exhibited increased proliferation, and deficits in cell-autonomous and cue-directed neuronal differentiation, and following orthotopic transplantation into naïve fetuses, were unable to integrate into neurogenic niches. CD24(depleted cells retained neurosphere regeneration capacity, but following ethanol exposure, generated increased numbers of CD24(+ cells relative to controls. CONCLUSIONS: Neuronal lineage committed CD24(+ cells exhibit specific vulnerability, and ethanol exposure persistently impairs this population's cell-autonomous differentiation capacity. CD24(+ cells may additionally serve as quorum sensors within neurogenic niches; their loss, leading to compensatory NSC activation, perhaps depleting renewal capacity. These data collectively advance a mechanistic hypothesis for teratogenesis leading to

  18. Anionic clay as the drug delivery vehicle: tumor targeting function of layered double hydroxide-methotrexate nanohybrid in C33A orthotopic cervical cancer model

    Directory of Open Access Journals (Sweden)

    Choi G

    2016-01-01

    Full Text Available Goeun Choi,1 Huiyan Piao,1 Zeid A Alothman,2 Ajayan Vinu,3 Chae-Ok Yun,4 Jin-Ho Choy1 1Center for Intelligent Nano-Bio Materials, Department of Chemistry and Nano Science, Ewha Womans University, Seoul, Korea; 2Advanced Materials Research Chair, Chemistry Department, College of Science, King Saud University, Riyadh, Saudi Arabia; 3Future Industries Institute, University of South Australia, Mawson Lakes, SA, Australia; 4Department of Bioengineering, College of Engineering, Hanyang University, Seoul, Korea Abstract: Methotrexate (MTX, an anticancer agent, was successfully intercalated into the anionic clay, layered double hydroxides to form a new nanohybrid drug. The coprecipitation and subsequent hydrothermal method were used to prepare chemically, structurally, and morphologically well-defined two-dimensional drug-clay nanohybrid. The resulting two-dimensional drug-clay nanohybrid showed excellent colloidal stability not only in deionized water but also in an electrolyte solution of Dulbecco’s Modified Eagle’s Medium with 10% fetal bovine serum, in which the average particle size in colloid and the polydispersity index were determined to be around 100 and 0.250 nm, respectively. The targeting property of the nanohybrid drug was confirmed by evaluating the tumor-to-blood and tumor-to-liver ratios of the MTX with anionic clay carrier, and these ratios were compared to those of free MTX in the C33A orthotopic cervical cancer model. The biodistribution studies indicated that the mice treated with the former showed 3.5-fold higher tumor-to-liver ratio and fivefold higher tumor-to-blood ratio of MTX than those treated with the latter at 30 minutes postinjection. Keywords: anionic clay, biodistribution, cervical cancer, colloidal stability, layered double hydroxide, methotrexate 

  19. Respiration gating and Bloch fitting improve pH measurements with acidoCEST MRI in an ovarian orthotopic tumor model

    Science.gov (United States)

    Jones, Kyle M.; Randtke, Edward A.; Howison, Christine M.; Pagel, Mark D.

    2016-03-01

    We have developed a MRI method that can measure extracellular pH in tumor tissues, known as acidoCEST MRI. This method relies on the detection of Chemical Exchange Saturation Transfer (CEST) of iopamidol, an FDA-approved CT contrast agent that has two CEST signals. A log10 ratio of the two CEST signals is linearly correlated with pH, but independent of agent concentration, endogenous T1 relaxation time, and B1 inhomogeneity. Therefore, detecting both CEST effects of iopamidol during in vivo studies can be used to accurately measure the extracellular pH in tumor tissues. Past in vivo studies using acidoCEST MRI have suffered from respiration artifacts in orthotopic and lung tumor models that have corrupted pH measurements. In addition, the non-linear fitting method used to analyze results is unreliable as it is subject to over-fitting especially with noisy CEST spectra. To improve the technique, we have recently developed a respiration gated CEST MRI pulse sequence that has greatly reduced motion artifacts, and we have included both a prescan and post scan to remove endogenous CEST effects. In addition, we fit the results by parameterizing the contrast of the exogenous agent with respect to pH via the Bloch equations modified for chemical exchange, which is less subject to over-fitting than the non-linear method. These advances in the acidoCEST MRI technique and analysis methods have made pH measurements more reliable, especially in areas of the body subject to respiratory motion.

  20. HBV-INFECTION DE NOVO AFTER ORTHOTOPIC LIVER TRANSPLANTATION: CLINICAL AND VIROLOGICAL CHARACTERISTICS, ASSESSMENT OF ANTIVIRUS THERAPY EFFECTIVENESS

    Directory of Open Access Journals (Sweden)

    O. I. Malomuzh

    2012-01-01

    Full Text Available We studied 11 cases of HBV-infection de novo in patients after orthotopic liver transplantation performed because of non-viral cirrhosis. Serum НBeAg, was revedled in all patients. In most cases clinical course of HBV-infection was benign. Treatment with entecavir was more effective than lamivudin, and brought to НBsAg elimination in 4 patients. Treatment with lamivudin led to descrease viral load in all patients and HBsAg elimination in one case. 

  1. Technical steps of open radical cystectomy and orthotopic neobladder to achieve the goals of "minimally invasive surgery"?

    Directory of Open Access Journals (Sweden)

    Anil Mandhani

    2010-01-01

    Full Text Available Technical modifications in open approach to radical cystectomy and orthotopic neobladder (ONB, that is, Pfannenstiel incision, single urethral catheter, internal splint, and extraperitonealization of the ONB were done in 36 patients. Median operative time was 300 (240-360 min. Median time to move the bowel and start of oral intake was 4 days (2-8 days. Major complications occurred in 3 (8.33% patients. Mean postoperative pain score was 2 (1-4. These modifications in open radical cystectomy resulted in better cosmesis, less pain, and more comfort to the patients as they had to carry one urobag for 3 weeks.

  2. MELD score measured day 10 after orthotopic liver transplantation predicts death and re-transplantation within the first year

    DEFF Research Database (Denmark)

    Rostved, Andreas A; Lundgren, Jens D; Hillingsø, Jens;

    2016-01-01

    OBJECTIVE: The impact of early allograft dysfunction on the outcome after liver transplantation is yet to be established. We explored the independent predictive value of the Model for End-Stage Liver Disease (MELD) score measured in the post-transplant period on the risk of mortality or re......-transplantation. MATERIAL AND METHODS: Retrospective cohort study on adults undergoing orthotopic deceased donor liver transplantation from 2004 to 2014. The MELD score was determined prior to transplantation and daily until 21 days after. The risk of mortality or re-transplantation within the first year was assessed...

  3. Successful treatment of multiple hepatocellular adenomas with percutaneous radiofrequency ablation

    OpenAIRE

    Ahn, Sun Young; Park, Soo Young; Kweon, Young Oh; Tak, Won Young; Bae, Han Ik; Cho, Seung Hyun

    2013-01-01

    Hepatocellular adenoma (HCA) is one of the important complications of glycogen storage disease type Ia (GSD-Ia) because it can be transformed into hepatocellular carcinoma. Although surgical resection is a standard treatment of choice for solitary HCA, multiple HCAs in GSD-Ia patients present as therapeutic challenges for curative treatment. Therefore, treatment strategy according to malignant potential is important in management of HCAs in GSD-Ia. The authors present a case of histologically...

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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

  9. 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.

  10. 小鼠原位肝癌移植模型中髓系来源抑制性细胞的表达%The expression of myeloid-derived suppressor cells in an orthotopic transplantation liver tumor model in mice

    Institute of Scientific and Technical Information of China (English)

    赵文秀; 张正奇; 许雅苹; 尹震宇; 王效民

    2013-01-01

    目的 观察小鼠原位肝癌移植模型中髓系来源抑制性细胞(MDSCs)的表达.方法 将10只BALB/c小鼠随机分为两组:正常组和荷瘤组,后组是将H22肝癌细胞注射到肝左外叶,制作小鼠原位肝癌移植模型.10d后处死小鼠.流式细胞术检测两组小鼠外周血、骨髓、脾脏及肝脏组织中MDSCs的表达.结果 荷瘤组小鼠外周血、骨髓和脾脏中的MDSCs比例为[(47.73±6.00)、(71.90±4.30)、(11.21±1.19)%],均明显高于正常组小鼠[(18.33±2.31)、(59.03±4.50)、(5.82±0.58)%];正常小鼠肝组织中MDSCs占肝内白细胞6.5%,荷瘤小鼠肝癌组织、癌旁组织中MDSCs占肝内白细胞分别为43.8%和12.8%.结论 在小鼠原位肝癌移植模型中,MDSCs表达明显上调,为研究MDSCs在肝癌发生发展中的作用提供了良好的动物模型.%Objective To investigate the expression of myeloid-derived suppressor cells (MDSCs)in an orthotopic transplantation liver tumour model in BALB/c mice.Methods Ten healthy BALB/c mice were randomly divided into two groups (n =5 each):normal group and tumor-bearing group.The murine hepatic cancer cell line H22 cells were transplanted into the left liver lobe of mice to establish an orthotopic transplantation liver tumor model.The mice were sacrificed at 10th day.The expression of MDSCs in peripheral blood,bone marrow,spleen and liver was analyzed by flow cytometry.Results The presence of CD11b+ Gr-1 + MDSCs was significantly increased in the peripheral blood,bone marrow,and spleen of tumor-bearing mice [(47.73 ±.6.00),(71.90 ±4.30),(11.21 ± 1.19)%] as compared with normal mice [(18.33 ±2.31),(59.03 ±4.50),(5.82 ±0.58)%].The percentage of CD11b+ Gr-1 + MDSCs of intrahepatic leukocytes in normal mice was 6.5%.However,the percentage of MDSCs of intrahepatic leukocytes in tumor and paracancerous tissue was up to 43.8% and 12.8% respectively.Conclusion MDSCs were elevated in an orthotopic transplantation tumor mouse model

  11. Detection of Phosphatidylcholine-Coated Gold Nanoparticles in Orthotopic Pancreatic Adenocarcinoma using Hyperspectral Imaging.

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    England, Christopher G; Huang, Justin S; James, Kurtis T; Zhang, Guandong; Gobin, André M; Frieboes, Hermann B

    2015-01-01

    Nanoparticle uptake and distribution to solid tumors are limited by reticuloendothelial system systemic filtering and transport limitations induced by irregular intra-tumoral vascularization. Although vascular enhanced permeability and retention can aid targeting, high interstitial fluid pressure and dense extracellular matrix may hinder local penetration. Extravascular diffusivity depends upon nanoparticle size, surface modifications, and tissue vascularization. Gold nanoparticles functionalized with biologically-compatible layers may achieve improved uptake and distribution while enabling cytotoxicity through synergistic combination of chemotherapy and thermal ablation. Evaluation of nanoparticle uptake in vivo remains difficult, as detection methods are limited. We employ hyperspectral imaging of histology sections to analyze uptake and distribution of phosphatidylcholine-coated citrate gold nanoparticles (CGN) and silica-gold nanoshells (SGN) after tail-vein injection in mice bearing orthotopic pancreatic adenocarcinoma. For CGN, the liver and tumor showed 26.5 ± 8.2 and 23.3 ± 4.1 particles/100 μm2 within 10 μm from the nearest source and few nanoparticles beyond 50 μm, respectively. The spleen had 35.5 ± 9.3 particles/100 μm2 within 10 μm with penetration also limited to 50 μm. For SGN, the liver showed 31.1 ± 4.1 particles/100 μm2 within 10 μm of the nearest source with penetration hindered beyond 30 μm. The spleen and tumor showed uptake of 22.1 ± 6.2 and 15.8 ± 6.1 particles/100 μm2 within 10 μm, respectively, with penetration similarly hindered. CGH average concentration (nanoparticles/μm2) was 1.09 ± 0.14 in the liver, 0.74 ± 0.12 in the spleen, and 0.43 ± 0.07 in the tumor. SGN average concentration (nanoparticles/μm2) was 0.43 ± 0.07 in the liver, 0.30 ± 0.06 in the spleen, and 0.20 ± 0.04 in the tumor. Hyperspectral imaging of histology sections enables analysis of phosphatidylcholine-coated gold-based nanoparticles in

  12. Effects of different vasopressors on hemodynamics in patients undergoing orthotopic liver transplantation

    Institute of Scientific and Technical Information of China (English)

    ZHANG Li-ping; LI Min; YANG Lu

    2005-01-01

    Background The hyperdynamic circulatory state in end-stage liver disease is similar to the hemodynamic state in endotoxic shock. Recent research indicated that proper use of norepinephrine (NE) in patients with endotoxic shock could improve the perfusion of visceral organs and raise the survival rate. In this study, dopamine (DA) or NE combined with DA was infused during the orthotopic liver transplantation (OLT) to observe and compare their effects on hemodynamics, oxygenation, and renal function during different stages of the operation. Methods Thirty American Society of Anesthesiology (ASA) Ⅲ-Ⅳ patients undergoing OLT were randomly divided into group DA and group NE with 15 patients in each group. Vasopressors were infused after induction of anesthesia. DA was infused in group DA; DA and NE in group NE. Data of hemodynamics, oxygenation and renal function were collected after induction, 1 hour in preanhepatic, anhepatic, neohepatic phase and at the end of operation.Results Heart rate(HR) and mean arterial pressure (MAP) of the two groups were stable. In anhepatic phase, central venous pressure(CVP), mean pulmonary arterial pressure(MPAP), pulmonary arterial wedge pressure(PAWP), cardiac output (CO), and cardiac index (CI) decreased, whereas systemic vascular resistance (SVR) and systemic vascular resistance index (SVRI) increased significantly (P<0.05). The hemodynamic variables of group NE were more stable than that of group DA. Pulmonary vascular resistance(PVR), pulmonary vascular resistance index(PVRI), power of hydrogen(pH), and mixed venous oxygen saturation (SvO2) had no significant changes. Oxygen delivery (DO2) and oxygen consumption(VO2) decreased during anhepatic phase (P<0.05), but lactic acid (LAC)increased since anhepatic phase. Blood urea nitrogen (BUN) maintained relatively stable during different phases. Group NE had more urine output (F=4.733, P=0.039). Conclusions During OLT, both DA and NE combined with DA can maintain hemodynamics stable

  13. Hepatic artery complications after orthotopic liver transplantation: interventional treatment or retransplantation?

    Institute of Scientific and Technical Information of China (English)

    YANG Yang; YI Shu-hong; ZHANG Jian; ZHANG Jun-feng; YI Hui-min; JIANG Nan; JIANG Hua; ZHU Kang-shun; JIANG Zai-bo; SHAN Hong; CHEN Gui-hua; LI Hua; FU Bin-sheng; ZHANG Qi; ZHANG Ying-cai; LU Ming-qiang; CAI Chang-jie; XU Chi; WANG Gen-shu

    2008-01-01

    Background The main therapeutic treatments for hepatic artery complications after orthotopic liver transplantation (OLT) include thrombolysis, percutaneous transluminal angioplasty, stent placement, and liver retransplantation. The prognosis of hepatic artery complications after OLT is not only related to the type, extent, and timing but also closely associated with the selection and timing of the therapeutic methods. However, there is no consensus of opinion regarding the treatment of these complications. The aim of this study was to determine optimal treatment for hepatic artery complications after OLT.Methods The clinical data of 25 patients diagnosed with hepatic artery thrombosis (HAT) and hepatic artery stenosis (HAS) between October 2003 and March 2007 were retrospectively reviewed. Treatments included liver retransplantation and interventions which contain thrombolysis, percutaneous transluminal angioplasty and stent placement. Results Among five patients with HAT, 3 were treated with thrombolysis. One recovered, one died after thrombolysis and another one died of multi-organ failure after retransplantation because of recurrent HAT. The remaining 2 patients underwent successful retransplantation and have survived after that. Among 12 patients presented with HAS within 1 month postoperatively, 2 patients underwent retransplantation due to irreversible liver failure and another 10 patients were treated with interventions. The liver function failed to improve in 3 patients and retransplantations were performed in 4 patients after stent placement because of ischemic cholangitis. Among 6 patients undergoing liver retransplantations, two died of intracranial hemorrhage and infection respectively. Eight patients presented with HAS after 1 month postoperatively, 5 patients were treated with interventional management and recovered after stent placement. Among another 3 patients presented with HAS, 2 patients' liver function was stable and one patient received late

  14. IL-18 inhibits growth of murine orthotopic prostate carcinomas via both adaptive and innate immune mechanisms.

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    Brian Wan-Chi Tse

    Full Text Available Interleukin(IL-18 is a pleiotrophic cytokine with functions in immune modulation, angiogenesis and bone metabolism. In this study, the potential of IL-18 as an immunotherapy for prostate cancer (PCa was examined using the murine model of prostate carcinoma, RM1 and a bone metastatic variant RM1(BM/B4H7-luc. RM1 and RM1(BM/B4H7-luc cells were stably transfected to express bioactive IL-18. These cells were implanted into syngeneic immunocompetent mice, with or without an IL-18-neutralising antibody (αIL-18, SK113AE4. IL-18 significantly inhibited the growth of both subcutaneous and orthotopic RM1 tumors and the IL-18 neutralizing antibody abrogated the tumor growth-inhibition. In vivo neutralization of interferon-gamma (IFN-γ completely eliminated the anti-tumor effects of IL-18 confirming an essential role of IFN-γ as a down-stream mediator of the anti-tumor activity of IL-18. Tumors from mice in which IL-18 and/or IFN-γ was neutralized contained significantly fewer CD4(+ and CD8(+ T cells than those with functional IL-18. The essential role of adaptive immunity was demonstrated as tumors grew more rapidly in RAG1(-/- mice or in mice depleted of CD4(+ and/or CD8(+ cells than in normal mice. The tumors in RAG1(-/- mice were also significantly smaller when IL-18 was present, indicating that innate immune mechanisms are involved. IL-18 also induced an increase in tumor infiltration of macrophages and neutrophils but not NK cells. In other experiments, direct injection of recombinant IL-18 into established tumors also inhibited tumor growth, which was associated with an increase in intratumoral macrophages, but not T cells. These results suggest that local IL-18 in the tumor environment can significantly potentiate anti-tumor immunity in the prostate and clearly demonstrate that this effect is mediated by innate and adaptive immune mechanisms.

  15. The Vascular-Targeting Fusion Toxin VEGF121/rGel Inhibits the Growth of Orthotopic Human Bladder Carcinoma Tumors

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    Khalid Mohamedali

    2005-10-01

    Full Text Available Vascular endothelial growth factor. (VEGF and its receptors. (FLT-1 and KDR are overexpressed by human bladder cancer cells and tumor endothelial cells, respectively. Strategies that target VEGF receptors hold promise as antlanglogenic therapeutic approaches to bladder cancer. A fusion protein of VEGF121 and the plant toxin gelonin (rGel was constructed, expressed in bacteria, purified to homogeneity. Cytotoxicity experiments of VEGF121/rGel on the highly metastatic 253J B-V human bladder cancer cell line demonstrated that the VEGF121/rGel does not specifically target these cells, whereas Western blot analysis showed no defectable expression of KDR. Treatment with VEGF121/rGel against orthotopically implanted 253J B-V xenografts in nude mice resulted in a significant suppression of bladder tumor growth (-60% inhibition; P < .05 compared to controls. lmmunohistochemistry studies of orthotopic 253J B-V tumors demonstrated that KDR is highly overexpressed in tumor vasculature. Immunofluorescence staining with antibodies to CD-31 (blood vessel endothelium and reel demonstrated a dramatic colocalization of the construct on tumor neovasculature. Treated tumors also displayed an increase in terminal deoxynucleotidyl transferase-mediated dUTPblotin end labeling staining compared to controls. Thus, VEGF121/rGel inhibits the growth of human bladder cancer by cytotoxic effects directed against the tumor vascular supply and has significant potential as a novel antlangiogenic therapeutic against human bladder cancer.

  16. An orthotopic xenograft model of intraneural NF1 MPNST suggests a potential association between steroid hormones and tumor cell proliferation.

    Science.gov (United States)

    Perrin, George Q; Li, Hua; Fishbein, Lauren; Thomson, Susanne A; Hwang, Min S; Scarborough, Mark T; Yachnis, Anthony T; Wallace, Margaret R; Mareci, Thomas H; Muir, David

    2007-11-01

    Malignant peripheral nerve sheath tumors (MPNST) are the most aggressive cancers associated with neurofibromatosis type 1 (NF1). Here we report a practical and reproducible model of intraneural NF1 MPNST, by orthotopic xenograft of an immortal human NF1 tumor-derived Schwann cell line into the sciatic nerves of female scid mice. Intraneural injection of the cell line sNF96.2 consistently produced MPNST-like tumors that were highly cellular and showed extensive intraneural growth. These xenografts had a high proliferative index, were angiogenic, had significant mast cell infiltration and rapidly dominated the host nerve. The histopathology of engrafted intraneural tumors was consistent with that of human NF1 MPNST. Xenograft tumors were readily examined by magnetic resonance imaging, which also was used to assess tumor vascularity. In addition, the intraneural proliferation of sNF96.2 cell tumors was decreased in ovariectomized mice, while replacement of estrogen or progesterone restored tumor cell proliferation. This suggests a potential role for steroid hormones in supporting tumor cell growth of this MPNST cell line in vivo. The controlled orthotopic implantation of sNF96.2 cells provides for the precise initiation of intraneural MPNST-like tumors in a model system suitable for therapeutic interventions, including inhibitors of angiogenesis and further study of steroid hormone effects on tumor cell growth.

  17. Models of Human Metastatic Colon Cancer in Nude Mice Orthotopically Constructed by Using Histologically Intact Patient Specimens

    Science.gov (United States)

    Fu, Xinyu; Besterman, Jeffrey M.; Monosov, Ann; Hoffman, Robert M.

    1991-10-01

    There is an important need for clinically relevant animal models for human cancers. Toward this goal, histologically intact human colon-cancer specimens derived surgically from patients were implanted orthotopically to the colon or cecum of nude mice. We have observed extensive orthotopic growth in 13 of 20 cases of implanted patient colon tumors. These showed various growth patterns with subsequent regional, lymph-node, and liver metastasis, as well as general abdominal carcinomatosis. Thus, models for human colon cancer have been developed that show (i) local growth, (ii) abdominal metastasis, (iii) general abdominal carcinomatosis with extensive peritoneal seeding, (iv) lymph-node metastasis, (v) liver metastasis, and (vi) colonic obstruction. These models permit the passage of the tumors to form large cohorts. They will facilitate research into the biology of colon cancer metastatic capability and the development of new drugs active against metastatic cancer. These models may also predict the clinical course and the in vivo response to drugs of the cancer of individual patients.

  18. A simplified subnormothermic machine perfusion system restores ischemically damaged liver grafts in a rat model of orthotopic liver transplantation

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    Berendsen Tim A

    2012-05-01

    Full Text Available Abstract Background Liver donor shortages stimulate the development of strategies that incorporate damaged organs into the donor pool. Herein we present a simplified machine perfusion system without the need for oxygen carriers or temperature control, which we validated in a model of orthotopic liver transplantation. Methods Rat livers were procured and subnormothermically perfused with supplemented Williams E medium for 3 hours, then transplanted into healthy recipients (Fresh-SNMP group. Outcome was compared with static cold stored organs (UW-Control group. In addition, a rat liver model of donation after cardiac death was adapted using a 60-minute warm ischemic period, after which the grafts were either transplanted directly (WI group or subnormothermically perfused and transplanted (WI-SNMP group. Results One-month survival was 100% in the Fresh-SNMP and UW-Control groups, 83.3% in the WI-SNMP group and 0% in the WI group. Clinical parameters, postoperative blood work and histology did not differ significantly between survivors. Conclusion This work demonstrates for the first time in an orthotopic transplantation model that ischemically damaged livers can be regenerated effectively using practical subnormothermic machine perfusion without oxygen carriers.

  19. High Resolution Ultrasound and Photoacoustic Imaging of Orthotopic Lung Cancer in Mice: New Perspectives for Onco-Pharmacology

    Science.gov (United States)

    Sobilo, Julien; Le Mée, Marilyne; Rétif, Stéphanie; Natkunarajah, Sharuja; Lerondel, Stéphanie; Le Pape, Alain

    2016-01-01

    Objectives We have developed a relevant preclinical model associated with a specific imaging protocol dedicated to onco-pharmacology studies in mice. Materials and Methods We optimized both the animal model and an ultrasound imaging procedure to follow up longitudinally the lung tumor growth in mice. Moreover we proposed to measure by photoacoustic imaging the intratumoral hypoxia, which is a crucial parameter responsible for resistance to therapies. Finally, we compared ultrasound data to x-ray micro computed tomography and volumetric measurements to validate the relevance of this approach on the NCI-H460 human orthotopic lung tumor. Results This study demonstrates the ability of ultrasound imaging to detect and monitor the in vivo orthotopic lung tumor growth by high resolution ultrasound imaging. This approach enabled us to characterize key biological parameters such as oxygenation, perfusion status and vascularization of tumors. Conclusion Such an experimental approach has never been reported previously and it would provide a nonradiative tool for assessment of anticancer therapeutic efficacy in mice. Considering the absence of ultrasound propagation through the lung parenchyma, this strategy requires the implantation of tumors strictly located in the superficial posterior part of the lung. PMID:27070548

  20. 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

  1. Salinomycin inhibits proliferation and induces apoptosis of human hepatocellular carcinoma cells in vitro and in vivo.

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    Fan Wang

    Full Text Available The anti-tumor antibiotic salinomycin (Sal was recently identified as a selective inhibitor of breast cancer stem cells; however, the effect of Sal on hepatocellular carcinoma (HCC is not clear. This study aimed to determine the anti-tumor efficacy and mechanism of Sal on HCC. HCC cell lines (HepG2, SMMC-7721, and BEL-7402 were treated with Sal. Cell doubling time was determinated by drawing growth curve, cell viability was evaluated using the Cell Counting Kit 8. The fraction of CD133(+ cell subpopulations was assessed by flow cytometry. We found that Sal inhibits proliferation and decreases PCNA levels as well as the proportion of HCC CD133(+cell subpopulations in HCC cells. Cell cycle was analyzed using flow cytometry and showed that Sal caused cell cycle arrest of the various HCC cell lines in different phases. Cell apoptosis was evaluated using flow cytometry and Hoechst 33342 staining. Sal induced apoptosis as characterized by an increase in the Bax/Bcl-2 ratio. Several signaling pathways were selected for further mechanistic analyses using real time-PCR and Western blot assays. Compared to control, β-catenin expression is significantly down-regulated upon Sal addition. The Ca(2+ concentration in HCC cells was examined by flow cytometry and higher Ca(2+ concentrations were observed in Sal treatment groups. The anti-tumor effect of Sal was further verified in vivo using the hepatoma orthotopic tumor model and the data obtained showed that the size of liver tumors in Sal-treated groups decreased compared to controls. Immunohistochemistry and TUNEL staining also demonstrated that Sal inhibits proliferation and induces apoptosis in vivo. Finally, the role of Sal on in vivo Wnt/β-catenin signaling was evaluated by Western blot and immunohistochemistry. This study demonstrates Sal inhibits proliferation and induces apoptosis of HCC cells in vitro and in vivo and one potential mechanism is inhibition of Wnt/β-catenin signaling via increased

  2. Indicators of prognosis after liver transplantation in Chinese hepatocellular carcinoma patients

    Institute of Scientific and Technical Information of China (English)

    Jin Li; Lu-Nan Yan; Jian Yang; Zhe-Yu Chen; Bo Li; Yong Zeng; Tian-Fu Wen; Ji-Chun Zhao; Wen-Tao Wang; Jia-Yin Yang; Ming-Qing Xu; Yu-Kui Ma

    2009-01-01

    AIM:To identify prognostic factors of patients with hepatocellular carcinoma (HCC), who were treated by orthotopic liver transplantation (OLT).METHODS: From January 2000 to October 2006,165 patients with HCC underwent OLT. Various clinicopathological risk factors for actuarial and recurrencefree survival were identified using the Kaplan-Meier method with the log-rank test. The Cox proportional hazards model was used to identify independently predictive factors for actuarial and recurrence-free survival, which were used to propose new selection criteria. We compared the outcome of the subgroup patients meeting different criteria. Survival analysis was performed using the Kaplan-Meier method with the log-rank test.RESULTS: The median follow-up was 13.0 mo (2.8-69.5 mo). Overall, 1-, 2-, 3- and 5-year actuarial survival was 73.3%, 45.6%, 35.4% and 32.1%, respectively.One-, 2-, 3- and 5-year overall recurrencefree survival was 67.0%, 44.3%, 34.5% and 34.5%,respectively. In univariate analysis, number of tumors,total tumor size, lobar distribution, differentiation, macrovascular invasion, microvascular invasion, capsulation of the tumor, and lymph node metastasis were found to be associated significantly with actuarial and tumor-free survival. By means of using the multivariate Cox proportional hazards model, total tumor size and macrovascular invasion were found to be independent predictors of actuarial and tumor-free survival. When the selection criteria were expanded into the proposed criteria, there was no significant difference in 1-, 2-, 3- and 5-year actuarial and tumor-free survival of the 49 patients who met the proposed criteria (97.6%, 82.8%, 82.8% and 82.8%, and 90.7%, 82.8%, 68.8% and 68.8%, respectively)compared with that of patients who met the Milan or University of California, San Francisco (UCSF) criteria.CONCLUSION: Macrovascular invasion and total tumor diameter are the strongest prognostic factors.The proposed criteria do not adversely affect the

  3. Establishment of cell clones with different metastatic potential from the metastatic hepatocellular carcinoma cell line MHCC97

    Institute of Scientific and Technical Information of China (English)

    Yan Li; Zhao-You Tang; Sheng-Long Ye; Yin-Kun Liu; Jie Chen; Qiong Xue; Jun Chen; Dong-Mei Gao; Wei-Hua Bao

    2001-01-01

    ALM To establish clone cells with different metastatic potential for the study of metastasis-related mechanisms. METHODS Cloning procedure was performed on parental hepatocellular carcinoma (HCC) cell line MHCC97. andbiological characteristics of the target clones selected by in vivo screening were studied.``RESULTS Two clones with high MHCC97-H and IowMHCC9--L1 metastatic potential were isolated from theparent cell line. Compared with MHCC97-L. MHCC97-H hadsmaller cell size average cell diameter 43 um vs 50 μmand faster in vitro and in vivo growth rate tumor celldoubling time was 34.2 h vs 60.0 h. The main ranges ofchromosomes were 5.5 58 in MHCC97-H and 57 62 inMHCC97-L. Boyden chamber in vitro invasion assay demonstrated that the number of penetrating cells through the artificial basement membrane was 137.5 - 11 .0) cellsfield for MHC_C99--H vs 17.7 - 6.3) field for MHCC97-L.The proportions of cells in GO Gl phase. S phase, and G_ M phase for MHCC97-H MHCC97-L were 0.56 6.65.0.28 0.25 and 0.l6 0.10, respectively, as measured by flow cytometry. The serum AFP levels in nude mice 5 wk after orthotopic implantation of tumor tissue were ( 24666 μg. L for MHCC97-H and (91- 66) μg' L 1 for MHCC97L. The pulmonary metastatic rate was 100% (10-10) vs40% 4- 10).``CONCLUSION Two clones of the same genetic background but with different biological behaviors were established, which could be valuable models for investigation on HCC metastasis.``

  4. Tanshinone IIA inhibits metastasis after palliative resection of hepatocellular carcinoma and prolongs survival in part via vascular normalization

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    Wang Wen-Quan

    2012-11-01

    Full Text Available Abstract Background Promotion of endothelial normalization restores tumor oxygenation and obstructs tumor cells invasion, intravasation, and metastasis. We therefore investigated whether a vasoactive drug, tanshinone IIA, could inhibit metastasis by inducing vascular normalization after palliative resection (PR of hepatocellular carcinoma (HCC. Methods A liver orthotopic double-tumor xenograft model in nude mouse was established by implantation of HCCLM3 (high metastatic potential and HepG2 tumor cells. After removal of one tumor by PR, the effects of tanshinone IIA administration on metastasis, tumor vascularization, and survival were evaluated. Tube formation was examined in mouse tumor-derived endothelial cells (TECs treated with tanshinone IIA. Results PR significantly accelerated residual hepatoma metastases. Tanshinone IIA did not inhibit growth of single-xenotransplanted tumors, but it did reduce the occurrence of metastases. Moreover, it inhibited PR-enhanced metastases and, more importantly, prolonged host survival. Tanshinone IIA alleviated residual tumor hypoxia and suppressed epithelial-mesenchymal transition (EMT in vivo; however, it did not downregulate hypoxia-inducible factor 1α (HIF-1α or reverse EMT of tumor cells under hypoxic conditions in vitro. Tanshinone IIA directly strengthened tube formation of TECs, associated with vascular endothelial cell growth factor receptor 1/platelet derived growth factor receptor (VEGFR1/PDGFR upregulation. Although the microvessel density (MVD of residual tumor tissue increased after PR, the microvessel integrity (MVI was still low. While tanshinone IIA did not inhibit MVD, it did dramatically increase MVI, leading to vascular normalization. Conclusions Our results demonstrate that tanshinone IIA can inhibit the enhanced HCC metastasis associated with PR. Inhibition results from promoting VEGFR1/PDGFR-related vascular normalization. This application demonstrates the potential clinical

  5. SM5-1-conjugated PLA nanoparticles loaded with 5-fluorouracil for targeted hepatocellular carcinoma imaging and therapy.

    Science.gov (United States)

    Ma, Xibo; Cheng, Zhen; Jin, Yushen; Liang, Xiaolong; Yang, Xin; Dai, Zhifei; Tian, Jie

    2014-03-01

    SM5-1 is a humanized mouse antibody which has a high binding specificity for a membrane protein of about 230 kDa overexpressed in hepatocellular carcinoma (HCC), melanoma and breast cancer. In this study, SM5-1-conjugated poly D, L (lactide-coglycolide) (PLA) PLA containing Cy7 (PLA-Cy7-SM5-1) was prepared to study the targeting specificity of the bioconjugate to HCC-LM3-fLuc cell. Then, SM5-1-conjugated PLA containing 5-fluorouracil (5-FU) (PLA-5FU-SM5-1) and PLA containing 5-FU (PLA-5FU) were prepared for treatment of subcutaneous HCC-LM3-fLuc tumor mice. The results showed that PLA-5FU-SM5-1, PLA-5FU and 5-FU induced a 45.07%, 23.56% and 19.05% tumor growth inhibition rate, respectively, on day 31 post-treatment as determined by bioluminescent intensity. In addition, in order to evaluate the antitumor efficacy of PLA-5FU-SM5-1, HCC-LM3-fLuc cells were injected into the liver to establish the experimental orthotopic liver tumor models. The experiments showed that PLA-5FU-SM5-1, PLA-5FU and 5-FU induced a 53.24%, 31.00%, and 18.11% tumor growth inhibition rate, respectively, on day 31 post-treatment determined by the bioluminescent intensity of the abdomen in tumor-bearing mice. Furthermore, we have calculated the three-dimensional location of the liver cancer in mice using a multilevel adaptive finite element algorithm based on bioluminescent intensity decay calibration. The reconstruction results demonstrated that PLA-5FU-SM5-1 inhibited the tumor rapid progression, which were consistent with the results of subcutaneous tumor mice experiments and in vitro cell experiment results.

  6. Berberine suppresses Id-1 expression and inhibits the growth and development of lung metastases in hepatocellular carcinoma.

    Science.gov (United States)

    Tsang, Chi Man; Cheung, Kenneth Chat Pan; Cheung, Yuk Chun; Man, Kwan; Lui, Vivian Wai-Yan; Tsao, Sai Wah; Feng, Yibin

    2015-03-01

    Hepatocellular carcinoma (HCC) is an invasive cancer with a high rate of recurrence and metastasis. Agents with anti-proliferative as well as anti-metastatic activity will be ideal for effective treatment. Here, we demonstrated that berberine, an isoquinoline alkaloid, harbored potent anti-metastatic and anti-proliferative activities in vivo. Using an orthotopic model of HCC (MHCC-97L), which spontaneously develops lung metastases (one of the most common sites of HCC metastasis), we found that berberine treatment (10mg/kg/2days) significantly reduced lung metastasis from the liver tumors by ~85% (quantitated by bioluminescence emitted from lung metastases). Histological examination also confirmed the reduced incidence and number of lung metastases in berberine-treated mice. Furthermore, berberine effectively suppressed extra-tumor invasion of the primary HCC implant into the surrounding normal liver tissue, illustrating its potent anti-metastatic action in vivo. Consistent with previous reports in other cancer, berberine's anti-tumor activity was accompanied by suppression of cellular proliferation, invasiveness and HIF-1α/VEGF signaling. Strikingly, further mechanistic investigation revealed that berberine exerted profound inhibitory effect on the expression of Id-1, which is a key regulator for HCC development and metastasis. Berberine could suppress the transcription level of Id-1 through inhibiting its promotor activity. Specific downregulation of Id-1 by knocking down its RNA transcripts in HCC cells inhibited cellular growth, invasion and VEGF secretion, demonstrating the functional relevance of Id-1 downregulation induced by berberine. Lastly, berberine's anti-proliferative and anti-invasive activities could be partially rescued by Id-1 overexpression in HCC models, revealing a novel anti-cancer/anti-invasive mechanism of berberine via Id-1 suppression.

  7. MicroRNA-Based Classification of Hepatocellular Carcinoma and Oncogenic Role of miR-517a

    Science.gov (United States)

    TOFFANIN, SARA; HOSHIDA, YUJIN; LACHENMAYER, ANJA; VILLANUEVA, AUGUSTO; CABELLOS, LAIA; MINGUEZ, BEATRIZ; SAVIC, RADOSLAV; WARD, STEPHEN C.; THUNG, SWAN; CHIANG, DEREK Y.; ALSINET, CLARA; TOVAR, VICTORIA; ROAYAIE, SASAN; SCHWARTZ, MYRON; BRUIX, JORDI; WAXMAN, SAMUEL; FRIEDMAN, SCOTT L.; GOLUB, TODD; MAZZAFERRO, VINCENZO; LLOVET, JOSEP M.

    2013-01-01

    BACKGROUND & AIMS Hepatocellular carcinoma (HCC) is a heterogeneous tumor that develops via activation of multiple pathways and molecular alterations. It has been a challenge to identify molecular classes of HCC and design treatment strategies for each specific subtype. MicroRNAs (miRNAs) are involved in HCC pathogenesis and their expression profiles have been used to classify cancers. We analyzed miRNA expression in human HCC samples to identify molecular subclasses and oncogenic miRNAs. METHODS We performed miRNA profiling of 89 HCC samples using a ligation-mediated amplification method. Subclasses were identified by unsupervised clustering analysis. We identified molecular features specific for each subclass using expression pattern (Affymetrix U133 2.0), DNA change (Affymetrix STY Mapping Array), mutation (CTNNB1), and immunohistochemical (phosphor[p]-Akt, p-IGF-IR, p-S6, p-EGFR, β-catenin) analyses. The roles of selected miRNAs were investigated in cell lines and in an orthotopic model of HCC. RESULTS We identified 3 main clusters of HCCs: the Wnt (32 of 89; 36%), interferon-related (29 of 89; 33%), and proliferation (28 of 89; 31%) subclasses. A subset of patients with tumors in the proliferation subclass (8 of 89; 9%) overexpressed a family of poorly characterized miRNAs from chr19q13.42. Expression of miR-517a and miR-520c (from ch19q13.42) increased proliferation, migration, and invasion of HCC cells in vitro. MiR-517a promoted tumorigenesis and metastatic dissemination in vivo. CONCLUSIONS We propose miRNA-based classification of 3 subclasses of HCC. Among the proliferation class, miR-517a is an oncogenic miRNA that promotes tumor progression. There is rationale for developing therapies that miRNA 517 for patients with HCC. PMID:21324318

  8. Epigenetic regulation of pluripotent genes mediates stem cell features in human hepatocellular carcinoma and cancer cell lines.

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    Xiao Qi Wang

    Full Text Available Activation of the stem cell transcriptional circuitry is an important event in cancer development. Although cancer cells demonstrate a stem cell-like gene expression signature, the epigenetic regulation of pluripotency-associated genes in cancers remains poorly understood. In this study, we characterized the epigenetic regulation of the pluripotency-associated genes NANOG, OCT4, c-MYC, KLF4, and SOX2 in a variety of cancer cell lines and in primary tumor samples, and investigated the re-activation of pluripotency regulatory circuits in cancer progression. Differential patterns of DNA methylation, histone modifications, and gene expression of pluripotent genes were demonstrated in different types of cancers, which may reflect their tissue origins. NANOG promoter hypomethylation and gene upregulation were found in metastatic human liver cancer cells and human hepatocellular carcinoma (HCC primary tumor tissues. The upregulation of NANOG, together with p53 depletion, was significantly associated with clinical late stage of HCC. A pro-metastatic role of NANOG in colon cancer cells was also demonstrated, using a NANOG-overexpressing orthotopic tumor implantation mouse model. Demethylation of NANOG promoter was observed in CD133+(high cancer cells. In accordance, overexpression of NANOG resulted in an increase in the population of CD133+(high cells. In addition, we demonstrated a cross-regulation between OCT4 and NANOG in cancer cells via reprogramming of promoter methylation. Taken together, epigenetic reprogramming of NANOG can lead to the acquisition of stem cell-like properties. These results underscore the restoration of pluripotency circuits in cancer cells as a potential mechanism for cancer progression.

  9. A novel small-molecule compound targeting CD147 inhibits the motility and invasion of hepatocellular carcinoma cells.

    Science.gov (United States)

    Fu, Zhi-guang; Wang, Li; Cui, Hong-yong; Peng, Jian-long; Wang, Shi-jie; Geng, Jie-jie; Liu, Ji-de; Feng, Fei; Song, Fei; Li, Ling; Zhu, Ping; Jiang, Jian-li; Chen, Zhi-nan

    2016-02-23

    CD147, a type I transmembrane glycoprotein, is highly expressed in various cancer types and plays important roles in tumor progression, especially by promoting the motility and invasion of hepatocellular carcinoma (HCC) cells. These crucial roles make CD147 an attractive target for therapeutic intervention in HCC, but no small-molecule inhibitors of CD147 have been developed to date. To identify a candidate inhibitor, we used a pharmacophore model derived from the structure of CD147 to virtually screen over 300,000 compounds. The 100 highest-ranked compounds were subjected to biological assays, and the most potent one, dubbed AC-73 (ID number: AN-465/42834501), was studied further. We confirmed that AC-73 targeted CD147 and further demonstrated it can specifically disrupt CD147 dimerization. Moreover, molecular docking and mutagenesis experiments showed that the possible binding sites of AC-73 on CD147 included Glu64 and Glu73 in the N-terminal IgC2 domain, which two residues are located in the dimer interface of CD147. Functional assays revealed that AC-73 inhibited the motility and invasion of typical HCC cells, but not HCC cells that lacked the CD147 gene, demonstrating on-target action. Further, AC-73 reduced HCC metastasis by suppressing matrix metalloproteinase (MMP)-2 via down-regulation of the CD147/ERK1/2/signal transducer and activator of transcription 3 (STAT3) signaling pathway. Finally, AC-73 attenuated progression in an orthotopic nude mouse model of liver metastasis, suggesting that AC-73 or its derivatives have potential for use in HCC intervention. We conclude that the novel small-molecule inhibitor AC-73 inhibits HCC mobility and invasion, probably by disrupting CD147 dimerization and thereby mainly suppressing the CD147/ERK1/2/STAT3/MMP-2 pathways, which are crucial for cancer progression.

  10. The Risk of Hepatocellular Carcinoma After Directly Acting Antivirals for Hepatitis C Virus Treatment in Liver Transplanted Patients: Is It Real?

    Science.gov (United States)

    Strazzulla, Alessio; Maria Rita Iemmolo, Rosa; Carbone, Ennio; Concetta Postorino, Maria; Mazzitelli, Maria; De Santis, Mario; Di Benedetto, Fabrizio; Maria Cristiani, Costanza; Costa, Chiara; Pisani, Vincenzo; Torti, Carlo

    2016-01-01

    Introduction Since directly acting antivirals (DAAs) for treatment of hepatitis C virus (HCV) were introduced, conflicting data emerged about the risk of hepatocellular carcinoma (HCC) after interferon (IFN)-free treatments. We present a case of recurrent, extra-hepatic HCC in a liver-transplanted patient soon after successful treatment with DAAs, along with a short review of literature. Case Presentation In 2010, a 53-year old man, affected by chronic HCV (genotype 1) infection and decompensated cirrhosis, underwent liver resection for HCC and subsequently received orthotopic liver transplantation. Then, HCV relapsed and, in 2013, he was treated with pegylated-IFN plus ribavirin; but response was null. In 2014, he was treated with daclatasvir plus simeprevir to reach sustained virological response. At baseline and at the end of HCV treatment, computed tomography (CT) scan of abdomen excluded any lesions suspected for HCC. However, alpha-fetoprotein was 2.9 ng/mL before DAAs, increasing up to 183.1 ng/mL at week-24 of follow-up after the completion of therapy. Therefore, CT scan of abdomen was performed again, showing two splenic HCC lesions. Conclusions Overall, nine studies have been published about the risk of HCC after DAAs. Patients with previous HCC should be carefully investigated to confirm complete HCC remission before starting, and proactive follow-up should be performed after DAA treatment. PMID:28070200

  11. Liver transplantation in a patient with hepatitis B, C and D coinfection associated with hepatocellular carcinoma: a management strategy for a rare condition. Case report

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    Lucas Carvalho Dantas

    Full Text Available CONTEXT: Orthotopic liver transplantation (OLT is the treatment of choice for end-stage liver disease. Cirrhosis due to hepatitis C infection is the leading indication for liver transplantation worldwide. However, patients who are given transplants because of viral liver diseases often present clinical coinfections, including hepatitis B together with hepatitis D. Currently, different strategies exist for patient management before and after liver transplantation, and these are based on different protocols developed by the specialized transplantation centers. CASE REPORT: We present a rare case of a 58-year-old man with chronic hepatitis B, C and D coinfection. The patient developed cirrhosis and hepatocellular carcinoma. His treatment comprised antiviral therapy for the three viruses and OLT. The patient's outcome was satisfactory. CONCLUSION: OLT, in association with antiviral therapy using entecavir, which was administered before and after transplantation, was effective for sustained clearance of the hepatitis B and D viruses. A recurrence of hepatitis C infection after transplantation responded successfully to standard treatment comprising peginterferon alfa-2A and ribavirin.

  12. 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....

  13. 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.

  14. 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

  15. 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

  16. Serological Biomarkers of Hepatocellular Carcinoma in Egyptian Patients

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    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.

  17. 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.

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

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    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.

  19. 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.

  20. 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)

  1. 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

  2. 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

  3. 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.

  4. 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.

  5. 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

  6. 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.

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

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  2. File list: ALL.Liv.10.AllAg.Carcinoma,_Hepatocellular [Chip-atlas[Archive

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  3. The bone-regenerative properties of Emdogain adsorbed onto poly(D,L-lactic-coglycolic acid)/calcium phosphate composites in an ectopic and an orthotopic rat model.

    NARCIS (Netherlands)

    Plachokova, A.S.; Dolder, J. van den; Jansen, J.A.

    2008-01-01

    BACKGROUND AND OBJECTIVE: The aim of this study was to evaluate the bone-regenerative properties of Emdogain in osseous and nonosseous sites. MATERIAL AND METHODS: For the orthotopic study, unloaded poly(D,L-lactic-coglycolic acid)/calcium phosphate implants, and poly(D,L-lactic-coglycolic acid)/cal

  4. Dependence of Wilms tumor cells on signaling through insulin-like growth factor 1 in an orthotopic xenograft model targetable by specific receptor inhibition

    DEFF Research Database (Denmark)

    Bielen, Aleksandra; Box, Gary; Perryman, Lara;

    2012-01-01

    pathway inactivation. By contrast, Wilms tumor cells established orthotopically within the kidney were histologically accurate and exhibited significantly elevated insulin-like growth factor-mediated signaling, and growth was significantly reduced on treatment with NVP-AEW541 in parallel with signaling...

  5. In Vivo Imaging of Hypoxia-Inducible Factor Regulation in a Subcutaneous and Orthotopic GL261 Glioma Tumor Model Using a Reporter Gene Assay

    Directory of Open Access Journals (Sweden)

    Sandra Bürgi

    2014-11-01

    Full Text Available Intratumoral hypoxia changes the metabolism of gliomas, leading to a more aggressive phenotype with increased resistance to radio- and chemotherapy. Hypoxia triggers a signaling cascade with hypoxia-inducible factor (HIF as a key regulator. We monitored activation of the HIF pathway longitudinally in murine glioma tumors. GL261 cells, stably transfected with a luciferase reporter driven under the control of a promoter comprising the HIF target gene motive hypoxia response element, were implanted either subcutaneously or orthotopically. In vivo experiments were carried out using bioluminescence imaging. Tumors were subsequently analyzed using immunofluorescence staining for hypoxia, endothelial cells, tumor perfusion, and glucose transporter expression. Transient upregulation of the HIF signaling was observed in both subcutaneous and orthotopic gliomas. Immunofluorescence staining confirmed hypoxic regions in subcutaneous and, to a lesser extent, intracranial tumors. Subcutaneous tumors showed substantial necrosis, which might contribute to the decreased bioluminescence output observed toward the end of the experiment. Orthotopic tumors were less hypoxic than subcutaneous ones and did not develop extensive necrotic areas. Although this may be the result of the overall smaller size of orthotopic tumors, it might also reflect differences in the local environment, such as the better intrinsic vascularization of brain tissue compared to the subcutaneous tissue compartment.

  6. Changes in portal hemodynamics and acute rejection in the first 2 weeks after orthotopic liver transplantation - A prospective Doppler ultrasound study

    NARCIS (Netherlands)

    Kok, T; Slooff, MJH; Peeters, PMJG; Zwaveling, JH; Bijleveld, CMA; GiVanLoon, CETP; Klompmaker, IJ; Haagsma, EB

    1996-01-01

    RATIONALE AND OBJECTIVES. To analyze changes in Doppler ultrasound variables of the portal vein in relation to liver biopsy findings, the authors performed a prospective study of 316 Doppler ultrasound examinations in the first 2 weeks after orthotopic liver transplantation on 23 patients. METHODS.

  7. Optical Imaging of Tumor Response to Hyperbaric Oxygen Treatment and Irradiation in an Orthotopic Mouse Model of Head and Neck Squamous Cell Carcinoma

    NARCIS (Netherlands)

    J.A.M. Braks (Joanna); L. Spiegelberg (Linda); S. Koljenovic (Senada); Y. Ridwan (Yanto); S. Keereweer (Stijn); R. Kanaar (Roland); E.B. Wolvius (Eppo); J. Essers (Jeroen)

    2015-01-01

    textabstractPurpose: Hyperbaric oxygen therapy (HBOT) is used in the treatment of radiation-induced tissue injury but its effect on (residual) tumor tissue is indistinct and therefore investigated in this study. Procedures: Orthotopic FaDu tumors were established in mice, and the response of the (ir

  8. Estimation of Tumor Volumes by 11C-MeAIB and 18F-FDG PET in an Orthotopic Glioblastoma Rat Model

    DEFF Research Database (Denmark)

    Halle, Bo; Thisgaard, Helge; Hvidsten, Svend

    2015-01-01

    UNLABELLED: Brain tumor volume assessment is a major challenge. Molecular imaging using PET may be a promising option because it reflects the biologically active cells. We compared the agreement between PET- and histology-derived tumor volumes in an orthotopic glioblastoma rat model with a noninf...

  9. Enhanced Metastatic Recurrence Via Lymphatic Trafficking of a High-Metastatic Variant of Human Triple-Negative Breast Cancer After Surgical Resection in Orthotopic Nude Mouse Models.

    Science.gov (United States)

    Yano, Shuya; Takehara, Kiyoto; Tazawa, Hiroshi; Kishimoto, Hiroyuki; Kagawa, Shunsuke; Bouvet, Michael; Fujiwara, Toshiyoshi; Hoffman, Robert M

    2017-03-01

    We previously developed and characterized a highly invasive and metastatic triple-negative breast cancer (TNBC) variant by serial orthotopic implantation of MDA-MB-231 human breast cancer cells in nude mice. Eventually, a highly invasive and metastatic variant of human TNBC was isolated after lymph node metastases was harvested and orthotopically re-implanted into the mammary gland of nude mice for two cycles. The variant thereby isolated is highly invasive in the mammary gland and metastasized to lymph nodes in 10 of 12 mice compared to 2 of 12 of the parental cell line. In the present report, we observed that high-metastatic MDA-MB-231H-RFP cells produced significantly larger subcutaneous tumors compared with parental MDA-MB-231 cells in nude mice. Extensive lymphatic trafficking by high-metastatic MDA-MB-231 cells was also observed. High-metastatic MDA-MB-231 developed larger recurrent tumors 2 weeks after tumor resection compared with tumors that were not resected in orthotopic models. Surgical resection of the MDA-MB-231 high-metastatic variant primary tumor in orthotopic models also resulted in rapid and enhanced lymphatic trafficking of residual cancer cells and extensive lymph node and lung metastasis that did not occur in the non-surgical mice. These results suggest that surgical resection of high metastatic TNBC can greatly increase the malignancy of residual cancer. J. Cell. Biochem. 118: 559-569, 2017. © 2016 Wiley Periodicals, Inc.

  10. 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.

  11. 原位肝移植3例报告%Orthotopic Liver Transplantation:3 Cases Report

    Institute of Scientific and Technical Information of China (English)

    钱海鑫; 田力平; 胡浩; 秦磊; 周晓俊; 陈易人

    2001-01-01

    目的 探讨原位肝移植的手术技巧、围手术期处理及疗效。方法 2000年8~11月间,该院对2例Wilson病及1例肝门部肝内胆管癌实施了原位肝移植术,其中,采用“背驮式肝移植术”1例,“经典式肝移植术”2例。术后用“FK506+MMF+Pred”三联方案预防免疫排斥反应。结果 2例移植肝脏术后迅速恢复功能;另1例于术后22d出现不典型的轻度排斥反应,经对症治疗后好转。结论 肝移植是治疗良性终末期肝病唯一有效的方法.%Objective To investigate the surgical techniques,perioperational treatment and therapeutic effects of orthotopic liver transplantation (OLT).Methods From August to November 2000,OLT was successfully performed on 3 patients with liver diseases in our hospital,two of them were with Wilsons disease,the other was with Klatskin tumor.In case 1 the patient underwent piggyback orthotopic liver transplantation,and case 2 and in case 3 the patients classic orthotopic liver transplantation.Immunosuppressive drugs consisted of tacrolimus (FK506),mycophenolate mofetic (MMF) and prednisone.Results Three of transplantation organs had rapidly normal functions postoperation,except that in case 1 the patient suffered from atypical mild rejection on the 22nd day but pilled through that at the end.In the other two cases patients recovered well.And now,3 patients have been discharged with normal life quality.Conclusion OLT is the only effective treatment for benign terminal liver diseases,such as Wilsons disease.

  12. Neoadjuvant chemoradiation followed by orthotopic liver transplantation in cholangiocarcinomas: the emory experience

    Science.gov (United States)

    Landry, Jerome C.

    2016-01-01

    Background Cholangiocarcinoma (CCA) is a bile duct tumor with a grim prognosis. The median survival after radiotherapy of unresectable disease is 9-12 months. The following is a review of our experience with neoadjuvant (NEO) chemoradiation followed by orthotopic liver transplantation (OLT) for CCA. Methods Ten patients with CCAs were selected as candidates for NEO-OLT between 2008-2011. Patients with unresectable CCA above the cystic duct without intra or extrahepatic metastases were eligible. Primary sclerosing cholangitis (PSC) patients were included due to their poor resection response. Patients initially received external-beam radiation [via conventional fields or volumetric-modulated arc therapy (VMAT)] plus capecitabine (XEL) or 5-fluorouracil (5-FU), followed by either Iridium192 (Ir192) brachytherapy high dose rate (HDR) or external boost. 5-FU or XEL was administered until OLT. Patients underwent periodic surveillance computed tomography (CT)/MRIs after OLT. Primary endpoints included actuarial rates (AR)/crude rates (CR) of overall survival (OS), and local control (LC) at 6, 12, and 24 months. Results Five males and five females were identified. Mean age was 58.3 years (range, 38-71 years). Mean composite radiation dose delivered was 59.0 Gy (range, 54-71.4 Gy). Forty percent of patients had an HDR boost. Fifty percent of patients received XEL during NEO. Two patients were excluded from the analysis as they did not go on to OLT due to metastases (n=1) and death due to GI bleed (n=1). Thirty-eight percent of the OLT patients had a pathological complete response (pCR) after NEO, while 25% required a Whipple due to positive margins. Median follow-up for the OLT group was 23 months (range, 6.5-37 months). Six, twelve, and twenty-four months LC AR was 100%. LC CR was 100% at longest interval (30 months). Six, twelve, and twenty-four months OS AR was 100%, 87.5%, and 87.5%, respectively. Mean OS AR was 30.2 months (95% CI: 22.8-37.7). OS CR was 75% at longest

  13. Self-assembled tumor-targeting hyaluronic acid nanoparticles for photothermal ablation in orthotopic bladder cancer.

    Science.gov (United States)

    Lin, Tingsheng; Yuan, Ahu; Zhao, Xiaozhi; Lian, Huibo; Zhuang, Junlong; Chen, Wei; Zhang, Qing; Liu, Guangxiang; Zhang, Shiwei; Chen, Wei; Cao, Wenmin; Zhang, Chengwei; Wu, Jinhui; Hu, Yiqiao; Guo, Hongqian

    2017-02-15

    Bladder cancer is one of the most frequent malignancies in the urinary system. Radical cystectomy is inevitable when bladder cancer progresses to a muscle-invasive disease. However, cystectomy still causes a high risk of death and a low quality of life (such as ureter-abdomen ostomy, uroclepsia for ileal-colon neobladder). Therefore, more effective treatments as well as bladder preservation are needed. We developed self-assembled tumor-targeting hyaluronic acid-IR-780 nanoparticles for photothermal ablation in over-expressing CD44 (the receptor for HA) bladder cancer, which show high tumor selectivity, high treatment efficacy, good bioavailability, and excellent biocompatibility. The nanoparticles demonstrated a stable spherical nanostructure in aqueous conditions with good mono-dispersity, and their average size was 171.3±9.14nm. The nanoparticles can be degraded by hyaluronidase when it is over-expressed in bladder cells; therefore, they appear to have a hyaluronidase-responsive "OFF/ON" behavior of a fluorescence signal. HA-IR-780 NPs also showed high photothermal efficiency; 2.5, 5, 10 and 20μg/mL of NPs had a maximum temperature increase of 11.2±0.66°C, 18.6±0.75°C, 26.8±1.11°C and 32.3±1.42°C. The in vitro cell viability showed that MB-49 cells could be efficiently ablated by combining HA-IR-780 NPs with 808nm laser irradiation. Then, in vivo biodistribution showed the HA-IR-780 NPs are targeted for accumulation in bladder cancer cells but have negligible accumulation in normal bladder wall. The photothermal therapeutic efficacy of HA-IR-780 NPs in the orthotopic bladder cancer model showed tumors treated with NPs had a maximum temperature of 48.1±1.81°C after 6min of laser irradiation. The tumor volume was approximately 65-75mm(3) prior to treatment. After 12days, the tumor sizes for the PBS, PBS plus laser irradiation and HA-IR-780 NPs-treated groups were 784.75mm(3), 707.5mm(3), and 711.37mm(3), respectively. None of the tumors in the HA-IR-780

  14. Prevention of hepatocellular carcinoma: Focusing onantioxidant therapy

    Institute of Scientific and Technical Information of China (English)

    Koji Miyanishi; Toshifumi Hoki; Shingo Tanaka; Junji Kato

    2015-01-01

    Oxidative stress has been investigated in the context ofalcoholic liver injury for many years and shown to be acausal factor of chronic hepatitis C (CHC), nonalcoholicsteatohepatitis (NASH), drug-induced liver injury, Wilson's disease, and hemochromatosis. In CHC, it has beendemonstrated that oxidative stress plays an importantrole in hepatocarcinogenesis. In cases with persistenthepatitis due to failure of hepatitis C virus eradication,or chronic liver disease, such as NASH, the treatment ofwhich remains unestablished, it is important to reduceserum alanine aminotransferase levels and prevent liverfibrosis and development of hepatocellular carcinoma.This also suggests the importance of antioxidanttherapy. Among treatment options where it would beexpected that anti-inflammatory activity plays a rolein their confirmed efficacy for chronic hepatitis, irondepletion therapy, glycyrrhizin, ursodeoxycholic acid,Sho-Saiko-To, and vitamin E can all be consideredantioxidant therapies. To date, however, the ability ofthese treatments to prevent cancer has been confirmedonly in CHC. Nevertheless, anti-inflammatory and antifibroticeffects have been demonstrated in other liverdiseases and these therapies may potentially be effectivefor cancer prevention.

  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. In Utero Hepatocellular Transplantation in Rats

    Directory of Open Access Journals (Sweden)

    Emma Muñoz-Sáez

    2013-01-01

    Full Text Available This work represents a step forward in the experimental design of an in utero hepatocellular transplantation model in rats. We focused on the enrichment optimization of isolated fetal hepatocytes suspension, arranging the surgery methodology of in utero transplantation, monitoring the biodistribution of the transplanted hepatocytes, and assessing the success of the transplants. Rat fetuses have been transplanted at the 17th embryonic day (ED17 with fetal hepatocytes isolated from rats at the end of pregnancy (ED21. We assessed possible differences between lymphocyte population, CD4 positive, CD8 positive, double-positive T-cells, and anti-inflammatory cytokines interleukins 4 and 10 (IL4 and IL10 as well. Cellular viability reached the rates of 90–95%. Transplanted groups had a limited success. Transplanted hepatocytes were not able to pass through the hematoplacental barrier. The hepatocytes injected were primarily located in the liver. There was an upward trend in the whole amount of T CD4 and T CD8 cells. There was an increased IL4 in the transplanted groups observed in the pregnant rats. The possibility to induce tolerance in fetuses with a hepatocyte transplant in utero could be a key point to avoid the immunosuppression treatments which must be undergone by transplanted patients.

  17. 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.

  18. 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.

  19. 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

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. Mast cells and human hepatocellular carcinoma

    Institute of Scientific and Technical Information of C