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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. Impact of Metronomic UFT/Cyclophosphamide Chemotherapy and Antiangiogenic Drug Assessed in a New Preclinical Model of Locally Advanced Orthotopic Hepatocellular Carcinoma

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    Terence C. Tang

    2010-03-01

    Full Text Available Hepatocellular carcinoma (HCC is an intrinsically chemotherapy refractory malignancy. Development of effective therapeutic regimens would be facilitated by improved preclinical HCC models. Currently, most models consist of subcutaneous human tumor transplants in immunodeficient mice; however, these do not reproduce the extensive liver disease associated with HCC or metastasize. To address this deficiency, we developed an orthotopic model. Human HCC cells were transfected with the gene encoding secretable β-subunit human choriogonadotropin (β-hCG, which was used as a surrogate marker of tumor burden. The HCC cells were implanted into the left liver lobe of severe combined immunodeficient (SCID mice, after which the efficacy of different therapies was evaluated on established, but liver-confined human Hep3B cell line HCC. Treatments included sorafenib or metronomic chemotherapy using cyclophosphamide (CTX, UFT, an oral 5-fluorouracil prodrug, or doxorubicin either alone or in various combinations, with or without an antiangiogenic agent, DC101, an anti-vascular endothelial growth factor receptor-2 antibody. Sorafenib inhibited tumor growth in a dose-dependent manner but caused severe weight loss in SCID mice, thus necessitating use of DC101 in subsequent experiments. Although less toxicity was observed using either single or doublet metronomic chemotherapy without any added antiangiogenic agent, none, provided survival benefit. In contrast, significantly improved overall survival was observed using various combinations of metronomic chemotherapy regimens such as UFT + CTX with DC101. In conclusion, using this model of liver-confined but advanced HCC suggests that the efficacy of a targeted antiangiogenic drug or metronomic chemotherapy can be mutually enhanced by concurrent combination treatment.

  3. 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

  4. Multimodal imaging of orthotopic hepatocellular carcinoma using small animal PET, bioluminescence and contrast enhanced CT imaging

    International Nuclear Information System (INIS)

    Molecular imaging with small-animal PET and bioluminescence imaging has been used as an important tool in cancer research. One of the disadvantages of these imaging modalities is the lack of anatomic information. To obtain fusion images with both molecular and anatomical information, small-animal PET and bioluminescence images fused with contrast enhance CT image in orthotopic hepatocellular carcinoma (HCC) model. We retrovially transfected dual gene (HSV1-tk and firefly luciferase) to morris hepatoma cells. The expression of HSV1-tk and luciferase was checked by optical imager and in vitro radiolabeled FIAU uptake, respectively and also checked by RT-PCR analysis. MCA-TL cells (5X105/ 0.05 ml) mixed with matrigel (1: 10) injected into left lobe of liver in nude mice. 124I-FIAU-PET, bioluminescence and contrast enhanced CT images were obtained in the orthotopic HCC model and digital whole body autoradiography (DWBA) was performed. Small animal PET image was obtained at 2 h post injection of 124I-FIAU and contrast enhanced CT image was obtained at 3 h post injection of Fenestra LC (0.3 ml). MCA-TL cells showed more specific 124I-FIAU uptake and higher luminescent activity than parental cells. The orthotopic HCC was detected by 124I-FIAU PET, contrast enhanced CT, and BLI and confirmed by DWBA. Registered image in orthotopic HCC t models showed a good correlation of images from both PET and CT. Contrast enhanced CT image delineated margin of HCC. Multimodal imaging with 124I-FIAU PET, bioluminescence and contrast enhanced CT allows a precise and improved detection of tumor in orthotopic hepatocellular carcinoma model. Multimodal imaging is potentially useful for monitoring progression of hepatic metastasis and for the evaluation of cancer treatments

  5. Challenges of advanced hepatocellular carcinoma.

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    Colagrande, Stefano; Inghilesi, Andrea L; Aburas, Sami; Taliani, Gian G; Nardi, Cosimo; Marra, Fabio

    2016-09-14

    Hepatocellular carcinoma (HCC) is an aggressive malignancy, resulting as the third cause of death by cancer each year. The management of patients with HCC is complex, as both the tumour stage and any underlying liver disease must be considered conjointly. Although surveillance by imaging, clinical and biochemical parameters is routinely performed, a lot of patients suffering from cirrhosis have an advanced stage HCC at the first diagnosis. Advanced stage HCC includes heterogeneous groups of patients with different clinical condition and radiological features and sorafenib is the only approved treatment according to Barcelona Clinic Liver Cancer. Since the introduction of sorafenib in clinical practice, several phase III clinical trials have failed to demonstrate any superiority over sorafenib in the frontline setting. Loco-regional therapies have also been tested as first line treatment, but their role in advanced HCC is still matter of debate. No single agent or combination therapies have been shown to impact outcomes after sorafenib failure. Therefore this review will focus on the range of experimental therapeutics for patients with advanced HCC and highlights the successes and failures of these treatments as well as areas for future development. Specifics such as dose limiting toxicity and safety profile in patients with liver dysfunction related to the underlying chronic liver disease should be considered when developing therapies in HCC. Finally, robust validated and reproducible surrogate end-points as well as predictive biomarkers should be defined in future randomized trials. PMID:27678348

  6. 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.

  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. PMID:25605207

  8. Novel synergistic antitumor effects of rapamycin with bortezomib on hepatocellular carcinoma cells and orthotopic tumor model

    International Nuclear Information System (INIS)

    Despite recent advances in the treatment of hepatocellular carcinoma (HCC), the chemotherapy efficacy against HCC is still unsatisfactory. The mammalian target of rapamycin (mTOR) has been emerged as an important cancer therapeutic target. However, HCC cells often resistant to rapamycin because of the paradoxical activation of Akt by rapamycin. In this study, we investigated whether bortezomib could enhance the antitumor effects of rapamycin. The effects of rapamycin and bortezomib on HCC proliferation, apoptosis, migration, and invasiveness in vitro were assessed by CCK-8 analysis, flow cytometry, Hoechst 33342 staining and transwell assays, respectively. Total and phosphorylated protein levels of Akt were detected by Western blotting. The effects of rapamycin and/or bortezomib on the mRNA expression levels of p53, p27, p21 and Bcl-2 family in HCCLM3 cells were evaluated by RT-PCR. The roles of rapamycin and bortezomib on HCC growth and metastasis in xenograft models were evaluated by tumor volumes and fluorescent signals. The effects of rapamycin and bortezomib on cell proliferation and apoptosis in vivo were test by PCNA and TUNEL staining. Bortezomib synergized with rapamycin to reduce cell growth, induce apoptosis, and inhibit cell mobility in vitro. Further mechanistic studies showed that bortezomib inhibited rapamycin-induced phosphorylated Akt, which in turn enhanced apoptosis of HCC cell lines. The alteration of the mRNA expression of cell cycle inhibitors p53, p27, p21 and apoptosis associated genes Bcl-2, Bax were also involved in the synergistic antitumor effects of rapamycin and bortezomib. P53 inhibitor PFT-α significantly attenuate the effect of rapamycin and bortezomib on cell apoptosis, which indicated that the pro-apoptotic effect of rapamycin and bortezomib may be p53-dependent. Treatment of HCCLM3-R bearing nude mice with rapamycin and bortezomib significantly enhanced tumor growth inhibition (72.4%), comparing with either rapamycin- (54.7%) or

  9. Sorafenib in advanced hepatocellular carcinoma

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    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 we...

  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. Applying advanced imaging techniques to a murine model of orthotopic osteosarcoma

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    Matthew Lawrence Broadhead

    2015-08-01

    Full Text Available IntroductionReliable animal models are required to evaluate novel treatments for osteosarcoma. In this study, the aim was to implement advanced imaging techniques in a murine model of orthotopic osteosarcoma to improve disease modeling and the assessment of primary and metastatic disease.Materials and methodsIntra-tibial injection of luciferase-tagged OPGR80 murine osteosarcoma cells was performed in Balb/c nude mice. Treatment agent (pigment epithelium-derived factor; PEDF was delivered to the peritoneal cavity. Primary tumors and metastases were evaluated by in vivo bioluminescent assays, micro-computed tomography, [18F]-Fluoride-PET and [18F]-FDG-PET. Results[18F]-Fluoride-PET was more sensitive than [18F]-FDG-PET for detecting early disease. Both [18F]-Fluoride-PET and [18F]-FDG-PET showed progressive disease in the model, with 4-fold and 2-fold increases in SUV (p<0.05 by the study endpoint, respectively. In vivo bioluminescent assay showed that systemically delivered PEDF inhibited growth of primary osteosarcoma.DiscussionApplication of [18F]-Fluoride-PET and [18F]-FDG-PET to an established murine model of orthotopic osteosarcoma has improved the assessment of disease. The use of targeted imaging should prove beneficial for the evaluation of new approaches to osteosarcoma therapy.

  13. Advances in Management of Hepatocellular Carcinoma.

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    Intaraprasong, Pongphob; Siramolpiwat, Sith; Vilaichone, Ratha-Korn

    2016-01-01

    Hepatocellular carcinoma (HCC) is the most frequent type of malignant liver tumor and a high impact health problem worldwide. The prevalence of HCC is particularly high in many Asian and African countries. Some HCC patients have no symptoms prior to diagnosis and many of them therefore present at late stage and have a grave prognosis. The well-established causes of HCC are chronic hepatitis B virus (HBV) or chronic hepatitis C virus (HCV) infection or alcoholic cirrhosis and nonalcoholic steatohepatitis. The Barcelona Clinic Liver Cancer (BCLC) Staging System remains the most widely used for HCC management guidelines. To date, the treatments for HCC are still very challenging for physicians due to limited resources in many parts of the world, but many options of management have been proposed, including hepatic resection, liver transplantation, ablative therapy, chemoembolization, sora nib and best supportive care. This review article describes the current evidence-based management of HCC with focus on early to advance stages that impact on patient overall survival. PMID:27644603

  14. Hepatic Arterial Infusion Chemotherapy for Advanced Hepatocellular Carcinoma in Japan

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    Ryuichi Kita; Toru Kimura; Hiroki Nishikawa; Yukio Osaki

    2012-01-01

    Transcatheter methods such as transcatheter arterial chemoembolization (TACE) and hepatic arterial infusion chemotherapy (HAIC) have an important role in the treatment for advanced hepatocellular carcinoma (HCC). Recently, sorafenib, an inhibitor of tyrosine kinases, has been found to obtain survival benefits in patients with HCC, leading to major advances in the treatment of advanced HCC. However, it is associated with a low tumor response rate, minimal survival advantage, and high rates of ...

  15. High immunosuppressive burden in advanced hepatocellular carcinoma patients

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    Lugade, Amit A.; Kalathil, Suresh; Miller, Austin; Iyer, Renuka; Thanavala, Yasmin

    2013-01-01

    The accumulation of immunosuppressive cells and exhausted effector T cells highlight an important immune dysfunction in advanced stage hepatocellular carcinoma (HCC) patients. These cells significantly hamper the efficacy immunotherapies and facilitate HCC progression. We have recently demonstrated that the multipronged depletion of immunosuppressive cells potentially restores effector T-cell function in HCC.

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

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    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...

  17. 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.

  18. Recent Advances in Tumor Ablation for Hepatocellular Carcinoma

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    Kang, Tae Wook; Rhim, Hyunchul

    2015-01-01

    Image-guided tumor ablation for early stage hepatocellular carcinoma (HCC) is an accepted non-surgical treatment that provides excellent local tumor control and favorable survival benefit. This review summarizes the recent advances in tumor ablation for HCC. Diagnostic imaging and molecular biology of HCC has recently undergone marked improvements. Second-generation ultrasonography (US) contrast agents, new computed tomography (CT) techniques, and liver-specific contrast agents for magnetic r...

  19. 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.

  20. Hepatic Arterial Infusion Chemotherapy for Advanced Hepatocellular Carcinoma in Japan

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    Nishikawa, Hiroki, E-mail: h-nishikawa@osaka-med.jrc.or.jp; Osaki, Yukio; Kita, Ryuichi; Kimura, Toru [Department of Gastroenterology and Hepatology, Osaka Red Cross Hospital, 5-30 Fudegasaki-cho, Tennoji-ku, Osaka 543-0027 (Japan)

    2012-02-21

    Transcatheter methods such as transcatheter arterial chemoembolization (TACE) and hepatic arterial infusion chemotherapy (HAIC) have an important role in the treatment for advanced hepatocellular carcinoma (HCC). Recently, sorafenib, an inhibitor of tyrosine kinases, has been found to obtain survival benefits in patients with HCC, leading to major advances in the treatment of advanced HCC. However, it is associated with a low tumor response rate, minimal survival advantage, and high rates of adverse events. On the other hand, high rates of objective treatment response with HAIC for advanced HCC have been reported, although convincing evidence of it contributing to overall survival in HAIC has been lacking. In Japan, HAIC still tends to be the preferred method for the treatment of advanced HCC, even in patients with poor liver function. However, the choice of chemotherapeutic agents in TACE/HAIC for HCC varies between institutions. In this review, based on studies reported to date in the literature, we refer to current knowledge regarding the chemotherapeutic agents used for TACE/HAIC for HCC in Japan and consider the future perspectives for HAIC for this cancer.

  1. Hepatic Arterial Infusion Chemotherapy for Advanced Hepatocellular Carcinoma in Japan

    Directory of Open Access Journals (Sweden)

    Ryuichi Kita

    2012-02-01

    Full Text Available Transcatheter methods such as transcatheter arterial chemoembolization (TACE and hepatic arterial infusion chemotherapy (HAIC have an important role in the treatment for advanced hepatocellular carcinoma (HCC. Recently, sorafenib, an inhibitor of tyrosine kinases, has been found to obtain survival benefits in patients with HCC, leading to major advances in the treatment of advanced HCC. However, it is associated with a low tumor response rate, minimal survival advantage, and high rates of adverse events. On the other hand, high rates of objective treatment response with HAIC for advanced HCC have been reported, although convincing evidence of it contributing to overall survival in HAIC has been lacking. In Japan, HAIC still tends to be the preferred method for the treatment of advanced HCC, even in patients with poor liver function. However, the choice of chemotherapeutic agents in TACE/HAIC for HCC varies between institutions. In this review, based on studies reported to date in the literature, we refer to current knowledge regarding the chemotherapeutic agents used for TACE/HAIC for HCC in Japan and consider the future perspectives for HAIC for this cancer.

  2. Technical advances in external radiotherapy for hepatocellular carcinoma.

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    Park, Shin-Hyung; Kim, Jae-Chul; Kang, Min Kyu

    2016-08-28

    Radiotherapy techniques have substantially improved in the last two decades. After the introduction of 3-dimensional conformal radiotherapy, radiotherapy has been increasingly used for the treatment of hepatocellular carcinoma (HCC). Currently, more advanced techniques, including intensity-modulated radiotherapy (IMRT), stereotactic ablative body radiotherapy (SABR), and charged particle therapy, are used for the treatment of HCC. IMRT can escalate the tumor dose while sparing the normal tissue even though the tumor is large or located near critical organs. SABR can deliver a very high radiation dose to small HCCs in a few fractions, leading to high local control rates of 84%-100%. Various advanced imaging modalities are used for radiotherapy planning and delivery to improve the precision of radiotherapy. These advanced techniques enable the delivery of high dose radiotherapy for early to advanced HCCs without increasing the radiation-induced toxicities. However, as there have been no effective tools for the prediction of the response to radiotherapy or recurrences within or outside the radiation field, future studies should focus on selecting the patients who will benefit from radiotherapy. PMID:27621577

  3. Technical advances in external radiotherapy for hepatocellular carcinoma

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    Park, Shin-Hyung; Kim, Jae-Chul; Kang, Min Kyu

    2016-01-01

    Radiotherapy techniques have substantially improved in the last two decades. After the introduction of 3-dimensional conformal radiotherapy, radiotherapy has been increasingly used for the treatment of hepatocellular carcinoma (HCC). Currently, more advanced techniques, including intensity-modulated radiotherapy (IMRT), stereotactic ablative body radiotherapy (SABR), and charged particle therapy, are used for the treatment of HCC. IMRT can escalate the tumor dose while sparing the normal tissue even though the tumor is large or located near critical organs. SABR can deliver a very high radiation dose to small HCCs in a few fractions, leading to high local control rates of 84%-100%. Various advanced imaging modalities are used for radiotherapy planning and delivery to improve the precision of radiotherapy. These advanced techniques enable the delivery of high dose radiotherapy for early to advanced HCCs without increasing the radiation-induced toxicities. However, as there have been no effective tools for the prediction of the response to radiotherapy or recurrences within or outside the radiation field, future studies should focus on selecting the patients who will benefit from radiotherapy. PMID:27621577

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

    International Nuclear Information System (INIS)

    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. 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. 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 < 0.001) or a low AFP-level (p < 0.001) were associated with better survival, but not therapy modalities other than thymostimulin (p = 0.1) or signs of an invasive HCC phenotype such as vascular invasion (p = 0.3) and metastases (p = 0.1). The only variables independently related to survival in the Cox's regression model were Okuda stage and presence of liver cirrhosis (p < 0.01) as well as response to thymostimulin (p < 0.05). Of 39/44 patients evaluable for response, two obtained complete responses (one after concomitant radiofrequency ablation), five partial responses (objective response 18%), twenty-four stable disease (tumor control rate 79%) and eight progressed. Median progression-free survival was 6.4 months (95% CI 0.8–12). Grade 1 local reactions following injection were the only side effects. 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

  5. Hepatocellular carcinoma:current management and recent advances

    Institute of Scientific and Technical Information of China (English)

    Wan-Yee Lau; Eric C. H. Lai

    2008-01-01

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

  6. MRI-detectable polymeric micelles incorporating platinum anticancer drugs enhance survival in an advanced hepatocellular carcinoma model

    Directory of Open Access Journals (Sweden)

    Vinh NQ

    2015-06-01

    Full Text Available Nguyen Quoc Vinh,1 Shigeyuki Naka,1 Horacio Cabral,2 Hiroyuki Murayama,1 Sachiko Kaida,1 Kazunori Kataoka,2 Shigehiro Morikawa,3 Tohru Tani4 1Department of Surgery, Shiga University of Medical Science, Shiga, Japan; 2Department of Bioengineering, Graduate School of Engineering, The University of Tokyo, Tokyo, Japan; 3Department of Nursing, Shiga University of Medical Science, Shiga, Japan; 4Biomedical Innovation Center, Shiga University of Medical Science, Shiga, Japan Abstract: Hepatocellular carcinoma (HCC is one of the most intractable and lethal cancers; most cases are diagnosed at advanced stages with underlying liver dysfunction and are frequently resistant to conventional chemotherapy and radiotherapy. The development of tumor-targeting systems may improve treatment outcomes. Nanomedicine platforms are of particular interest for enhancing chemotherapeutic efficiency, and they include polymeric micelles, which enable targeting of multiple drugs to solid tumors, including imaging and therapeutic agents. This allows concurrent diagnosis, targeting strategy validation, and efficacy assessment. We used polymeric micelles containing the T1-weighted magnetic resonance imaging contrast agent gadolinium-diethylenetriaminpentaacetic acid (Gd-DTPA and the parent complex of the anticancer drug oxaliplatin [(1,2-diaminocyclohexaneplatinum(II (DACHPt] for simultaneous imaging and therapy in an orthotopic rat model of HCC. The Gd-DTPA/DACHPt-loaded micelles were injected into the hepatic artery, and magnetic resonance imaging performance and antitumor activity against HCC, as well as adverse drug reactions were assessed. After a single administration, the micelles achieved strong and specific tumor contrast enhancement, induced high levels of tumor apoptosis, and significantly suppressed tumor size and growth. Moreover, the micelles did not induce severe adverse reactions and significantly improved survival outcomes in comparison to oxaliplatin or

  7. Therapeutic options for intermediate-advanced hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

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

    2011-01-01

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

  8. Recent Advances in Tumor Ablation for Hepatocellular Carcinoma.

    Science.gov (United States)

    Kang, Tae Wook; Rhim, Hyunchul

    2015-09-01

    Image-guided tumor ablation for early stage hepatocellular carcinoma (HCC) is an accepted non-surgical treatment that provides excellent local tumor control and favorable survival benefit. This review summarizes the recent advances in tumor ablation for HCC. Diagnostic imaging and molecular biology of HCC has recently undergone marked improvements. Second-generation ultrasonography (US) contrast agents, new computed tomography (CT) techniques, and liver-specific contrast agents for magnetic resonance imaging (MRI) have enabled the early detection of smaller and inconspicuous HCC lesions. Various imaging-guidance tools that incorporate imaging-fusion between real-time US and CT/MRI, that are now common for percutaneous tumor ablation, have increased operator confidence in the accurate targeting of technically difficult tumors. In addition to radiofrequency ablation (RFA), various therapeutic modalities including microwave ablation, irreversible electroporation, and high-intensity focused ultrasound ablation have attracted attention as alternative energy sources for effective locoregional treatment of HCC. In addition, combined treatment with RFA and chemoembolization or molecular agents may be able to overcome the limitation of advanced or large tumors. Finally, understanding of the biological mechanisms and advances in therapy associated with tumor ablation will be important for successful tumor control. All these advances in tumor ablation for HCC will result in significant improvement in the prognosis of HCC patients. In this review, we primarily focus on recent advances in molecular tumor biology, diagnosis, imaging-guidance tools, and therapeutic modalities, and refer to the current status and future perspectives for tumor ablation for HCC. PMID:26674766

  9. Efficacy, Safety, and Biomarkers of Single-Agent Bevacizumab Therapy in Patients with Advanced Hepatocellular Carcinoma

    OpenAIRE

    Boige, Valérie; Malka, David; Bourredjem, Abderrahmane; Dromain, Clarisse; Baey, Charlotte; Jacques, Nathalie; Pignon, Jean-Pierre; Vimond, Nadege; Bouvet-Forteau, Nathalie; De Baere, Thierry; Ducreux, Michel; Farace, Françoise

    2012-01-01

    The safety, efficacy, and potential biomarkers of activity of bevacizumab in patients with advanced hepatocellular carcinoma were assessed. Bevacizumab was active and well tolerated. The clinical value of circulating endothelial cells and interleukin-6 and -8 warrants further investigation.

  10. 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.

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

    Institute of Scientific and Technical Information of China (English)

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

    2005-01-01

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

  12. Concomitant lung metastasis in patients with advanced hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Tian Yang; Jun-Hua Lu; Chuan Lin; Song Shi; Ting-Hao Chen; Rong-Hua Zhao; Yi Wang; Meng-Chao Wu

    2012-01-01

    AIM:To investigate the clinical features and prognostic factors of advanced hepatocellular carcinoma (HCC) patients presenting with lung metastasis at initial diagnosis.METHODS:Between 2001 and 2010,we recruited 76consecutive HCC patients initially presenting with lung metastasis,without co-existing metastasis from other sites.These patients were divided into three groups:untreated group (n =22),single treatment group (n =19),and combined treatment group (n =35).RESULTS:Metastasis of bilateral lung lobes was common and noted in 35 patients (46.1%),and most of patients (59/76,77.6%) presented with multiple lung metastatic nodules.Nineteen patients (25.0%)received single-method treatment,including hepatectomy in 4,transcatheter arterial chemoembolization in 6,radiotherapy in 5,and oral sorafenib in 4.Thirty-five patients (46.1%) received combined treatment modalities.The overall median survival of the all patients was 8.7 ± 0.6 mo; 4.1 ± 0.3,6.3 ± 2.5 and 18.6 ± 3.9 mo,respectively in the untreated group,single treatment group and combined treatment group,respectively,with a significant difference (log-rank test,P < 0.001).Multivariate analysis revealed that Child-Pugh score,the absence or presence of portal vein tumor thrombus,and treatment modality were three independent prognostic factors affecting survival of patients with advanced HCC and concomitant lung metastasis.CONCLUSION:Combined treatment modalities tend to result in a better survival as compared with the conservative treatment or single treatment modality for HCC patients initially presenting with lung metastasis.

  13. Sorafenib in advanced hepatocellular carcinoma: current status and future perspectives

    Directory of Open Access Journals (Sweden)

    Hsu CH

    2014-06-01

    Full Text Available Chih-Hung Hsu,1,4 Ying-Chun Shen,1,2 Yu-Yun Shao,1,4 Chiun Hsu,1,4 Ann-Lii Cheng,1,3,41Department of Oncology, 2Department of Medical Research, 3Department of Internal Medicine, National Taiwan University Hospital, 4Graduate Institute of Oncology, College of Medicine, National Taiwan University, Taipei, TaiwanAbstract: The approval of sorafenib, a multikinase inhibitor targeting primarily Raf kinase and the vascular endothelial growth factor receptor, in 2007 for treating advanced hepatocellular carcinoma (HCC has generated considerable enthusiasm in drug development for this difficult-to-treat disease. However, because several randomized Phase III studies testing new multikinase inhibitors failed, sorafenib remains the standard of first-line systemic therapy for patients with advanced HCC. Field practice studies worldwide have suggested that in daily practice, physicians are adopting either a preemptive dose modification or a ramp-up strategy to improve the compliance of their patients. In addition, accumulating data have suggested that patients with Child–Pugh class B liver function can tolerate sorafenib as well as patients with Child–Pugh class A liver function, although the actual benefit of sorafenib in patients with Child–Pugh class B liver function has yet to be confirmed. Whether sorafenib can be used as an adjunctive therapy to improve the outcomes of intermediate-stage HCC patients treated with transcatheter arterial chemoembolization or early-stage HCC patients after curative therapies is being investigated in several ongoing randomized Phase III studies. An increasing number of studies have reported that sorafenib exerts "off-target" effects, including the modulation of signaling pathways other than Raf/MEK/ERK pathway, nonapoptotic cell death mechanisms, and even immune modulation. Finally, although sorafenib in combination with chemotherapy or other targeted therapies has the potential to improve therapeutic efficacy in

  14. 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.

  15. 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

  16. Intra-Arterial Chemotherapy with Doxorubicin and Cisplatin Is Effective for Advanced Hepatocellular Cell Carcinoma

    OpenAIRE

    Ming-Chun Ma; Yen-Yang Chen; Shau-Hsuan Li; Yu-Fan Cheng; Chih-Chi Wang; Tai-Jan Chiu; Sung-Nan Pei; Chien-Ting Liu; Tai-Lin Huang; Chen-Hua Huang; Yu-Li Su; Yen-Hao Chen; Sheng-Nan Lu; Kun-Ming Rau

    2014-01-01

    Advanced hepatocellular carcinoma (HCC) remains a fatal disease even in the era of targeted therapies. Intra-arterial chemotherapy (IACT) can provide therapeutic benefits for patients with locally advanced HCC who are not eligible for local therapies or are refractory to targeted therapies. The aim of this retrospective study was to analyze the effect of IACT with cisplatin and doxorubicin on advanced HCC. Methods. Patients with advanced HCC who were not eligible for local therapies or were r...

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

    Directory of Open Access Journals (Sweden)

    Christian Steinberg

    2013-01-01

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

  18. Sorafenib-induced acute interstitial pneumonia in patients with advanced hepatocellular carcinoma: report of three cases

    OpenAIRE

    Takeda, Haruhiko; Nishikawa, Hiroki; Iguchi, Eriko; Matsuda, Fumihiro; Kita, Ryuichi; Kimura, Toru; Osaki, Yukio

    2012-01-01

    Little is known about acute interstitial pneumonia (AIP) induced by sorafenib therapy in patients with advanced hepatocellular carcinoma (HCC). Here, we present three patients with advanced HCC who developed AIP during sorafenib therapy, with fatal complications in two cases. Case 1 was a 76-year-old man who developed dyspnea. Chest CT showed interstitial pneumonia. Sorafenib was discontinued immediately, and prednisolone was started. His pneumonia resolved. A drug-induced lymphocyte stimulat...

  19. 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.

  20. The observation and nursing for advanced hepatocellular carcinoma patients treated with Sorafenib

    International Nuclear Information System (INIS)

    Objective: To summarize the author's experience which was obtained in observing and nursing the adverse reactions of advanced hepatocellular carcinoma patients who were treated with Sorafenib. Methods: The adverse reactions and their severity observed in 34 patients with advanced hepatocellular carcinoma who were treated with Sorafenib were retrospectively analyzed. Results: Side effects or toxic reaction were observed in all the patients, which included neutropenia, foot-hand syndrome (FHS), fatigue, diarrhea, hypertention, rash, etc. Five patients had to cut down the dose of Sorafenib in order to relieve the symptom, among them one patient had grade 4 FHS, 3 patients had grade 3 FHS and one patient had grade 3 neutropenia. Conclusion: Being familiar with sorafenib's adverse reaction, closely observing the patients condition and affording appropriate nursing measures, all the above items can definitely improve the therapeutic results and patient's living quality. (authors)

  1. 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.

  2. Cost-effectiveness of sorafenib versus SBRT for unresectable advanced hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Stereotactic body radiotherapy (SBRT) has been shown to improve overall survival in patients with advanced hepatocellular carcinoma. This study aimed to assess the cost-effectiveness of SBRT compared to sorafenib which is the only drug for advanced hepatocellular carcinoma. A Markov decision-analytic model was performed to compare the cost-effectiveness of SBRT and sorafenib for unresectable advanced hepatocellular carcinoma. Patients transitioned between three health states: stable disease, progression disease and death. We calculated the data on cost from the perspective of our National Health Insurance Bureau. Sensitivity analyses were conducted to determine the impact of several variables. The incremental cost effectiveness ratio (ICER) for sorafenib compared to SBRT was NT$3,788,238 per quality-adjusted life year gained (cost/QALY), which was higher than the willingness to pay threshold of Taiwan according to WHO’s guideline. One-way sensitivity analysis revealed that the utility of progression disease for the sorafenib treatment, utility of progression free survival for SBRT, utility of progression free survival for sorafenib, utility of PFS to progression disease for SBRT and transition probability of progression disease to dead for SBRT were the most sensitive parameters in all cost scenarios. The Monte-Carlo simulation demonstrated that the probability of cost-effectiveness at a willingness to pay threshold of NT$ 2,213,145 per QALY was 100 % and 0 % chance for SBRT and sorafenib. This study indicated that SBRT for advanced hepatocellular carcinoma is cost-effective at a willingness to pay threshold as defined by WHO guideline in Taiwan

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

    OpenAIRE

    ISHIKAWA, TORU

    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 u...

  4. 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.

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

    International Nuclear Information System (INIS)

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

  6. 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.

  7. 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

  8. [Transarterial infusion chemotherapy using fine-powder cisplatin in patients with advanced hepatocellular carcinoma].

    Science.gov (United States)

    Hatanaka, Takeshi; Kakizaki, Satoru; Ueno, Takashi; Takeuchi, Suguru; Takizawa, Daichi; Katakai, Kenji

    2014-02-01

    We investigated the therapeutic effects and safety of fine powder cisplatin for patients with advanced hepatocellular carcinoma( HCC). From January 2006 to March 2012, 123 patients with advanced HCC were treated by transarterial infusion chemotherapy(TAI)with fine-powder cisplatin(IA-call®, Nippon Kayaku Co. Ltd., Tokyo, Japan). The drug was infused into the liver through the feeding artery at a dose of 65 mg/m2. The treatment was repeated every 4 to 8 weeks until evidence of either tumor progression or unacceptable toxicity appeared. Treatment responses were classified as complete response(CR), partial response(PR), stable disease(SD), and progressive disease(PD)in 3.2%, 12.0%, 32.2%, and 52.4% of patients, respectively. The median survival durations were as follows: overall, 12.2 months; CR/PR patients, 23.8 months; and SD/PD patients, 10.6 months. The cumulative survival rates of CR/PR patients were significantly higher than those of SD/PD patients (pPIVKA- II )were predictive factors of survival duration. Problematic adverse events were not observed in any of the patients. Our results suggest that TAI using fine-powder cisplatin can be safely administered for advanced HCC and can improve the prognosis of patients with advanced disease. PMID:24743198

  9. 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

  10. 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.

  11. Clinical observation of transcatheter arterial chemoembolization combined with sorafenib on intermediate-advanced hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Objective: To evaluate the treatment effect and security of transcatheter arterial chemoembolization (TACE) combined with sorafenib for intermediate-advanced hepatocellular carcinoma. Methods: From July 2008 to November 2010,the treatment effects of two groups of patients with advanced hepatocellular carcinoma were retrospectively analyzed and compared, including 44 patients treated by sorafenib combined with TACE (test group) and the other 44 patients treated only with TACE (control group). To assess the treatment effect based on mRECIST, the time for patients' tumor progression (TTP), overall survival (OS) time and adverse events were recorded. Survival rate were analyzed using Kaplan-Meier method and Log-rank analysis in SPSS 18.0. Results: Till January 2011, 24 patients (54.5%) survived and 20 patients (include patients lost to visit) died (45.5%) among the test group, 13 patients survived (29.5 %) and 31 patients (include patients lost to visit) died (70.5 %) among the control group. No complete remission condition was observed in all patients. Among the test group, 1 patient got partial remission, 24 ones remain stable and 19 patients got progression. While among the control group, conditions remained stable in 21 patients and progressed in rest 23 ones. The disease control rate (DCR) in the test group and control group were 56.8% (25/44) and 47.7% (21/44) respectively, with no statistical significance (χ2=0.729, P=0.393). The median overall survival time (mOS) of test group and control group were 21.0 (95% CI: 14.9-27.1)months and 10.0 (95% CI: 6.4-13.6) months respectively, and the difference reached statistical significance (χ2=7.436, P=0.006). The median time to tumor progression (mTTP) of test group and control group was 11.0 (95% CI: 8.7-13.3) and 6.0 (95% CI: 3.9-8.1) months respectively, and the difference had statistical significance (χ2=10.437, P=0.001). The adverse events of test group mainly included hand-foot skin reaction, loss of

  12. Orthotopic neobladder reconstruction

    OpenAIRE

    Chang, Dwayne T. S.; Nathan Lawrentschuk

    2015-01-01

    Orthotopic neobladder reconstruction is becoming an increasingly common urinary diversion following cystectomy for bladder cancer. This is in recognition of the potential benefits of neobladder surgery over creation of an ileal conduit related to quality of life (QoL), such as avoiding the need to form a stoma with its cosmetic, psychological and other potential complications. The PubMed database was searched using relevant search terms for articles published electronically between January 19...

  13. [Plasma Biomarkers as Predictive Factors for Advanced Hepatocellular Carcinoma with Sorafenib].

    Science.gov (United States)

    Shiozawa, Kazue; Watanabe, Manabu; Ikehara, Takashi; Matsukiyo, Yasushi; Kogame, Michio; Shinohara, Mie; Kikuchi, Yoshinori; Igarashi, Yoshinori; Sumino, Yasukiyo

    2016-07-01

    We examined plasma biomarkers as predictive factors for advanced hepatocellular carcinoma(ad-HCC)patients treated with sorafenib. We analyzed a-fetoprotein(AFP), AFP-L3, des-g-carboxy prothrombin(DCP), neutrophil-to-lymphocyte ratio(NLR), platelet-to-lymphocyte ratio(PLR), and vascular endothelial growth factor(VEGF)before sorafenib therapy, and changes in AFP-L3, NLR, PLR, and VEGF 1 month after sorafenib therapy in 16 patients. High AFP-L3(hazard ratio: 1.058, 95%CI: 1.019-1.098, p=0.003)and high NLR(hazard ratio: 1.475, 95%CI: 1.045-2.082, p=0.027)were significantly associated with poor prognosis in ad-HCC patients treated with sorafenib. There were no significant differences in changes in AFP-L3, NLR, PLR, and VEGF 1 month after sorafenib therapy. We suggest that AFP-L3 and NLR levels before sorafenib therapy in patients with ad-HCC are an important predictive factor for the therapeutic effect of sorafenib and patient survival. PMID:27431630

  14. Recent Advances in the Imaging Diagnosis of Hepatocellular Carcinoma: Value of Gadoxetic Acid-Enhanced MRI.

    Science.gov (United States)

    Joo, Ijin; Lee, Jeong Min

    2016-02-01

    Magnetic resonance imaging (MRI) using gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DPTA), or gadoxetic acid for short, is a hepatocyte-specific contrast agent which is now increasingly used for the detection and characterization of focal hepatic lesions, particularly in patients at high-risk of developing hepatocellular carcinomas (HCC). In fact, several recent guidelines now recognize gadoxetic acid-enhanced MRI (Gd-EOB-MRI) as the primary diagnostic imaging modality for the noninvasive diagnosis of HCC, although it must be noted that several major guidelines still include only extracellular contrast media-enhanced computed tomography and MRI. The primary merits of Gd-EOB-MRI lie in the fact that it can provide not only dynamic imaging, but also hepatobiliary phase (HBP) imaging which can lead to high lesion-to-liver contrast and give additional information regarding hepatocyte uptake via organic anion transporting polypeptides. This, in turn, allows higher sensitivity in detecting small HCCs and helps provide additional information regarding the multistep process of hepatocarcinogenesis. Indeed, many recent studies have investigated the diagnostic value of Gd-EOB-MRI for early HCCs as well as its role as a potential imaging biomarker in predicting outcome. We herein review the recent advances in the imaging diagnosis of HCCs focusing on the applications of Gd-EOB-MRI and the challenging issues that remain. PMID:26989660

  15. Factors Associated with Post-Progression Survival in Patients with Advanced Hepatocellular Carcinoma Treated with Sorafenib

    Directory of Open Access Journals (Sweden)

    Taiga Otsuka

    2015-05-01

    Full Text Available Sorafenib exerts modest antitumor activity in patients with advanced hepatocellular carcinoma (HCC, and radiological progressive disease (rPD does not always correspond to so-called clinical progressive disease (cPD. We evaluated 101 patients who initiated sorafenib treatment for HCC and assessed post-progression survival (PPS using the Cox proportional hazards model. PPS was calculated from the date of the first rPD until the date of death or the last follow-up. Using Cox model analysis of the 76 patients who experienced first rPD, we identified the Child-Pugh class, Eastern Cooperative Oncology Group performance status, the best antitumor response during treatment (using Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1 and α-fetoprotein levels as independent factors affecting PPS. When these factors were used to define scores ranging from zero to five with a cutoff value of two, PPS of patients who received best supportive care (BSC after rPD was not statistically significantly different from that of patients who received post-rPD therapy with scores ≥2 (p = 0.220. In contrast, the PPS for the post-rPD therapy group was significantly longer compared with the BSC patients with scores <2 (p < 0.001. Patients who scored ≥2 at their first rPD were judged cPD and as candidates for BSC.

  16. 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

  17. 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.

  18. Efficacy, Safety, and Biomarkers of Single-Agent Bevacizumab Therapy in Patients with Advanced Hepatocellular Carcinoma

    Science.gov (United States)

    Malka, David; Bourredjem, Abderrahmane; Dromain, Clarisse; Baey, Charlotte; Jacques, Nathalie; Pignon, Jean-Pierre; Vimond, Nadege; Bouvet-Forteau, Nathalie; De Baere, Thierry; Ducreux, Michel; Farace, Françoise

    2012-01-01

    Objective. Hepatocellular carcinoma (HCC) is a highly vascularized tumor in which neoangiogenesis contributes to growth and metastasis. We assessed the safety, efficacy, and potential biomarkers of activity of bevacizumab in patients with advanced HCC. Methods. In this phase II trial, eligible patients received bevacizumab, 5 mg/kg or 10 mg/kg every 2 weeks. The disease-control rate at 16 weeks (16W-DCR) was the primary endpoint. Circulating endothelial cells (CECs) and plasma cytokines and angiogenic factors (CAFs) were measured at baseline and throughout treatment. Results. The 16W-DCR was 42% (95% confidence interval, 27%–57%). Six of the 43 patients who received bevacizumab achieved a partial response (objective response rate [ORR], 14%). Grade 3–4 asthenia, hemorrhage, and aminotransferase elevation occurred in five (12%), three (7%), and three (7%) patients, respectively. During treatment, placental growth factor markedly increased, whereas vascular endothelial growth factor (VEGF)-A dramatically decreased (p < .0001); soluble VEGF receptor-2 (p < .0001) and CECs (p = .03) transiently increased on day 3. High and increased CEC counts at day 15 were associated with the ORR (p = .04) and the 16W-DCR (p = .02), respectively. Lower interleukin (IL)-8 levels at baseline (p = .01) and throughout treatment (p ≤ .04) were associated with the 16W-DCR. High baseline IL-8 and IL-6 levels predicted shorter progression-free and overall survival times (p ≤ .04). Conclusion. Bevacizumab is active and well tolerated in patients with advanced HCC. The clinical value of CECs, IL-6, and IL-8 warrants further investigation. PMID:22707516

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

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

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

  20. 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

  1. Orthotopic neobladder reconstruction

    Directory of Open Access Journals (Sweden)

    Dwayne T. S. Chang

    2015-01-01

    Full Text Available Orthotopic neobladder reconstruction is becoming an increasingly common urinary diversion following cystectomy for bladder cancer. This is in recognition of the potential benefits of neobladder surgery over creation of an ileal conduit related to quality of life (QoL, such as avoiding the need to form a stoma with its cosmetic, psychological and other potential complications. The PubMed database was searched using relevant search terms for articles published electronically between January 1994 and April 2014. Full-text articles in English or with English translation were assessed for relevance to the topic before being included in the review. Patients with neobladders have comparable or better post-operative sexual function than those with ileal conduits. They also have comparable QoL to those with ileal conduits. Orthotopic neobladder is a good alternative to ileal conduit in suitable patients who do not want a stoma and are motivated to comply with neobladder training. However, the selection of a neobladder as the urinary diversion of choice requires that patients have good renal and liver functions and are likely to be compliant with neobladder training. With benefits also come potential risks of neobladder formation. These include electrolyte abnormalities and nocturnal incontinence. This short review highlights current aspects of neobladder formation and its potential advantages.

  2. 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.

  3. Sorafenib for the treatment of intermediate-advanced hepatocellular carcinomas: its safety and prognostic factors

    International Nuclear Information System (INIS)

    Objective: To discuss the safety and prognostic factors of Sorafenib in treating intermediate- advanced hepatocellular carcinoma (HCC). Methods: From February 2006 to December 2012, eighty-nine patients with pathologically-or clinically-confirmed HCC were treated with Sorafenib targeted therapy. Ten factors, including gender, age, PS score, Child-Pugh, BCLC stage, AFP, vascular invasion, metastasis, therapy model, and regular oral Sorafenib, were evaluated by using univariate analysis and multivariate analysis. The adverse events that were related to Sorafenib targeted therapy were recorded. Results: Follow- up made in March 2013 showed that 27 patients survived, 45 patients died, and 2 patients were lost in touch. The disease control rate (DCR) was 85.14%, mTTP 6.53 months (95%CI: 4.79-8.26), mOS 9.93 months (95%CI: 8.13-11.74). Univariate analysis indicated that low PS score, low Child-Pugh (CP) score, early BCLC stage, non-vascular invasion, and sequential therapy model were significantly associated with longer overall survival (OS) (P<0.05). Multivariate analysis showed that CP score and therapy model were the independent prognostic factors (P<0.05). The adverse events related to oral Sorafenib included mainly hand-foot skin reaction, adverse effect of gastrointestinal tract, fatigue, marrow suppression, etc. Conclusion: The sufficient liver function and TACE with postoperative sequential oral Sorafenib can prolong survival time as well as disease-stable duration. The Sorafenib-related adverse events can be well tolerated by the patients. (authors)

  4. High telomerase activity and long telomeres in advanced hepatocellular carcinomas with poor prognosis.

    Science.gov (United States)

    Oh, Bong-Kyeong; Kim, Haeryoung; Park, Young Nyun; Yoo, Jeong Eun; Choi, Jinsub; Kim, Kyung-Sik; Lee, Jae Jung; Park, Chanil

    2008-02-01

    Telomerase reactivation and telomere maintenance are crucial in carcinogenesis and tumor progression. In this study, the relationships between telomere parameters, chromosomal instability and clinicopathological features were evaluated in hepatocellular carcinomas (HCCs). Telomere length (TL), telomerase activity (TA) and human telomerase reverse transcriptase (hTERT) mRNA levels were measured in 49 hepatitis B virus (HBV)-related HCCs and corresponding non-tumorous tissues. The results were compared with clinicopathological data, including differentiation, multipolar mitosis (MM), anaphase bridge, immunohistochemical stain results for cytokeratin 19 (CK19) and patient outcome. TL of HCCs ranged from 4.7 to 13.1 kb, and 44.4% of HCCs showed telomere lengthening. hTERT mRNA levels and TA were closely related (P=0.008), and were significantly higher in HCCs than non-tumorous tissues. TL was significantly higher in HCCs with strong TA (P=0.048), high hTERT mRNA levels (P=0.001) and poor differentiation (P=0.041). Frequent MM was associated with poor differentiation (P=0.007) and advanced stage (Ptelomeres than CK19- HCCs (P=0.046). Overall survival was poor in HCCs with MM >0.4 per field (P=0.016), high TA (P=0.009) and high TL ratio (HCC/non-HCC) >0.8 (P=0.044). Our results show that long telomeres, high TA and high mitotic instability are poor prognostic markers for HBV-related HCCs and their close association suggests that telomere maintenance may be important for the progression of HCCs with high chromosomal instability to more aggressive ones. PMID:18158557

  5. 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.

  6. 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.

  7. Therapeutic effect of transarterial licartin infusion in combination with transcatheter arterial chemoembolization for advanced hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Objective: To investigate the short term effect of licartin transarterial infusion in combination with chemoembolization (LTACE) and compare its effect with conventional transcatheter arterial chemoembolization (TACE) for advanced hepatocellular carcinoma (HCC). Methods: Seventy-two cases of advanced HCC were included in this analysis. There were 50 males and 22 females with the average age of (58 ± 12) yrs (range 34-86 yrs). Twenty-nine patients received LTACE treatment while the other forty three patients received conventional TACE treatment. Before intervention, there was no variation (P>0.05) in gender (χ2=0.202), Child-Pugh grading for hepatic function (χ2=2.428), as well as in white blood cell count (t=1.101) and platelet count (t=0.080) between the two groups except for age and portal vein thrombosis. For LTACE group, 30 minutes after the infusion of licartin (27.75 MBq/kg) into proper hepatic artery, an emulsion of 40 mg pharmorubicin and 30 ml ultrafluid lipidol was infused until hemostasis within target artery. For TACE group, only an emulsion of 40 mg pharmorubicin and 30ml ultrafluid lipidol was infused until hemostasis within target artery. Following these interventions, the two groups were given the same treatment to stabilize hepatic function and relief embolization-relating symptoms; Patients' follow-up included clinical symptoms and signs, hepatic and renal function, peripheral blood test, CT and radionuclide study(ECT). All data were analyzed with SPSS 11.5. Measurement data were expressed with mean and processed by t test; numeration data were processed by Chi square test and Fisher precise test; Kaplan-Meier analysis and log-rank test were applied for comparing the survival rate of the two groups. P0.05]. ECT imaging demonstrated a 55.17% (16/29) uptake ratio of licartin within tumor areas by the time of 7-days follow-up study. The lesions in both LTACE and TACE groups exhibited a decrease in their size and statistically significant

  8. 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

  9. Advances in Experimental and Translational Research in the Treatment of Hepatocellular Carcinoma

    OpenAIRE

    Kidner, Travis; Dai, Menghua; Adusumilli, Prasad S.; Fong, Yuman

    2008-01-01

    Hepatocellular cancer (HCC) is the fifth-leading cause of cancer and the third-leading cause of cancer related deaths worldwide. Current treatment options are limited as HCC has been shown to be a highly resistant type of cancer to most current treatment modalities. Novel approaches are being explored in the fields of gene therapy, viral oncolytics, radioembolization, and several new biologic therapies. This chapter serves to summarize these recent clinical findings and to discuss what role t...

  10. 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.

  11. 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

  12. 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

  13. 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.

  14. Living Donor Liver Transplantation for Advanced Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis after Concurrent Chemoradiation Therapy.

    Science.gov (United States)

    Han, Dai Hoon; Joo, Dong Jin; Kim, Myoung Soo; Choi, Gi Hong; Choi, Jin Sub; Park, Young Nyun; Seong, Jinsil; Han, Kwang Hyub; Kim, Soon Il

    2016-09-01

    Locally advanced hepatocellular carcinoma (HCC) with portal vein thrombosis carries a 1-year survival rate advanced HCC at initial diagnosis were given CCRT, followed by HAIC, and underwent LDLT at the Severance Hospital, Seoul, Korea. CCRT [45 Gy over 5 weeks with 5-fluorouracil (5-FU) as HAIC] was followed by HAIC (5-FU/cisplatin combination every 4 weeks for 3-12 months), adjusted for tumor response. Down-staging succeeded in all eight patients, leaving no viable tumor thrombi in major vessels, although three patients first underwent hepatic resections. Due to deteriorating liver function, transplantation was the sole therapeutic option and offered a chance for cure. The 1-year disease-free survival rate was 87.5%. There were three instances of post-transplantation tumor recurrence during follow-up monitoring (median, 17 months; range, 10-22 months), but no deaths occurred. Median survival time from initial diagnosis was 33 months. Four postoperative complications recorded in three patients (anastomotic strictures: portal vein, 2; bile duct, 2) were resolved through radiologic interventions. Using an intensive tumor down-staging protocol of CCRT followed by HAIC, LDLT may be a therapeutic option for selected patients with locally advanced HCC and portal vein tumor thrombosis. PMID:27401662

  15. 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.

  16. 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

  17. Current and Future Treatment Strategies for Patients with Advanced Hepatocellular Carcinoma: Role of mTOR Inhibition.

    Science.gov (United States)

    Finn, Richard S

    2012-11-01

    Hepatocellular carcinoma (HCC) is a common cancer that has the third highest cancer-related mortality rate worldwide. Although potentially curable by transplantation if detected early, the majority of cases are diagnosed at an advanced stage of disease for which limited treatment options are available. The only proven systemic therapy for advanced HCC is sorafenib, a multi-kinase inhibitor that has demonstrated modest efficacy and reasonable tolerability in patients with advanced HCC. Five years after the approval of sorafenib, no other agent has been proven to be beneficial in the first- or second-line setting in advanced HCC. While molecular studies have highlighted various potential targets in HCC, the mammalian target of rapamycin (mTOR) has emerged as an exciting target for cancer therapy including HCC. Laboratory data have linked the phosphatidylinositol 3-kinase/AKT/mTOR axis to various oncogenic processes, including survival and angiogenesis. Historically, mTOR inhibitors have been used for their immunosuppressive properties, but more recently they have been approved as anticancer agents. Retrospective HCC studies suggest that the inclusion of mTOR inhibition as part of an immunosuppressant regimen after transplantation may reduce HCC recurrence compared with other immunosuppressive agents such as calcineurin inhibitors. More recently, single-arm, phase I/II studies have shown that mTOR inhibitors also have activity as monotherapy in cases of recurrent HCC or de novo advanced HCC. This article will review the rationale for targeting the mTOR pathway in HCC, and the currently available clinical data supporting its development for HCC. PMID:24159589

  18. 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.

  19. Phase II trial of bevacizumab and erlotinib as a second-line therapy for advanced hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Kaseb AO

    2016-02-01

    Full Text Available Ahmed O Kaseb,1 Jeffrey S Morris,2 Michiko Iwasaki,1 Humaid O Al-Shamsi,1 Kanwal Pratap Singh Raghav,1 Lauren Girard,1 Sheree Cheung,1 Van Nguyen,3 Khaled M Elsayes,4 Lianchun Xiao,2 Reham Abdel-Wahab,1,5 Ahmed S Shalaby,1 Manal Hassan,1 Hesham M Hassabo,1 Robert A Wolff,1 James C Yao1 1Department of Gastrointestinal Medical Oncology, 2Department of Biostatistics, 3Department of Pharmacy, 4Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA; 5Department of Clinical Oncology, Assiut University Hospital, Assiut, Egypt Trial registry: Clinicaltrials.gov #NCT01180959. Background: Early clinical studies of bevacizumab and erlotinib in advanced hepatocellular carcinoma (HCC have a tolerable toxicity and a promising clinical outcome. We evaluated the efficacy and tolerability of this combination as a second-line therapy for HCC refractory to sorafenib. Methods: For this single-arm, Phase II study, we recruited patients with Child–Pugh class A or B liver disease, Eastern Cooperative Oncology Group performance status 0–2, and advanced HCC that was not amenable to surgical or regional therapies and treatment with sorafenib had failed (disease progressed or patient could not tolerate sorafenib. Patients received 10 mg/kg intravenous bevacizumab every 14 days and 150 mg oral erlotinib daily for 28-day cycles until progression. Tumor response was evaluated every two cycles using Response Evaluation Criteria in Solid Tumors. The primary end point was the 16-week progression-free survival rate. Secondary end points included time to progression and overall survival. Results: A total of 44 patients were enrolled and had a median follow-up time of 33.8 months (95% confidence interval [CI]: 23.5 months – not defined. The 16-week progression-free survival rate was 43% (95% CI: 28%–59%, median time to progression was 3.9 months (95% CI: 2.0–8.3 months, and median overall survival duration was 9.9 months

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. Application of tumor-node-metastasis staging 2002 version in locally advanced hepatocellular carcinoma: is it predictive of surgical outcome?

    International Nuclear Information System (INIS)

    Locally advanced (pT3-4N0M0) hepatocellular carcinoma (HCC) is a heterogeneous group of tumors, which consists of four different categories, including HCC with 'multiple tumors more than 5 cm', 'major vascular invasion', 'invasion of adjacent organs', and 'perforation of visceral peritoneum'. The aim of our study was to verify whether the 2002 version of the Tumor-Node-Metastasis staging system could predict surgical outcomes in patients with locally advanced HCC. We retrospectively reviewed 298 patients with pT3-4N0M0 HCC who underwent hepatic resection from 1993 to 2000 in an academic tertiary hospital. Overall survival (OS) and cumulative recurrence rate (CRR) of the four categories of locally advanced HCC patients were compared. In multivariate analysis, major vascular invasion was identified as the most significant factor (HR = 3.291, 95% CI 2.362-4.584, P < 0.001) followed by cirrhosis status on OS, and was found to be the only independent factor of CRR (HR = 2.242, 95% CI 1.811-3.358, P < 0.001) in patients with locally advanced HCC. Among the four categories of locally advanced HCC, OS was significantly worse, and CRR was significantly higher in patients with HCC with major vascular invasion (pT3) than with multiple tumors more than 5 cm (pT3); or tumor invasion of adjacent organs (pT4); or perforation of visceral peritoneum (pT4). No significant differences were observed in OS or CRR between the latter three groups of patients. HCC with major vascular invasion, which are classified as pT3 under the current TNM staging, have the worst prognosis when compared with the other categories of pT3-4 disease. There is a need to redefine the T classification and to stratify locally advanced HCC

  5. 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.

  6. 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.

  7. Sorafenib for Egyptian patients with advanced hepatocellular carcinoma; single center experience

    Directory of Open Access Journals (Sweden)

    Omar Abdel-Rahman

    2014-03-01

    Conclusions: In limited resource countries like Egypt, we suggest that the use of sorafenib for the treatment of advanced HCC cases should be restricted to a highly selected subgroup of patients with good performance and child A.

  8. Sorafenib in Advanced Hepatocellular Carcinoma: A Nationwide Retrospective Study of Efficacy and Tolerability

    OpenAIRE

    Anne Helene Køstner; Morten Sorensen; René Krøjgaard Olesen; Henning Grønbæk; Ulrik Lassen; Morten Ladekarl

    2013-01-01

    Background. 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 we explore the role of alpha-fetoprotein ( α FP) as a potential biomarker for treatment efficacy and correlation to survival. Methods. Seventy-six patients with advanced HCC, not eligible ...

  9. 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.

  10. 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.

  11. Clinical trial of combination therapy using systemic interleukin-2 infusion and low-dose tumor irradiation for advanced hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Although recent progress in surgical techniques and interventional radiology enables patients with hepatocellular carcinoma (HCC) to survive longer, there are still many who cannot receive them due to disease progression. We are currently investigating the therapeutic efficacy of the combination of systemic recombinant interleukin-2 (IL-2) administration and local tumor irradiation for HCC patients in the advanced stage. First, the results of the basic experiment to analyze the optimal dose and timing of IL-2 infusion were demonstrated. Intensive administration of high-dose IL-2 caused acute death, whereas intermittent low-dose IL-2 administration resulted in complete tumor regression followed by the acquisition of tumor-specific immunity. Our data suggested that the tumor-bearing state increased the responsiveness to IL-2 treatment, and that an excessively high-dose regimen is not prerequisite for the optimal IL-2 treatment. With regard to the effectiveness of radiotherapy for HCC, human hepatoma cells exhibited apoptotic death when hepatoma cells were cocultured with LAK cells, or were irradiated in vitro with relatively low-dose irradiation. These results suggested the possible synergistic effect of killer cells and low-dose irradiation. Finally, we presented six eligible cases of advanced HCC treated by combination therapy of IL-2 infusion and local low-dose tumor irradiation. Direct anti-tumor effects were one CR, one MR, two NC, and two PD. One CR case and a NC case have survived now for longer than 40 months. In all cases, NK cell activity increased prominently, and side effects wee mild flu-like symptoms except macroscopic hematuria and moderate VLS-like symptoms in two cases in which therapy was continued for longer than 2 years. Hepatic reserve function like prothrombin time or hepaplastic time improved. The apparent clinical effectiveness of the combination therapy presented here might give promising hints for a new therapeutic strategy for HCC. (author)

  12. [A case of advanced hepatocellular carcinoma successfully treated by liver resection after complete response induced by sorafenib administration].

    Science.gov (United States)

    Kim, Yongkook; Hosoda, Yohei; Kakita, Naruyasu; Yamada, Yukinori; Yamasaki, Masaru; Nishino, Masaya; Okano, Miho; Nagai, Kenichi; Yasui, Masayoshi; Tsujinaka, Toshimasa

    2014-11-01

    A 50-year-old man presented to our hospital with the chief complaint of right hypochondriac pain and a palpable tumor. Advanced hepatocellular carcinoma (HCC) and chronic hepatitis B infection were diagnosed and treated by twice-repeated transcatheterarterial chemoembolization (TACE) followed by administration of entecavir. Two months after the last TACE, alpha-fetoprotein(AFP)and protein induced by vitamin K absence or antagonistII (PIVKA-II) levels had elevated, and multiple small early enhancing nodules were detected on computed tomography(CT)scan. Based on his age and liver function (Child-Pugh score A5), a full dose of sorafenib (800 mg/day) was administered. The sorafenib dose was decreased after one month to 400mg/day because of hand-foot syndrome. Following sorafenib administration, the lesions shrank markedly, and complete response (CR) according to modified Response Evaluation Criteria In Solid Tumors(mRECIST)was achieved within 4 months. Six months after sorafenib treatment was begun, recurrent HCC was detected in segment 6, near the previously treated lesion. The decreased size of the main tumor and normalization of AFP levels allowed curative surgical resection. The patient was discharged 5 days after surgery and is currently treated with a half dose of sorafenib. Thirteen months after surgery, a small early enhancing lesion is visible on postoperative CT scan, but AFP and PIVKA-II levels are still keeping in a normal range. This case demonstrates that if sorafenib treatment is effective, then subsequent surgical treatment can be reconsidered in patients with advanced HCC responding to this combined therapy. PMID:25731444

  13. 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.

  14. Sorafenib combined with transarterial chemoembolization versus transarterial chemoembolization alone for advanced-stage hepatocellular carcinoma: a propensity score matching study.

    Directory of Open Access Journals (Sweden)

    Hao Hu

    Full Text Available AIMS: The purpose of the present study was to compare the efficacies of transarterial chemoembolization (TACE combined with sorafenib versus TACE monotherapy for treating patients with advanced hepatocellular carcinoma (HCC. METHODS: We enrolled 321 patients and selected 280 with advanced HCC (Barcelona Clinic Liver Cancer stage C who underwent TACE therapy between February 2009 and February 2013. TACE alone (monotherapy group was administered to 198 patients (70.7%, and the remaining 82 (29.3% underwent repeat combined TACE and sorafenib therapy (combined group. To minimize selection bias, these latter 82 patients were matched using propensity-score matching at a 1∶2 ratio with 164 patients who received TACE monotherapy. The primary endpoints were overall survival (OS and related subgroup analysis. The secondary endpoints were time to progression (TTP and treatment-related adverse events. RESULTS: Of the respective patients in the combined and monotherapy groups, 64.6% and 49.2% had vascular invasion, 87.8% and 91.1% had extrahepatic metastasis, and 54.3% and 47.1% had both. In the propensity-score-matched cohort, the OS survival of the combined group was significantly higher compared with the monotherapy group (7.0 months vs. 4.9 months, respectively, P = 0.003. The TTP was significantly longer in the combined group (2.6 months vs. 1.9 months, respectively, P = 0.001. Subgroup analysis showed that the outcomes of patients with advanced HCC without main portal vein invasion who were treated with combined therapy were significantly better compared with those who received monotherapy (P<0.05. Univariate and subsequent multivariate analyses revealed that the addition of sorafenib was an independent predictor of favorable OS and TTP (adjusted hazard ratios, 0.63 and 0.62, respectively; P<0.05 for both. CONCLUSION: Sorafenib plus TACE was more effective than TACE monotherapy for treating patients with advanced HCC without main portal vein

  15. 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.

  16. Sorafenib for Egyptian patients with advanced hepatocellular carcinoma; single center experience

    International Nuclear Information System (INIS)

    Background: According to the results of a number of phase 3 randomized studies, sorafenib is the only approved systemic therapy for advanced HCC; however the issue of high eco- Sorafenib nomic cost remains challenging; thus we have conducted this retrospective analysis of our HCC patients treated with sorafenib. Methods: HCC Shams University Hospitals, in the period between 2010 and 2012 were reviewed. Eligible patients were those who had received sorafenib for advanced HCC not eligible for or progressed after surgery or locoregional therapy. We investigated the impact of baseline clinico pathological factors (age, gender, child status, performance score, BCLC tumor stage, cause of chronic liver disease, median baseline alpha fetoprotein level and previous treatment received for HCC) on overall survival (OS) in an adjusted Cox regression model. Results: 41 patients were included in the analysis fulfilling the inclusion criteria. At a median follow up period of 13 months, the median PFS for the whole group was 4 months; the median OS for the whole group is 6.25 months. Multivariate analysis identified three baseline characteristics that were prognostic indicators for overall survival: ECOG performance status (median OS for ECOG 1 = 7.01 months and for ECOG 2 = 3.03 months), Child-Pugh status (median OS for child A = 12.04 months and for child B = 5.23 months), and median baseline levels of alpha-fetoprotein. Conclusions: In limited resource countries like Egypt, we suggest that the use of sorafenib for the treatment of advanced HCC cases should be restricted to a highly selected subgroup of patients with good performance and child A.

  17. Early MRI response monitoring of patients with advanced hepatocellular carcinoma under treatment with the multikinase inhibitor sorafenib

    Directory of Open Access Journals (Sweden)

    Gregor Michael

    2009-06-01

    Full Text Available Abstract Background New therapeutic principles in clinical oncology require the adjustment of response criteria to govern therapy decisions. For advanced hepatocellular carcinoma (HCC a new era has recently begun by the approval of the multikinase inhibitor sorafenib. As a unique feature, HCC usually develops in a diseased liver and current imaging technologies employing classical response criteria have not been prospectively evaluated for this new treatment. Methods MRI signal patterns were assessed in 21 advanced HCC patients receiving sorafenib. MRI was performed at baseline and in short-term intervals thereafter. Signal changes under therapy on T1WI, T2WI and post-gadolinium images including necrosis volume and its ratio to the entire tumor volume were compared to baseline imaging. To assess the association between the categorical variables, Fisher's exact tests were applied for a statistical analysis. Survey time ranged from 2–65 weeks, and a total of 39 target lesions were evaluated. Results Signal abnormalities during sorafenib therapy were disclosed by T1WI and T2WI in 15/21 patients. The predominant tumor signal change was hyperintensity on both T1WI and T2WI. Interestingly, most patients developed MRI signal changes within 4 weeks of therapy; in contrast, two non-responders did not show any signal alteration at follow-up. Under therapy, 16/21 patients presented with new or progressive necrosis, whereas 7 patients achieved temporarily >75% tumor necrosis under sorafenib. Significantly associated MRI variables were increase in T1WI signal and tumor necrosis (p = 0.017 as well as increase of tumor necrosis with an elevated ratio of necrotic to vital tumor areas (p = 0.002. Remarkably, some (3/13 of the patients developing necrotic tumor areas showed a relevant (>20% increase in tumor volume, which should be considered in the assessment of imaging studies. Conclusion As sorafenib induces early intralesional necrosis with profound changes

  18. [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.

  19. Societal reintegration following cadaveric orthotopic liver transplantation

    Science.gov (United States)

    Kelly, Ryan; Hurton, Scott; Ayloo, Subhashini; Cwinn, Mathew; De Coutere-Bosse, Sarah

    2016-01-01

    Background Studies on patients’ societal reintegration following orthotopic liver transplantation (OLT) are scarce. Methods Between September 2006 and January 2008, all adults who were alive after 3 years post OLT were included in this prospective cohort study. Validated questionnaires were administered to all candidates with the primary aim of investigating the rate of their social re-integration following OLT and potential barriers they might have encountered. Results Among 157 eligible patients 110 (70%) participated. Mean participants’ age was 57 years (SD 11.4) and 43% were females. Prior to OLT, 75% of patients were married and 6% were divorced. Following OLT there was no significant difference in marital status. Employment rate fell from 72% to 30% post-OLT. Patients who had been employed in either low-skill or advanced-skill jobs were less likely to return to work. After OLT, personal income fell an average of 4,363 Canadian dollars (CAN$) (SD 20,733) (P=0.03) but the majority of recipients (80%) reported high levels of satisfaction for their role in society. Conclusions Although patients’ satisfaction post-OLT is high, employment status is likely to be negatively affected for individuals who are not self-employed. Strategies to assist recipients in returning to their pre-OLT jobs should be developed to improve patients’ economical status and societal ability to recoup resources committed for OLT. PMID:27275465

  20. Models of Hepatocellular Carcinoma and Biomarker Strategy

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-07-07

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

  1. Models of Hepatocellular Carcinoma and Biomarker Strategy

    International Nuclear Information System (INIS)

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

  2. Current status of auxiliary partial orthotopic liver transplantation for acute liver failure.

    Science.gov (United States)

    Rela, Mohamed; Kaliamoorthy, Ilankumaran; Reddy, Mettu Srinivas

    2016-09-01

    Auxiliary partial orthotopic liver transplantation (APOLT) is a technique of liver transplantation (LT) where a partial liver graft is implanted in an orthotopic position after leaving behind a part of the native liver. APOLT was previously considered technically challenging with results inferior to orthotopic liver transplantation. Results of this procedure have continued to improve with improving surgical techniques and a better understanding of the natural history of acute liver failure (ALF) and liver regeneration. The procedure is being increasingly accepted as a valid treatment option for ALF-especially in children. This article reviews the historical background to this operation, advances in the technique, and its current place in the management of ALF. Liver Transplantation 22 1265-1274 2016 AASLD. PMID:27357489

  3. Immunology of hepatocellular carcinoma

    OpenAIRE

    Sachdeva, Meenakshi; Chawla, Yogesh K.; Arora, Sunil K

    2015-01-01

    Hepatocellular carcinoma (HCC) is primarily a malignancy of the liver, advancing from a damaged, cirrhotic liver to HCC. Globally, HCC is the sixth most prevalent cancer and the third-most prevalent reason for neoplastic disease-related deaths. A diverse array of infiltrating immunocytes regulates the development and progression of HCC, as is the case in many other cancers. An understanding of the various immune components during HCC becomes necessary so that novel therapeutic strategies can ...

  4. Comparison of five models for end-stage liver disease in predicting the survival rate of patients with advanced hepatocellular carcinoma.

    Science.gov (United States)

    Hong, Ying-Fen; Chen, Zhan-Hong; Ma, Xiao-Kun; Li, Xing; Wu, Dong-Hao; Chen, Jie; Dong, Min; Wei, Li; Wang, Tian-Tian; Ruan, Dan-Yun; Lin, Ze-Xiao; Wen, Jing-Yun; Lin, Qu; Jia, Chang-Chang; Wu, Xiang-Yuan

    2016-04-01

    Prognosis of patients with advanced hepatocellular carcinoma (HCC) is under expectation. Life expectancy more than 3 months is one inclusion criteria for molecular targeted drugs in clinical trials. The main purpose of this research is to compare Model for End-Stage Liver Disease (MELD) and four MELD-based prognostic models in predicting the survival rate of advanced HCC patients. One hundred eighty-three patients with advanced HCC who were not amendable to standard anti-tumor therapy were retrospectively analyzed. Data were collected to classify patients according to MELD, Model for End-Stage Liver Disease with the incorporation of serum sodium (MELD-NA), Model for End-Stage Liver Disease to ascites and sodium (MELD-AS), integrated Model for End-Stage Liver Disease (iMELD), and Model for End-Stage Liver Disease to sodium (MESO) scores at diagnosis. 1-, 3-, and 6-month survivals were the end points used in the analysis. When predicting 1-month survival, MELD-AS, MELD, and MESO were the top 3 ranking staging systems. When predicting 3-month survival, area under the receiver operating characteristic curve (AUC) of MELD-AS is significantly higher than that of the other models (P best model in the prediction of short and intermediate survival among the five models for end-stage liver disease analyzed for Chinese advanced HCC patients. PMID:26561464

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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...

  10. Assessment of a model based optimization engine for volumetric modulated arc therapy for patients with advanced hepatocellular cancer

    International Nuclear Information System (INIS)

    To evaluate in-silico the performance of a model-based optimization process for volumetric modulated arc therapy (RapidArc) applied to hepatocellular cancer treatments. 45 clinically accepted RA plans were selected to train a knowledge-based engine for the prediction of individualized dose-volume constraints. The model was validated on the same plans used for training (closed-loop) and on a set of other 25 plans not used for the training (open-loop). Dose prescription, target size, localization in the liver and arc configuration were highly variable in both sets to appraise the power of generalization of the engine. Quantitative dose volume histogram analysis was performed as well as a pass-fail analysis against a set of 8 clinical dose-volume objectives to appraise the quality of the new plans. Qualitative and quantitative equivalence was observed between the clinical and the test plans. The use of model-based optimization lead to a net improvement in the pass-rate of the clinical objectives compared to the plans originally optimized with standard methods (this pass-rate is the frequency of cases where the objectives are respected vs. the cases where constraints are not fulfilled). The increase in the pass-rate resulted of 2.0%, 0.9% and 0.5% in a closed-loop and two different open-loop validation experiments. A knowledge-based engine for the optimization of RapidArc plans was tested and lead to clinically acceptable plans in the case of hepatocellular cancer radiotherapy. More studies are needed before a broad clinical use

  11. The Next Generation of Orthotopic Thyroid Cancer Models: Immunocompetent Orthotopic Mouse Models of BRAFV600E-Positive Papillary and Anaplastic Thyroid Carcinoma

    OpenAIRE

    Vanden Borre, Pierre; McFadden, David G.; Gunda, Viswanath; Sadow, Peter M.; Varmeh, Shohreh; Bernasconi, Maria; Jacks, Tyler; Parangi, Sareh

    2014-01-01

    Background: While the development of new treatments for aggressive thyroid cancer has advanced in the last 10 years, progress has trailed headways made with other malignancies. A lack of reliable authenticated human cell lines and reproducible animal models is one major roadblock to preclinical testing of novel therapeutics. Existing xenograft and orthotopic mouse models of aggressive thyroid cancer rely on the implantation of highly passaged human thyroid carcinoma lines in immunodeficient m...

  12. 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.

  13. 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.

  14. miRNA在肝癌中的研究进展%ADVANCES ON RESEARCH OF MIRNA AND HEPATOCELLULAR CARCINOMA

    Institute of Scientific and Technical Information of China (English)

    朱贵忠; 聂明

    2011-01-01

    MiRNAs are a group of tiny RNAs with a fundamental role in the rugulation of gene expression. The role of miRNAs either as ontogenesis or tumor suppressors has been established. Aberrant expression of several miRNAs was found to be involved in human hepatocarcinogenesis. MiRNA expression signatures were correlated with bio-pathological and clinical features of hepatocellular carcinoma (HCC). Aberrantly expressed miRNAs could be linked to cancer-associated pathways, indicating a direct role in liver carcinogenesis. These findings suggest that miRNAs could become novel molecular targets for HCC treatment%miRNAs是一类小RNAs,调节基因的表达,有致癌基因和肿瘤抑制基因的作用.部分miRNAs的差异表达参与了人类的肝脏肿瘤形成,miRNAs的表达与HCC的生物病理和临床特征相关.研究报道差异表达的miRNAs与肿瘤相关的转导通路有联系,提示在HCC形成中发挥直接作用,使得miRNAs可能成为HCCs治疗的理想分子靶标.

  15. 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

  16. Orthotopic Injection of Pancreatic Cancer Cells.

    Science.gov (United States)

    Aiello, Nicole M; Rhim, Andrew D; Stanger, Ben Z

    2016-01-01

    Pancreatic ductal adenocarcinoma is an aggressive disease with a 5-yr survival rate of only 5%. The location of the pancreas in the abdomen, where it is obscured by other organs, makes it a difficult tissue to study and manipulate. This protocol describes in detail how to orthotopically inject cancer cells into the pancreas in mice. This technique is particularly useful when the cells must be manipulated in ways that cannot be modeled genetically. PMID:26729902

  17. Development of Orthotopic Pancreatic Tumor Mouse Models

    OpenAIRE

    Qiu, Wanglong; Gloria H. Su

    2013-01-01

    Genetically engineered mouse models of pancreatic cancer that recapitulate human pancreatic tumorigenesis have been established. However, the cost associated with generating and housing these mice can be prohibitive. Tumor latency and progression to invasive diseases in these models are also highly variable. Xenograft mouse models of human pancreatic cancer including heterotopic and orthotopic have been widely used in preclinical studies for their comparatively low cost and rapid, predictable...

  18. 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).

  19. 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.

  20. 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

  1. 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.

  2. 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.

  3. Successful twin pregnancy after orthotopic liver transplantation

    Directory of Open Access Journals (Sweden)

    Coelho Júlio Cezar Uili

    2002-01-01

    Full Text Available AIM: Report of a case of successful twin pregnancy following liver transplantation. PATIENT AND METHOD: A 42-year-old nulliparous-woman was subjected to an orthotopic liver transplantation due to Budd-Chiari syndrome. Sixteen months after the transplantation, an ultrasonography revealed twin pregnancy. Her prenatal course was uneventful, except for mild arterial hypertension. The immunosuppressive agents used during pregnancy were cyclosporine and prednisone. RESULT: The patient gave birth to two healthy girls at 37 weeks of gestation. The patient's postpartum course was uneventful with normal liver and renal function tests. CONCLUSION: Following successful pregnancy, women may become pregnant and give birth to normal children, including twins

  4. Relationship between therapeutic efficacy of arterial infusion chemotherapy and expression of P-glycoprotein and p53 protein in advanced hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Masahide Akimoto; Masaharu Yoshikawa; Masaaki Ebara; Tsunenobu Sato; Hiroyuki Fukuda; Fukuo Kondo; Hiromitsu Saisho

    2006-01-01

    AIM: To investigate the relationship between the chemotherapeutic drug efficacy and the expression of P-glycoprotein (PGP) and p53 protein in advanced hepatocellular carcinoma (HCC).METHODS: The study was conducted on 41 patients with advanced HCC who were treated by repeated arterial infusion chemotherapy. Biopsy specimens from the tumor were collected before the start of treatment in all the patients, and the specimens were stored frozen until immunohistochemical staining, which was performed after the start of treatment, to detect PGP and p53 protein expressions. Twenty of the fortyone patients were treated with an anthracycline drug (epirubicin hydrochloride; anthracycline group), and the remaining 21 were treated with a non-anthracycline drug (mitoxantrone hydrochloride in 11 patients and carboplatin in 10 patients; non-anthracycline group). The relationship between the chemotherapeutic efficacy and the results of immunostaining were compared between the two groups.RESULTS: Before the start of the treatment, PGPpositive rate was 90.2% (strongly-positive, 36.6%) and p53 protein-positive rate was 34.1% (strongly-positive,19.5%). In the anthracycline group, the response rate was 40.0%. The number of patients showing poor response to the treatment was significantly larger in the patients with strongly positive PGP expression (P= 0.005),and their prognoses were poor (P=0.001). In the nonanthracycline group, the response rate was 42.9%,and there was no significant relationship between the chemotherapeutic drug efficacy and the PGP or p53protein expression. When only the data from the 11patients treated with anthraquinone drug, mitoxantrone,were analyzed, however, the number of patients who showed poor response to treatment was significantly higher among the p53-positive patients (P=0.012),irrespective of the survival outcome.CONCLUSION: The chemotherapeutic efficacy with an anthracycline drug for advanced HCC can be predicted by immunohistochemical analysis of PGP

  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. A phase I study on combined therapy with proton-beam radiotherapy and in situ tumor vaccination for locally advanced recurrent hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Proton-beam radiotherapy (PBT) has been shown to be effective to hepatocellular carcinoma (HCC) as a nonsurgical local treatment option. However, HCC still remains as one of the most difficult cancers to be cured because of frequent recurrences. Thus, methods to inhibit the recurrence need to be explored. To prevent the HCC recurrence, we here report on a prospective phase I study of ‘in situ’ tumor vaccination using CalTUMP, a newly developed immunoadjuvant consisting of BCG extract bound to hydroxyapatite and microparticulated tuberculin, following local PBT for HCC. Patients with locally advanced recurrent HCC, which had been heavily pretreated with various treatments, were enrolled. PBT was performed with the conventional method to the target HCC. Subsequently, CalTUMP was injected into the same irradiated-tumor three times at one-week intervals. Three dose-levels of CalTUMP (1/10, 1/3, and 1/1) were administered to 3 patients each. Vital signs, blood samples, ultrasound, and computed tomographic scans were monitored to evaluate the safety. Three intratumoral injections of CalTUMP following PBT (median dose: 72.6 GyE) were accomplished in 9 patients. Transient low-grade fever and minor laboratory changes were observed in 7 patients after CalTUMP injections. No other treatment-related adverse events were observed. Median progression-free survival was 6.0 months (range: 2.1-14.2) and 4 patients were progression-free for more than 1 year. Intratumoral injection of CalTUMP following PBT was feasible and safe in patients with heavily pre-treated HCC. Further clinical studies to evaluate the efficacy of this in situ tumor vaccination are warranted

  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. Tumor lysis syndrome following transarterial chemoembolization for advanced hepatocellular carcinoma:report of one case%原发性肝癌TACE术后肿瘤坏死综合征一例

    Institute of Scientific and Technical Information of China (English)

    贾中芝; 田丰; 蒋国民

    2014-01-01

    Tumor lysis syndrome (TLS) results from a sudden and rapid release of nuclear and cytoplasmic degradation products from malignant cells. It is a rare complication in adult patients with solid tumors who are undergoing treatment. Herein, the authors present a case with advanced hepatocellular carcinoma (HCC) who developed TLS after transarterial chemoembolization (TACE), which was successfully treated with aggressive fluid administration, oral allopurinol and urine alkalization, hemodialysis and other supportive therapies. TLS following TACE should be suspected in HCC patients who has large and rapidly-growing lesion.

  9. Gene expression-based chemical genomics identifies potential therapeutic drugs in hepatocellular carcinoma.

    Directory of Open Access Journals (Sweden)

    Ming-Huang Chen

    Full Text Available Hepatocellular carcinoma (HCC is an aggressive tumor with a poor prognosis. Currently, only sorafenib is approved by the FDA for advanced HCC treatment; therefore, there is an urgent need to discover candidate therapeutic drugs for HCC. We hypothesized that if a drug signature could reverse, at least in part, the gene expression signature of HCC, it might have the potential to inhibit HCC-related pathways and thereby treat HCC. To test this hypothesis, we first built an integrative platform, the "Encyclopedia of Hepatocellular Carcinoma genes Online 2", dubbed EHCO2, to systematically collect, organize and compare the publicly available data from HCC studies. The resulting collection includes a total of 4,020 genes. To systematically query the Connectivity Map (CMap, which includes 6,100 drug-mediated expression profiles, we further designed various gene signature selection and enrichment methods, including a randomization technique, majority vote, and clique analysis. Subsequently, 28 out of 50 prioritized drugs, including tanespimycin, trichostatin A, thioguanosine, and several anti-psychotic drugs with anti-tumor activities, were validated via MTT cell viability assays and clonogenic assays in HCC cell lines. To accelerate their future clinical use, possibly through drug-repurposing, we selected two well-established drugs to test in mice, chlorpromazine and trifluoperazine. Both drugs inhibited orthotopic liver tumor growth. In conclusion, we successfully discovered and validated existing drugs for potential HCC therapeutic use with the pipeline of Connectivity Map analysis and lab verification, thereby suggesting the usefulness of this procedure to accelerate drug repurposing for HCC treatment.

  10. Cryotherapy for hepatocellular carcinoma

    DEFF Research Database (Denmark)

    Awad, Tahany; Thorlund, Kristian; Gluud, Christian

    2009-01-01

    BACKGROUND: Hepatocellular carcinoma is the most common primary malignant cancer of the liver. Evidence for the role of cryotherapy in the treatment of hepatocellular carcinoma is controversial. OBJECTIVES: The aim of this review is to evaluate the potential benefits and harms of cryotherapy for...... the treatment of hepatocellular carcinoma. SEARCH STRATEGY: We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and LILACS until June 2009. We identified further studies by...... hepatocellular carcinoma. Randomised clinical trials with low-risk of bias may help in defining the role of cryotherapy in the treatment of hepatocellular carcinoma....

  11. Necrotizing Encephalitis Caused by Disseminated Aspergillus Infection after Orthotopic Liver Transplantation

    Directory of Open Access Journals (Sweden)

    Luis E. Barrera-Herrera

    2015-01-01

    Full Text Available Liver transplantation is the only available treatment for some patients with end-stage liver disease. Despite reduction in mortality rates due to advances related to surgical techniques, intensive medical management and immunosuppressive therapy, invasive fungal infections remain a serious complication in orthotopic liver transplantation. We report the case of an 18-year-old male diagnosed with autoimmune cirrhosis in 2009 who was assessed and listed for liver transplantation for massive variceal hemorrhage. One year after listing a successful orthotopic liver transplantation was performed. Uneventful early recovery was achieved; however, he developed pulmonary and neurological Aspergillus infection 23 and 40 days after surgery, respectively. Antibiotic therapy with voriconazole and amphotericin was started early, with no major response. Neuroimaging revealed multiple right frontal and right parietal lesions with perilesional edema; surgical management of the brain abscesses was performed. A biopsy with periodic acid-Schiff and Gomori stains revealed areas with mycotic microorganisms morphologically consistent with Aspergillus, later confirmed by culture. The patient developed necrotizing encephalitis secondary to aspergillosis and died. Necrotizing encephalitis as a clinical presentation of Aspergillus infection in an orthotopic liver transplant is not common, and even with adequate management, early diagnosis and prompt antifungal treatment, mortality rates remain high.

  12. Hepatocellular carcinoma.

    Science.gov (United States)

    Edwards, J T; Macdonald, G A

    2000-05-01

    The incidence of hepatocellular carcinoma (HCC) appears to be declining in Taiwan and potentially in other high-prevalence areas as a consequence of vaccination for hepatitis B virus (HBV). However, there is evidence that the incidence of HCC is increasing in North America and Europe. This appears to be related to the increasing prevalence and duration of hepatitis C virus (HCV) infection in these countries. There is also growing evidence to support an increase in the risk of HCC in patients with HCV who are coinfected with occult HBV (patients who have lost HBV surface antigen but still have detectable HBV DNA either in blood or liver). Occult HBV infection in patients with HCV may be more common than previously thought, and HCC that occurs in this setting appears to have a worse prognosis. There is continuing interest in the effect of interferon therapy on the incidence of HCC in patients with HCV. Several studies from Japan have shown a benefit in patients without cirrhosis, although there are a number of potentially confounding variables that may partly explain these results. Prospective randomized studies are needed to investigate this important question. The molecular biology of HCC and the events of malignant transformation in the liver continue to be areas of intense study. Recently, there has been considerable interest in telomeres, the repeat units on the ends of chromosomes, and the enzyme that maintains these, telomerase. Telomeres shorten with each cell division and can be used to determine the number of divisions a cell has undergone. Eventually they reach a critical length, with further loss resulting in cellular senescence. Telomerase restores telomere length and may help malignant cells escape senescence. Nearly all HCCs have telomerase activity and assessments of telomeres and telomerase may be clinically useful. PMID:17023886

  13. 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.

  14. Octreotide for advanced hepatocellular carcinoma:Meta-analysis of randomized controlled trials%奥曲肽治疗晚期肝癌的Meta分析

    Institute of Scientific and Technical Information of China (English)

    黄伟平; 俞力军

    2010-01-01

    Objective To evaluate the effect of octreotide on the survival of patients with advanced hepatocellular carcinoma(HCC).Methods Electronic databases searches were conducted.Meta-analysis of all randomized controlled trials (RCTs) comparing octreotide versus placebo or no treatment was performed.Results Five RCTs including 579 patients with HCC wers assessed.Meta-analysis of the five studies showed that octreotide had no significant effect on the 6,12 and 24 months survival rates of the patients(6months:OR=1.69,95%CI 0.89-3.21,P=0.11;12 months:OR=2.41,95%CI 0.83-6.93,P=0.10;24months:OR=0.58,95%CI 0.28-1.17,P=0.13).To perform the sensitivity analysis,the blank study,the trial detecting somatostatin receptor expression,the study with short survival or the two trials with short follow-up intervals were excluded,and the results also showed that the octreotide treatment had no significant effect on the 6 and 12 months survival rates.A sensitivity analysis based on two trials indicated that the 24months survival rate of the octreotide group was even lower than that of the control group(OR=0.51,95% CI0.27-0.98,P=0.04).Conclusions This Meta-analysis demonstrates that octreotide could not improve the survival of patients with advanced HCC.The administration of octreotide should not be recommended for the treatment of advaneed HCC.%目的 综合评价奥曲肽对晚期肝癌患者生存期的影响.方法 检索各种电子数据库,对所有关于奥曲肽治疗晚期肝癌的随机对照试验进行Meta分析.结果 共纳入5项随机对照临床试验,579例晚期肝癌患者.Meta分析显示奥曲肽治疗对于患者的6、12和24个月生存率无显著影响(6个月:OR值1.69,95%CI 0.89~3.21,P=0.11;12个月:OR值2.41,95%CI 0.83~6.93,P=0.10;24个月:OR值0.58,95%CI 0.28~1.17,P=0.13).敏感性分析中分别剔除了空白对照的研究、排除生长抑素受体阴性患者的研究、患者生存期较短的研究和随访期较短的研究,结果均显示

  15. Hepatocellular carcinoma.

    Science.gov (United States)

    Okuda, K

    2000-01-01

    Hepatocellular carcinoma (HCC) is increasing in many countries as a result of an increase in hepatitis C virus (HCV) infection since World War II. The epidemiology of HCC varies with the global region. There have been conflicting observations from different parts of the world concerning the frequency of HCC in patients who in the distant past had post-transfusion non-A, non-B hepatitis. The genetic basis of hepatocarcinogenesis is still poorly understood. In hepatitis B virus (HVB) associated HCC, codon 249 mutation in the p 53 gene seems more related to exposure to aflatoxin B1 than to hepatocarcinogenesis itself. HCC that occurs in children in high HBV endemic regions could be associated with germ-line mutations, but little information is available; not much is known about chemical hepatocarcinogens in the environment other than aflatoxins. The X gene of HBV seems to play an important role in HBV-associated hepatocarcinogenesis. There are preliminary observations on the molecular mechanism of HCV-associated HCC, such as HCV core protein inducing HCC in transgenic mice and the NS3 genome transforming NIH 3T3 cells. Pathological distinction between preneoplastic and very early transformed lesions still depends on classical morphology, and a more genetically oriented differential diagnosis is required. Clinical diagnosis based on modern imaging has improved greatly, but is still unsatisfactory in the differential diagnosis of preneoplastic and early transformed nodules, because the vasculature changes that occur within the nodule are not accurately discerned with the current imaging. Use of sensitive des-gamma-carboxy prothrombin (PIVKA II) assay, and lectin affinity chromatography separating HCC specific subspecies of AFP molecules with a more practical biochemical technique will further improve diagnosis. Early diagnosis and transplantation are the best treatment at the moment, but transplantation is not widely available because of the donor shortage. Despite

  16. Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Mohammad Hossein Somi

    2005-09-01

    Full Text Available IntroductionHepatocellular carcinoma (HCC is one of the most common malignant tumors worldwide(1, with over four hundred thousand new cases and almost as many deaths each year(2. The incidence ranges from <10 cases per 100,000 population in North America and Western Europe to 50-150 cases per 100,000 population in parts of Africa and Asia where HCC is responsible for a large proportion of cancer deaths. Studies from the USA, UK, mainland Europe and Australia have shown a rising incidence of HCC(3-6, which probably relates to the increasing prevalence of hepatitis B and C due to immigration(7. Improved care for individuals with cirrhosis has resulted in prolonged and a relatively greater opportunity for malignant changes to develop. HCC is a disease of multifactorial etiology; the development of a carcinoma in a given individual is a multi-step process and the result of an accumulation of risks. It is estimated that persistent infection with hepatotrophic viruses account for well over 80% of the world's liver cancer(8. Hepatocellular carcinoma is the major cause of death in cirrhotic patients in Europe(9,10,11. Once cirrhosis is present, up to 20% of patients will develop HCC over 10 years(12. Genetic alterations are fundamental to the development of HCC by resulting in uncontrolled cellular proliferation and de-differentiation. Without treatment, the prognosis is dismal, with only a few months survival(13. Several surgical and non-surgical therapeutic modalities have been used for the treatment of HCC. Surgical resection, liver transplantation and local ablation therapies demonstrate potentially curative treatment options that should always be considered when the tumor is restricted to liver.EpidemiologyThe incidence of HCC varies widely by geographic location. The distribution of HCC also differs among ethnic groups and regions within the same country(14. High incidence regions (more than 15 cases per 100,000 populations per year include sub

  17. 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.

  18. 肝细胞癌免疫逃逸机制的研究进展%The advance research of hepatocellular carcinoma immune escape'mechanism

    Institute of Scientific and Technical Information of China (English)

    王拱辰

    2012-01-01

    Hepatocellular carcinoma in the process which are in the formation , development, invade , metastasis present autoantigen abnormal expression and to express some new antigens , that als can unusually secrete many biological active cytokine and many metabolic products in the meantime as well , these changes can avoid body immune systems attacks and impair body' cellular and humoral immune function , and also change carcinoma cellular immunomicroenvir-onment , many factors and many mechanismses escape body' immune recognitions and immune attacks, namely: hepatocellular carcinoma immune escapes, this text overview recent years a related mechanism at home and abroad of hepatocellular carcinoma immune escape%肝细胞癌在形成、发展及外侵和转移过程中出现自身抗原异常表达和新表达一些抗原,同时也可以异常分泌许多具有生物活性因子和许多代谢物质,这些改变可以避免机体免疫系统打击同时也可以使机体细胞和体液免疫功能下降,而且也可以使肿瘤细胞所处的免疫微环境发生变化,多因素、多机制逃避机体免疫系统识别和被免疫系统打击,即:肝细胞癌的免疫逃逸.本文就近年国内外原发性肝细胞癌与免疫逃逸相关机制作一综述.

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

    Institute of Scientific and Technical Information of China (English)

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

    2013-01-01

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

  20. Orthotopic ileal neobladder similar to original bladder

    Institute of Scientific and Technical Information of China (English)

    黄健; 许可慰; 姚友生; 郭正辉; 林天歆; 江春

    2003-01-01

    Objective To report the surgical techniques and results of an 8-year follow-up study of 42 patients with a modified orthotopic ileal neobladder restoring normal anatomical relationship.Methods Total cystoprostatectomy was performed extraperitoneally. A 45-50 cm segment of the ileal loop was isolated, detubularized, and reconfigured into an "M"-shape to form a pouch. Bilateral ureters were implanted by inserting 1 cm distal segment into the pouch. The bottom of pouch was opened and anastomosed with the urethra.Results Forty-two patients were followed up for 6 to 96 months,90.5% of whom were continent in the daytime, and 85.7% at night. Two patients had a difficulty in urination. The average volume of the pouch was (361±48) ml at 12 months postoperation. Urodynamic examination showed the average peak voiding pressure was (86.8±21.4) cmH2O. The average maximum flow rate (Qmax) was (18.4±6.1) ml/s. No remarkable ureter reflux and obstruction were found. No patient was detected to have urethral carcinoma.Conclusions Extraperitoneal cystectomy can avoid the tumor contamination of the abdomen and intestinal interference of the operative field. The ureter-inserting implantation technique is a simple anti-reflux anastomosis method with less ureter stenosis rate. Isolating the neobladder and ureters from the peritoneal cavity can reduce the postoperative complications, such as adhesive ileus, internal hernia, and urine leakage into the peritoneal cavity. The neobladder is similar to the original bladder in position, volume, shape and anti-reflux ureter connection.

  1. Quantification of dynamic contrast-enhanced ultrasound in HCC: prediction of response to a new combination therapy of sorafenib and panobinostat in advanced hepatocellular carcinoma.

    Science.gov (United States)

    Knieling, Ferdinand; Waldner, Maximilian J; Goertz, Ruediger S; Strobel, Deike

    2012-01-01

    Here, we report the case of a patient, who showed an antitumour response to a new combination therapy of sorafenib and the histon deacetylase inhibitor panobinostat (LBH-589). D-CEUS (Dynamic contrast-enhanced ultrasonography) was able to predict response to the new therapy regime and may be an interesting tool in the early evaluation of response to therapy. It might be especially useful to differentiate between responders and non-responders of new-targeted pharmaceuticals like multikinase inhibitors in hepatocellular carcinomas. PMID:23257272

  2. Oncogenic viruses and hepatocellular carcinoma.

    Science.gov (United States)

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

    2015-05-01

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

  3. 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.

  4. 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.

  5. Caroli's disease and orthotopic liver transplantation.

    Science.gov (United States)

    Habib, Shahid; Shakil, Obaid; Couto, Osvaldo F; Demetris, Anthony J; Fung, John J; Marcos, Amadeo; Chopra, Kapil

    2006-03-01

    Caroli's disease is a rare congenital hepatic disease, characterized by segmental dilatation of the biliary tree. Patients who have recurrent bouts of biliary infection, particularly those with complications related to portal hypertension, may require orthotopic liver transplantation (OLT). Few case reports have described the outcome of OLT in patients with Caroli's disease and to date there is no large series reported in the literature. We retrospectively analyzed the outcome of OLT in patients with Caroli's disease who underwent OLT between 1982 and 2002 at Starzl Transplantation Institute, University of Pittsburgh. Patients were identified and data was collected by computerized search of the electronic database system. All patients had confirmation of diagnosis by histopathology of explanted liver. A total of 33 patients with Caroli's disease were listed for liver transplantation, 3 of whom were excluded, as they were not transplanted. A total of 90% had signs of hepatic decompensation at the time of OLT. Median posttransplantation follow-up was 7.7 yr. Short-term graft and patient survival at 1 month was 83% and 86%, whereas overall long-term graft survival rates at 1, 5, and 10 yr were 73%, 62%, and 53%, respectively, and patient survival rates were 76%, 65%, and 56%, respectively. Long-term outcome in patients who survived the first year after transplantation was significantly better. Their survival rate at 5 and 10 yr was 90% and 78%. On univariable analysis, recipient age, donor male gender, coexistent congenital hepatic fibrosis, and re-OLT were associated with poor patient survival. Eight patients were retransplanted, 3 of whom had primary nonfunction. A total of 13 patients died; the most common cause of death being sepsis and cardiovascular complications. Patients who died of sepsis had cholangitis pre-OLT. In conclusion, OLT is a form of curative and life-saving therapy in patients with Caroli's disease, especially in those with decompensated liver

  6. Impact of more detailed categorization of shrinkage or progression ratio at initial imaging response after sorafenib treatment in advanced hepatocellular carcinoma patients

    Directory of Open Access Journals (Sweden)

    Wada Y

    2015-11-01

    Full Text Available Yoshiyuki Wada, Yuko Takami, Masaki Tateishi, Tomoki Ryu, Kazuhiro Mikagi, Hideki Saitsu Department of Hepato-Biliary-Pancreatic Surgery, Clinical Research Institute, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan Background: Sorafenib therapy improves survival in unresectable hepatocellular carcinoma (HCC patients without an objective response. The present study investigated whether the initial imaging response might be a prognostic indicator after administration of sorafenib therapy in HCC patients.Patients and methods: This retrospective study reviewed unresectable HCC patients undergoing sorafenib therapy. Patients evaluated without complete response, partial response (PR, or progressive disease (PD at the initial imaging response evaluation by modified Response Evaluation Criteria in Solid Tumors were divided into three groups according to more detailed categorization of the shrinkage/progression ratio in initial imaging response. A comparison of progression-free and overall survival among these groups was performed.Results: Of the 43 non-PR non-PD patients with target lesions, ten (23.3% exhibited mild response (MR; -30% to -5%, 14 (32.6% exhibited no change (NC; -5% to +5%, and 19 (44.2% exhibited mild-PD (MPD; +5% to +20%. There was no statistical difference in progression-free or overall survival between MR and NC patients. The median progression-free survivals in NC+MR and mild-PD patients were 15.0 and 5.3 months, respectively (P<0.01, and the median survival times were 31.9 and 17.1 months, respectively (P<0.001. In multivariate analysis, etiology (hepatitis C virus and initial imaging response (MR+NC was identified as an independently good prognostic factor.Conclusion: More detailed categorization of shrinkage or progression at the initial imaging response evaluation may be a useful marker for predicting sorafenib treatment outcomes in HCC patients. If the initial imaging response is not progression but

  7. Persistent medical management of chylopericardium following orthotopic heart transplant

    OpenAIRE

    Jackson, E; Khan, A.; N Yonan

    2010-01-01

    We describe a case of chylopericardium post orthotopic heart transplant, having had previous cardiac surgeries. This was managed conservatively for a prolonged period after which the patient recovered. We emphasise the fact that medical management works although the recovery time may be prolonged.

  8. 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

  9. 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 older. ...

  10. Early Decreases in α-Fetoprotein and Des-γ-carboxy Prothrombin Predict the Antitumor Effects of Hepatic Transarterial Infusion Chemotherapy with Cisplatin (CDDP) Powder in Patients with Advanced Hepatocellular Carcinoma.

    Science.gov (United States)

    Hatanaka, Takeshi; Kakizaki, Satoru; Shimada, Yasushi; Takizawa, Daichi; Katakai, Kenji; Yamazaki, Yuichi; Sato, Ken; Kusano, Motoyasu; Yamada, Masanobu

    2016-01-01

    Objective We retrospectively investigated the relationship between the tumor response and serial changes in α-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP) during hepatic arterial infusion of a cisplatin powder formulation (CDDP powder) in patients with advanced hepatocellular carcinoma (HCC). Methods Seventy-six advanced HCC patients were analyzed. All HCC patients received high-concentration cisplatin (1.43 mg/mL) via the haptic artery at a dose of 65 mg/m(2). AFP and DCP were measured at baseline and four to eight weeks after treatment, and the antitumor responses were evaluated according to the response evaluation criteria in solid tumours (RECIST) criteria after one or two courses of treatment. The patients were classified into two groups, a decreased group and a non-decreased group, according to the change in the serum levels of AFP and DCP at four to eight weeks compared to baseline. Results The response to treatment of the decreased group (n=16) and non-decreased group (n=60) was complete response/partial response/stable disease/progressive disease (CR/PR/SD/PD) in 4/4/5/3 and 1/11/8/40 patients, respectively. The response rate and disease control rate of the decreased group were significantly higher than those of the non-decreased group (p=0.016 and pAFP and DCP after the first treatment with CDDP powder is a good predictor for the antitumor effect and the prognosis. PMID:27522991

  11. Capecitabine plus cisplatin treatment in patients with advanced hepatocellular carcinoma%进展期肝细胞癌患者的卡培他滨加顺铂的联合治疗

    Institute of Scientific and Technical Information of China (English)

    Manal M Abdel Wahab; Lobna R Ezz Elarab; Mohamed A Ezz Elarab

    2010-01-01

    Objective:Hepatocellular carcinoma(HCC)is the sixth most common cancer in the wodd and the third leading cause of cancer related death globally.Parentral treatment of Egyptian patients of bilharziasis contributed to the high incidence of viral hepatitis,and subsequently liver cirrhosis and HCC.Capecitabine plus cisplatin protocol was evaluated regarding the efficacy and safety in patients with advanced HCC as first line chemotherapy.Methods:One hundred patients trial).Results:Baseline characteristics were comparable in beth groups.According to Barcelona Clinic Liver Cancer Staging System,stage C was the most predominant(82% vs.75%)in both groups.Median OS was 12 months versus 10 months in favor of the treated group(P value <0.05).Median TTP was significantly higher in the chemotherapy group(7 months vs.4.5 months)as well as disease control rate(40% vs.29%),no patient had achieved complete response.Grade 3 toxicity was more pronounced in the treatment group,as regards vomiting and diarrhea(10% vs.2%),neurotoxicity(6% vs.2%),elevation of aminotransferase and bilirubin(9.8% vs.4.9%),hand and foot syndrome reaction was recorded only in chemotherapy group.Conclusion:Capecitabine plus cisplatin regimen showed modest antitumor activity with tolerable toxicity in patients with advanced HCC.Moreover,because of the significantly prolonged time to progression,we demand further attention to this convenient,outpatient,and economic profile based chemotherapy protocol.

  12. [Combination Chemotherapy Using Sorafenib and Hepatic Arterial Infusion with a Fine-Powder Formulation of Cisplatin for Advanced Hepatocellular Carcinoma with Portal Vein Tumor Thrombosis--A Case Report].

    Science.gov (United States)

    Tsukamoto, Tadashi; Kanazawa, Akishige; Shimizu, Sadatoshi; Murata, Akihiro; Sakae, Masayuki; Kurihara, Shigeaki; Tashima, Tetsuzo; Deguchi, Sota; Nakai, Takashi; Kawasaki, Yasuko; Kioka, Kiyohide

    2015-11-01

    Sorafenib has been a standard therapy for advanced hepatocellular carcinoma (HCC) with portal vein thrombosis. Hepatic arterial infusion chemotherapy (HAIC) is still preferably performed in Japan because of its relatively good tumor-shrinking effect. We report a case of advanced multiple HCC with portal thrombus that responded to combination chemotherapy with sorafenib and repeat hepatic arterial infusion with a fine-powder formulation of cisplatin (IA-call®). A 57-year-old man presented for the treatment of HCC with alcoholic cirrhosis. Multiple HCC were found to be rapidly progressing with portal thrombosis. HAIC with IA-call® was performed, but the tumors progressed. TAE was performed 3 times thereafter and the main tumor shrunk to some extent. A month after the last TAE, the HCC was found to progress again, and oral sorafenib was administered. A reservoir and catheter were placed and HAIC with low-dose 5-fluorouracil and cisplatin was performed for 3 cycles following 1 HAIC cycle with epirubicin and mitomycin C, which was not effective. For 10 months after initial therapy, HAIC using IA-call® has been performed once for 6 weeks. After performing HAIC with IA-call® 5 times, the serum levels of HCC tumor markers AFP and PIVKA-Ⅱdecreased, and the tumors continued to shrink and were not stained on enhanced CT scan. The patient has been alive for 23 months after the initial therapy and has maintained stable disease. PMID:26805203

  13. 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

  14. 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.

  15. 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.

  16. 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. PMID:26518968

  17. 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.

  18. Prolonged Intraoperative Cardiac Resuscitation Complicated by Intracardiac Thrombus in a Patient Undergoing Orthotopic Liver Transplantation.

    Science.gov (United States)

    Kim, Sang; DeMaria, Samuel; Cohen, Edmond; Silvay, George; Zerillo, Jeron

    2016-09-01

    We report the case of successful resuscitation after prolonged cardiac arrest during orthotopic liver transplantation. After reperfusion, the patient developed ventricular tachycardia, complicated by intracardiac clot formation and massive hemorrhage. Transesophageal echocardiography demonstrated stunned and nonfunctioning right and left ventricles, with developing intracardiac clots. Treatment with heparin, massive transfusion and prolonged cardiopulmonary resuscitation ensued for 51 minutes. Serial arterial blood gases demonstrated adequate oxygenation and ventilation during cardiopulmonary resuscitation. Cardiothoracic surgery was consulted for potential use of extracorporeal membrane oxygenation, however, the myocardial function improved and the surgery was completed without further intervention. On postoperative day 6, the patient was extubated without neurologic or cardiac impairment. The patient continues to do well 2 years posttransplant, able to perform independent daily activities of living and his previous job. This case underscores the potential for positive outcomes with profoundly prolonged, effective advanced cardiovascular life support in patients who experience postreperfusion syndrome. PMID:27233818

  19. 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.

  20. [Hepatocellular Carcinoma: therapeutic options 2015].

    Science.gov (United States)

    Schultheiß, Michael; Bettinger, Dominik; Neeff, Hannes P; Brunner, Thomas B; Thimme, Robert

    2015-07-01

    The incidence of hepatocellular carcinoma (HCC), a common neoplasm, is rising and the prognosis is poor. Many factors have to be taken into account when deciding on the best mode of therapy, like tumor size and number, liver function, sequelae of portal hypertension or other comorbidities. These factors are reflected in the Barcelona Clinic Liver Cancer (BCLC) classification. Resection, radiofrequency ablation (RFA) and liver transplantation can be seen as curative therapies for the early and localized HCC. For the intermediate state of the HCC, there are other therapeutic modalities in therapy available: transarterial chemoembolization (TACE), selective internal radiation therapy (SIRT, rarer occasions), off label: stereotactic body radiation therapy (SBRT). At the moment, Sorafenib is the only option in treating advanced stages of HCC. Alternative treatment strategies, like e.g. immunological therapies, are being investigated. PMID:26182255

  1. 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.

  2. 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.

  3. 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.

  4. Ectopic goitrous submandibular thyroid with goitrous orthotopic thyroid gland.

    Science.gov (United States)

    Bhardwaj, Avinash Kumar; Mani, Vinayaga; Dixit, Rashmi; Garg, Anju

    2016-01-01

    Ectopic thyroid is a rare developmental anomaly with lingual thyroid accounting for majority of the cases. The presence of ectopic thyroid tissue lateral to the midline is very rare, and very few cases located in the submandibular region have been reported. The simultaneous finding of submandibular ectopic thyroid tissue and a functional orthotopic thyroid gland is even rarer. In the differential diagnosis of an ectopic submandibular thyroid, it is fundamental to exclude a metastasis from well-differentiated thyroid cancer, even when primary thyroid carcinoma is not demonstrable.

  5. Ectopic goitrous submandibular thyroid with goitrous orthotopic thyroid gland

    Science.gov (United States)

    Bhardwaj, Avinash Kumar; Mani, Vinayaga; Dixit, Rashmi; Garg, Anju

    2016-01-01

    Ectopic thyroid is a rare developmental anomaly with lingual thyroid accounting for majority of the cases. The presence of ectopic thyroid tissue lateral to the midline is very rare, and very few cases located in the submandibular region have been reported. The simultaneous finding of submandibular ectopic thyroid tissue and a functional orthotopic thyroid gland is even rarer. In the differential diagnosis of an ectopic submandibular thyroid, it is fundamental to exclude a metastasis from well-differentiated thyroid cancer, even when primary thyroid carcinoma is not demonstrable.

  6. A phase II open label trial evaluating safety and efficacy of a telomerase peptide vaccination in patients with advanced hepatocellular carcinoma

    Directory of Open Access Journals (Sweden)

    Ayuso Carmen

    2010-05-01

    Full Text Available Abstract Background The sole effective option for patients with advanced HCC is sorafenib and there is an urgent need to develop new therapeutic approaches. Immunotherapy is a promising option that deserves major investigation. In this open label, single arm clinical trial, we analyzed the effect of a low dose cyclophosphamide treatment in combination with a telomerase peptide (GV1001 vaccination in patients with advanced HCC. Methods 40 patients with advanced HCC were treated with 300 mg/m2 cyclophosphamide on day -3 followed by GM-CSF + GV1001 vaccinations on days 1, 3, 5, 8, 15, 22, 36 followed by 4-weekly injections. Primary endpoint of this phase II trial was tumor response; secondary endpoints evaluated were TTP, TTSP, PFS, OS, safety and immune responses. Results None of the patients had a complete or partial response to treatment, 17 patients (45.9% demonstrated a stable disease six months after initiation of treatment. The median TTP was 57.0 days; the median TTSP was estimated to be 358.0 days. Cyclophosphamide, GV1001 and GM-CSF treatment were well tolerated and most adverse events, which were of grade 1 or 2, were generally related to the injection procedure and injection site reactions. GV1001 treatment resulted in a decrease in CD4+CD25+Foxp3+ regulatory T cells; however, no GV1001 specific immune responses were detected after vaccination. Conclusions Low dose cyclophosphamide treatment followed by GV1001 vaccinations did not show antitumor efficacy as per tumor response and time to progression. Further studies are needed to analyze the effect of a combined chemo-immunotherapy to treat patients with HCC. Trial registration NCT00444782

  7. A phase II open label trial evaluating safety and efficacy of a telomerase peptide vaccination in patients with advanced hepatocellular carcinoma

    International Nuclear Information System (INIS)

    The sole effective option for patients with advanced HCC is sorafenib and there is an urgent need to develop new therapeutic approaches. Immunotherapy is a promising option that deserves major investigation. In this open label, single arm clinical trial, we analyzed the effect of a low dose cyclophosphamide treatment in combination with a telomerase peptide (GV1001) vaccination in patients with advanced HCC. 40 patients with advanced HCC were treated with 300 mg/m2 cyclophosphamide on day -3 followed by GM-CSF + GV1001 vaccinations on days 1, 3, 5, 8, 15, 22, 36 followed by 4-weekly injections. Primary endpoint of this phase II trial was tumor response; secondary endpoints evaluated were TTP, TTSP, PFS, OS, safety and immune responses. None of the patients had a complete or partial response to treatment, 17 patients (45.9%) demonstrated a stable disease six months after initiation of treatment. The median TTP was 57.0 days; the median TTSP was estimated to be 358.0 days. Cyclophosphamide, GV1001 and GM-CSF treatment were well tolerated and most adverse events, which were of grade 1 or 2, were generally related to the injection procedure and injection site reactions. GV1001 treatment resulted in a decrease in CD4+CD25+Foxp3+ regulatory T cells; however, no GV1001 specific immune responses were detected after vaccination. Low dose cyclophosphamide treatment followed by GV1001 vaccinations did not show antitumor efficacy as per tumor response and time to progression. Further studies are needed to analyze the effect of a combined chemo-immunotherapy to treat patients with HCC. NCT00444782

  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. Prevention of hepatocellular carcinoma.

    Science.gov (United States)

    Kew, Michael C

    2010-01-01

    Because of its frequency and grave prognosis, preventing hepatocellular carcinoma is an urgent priority. Prevention should be possible because environmental carcinogens-chronic hepatitis B and C virus infections, dietary exposure to aflatoxins, and iron overload-cause the great majority of these tumors. Chronic hepatitis B virus infection accounts for 55% of global hepatocellular carcinomas and 80% of those in the high-incidence Asia Pacific and sub-Saharan African regions. In these regions the infection that becomes chronic is predominantly acquired very early in life. A safe and effective vaccine against this virus is available and its universal inclusion in the immunization of infants has already resulted in a marked reduction of chronic infection and a 70% decrease in the occurrence of hepatocellular carcinoma in those immunized. Chronic hepatitis C virus infection is the major cause of hepatocellular carcinoma in industrialized countries. The infection is mainly acquired in adulthood and, until a vaccine becomes available, prevention will consist mainly of identifying, counselling, and treating chronically infected individuals, preventing spread of the virus by the use of safe injection practices (particularly in intravenous drug abusers), and screening all donated blood for the presence of the virus. 4.5 billion of the world.s population are exposed to dietary aflatoxins. Prevention involves treating susceptible crops to prevent fungal contamination, and handling the foodstuffs in such a way as to prevent contamination during storage. Iron overload in hereditary hemochromatosis can be prevented by repeated venesection and in African dietary iron overload by fermenting the home-brewed beer in iron-free containers. PMID:20526004

  10. 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

  11. Adrenal hemorrhage after orthotopic liver transplantation: MR appearance

    International Nuclear Information System (INIS)

    The purpose of this paper is to describe the MR imaging findings of right adrenal hemorrhage after orthotopic liver transplantation. Twenty-seven orthotopic liver transplantation patients underwent MR studies of the liver and/or biliary system. Patients were referred to MR examination because of suspected biliary complications (n=22) or for evaluation of mass lesions (n=5). The standard MR protocol included T1-weighted spin-echo (SE) or gradient-recalled echo (GRE) images and T2-weighted turbo SE (TSE) images with fat suppression. In addition, cholangiography pulse sequences and/or contrast-enhanced T1-weighted images were obtained according to specific indications. In 2 patients a right adrenal mass was detected at MR imaging. Three to 4 weeks after transplantation, the lesions were markedly hyperintense on T2-weighted images and showed a hypointense capsule. Follow-up MR examinations revealed a slight decrease in size and a change in morphology. Computed tomography examinations of these 2 patients, obtained 10 weeks after transplantation, showed resolution of the hemorrhage and transformation into a cystic lesion in one case and a complete resolution of the hemorrhage and a normal right adrenal gland in the other case. Adrenal hemorrhage after liver transplantation shows typical MR features and should not be mistaken for an adrenal tumor or a postoperative abscess. (orig.)

  12. Orthotopic liver transplantation for giant liver haemangioma: A case report.

    Science.gov (United States)

    Lange, Undine G; Bucher, Julian N; Schoenberg, Markus B; Benzing, Christian; Schmelzle, Moritz; Gradistanac, Tanja; Strocka, Steffen; Hau, Hans-Michael; Bartels, Michael

    2015-12-24

    In liver haemangiomas, the risk of complication rises with increasing size, and treatment can be obligatory. Here we present a case of a 46-year-old female who suffered from a giant haemangioma causing severe portal hypertension and vena cava compression, leading to therapy refractory ascites, hyponatremia and venostasis-associated thrombosis with pulmonary embolism. The patients did not experience tumour rupture or consumptive coagulopathy. Surgical resection was impossible because of steatosis of the non-affected liver. Orthotopic liver transplantation was identified as the only treatment option. The patient's renal function remained stable even though progressive morbidity and organ allocation were improbable according to the patient's lab model for end-stage liver disease (labMELD) score. Therefore, non-standard exception status was approved by the European organ allocation network "Eurotransplant". The patient underwent successful orthotopic liver transplantation 16 mo after admission to our centre. Our case report indicates the underrepresentation of morbidity associated with refractory ascites in the labMELD-based transplant allocation system, and it indicates the necessity of promptly applying for non-standard exception status to enable transplantation in patients with a severe clinical condition but low labMELD score. Our case highlights the fact that liver transplantation should be considered early in patients with non-resectable, symptomatic benign liver tumours. PMID:26722664

  13. Maintenance of Sorafenib following combined therapy of three-dimensional conformal radiation therapy/intensity-modulated radiation therapy and transcatheter arterial chemoembolization in patients with locally advanced hepatocellular carcinoma: a phase I/II study

    International Nuclear Information System (INIS)

    Three-dimensional conformal radiation therapy (3DCRT)/intensity-modulated radiation therapy (IMRT) combined with or without transcatheter arterial chemoembolization (TACE) for locally advanced hepatocellular carcinoma (HCC) has shown favorable outcomes in local control and survival of locally advanced HCC. However, intra-hepatic spreading and metastasis are still the predominant treatment failure patterns. Sorafenib is a multikinase inhibitor with effects against tumor proliferation and angiogenesis. Maintenance Sorafenib would probably prevent or delay the intrahepatic and extrahepatic spread of HCC after radiotherapy, which provides the rationale for the combination of these treatment modalities. Patients with solitary lesion (bigger than 5 cm in diameter) histologically or cytologically confirmed HCC receive TACE (1-3 cycles) plus 3DCRT/IMRT 4-6 weeks later. Maintenance Sorafenib will be administered only for the patients with non-progression disease 4 to 6 weeks after the completion of radiotherapy. The dose will be 400 mg, p.o., twice a day. Sorafenib will be continuously given for 12 months unless intolerable toxicities and/or tumor progression. If no more than 3 patients discontinue Sorafenib treatment who experience dose-limiting toxicity after necessary dose modification and delay and/or radiation-induced liver disease in the first 15 enrolled patients, the study will recruit second fifteen patients for further evaluating safety and efficacy of treatment. Hypothesis of the current study is that Sorafenib as a maintenance therapy after combined therapy of 3DCRT/IMRT and TACE is safe and superior to radiotherapy combined with TACE alone in terms of time to progression (TTP), progression-free survival (PFS) and overall survival (OS) in comparison to historical data. A recent meta-analysis showed TACE in combination with radiotherapy, improved the survival and the tumor response of patients, and was thus more therapeutically beneficial. In this study, local

  14. 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.

  15. Research progress on treatment of sorafenib for Chinese patients with advanced hepatocellular carcinoma%索拉非尼治疗国人晚期肝细胞癌的临床研究进展∗

    Institute of Scientific and Technical Information of China (English)

    龚新雷; 秦叔逵

    2015-01-01

    Primary liver cancer is a very common malignant tumor with especially higher incidence in China, very tough treat⁃ment and poor prognosis, which mainly consisted of hepatocellular carcinoma (HCC). The pathogenesis, clinical features, biological behavior, prognosis and treatment selection in Chinese patients are markedly different from those patients in western countries. It is of great significance to explore reasonable treatment strategies of Chinese population. Sorafenib is an oral, multi⁃targeted, multi⁃kinase in⁃hibitor, which has been proved to prolong the survival of patients with advanced HCC by large scale, international clinical studies. Sor⁃afenib has been used in China for more than 6 years and demonstrated its good efficacy and safety. However, there are many shortcom⁃ings of it. Recently, the domestic scholars have carried out many clinical studies of sorafenib monotherapy and in combination with other drugs or methods to improve its efficacy. This paper comprehensively reviews current situation and progress of related studies.%原发性肝癌,主要是肝细胞癌(HCC),是我国高发、常见的恶性肿瘤,晚期患者治疗棘手、预后恶劣。我国的HCC 在发病原因、生物学行为、临床特征、治疗选择和预后上,都与西方国家明显不同,积极探索适合我国 HCC 患者合理规范的治疗具有重要意义。分子靶向药物索拉非尼作为口服多靶点多激酶抑制剂,经国际大型临床研究证实可以延长晚期 HCC患者的生存期,在我国上市应用6年多,其疗效和安全性较好,但也存在一些问题。为了合理用药,进一步提高疗效,近年来,国内学者陆续开展了一系列索拉非尼单药、联合其他药物或手段治疗国人晚期 HCC 的临床研究和观察。本文拟对其相关研究进展进行综述和讨论,以提供临床参考。

  16. 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.

  17. 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

  18. Real Time Metastatic Route Tracking of Orthotopic PC-3-GFP Human Prostate Cancer Using Intravital Imaging.

    Science.gov (United States)

    Zhang, Yong; Wang, Xiaoen; Hoffman, Robert M; Seki, Naohiko

    2016-04-01

    The cellular basis of metastasis is poorly understood. An important step to understanding this process is to be able to visualize the routes by which cancer cells migrate from the primary tumor to various distant sites to eventually form metastasis. Our laboratory previously developed single-cell in vivo imaging using fluorescent proteins to label cancer cells. In the present study, using PC-3 human prostate cancer cells labeled with green fluorescent protein (GFP) and orthotopic tumor transplantation, we have imaged in live mice various highly diverse routes by which PC-3 cells metastasize superiorly and inferiorly to distant sites, including in the portal area, stomach area, and urogenital system. Imaging began at day 9, at which time distant metastasis had already occurred, and increased at each imaging point at days 10, 13, 14, and 16. Metastatic cells were observed migrating superiorly and inferiorly from the primary tumor as well as in lymphatic channels and trafficking in various organ systems demonstrating that PC-3 has multiple metastatic routes similar to hormone-independent advanced-stage prostate cancer in the clinic. PMID:26515240

  19. 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.

  20. 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.

  1. 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).

  2. 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.

  3. 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.

  4. 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.

  5. Population pharmacokinetics of remifentanil in patients undergoing orthotopic liver transplantation

    Institute of Scientific and Technical Information of China (English)

    ZHANG Li-ping; YANG Lu; BI Shan-shan; LU Wei; ZHANG Xian-hua; ZHAI Suo-di; DUAN Li-ping

    2009-01-01

    Backgroud Little is known about the influence of liver transplantation on the pharmacokinetics of most anesthetic drugs. The goal of this study was to study the population pharmacokinetics of remifentanil in the different phases of orthotopic liver transplantation (OLT) and the influence of relevant factors.Methods Thirteen adult patients undergoing OLT were enrolled. A single bolus infusion of remifentanil 5 μg/kg was administered during the preanhepatic, anhepatic and neohepatic phases of OLT. Arterial blood samples of 1.5 ml were collected at 0 (baseline), 1, 2, 3, 5, 7, 10, 15, 20, 25, 30, 45, 60 and 90 minutes after drug administration. Remifentanil concentration was assayed by high-performance liquid chromatography/mass spectrometry/mass spectrometry (HPLC/MS/MS). Population pharmacokinetic modeling was performed using nonlinear mixed-effects modeling (NONMEM).Results The pharmacokinetics of remifentanil in patients undergoing OLT was best described by a two-compartment open model. The pharmacokinetic parameters were not influenced by age, gender, operative phase, blood temperature, rehydration volume, or blood loss volume during sampling. The volume of distribution in the central compartment (V1) and the volume of distribution in the peripheral compartment (V2) were influenced by body weight. Conclusions The population pharmacokinetics of remifentanil in patients undergoing OLT can be well described by a two-compartment open model. The functional status of the liver does not significantly affect the pharmacokinetics of remifentanil, but the body weight is an influential factor of V1 and V2.

  6. Permanent and temporary pacemaker implantation after orthotopic heart transplantation

    Directory of Open Access Journals (Sweden)

    Bacal Fernando

    2000-01-01

    Full Text Available PURPOSE:To determine the indication for and incidence and evolution of temporary and permanent pacemaker implantation in cardiac transplant recipients. METHODS: A retrospective review of 114 patients who underwent orthotopic heart transplantation InCor (Heart Institute USP BR between March 1985 and May 1993. We studied the incidence of and indication for temporary pacing, the relationship between pacing and rejection, the need for pemanent pacing and the clinical follow-up. RESULTS: Fourteen of 114 (12%heart transplant recipients required temporary pacing and 4 of 114 (3.5% patients required permanent pacing. The indication for temporary pacing was sinus node dysfunction in 11 patients (78.5% and atrioventricular (AV block in 3 patients (21.4%. The indication for permanent pacemaker implantation was sinus node dysfunction in 3 patients (75% and atrioventricular (AV block in 1 patient (25%. We observed rejection in 3 patients (21.4% who required temporary pacing and in 2 patients (50% who required permanent pacing. The previous use of amiodarone was observed in 10 patients (71.4% with temporary pacing. Seven of the 14 patients (50% died during follow-up. CONCLUSION: Sinus node dysfunction was the principal indication for temporary and permanent pacemaker implantation in cardiac transplant recipients. The need for pacing was related to worse prognosis after cardiac transplantation.

  7. 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.

  8. 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.

  9. An improved animal model of orthotopic liver transplantation in swine

    Institute of Scientific and Technical Information of China (English)

    ZHENG Shu-guo; DONG Jia-hong; LENG Jian-jun; FENG Xiao-bin; MA Zheng-wei; YAN Yi

    2005-01-01

    Objective: To establish a swine model of orthotopic liver transplantation (OLT) which has high standardization, superior reproducibility and stability. Methods: The rate of success, reproducibility and stability were investigated on the modification of OLTs in closed miniature swine with series of improvements. Results: 20 OLTs were performed on the basis of improvements in experimental animals,surgical procedures and operative monitorings. The mean operation time and anhepatic phase was (181±25.8) and (28.43.2) min respectively, which were significantly shorter than those of the previous re ports. Liver function of the animals recovered shortly after operation. One-week survival rate was 90%,and 15 animals survived more than 1 month. The incidence of vascular and biliary complications was lower in animals with long-term survival. Conclusion: The improved animal model of OLTs in swine is easy to operate with high standardization and rate of success, superior reproducibility and stability. It is an ideal model for series studies related to liver transplantation in big animals.

  10. Simultaneous Resection of Disseminated Hepatocellular Carcinoma and Colon Cancer

    OpenAIRE

    Haga, Yuki; Chiba, Tetsuhiro; Ohira, Gaku; Kanai, Fumihiko; Yokota, Hajime; Motoyama, Tenyu; Ogasawara, Sadahisa; Suzuki, Eiichiro; Ooka, Yoshihiko; Tawada, Akinobu; Miyauchi, Hideaki; Matubara, Hisahiro; Yokosuka, Osamu

    2013-01-01

    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...

  11. 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.

  12. Intratracheally Administered 5-Azacytidine Is Effective Against Orthotopic Human Lung Cancer Xenograft Models and Devoid of Important Systemic Toxicity

    Science.gov (United States)

    Mahesh, Sameer; Saxena, Ashish; Qiu, Xuan; Perez-Soler, Roman; Zou, Yiyu

    2014-01-01

    Introduction Hypermethylation of key tumor suppressor genes plays an important role in lung carcinogenesis. The purpose of this study is to explore the therapeutic potential of regional administration (via the airways) of the demethylating agent 5-azacytidine (5-Aza) for the treatment of early lung cancer. Patients and Methods We administered 5-Aza solution directly into the trachea in imprinting control region (ICR) mice (to study its toxicity) and in nude mice bearing orthotopic human lung cancer xenografts (to assess its antitumor activity). Results In vitro, 5-Aza inhibited the growth of human lung cancer cell lines H226, H358, and H460 in a dose-dependent manner. The concentrations to inhibit cell growth by 50% (IC50) were about 0.6-4.9 μg/mL. 5-Azacytidine reversed hypermethylation in the promoter of tumor suppressor gene RASSF1a in the H226 cells at a 6000-fold lower concentration than its IC50. In animal studies, intratracheal (I.T.) administration of 90 mg/kg 5-Aza (the maximum tolerated dose of 5-Aza intravenous injection [I.V.]) resulted in moderate pulmonary toxicity and 5-fold reduced myelosuppression compared with the same dose of I.V. 5-Aza. Using an optimized multiple dose schedule, I.T. 5-Aza was about 3-fold more effective than I.V. 5-Aza in prolonging the survival of mice bearing orthotopic H460 and H358 xenografts, and did not cause any detectable toxicity. Conclusion 5-Azacytidine can reverse the hypermethylation in the human lung cancer cell lines at a nontoxic dose. Regional administration to the airways enhances the therapeutic index of 5-Aza by 75-fold. The potential of regional administration of 5-Aza (including by aerosolization) for the treatment of advanced bronchial premalignancy deserves further investigation. PMID:21062731

  13. 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.

  14. An Orthotopic Mouse Model of Spontaneous Breast Cancer Metastasis.

    Science.gov (United States)

    Paschall, Amy V; Liu, Kebin

    2016-01-01

    Metastasis is the primary cause of mortality of breast cancer patients. The mechanism underlying cancer cell metastasis, including breast cancer metastasis, is largely unknown and is a focus in cancer research. Various breast cancer spontaneous metastasis mouse models have been established. Here, we report a simplified procedure to establish orthotopic transplanted breast cancer primary tumor and resultant spontaneous metastasis that mimic human breast cancer metastasis. Combined with the bioluminescence live tumor imaging, this mouse model allows tumor growth and progression kinetics to be monitored and quantified. In this model, a low dose (1 x 10(4) cells) of 4T1-Luc breast cancer cells was injected into BALB/c mouse mammary fat pad using a tuberculin syringe. Mice were injected with luciferin and imaged at various time points using a bioluminescent imaging system. When the primary tumors grew to the size limit as in the IACUC-approved protocol (approximately 30 days), mice were anesthetized under constant flow of 2% isoflurane and oxygen. The tumor area was sterilized with 70% ethanol. The mouse skin around the tumor was excised to expose the tumor which was removed with a pair of sterile scissors. Removal of the primary tumor extends the survival of the 4T-1 tumor-bearing mice for one month. The mice were then repeatedly imaged for metastatic tumor spreading to distant organs. Therapeutic agents can be administered to suppress tumor metastasis at this point. This model is simple and yet sensitive in quantifying breast cancer cell growth in the primary site and progression kinetics to distant organs, and thus is an excellent model for studying breast cancer growth and progression, and for testing anti-metastasis therapeutic and immunotherapeutic agents in vivo. PMID:27584043

  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. 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.

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

    Science.gov (United States)

    Alanis, Lourdes; Cho, Sung-Ki; Saab, Sammy

    2016-01-01

    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. PMID:27390539

  18. Progression of renal cell carcinoma is inhibited by genistein and radiation in an orthotopic model

    Directory of Open Access Journals (Sweden)

    Kucuk Omer

    2007-01-01

    Full Text Available Abstract Background We have previously reported the potentiation of radiotherapy by the soy isoflavone genistein for prostate cancer using prostate tumor cells in vitro and orthotopic prostate tumor models in vivo. However, when genistein was used as single therapy in animal models, it promoted metastasis to regional para-aortic lymph nodes. To clarify whether these intriguing adverse effects of genistein are intrinsic to the orthotopic prostate tumor model, or these results could also be recapitulated in another model, we used the orthotopic metastatic KCI-18 renal cell carcinoma (RCC model established in our laboratory. Methods The KCI-18 RCC cell line was generated from a patient with papillary renal cell carcinoma. Following orthotopic renal implantation of KCI-18 RCC cells and serial in vivo kidney passages in nude mice, we have established a reliable and predictable metastatic RCC tumor model. Mice bearing established kidney tumors were treated with genistein combined with kidney tumor irradiation. The effect of the therapy was assessed on the primary tumor and metastases to various organs. Results In this experimental model, the karyotype and histological characteristics of the human primary tumor are preserved. Tumor cells metastasize from the primary renal tumor to the lungs, liver and mesentery mimicking the progression of RCC in humans. Treatment of established kidney tumors with genistein demonstrated a tendency to stimulate the growth of the primary kidney tumor and increase the incidence of metastasis to the mesentery lining the bowel. In contrast, when given in conjunction with kidney tumor irradiation, genistein significantly inhibited the growth and progression of established kidney tumors. These findings confirm the potentiation of radiotherapy by genistein in the orthotopic RCC model as previously shown in orthotopic models of prostate cancer. Conclusion Our studies in both RCC and prostate tumor models demonstrate that the

  19. 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.

  20. 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.

  1. 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.

  2. 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

  3. Asystole after Orthotopic Lung Transplantation: Examining the Interaction of Cardiac Denervation and Dexmedetomidine

    Directory of Open Access Journals (Sweden)

    Christopher Allen-John Webb

    2012-01-01

    Full Text Available Dexmedetomidine is an α2-receptor agonist commonly used for sedation and analgesia in ICU patients. Dexmedetomidine is known to provide sympatholysis and also to have direct atrioventricular and sinoatrial node inhibitory effects. In rare instances, orthotopic lung transplantation has been associated with disruption of autonomic innervation of the heart. The combination of this autonomic disruption and dexmedetomidine may be associated with severe bradycardia and/or asystole. Since orthotopic lung transplant patients with parasympathetic denervation will not respond with increased heart rate to anticholinergic therapy, bradyarrhythmias must be recognized and promptly treated with direct acting beta agonists to avoid asystolic cardiac events.

  4. Exercise modulation of the host-tumor interaction in an orthotopic model of murine prostate cancer

    OpenAIRE

    Jones, Lee W.; Antonelli, Jodi; Masko, Elizabeth M.; Broadwater, Gloria; Lascola, Christopher D.; Fels, Diane; Dewhirst, Mark W.; Jason R.B. Dyck; Nagendran, Jeevan; Flores, Catherine T.; Betof, Allison S.; Nelson, Erik R.; Pollak, Michael; Dash, Rajesh C.; Young, Martin E.

    2012-01-01

    The purpose of this study is to investigate the effects of exercise on cancer progression, metastasis, and underlying mechanisms in an orthotopic model of murine prostate cancer. C57BL/6 male mice (6–8 wk of age) were orthotopically injected with transgenic adenocarcinoma of mouse prostate C-1 cells (5 × 105) and randomly assigned to exercise (n = 28) or a non-intervention control (n = 31) groups. The exercise group was given voluntary access to a wheel 24 h/day for the duration of the study....

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

    OpenAIRE

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

    2013-01-01

    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) pat...

  6. 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

  7. Orthotopic liver transplantation with extracorporeal venovenous bypass:One case report%体外静脉转流原位肝移植一例

    Institute of Scientific and Technical Information of China (English)

    耿小平; 孟翔凌; 熊奇如; 余宏铸; 张宗耀; 吴蓉蓉; 戴秀萍; 杜鹃

    1999-01-01

    Objective Orthotopic liver transplantation was successfully performed on a patient with hepatocellular carcinoma(HCC)associated with liver cirrhosis and portal hypertension.Methods On the basis of the animal experiment.the liver was perfused and preserved with 4℃ UW solution after harvesting quickly.The operation was performed under the extracoporeal venovenous bypass.Results The operation lasted 12 h and the duration of anhepatic phase was 100 min.During the operation there was no significant haemodynamic changes.Postoperative renal function Was normal and the patient had good recovery.Conclusion It is essential to perform venovenous bypass during liver transplantation in HCC patients with cirrhosis and portal hypertension.%目的 采用肝脏移植治疗伴有肝硬化的原发性肝癌.方法 在动物实验的基础上,供肝采用快速切取,4℃ UW液灌注和保存,手术采用体外静脉转流肝脏移植技术.结果 手术历时12小时,无肝期100分钟,术中血流动力学平稳,术后肾功能正常.结论 肝移植治疗肝硬化肝癌的术中应用体外静脉转流是十分重要的.

  8. 以索拉非尼为基础治疗晚期肝细胞癌的疗效和不良反应临床观察%Clinical observation on efficacy and adverse reactions of sorafenib in treating advanced hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    苑珩珩; 白玉贤; 张婷婷; 黄鹏

    2012-01-01

    Background and purpose: Two clinical trials SHARP and ORIENTAL confirmed that sorafenib, a multi-kinase inhibitor could significantly improve PFS as well as TTP, and prolong OS for patients with hepatocellular carcinoma. Therefore sorafenib was approved to treat advanced hepatocellular carcinoma in 2008. Our study was designed to observe efficacy and adverse reactions of sorafenib alone or in combination with TACE in treating 30 patients with advanced hepatocellular carcinoma. Methods: From Mar 2009 to Jan 2011, a total of 30 patients with clinical or pathological diagnosis of advanced primary hepatocellular carcinoma orally took sorafenib with dosage of 400 mg each time, 2 times a day, and treatment duration was at least more than 2 months. Twenty patients received TACE for 1 to 9 times in combination with sorafenib, and 10 patients took sorafenib alone. In accordance with RESIST, efficacy was evaluated each two-month and follow-up was performed to achieve TTP and OS. Results: Among 30 patients, there were 3 patients of PR, 16 patients of SD, and 11 patients of PD, with clinical benefit rate (CBR) of 63.3%. Among 10 patients who took sorafenib alone, there were 1 patient of PR, 5 patients of SD, and 4 patients of PD, with CBR of 60.0%. Among 20 patients who took sorafenib in combination with TACE, there were 2 patients of PR, 11 patients of SD, and 7 patients of PD, with CBR of 65.0%. All 27 patients survived for more than 3 months, 24 patientssurvived for more than 6 months, 21 patients survived for more than 9 months, and 9 patients survived for even more than 1 year. TTP was 7 months, and OS was 9 months, with P=0.067 2 and P=0.058 9. Patients demonstrated adverse effects 1-2 weeks after administration. Twenty-three patients had hand and foot symptom, 24 patients had diarrhea, 14 patients had hypertension, 24 patients had fatigue, 9 patients had hair loss. There were 10 cases of degree 3 adverse reaction in total, and patients could accomplish the whole therapy

  9. Surgical techniques of arterialized orthotopic liver transplantation in rats

    Institute of Scientific and Technical Information of China (English)

    MA Yi; WANG Guo-dong; GUO Zhi-yong; GUO Zhi-gang; HE Xiao-shun; CHEN Gui-hua

    2007-01-01

    Background Recently, much attention has been paid to hepatic artery reconstruction in rat liver transplantation, which can prevent bile duct ischemia and preserve better liver structure. In this study, three methods of graft arterialization,including sleeve, cuff, and stent anastomosis, were conducted and the results were compared.Methods Orthotopic liver transplantation (OLT) with rearterialization was conducted in 90 rats, which were divided into sleeve, cuff, and stent groups (n=30 in each). Ninety-six rats received OLTs with standardized two-cuff technique without rearterialization as a control. The sleeve technique included an end-to-end anastomosis between the donor common hepatic artery and recipient proper hepatic artery, or between the donor celiac artery and recipient common hepatic artery.Cuff technique involved an anastomosis between the donor common hepatic artery and recipient common hepatic artery.In the stent technique, the recipient hepatic artery and donor hepatic artery were connected using an intraluminal polyethylene stent. The arterial anastomosis time and arterial patency rate in each group were recorded. The liver graft survival and bile duct complication rates were measured.Results The total surgical time of OLT with rearterialization was (118.3±12.9) minutes in the sleeve group, (106.2±11.6)minutes in the cuff, (93.8±10.2) minutes in the stent, and (88.2±9.6) minutes in the control. The corresponding anhepatic phase was (19.6±2.8), (19.2±2.2), (18.6±1.8), and (20.0±2.5) minutes respectively in the sleeve, cuff, stent, and control groups. One-week survival rate was 86.5% in the control, and 86.7% in the groups with rearterialization. No significant difference was detected in the survival rate between them (P>0.05). The incidence of biliary complications in non-rearterialized group (17.7%) was significantly higher than that in the rearterialized group (6.7%, P<0.05). No significant difference was found in the incidence of biliary

  10. 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

  11. 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.

  12. 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.

  13. 冷极射频序贯索拉非尼与索拉非尼单药治疗进展期肝细胞癌的对比研究%Comparative Study of Radiofrequency Ablation plus Sorafenib Treatment and Sorafenib Monotherapy for Advanced Hepatocellular Carcinoma

    Institute of Scientific and Technical Information of China (English)

    刘炼; 杨波; 姜孝新; 黄菊芳

    2012-01-01

      目的比较冷极射频序贯索拉非尼与索拉非尼单药治疗进展期肝细胞癌的疗效和不良反应.方法将22例晚期肝细胞癌患者随机分为观察组(10例,冷极射频序贯索拉非尼治疗)和对照组(12例,索拉非尼单药治疗),治疗3个月后比较两组患者的治疗有效率、临床获益率及生存期;同时观察比较两组患者的不良反应.结果治疗后观察组的治疗有效率为60.0%,临床获益率为80.0%;对照组的治疗有效率为8.3%,临床获益率为66.7%,观察组的有效率及临床获益率较高(P0.05).结论与索拉非尼单药治疗相比较,冷极射频序贯索拉非尼治疗进展期肝细胞癌疗效更好,安全性相似,值得临床推广应用.%  Objective To compare the clinical effect and adverse effects between Radiofrequency ablation plus Sor-afenib treatment and Sorafenib monotherapy for advanced hepatocellular carcinoma. Methods 22 patients with advanced liver cancer were randomly divided into two groups, one is observation group, with 10 cases, given Radiofrequency ab-lation plus Sorafenib treatment, and one is control group, with 12 cases, given Sorafenib monotherapy. After three months treatment, the treatment efficiency, clinical benefit rate and survival rate of the two groups were compared. Results The treatment efficiency was 60.0%in observation group, but 8.3%in control group (P0.05). Conclusion Compared with Sorafenib used alone, radiofrequency ablation in combination with Sorafenib has better efficacy and similar safety in advanced hepatocellular carcinoma treatment. It deserves clinical application.

  14. 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

  15. Complementarity of ultrasound and fluorescence imaging in an orthotopic mouse model of pancreatic cancer

    International Nuclear Information System (INIS)

    Pancreatic cancer is a devastating disease characterized by dismal 5-year survival rates and limited treatment options. In an effort to provide useful models for preclinical evaluation of new experimental therapeutics, we and others have developed orthotopic mouse models of pancreatic cancer. The utility of these models for pre-clinical testing is dependent upon quantitative, noninvasive methods for monitoring in vivo tumor progression in real time. Toward this goal, we performed whole-body fluorescence imaging and ultrasound imaging to evaluate and to compare these noninvasive imaging modalities for assessing tumor burden and tumor progression in an orthotopic mouse model of pancreatic cancer. The human pancreatic cancer cell line XPA-1, engineered for stable, high-level expression of red fluorescent protein (RFP), was implanted into the pancreas of nude mice using orthotopic implantation. The tumors were allowed to grow over a period of one to several weeks during which time the mice were imaged using both fluorescence imaging and ultrasound imaging to measure tumor burden and to monitor tumor growth. Whole-body fluorescence imaging and ultrasound imaging both allowed for the visualization and measurement of orthotopic pancreatic tumor implants in vivo. The imaging sessions were well-tolerated by the mice and yielded data which correlated well in the quantitative assessment of tumor burden. Whole-body fluorescence and two-dimensional ultrasound imaging showed a strong correlation for measurement of tumor size over a range of tumor sizes (R2 = 0.6627, P = 0.003 for an exposure time of 67 msec and R2 = 0.6553, P = 0.003 for an exposure time of 120 msec). Our findings suggest a complementary role for fluorescence imaging and ultrasound imaging in assessing tumor burden and tumor progression in orthotopic mouse models of human cancer

  16. [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.

  17. 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....

  18. The advances in the study of circulating DNA in early diagnosis and treatment for hepatocellular carcinoma%外周血循环DNA在肝细胞癌早期诊治的研究进展

    Institute of Scientific and Technical Information of China (English)

    胡捷; 周俭; 王征; 樊嘉

    2009-01-01

    Circulating DNA is cell-free DNA existing in plasma or serum. It has already been verified that circulating DNA of cancer patients is derived from tumor cells. Therefore, it is of great value to detect the changes in the quantity and quality of the circulating DNA in cancer patients for early diagnosis and prognosis. The advantages of the detection of circulating DNA such as micro-trauma, convenient access to samples, possibility of continuous and dynamic monitoring, make it a promising tumor mark. This review recapitulates the application of circulating DNA analysis in hepatocellular carcinoma patients for diagnosis and prognosis.%循环DNA是存在于血浆/血清中的游离DNA.已有研究证实肿瘤患者循环DNA来源于肿瘤细胞.因此,检测肿瘤患者循环DNA质和量的改变对肿瘤的早期诊断和预后分析具有较大价值.循环DNA检测具有微创性、标本获取方便、可连续动态检测等优点,是一种极具前景的肿瘤标志物.有关肝癌患者循环DNA的研究不多,本文就循环DNA检测在肝癌诊断和预后分析中的研究进展做一综述.

  19. Advances in nonalcoholic fatty liver disease and hepatocellular carcinoma research%非酒精性脂肪性肝病与肝细胞癌关系的研究进展

    Institute of Scientific and Technical Information of China (English)

    代鸿华; 梅礼强

    2012-01-01

    非酒精性脂肪性肝病(NAFLD)作为一种与机体代谢紊乱相关的疾病,其发病率呈逐年上升趋势,随之引起肝脏代谢功能失调及相关病程进展,最终发展为脂肪性肝炎、隐源性肝硬化,甚至有可能发展为肝细胞癌(HCC).本文就NAFLD相关HCC的发病机制、危险因素、诊断等作一综述.%The incidence of nonalcoholic fatty liver disease ( NAFLD ) is continuing to rise. Substantial research efforts have been allocated to uncover the etiologies and pathogenic mechanisms of this disease. These studies have revealed that NAFLD initially manifests as metabolic disturbance of liver function and can progress to adiposis hepatica, idiopathic cirrhosis, and hepatocellular carcinoma (HCC) ; however, the molecular processes, risk factors, and diagnostic indicators of NAFLD have yet to be definitively established. In this review, we summarize and discuss the latest research findings on these topics in order to provide a comprehensive overview of the current knowledge of NAFLD progression to HCC and the aspects that remain to be elucidated.

  20. 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.

  1. Present and future possibilities for early diagnosis of hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Piotr; Stefaniuk; Janusz; Cianciara; Alicja; Wiercinska-Drapalo

    2010-01-01

    Hepatocellular carcinoma(HCC) represents the fifth most common cancer in the world,and the third most frequent oncological cause of death.The incidence of HCC is on the increase.HCC typically develops in patients with chronic liver diseases,and cirrhosis,usually with viral etiology,is the strongest predisposing factor.Nowadays HCC diagnosis is a multistage process including clinical,laboratory,imaging and pathological examinations.The prognosis of HCC is mostly poor,because of detection at an advanced,non-r...

  2. 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.

  3. 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.

  4. Detection and quantitation of circulating tumor cell dynamics by bioluminescence imaging in an orthotopic mammary carcinoma model.

    Directory of Open Access Journals (Sweden)

    Laura Sarah Sasportas

    Full Text Available Circulating tumor cells (CTCs have been detected in the bloodstream of both early-stage and advanced cancer patients. However, very little is know about the dynamics of CTCs during cancer progression and the clinical relevance of longitudinal CTC enumeration. To address this, we developed a simple bioluminescence imaging assay to detect CTCs in mouse models of metastasis. In a 4T1 orthotopic metastatic mammary carcinoma mouse model, we demonstrated that this quantitative method offers sensitivity down to 2 CTCs in 0.1-1mL blood samples and high specificity for CTCs originating from the primary tumor, independently of their epithelial status. In this model, we simultaneously monitored blood CTC dynamics, primary tumor growth, and lung metastasis progression over the course of 24 days. Early in tumor development, we observed low numbers of CTCs in blood samples (10-15 cells/100 µL and demonstrated that CTC dynamics correlate with viable primary tumor growth. To our knowledge, these data represent the first reported use of bioluminescence imaging to detect CTCs and quantify their dynamics in any cancer mouse model. This new assay is opening the door to the study of CTC dynamics in a variety of animal models. These studies may inform clinical decision on the appropriate timing of blood sampling and value of longitudinal CTC enumeration in cancer patients.

  5. Congenital hepatic fibrosis leading to cirrhosis and hepatocellular carcinoma: a case report

    Directory of Open Access Journals (Sweden)

    Bagheri Mohammad

    2011-04-01

    Full Text Available Abstract Introduction Congenital hepatic fibrosis is an uncommon cause of portal hypertension. Despite the presence of portal hypertension, hepatocellular and renal function are usually well preserved. Congenital hepatic fibrosis is included in the group of congenital diseases of fibropolycystic disorders. These include a broad spectrum of clinical diseases which are usually accompanied by hepatic involvement. Case presentation We report the case of a 27-year-old Iranian woman with congenital hepatic fibrosis leading to cirrhosis and subsequently hepatocellular carcinoma. Conclusion Advanced cirrhosis was diagnosed and our patient was scheduled for liver transplantation. During preparation for transplant, a hepatic mass was discovered which was found to be hepatocellular carcinoma. Radiofrequency ablation was performed and our patient was referred for transplantation.

  6. 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.

  7. Multispectral optoacoustic and MRI coregistration for molecular imaging of orthotopic model of human glioblastoma.

    Science.gov (United States)

    Attia, Amalina Binte Ebrahim; Ho, Chris Jun Hui; Chandrasekharan, Prashant; Balasundaram, Ghayathri; Tay, Hui Chien; Burton, Neal C; Chuang, Kai-Hsiang; Ntziachristos, Vasilis; Olivo, Malini

    2016-07-01

    Multi-modality imaging methods are of great importance in oncologic studies for acquiring complementary information, enhancing the efficacy in tumor detection and characterization. We hereby demonstrate a hybrid non-invasive in vivo imaging approach of utilizing magnetic resonance imaging (MRI) and Multispectral Optoacoustic Tomography (MSOT) for molecular imaging of glucose uptake in an orthotopic glioblastoma in mouse. The molecular and functional information from MSOT can be overlaid on MRI anatomy via image coregistration to provide insights into probe uptake in the brain, which is verified by ex vivo fluorescence imaging and histological validation. In vivo MSOT and MRI imaging of an orthotopic glioma mouse model injected with IRDye800-2DG. Image coregistration between MSOT and MRI enables multifaceted (anatomical, functional, molecular) information from MSOT to be overlaid on MRI anatomy images to derive tumor physiological parameters such as perfusion, haemoglobin and oxygenation. PMID:27091626

  8. Postoperative imaging findings in children with auxiliary partial orthotopic liver transplant (APOLT).

    Science.gov (United States)

    Ayyala, Rama S; Martinez, Mercedes; Lobritto, Steven J; Kato, Tomoaki; Ruzal-Shapiro, Carrie

    2016-07-01

    Auxiliary partial orthotopic liver transplant (APOLT) is a treatment technique for people who have acute hepatic failure secondary to fulminant hepatic failure and might ultimately recover normal liver function. This surgical procedure is complicated, involving the placement of a liver graft while maintaining viability of the remaining native portion of the liver. This method allows the native liver to recover hepatic function, therefore eliminating the need for long-term immunosuppression, as is typically needed in post-transplant settings. Postoperative imaging in these cases can be challenging given the complex anatomy, specifically the vascular anastomosis. Therefore it is important for radiologists and clinicians to be aware of the anatomy as well as the variable imaging appearances of the liver. We review the imaging findings in children who have undergone auxiliary partial orthotopic liver transplant (APOLT). PMID:26867605

  9. Allogeneic unresponsiveness to orthotopic cardiac transplants in DL-A-identical radiation chimeras

    International Nuclear Information System (INIS)

    Nine Cooperstown beagles of known DL-A genotypes were exposed to supralethal total-body irradiation and received bone-marrow allografts from DL-A-identical donors. Four to 5 months later, the resulting chimeras received orthotopic cardiac allografts from their corresponding donors of marrow. Six chimeras died of operative complications in the immediate postoperative period. The other 3 chimeras survived from 173 to 547 days; 1 dog died at 173 days as a result of right-sided heart failure, secondary to stenosis at the site of the pulmonary artery anastomosis. The other two recipients continue to be active and healthy at 545 and 547 days. The results indicate that dogs can be rendered specifically tolerant to orthotopic cardiac allografts by supralethal total-body irradiation and the transplantation of marrow obtained from the prospective allograft donor

  10. TRANSIENT SUDDEN BILATERAL VISUAL LOSS AFTER ORTHOTOPIC HEART TRANSPLANTATION: A CASE REPORT

    Directory of Open Access Journals (Sweden)

    S. K. Forouzannia

    2005-07-01

    Full Text Available Post cardiac surgery ophthalmic complications are uncommon, and sudden visual loss is one of the most important ophthalmic problems in these patients. We report a 54-year-old woman that suffered transient sudden bilateral visual loss seven days after orthotopic heart transplantation. In ophthalmologic examination positive findings were bilateral normal size pupils without direct and indirect pupillary light reflex and bilateral severe diffuse vasospasm of retinal arteries. Other ophthalmologic findings were normal. Problem lasts for 12 hours and resolved spontaneously. Funduscopic examination identified bilateral normal retina at this time and fluorescein angiography revealed normal retinal vasculature. This presentation suggests retinal vasospasm as an unusual benign cause of bilateral sudden visual loss after orthotopic heart transplantation.

  11. 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.

  12. Comparison Between Ambulatory and Conventional Urodynamics of the Modified Orthotopic Hautmann Neobladder

    OpenAIRE

    Apostolos, Malioris; Georgios, Dimitriadis; Spyridon, Kampantais; Georgios, Gkotsos; Ioannis, Vakalopoulos; Stavros, Ioannidis; Konstantinos, Hatzimoutatidis; Dimitrios, Hatzichristou

    2015-01-01

    Purpose: The aim of the present study was to determine the diagnostic accuracy of conventional and ambulatory urodynamic studies (UDS) in estimating neobladder function. Methods: We evaluated 32 patients who underwent radical cystectomy and orthotopic Hautmann W neobladder with Abol-Enein-Ghoneim uretero-intestinal anastomosis for bladder cancer. The patients were initially examined by using both conventional and ambulatory UDS. Results: Conventional UDS detected a very high mean intravesical...

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

    OpenAIRE

    Yongchun ZHOU; Chen, Yan; Xicai WANG; Liu, Xin; Hutao SHI; Yao, Qian; Jin, Congguo; Wu, Zhiping; Huang, Yunchao

    2012-01-01

    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, spontane...

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

    OpenAIRE

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

    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 covere...

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

    OpenAIRE

    David Snipelisky; Sean Donovan; Michael Levy,; Raj Satyanarayana; Brian Shapiro

    2013-01-01

    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 leve...

  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. 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.

  18. Transhemangioma Ablation of Hepatocellular Carcinoma

    International Nuclear Information System (INIS)

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

  19. Transhemangioma Ablation of Hepatocellular Carcinoma

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-12-15

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

  20. Management of ischemic-type biliary injury induced by hepatic artery stricture after orthotopic liver transplantation

    International Nuclear Information System (INIS)

    Objective: To discuss the treatment of ischemic-type biliary injury due to hepatic artery stricture after orthotopic liver transplantation and to estimate its prognosis. Methods: The clinical data of 11 patients with ischemic-type biliary injury due to hepatic artery stricture after orthotopic liver transplantation encountered during the period of June 2004-June 2008, who underwent hepatic artery stenting together with endoscopic retrograde cholangiopancreatography (ERCP) and/or percutaneous transhepatic cholangial drainage (PTCD), were retrospectively analyzed. Results: A total of 12 balloon-expandable coronary stents was successfully implanted in 11 patients. In 5 patients only ERCP was adopted and in 3 patients only PTCD was used. The remaining 3 patients received PTCD after they failed to respond to ERCP. During a follow-up period of 4 months-4 years, 6 cases died of infection, of which 5 died within one year. Three patients accepted liver transplantation once more. The other 2 patients survived so far. Conclusion: The overall therapeutic result of ischemic-type biliary injury due to hepatic artery stricture after orthotopic liver transplantation is not ideal at present. Hepatic artery stenting combined with longstanding PTCD may prolong the survival time of the grafted liver and, therefore, provide opportunity for re-transplantation. (authors)

  1. Long-term urodynamic evaluation of laparoscopic radical cystectomy with orthotopic ileal neobladder for bladder cancer.

    Science.gov (United States)

    Wang, Dong; Li, Li-Jun; Liu, Jing; Qiu, Ming-Xing

    2014-09-01

    The long-term urodynamics of laparoscopic radical cystectomy with orthotopic ileal neobladder for bladder cancer remain unclear in the clinical setting. The present prospective observational study was conducted between January 2010 and December 2012 to evaluate the 6-month and 12-month follow-up data of urodynamic changes of bladder cancer patients who were initially treated by laparoscopic radical cystectomy with orthotopic ileal neobladder. A total of 53 eligible patients were included, and all patients were followed up for at least 12 months, with a median time of 18 months. During the follow-up period, no patients reported difficulty urinating, and the daily frequency of urination and the urine output were gradually improved with time. Dynamic urodynamic examinations showed that the maximum flow rate (11.4±1.1 vs. 7.3±1.4 ml/sec; Pcompliance (26.9±13 vs. 27.4±13.1 cm H2O; P=0.848) at 12 and 6 months after initial surgical treatment. In conclusion, the urodynamics of this orthotopic ileal neobladder gradually improve, and its long-term urine storage and voiding functions are acceptable. PMID:25120652

  2. 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.

  3. 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.

  4. A Versatile Orthotopic Nude Mouse Model for Study of Esophageal Squamous Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Joseph Chok Yan Ip

    2015-01-01

    Full Text Available Increasing evidence indicates tumor-stromal interactions play a crucial role in cancer. An in vivo esophageal squamous cell carcinoma (ESCC orthotopic animal model was developed with bioluminescence imaging established with a real-time monitoring platform for functional and signaling investigation of tumor-stromal interactions. The model was produced by injection of luciferase-labelled ESCC cells into the intraesophageal wall of nude mice. Histological examination indicates this orthotopic model is highly reproducible with 100% tumorigenesis among the four ESCC cell lines tested. This new model recapitulates many clinical and pathological properties of human ESCC, including esophageal luminal stricture by squamous cell carcinoma with nodular tumor growth, adventitia invasion, lymphovascular invasion, and perineural infiltration. It was tested using an AKT shRNA knockdown of ESCC cell lines and the in vivo tumor suppressive effects of AKT knockdown were observed. In conclusion, this ESCC orthotopic mouse model allows investigation of gene functions of cancer cells in a more natural tumor microenvironment and has advantages over previous established models. It provides a versatile platform with potential application for metastasis and therapeutic regimen testing.

  5. Simplified technique for auxiliary orthotopic liver transplantation using a whole graft

    Science.gov (United States)

    ROCHA-SANTOS, Vinicius; NACIF, Lucas Souto; PINHEIRO, Rafael Soares; DUCATTI, Liliana; ANDRAUS, Wellington; D'ALBURQUERQUE, Luiz Carneiro

    2015-01-01

    Background Acute liver failure is associated with a high mortality rate and the main purposes of treatment are to prevent cerebral edema and infections, which often are responsible for patient death. The orthotopic liver transplantation is the gold standard treatment and improves the 1-year survival. Aim To describe an alternative technique to auxiliary liver transplant on acute liver failure. Method Was performed whole auxiliary liver transplantation as an alternative technique for a partial auxiliary liver transplantation using a whole liver graft from a child removing the native right liver performed a right hepatectomy. The patient met the O´Grady´s criteria and the rational to indicate an auxiliary orthotopic liver transplantation was the acute classification without hemodynamic instability or renal failure in a patient with deterioration in consciousness. Results The procedure improved liver function and decreased intracranial hypertension in the postoperative period. Conclusion This technique can overcome some postoperative complications that are associated with partial grafts. As far as is known, this is the first case of auxiliary orthotopic liver transplantation in Brazil. PMID:26176253

  6. OB glue paste technique for establishing nude mouse human gastric cancer orthotopic transplantation models

    Institute of Scientific and Technical Information of China (English)

    Jun Shi; Guo-Jing Zheng; Xiao-Mei Su; Ya-Lin Chen; Yan-Fang Liu; Ling Xu; Pin-Kang Wei; Shen Zhang; Zhi-Feng Qin; Jun Li; Da-Zhi Sun; Yan Xiao; Zhi-Hong Yu; Hui-Ming Lin

    2008-01-01

    AIM: To establish nude mouse human gastric cancer orthotopic transplantation models using OB glue paste technique.METHODS: Using OB glue paste technique,orthtopic transplantation models were established by implanting SGC-7901 and MKN-45 human gastric cancer cell strains into the gastric wall of nude mice.Biological features,growth of the implanted tumors,the success rate of transplantation and the rate of auto-metastasis of the two models were observed.RESULTS: The success rates of orthotopic transplantation of the two models were 94.20% and 96%.The rates of hepatic metastasis,pulmonary metastasis,peritoneal metastasis,lymphocytic metastasis and splenic metastasis were 42.13% and 94.20%,48.43% and 57.97%,30.83% and 36.96%,67.30% and 84.06%,and 59.75% and 10.53%,respectively.The occurrence of ascites was 47.80% and 36.96%.CONCLUSION: OB glue paste technique is easy to follow.The biological behaviors of the nude mouse human gastric cancer orthotopic transplantation models established with this technique are similar to the natural processes of growth and metastasis of human gastric cancer,and,therefore,can be used as an ideal model for experimental research of proliferative metastasis of tumors.

  7. 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.

  8. Cancer-associated fibroblasts in hepatocellular carcinoma.

    Science.gov (United States)

    Kubo, Norio; Araki, Kenichiro; Kuwano, Hiroyuki; Shirabe, Ken

    2016-08-14

    The hepatic stellate cells in the liver are stimulated sustainably by chronic injury of the hepatocytes, activating myofibroblasts, which produce abundant collagen. Myofibroblasts are the major source of extracellular proteins during fibrogenesis, and may directly, or secreted products, contribute to carcinogenesis and tumor progression. Cancer-associated fibroblasts (CAFs) are one of the components of the tumor microenvironment that promote the proliferation and invasion of cancer cells by secreting various growth factors and cytokines. CAFs crosstalk with cancer cells stimulates tumor progression by creating a favorable microenvironment for progression, invasion, and metastasis through the epithelial-mesenchymal transition. Basic studies on CAFs have advanced, and the role of CAFs in tumors has been elucidated. In particular, for hepatocellular carcinoma, carcinogenesis from cirrhosis is a known fact, and participation of CAFs in carcinogenesis is supported. In this review, we discuss the current literature on the role of CAFs and CAF-related signaling in carcinogenesis, crosstalk with cancer cells, immunosuppressive effects, angiogenesis, therapeutic targets, and resistance to chemotherapy. The role of CAFs is important in cancer initiation and progression. CAFtargeted therapy may be effective for suppression not only of fibrosis but also cancer progression. PMID:27570421

  9. Comprehensive sequential interventional therapy for hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

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

    2009-01-01

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

  10. Management of hepatocellular carcinoma in the elderly

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    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

  12. 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.

  13. 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)。

  14. Benign hepatocellular nodules: what have we learned using the patho-molecular classification.

    Science.gov (United States)

    Sempoux, Christine; Chang, Charissa; Gouw, Annette; Chiche, Laurence; Zucman-Rossi, Jessica; Balabaud, Charles; Bioulac-Sage, Paulette

    2013-09-01

    Focal nodular hyperplasia (FNH) and hepatocellular adenoma (HCA) are benign hepatocellular tumors that develop most frequently in females and in non-cirrhotic livers. HCA are prone to bleed and to transform into hepatocellular carcinoma (HCC). Four major subgroups of HCA have been thus far identified: HNF1α mutated HCA, inflammatory HCA (IHCA), β-catenin mutated HCA (b-HCA and b-IHCA), based on mutations in specific oncogenes and tumor suppressors. B-HCA and b-IHCA are strongly associated with HCC transformation. Benign hepatocellular tumors can be classified using immunohistochemistry (LFABP, CRP, GS, b-catenin). Analysis of HCA phenotypes has led to the identification of patients at risk of HCC transformation and therefore improved the indications provided by invasive and non-invasive diagnostic techniques, such as biopsies and MRI. These recent advances have broadened the clinical scope of HCA in various conditions, such as their presence in males, in obese patients, in patients suffering from liver vascular disorders, genetic diseases. However, specific immunohistochemistry has shown limitations particularly for the identification of b-HCA, thereby, outlining the importance of molecular studies to improve the diagnosis/prognosis of HCA. If evaluation of prognosis and treatment has benefited from these advances, much more needs to be done to obtain guidelines for good clinical practice. PMID:23876350

  15. 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

  16. Transcriptomic characterization of fibrolamellar hepatocellular carcinoma

    OpenAIRE

    Simon, Elana P.; Freije, Catherine A.; Farber, Benjamin A.; Lalazar, Gadi; Darcy, David G.; Honeyman, Joshua N.; Chiaroni-Clarke, Rachel; Dill, Brian D.; Molina, Henrik; Umesh K Bhanot; La Quaglia, Michael P.; Rosenberg, Brad R.; Simon, Sanford M.

    2015-01-01

    Fibrolamellar hepatocellular carcinoma (FLHCC) is a rare pediatric liver cancer. A deletion of ∼400 kb in one copy of chromosome 19 results in a chimeric protein, an activated protein kinase A. No other deletions, amplifications, mutations, or structural variants were found. This strongly implicates the chimera as the driving mutation. This paper examines gene expression in FLHCC. The results establish FLHCC as a single disease distinct from other cancers, including hepatocellular carcinoma. ...

  17. Contemporary management of fibrolamellar hepatocellular carcinoma

    OpenAIRE

    Tefera Kassahun, Woubet

    2016-01-01

    Fibrolamellar hepatocellular carcinoma (FL-HCC) is a malignant liver tumor which is thought to be a variant of conventional hepatocellular carcinoma (HCC). It accounts for a small proportion of HCC cases and occurs in a distinctly different group of patients which are young and usually not in the setting of chronic liver disease. The diagnosis of FL-HCC requires the integration of clinical information, imaging studies, and histology. In terms of the treatment options, the only potentially cur...

  18. 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.

  19. Alcoholic cirrhosis and hepatocellular carcinoma.

    Science.gov (United States)

    Stickel, Felix

    2015-01-01

    Hepatocellular carcinoma shows a rising incidence worldwide, and the largest burden of disease in Western countries derives from patients with alcoholic liver disease (ALD) and cirrhosis, the latter being the premier premalignant factor for HCC. The present chapter addresses key issues including the epidemiology of alcohol-associated HCC, and its link to other coexisting non-alcoholic liver diseases, and additional host and environmental risk factors including the underlying genetics. Also discussed are molecular mechanisms of alcohol-associated liver cancer evolution involving the mediators of alcohol toxicity and carcinogenicity, acetaldehyde and reactive oxygen species, as well as the recently described mutagenic adducts which these mediators form with DNA. Specifically, interference of alcohol with retinoids and cofactors of transmethylation processes are outlined. Information presented in this chapter illustrates that the development of HCC in the context of ALD is multifaceted and suggests several molecular targets for prevention and markers for the screening of risk groups. PMID:25427904

  20. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  2. Percutaneous microwave ablation vs radiofrequency ablation in the treatment of hepatocellular carcinoma.

    Science.gov (United States)

    Poulou, Loukia S; Botsa, Evanthia; Thanou, Ioanna; Ziakas, Panayiotis D; Thanos, Loukas

    2015-05-18

    Hepatocellular cancer ranks fifth among cancers and is related to chronic viral hepatitis, alcohol abuse, steatohepatitis and liver autoimmunity. Surgical resection and orthotopic liver transplantation have curative potential, but fewer than 20% of patients are suitable candidates. Interventional treatments are offered to the vast majority of patients. Radiofrequency (RFA) and microwave ablation (MWA) are among the therapeutic modalities, with similar indications which include the presence of up to three lesions, smaller than 3 cm in size, and the absence of extrahepatic disease. The therapeutic effect of both methods relies on thermal injury, but MWA uses an electromagnetic field as opposed to electrical current used in RFA. Unlike MWA, the effect of RFA is partially limited by the heat-sink effect and increased impedance of the ablated tissue. Compared with RFA, MWA attains a more predictable ablation zone, permits simultaneous treatment of multiple lesions, and achieves larger coagulation volumes in a shorter procedural time. Major complications of both methods are comparable and infrequent (approximately 2%-3%), and they include haemorrhage, infection/abscess, visceral organ injury, liver failure, and pneumothorax. RFA may incur the additional complication of skin burns. Nevertheless, there is no compelling evidence for differences in clinical outcomes, including local recurrence rates and survival. PMID:26052394

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

    Directory of Open Access Journals (Sweden)

    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.

  4. 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.

  5. Re-188 Lipiodol therapy of hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Full text: Hepatocellular carcinoma (HCC) is a malignant epithelial tumour arising from parenchymatous liver cells. It is one of the world's most common malignancies, causing almost one million deaths annually. About 315,000 new cases of HCC are reported per year which constitutes 5.6% of all cancers among males and 2.7% of all cancers among females. Control strategies to prevent occurrence of HCC are sub-optimal; this is evident by the rising incidence of HCC even in developed nations like the USA, where the prevalence of the disease is one of the lowest in the world. Currently, patients with HCC have an extremely poor prognosis with a five year survival rate of less than 5% . However, morbidity and mortality in such patients are not determined by the presence of HCC alone, but are also influenced by the activity of the underlying liver disease, as well as the functional status of the liver. The stage of the tumor (size, number, vascular invasion, extra hepatic spread) has been consistently documented to be an important determinant of the natural course of the disease. These factors are major variables that influence various therapeutic strategies directed against this tumor in recent times. Therefore, therapy in HCC needs to be optimized depending upon the above mentioned influences on the final outcome of the disease. Various forms of therapy such as surgical resection, orthotopic liver transplantation (OLT), percutaneous injection to induce coagulative necrosis of the tumor using agents like ethanol, acetic acid, hot saline, microwave and laser have been considered as radical treatment of HCC, aiming at curing the disease. The understanding of pathology, pathogenesis, natural course and risk factors of HCC during the last three decades has resulted in the development of multiple therapeutic approaches with promising yet varying results. Most patients with hepatoma from the developing countries at the time of their presentation to the doctor fall into the

  6. Creation of a murine orthotopic hepatoma model with intra-abdominal metastasis

    Science.gov (United States)

    Harris, Jamie; Kajdacsy-Balla, Andre; Chiu, Bill

    2016-01-01

    Aim: To create an orthotopic hepatoma model with local metastasis monitored with ultrasound could be created as a platform for testing new treatments. Background: Hepatoma accounts for 25% of liver tumors in children with poor overall survival. Intraabdominal metastasis are present in 35% of patients at time of diagnosis. We hypothesized that an orthotopic tumor model with local metastasis could be created as a platform for testing treatment modalities and could be monitored with ultrasound. Patients and methods: One million human hepatoma cells (Hep3B) were injected into the left lobe of the liver of immunocompromised mice. Tumor volume was monitored with high frequency-ultrasound until it reached 1,000mm3. At that time animals were sacrificed and examined for gross metastatic disease. Tumor sections were analyzed with hematoxylin and eosin (H&E) staining. Results: Tumor formed in 8/15 mice. The tumor was detected as small as 19.59mm3 on ultrasound. Of the forming tumors, tumor size was 145±177.93mm3 at 60 days post-injection, 665±650.39mm3 at 67 days, and reached >1000mm3 by 76.6±9.9 days. At necropsy, four mice (50%) had tumor only within the liver, four (50%) had additional tumors in omentum, pelvis and peritoneum. H&E showed tumor within the normal liver parenchyma, with multiple mitotic figures, small areas of necrosis, and hemorrhage within the tumor. Conclusion: We have successfully established an orthotopic hepatoma murine model, with a local metastatic rate of 50%. Non-invasive tumor monitoring is feasible via ultrasound.

  7. 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

  8. 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

  9. 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

  10. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  12. Laparoscopic radical cystectomy with orthotopic ileal neobladder in the female: report of 14 cases

    Institute of Scientific and Technical Information of China (English)

    LIN Tian-xin; YIN Xin-bao; HUANG Jian; ZHANG Cai-xia; XU Ke-wei; HUANG Hai; JIANG Chun; HAN Jin-li; YAO You-sheng; GUO Zheng-hui; XIE Wen-lian

    2008-01-01

    Background Bladder carcinoma is the most common malignant urological tumor in China. We present our preliminary experience and results of laparoscopic radical cystectomy (LRC) with orthotopic ileal neobladder in female patients with bladder carcinoma.Methods From February 2003 to February 2008, 14 female patients with bladder carcinoma underwent LRC with orthotopic ileal neobladder. Nine of these patients underwent hysterectomy and ovariectomy, and the other 5 had preservation of the uterus and ovarian appendage. Standard bilateral pelvic lymphadenectomy was followed by radical cystectomy that was completed laparoscopically with hysterectomy and ovariectomy when needed. The tumor was removed by a 4-5 cm lower midline abdominal incision, followed by the construction of ileal neobladder and the extracorporeal anastomosis of ureter-neobladder. The neobladder was anastomosed to the urethral stump under a laparoscope.Results The mean operative time and blood loss in the 14 patients were 350.2 minutes and 349.8 ml, respectively.Postoperative complications included uretero-pouch anastomotic stricture in 1 patient and pouch-vaginal fistula in 1 patient. Follow-up time of all patients ranged from 3 to 60 months, and 12 patients were followed up for more than 6 months and achieved micturition in half a year. One patient had occasional day-time urinary incontinence and 2 had night-time incontinence. Two patients who had undergone hystectomy and ovariectomy had voiding difficulties after one year, which was treated by intermittent self-catheterization. The mean volume of the neobladder and the residual urine were 333.6 ml and 31.2 ml, respectively. Surgical margins were tumor free for all patients. One patient had bone metastasis and died 11 months after the operation.Conclusions LRC with orthotopic ileal neobladder in female patients is a technically feasible, safe and mini-invasive procedure with a low morbidity and acceptable neobladder function. Long-term follow-up is

  13. 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.

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

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    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.

  15. Management of biliary complications after orthotopic liver transplantation: The role of endoscopy

    Institute of Scientific and Technical Information of China (English)

    Maria C Londo(n)o; Domingo Balderramo; Andrés Cárdenas

    2008-01-01

    Biliary complications are significant causes of morbidity and mortality after orthotopic liver transplantation (OLT). The estimated incidence of biliary complications after OLT ranges between 10%-25%, however, these numbers continue to decline due to improvement in surgical techniques. The most common biliary complications are strictures (both anastomotic and non-anastomotic) and bile leaks. Most of these problems can be appropriately managed with endoscopic retrograde colangiography (ERC). Other complications such as bile duct stones, bile casts, sphincter of Oddi dysfunction, and hemobilia, are less frequent and also can be managed with ERC. This article will review the risk factors, diagnosis, and endoscopic management of the most common biliary complications after OLT.

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

    OpenAIRE

    Boraschi, Piero; Donati, Francescamaria; Gigoni, Roberto; Filipponi, Franco

    2016-01-01

    Purpose To assess whether contrast-enhanced T1-weighted MR Cholangiography may provide additional information in the evaluation of biliary complications in orthotopic liver transplant recipients. Material and methods Eighty liver transplant patients with suspicion of biliary adverse events underwent MR imaging at 1.5 T scanner. After acquisition of axial T1-/T2-weighted images and conventional T2-weighted MR Cholangiography (image set 1), 3D gradient-echo T1-weighted fat-suppressed LAVA (Live...

  17. Establishment of a syngeneic orthotopic model of prostate cancer in immunocompetent rats

    OpenAIRE

    Suzuki, Shugo; Naiki-Ito, Aya; KUNO, Toshiya; Punfa, Wanisa; Long, Ne; Kato, Hiroyuki; Inaguma, Shingo; Komiya, Masami; Shirai, Tomoyuki; TAKAHASHI,Satoru

    2014-01-01

    We previously established 3 cell lines (PLS10, PLS20 and PLS30) from a chemically-induced prostate carcinoma in F344 rats, and demonstrated high potential for metastasis in nude mice. In the present study, we investigated the feasibility of establishing an orthotopic model using the 3 rat prostate cancer cell lines in immunocompetent rats with the aim of resolving species-mismatch problems and defects of immune systems. The PLS10, PLS20 and PLS30 cell lines were injected into the ventral pros...

  18. Armc8 regulates the invasive ability of hepatocellular carcinoma through E-cadherin/catenin complex.

    Science.gov (United States)

    Zhao, Yang; Peng, Songlin; Jia, Changjun; Xu, Feng; Xu, Yongqing; Dai, Chaoliu

    2016-08-01

    Armc8 (armadillo-repeat-containing protein 8) was proved to promote disruption of E-cadherin complex through regulating α-catenin degradation. In this study, we investigated Armc8 expression in hepatocellular carcinoma using immunohistochemistry (IHC). The positive rate of Armc8 expression in hepatocellular carcinoma was 53.9 % and higher than that in normal hepatic tissues (9.2 %) (p < 0.05). Clinicopathological analysis shows that Armc8 expression in hepatocellular carcinoma was significantly associated with larger tumor size (≥5 cm), multiple tumor numbers, higher pathological grade (media and poor), advanced TNM stages (II/III), and advanced BCLC stages (B/C). Western blot study also detected higher Armc8 expression in hepatocellular carcinoma cells including HepG2, HCC97L, and SMMC-7721 than in human hepatic cell Bel-7402. We further use specific small interfering RNAs (siRNAs) to knock down Armc8 expression in HepG2 cells and found that knockdown of Armc8 expression significantly inhibited the invasive ability of HepG2 cells. Downregulation of Armc8 expression significantly upregulated α-catenin, β-catenin, and E-cadherin expression in HepG2 cells. Immunofluorescent study shows that knockdown of Armc8 expression restored E-cadherin expression in membrane of HepG2 cells. These results indicate that Armc8 may be a potential cancer marker in hepatocellular carcinoma and may regulate cancer invasion through E-cadherin/catenin complex. PMID:26944057

  19. Three agonist antibodies in combination with high-dose IL-2 eradicate orthotopic kidney cancer in mice

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    Sharkey Janelle

    2010-04-01

    Full Text Available Abstract Background Combination immunotherapies can be effective against subcutaneous tumors in mice but the effect against orthotopic malignant disease is less well characterized. In particular, a combination of three agonist antibodies, termed Tri-mAb, consisting of anti-DR5, anti-CD40 and anti-CD137 has previously been demonstrated to eradicate a large proportion of subcutaneous renal cell carcinoma (Renca tumors (75% long-term survival, but the effect against orthotopic disease is not known. Purpose To determine the relative response of orthotopic tumors, we inoculated Renca into the kidney followed by treatment with Tri-mAb. Results We found that orthotopic tumors responded much less to treatment (~13% survival, but a significant improvement in survival was achieved through the addition of IL-2 to the treatment regimen (55% survival. All three agonist antibodies and high dose IL-2, 100,000 IU for up to six doses, were required. CD8+ T cells were also required for optimal anti-tumor responses. Coadministration of IL-2 led to enhanced T cell activity as demonstrated by an increased frequency of IFN-gamma-producing T cells in tumor-draining lymph nodes, which may have contributed to the observed improvement of therapy against kidney tumors. Implications Responses of subcutaneous tumors to immunotherapy do not necessarily reflect how orthotopic tumors respond. The use of combination immunotherapy stimulating multiple facets of immunity and including cytokine support for T cells can induce effective anti-tumor responses against orthotopic and metastatic tumors.

  20. Clonal Origin of Hepatocellular Carcinoma and Recurrence After Liver Transplantation.

    Science.gov (United States)

    Wang, Zhenglu; Gong, Weihua; Shou, Dawei; Zhang, Luzhou; Gu, Xiangqian; Wang, Yuliang; Teng, Dahong; Zheng, Hong

    2016-01-01

    BACKGROUND This study aimed to determine whether patterns of tumor clonal origin in pluri-nodular hepatocellular carcinoma (PNHC) could serve as an indicator of tumor recurrence following liver transplantation. MATERIAL AND METHODS Tumor tissue samples from 60 PNHC patients who underwent liver transplantation were examined. The diagnosis of patients conformed to the University of California San Francisco (UCSF) standards for pluri-nodular hepatocellular carcinoma. We performed loss of heterozygosity tests at multiple microsatellite sites to determine the clonal origins of the tumors. Clinical information, pathological data, preoperative serum alpha-feto protein (AFP) and postoperative follow-ups were obtained and correlations between the clonal origin of the tumor, tumor-free survival, pathological characteristics, and AFP levels in serum were studied. RESULTS A total of 165 tumor nodules were collected. Tumor clonal origins were identified as intrahepatic metastasis (IM; 41.67%), multicentric occurrence (MO; 55%) or unidentified (3.33%). Three-year tumor-free survival for the IM group was 48% compared to 75.76% in the MO group (pAFP concentration for these groups was 226.80 μg/L (2.78-3000 μg/L) and 24.59 μg/L (1.16-531. 30 μg/L; pAFP levels, the risk of recurrence can be established in advance. PMID:27487734

  1. Adenoviral targeting of malignant melanoma for fluorescence-guided surgery prevents recurrence in orthotopic nude-mouse models

    Science.gov (United States)

    Yano, Shuya; Takehara, Kiyoto; Kishimoto, Hiroyuki; Urata, Yasuo; Kagawa, Shunsuke; Bouvet, Michael; Fujiwara, Toshiyoshi; Hoffman, Robert M.

    2016-01-01

    Malignant melanoma requires precise resection in order to avoid metastatic recurrence. We report here that the telomerase-dependent, green fluorescent protein (GFP)-containing adenovirus OBP-401 could label malignant melanoma with GFP in situ in orthotopic mouse models. OBP-401-based fluorescence-guided surgery (FGS) resulted in the complete resection of malignant melanoma in the orthotopic models, where conventional bright-light surgery (BLS) could not. High-dose administration of OBP-401 enabled FGS without residual cancer cells or recurrence, due to its dual effect of cancer-cell labeling with GFP and killing. PMID:26701857

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

    Directory of Open Access Journals (Sweden)

    Ajay Vallakati

    2011-01-01

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

  3. 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.

  4. Progress in clinical oncolytic virus-based therapy for hepatocellular carcinoma

    OpenAIRE

    Jebar, AH; Errington-Mais, F; Vile, RG; Selby, PJ; Melcher, AA; S. Griffin(Physics Department, McGill University, Montreal, QC H3A 2T8, Canada)

    2015-01-01

    Hepatocellular carcinoma (HCC) carries a dismal prognosis, with advanced disease being resistant to both radiotherapy and conventional cytotoxic drugs, whilst anti-angiogenic drugs are marginally efficacious. Oncolytic viruses (OVs) offer the promise of selective cancer therapy through direct and immune-mediated mechanisms. The premise of OVs lies in their preferential genomic replication, protein expression and productive infection of malignant cells. Numerous OVs are being tested in preclin...

  5. Functional study of suppressor of variegation 3-9 homolog 1 in hepatocellular carcinoma

    OpenAIRE

    Fan, Ngo-yin.; 樊傲賢.

    2012-01-01

    Hepatocellular carcinoma (HCC) is the major type of primary liver cancer which is well-known for its high heterogenicity and metastatic potential. Despite of the current advancement in surgical resection and the availability of targeted therapy, HCC remains a barely curable and fatal disease. We previously demonstrated that deregulation of epigenetic regulators is a common event in human HCC. Herein, we identified the frequent up-regulation of the prototype of H3K9 tri-methyltransferase SUV3...

  6. 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

  7. Surgical management of spontaneous ruptured hepatocellular adenoma

    Directory of Open Access Journals (Sweden)

    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.

  8. 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.

  9. Regression of orthotopic neuroblastoma in mice by targeting the endothelial and tumor cell compartments

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    Stridsberg Mats

    2009-03-01

    Full Text Available Abstract Background High-risk neuroblastoma has an overall five-year survival of less than 40%, indicating a need for new treatment strategies such as angiogenesis inhibition. Recent studies have shown that chemotherapeutic drugs can inhibit angiogenesis if administered in a continuous schedule. The aim of this study was primarily to characterize tumor spread in an orthotopic, metastatic model for aggressive, MYCN-amplified neuroblastoma and secondarily to study the effects of daily administration of the chemotherapeutic agent CHS 828 on tumor angiogenesis, tumor growth, and spread. Methods MYCN-amplified human neuroblastoma cells (IMR-32, 2 × 106 were injected into the left adrenal gland in SCID mice through a flank incision. Nine weeks later, a new laparotomy was performed to confirm tumor establishment and to estimate tumor volume. Animals were randomized to either treatment with CHS 828 (20 mg/kg/day; p.o. or vehicle control. Differences between groups in tumor volume were analyzed by Mann-Whitney U test and in metastatic spread using Fisher's exact test. Differences with p Results The orthotopic model resembled clinical neuroblastoma in respect to tumor site, growth and spread. Treatment with CHS 828 resulted in tumor regression (p Conclusion The metastatic animal model in this study resembled clinical neuroblastoma and is therefore clinically relevant for examining new treatment strategies for this malignancy. Our results indicate that daily scheduling of CHS 828 may be beneficial in treating patients with high-risk neuroblastoma.

  10. 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.

  11. 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.

  12. 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

  13. The use of coronary stent in hepatic artery stenosis after orthotopic liver transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Huang Mingsheng [Department of Radiology, the Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510630, Guangdong Province (China); Shan Hong [Department of Radiology, the Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510630, Guangdong Province (China)]. E-mail: gzshsums@public.guangzhou.gd.cn; Jiang Zaibo [Department of Radiology, the Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510630, Guangdong Province (China); Li Zhengran [Department of Radiology, the Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510630, Guangdong Province (China); Zhu Kangshun [Department of Radiology, the Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510630, Guangdong Province (China); Guan Shouhai [Department of Radiology, the Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510630, Guangdong Province (China); Qian Jiesheng [Department of Radiology, the Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510630, Guangdong Province (China); Chen Guihua [Transplantation Center, the Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510630, Guangdong Province (China); Lu Minqiang [Transplantation Center, the Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510630, Guangdong Province (China); Yang Yang [Transplantation Center, the Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510630, Guangdong Province (China)

    2006-12-15

    Purpose: This retrospective study was undertaken to evaluate the effectiveness of coronary stent placement in hepatic artery stenosis after orthotopic liver transplantation (OLT). Materials and methods: Of 430 consecutive adult orthotopic liver transplant recipients between November 2003 and September 2005, 17 had hepatic artery stenosis (HAS). Fourteen of them underwent coronary stent placement in the HAS. The technical results, complications, hepatic artery patency and clinical outcome were reviewed. Results: Technical and immediate success was 100%. After a mean follow-up of 159.4 days (range, 9-375 days), all patients obtained patent hepatic arteries except 2 patients occurred hepatic artery restenoses at 26 and 45 days after stent placement, respectively. Kaplan-Meier curve of patency showed cumulated stent patency at 3, 6, and 12 months of 78%, 58% and 45%, respectively. During the follow-up, 8 patients survived, 5 died of septic multiple-organ failure, 1 received retransplantation because of refractory biliary infection. Hepatic artery dissection induced by a guiding catheter occurred in one patient and was successfully treated with a coronary stent. Conclusion: Hepatic artery stenosis after OLT can be successfully treated with coronary stent placement with low complication rate and an acceptable 1-year hepatic artery patency rate.

  14. 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.

  15. Orthotopic liver transplantation in an adult with cholesterol ester storage disease.

    Science.gov (United States)

    Ambler, Graeme K; Hoare, Matthew; Brais, Rebecca; Shaw, Ashley; Butler, Andrew; Flynn, Paul; Deegan, Patrick; Griffiths, William J H

    2013-01-01

    Cholesterol ester storage disease (CESD) is a rare autosomal recessive lipid storage disorder associated with mutations of the gene encoding lysosomal acid lipase, manifestations of which include chronic liver disease and early atherosclerosis. Although normally presenting in childhood, severity is variable and the condition can occasionally remain undetected until middle age. Typical presentation is with asymptomatic hepatosplenomegaly and hyperlipidaemia, though the condition is probably underdiagnosed. Treatment is supportive and may include attention to cardiovascular risk factors. Phase I/II trials of enzyme replacement therapy are ongoing, but this approach remains experimental. We present the case of a 42-year-old woman diagnosed with CESD in childhood who ran an indolent course until re-presentation with cirrhotic hydrothorax. She underwent orthotopic liver transplantation but required re-transplantation for hepatic artery thrombosis. She remains well with excellent graft function 2 years later. Although atherosclerosis was apparent at assessment, and may have contributed to hepatic artery thrombosis, partial correction of the metabolic defect and restoration of liver function by transplantation together with ongoing medical therapy should permit reasonable survival over the longer term from both a liver and a vascular perspective. This is the first reported case of orthotopic liver transplantation for CESD in an adult, which was the only available option to improve survival. The case highlights the importance of monitoring patients with CESD through adulthood and suggests that liver replacement at a later stage may yet be indicated and remain of benefit. PMID:23430518

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

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    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.

  17. A New Cone-Shaped Aortic Valve Prosthesis for Orthotopic Position: An Experimental Study in Swine

    International Nuclear Information System (INIS)

    The aim of this experimental study was to evaluate a newly designed cone-shaped aortic valve prosthesis (CAVP) for one-step transcatheter placement in an orthotopic position. The study was conducted in 15 swine using either the transcarotid (11 animals) or the transfemoral (4 animals) artery approach. A 12- or 13-Fr sheath was inserted via arterial cutdown. The CAVP was deployed under fluoroscopic control and its struts, by design, induced significant native valve insufficiency. CAVP function was evaluated by aortography and aortic pressure curve tracing. In 11 of 15 swine the CAVP was properly deployed and functioned well throughout the scheduled period of 2-3 h. In three swine the CAVPs were placed lower than intended, however, they were functional even in the left ventricular outflow tract position. One swine expired due to inadvertent low CAVP placement that caused both aortic regurgitation and immobilization of the anterior mitral valve leaflet by the valve struts. We conclude that this design of CAVP is relatively easy to deploy, works well throughout a short time period (2-3 h), and, moreover, seems to be reliable even in a lower-than-orthotopic position (e.g., infra-annulary space). Longer-term studies are needed for its further evaluation.

  18. The prognostic molecular markers in hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Lun-Xiu Qin; Zhao-You Tang

    2002-01-01

    The prognosis of hepatocellular carcinoma (HCC) stillremains dismal, although many advances in its clinicalstudy have been made. It is important for tumor control toidentity the factors that predispose patients to death. Withnew discoveries in cancer biology, the pathological andbiological prognostic factors of HCC have been studied quiteextensively. Analyzing molecular markers (biomarkers) withprognostic significance is a complementary method. A largenumber of molecular factors have been shown to associatewith the invasiveness of HCC, and have potential prognosticsignificance. One important aspect is the analysis ofmolecular markers for the cellular malignancy phenotypeThese include alterations in DNA ploidy, cellularproliferation markers (PCNA, Ki-67, Mcm2, MIB1, MIA, andCSE1L/CAS protein), nuclear morphology, the p53 geneand its related molecule MDM2, other cell cycle regulators(cyclin A, cyclin D, cyclin E, cdc2, p27, p73), oncogenesand their receptors (such as ras, c-myc, c-fms, HGF, c-met, and erb-B receptor family members ), apoptosisrelated factors (Fas and FasL), as well as telomeraseactivity. Another important aspect is the analysis ofmolecular markers involved in the process of cancerinvasion and metastasis. Adhesion molecules (E-cadherin,catenins, serum intercellular adhesion molecule-1, CD44variants), proteinases involved in the clegradation ofextracellular matrix (MMP-2, MMP-9, uPA, uPAR, PAl), aswell as other molecules have been regarded as biomarkersfor the malignant phenotype of HCC, and are related toprognosis and therapeutic outcomes. Tumor angiogenesisis critical to both the growth and metastasis of cancersincluding HCC, and has drawn much attention in recentyears. Many angiogenesis-related markers, such as vascularendothelial growth factor (VEGF), basic fibroblast growthfactor (bFGF), platelet-derived endothelial cell growth factor( PD-ECGF ), thrombospondin ( TSP ), angiogenin,pleiotrophin, and endostatin (ES) levels, as well asinratumor

  19. 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.

  20. Metallothionein expression in hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Geng-Wen Huang; Lian-Yue Yang

    2002-01-01

    AIM: To investigate the expression of metallothioneins(MTs), which were recently thought to have closerelationship with tumors, in human hepatocellularcarcinoma.METHODS: Histological specimens of 35 cases of primaryhuman hepatocellular carcinoma with para-neoplasticliver tissue and 5 cases of normal liver were stainedfor MTs with monoclonal mouse anti-MTs serum (Eg)by the immunohistochemical ABC technique. RESULTS: MTs were stained in the 35 cases of HCC,including 6 cases negative (17.1 %), 23 weaklypositive (65.7 %), and 6 strongly positive(17.1%).But MTs were stained strongly positive in all the fivecases of normal liver and 35 cases of para-neoplasticliver tissue. The differences of MTs expression betweenHCC and normal liver tissue or para-neoplastic livertissue were highly significant (P<0.01). The rate ofMTs expression in HCC grade I was 100 percent,higher than that in grade Ⅱ(81%) and grade Ⅲand Ⅳ (78 %). But the differences were notsignificant (P>0.05). No obvious correlationsbetween MTs expression in HCC and tumor size,clinical stage or serum alpha fetoproteinconcentration were found (P>0.05).CONCLUSION: Decrease of MTs expression in HCC mayplay a role in carcinogenesis of HCC. MTs are stainedheterogenously in HCC. We can choose the anticanceragents according to the MTs concentraiton in HCC, whichmay improve the results of chemotherapy for HCC.

  1. 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.

  2. 索拉非尼治疗进展期肝细胞癌的疗效及预后因素分析%Efficacy of Sorafenib for Advanced Hepatocellular Carcinoma and Prognostic Factors

    Institute of Scientific and Technical Information of China (English)

    王春平; 杨永平; 解放军; 陆荫英; 高旭东; 王鋐; 白文林; 曲建慧; 曾珍; 张敏娜; 常秀娟

    2012-01-01

    目的 评价索拉非尼治疗进展期肝细胞癌(HCC)的疗效及分析其预后影响因素.方法 前瞻性分析2007年8月至2009年7月间110例接受索拉非治疗的进展期HCC患者,评价其疗效、不良反应,以总生存期和无肿瘤进展生存期为预后指标进行单因素和Cox比例风险模型多因素分析.结果 110例患者随访中位时间9(2~18)个月,服用索拉非尼中位时间6.5(2~18)个月.14例(12.7%)获得完全缓解(CR),16例(14.5%)部分缓解(PR),40例(36.4%)病情稳定(SD),总有效率为70例(63.6%).中位生存期和无肿瘤进展生存期分别为10.5个月(95%CI:8.7~12.3)和5.0个月(95%CI:3.7~6.3).多因素分析显示:联合局部治疗(肝动脉化疗栓塞或氩氦刀)、美国东部肿瘤协作组活动状态评分(Eastern Cooperative Oncology Group performance status score,ECOG PS)和Child-Pugh分级是影响无肿瘤进展生存时间的独立预后因素,而联合局部治疗、ECOG PS评分和AFP(alfa-fetopro-tein)水平是影响总生存期的独立预后因素.亚组分析显示:在肝癌进展组患者中继续服用索拉非尼其总生存期明显长于终止索拉非尼治疗者(11个月vs.7.5个月,P<0.001).结论 索拉非尼治疗进展期HCC,ECOG PS评分是影响生存期的一个重要因素,联合局部治疗有益于改善生存期.%Objective: To evaluate the efficacy arid analyze the prognostic factors of sorafenib treatment in patients with advanced hepatoccllular carcinoma ( HCC ). Methods: Baseline characteristics and outcomes of 110 patients with advanced HCC treated with sorafenib with/without local therapy from a single liver cancer center were collected. Predictors of progress-free survival ( PFS ) and overall survival ( OS ) were determined by muliivariable analysis. Results: Complete response was observed in 14 patients ( 12.7% ), partial response ( PR) in 16 patients ( 14.5%), and stable disease ( SD ) in 40 patients ( 36.4% ). The therapeutic effective rate was 63

  3. 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...

  4. 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

  5. Staging systems for hepatocellular carcinoma: Currentstatus and future perspectives

    Institute of Scientific and Technical Information of China (English)

    Akiyoshi Kinoshita; Hiroshi Onoda; Nao Fushiya; Kazuhiko Koike; Hirokazu Nishino; Hisao Tajiri

    2015-01-01

    Hepatocellular carcinoma (HCC) is a major healthconcern worldwide and the third cause of cancer-relateddeath. Despite advances in treatment as well as carefulsurveillance programs, the mortality rates in mostcountries are very high. In contrast to other cancers,the prognosis and treatment of HCC depend on thetumor burden in addition to patient's underlying liverdisease and liver functional reserve. Moreover, thereis considerable geographic and institutional variationin both risk factors attributable to the underlying liverdiseases and the management of HCC. Therefore,although many staging and/or scoring systems havebeen proposed, there is currently no globally acceptedsystem for HCC due to the extreme heterogeneityof the disease. The aim of this review is to focus oncurrently available staging systems as well as thosenewly reported in the literatures since 2012. Moreover,we describe problems with currently available stagingsystems and attempts to modify and/or add variables toexisting staging systems.

  6. 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。

  7. 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

  8. 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.

  9. Coronary stent placement via radial artery for the treatment of circuitous hepatic artery stenosis after orthotopic liver transplantation

    International Nuclear Information System (INIS)

    Objective: To evaluate the feasibility and effectiveness of coronary stent placement via radial artery in the treatment of circuitous hepatic artery stenosis after orthotopic liver transplantation. Methods: Six patients with circuitous hepatic artery stenosis after orthotopic liver transplantation, encountered during the period of June 2006-Apr. 2008, were enrolled in this study. The stenosis occurred in 6-110 days (mean 47 days) after orthotopic liver transplantation. Stent placement through the left radial artery was carried out in 2 patients after the catheterization via the right femoral artery failed. Based on the preoperative CTA findings, stent placement through left radial artery was straightly performed in 4 patients. Thrombolytic therapy with 500,000 unit of urokinase was adopted in one patient with hepatic thrombus before stent placement. Percutaneous transhepatic biliary drainage (PTCD) was simultaneously performed with stent placement in two patients with dilated biliary tract. Results: The technical success rate was 100%. Thrombolytic therapy was successful in one patient with hepatic thrombus and PTCD had a curative effect on the biliary tract dilatation in two patients. During a follow-up period of 36-148 days (median 76 days), no stent stenosis was found on color Doppler ultrasonogram, the hepatic arteries remained patent in all patients. The hepatic functional parameters were improved in all cases. Conclusion: Coronary stent placement via radial artery is an effective treatment for circuitous hepatic artery stenosis after orthotopic liver transplantation. (authors)

  10. 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

  11. 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

  12. Microwave ablation of hepatocellular carcinoma.

    Science.gov (United States)

    Poggi, Guido; Tosoratti, Nevio; Montagna, Benedetta; Picchi, Chiara

    2015-11-01

    Although surgical resection is still the optimal treatment option for early-stage hepatocellular carcinoma (HCC) in patients with well compensated cirrhosis, thermal ablation techniques provide a valid non-surgical treatment alternative, thanks to their minimal invasiveness, excellent tolerability and safety profile, proven efficacy in local disease control, virtually unlimited repeatability and cost-effectiveness. Different energy sources are currently employed in clinics as physical agents for percutaneous or intra-surgical thermal ablation of HCC nodules. Among them, radiofrequency (RF) currents are the most used, while microwave ablations (MWA) are becoming increasingly popular. Starting from the 90s', RF ablation (RFA) rapidly became the standard of care in ablation, especially in the treatment of small HCC nodules; however, RFA exhibits substantial performance limitations in the treatment of large lesions and/or tumors located near major heat sinks. MWA, first introduced in the Far Eastern clinical practice in the 80s', showing promising results but also severe limitations in the controllability of the emitted field and in the high amount of power employed for the ablation of large tumors, resulting in a poor coagulative performance and a relatively high complication rate, nowadays shows better results both in terms of treatment controllability and of overall coagulative performance, thanks to the improvement of technology. In this review we provide an extensive and detailed overview of the key physical and technical aspects of MWA and of the currently available systems, and we want to discuss the most relevant published data on MWA treatments of HCC nodules in regard to clinical results and to the type and rate of complications, both in absolute terms and in comparison with RFA. PMID:26557950

  13. Newer markers for hepatocellular carcinoma.

    Science.gov (United States)

    Marrero, Jorge A; Lok, Anna S F

    2004-11-01

    The incidence of hepatocellular carcinoma (HCC) is increasing worldwide; the overall survival of patients with HCC is grim because most patients are diagnosed late, when curative treatment is not possible. Cirrhosis is the strongest risk factor for the development of HCC. HCC surveillance with alpha-fetoprotein (AFP) and ultrasonography has been recommended for persons with cirrhosis. However, AFP level is insensitive for the early detection of HCC, and ultrasonography is expensive and operator dependent. Clearly, there is a need for novel strategies for the early detection of HCC. The ideal biomarker assay for HCC would be sensitive, specific, noninvasive, reproducible, inexpensive, and acceptable to patients. The Early Detection Research Network of the National Cancer Institute has proposed 5 phases for biomarker validation: preclinical exploratory studies, clinical assay development for disease, retrospective longitudinal study to detect preclinical disease, prospective screening study, and cancer control studies. Several biomarkers, such as des-gamma carboxyprothrombin, lens culinaris agglutinin-reactive AFP, human hepatocyte growth factor, and insulin-like growth factor-1, are promising, but none of these markers has been validated for clinical use. Limitations of the current literature include inadequate sample size, heterogeneity in biomarker assay methods and result reporting, limited analysis of demographics and cause of liver disease as covariates in the expression of these markers, and a scarcity of longitudinal studies evaluating the ability of biomarkers to detect preclinical disease. There is an urgent need for novel biomarkers for the detection of early HCC; the National Cancer Institute proposal provides a framework for future validation studies. PMID:15508074

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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).

  19. 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. PMID:26548537

  20. 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.

  1. 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.

  2. Hepatocellular carcinoma: risk groups, surveillance and outcome

    NARCIS (Netherlands)

    Meer, S. van

    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

  3. Hyperkalaemia after radiofrequency ablation of hepatocellular carcinoma

    NARCIS (Netherlands)

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

    2002-01-01

    Radiofrequency ablation of liver tumours is a useful therapy for otherwise unresectable tumours. The complication rate is said to be low. In this case report we describe hyperkalaemia after radiofrequency ablation of a hepatocellular carcinoma in a patient with end-stage renal insufficiency. (C) 200

  4. Liver transplantation in patients with hepatocellular carcinoma

    NARCIS (Netherlands)

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

    2008-01-01

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

  5. BDNF signaling contributes to oral cancer pain in a preclinical orthotopic rodent model

    Science.gov (United States)

    Chodroff, Leah; Bendele, Michelle; Valenzuela, Vanessa; Henry, Michael

    2016-01-01

    The majority of patients with oral cancer report intense pain that is only partially managed by current analgesics. Thus, there is a strong need to study mechanisms as well as develop novel analgesics for oral cancer pain. Current study employed an orthotopic tongue cancer model with molecular and non-reflexive behavioral assays to determine possible mechanisms of oral cancer pain. Human oral squamous cell carcinoma cells line, HSC2, was injected into the tongue of male athymic mice and tumor growth was observed by day 6. Immunohistological analyses revealed a well-differentiated tumor with a localized immune response and pronounced sensory and sympathetic innervation and vascularization. The tumor expressed TMPRSS2, a protein previously reported with oral squamous cell carcinoma. ATF3 expression in trigeminal ganglia was not altered by tumor growth. Molecular characterization of the model demonstrated altered expression of several pain-related genes, out of which up-regulation of BDNF was most striking. Moreover, BDNF protein expression in trigeminal ganglia neurons was increased and inhibition of BDNF signaling with a tyrosine kinase B antagonist, ANA-12, reversed pain-like behaviors induced by the oral tumor. Oral squamous cell carcinoma tumor growth was also associated with a reduction in feeding, mechanical hypersensitivity in the face, as well as spontaneous pain behaviors as measured by the conditioned place preference test, all of which were reversed by analgesics. Interestingly, injection of HSC2 into the hindpaw did not reproduce this spectrum of pain behaviors; nor did injection of a colonic cancer cell line into the tongue. Taken together, this orthotopic oral cancer pain model reproduces the spectrum of pain reported by oral cancer patients, including higher order cognitive changes, and demonstrates that BDNF signaling constitutes a novel mechanism by which oral squamous cell carcinoma induces pain. Identification of the key role of tyrosine kinase B

  6. SERPINI1 regulates epithelial-mesenchymal transition in an orthotopic implantation model of colorectal cancer.

    Science.gov (United States)

    Matsuda, Yasufumi; Miura, Koh; Yamane, Junko; Shima, Hiroshi; Fujibuchi, Wataru; Ishida, Kazuyuki; Fujishima, Fumiyoshi; Ohnuma, Shinobu; Sasaki, Hiroyuki; Nagao, Munenori; Tanaka, Naoki; Satoh, Kennichi; Naitoh, Takeshi; Unno, Michiaki

    2016-05-01

    An increasingly accepted concept is that the progression of colorectal cancer is accompanied by epithelial-mesenchymal transition (EMT). In our study, in order to characterize the properties of EMT in 16 colorectal cancer cell lines, the cells were first orthotopically implanted into nude mice, and the tumors in vivo, as well as cells cultured in vitro, were immunostained for EMT markers. The immunostaining revealed that seven of the cells had an epithelial phenotype with a high expression of E-cadherin, whereas other cells showed opposite patterns, such as a high expression of vimentin (CX-1, COLO205, CloneA, HCT116, and SW48). Among the cells expressing vimentin, some expressed vimentin in the orthotopic tumors but not in the cultured cells (SW480, SW620, and COLO320). We evaluated these findings in combination with microarray analyses, and selected five genes: CHST11, SERPINI1, AGR2, FBP1, and FOXA1. Next, we downregulated the expression of SERPINI1 with siRNA in the cells, the results of which showed reverse-EMT changes at the protein level and in the cellular morphology. Along with immunohistochemical analyses, we confirmed the effect of the intracellular and secreted SERPINI1 protein of SW620 cells, which supported the importance of SERPINI1 in EMT. The development of therapeutic strategies targeting EMT is ongoing, including methods targeting the transforming growth factor-β signaling pathway as well as the Wnt pathway. SERPINI1 is an important regulator of EMT. Our findings help to elucidate the signaling pathways of EMT, hopefully clarifying therapeutic pathways as well. PMID:26892864

  7. Expression of liver fatty acid binding protein in hepatocellular carcinoma.

    Science.gov (United States)

    Cho, Soo-Jin; Ferrell, Linda D; Gill, Ryan M

    2016-04-01

    Loss of expression of liver fatty acid binding protein (LFABP) by immunohistochemistry has been shown to be characteristic of a subset of hepatocellular adenomas (HCAs) in which HNF1A is inactivated. Transformation to hepatocellular carcinoma is thought to be a very rare phenomenon in the HNF1A-inactivated variant of HCA. However, we recently observed 2 cases at our institution, 1 definite hepatocellular carcinoma and 1 possible hepatocellular carcinoma, with loss of LFABP staining, raising the possibility that LFABP down-regulation may be associated with hepatocellular carcinogenesis. Our aim was to evaluate hepatocellular carcinomas arising in various backgrounds and with varying degrees of differentiation for loss of LFABP staining. Twenty total cases of hepatocellular carcinoma were examined. Thirteen cases arose in a background of cirrhosis due to hepatitis C (n = 8) or steatohepatitis (n = 5); 7 cases arose in a noncirrhotic background, with 2 cases arising within HNF1A-inactivated variant HCA and 2 cases arising within inflammatory variant HCA. Complete loss of expression of LFABP was seen in 6 of 20 cases, including 2 cases of hepatocellular carcinoma arising within HNF1A-inactivated variant HCA. Thus, loss of staining for LFABP appears to be common in hepatocellular carcinoma and may be seen in well-differentiated hepatocellular carcinoma. Therefore, LFABP loss should not be interpreted as evidence for hepatocellular adenoma over carcinoma, when other features support a diagnosis of hepatocellular carcinoma. The findings raise consideration for a role of HNF1A inactivation in hepatocellular carcinogenesis, particularly in less differentiated tumors. PMID:26997447

  8. Transcatheter Arterial Chemoembolization Based on Hepatic Hemodynamics for Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Satoru Murata

    2013-01-01

    Full Text Available Hepatocellular carcinoma (HCC is the sixth most common cancer and the third leading cause of cancer-related deaths in the world. The Barcelona Clinic Liver Cancer (BCLC classification has recently emerged as the standard classification system for clinical management of patients with HCC. According to the BCLC staging system, curative therapies (resection, transplantation, and percutaneous ablation can improve survival in HCC patients diagnosed at an early stage and offer potential long-term curative effects. Patients with intermediate-stage HCC benefit from transcatheter arterial chemoembolization (TACE, and those diagnosed at an advanced stage receive sorafenib, a multikinase inhibitor, or conservative therapy. Most patients receive palliative or conservative therapy only, and approximately 50% of patients with HCC are candidates for systemic therapy. TACE is often recommended for advanced-stage HCC patients all over the world because these patients desire therapy that is more effective than systemic chemotherapy or conservative treatment. This paper aims to summarize both the published data and important ongoing studies for TACE and to discuss technical improvements in TACE for advanced-stage HCC.

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  4. 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.

  5. 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

  6. 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

  7. 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.

  8. Identification of Driver Genes in Hepatocellular Carcinoma by Exome Sequencing

    OpenAIRE

    Sean P Cleary; Jeck, William R.; Zhao, Xiaobei; Chen, Kui; Selitsky, Sara R.; Savich, Gleb L.; Tan, Ting-Xu; Wu, Michael C.; Getz, Gad; Lawrence, Michael S.; Joel S Parker; Li, Jinyu; Powers, Scott; Kim, Hyeja; Fischer, Sandra

    2013-01-01

    Genetic alterations in specific driver genes lead to disruption of cellular pathways and are critical events in the instigation and progression of hepatocellular carcinoma. As a prerequisite for individualized cancer treatment, we sought to characterize the landscape of recurrent somatic mutations in hepatocellular carcinoma. We performed whole exome sequencing on 87 hepatocellular carcinomas and matched normal adjacent tissues to anaverage coverage of 59x. The overall mutation rate was rough...

  9. Evaluation of magnetic fluid hyperthermia (MFH) combined with external radiation in an orthotopic rat model of prostate cancer

    International Nuclear Information System (INIS)

    Full text: Magnetic fluid hyperthermia (MFH) is a new concept of cancer treatment based on AC magnetic field-induced excitation of biocompatible superparamagnetic nanoparticles. Preliminary studies of MFH using nanoscaled aminosilan-coated magnetites have demonstrated the feasibility of minimally invasive MFH in the Dunning tumor model. Here we evaluated the effect of two sequential MFH treatments, combined with external radiation, in an orthotopic Dunning R3327-MatLyLu prostate cancer model. MFH led to a significant growth inhibition in this orthotopic model of the aggressive MatLyLu tumor variant. Furthermore, combined MFH and radiation with 20 Gy equally effective in inhibiting tumor growth as radiation with 60 Gy, suggesting a significant synergistic effect. Intratumoral deposition of magnetic fluids was found to be stable, allowing for serial MFH treatments without repeated injection. The optimal treatment schedules of this combination regarding temperatures, sequencing and fractionation need to be defined in further experimental studies. (author)

  10. 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.

  11. 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

  12. 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.

  13. 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.

  14. 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.

  15. 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

  16. Expression level of augmenter of liver regeneration in patients with hepatic failure and hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Hai-YingYu; Dai-RongXiang; Hai-JunHuang; JunLi; Ji-FangSheng

    2010-01-01

    BACKGROUND: Augmenter of liver regeneration (ALR) is an important polypeptide in the process of liver regeneration. This study aimed to determine the expression level of ALR in different liver diseases and its significance. METHODS: We prepared murine polyclonal antibody against ALR protein from Balb/C mice and purified the IgG fraction, which specifically combined to ALR protein as shown by Western blotting. Serum ALR levels in patients with hepatocellular carcinoma (HCC), hepatic failure (HF), chronic hepatitis B, and healthy persons were compared by ELISA. ALR mRNA expression levels in liver tissues in some of these patients were also compared by real-time RT-PCR. Immunohistochemical analysis was carried out on HF and HCC liver tissues. RESULTS: Different serum ALR levels foreshowed completely different prognoses in 18 HF patients. Higher ALR levels were noted in 6 improved patients (1613.5±369.6 pmol/ml) than in 12 deteriorating patients (462.3±235.8 pmol/ml). Similar levels were found in 20 HCC patients (917.9±332. 7 pmol/ml), 24 chronic hepatitis B patients (969.2±332.5 pmol/ml) and 10 healthy persons (806.9±240.8 pmol/ml). ALR mRNA levels in HCC liver tissues [10E6.24 (1.74×106) copies/μl] were much higher than in those of HF patients receiving orthotopic liver transplantation [10E3.45 (2.82×103)copies/μl] or in healthy liver tissues [10E4.31 (2.04×104) copies/μl]. In immunohistochemical analysis, positive immunostaining in HCC liver tissue was more intense than that in HF liver tissue. CONCLUSION: Serum ALR level is helpful in estimating the survival time of patients with HF, and ALR may play an important role in hepatocarcinogenesis.

  17. 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.

  18. Spur cell anaemia and hepatic iron stores in patients with alcoholic liver disease undergoing orthotopic liver transplantation

    OpenAIRE

    Pascoe, A; Kerlin, P; Steadman, C; Clouston, A; Jones, D.; Powell, L; Jazwinska, E; Lynch, S; Strong, R

    1999-01-01

    BACKGROUND—Following orthotopic liver transplantation (OLT) histological examination of explant livers from patients with alcoholic liver disease (ALD) sometimes shows extensive iron deposits in a distribution suggestive of homozygous haemochromatosis.
AIMS—To use haemochromatosis gene (HFE) assays to distinguish between ALD with notable siderosis and hereditary haemochromatosis. To evaluate the possible influence of spur cell haemolytic anaemia on hepatic iron loading.
PATIENTS—Thirty seven ...

  19. Treatment of a Giant Haemangioma of the Liver With Kasabach-Merritt Syndrome by Orthotopic Liver Transplant

    OpenAIRE

    J-H. Longeville; Hall, P. De La M.; Dolan, P.; A. W. Holt; Lillie, P. E.; Williams, J. A. R.; Padbury, R. T. A.

    1997-01-01

    We describe a case of giant cavernous haemangioma of the liver with disseminated intravascular coagulopathy (Kasabach-Merritt syndrome) which was cured by orthotopic liver transplant. A 47 year old man presented with bleeding and tender massive hepatomegaly after tooth extraction. Investigations showed disseminated intravascular coagulopathy and a giant hepatic haemangioma involving both lobes of the liver. Initial treatment failed to resolve the coagulopathy and liver resection was attempted...

  20. Targeting Hypoxia-inducible Factor 1α in a New Orthotopic Model of Glioblastoma Recapitulating the Hypoxic Tumor Microenvironment

    OpenAIRE

    Nigim, Fares; Cavanaugh, Jill; Patel, Anoop P.; Curry, William T.; Esaki, Shin-ichi; Kasper, Ekkehard M.; Chi, Andrew S.; Louis, David N.; Martuza, Robert L.; Rabkin, Samuel D.; Wakimoto, Hiroaki

    2015-01-01

    Tissue hypoxia and necrosis represent pathophysiological and histological hallmarks of glioblastoma (GBM). Although hypoxia inducible factor 1α (HIF-1α) plays crucial roles in the malignant phenotypes of GBM, developing HIF-1α-targeted agents has been hampered by the lack of a suitable preclinical model that recapitulates the complex biology of clinical GBM. We present a new GBM model, MGG123, which was established from a recurrent human GBM. Orthotopic xenografting of stem-...

  1. Scedosporium apiosermum infection of the “Native” valve: Fungal endocarditis in an orthotopic heart transplant recipient

    OpenAIRE

    Clement, Meredith E.; Eileen K. Maziarz; Schroder, Jacob N.; Patel, Chetan B.; Perfect, John R.

    2015-01-01

    Scedosporium apiospermum is an increasingly appreciated pathogen in immunosuppressed patients. We present a case of S. apiospermum endocarditis in a 70-year-old male who had undergone orthotopic heart transplant. Echocardiogram demonstrated a 1.4 cm tricuspid valve vegetation. He underwent valve replacement, complicated by fatal massive post-operative haemorrhage. Valve cultures grew S. apiospermum. To our knowledge, our case is the first reported instance of endocarditis caused by S. apiospe...

  2. 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.

  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. Primary hepatocellular carcinoma in extrahepatic bile duct

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Seok Tae; Ham, Soo Youn; Park, Cheol Min; Kim, Jung Hyuk; Cha, In Ho; Chung, Kyoo Byung; Suh, Woon Hyuck; Lee, Chang Hong [College of Medicine, Korea University, Seoul (Korea, Republic of)

    1991-03-15

    Obstructive jaundice due to hepatocellular carcinoma in an extrahepatic bile duct, without a mass lesion in the liver parenchyma, is extremely rare. We experienced two cases of primary hepatocellular carcinoma arising from an extrahepatic bile duct: one in a 53-year-old man whose {alpha} -fetoprotein value was 800 ng/ml, and another in a 39-year-old woman, in whom the mass lesion was found to be attached to an extrahepatic bile duct. These tumors had a well-marginated sausage-like shape on CT and US, and the contrast media passed freely along their margins on both PTC and ERCP. Recurrences of these tumors were observed in the extrahepatic bile duct 6 and 2 months after surgery, respectively.

  5. Welcome to Journal of Hepatocellular Carcinoma

    OpenAIRE

    Kaseb AO

    2015-01-01

    Ahmed O Kaseb Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA Hepatocellular carcinoma (HCC) develops as a consequence of underlying chronic liver disease, most commonly cirrhosis. Therefore, HCC management draws on the expertise of a wide range of medical specialists. Currently, novel therapeutic modalities for HCC are investigated within the framework of a multidisciplinary approach. Therefore, there is a critical nee...

  6. Prevention of hepatocellular carcinoma by immunization*

    OpenAIRE

    1983-01-01

    The evidence for an association between the carrier state of hepatitis B virus infection and hepatocellular carcinoma (liver cell cancer) is now sufficiently strong to justify the use of a vaccine against this infection as a means of preventing this cancer. Effective vaccines are available and have been tested in feasibility studies, and their use in field trials to test their effectiveness against the long-term risk of developing this cancer is now possible. At the present time, only limited...

  7. Imaging appearance of treated hepatocellular carcinoma.

    OpenAIRE

    Agnello, F; SALVAGGIO, G; G. Cabibbo(); Maida, M; Lagalla, R.; Midiri, M; Brancatelli, G

    2013-01-01

    Surgical resection and imaging guided treatments play a crucial role in the management of hepatocellular carcinoma (HCC). Although the primary end point of treatment of HCC is survival, radiological response could be a surrogate end point of survival, and has a key role in HCC decision-making process. However, radiological assessment of HCC treatment efficacy is often controversial. There are few doubts on the evaluation of surgical resection; in fact, all known tumor sites should be removed....

  8. Targeting cancer stem cells in hepatocellular carcinoma

    OpenAIRE

    MISHRA, LOPA

    2014-01-01

    Aiwu Ruth He,1 Daniel C Smith,1 Lopa Mishra2 1Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, 2Department of Gastroenterology, Hepatology, and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX, USA Abstract: The poor outcome of patients with hepatocellular carcinoma (HCC) is attributed to recurrence of the disease after curative treatment and the resistance of HCC cells to conventional chemotherapy, which may be explained partly by the fun...

  9. Welcome to Journal of Hepatocellular Carcinoma

    OpenAIRE

    Kaseb AO

    2015-01-01

    Ahmed O Kaseb Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA Hepatocellular carcinoma (HCC) develops as a consequence of underlying chronic liver disease, most commonly cirrhosis. Therefore, HCC management draws on the expertise of a wide range of medical specialists. Currently, novel therapeutic modalities for HCC are investigated within the framework of a multidisciplinary approach. Therefore, there is a critical...

  10. 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.

  11. The application of biliary catheter folding technique in the treatment of hilar nonanastomotic biliary strictures after orthotopic liver transplantation

    International Nuclear Information System (INIS)

    Objective: To introduce a newly-designed percutaneous single catheter folding technique, by which bilateral biliary drainage and stenting can be completed through single access, and to assess the effectiveness and safety of this technique in treating hilar nonanastomotic strictures occurred after orthotopic liver transplantation. Methods: A total of 10 patients with nonanastomotic strictures, who were encountered during the period from July 2000 to July 2010 in authors' hospital, were enrolled in this study. Balloon dilatation was used for the biliary tract stenosis. After the placement of biliary drainage tube, the catheter was folded into 'Y' shape within the biliary duct at hepatic portal region, and triaxial supporting drainage, i.e. the left hepatic duct, the right hepatic duct and the common hepatic duct, was established. The technical success rate, the clinical efficacy, the complications and the recurrence were documented and analyzed. Results: Technical success rate was 100% (10/10). In 9 patients, the clinical symptoms were obviously relieved, the biochemical indexes were gradually restored to normal and the imaging findings were markedly improved. During the follow-up lasting 26 months (median), no recurrence was seen. Minor complications occurred in two cases. One patient died after he received second orthotopic liver transplantation because of failure to respond to initial treatment. Conclusion: Percutaneous transhepatic biliary catheter folding technique is technically feasible. The results of this study indicate that this technique carries satisfactory success rate and is very effective and safe for the treatment of hilar nonanastomotic strictures occurred after orthotopic liver transplantation. (authors)

  12. Hemodynamic and metabolic characterization of orthotopic rat prostate carcinomas using dynamic MRI and proton magnetic resonance spectroscopy

    International Nuclear Information System (INIS)

    The aim of this study was the noninvasive characterization of prostate carcinoma orthotopically implanted in rats using Gd-DTPA-assisted dynamic MRI (dMRI) and proton magnetic resonance spectroscopy (1H-MRS). After surgical exposure of the prostate, Dunning R3327 orthotopic prostate carcinoma was induced by injecting cells of the MAT-LyLu subline. Six rats were examined 5 and 14 days after tumor induction with dMRI and 1H-MRS at 1.5 T. Six tumor-free rats served as controls. Using an open two-compartment model, the parameters A (amplitude) and kep (exchange rate constants) were calculated from the signal time curves of the dMRI. The relative signal intensities (Cho/Cr) of the resonances of choline (Cho) and the creatine-phosphocreatine complex (Cr) were computed from the MR spectra. Already after 5 days, the tumors in the prostate could be clearly identified based on the decrease in signal intensity to T2w and increase of A and kep. High Cho/Cr levels and resonances of two lipid fractions (Lip1 at 0.8-1.5 ppm and Lip2 at 2.0-2.2 ppm) were observed by MRS in the highly necrotic tumors. The orthotopic rat prostate carcinoma model resembles human prostate carcinoma in regard to MR morphology, dMRI, and 1H-MRS. The noninvasive characterization of perfusion and metabolism makes a comparative examination of different treatment modalities possible. (orig.)

  13. 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

  14. Hepatocellular carcinoma: Will novel targeted drugs really impact the next future?

    Science.gov (United States)

    Montella, Liliana; Palmieri, Giovannella; Addeo, Raffaele; Del Prete, Salvatore

    2016-01-01

    Cancer treatment has been revolutionized by the advent of new molecular targeted and immunotherapeutic agents. Identification of the role of tumor angiogenesis changed the understanding of many tumors. After the unsuccessful results with chemotherapy, sorafenib, by interfering with angiogenic pathways, has become pivotal in the treatment of hepatocellular carcinoma. Sorafenib is the only systemic treatment to show a modest but statistically significant survival benefit. All novel drugs and strategies for treatment of advanced hepatocellular carcinoma must be compared with the results obtained with sorafenib, but no new drug or drug combination has yet achieved better results. In our opinion, the efforts to impact the natural history of the disease will be directed not only to drug development but also to understanding the underlying liver disease (usually hepatitis B virus- or hepatitis C virus-related) and to interrupting the progression of cirrhosis. It will be important to define the role and amount of mutations in the complex pathogenesis of hepatocellular carcinoma and to better integrate locoregional and systemic therapies. It will be important also to optimize the therapeutic strategies with existing chemotherapeutic drugs and new targeted agents.

  15. 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 

  16. Multidisciplinary perspective of hepatocellular carcinoma: APacific Northwest experience

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Hepatocellular carcinoma (HCC) is the most rapidlyincreasing type of cancer in the United States. HCCis a highly malignant cancer, accounting for at least14000 deaths in the United States annually, and it ranksthird as a cause of cancer mortality in men. One majordifficulty is that most patients with HCC are diagnosedwhen the disease is already at an advanced stage, andthe cancer cannot be surgically removed. Furthermore,because almost all patients have cirrhosis, neitherchemotherapy nor major resections are well tolerated.Clearly there is need of a multidisciplinary approach forthe management of HCC. For example, there is a needfor better understanding of the fundamental etiologicmechanisms that are involved in hepatocarcinogenesis,which could lead to the development of successfulpreventive and therapeutic modalities. It is also essentialto define the cellular and molecular bases for malignanttransformation of hepatocytes. Such knowledge would(1) greatly facilitate the identification of patients atrisk; (2) prompt efforts to decrease risk factors; and(3) improve surveillance and early diagnosis throughdiagnostic imaging modalities. Possible benefits extendalso to the clinical management of this disease. Becausethere are many factors involved in pathogenesis of HCC,this paper reviews a multidisciplinary perspective ofrecent advances in basic and clinical understanding ofHCC that include: molecular hepatocarcinogenesis, noninvasivediagnostics modalities, diagnostic pathology,surgical modality, transplantation, local therapy andoncological/target therapeutics.

  17. Management strategies for hepatocellular carcinoma: old certainties and new realities.

    Science.gov (United States)

    Mazzoccoli, Gianluigi; Tarquini, Roberto; Valoriani, Alice; Oben, Jude; Vinciguerra, Manlio; Marra, Fabio

    2016-08-01

    Hepatocellular carcinoma (HCC) is a highly prevalent disease ranking among the ten most common cancers worldwide with increasing trend of incidence in most developed countries. The great healthcare costs and economic burden of HCC dictate proper preventive interventions as well as surveillance and screening programs to decrease disease incidence and allow early diagnosis. HCC treatment outcomes are affected by several variables, including liver function, patient's performance status, and tumor stage. In line with the Barcelona Clinic Liver Cancer (BCLC) staging curative treatments, such as surgery or radio-frequency ablation, are indicated in early-stage HCC (BCLC-A), and the noncurative treatments are indicated in intermediate and advanced stages of HCC (BCLC-B, C). Transarterial chemoembolization (TACE) represents the treatment of choice for intermediate-stage HCC with Child-Pugh A cirrhosis, and the long-term survival after liver transplantation is inferior to that of early-stage HCCs. In advanced-stage HCC or when complete necrosis is not achieved or early recurrence after TACE develops, individualized treatments such as systemic treatment or combined radiation therapy are indicated. The increasing knowledge of the genomic landscape of HCC and the development of molecular-targeted therapies is heading toward expanding the armamentarium for HCC management. PMID:26077653

  18. Current role of ultrasound for the management of hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Hitoshi Maruyama; Masaharu Yoshikawa; Osamu Yokosuka

    2008-01-01

    Hepatocellular carcinoma (HCC) has a decisive influence on the prognosis of cirrhotic patients. Although a-fetoprotein (AFP) is a known and specific tumor maker for HCC, it is not suitable for the screening and surveillance of HCC because of its poor predictive value and low sensitivity. The use of imaging modalities is essential for the screening, diagnosis and treatment of HCC. Ultrasound (US) plays a major role among them, because it provides real-time and non-invasive observation by a simple and easy technique. In addition, US-guided needle puncture methods are frequently required for the diagnosis and/or treatment process of HCC. The development of digital technology has led to the detection of blood flow by color Doppler US, and the sensitivity for detecting tumor vascularity has shown remarkable improvement with the introduction of microbubble contrast agents. Moreover, near realtime 3-dimensional US images are now available. As for the treatment of HCC, high intensity focused ultrasound (HIFU) was developed as a novel technology that provides transcutaneous ablation effect without needle puncture. These advancements in the US field have led to rapid progress in HCC management, and continuing advances are expected. This article reviews the current application of US for HCC in clinical practice.

  19. Total vascular exclusion technique for resection of hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Zhen-Yu Yin; Xiao-Ming Wang; Ren-Xiang Yu; Bai-Meng Zhang; Ke-Ke Yu; Ning Li; Jie-Shou Li

    2003-01-01

    AIM: To improve the low resection rate, poor prognosis and to control the massive hemorrhage during operation,total vascular exclusion (TVE) technique was used in hepatectomies of advanced and complicated hepatocellular carcinomas (HCCs).METHODS: Five hundred and thirty patients with HCCs were admitted in our hospital. They were divided into TVE technique group (group A:n=78), Pringle maneuver method group (group B:n=176) and unresectable group (group C:n=276). The clinical, operative, pathological parameters and outcome of the patients were statistically evaluated.RESULTS: Group A had a significantly higher resection rate than group B (accounting for 47.92% and 33.21%respectively). There was no significant difference in blood loss, blood transfusion and perioperative mortality betweengroups A and B. Both groups had the similar median disease free survival time (14.6 VS 16.3 months) and 1 year survival rate (92.9% VS95.5%). The TVE group had a medial survival time of 40.5 months and its 5-year survival rate was 34.6%.CONCLUSION: As compared with Pringle maneuver method, the total vascular exclusion is a safe and effective technique to increase the total resection rate of advanced and complicated HCCs.

  20. Update in management of hepatocellular carcinoma in Eastern population.

    Science.gov (United States)

    Chu, Kevin Ka Wan; Cheung, Tan To

    2015-06-18

    Hepatocellular carcinoma (HCC) is one of the commonest malignant tumours in the East. Although the management of HCC in the West is mainly based on the Barcelona Clinic for Liver Cancer staging, it is considered too conservative by Asian countries where the number of HCC patients is huge. Scientific and clinical 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 must take into account the presence and stage of chronic liver disease. The major treatment modalities of HCC include: (1) surgical resection; (2) liver transplantation; (3) local ablation therapy; (4) transarterial locoregional treatment; and (5) systemic treatment. Among these, resection, liver transplantation and ablation therapy for small HCC are considered as curative treatment. Portal vein embolisation and the associating liver partition with portal vein ligation for staged hepatectomy may reduce dropout in patients with marginally resectable disease but the midterm and long-term results are still to be confirmed. Patient selection for the best treatment modality is the key to success of treatment of HCC. The purpose of current review is to provide a description of the current advances in diagnosis, staging, pre-operative liver function assessment and treatment options for patients with HCC in the east. PMID:26085915

  1. 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.

  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. 射频消融术联合DC-CIK治疗中晚期肝细胞癌的疗效及其对患者生命质量的影响%Clinical efficacy of radiofrequency ablation combined with DC-CIK and its effect on quality of life in patients with advanced hepatocellular caicinoma

    Institute of Scientific and Technical Information of China (English)

    刘红梅; 史丽丽; 李金瑞; 钟鑫平

    2015-01-01

    目的 观察超声引导下射频消融术联合树突状细胞-细胞因子诱导的杀伤细胞(DC-CIK)治疗中晚期肝细胞癌患者的临床疗效,并探讨其对患者生命质量的影响.方法 选取中国医科大学普通外科2011年1月至2014年1月收治的156例诊断为中晚期肝细胞癌的患者,按照入选先后顺序随机分为观察组82例和对照组74例.两组患者均静脉输注DC-CIK免疫细胞治疗,观察组在细胞治疗的基础上行超声引导下经皮腹腔穿刺射频消融术,连续治疗6周,治疗前后用"肿瘤生命质量核心问卷(QLQ-C30)"进行评估并比较两组患者的生命质量,观察并记录治疗过程中的不良反应并评估两组患者近期及远期临床疗效.结果 治疗后两组患者的QLQ-C30问卷中整体功能、特异性症状模块各个指标及整体生命质量评分均明显优于治疗前,且治疗后观察组上述指标均优于对照组,差异均有统计学意义(P0.05);观察组术后出现腹痛、恶心伴呕吐、肝周血肿;治疗后观察组近期临床疗效与对照组比较差异无统计学意义(P>0.05),但远期临床疗效优于对照组,且生存期长于对照组,差异均有统计学意义(P0.05), and the observation group showed abdominal pain, nausea and vomiting, peripheral hepatic hematoma af-ter operation. After treatment, the two groups showed no statistically significant differences in short-term clinical effi-cacy (P>0.05), but the observation group was found to had significantly better long-term clinical efficacy and longer median survival time (P<0.05). Conclusion Radiofrequency ablation combined with DC-CIK can raise the long-term clinical efficiency and improve the quality of life of patients with advanced hepatocellular caicinoma.

  4. 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

  5. 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

  6. 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.

  7. Prolonged Delirium With Catatonia Following Orthotopic Liver Transplant Responsive to Memantine.

    Science.gov (United States)

    Brown, Gregory D; Muzyk, Andrew J; Preud'homme, Xavier A

    2016-03-01

    A 59-year-old man with nonalcoholic steatohepatitis cirrhosis underwent an orthotopic liver transplant and experienced a complicated postoperative course, including a prolonged delirium. After discharge to rehabilitation, he had 2 subsequent admissions for delirium. On the first readmission, the transplant team started the patient on risperidone and resumed treatment with sertraline. On his second readmission, neurology and psychiatry were consulted. On evaluation, the patient demonstrated signs of catatonia. On the basis of recommendations from psychiatry, the risperidone and sertraline were stopped, and the patient was started on mirtazapine. He failed to demonstrate improvement within the next 48 hours. Extensive work-up demonstrated a multifactorial etiology for his delirium, including calcineurin-related neuropsychiatric toxicity from tacrolimus leading to possible posterior reversible encephalopathy syndrome. However, after the initiation of memantine on hospital day 3-before the cessation of tacrolimus-the patient demonstrated marked improvement in mental status and motor symptoms. His magnetic resonance imaging, in addition to findings that raised concerns about posterior reversible encephalopathy syndrome, had demonstrated bilateral basal ganglia abnormalities on T1 imaging of uncertain origin. It is postulated that these findings served as predisposing factors for the patient's catatonic symptoms. Although it has been described in case reports following liver transplant, catatonia remains an underrecognized neuropsychiatric complication following liver transplant. This case demonstrates the effectiveness of memantine, an N-methyl-D-aspartic acid antagonist that decreases glutamine excitotoxicity, as a potential treatment for catatonia in postliver transplant patients. PMID:27138082

  8. Serial observations on an orthotopic gastric cancer model constructed using improved implantation technique

    Institute of Scientific and Technical Information of China (English)

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

    2011-01-01

    AIM: To establish a gastric cancer nude-mouse model with improved orthotopic implantation and investigate its biological characteristics at different time points. METHODS: Human gastric cancer SGC-7901 cell suspensions were injected subcutaneously into a nude mouse to develop solid tumors, and the tumor tissue pieces were implanted under the serous coat. The nude mice were then euthanized in group every two weeks to observe the primary tumor growth and metastases. RESULTS: Within 2-4 wk, there were no obvious changes about the primary tumor in stomach. At the sixth week, the primary tumor began to grow fast, resulting in incrassation of the gastric wall and stenosis of the gastric cavity, and metastases into the liver and lymph nodes were detected. The tumor, which compressed the adjacent organs, gradually became bigger and bigger followed by stenosis or vanishment of the gastric cavity from 8 to 12 wk. There were massive metastases, and the rate of metastasis was 58% in lymph nodes, 78% in liver, 39% in kidney, and 81% in peritoneum or septum. CONCLUSION: A gastric cancer model is established, which can simulate the clinical tumor behavior and provide experimental carrier for clinical trials of gastric cancer treatment.

  9. Transcatheter Splenic Artery Occlusion for Treatment of Splenic Artery Steal Syndrome After Orthotopic Liver Transplantation

    International Nuclear Information System (INIS)

    Purpose: To review some aspects of the problem of splenic artery steal syndrome as cause of ischemia in transplanted livers and treatment by selective splenic artery occlusion. Materials and Methods: Eleven liver transplant patients from a group of 350 patients, nine men and two women,ranging in age from 40 years to 61 years (mean 52 years), presented with biochemical evidences of liver ischemia and failure, ranging from one to 60 days following orthotopic liver transplantation. Diagnosis of splenic artery steal syndrome was suspected by elevated enzymes, Doppler ultrasound and confirmed by celiac angiogram. Patients with confirmed hepatic artery thrombosis before angiography were excluded from the study. Embolization with Gianturco coils was performed. Results: All patients were treated by splenic artery embolization with Gianturco coils. The 11 patients improved clinically within 24 hours of the procedure with significant change in the biochemical and clinical parameters. Followup ranged from one month to two years. One of the 11 patient initially improved, but developed hepatic artery thrombosis within 24 hours of the embolic treatment,requiring surgical repair. Conclusion: Splenicartery steal syndrome following liver transplantation surgery can be diagnosed by celiac angiography, and effectively treated by splenic artery embolization with coils. Embolization is one of the treatments available, it is minimally invasive, and leads to immediate clinical improvement. Hepatic artery thrombosis is a possible complication of the procedure

  10. 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. PMID:20635385

  11. Use of multiphoton microscopy to diagnose liver cancer and lung metastasis in an orthotopic rat model.

    Science.gov (United States)

    Yan, Jun; Zhuo, Shuangmu; Chen, Gang; Tan, Changjun; Zhu, Weifeng; Lu, Jianping; Fan, Jia; Chen, Jianxin; Zhou, Jian

    2012-01-01

    Liver or lung biopsy for suspicious lesions has several disadvantages such as bleeding, bile leak or pneumothorax, needle track seeding, and time-consuming histopathological procedure. The ability to directly observe cellular and subcellular details and then perform "optical biopsy" is a major goal in the development of new interventional techniques. Multiphoton microscopy (MPM) enables real-time noninvasive visualization of tissue architecture and cell morphology in live tissue. We performed a study to evaluate whether MPMcan make real-time optical diagnosis for liver cancer and lung metastasis using an orthotopic rat model with Morris hepatoma. We found that real-time high-resolution MPMimaging could clearly show tissue architecture and cell morphology. In the normal liver tissue, MPMimaging clearly revealed the blood-filled sinusoids and cords of hepatocytes. In the cancerous tissue, MPMimaging clearly illustrated that cancer cells displayed marked cellular and nuclear pleomorphism. MPMimages were comparable to golden standard hematoxylin-eosin staining images. Moreover, MPMimaging had deep penetration with the capability of optical sectioning. In short, MPMcan make real-time optical diagnosis for liver cancer and lung metastasis. This study provides the groundwork for further using multiphoton endoscopy to perform real-time noninvasive "optical biopsy" for liver cancer and lung metastasis in the near future. PMID:22331704

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. In-hospital cerebrovascular complications following orthotopic liver transplantation: A retrospective study

    Directory of Open Access Journals (Sweden)

    Liang Zhijian

    2008-12-01

    Full Text Available Abstract Background Cerebrovascular complications are severe events following orthotopic liver transplantation (OLT. This study aimed to observe the clinical and neuroimaging features and possible risk factors of in-hospital cerebrovascular complications in the patients who underwent OLT. Patients and methods We retrospectively reviewed 337 consecutive patients who underwent 358 OLTs. Cerebrovascular complications were determined by clinical and neuroimaging manifestations, and the possible risk factors were analyzed in the patients with intracranial hemorrhage. Results Ten of 337 (3.0% patients developed in-hospital cerebrovascular complications (8 cases experienced intracranial hemorrhage and 2 cases had cerebral infarction, and 6 of them died. The clinical presentations were similar to common stroke, but with rapid deterioration at early stage. The hematomas on brain CT scan were massive, irregular, multifocal and diffuse, and most of them were located at brain lobes and might enlarge or rebleed. Infarcts presented lacunar and multifocal lesions in basal gangliar but with possible hemorrhagic transformation. The patients with intracranial hemorrhage had older age and a more frequency of systemic infection than non-intracranial hemorrhage patients. (P = 0.011 and 0.029, respectively. Conclusion Posttransplant cerebrovascular complications have severe impact on outcome of the patients who received OLT. Older age and systemic infection may be the possible risk factors of in-hospital intracranial hemorrhage following OLT.

  17. 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.

  18. Near-infrared spectroscopy for evaluation of cerebral autoregulation during orthotopic liver transplantation

    DEFF Research Database (Denmark)

    Nissen, P.; Pacino, H.; Frederiksen, H.J.;

    2009-01-01

    detected, S(c)O(2) varied in parallel with mean arterial pressure (MAP) for 3 patients and, therefore, an autoregulation curve could not be established and yet, there was detected no change in S(c)O(2) to a lowest MAP ranging from 42 to 66 mmHg for 20 patients, while for 8 patients a decrease in S(c)O(2......) was detected at a MAP of 69 (50-90) mmHg; (median and range). As detected by NIRS, the present study confirms that some patients undergoing liver transplantation do not demonstrate cerebral autoregulation but for the majority of the patients, S(c)O(2) was stable over a wide range of MAP suggesting......INTRODUCTION: The present study evaluated whether frontal lobe cerebral oxygenation (S(c)O(2)), as assessed by near-infrared spectroscopy (NIRS), can detect cerebral autoregulation in patients undergoing orthotopic liver transplantation. METHODS: We studied changes in frontal lobe S(c)O(2) assessed...

  19. Postoperative left ventricular apical ballooning: Transient Takotsubo cardiomyopathy following orthotopic liver transplantation

    Science.gov (United States)

    Bedanova, Helena; Orban, Marek; Nemec, Petr

    2013-01-01

    Patient: Female, 51 Final Diagnosis: Takotsubo cardiomyopathy Symptoms: — Medication: — Clinical Procedure: — Specialty: Cardiology • Transplantology Objective: Rare disease Background: Left ventricular apical ballooning syndrome (LVAB), also known as Takotsubo cardiomyopathy, is a cardiac syndrome characterized by transient left ventricular dysfunction in the absence of obstructive atherosclerotic coronary artery disease. An episode of emotional stress, typically in female patients, is believed to precede and trigger the development of this syndrome. Case Report: We report a case of Takotsubo cardiomyopathy that developed after orthotopic liver transplantation in a 51-year-old woman. On D2 (day 2) the patient had severe hemodynamic compromise. Echocardiography showed systolic dysfunction of the left ventricle (LV), with ejection fraction (EF) of 20% and anteroapical akinesis and ballooning of the apical 2/3 of the LV. Troponin T was elevated but other markers of myocardial necrosis were negative, as was coronary angiography. From D7 onward, there was an improvement in the hemodynamics in conjunction with a gradual increase of LV EF. The patient was dismissed from the hospital on D30 with signs of normal cardiac function and LV motion and EF of 50%. Liver function was also excellent. Conclusions: Every major operation, including liver transplantation, is associated with emotional stress for the patient. Therefore, it is necessary to consider Takotsubo cardiomyopathy in the differential diagnosis of heart failure developing early after LT, and clinicians should subsequently use adequate diagnostic and therapeutic measures. PMID:24298303

  20. Graft complications following orthotopic liver transplantation: Role of non-invasive cross-sectional imaging techniques.

    Science.gov (United States)

    Boraschi, Piero; Della Pina, Maria Clotilde; Donati, Francescamaria

    2016-07-01

    Orthotopic liver transplantation is the treatment of choice in adult patients with endstage liver disease. Survival of both graft and patient has progressively improved over time due to improvements in surgical and medical treatment. However, post-transplant complications still have a significant impact on morbidity and mortality associated with transplant surgery. The most common adverse events of the graft include vascular (arterial and venous stenosis and thrombosis), biliary (leakage, strictures, stones) and parenchymal complications (hepatitis virus C infection, HCC recurrence, liver abscesses). The diagnosis of these adverse events is often challenging because of the low specificity of clinical and biologic findings. Different diagnostic algorithms have been proposed for the detection of graft complications and, in this setting, radiological evaluation plays a key role in differential diagnosis of graft complications and the exclusion of other adverse events. Ultrasound examination is established the first-line method of identifying adverse events in liver transplant recipients but a normal or a technically unsatisfactory study cannot exclude the presence of biliary, vascular and/or parenchymal complications. In these circumstances, before planning any treatment, multi-detector CT and/or MR imaging and MR cholangiography should be performed for the evaluation of vascular structures, biliary system, liver parenchyma and fluid collections. The aim of this review is to illustrate the role and state-of-the-art of non-invasive cross-sectional imaging techniques in the diagnosis and management of complications which primarily affect the graft in patients after liver transplantation. PMID:27235874

  1. 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.

  2. 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.

  3. Role of McMaster model of family therapy in improving family function of patients with advanced hepatocellular carcinoma%McMaster模式家庭治疗在改善中晚期肝细胞癌患者家庭功能中应用的效果评价

    Institute of Scientific and Technical Information of China (English)

    仲冬梅; 毛鑫群; 赵疃; 丁俊俊

    2015-01-01

    Objective We aimed to investigate the role of McMaster model of family therapy in improving family function of patients with advanced hepatocellular carcinoma (HCC).Methods Patients who had advanced HCC and received transarterial embolization (TAE) or transarterial chemoembolization (TACE) from Department of Hepatobiliary Ⅰ,Eastern Hepatobiliary Surgery Hospital between October 1,2012 and June 25,2013 were randomly divided into two groups:the experimental group (51 patients) and the control group (49 patients).The control group received routine family support education.The experimental group not only executed routine family support education,but also was given McMaster model of family therapy according to evaluation results of family assessment device (FAD) on the second and third day of hospitalization.The status of family function of all patients were assessed by FAD on the fnrst day of hospitalization and fourth week after therapy.We compared the status of family function between the two groups.Results In age,gender,educational level,place of residence,occupation,family economic status,medical payment,liver or kidney function,HBV infection,cirrhosis and tumor burden,no statistical differences were found between the experimental group and the control group patients before TAE or TACE.Two groups were dysfunction in communication,roles,affective responsiveness,affective involvement,behavior control,and general function in addition to problem solving before TAE or TACE.No statistical differences were found between two groups.After the therapy,compared with the control group,those patients in the experimental group had a lower level scoring in communication,roles,affective responsiveness,affective involvement,behavior control,and general function in addition to problem solving on the fourth week after the therapy,t value was-2.544,-3.767,-3.904,-2.848,-4.950 and-4.953,the difference had statistical significance.Conclusions McMaster model of family therapy may help

  4. 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....

  5. Hypertrophic osteopathy associated with hepatocellular carcinoma in a dog

    OpenAIRE

    Randall, Victoria D.; Souza, Carlos; Vanderhart, Daniel; Boston, Sarah

    2015-01-01

    A 9-year-old spayed female dog diagnosed with hepatocellular carcinoma and hypertrophic osteopathy was negative for additional lesions on computed tomography of the thorax and abdomen. Resection of the affected liver lobe resulted in resolution of clinical signs. This is the first case of hypertrophic osteopathy secondary to hepatocellular carcinoma.

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

    Science.gov (United States)

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

    2015-10-28

    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. PMID:26516427

  7. Chemotherapeutic agents for the treatment of hepatocellular carcinoma: efficacy and mode of action

    Directory of Open Access Journals (Sweden)

    Saad Shaaban

    2014-05-01

    Full Text Available Hepatocellular carcinoma (HCC is a dreaded malignancy that every year causes half a million deaths worldwide. Being an aggressive cancer, its incidence exceeds 700,000 new cases per year worldwide with a median survival of 6-8 months. Despite advances in prognosis and early detection, effective HCC chemoprevention or treatment strategies are still lacking, therefore its dismal survival rate remains largely unchanged. This review will characterize currently available chemotherapeutic drugs used in the treatment of HCC. The respective mode(s of action, side effects and recommendations will be also described for each drug.

  8. Quality of Life in Hepatocellular Carcinoma Patients Treated with Transarterial Chemoembolization

    Directory of Open Access Journals (Sweden)

    Saleem Ahmed

    2016-01-01

    Full Text Available Hepatocellular carcinoma (HCC is one of the most commonly diagnosed cancers worldwide. Majority of patients with HCC are diagnosed in the advanced stages of disease and hence they are only suitable for palliative therapy. TACE (transarterial chemoembolization is the most commonly used treatment for unresectable HCC. It is however unclear if TACE improves the quality of life (QoL in patients with HCC. The aim of this review is to evaluate the impact of TACE on QoL of HCC patients.

  9. MK615 decreases RAGE expression and inhibits TAGE-induced proliferation in hepatocellular carcinoma cells

    Institute of Scientific and Technical Information of China (English)

    Yuhki; Sakuraoka; Tokihiko; Sawada; Toshie; Okada; Takayuki; Shiraki; Yoshikazu; Miura; Katsuya; Hiraishi; Tatsushi; Ohsawa; Masakazu; Adachi; Jun-ichi; Takino; Masayoshi; Takeuchi; Keiichi; Kubota

    2010-01-01

    AIM:To investigate the proliferative effect of advanced glycation end-products(AGEs) and the role of their cellular receptor(RAGE) on hepatocellular carcinoma(HCC) cells,and the inhibitory effects of MK615,an extract from Japanese apricot,against AGEs were also evaluated.METHODS:Two HCC cell lines,HuH7 and HepG2,were used.Expression of RAGE was investigated by poly-merase chain reaction,Western blotting,and flow cytemetry(FACS).The effect of MK615 on RAGE expression was also evaluated by FACS.The proliferat...

  10. 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.

  11. Development of a Resistance-like Phenotype to Sorafenib by Human Hepatocellular Carcinoma Cells Is Reversible and Can Be Delayed by Metronomic UFT Chemotherapy

    Directory of Open Access Journals (Sweden)

    Terence C. Tang

    2010-11-01

    Full Text Available Acquired resistance to antiangiogenic drugs, such as sorafenib, is a major clinical problem. We studied development of a resistance to sorafenib in new preclinical models of human hepatocellular carcinoma (HCC along with a strategy to delay such resistance—combination with metronomic chemotherapy. Three different xenograft models were studied using human Hep3B HCC cells, which are highly responsive to sorafenib, namely, orthotopic and subcutaneous transplant in severe combined immunodeficient mice, and an orthotopic transplant in nude mice. The complementary DNA for the β-subunit of human choriogonadotropin was transfected into HCC cells, and urine levels of the protein were monitored as a surrogate of tumor burden. Extended daily treatments, sometimes interrupted by a break period of 3 to 7 days to allow recovery from toxicity at sorafenib doses of 30 to 60 mg/kg, were maintained until and after evidence of tumor relapse. Initially responsive tumors seemed to develop a resistance-like phenotype after long-term daily treatment (e.g., >42 days at doses of 30 to 60 mg/kg. Transplantation of cell lines established from progressing tumors into new hosts showed that the resistant phenotype was not propagated. Furthermore, a regimen of daily metronomic uracil + tegafur (UFT, an oral 5-fluorouracil prodrug chemotherapy with a less toxic regimen of sorafenib (15 mg/kg per day significantly delayed the onset of resistance (>91 days. In conclusion, development of a resistance-like phenotype to sorafenib is reversible, and metronomic UFT plus sorafenib may be a promising and well-tolerated treatment for increasing efficacy by delaying emergence of such resistance.

  12. Quantitative detection of common deletion of mitochondrial DNA in hepatocellular carcinoma and hepatocellular nodular hyperplasia

    Institute of Scientific and Technical Information of China (English)

    Jian-Yong Shao; Hong-Yi Gao; Yu-Hong Li; Yu Zhang; You-Yong Lu; Yi-Xin Zeng

    2004-01-01

    AIM: To study the deletion of mitochondiral DNA in hepatocellular carcinoma and hepatocellular nodular hyperplasia and its significance in the development of cancer.METHODS: Deleted mtDNA (CD-mtDNA) and wild type mtDNA (WT-mtDNA) were quantitatively analyzed by using real-time PCR in 27 hepatocellular carcinomas (HCC)and corresponding noncancerous liver tissues and 27hepatocellular nodular hyperplasiae (HNH).RESULTS: A novel CD (4 981 bp) was detected in 85%(23/27) and 83%(22/27) of HCC and HNH tumor tissues,respectively, which were significantly higher than that in paired noncancerous liver tissues (57%, 15/27) (P<0.05).The CD/WT-mtDNA ratio in HCC tumors was 0.00092(median, interquartile range, 0.0001202-0.00105), which was significantly higher than that in paired noncancerous liver tissues (median, 0.000, quartile range, 0-0) (P=0.002,Mann-Whitney Test), and was 25 of times of that in HNH tissues (median, 0.0000374, quartile range, 0-0.0004225)(P=0.002, Mann-Whitney test).CONCLUSION: CD-mtDNA mutation plays an important role in the development and progression of HCC.

  13. 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.

  14. Innovative surgical approaches for hepatocellular carcinoma.

    Science.gov (United States)

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

    2016-05-01

    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 intrao-perative use of three dimensional models and augme-nted reality, as well as the potential application of fluore-scence. PMID:27168871

  15. 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...

  16. 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.

  17. 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.

  18. Pedunculated hepatocellular carcinoma and splenic metastasis

    Institute of Scientific and Technical Information of China (English)

    Mao-Lin Yan; Yao-Dong Wang; Zhi-De Lai; Yi-Feng Tian; Hong-Biao Chen; Fu-Nan Qiu; Song-Qiang Zhou

    2009-01-01

    Only a few cases of pedunculated hepatocellular carcinoma (P-HCC) have been reported in the literature. The common sites of extrahepatic metastases in patients with HCC are the lungs, regional lymph nodes,kidney, bone marrow and adrenals. Metastasis to spleen is mostly via hematogenous metastasis, direct metastasis to spleen was very rare. We report a case of P-HCC presenting as a left upper abdominal lesions which involved the spleen that was actually a P-HCC with splenic metastasis. This case is unique as P-HCC directly involved the spleen which is not via hematogenous metastasis.

  19. Hepatocellular carcinoma: Epidemiology, risk factors and pathogenesis

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Hepatocellular carcinoma (HCC) is the commonest primary malignant cancer of the liver in the world. Given that the burden of chronic liver disease is expected to rise owing to increasing rates of alcoholism, hepatitis B and C prevalence and obesity-related fatty liver disease, it is expected that the incidence of HCC will also increase in the foreseeable future. This article summarizes the international epidemiology, the risk factors and the pathogenesis of HCC, including the roles of viral hepatitis, toxins, such as alcohol and aflatoxin, and insulin resistance.

  20. 临床原位肝移植近展%Recent Advances in Clinical Orthotopic Liver Transplantation

    Institute of Scientific and Technical Information of China (English)

    Xia Suisheng

    1986-01-01

    @@ 自1983年美国国家卫生研究所评议开发会议(Consensus Development Conference of USA National Institutes of Health)正式发布文告(1),承认肝移植是终末期肝脏疾病的一个治疗方法,应予推广以来,肝移植发展加快,例数剧增,全球已达千例,新的中心不断涌现.1984年施行原位肝移植12例以上的中心有12个(北美5个、欧洲6个、我国1个),估计1986年可达20个(2).

  1. 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.

  2. 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.

  3. 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

  4. 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.

  5. 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.

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

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    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.

  7. 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

  8. 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.

  9. 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.

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

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    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.

  11. 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.

  12. 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.

  13. 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.

  14. Involvement of DNA Damage Response Pathways in Hepatocellular Carcinoma

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    Sheau-Fang Yang

    2014-01-01

    Full Text Available Hepatocellular carcinoma (HCC has been known as one of the most lethal human malignancies, due to the difficulty of early detection, chemoresistance, and radioresistance, and is characterized by active angiogenesis and metastasis, which account for rapid recurrence and poor survival. Its development has been closely associated with multiple risk factors, including hepatitis B and C virus infection, alcohol consumption, obesity, and diet contamination. Genetic alterations and genomic instability, probably resulted from unrepaired DNA lesions, are increasingly recognized as a common feature of human HCC. Dysregulation of DNA damage repair and signaling to cell cycle checkpoints, known as the DNA damage response (DDR, is associated with a predisposition to cancer and affects responses to DNA-damaging anticancer therapy. It has been demonstrated that various HCC-associated risk factors are able to promote DNA damages, formation of DNA adducts, and chromosomal aberrations. Hence, alterations in the DDR pathways may accumulate these lesions to trigger hepatocarcinogenesis and also to facilitate advanced HCC progression. This review collects some of the most known information about the link between HCC-associated risk factors and DDR pathways in HCC. Hopefully, the review will remind the researchers and clinicians of further characterizing and validating the roles of these DDR pathways in HCC.

  15. The effect of LOXL2 in hepatocellular carcinoma.

    Science.gov (United States)

    Wu, Linghong; Zhang, Yuan; Zhu, Ying; Cong, Qingwei; Xiang, Yan; Fu, Linlin

    2016-09-01

    Lysyl oxidase-like 2 (LOXL2) is key in the hepatocellular carcinoma (HCC) tumor microenvironment and metastatic niche formation. However, its effect on proliferation and clinical parameters in HCC require further elucidation. The present study aimed to investigate LOXL2 expression in HCC from in vitro and clinical aspects. The present study constructed LOXL2‑small interfering RNA with a lentiviral vector, investigated the effect of LOXL2 on proliferation using HCC cell lines via a series of assays, including reverse transcription‑quantitative polymerase chain reaction, cell counting, colony formation, assessment of cell cycle and apoptosis using flow cytometry, MTT and BrdU. Furthermore, 80 tissue samples from HCC patients at The First Affiliated Hospital of Dalian Medical University (Dalian, China) from 2007 to 2010. Immunohistochemical staining was used to clinically verify LOXL2 expression. The results of the present study demonstrate that LOXL2 silencing decreased cell numbers, proliferation, colony formations and cell growth, induced cell cycle arrest and increased apoptosis. Clinically, expression levels of LOXL2 was markedly increased in matched adjacent non‑tumor tissue (ANT) samples compared with levels in tumor tissue (TT) samples, and this gradually increased with higher histological grade and more advanced TNM classification in the matched ANT and TT samples. LOXL2 was determined to promote proliferation of HCC and demonstrated to be highly expressed in HCC ANT samples compared with TT samples. PMID:27430160

  16. Tissue- and Serum-Associated Biomarkers of Hepatocellular Carcinoma

    Science.gov (United States)

    Chauhan, Ranjit; Lahiri, Nivedita

    2016-01-01

    Hepatocellular carcinoma (HCC), one of the leading causes of cancer deaths in the world, is offering a challenge to human beings, with the current modes of treatment being a palliative approach. Lack of proper curative or preventive treatment methods encouraged extensive research around the world with an aim to detect a vaccine or therapeutic target biomolecule that could lead to development of a drug or vaccine against HCC. Biomarkers or biological disease markers have emerged as a potential tool as drug/vaccine targets, as they can accurately diagnose, predict, and even prevent the diseases. Biomarker expression in tissue, serum, plasma, or urine can detect tumor in very early stages of its development and monitor the cancer progression and also the effect of therapeutic interventions. Biomarker discoveries are driven by advanced techniques, such as proteomics, transcriptomics, whole genome sequencing, micro- and micro-RNA arrays, and translational clinics. In this review, an overview of the potential of tissue- and serum-associated HCC biomarkers as diagnostic, prognostic, and therapeutic targets for drug development is presented. In addition, we highlight recently developed micro-RNA, long noncoding RNA biomarkers, and single-nucleotide changes, which may be used independently or as complementary biomarkers. These active investigations going on around the world aimed at conquering HCC might show a bright light in the near future.

  17. Hepatocellular Carcinoma in Obesity, Type 2 Diabetes, and NAFLD.

    Science.gov (United States)

    Reeves, Helen L; Zaki, Marco Y W; Day, Christopher P

    2016-05-01

    Hepatocellular carcinoma (HCC) is the second commonest cause of cancer death worldwide. Rather than falling as a result of prevention and treatments for viral hepatitis, an increase is evident in developed nations consequent to the rising prevalence of obesity and type 2 diabetes mellitus (T2DM)-the two major risk factors for nonalcoholic fatty liver disease (NAFLD). The majority of patients with HCC complicating these conditions present with advanced disease as the tools for surveillance are inadequate, and the "at-risk" population is not well characterized. This review will summarize the epidemiological evidence linking obesity, T2DM, and NAFLD with HCC, what is known about the pathogenic mechanisms involved, as well as their relevance for clinicians managing patients at risk. There will also be an overview of the "unmet needs" surrounding this topic, with suggestions for the direction translational research should take in order to prevent progression of NAFLD to HCC, to improve early detection of HCC in those with NAFLD, as well as to improve outcomes for those affected. PMID:26921078

  18. Simultaneous Resection of Disseminated Hepatocellular Carcinoma and Colon Cancer

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    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.

  19. Hepatocellular Carcinoma in Pakistan: National Trends and Global Perspective.

    Science.gov (United States)

    Hafeez Bhatti, Abu Bakar; Dar, Faisal Saud; Waheed, Anum; Shafique, Kashif; Sultan, Faisal; Shah, Najmul Hassan

    2016-01-01

    Hepatocellular carcinoma (HCC) ranks second amongst all causes of cancer deaths globally. It is on a rise in Pakistan and might represent the most common cancer in adult males. Pakistan contributes significantly to global burden of hepatitis C, which is a known risk factor for HCC, and has one of the highest prevalence rates (>3%) in the world. In the absence of a national cancer registry and screening programs, prevalence of hepatitis and HCC only represents estimates of the real magnitude of this problem. In this review, we present various aspects of HCC in Pakistan, comparing and contrasting it with the global trends in cancer care. There is a general lack of awareness regarding risk factors of HCC in Pakistani population and prevalence of hepatitis C has increased. In addition, less common risk factors are also on a rise. Majority of patients present with advanced HCC and are not eligible for definitive treatment. We have attempted to highlight issues that have a significant bearing on HCC outcome in Pakistan. A set of strategies have been put forth that can potentially help reduce incidence and improve HCC outcome on national level. PMID:26955390

  20. 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

  1. 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.

  2. 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.

  3. 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.

  4. The HDACi Panobinostat Shows Growth Inhibition Both In Vitro and in a Bioluminescent Orthotopic Surgical Xenograft Model of Ovarian Cancer

    Science.gov (United States)

    Helland, Øystein; Popa, Mihaela; Bischof, Katharina; Gjertsen, Bjørn Tore; McCormack, Emmet; Bjørge, Line

    2016-01-01

    Background In most epithelial ovarian carcinomas (EOC), epigenetic changes are evident, and overexpression of histone deacetylases (HDACs) represents an important manifestation. In this study, we wanted to evaluate the effects of the novel HDAC inhibitor (HDACi) panobinostat, both alone and in combination with carboplatin, on ovarian cancer cell lines and in a murine bioluminescent orthotopic surgical xenograft model for EOC. Methods The effects of panobinostat, both alone and in combination with carboplatin, on proliferation and apoptosis in ovarian cancer cell lines, were evaluated using colony and WST-1 assays, Hoechst staining and flow cytometry analysis. In addition, mechanisms were characterised by western blotting and phosphoflow analysis. Immuno-deficient mice were engrafted orthotopically with SKOV-3luc+ cells and serial bioluminescence imaging monitored the effects of treatment with panobinostat and/or carboplatin and/or surgery. Survival parameters were also measured. Results Panobinostat treatment reduced cell growth and diminished cell viability, as shown by the induced cell cycle arrest and apoptosis in vitro. We observed increased levels of cleaved PARP and caspase-3, downregulation of cdc2 protein kinase, acetylation of H2B and higher pH2AX expression. The combined administration of carboplatin and panobinostat synergistically increased the anti-tumour effects compared to panobinostat or carboplatin treatment alone. In our novel ovarian cancer model, the mice showed significantly higher rates of survival when treated with panobinostat, carboplatin or a combination of both, compared to the controls. Panobinostat was as efficient as carboplatin regarding prolongation of survival. No significant additional effect on survival was observed when surgery was combined with carboplatin/panobinostat treatment. Conclusions Panobinostat demonstrates effective in vitro growth inhibition in ovarian cancer cells. The efficacy of panobinostat and carboplatin was

  5. 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.

  6. 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.

  7. 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

  8. P08.10SINGLE BRAIN METASTASIS 9 YEARS AFTER ORTHOTOPIC LIVER TRANSPLANT WITH HISTOLOGICAL NEGATIVE EXPIANTED LIVER: CASE REPORT

    Science.gov (United States)

    Fornaro, R.; Agnoletti, A.; Specchia, F.M. Calamo; Garbossa, D.; Lanotte, M.; Ducati, A.

    2014-01-01

    We describe the case of a 67 years old man, that underwent orthotopic liver transplant (OLT) in 2004 for cirrhosis. Native liver hystological examination was negative for focal hepatocarcinoma (HCC) areas. In 2008, during regular follow up, pulmonary lesions were found and diagnosed as hepatocarcinoma metastasis.In 2013, patient accused vertigo and dizziness: neuroimaging showed a cerebellar lesion. Hystological diagnosis was HCC metastases. The peculiarity is the onset of lung metastasis after transplant, with negative analysis on native liver, and brain metastasis after stable disease. This case is also relevant due to long survival related to the unavailability of many oncologic therapies in transplanted patients.

  9. 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...

  10. 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. 

  11. Orthotopic human melanoma xenograft model systems for studies of tumour angiogenesis, pathophysiology, treatment sensitivity and metastatic pattern.

    OpenAIRE

    Rofstad, E. K.

    1994-01-01

    Adequate tumour models are a prerequisite in experimental cancer research. The purpose of the present work was to establish and assess the validity of four new orthotopic human melanoma xenograft model systems (A-07, D-12, R-18, U-25). Permanent cell lines were established in monolayer culture from subcutaneous metastases of four different melanoma patients by using an in vivo-in vitro procedure, and cells from these lines were inoculated intradermally in Balb/c nu/nu mice to form tumours. In...

  12. Hybrid SPECT/CT evaluation of dual ectopia of thyroid in the absence of orthotopic thyroid gland.

    Science.gov (United States)

    Harisankar, Chidambaram Natrajan Balasubramanian; Preethi, Govindababu Rajalakshmi; George, Mv

    2012-06-01

    Ectopic thyroid tissue (ETT) refers to all cases in which the thyroid gland is present at a location other than its usual site. The prevalence of ETT is approximately 1 per 100,000 to 300,000 persons and is reported to occur in 1 of 4000 to 8000 patients with thyroid disease. Multiple ectopia of the thyroid is extremely rare, with fewer than 35 cases published in literature to date. We report a 4-year-old girl with euthyroid and dual ectopia of thyroid without orthotopic thyroid gland. The role of hybrid SPECT/CT in the localization of the sites of ETT is also highlighted. PMID:22614198

  13. 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 

  14. 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.

  15. Imaging the microenvironment of pancreatic cancer patient-derived orthotopic xenografts (PDOX) growing in transgenic nude mice expressing GFP, RFP, or CFP.

    Science.gov (United States)

    Hoffman, Robert M; Bouvet, Michael

    2016-09-28

    We have developed a multi-color, imageable, orthotopic mouse model for individual patients with pancreatic cancer. The tumors are labeled by first passaging them orthotopically through transgenic nude mice expressing green fluorescent protein (GFP), red fluorescent protein (RFP), or cyan fluorescent protein (CFP). Passage of the tumors in these colored transgenic mice labels the stromal cells of the tumor. The cancer cells in the PDOX are labeled in situ with GFP by telomerase-dependent adenovirus OBP-401. The models are termed imageable patient-derived orthotopic xenografts (iPDOX). The tumors acquired brightly-fluorescent stromal cells from the transgenic host mice, which were stably associated with the tumors through multiple passages. The colored fluorescent protein-expressing stromal cells included cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs). This model enables powerful color-coded imaging of the interaction of cancer and stromal cells during tumor progression and treatment. PMID:26742463

  16. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  18. Portal vein complications after orthotopic liver transplantation: a report of 6 cases%原位肝移植术后门静脉并发症的诊治

    Institute of Scientific and Technical Information of China (English)

    蒋水明; 周光文; 申川; 彭承宏; 李宏为

    2008-01-01

    Objective To study the diagnosis and treatment of portal vein complications after orthotopic liver transplantation. Methods The clinical data of 173 patients receiving orthotopic liver transplantation in our hospital from 2002 to 2005 were retrospectively analyzed. Results The incidence of portal vein complications was 3.5% (6 cases). The incidence of portal vein stenosis was 1.2% and that of portal vein thrombosis was 2. 3%. Three cases had previously been treated for portal hypertension and three cases had had a history of portal vein thrombosis before liver transplantation. All the complicated patients recovered and were discharged after successful treatment. There was no complication related mortality. Conclusions A history of previous treatment for portal hypertension, portal vein thrombosis is a risk factor predisposing the patients to portal vein complications after orthotopic liver transplantation. Color Doppler sonography is a sensitive and specific method for monitoring the portal vein complications following orthotopic liver transplantation. The angiography of portal vein is essential for diagnosis of the complications. Thrombolysis treatment is unsatisfactory for advanced stage portal vein thrombosis. Balloon dilation and stenting are both a safe and effective management modality for simple portal vein stenosis.%目的 探讨原位肝移植术后门静脉并发症的诊断和治疗.方法 回顾性分析173例原位肝移植患者的临床资料.结果 本组原位肝移植术后有6例门静脉并发症(3.5%),门静脉狭窄发生率为1.2%,门静脉血栓发生率为2.3%,且术前3例有门静脉血栓,3例有门静脉高压症手术史.2例患者成功放置血管内支架,3例患者行套扎术或硬化剂治疗后好转出院,6例中无1例死亡.结论 术前存在门静脉高压症手术治疗史和门静脉血栓是门静脉并发症的高危因素.彩色多普勒超声检查是监测门静脉并发症的有效方法 ,确诊门静脉并发症

  19. 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

  20. 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

  1. Residual hepatocellular carcinoma after oxaliplatin treatment has increased metastatic potential in a nude mouse model and is attenuated by Songyou Yin

    International Nuclear Information System (INIS)

    The opposite effects of chemotherapy, which enhance the malignancy of treated cancers such as hepatocellular carcinoma (HCC), are not well understood. We investigated this phenomenon and corresponding mechanisms to develop a novel approach for improving chemotherapy efficacy in HCC. Human hepatocellular carcinoma cell lines HepG2 (with low metastatic potential) and MHCC97L (with moderate metastatic potential) were used for the in vitro study. An orthotopic nude mouse model of human HCC was developed using MHCC97L cells. We then assessed the metastatic potential of surviving tumor cells after in vitro and in vivo oxaliplatin treatment. The molecular changes in surviving tumor cells were evaluated by western blot, immunofluorescence, and immunohistochemistry. The Chinese herbal extract Songyou Yin (composed of five herbs) was investigated in vivo to explore its effect on the metastatic potential of oxaliplatin-treated cancer cells. MHCC97L and HepG2 cells surviving oxaliplatin treatment showed enhanced migration and invasion in vitro. Residual HCC after in vivo oxaliplatin treatment demonstrated significantly increased metastasis to the lung (10/12 vs. 3/12) when re-inoculated into the livers of new recipient nude mice. Molecular changes consistent with epithelial-mesenchymal transition (EMT) were observed in oxaliplatin-treated tumor tissues and verified by in vitro experiments. The Chinese herbal extract Songyou Yin (4.2 and 8.4 g/kg) attenuated EMT and inhibited the enhanced metastatic potential of residual HCC in nude mice (6/15 vs. 13/15 and 3/15 vs. 13/15, respectively). The surviving HCC after oxaliplatin treatment underwent EMT and demonstrated increased metastatic potential. Attenuation of EMT by Songyou Yin may improve the efficacy of chemotherapy in HCC

  2. 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

  3. Suppression of acute rejective response following orthotopic liver transplantation in experimental rats infected with Echinococcus multilocularis

    Institute of Scientific and Technical Information of China (English)

    LI Tao; ZHAO Jin-ming; ZHANG Yan; PAI Zu-la; ZHANG Wei; Tuxun Tuer-hongjiang; BAI Lei; WU Jiang; WEN Hao

    2011-01-01

    Background Hepatic alveolar echinococcosis (AE) is a parasitic disease in humans and caused by the Echinococcus multilocularis (Em). Orthotopic liver transplantation (OLT) may be the only effective treatment for end-stage hepatic AE. However, in some AE patients, extrahepatic Em can not be completely eliminated after OLT. We aimed to study whether the immunological changes caused by Em evasion may influence the rejective response.Methods Rat modles of AE were established by injecting the Em suspension into abdomen of Brown Norway (BN) rats.Three months later, in the experimental group, the liver was transplanted from Lewis (LEW) rats to Em-infected BN rats.In the control group, transplantation was from LEW rats to healthy BN rats. Liver tissue and peripheral blood (PB)samples were collected on days 1, 3, 5, and 7 after OLT. Liver tissue was analyzed after hematoxylin and eosin (H&E)staining; numbers of CD4, CD8, and CD28 on peripheral blood cells were detected by flow cytometry; and expression of the chemokine fractalkine (Fkn) was detected by reverse transcription PCR (RT-PCR). Interleukin-10 (IL-10) was measured in the serum by enzyme-linked immunosorbent assay (ELISA). In every group, eight BN rats were retained for observing survival time.Results The survival times of recipients in the experimental group were prolonged compared with those in the control group. The rejective response occurred later and was milder in the experimental group, percentage of CD4, CD8, CD28 T-cells and Fkn mRNA expression were lower in the experimental group. While the serum IL-10 levels were higher in the experimental group than those in the control group.Conclusions Acute rejective response after OLT was attenuated in the rats with Em infection, and the recipients survival time was prolonged. Em may play a role in this process by elevating IL-10 secretion, decreasing the effector T cells, inhibiting the expression of Fkn, which lead to reduce the inflammatory cells infiltration into

  4. 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

  5. The role of vasoactive substances in hyperhemodynamics after orthotopic liver transplantation in cirrhotic rats

    Institute of Scientific and Technical Information of China (English)

    曹晖; 吴志勇; 张效杰; 张海婴; 陈治平; 邝耀麟

    2003-01-01

    Objective To evaluate the role of endogenous vasoactive substances in hyperdynamic circulation after orthotopic liver transplantation (OLT) in cirrhotic rats.Methods Male SD rats were randomly divided into 4 groups: normal controls (NL, n=10), rats with intrahepatic portal hypertension (IHPH, n=10), normal rats with OLT (NL-OLT, n=9), and IHPH rats with OLT (IHPH-OLT, n=16). IHPH-OLT rats were divided into 2 subgroups: Group A (3 days after OLT, n=9) and Group B (7 days after OLT, n=7). IHPH was induced by injection of CCI4 and OLT was performed using cuffs for the anastomosis of suprahepatic inferior vena cava, infrahepatic vena cava and portal vein. Radioactive microsphere method was used for hemodynamic study. The concentrations of plasma glucagon (Glu), nitric oxide (NO), prostaglandin (PGI2), thromboxaneA2 (TXA2) and endothelin (ET) were measured by radioimmunoassay. Results No significant difference in hemodynamic changes was observed between NL-OLT and NL rats, except for mean arterial blood pressure. No significant changes in NO and PGI2 were seen between NL-OLT and NL rats. Glu, ET and TXA2 were significantly elevated in NL-OLT rats compared with NL rats (PIHPH-OLT A>IHPH-OLT B rats. The level of plasma PGI2 in IHPH rats was significantly elevated compared with NL rats, while PGI2 in IHPH-OLT A and B rats was found to be lower than in IHPH rats (P<0.05). There was no obvious difference in PGI2 between IHPH-OLT B and NL rats. Vasoconstrictors including ET and TXA2 were found elevated in IHPH-OLT rats. Conclusions OLT does not induce postoperative hyperhemodynamics per se. Vasodilators including NO and Glu, especially NO, play an important role in the hyperhemodynamics of IHPH and IHPH-OLT rats. The results of the present study demonstrate that the persistence of systemic and splanchnic hyperkinetic circulation in the early stages after OLT may result from those non-eliminated factors that caused hyperhemodynamics in liver cirrhosis patients with portal

  6. 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].

  7. BRAIN METASTASIS FROM HEPATOCELLULAR CARCINOMA: A RARE CASE

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    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. 

  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. 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.

  12. Lentivirus IL-10 gene therapy down-regulates IL-17 and attenuates mouse orthotopic lung allograft rejection.

    Science.gov (United States)

    Hirayama, S; Sato, M; Loisel-Meyer, S; Matsuda, Y; Oishi, H; Guan, Z; Saito, T; Yeung, J; Cypel, M; Hwang, D M; Medin, J A; Liu, M; Keshavjee, S

    2013-06-01

    The purpose of the study was to examine the effect of lentivirus-mediated IL-10 gene therapy to target lung allograft rejection in a mouse orthotopic left lung transplantation model. IL-10 may regulate posttransplant immunity mediated by IL-17. Lentivirus-mediated trans-airway luciferase gene transfer to the donor lung resulted in persistent luciferase activity up to 6 months posttransplant in the isograft (B6 to B6); luciferase activity decreased in minor-mismatched allograft lungs (B10 to B6) in association with moderate rejection. Fully MHC-mismatched allograft transplantation (BALB/c to B6) resulted in severe rejection and complete loss of luciferase activity. In minor-mismatched allografts, IL-10-encoding lentivirus gene therapy reduced the acute rejection score compared with the lentivirus-luciferase control at posttransplant day 28 (3.0 ± 0.6 vs. 2.0 ± 0.6 (mean ± SD); p = 0.025; n = 6/group). IL-10 gene therapy also significantly reduced gene expression of IL-17, IL-23, and retinoic acid-related orphan receptor (ROR)-γt without affecting levels of IL-12 and interferon-γ (IFN-γ). Cells expressing IL-17 were dramatically reduced in the allograft lung. In conclusion, lentivirus-mediated IL-10 gene therapy significantly reduced expression of IL-17 and other associated genes in the transplanted allograft lung and attenuated posttransplant immune responses after orthotopic lung transplantation. PMID:23601206

  13. Percutaneous Transluminal Angioplasty of Hepatic Artery Stenosis in Patients After Orthotopic Liver Transplantation: Mid-term Results

    International Nuclear Information System (INIS)

    Purpose: This study was designed to present our experience with percutaneous treatment of hepatic artery stenosis in orthotopic liver transplant patients and to evaluate the efficacy, technical outcomes, and mid-term clinical results of the procedure. Methods: Twenty-two percutaneous transluminal angioplasties (PTAs) were performed in 19 liver transplant recipients at our institution between 1998 and 2010. Stents were placed into the hepatic/celiac artery in 16 PTAs, but balloon dilatation alone was performed in 6 because of the anatomical condition of the vessel. PTA/stenting was indicated in 17 patients because of elevated liver enzymes; 2 patients were asymptomatic. The objective of treating stenosis was prevention of long-term complications, including thrombosis. Results: Technical success was achieved in all patients. There was only one complication: dissection of the treated artery without any subsequent adverse effects. In all patients, elevated liver enzyme levels improved after treatment. No restenosis was observed in any patient during a mean follow-up of 2.6 years (1 month to 5.5 years). Conclusions: Percutaneous angioplasty/stent placement is a safe method for the treatment of hepatic artery stenosis after orthotopic liver transplantation, with a high technical success rate and promising mid-term results.

  14. SLT-VEGF Reduces Lung Metastases, Decreases Tumor Recurrence, and Improves Survival in an Orthotopic Melanoma Model

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    Sini Skariah

    2010-08-01

    Full Text Available SLT-VEGF is a recombinant cytotoxin comprised of Shiga-like toxin (SLT subunit A fused to human vascular endothelial growth factor (VEGF. It is highly cytotoxic to tumor endothelial cells overexpressing VEGF receptor-2 (VEGFR-2/KDR/Flk1 and inhibits the growth of primary tumors in subcutaneous models of breast and prostate cancer and inhibits metastatic dissemination in orthotopic models of pancreatic cancer. We examined the efficacy of SLT-VEGF in limiting tumor growth and metastasis in an orthotopic melanoma model, using NCR athymic nude mice inoculated with highly metastatic Line IV Cl 1 cultured human melanoma cells. Twice weekly injections of SLT-VEGF were started when tumors became palpable at one week after intradermal injection of 1 × 106 cells/mouse. Despite selective depletion of VEGFR-2 overexpressing endothelial cells from the tumor vasculature, SLT-VEGF treatment did not affect tumor growth. However, after primary tumors were removed, continued SLT-VEGF treatment led to fewer tumor recurrences (p = 0.007, reduced the incidence of lung metastasis (p = 0.038, and improved survival (p = 0.002. These results suggest that SLT-VEGF is effective at the very early stages of tumor development, when selective killing of VEGFR-2 overexpressing endothelial cells can still prevent further progression. We hypothesize that SLT-VEGF could be a promising adjuvant therapy to inhibit or prevent outgrowth of metastatic foci after excision of aggressive primary melanoma lesions.

  15. Targeting Hypoxia-Inducible Factor 1α in a New Orthotopic Model of Glioblastoma Recapitulating the Hypoxic Tumor Microenvironment.

    Science.gov (United States)

    Nigim, Fares; Cavanaugh, Jill; Patel, Anoop P; Curry, William T; Esaki, Shin-ichi; Kasper, Ekkehard M; Chi, Andrew S; Louis, David N; Martuza, Robert L; Rabkin, Samuel D; Wakimoto, Hiroaki

    2015-07-01

    Tissue hypoxia and necrosis represent pathophysiologic and histologic hallmarks of glioblastoma (GBM). Although hypoxia inducible factor 1α (HIF-1α) plays crucial roles in the malignant phenotypes of GBM, developing HIF-1α-targeted agents has been hampered by the lack of a suitable preclinical model that recapitulates the complex biology of clinical GBM. We present a new GBM model, MGG123, which was established from a recurrent human GBM. Orthotopic xenografting of stem-like MGG123 cells reproducibly generated lethal tumors that were characterized by foci of palisading necrosis, hypervascularity, and robust stem cell marker expression. Perinecrotic neoplastic cells distinctively express HIF-1α and are proliferative in both xenografts and the patient tissue. The xenografts contain scattered hypoxic foci that were consistently greater than 50 μm distant from blood vessels, indicating intratumoral heterogeneity of oxygenation. Hypoxia enhanced HIF-1α expression in cultured MGG123 cells, which was abrogated by the HIF-1α inhibitors digoxin or ouabain. In vivo, treatment of orthotopic MGG123 xenografts with digoxin decreased HIF-1α expression, vascular endothelial growth factor mRNA levels, and CD34-positive vasculature within the tumors, and extended survival of mice bearing the aggressive MGG123 GBM. This preclinical tumor model faithfully recapitulates the GBM-relevant hypoxic microenvironment and stemness and is a suitable platform for studying disease biology and developing hypoxia-targeted agents. PMID:26083570

  16. 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.

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. Montelukast induced acute hepatocellular liver injury

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    Harugeri A

    2009-01-01

    Full Text Available A 46-year-old male with uncontrolled asthma on inhaled albuterol and formoterol with budesonide was commenced on montelukast. He developed abdominal pain and jaundice 48 days after initiating montelukast therapy. His liver tests showed an increase in serum total bilirubin, conjugated bilirubin, aspartate aminotranferase, alanine aminotranferase, and alkaline phosphatase. The patient was evaluated for possible non-drug related liver injury. Montelukast was discontinued suspecting montelukast induced hepatocellular liver injury. Liver tests began to improve and returned to normal 55 days after drug cessation. Causality of this adverse drug reaction by the Council for International Organizations of Medical Sciences or Roussel Uclaf Causality Assessment Method (CIOMS or RUCAM and Naranjo′s algorithm was ′probable′. Liver tests should be monitored in patients receiving montelukast and any early signs of liver injury should be investigated with a high index of suspicion for drug induced liver injury.

  3. Hepatocellular adenoma: what is new in 2008.

    Science.gov (United States)

    Bioulac-Sage, Paulette; Laumonier, Hervé; Laurent, Christophe; Zucman-Rossi, Jessica; Balabaud, Charles

    2008-09-01

    Patients (85%) with hepatocellular adenoma (HCA) are women taking oral contraceptives. They can be divided into four subgroups according to their genotype/phenotype features. (1) Hepatocyte nuclear factor 1alpha (HNF1alpha) biallelic somatic mutations are observed in 35% of the HCA cases. It occurs in almost all cases in women. HNF1alpha-mutated HCA are most of the time, highly steatotic, with a lack of expression of liver fatty acid binding protein (LFABP) in immunohistochemistry analyses. Adenomatosis is frequently detected in this context. An HNF1alpha germline mutation is observed in less than 5% of HCA cases and can be associated with MODY 3 diabetes. (2) An activating beta-catenin mutation was found in 10% of HCA. These beta-catenin activated HCAs are observed in men and women, and specific risk factors, such as male hormone administration or glycogenosis, are associated with their development. Immunohistochemistry studies show that these HCAs overexpress beta-catenin (nuclear and cytoplasmic) and glutamine synthetase. This group of tumours has a higher risk of malignant transformation into hepatocellular carcinoma. (3) Inflammatory HCAs are observed in 40% of the cases, and they are most frequent in women but are also found in men. Lesions are characterised by inflammatory infiltrates, dystrophic arteries, sinusoidal dilatation and ductular reaction. They express serum amyloid A and C-reactive protein. In this group, GGT is frequently elevated, with a biological inflammatory syndrome present. Also, there are more overweight patients in this group. An additional 10% of inflammatory HCAs express beta-catenin, and are also at risk of malignant transformation. (4) Currently, less than 10% of HCAs are unclassified. It is hoped that in the near future it will be possible with clinical, biological and imaging data to predict in which of the 2 major groups (HNF1alpha-mutated HCA and inflammatory HCA) the patient belongs and to propose better guidelines in terms of

  4. Stereotactic Body Radiation Therapy as a Bridge to Transplantation and for Recurrent Disease in the Transplanted Liver of a Patient with Hepatocellular Carcinoma

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    Ali Mazloom

    2014-01-01

    Full Text Available Hepatocellular carcinoma (HCC is one of the most common causes of cancer mortality worldwide. Despite orthotopic liver transplantation (OLT, recurrent HCC is a major cause of morbidity. In this case report, we evaluate the efficacy of stereotactic body radiation therapy (SBRT as a bridge to OLT and for recurrence in the transplanted liver of a patient with HCC. A 52-year-old male with a history of chronic hepatitis C presented with a 1.7-cm liver lesion radiographically consistent with HCC, which was subsequently treated with a course of SBRT to 50 Gy in 5 fractions followed by OLT in 2009. The patient had a 2.2-cm recurrence in the transplanted liver in 2012, which was treated with SBRT to 62.5 Gy in 5 fractions. He tolerated the course of radiotherapy well with no significant radiation-related toxicity and remains in complete remission approximately 1 year after SBRT. SBRT is a safe and effective modality for the treatment of recurrent HCC in the transplanted liver of the same patient initially treated with SBRT as a bridge to OLT.

  5. Prognostic Factors for Tumor Recurrence after a 12-Year, Single-Center Experience of Liver Transplantations in Patients with Hepatocellular Carcinoma

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    Matteo Cescon

    2010-01-01

    Full Text Available Background. Factors affecting outcomes after orthotopic liver transplantation (OLT for hepatocellular carcinoma (HCC have been extensively studied, but some of them have only recently been discovered or reassessed. Methods. We analyzed classical and more recently emerging variables with a hypothetical impact on recurrence-free survival (RFS in a single-center series of 283 patients transplanted for HCC between 1997 and 2009. Results. Five-year patient survival and RFS were 75% and 86%, respectively. Thirty-four (12% patients had HCC recurrence. Elevated preoperative alpha-fetoprotein (AFP levels, preoperative treatments of HCC, unfulfilled Milan and up-to-seven criteria at final histology, poor tumor differentiation, and tumor microvascular invasion negatively affected RFS by univariate analysis. Milan and up-to-seven criteria applied preoperatively, and the use of m-TOR inhibitors did not reach statistical significance. Cox's proportional hazard model showed that only elevated AFP levels (Odds Ratio=2.88; 95% C.I.=1.43–5.80; =.003, preoperative tumor treatments (Odds Ratio=4.84; 95% C.I.=1.42–16.42; =.01, and microvascular invasion (Odds Ratio=4.82; 95% C.I.=1.87–12.41; =.001 were predictors of lower RFS. Conclusions. Biological aggressiveness and preoperative tumor treatment, rather than traditional and expanded dimensional criteria, conditioned the outcomes in patients transplanted for HCC.

  6. 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.``

  7. Residual dormant cancer stem-cell foci are responsible for tumor relapse after antiangiogenic metronomic therapy in hepatocellular carcinoma xenografts.

    Science.gov (United States)

    Martin-Padura, Ines; Marighetti, Paola; Agliano, Alice; Colombo, Federico; Larzabal, Leyre; Redrado, Miriam; Bleau, Anne-Marie; Prior, Celia; Bertolini, Francesco; Calvo, Alfonso

    2012-07-01

    Hepatocellular carcinoma (HCC) is the fifth most common solid tumor and the third leading cause of cancer-related deaths. Currently available chemotherapeutic options are not curative due in part to tumor resistance to conventional therapies. We generated orthotopic HCC mouse models in immunodeficient NOD/SCID/IL2rγ null mice by injection of human alpha-feto protein (hAFP)- and/or luciferase-expressing HCC cell lines and primary cells from patients, where tumor growth and spread can be accurately monitored in a non-invasive way. In this model, low-dose metronomic administration of cyclophosphamide (LDM-CTX) caused complete regression of the tumor mass. A significant increase in survival (P<0.0001), reduced aberrant angiogenesis and hyperproliferation, and decrease in the number of circulating tumor cells were found in LDM-CTX-treated animals, in comparison with untreated mice. Co-administration of LDM-CTX with anti-VEGF therapy further improved the therapeutic efficacy. However, the presence of residual circulating hAFP levels suggested that some tumor cells were still present in livers of treated mice. Immunohistochemistry revealed that those cells had a hAFP+/CD13+/PCNA- phenotype, suggesting that they were dormant cancer stem cells (CSC). Indeed, discontinuation of therapy resulted in tumor regrowth. Moreover, in-vitro LDM-CTX treatment reduced hepatosphere formation in both number and size, and the resulting spheres were enriched in CD13+ cells indicating that these cells were particularly resistant to therapy. Co-treatment of the CD13-targeting drug, bestatin, with LDM-CTX leads to slower tumor growth and a decreased tumor volume. Therefore, combining a CD13 inhibitor, which targets the CSC-like population, with LDM-CTX chemotherapy may be used to eradicate minimal residual disease and improve the treatment of liver cancer. PMID:22546866

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

    Directory of Open Access Journals (Sweden)

    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

  9. 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

  10. In vivo and in vitro suppression of hepatocellular carcinoma by EF24, a curcumin analog.

    Directory of Open Access Journals (Sweden)

    Haitao Liu

    Full Text Available The synthetic compound 3,5-bis(2-flurobenzylidenepiperidin-4-one (EF24 is a potent analog of curcumin that exhibits enhanced biological activity and bioavailability without increasing toxicity. EF24 exerts antitumor activity by arresting the cell cycle and inducing apoptosis, suppressing many types of cancer cells in vitro. The antiproliferative and antiangiogenic properties of EF24 provide theoretical support for its development and application to liver cancers. We investigated the in vitro and in vivo activities of EF24 on liver cancer to better understand its therapeutic effects and mechanisms. EF24 induced significant apoptosis and G2/M-phase cell cycle arrest in mouse liver cancer cell lines, Hepa1-6 and H22. The expression levels of G2/M cell cycle regulating factors, cyclin B1 and Cdc2, were significantly decreased, pp53, p53, and p21 were significantly increased in EF24-treated cells. In addition, EF24 treatment significantly reduced Bcl-2 concomitant with an increase in Bax, enhanced the release of cytochrome c from the mitochondria into the cytosol, resulting in an upregulation of cleaved-caspase-3, which promoted poly (ADP-ribose polymerase cleavage. EF24-treated cells also displayed decreases in phosphorylated Akt, phosphorylated extracellular signal-regulated kinase and vascular endothelial growth factor. Our in vitro protein expression data were confirmed in vivo using a subcutaneous hepatocellular carcinoma (HCC tumor model. This mouse HCC model confirmed that total body weight was unchanged following EF24 treatment, although tumor weight was significantly decreased. Using an orthotopic HCC model, EF24 significantly reduced the liver/body weight ratio and relative tumor areas compared to the control group. In situ detection of apoptotic cells and quantification of Ki-67, a biomarker of cell proliferation, all indicated significant tumor suppression with EF24 treatment. These results suggest that EF24 exhibits anti-tumor activity

  11. 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...

  12. An Oncolytic Vaccinia Virus Expressing the Human Sodium Iodine Symporter Prolongs Survival and Facilitates SPECT/CT Imaging in an Orthotopic Model of Malignant Pleural Mesothelioma

    Science.gov (United States)

    Belin, Laurence J.; Ady, Justin W.; Lewis, Christina; Marano, Drew; Gholami, Sepideh; Mojica, Kelly; Eveno, Clarisse; Longo, Valerie; Zanzonico, Pat B.; Chen, Nanhai G.; Szalay, Aladar A.; Fong, Yuman

    2014-01-01

    Background The purpose of this original work is to examine the ability of an oncolytic vaccinia virus expressing the human sodium iodine transporter (hNIS) to provide real time monitoring of viral therapy and effective treatment of malignant pleural mesothelioma (MPM). Methods Infectivity and cytotoxic effect of GLV-1h153 on mesothelioma cell lines of all histologic subtypes was assayed in vitro. Viral replication was examined by standard viral plaque assay. Orthotopic MPM xenografts were generated in athymic nude mice and treated with intrapleural GLV-1h153 and assessed for effect on tumor burden and survival. Orthotopic tumors were also imaged on SPECT/CT after 131I administration. Results GLV-1h153 infected and killed all cell lines in a time and concentration dependent manner. Viral replication demonstrated over a 2.5 log increase in titer over 4 days. Intrapleural treatment of orthotopic MPM xenografts resulted in a significant reduction in tumor burden one week after treatment and an improvement in survival. Infection of orthotopic xenografts was both therapeutic and facilitated monitoring by 131I-SPECT/CT via expression of hNIS in infected tissue. Conclusions Our results suggest GLV-1h153 is a promising therapeutic agent for MPM and warrants further investigation. PMID:23890748

  13. 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

  14. 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.

  15. 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

  16. 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.

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

    Directory of Open Access Journals (Sweden)

    Catrin H Middleton

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

  18. 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.

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

    Institute of Scientific and Technical Information of China (English)

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

    2016-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2015-01-01

    BACKGROUND: Hepatocellular carcinoma (HCC) is a com-plex and heterog