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Successful Curative Extracorporeal Hepatic Resection for Far-Advanced Hepatocellular Carcinoma in an Adolescent Patient

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LIVER TRANSPLANTATION 2010年第5期16卷 685-687页

作者： Sugimachi, Keishi Shirabe, Ken Taketomi, Akinobu Soejima, Yuji Yoshizumi, Tomoharu Yamashita, Yo-Ichi Umeda, Kenji Morita, Kazutoyo Maehara, Yoshihiko Kyushu Univ Grad Sch Med Sci Dept Surg & Sci Higashi Ku Fukuoka 8128582 Japan

Hepatectomy is the principal treatment for hepatocellular carcinoma (HCC); however, some HCCs are not resectable by conventional hepatic resection. In such apparently incurable cases, extracorporeal hepatic resection (ECHR) may offer an option for survival.1 We recently encountered a juvenile patient with faradvanced HCC who was successfully treated by ECHR with favorable long-term survival.

关键词： Successful Extracorporeal Hepatic Hepatectomy Hepatic Organ System human-centered computing ectomy

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Liver Transplantation for Hepatocellular Carcinoma

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CANCER CONTROL 2010年第2期17卷 83-86页

作者： Alsina, Angel E. Tampa Gen Hosp LifeLink HealthCare Inst Dept Surg Tampa FL 33606 USA Tampa Gen Hosp LifeLink HealthCare Inst Dept Liver Transplantat Tampa FL 33606 USA Tampa Gen Hosp LifeLink HealthCare Inst Dept Hepatobiliary Surg Tampa FL 33606 USA

Background: The treatment of hepatocellular carcinoma (HCC) is challenging, but transplantation of the liver has emerged as one of the options in the therapeutic armamentarium against this disease. Methods: This article reviews the changing criteria for patient eligibility for liver transplantation for HCC and presents an initial evaluation of institutional treatment outcomes for this treatment modality. A method for evaluating prognosis is also described. Results: Patients are considered for liver transplantation if they meet the Milan criteria for eligibility or a UCSF-attributed expansion of these criteria that includes the "rule of 7," whereby the sum of the size of the largest nodule plus the total number of nodules cannot exceed 7. Preliminary institutional experience suggests a tumor recurrence rate of 11% in 91 patients with HCC who received liver transplants between 1996 and 2008. Conclusions: Liver transplantation offers an opportunity for long-term survival in patients with HCC and chronic cirrhosis whose tumor cannot be resected. Criteria for patient selection for this modality of treatment continue to be upgraded and refined.

关键词： Modality Patient Selection human-centered computing eligibility Treatment Outcome Liver Transplantation Repetition rate

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Hepatocyte IKKβ/NF-κB Inhibits Tumor Promotion and Progression by Preventing Oxidative Stress-Driven STAT3 Activation

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CANCER CELL 2010年第3期17卷 286-297页

作者： He, Guobin Yu, Guann-Yi Temkin, Vladislav Ogata, Hisanobu Kuntzen, Christian Sakurai, Toshiharu Sieghart, Wolfgang Peck-Radosavljevic, Markus Leffert, Hyam L. Karin, Michael Univ Calif San Diego Sch Med Lab Gene Regulat & Signal Transduct La Jolla CA 92093 USA Univ Calif San Diego Sch Med Hepatocyte Growth Control & Stem Cell Lab La Jolla CA 92093 USA Kyoto Univ Grad Sch Med Dept Clin Mol Biol Sakyo Ku Kyoto 6068507 Japan Med Univ Vienna Div Gastroenterol Hepatol Dept Internal Med 3 A-1090 Vienna Austria

The NF-kappa B activating kinase IKK beta suppresses early chemically induced liver tumorigenesis by inhibiting hepatocyte death and compensatory IKK beta's role in late tumor promotion and progression, we developed a transplant system that allows initiated mouse hepatocytes to form hepatocellular carcinomas (HCC) in host liver after along latency. Deletion of IKK beta long after initiation accelerated HCC development and enhanced proliferation of tumor initiating cells. These effects of IKK beta/NF-kappa B were cell autonomous and correlated with increased accumulation of reactive oxygen species that led to JNK and STAT3 activation. Hepatocyte-specific STAT3 ablation prevented HCC development. The negative crosstalk between NF-kappa B and STAT3, which is also evident in human HCC, is a critical regulator of liver cancer development and progression.

关键词： progressions Hepatocytes Cancer of Liver MAPK8 gene Tumor Promotion NF-kappa B human-centered computing

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Liver Transplantation for Hepatocellular Carcinoma in the Model for End-Stage Liver Disease Era

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JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS 2010年第5期210卷 727-734页

作者： Levi, David M. Tzakis, Andreas G. Martin, Paul Nishida, Seigo Island, Eddie Moon, Jang Selvaggi, Gennaro Tekin, Akin Madrazo, Beatrice L. Narayanan, Govindarajan Garcia, Monica T. Feun, Lynn G. Tryphonopoulos, Panagiotis Skartsis, Nikolaos Livingstone, Alan S. Univ Miami DeWitt Daughtry Family Dept Surg Miller Sch Med Miami FL 33136 USA Univ Miami Miller Sch Med Miami Transplant Inst Miami FL 33136 USA Univ Miami Miller Sch Med Dept Med Miami FL 33136 USA Univ Miami Miller Sch Med Dept Radiol Miami FL 33136 USA Univ Miami Miller Sch Med Dept Pathol Miami FL 33136 USA

BACKGROUND: Since March 2002, the United Network for Organ Sharing liver allocation policy has given extra priority to patients with hepatocellular carcinoma (HCC) who meet specific medical criteria. This study reviews our experience with liver transplantation for HCC under this system. STUDY DESIGN: Between March 2002 and April 2009, 244 patients with HCC underwent primary liver or liver-kidney transplantation under the current allocation system at the University of Miami. Outcomes including HCC recurrence-free survival (RFS) and patient survival (PS) were assessed retrospectively. Clinical variables that predicted outcomes were analyzed. RESULTS: The median time from listing to transplantation was 48 days. The median follow-up was 27.4 months, with an observed recurrence rate of 10.7%. The RFS rates at 1, 3, and 5 years after transplantation were 96.0%, 89.0%, and 83.6%, respectively. The PS rates at 1, 3, and 5 years after transplantation were 86.3%, 71.5%, and 61.7%, respectively. Among patients diagnosed with T2 HCC, a trend toward improved RFS was observed for those who received preoperative ablative therapy;PS was similar (p > 0.05). Outcomes (RFS and PS) for patients with T3 HCC were similar to those in patients with T2 HCC (p > 0.05). Patients with an alpha-fetoprotein >100 ng/mL had all RFS that was inferior to that in patients with an alpha-fetoprotein <= 100 ng/mL (p < 0.0001). CONCLUSIONS: Under the current allocation system, transplantation for HCC results in excellent RFS;PS depends Oil factors other than HCC;the value of preoperative ablative therapy for patients with T2 HCC is uncertain;the current criteria could be expanded to include selected patients with T3 HCC;and an elevated AFP level is associated with an increased risk of HCC recurrence after transplantation. (J Am Coll Surg 2010;210:727-736. (C) 2010 by the American College of Surgeons)

关键词： Hepatocellular Cancer End Stage Liver Disease Transplantation Allocation systems Liver Transplantation human-centered computing Polystyrenes Patients

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Hepatocellular carcinoma: a global view

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NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY 2010年第8期7卷 448-458页

作者： Yang, Ju Dong Roberts, Lewis R. Mayo Clin Coll Med Miles & Shirley Fiterman Ctr Digest Dis Rochester MN 55905 USA

Hepatocellular carcinoma (HCC) is a global health problem, although developing countries are disproportionally affected: over 80% of HCCs occur in such regions. About three-quarters of HCCs are attributed to chronic HBV and HCV infections. In areas endemic for HCV and HBV, viral transmission occurs at an early age, and infected individuals develop HCC in mid-adulthood. As these are their most productive years of life, HCC accounts for a substantial burden on the health-care system and drain of productive capacity in the low-income and middle-income countries most affected by HCV and HBV infections. Environments with disparate resource levels require different strategies for the optimal management of HCC. In high-resource environments, guidelines from the American Association for the Study of Liver Diseases or European Association for the Study of the Liver should be applied. In intermediate-resource or low-resource environments, the fundamental focus should be on primary prevention of HCC, through universal HBV vaccination, taking appropriate precautions and antiviral treatments. In intermediate-resource and low-resource environments, the infrastructure and capacity for abdominal ultrasonography, percutaneous ethanol injection, radiofrequency ablation and surgical resection should be established. Programs to provide targeted therapy at low cost, similar to the approach used for HIV therapy in the developing world, should be pursued.

关键词： Primary Prevention Global Health HIV therapy Molecular Targeted Therapy Hepatitis B virus Production capacity Liver Diseases human-centered computing European association

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Meta-analysis: interferon improves outcomes following ablation or resection of hepatocellular carcinoma

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ALIMENTARY PHARMACOLOGY & THERAPEUTICS 2010年第7期32卷 851-858页

作者： Singal, A. K. Freeman, D. H., Jr. Anand, B. S. Univ Texas Med Branch Dept Internal Med Div Gastroenterol & Hepatol Galveston TX 77555 USA Univ Texas Med Branch Dept Community Hlth & Prevent Med Div Epidemiol & Biostat Galveston TX 77555 USA Baylor Coll Med Dept Gastroenterol & Hepatol Michael E DeBakey VA Med Ctr Houston TX 77030 USA

P>Background Hepatocellular carcinoma (HCC) is third most common cause of tumour-related death in the US with hepatitis C virus (HCV) the most common aetiology. Surgical resection and tumour ablation are curative in patients who cannot be transplanted. With native liver having cirrhosis, HCC recurrence is a potential problem. Aim To perform a systematic review and meta-analysis of studies evaluating efficacy of IFN to prevent HCC recurrence after its curative treatment in HCV-related cirrhosis. Methods Ten studies (n = 645, 301 treated with IFN) on the use of IFN after resection or ablation of HCV-associated HCC were analysed. Results Pooled data showed benefit of IFN for HCC prevention with OR (95% CI) of 0.26 (0.15-0.45);P < 0.00001. The proportion of patients surviving at 5 years (n = 505 in 6 studies) was in favour of IFN with OR of 0.31 [(95% CI 0.21-0.46);P < 0.00001]. Data were homogeneous for HCC recurrence (chi 2 12.05, P = 0.21) and survival (chi 2 6.93, P = 0.44). The benefit of IFN was stronger with sustained virological response compared with nonresponders for HCC recurrence [0.19 (0.06-0.60);P = 0.005] and survival [0.31 (0.11-0.90);P = 0.03]. Conclusion Interferon treatment after curative resection or ablation of HCC in HCV-related cirrhotics prevents HCC recurrence and improves survival.

关键词： Interferons Meta-Analysis Hepatocellular Cancer Relapse curative treatment human-centered computing

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The Milan Criteria: No Room on the Metro for the King?

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LIVER TRANSPLANTATION 2010年第3期16卷 252-255页

作者： Marsh, J. Wallis Schmidt, Carl Univ Pittsburgh Sch Med Dept Surg Thomas E Starzl Transplantat Inst Pittsburgh PA 15213 USA Ohio State Univ Med Ctr Dept Surg Columbus OH 43210 USA

The incidence of hepatocellular carcinoma (HCC) continues to rise worldwide, and this is related primarily to the prevalence of viral hepatitis.1 Even though the majority of patients with HCC present too late in the course of the disease to be considered for anything other than medical/palliative therapy, there remains a small group of patients who are candidates for potentially curative therapy [liver transplantation (LT), liver resection, or cytoreductive therapy]. Fortunately, there is no absolute resource barrier to liver resection or cytoreductive therapies; however, the same is not true for LT.

关键词： Milan Criteria Room Level Trigger Small groups Subways Hepatectomy human-centered computing Medicine

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Radioembolization with Use of Yttrium-90 Resin Microspheres in Patients with Hepatocellular Carcinoma and Portal Vein Thrombosis

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JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY 2010年第8期21卷 1205-1212页

作者： Inarrairaegui, Mercedes Thurston, Kenneth G. Bilbao, Jose I. D'Avola, Delia Rodriguez, Macarena Arbizu, Javier Martinez-Cuesta, Antonio Sangro, Bruno Univ Navarra Clin Liver Unit Pamplona Spain Univ Navarra Clin Dept Intervent Radiol Pamplona Spain Univ Navarra Clin Dept Nucl Med Pamplona Spain CIBEREHD Barcelona Spain Sirtex Med US Holdings Wilmington MA USA

PURPOSE: Intraarterial delivery of yttrium-90 (Y-90)-bound microspheres (ie, radioembolization) is a promising treatment for hepatocellular carcinoma (HCC). An early concern was the "embolic" nature of the microspheres, and their potential to reduce hepatic arterial blood flow in patients with compromised portal blood flow secondary to portal vein thrombosis/occlusion (PVT). In this situation, the risk of liver failure could be enhanced, particularly in patients with cirrhosis who have increased hepatic arterial blood flow. This retrospective analysis was undertaken to assess the safety and clinical benefits of radioembolization with Y-90 resin microspheres in HCC with branch or main PVT. MATERIALS AND METHODS: A total of 25 patients presenting with unresectable HCC and compromised portal flow received segmental, lobar, or whole-liver infusion of Y-90 resin microspheres. For the analysis of tumor response, changes in target lesions, appearance of new lesions, and changes in portal vein thrombus were studied. Controlled disease was defined by absence of progression in all these components. RESULTS: Globally, controlled disease was achieved in 66.7% of patients at 2 months and 50% of patients at 6 months. No significant changes were observed in liver-related toxicities according to Common Toxicity Criteria (version 3.0) at 1 and 2 months after treatment. Median survival time was 10 months (95% CI, 6.6-13.3 months). CONCLUSIONS: Radioembolization of unresectable HCC and branch or main PVT with Y-90 resin microspheres was associated with minimal toxicity and a favorable median survival time. Further prospective studies are warranted to validate the findings in this clinically challenging patient population.

关键词： microparticles Blood Flow Hepatocellular Cancer Yttrium 90 Blood Circulation Yttrium-90 Microspheres RADIOEMBOLIZATION Resin Portal Vein Thrombosis human-centered computing Portal Vein Microspheres Patients

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Knockdown of Thrombomodulin Enhances HCC Cell Migration through Increase of ZEB1 and Decrease of E-cadherin Gene Expression

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ANNALS OF SURGICAL ONCOLOGY 2010年第12期17卷 3379-3385页

作者： Huang, Ming-Te Wei, Po-Li Liu, Jun-Jen Liu, Der-Zen Huey-Chun, Huang An, Jane Wu, Cheng-Chia Wu, Chih-Hsiung Ho, Yuan-Soon Yang, Yi-Yuan Chang, Yu-Jia Taipei Med Univ Dept Surg Taipei Taiwan Taipei Med Univ Shuang Ho Hosp Dept Surg Taipei Taiwan Taipei Med Univ Grad Inst Biomed Technol Taipei Taiwan Taipei Med Univ Grad Inst Biomed Mat & Engn Taipei Taiwan China Med Univ Dept Med Lab Sci & Biotechnol Coll Hlth Care Taichung Taiwan New York Med Coll Valhalla NY 10595 USA Taipei Med Univ Ctr Excellence Canc Res Taipei Taiwan Taipei Med Univ Grad Inst Clin Med Taipei Taiwan

Thrombomodulin (TM) is a key molecule mediating circulation homeostasis through its binding to thrombin. The TM-thrombin complex can activate protein C and thrombin-activatable fibrinolysis inhibitor to form a tight clot. In many cancer tissues, decrease of TM expression may correlate with cancer metastasis. However, the role of TM in hepatocellular carcinoma (HCC) progression is still unclear. We characterized TM expression in HCC cells (HepJ5 and skHep-1 cells) using real-time polymerase chain reaction (PCR) and Western blotting. We then manipulated TM expression using both TM-specific short hairpin RNA (shRNA) and overexpressing it in HCC cells. Transwell migration assay was performed to monitor the migratory ability of HCC cells under different levels of TM expression. We found that TM was ectopically highly expressed in skHep-1 at both transcriptional and translational levels. After silencing TM expression in skHep-1 cells, we found that metastatic capability was dramatically increased. Conversely, overexpression of TM in HepJ5 cells decreased metastatic ability. We investigated the possible mechanism and found that decreased TM-mediated enhancement of cell migration was dependent on upregulation of ZEB1, a repressor of E-cadherin. TM may be a modulator of cancer metastasis in HCC. Downregulation of TM expression may increase ZEB1 and decrease E-cadherin levels.

关键词： Cell Locomotion Zinc Finger E-box-Binding Homeobox 1 Thrombomodulin Neoplasm Metastasis thulium human-centered computing Cell Migration

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Chemoembolization with Lobaplatin Mixed with Iodized Oil for Unresectable Recurrent Hepatocellular Carcinoma after Orthotopic Liver Transplantation

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JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY 2010年第3期21卷 333-338页

作者： Zhou, Bin Shan, Hong Zhu, Kang-Shun Jiang, Zai-Bo Guan, Shou-Hai Meng, Xiao-Chun Zeng, Xian-Cheng Sun Yat Sen Univ Affiliated Hosp 3 Dept Radiol Guangzhou 510630 Guangdong Peoples R China Sun Yat Sen Univ Affiliated Hosp 3 Liver Transplant Ctr Guangzhou 510630 Guangdong Peoples R China

PURPOSE: To determine whether chemoembolization can benefit patients with unresectable recurrent hepatocellular carcinoma (HCC) after orthotopic liver transplantation (OLT). MATERIALS AND METHODS: Twenty-eight of 71 patients (39%) with unresectable recurrent HCC following OLT and without contradictions to chemoembolization were included: 14 patients received chemoembolization after OLT (chemoembolization group) and 14 matched control subjects who did not receive chemoembolization (non-chemoembolization group). Tumor response was determined with follow-up computed tomography after each chemoembolization procedure and classified into four grades according to Response Evaluation Criteria in Solid Tumors. Overall survival was evaluated from OLT and from the diagnosis of recurrent HCC. RESULTS: Within a median follow-up of 14.5-months, 12 of the 14 patients in the chemoembolization group (86%) and 13 of the 14 in the non-chemoembolization group (93%) developed new recurrences. Eight of the 14 patients in the chemoembolization group (57%) showed partial tumor response (>30% reduction in the size of target lesions). Moreover, patients who underwent chemoembolization had a significantly longer overall survival after OLT (P=.0133) and after the diagnosis of HCC recurrence (P=.0338) compared to those who did not. No severe complications developed in patients receiving chemoembolization during follow-up. CONCLUSIONS: Lobaplatin-based chemoembolization may elicit effective tumor response for recurrent HCCs and improve the overall survival of patients with unresectable HCC recurrence following OLT.

关键词： overall survival Recurrent Hepatocellular Carcinoma Iodized Oil lobaplatin chemoembolization human-centered computing Optical Line Terminal Liver Transplantation

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