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Contrast-enhanced ultrasound in differentiating malignant from benign portal vein thrombosis in hepatocellular carcinoma

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World Journal of Gastroenterology 2015年第32期21卷 9457-9460页

作者： Luciano Tarantino Pasquale Ambrosino Matteo Nicola Dario Di Minno Department of Surgery Interventional Hepatology Unit Andrea Tortora Hospital Department of Clinical Medicine and Surgery Federico II University Unit of Cell and Molecular Biology in Cardiovascular Diseases Centro Cardiologico Monzino

Portal vein thrombosis(PVT) may occur in liver cirrhosis patients. Malignant PVT is a common complication in cirrhotic patients with concomitant hepatocellular carcinoma(HCC) and, in some cases, it may be even the initial sign of an undetected HCC. Detection of malignant PVT in a patient with liver cirrhosis heavily affects the therapeutic strategy. Gray-scale ultrasound(US) is widely unreliable for differentiating benign and malignant thrombi. Although effective for this differential diagnosis, fine-needle biopsy remains an invasive technique. Sensitivity of color-doppler US in detection of malignant thrombi is highly dependent on the size of the thrombus. Contrast-enhanced computed tomography(CT) and contrast-enhanced magnetic resonance(MRI) can be useful to assess the nature of portal thrombus, while limited data are currently available about the role of positron emission tomography(PET) and PET-CT. In contrast with CT, MRI, PET, and PET-CT, contrast-enhanced ultrasound(CEUS) is a fast, effective, well tolerated and cheap technique, that can be performed even in the same session in which the thrombus has been detected. CEUS can be performed bedside and can be available also in transplanted patients. Moreover, CT and MRI only yield a snapshot analysis during contrast diffusion, while CEUS allows for a continuous real-time imaging of the microcirculation that lasts several minutes, so that the whole arterial phase and the late parenchymal phase of the contrast diffusion can be analyzed continuously by real-time US scanning. Continuous real-time monitoring of contrast diffusion entails an easy detection of thrombus maximum enhancement. Moreover, continuous quantitative analyses of enhancement(wash in- wash out studies) by CEUS during contrast diffusion is nowadays available in most CEUS machines, thus giving a more sophisticated and accurate evaluation of the contrast distribution and an increased confidence in diagnosis in difficult cases. In conclusion, CEUS is av

关键词： Contrast-enhanced ultrasound Hepatocellular carcin

Alpha-fetoprotein before and after pegylated interferon therapy for predicting hepatocellular carcinoma development

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World Journal of Hepatology 2015年第19期7卷 2220-2228页

作者： Yasuto Takeuchi Fusao Ikeda Toshiya Osawa Yasuyuki Araki Kouichi Takaguchi Youichi Morimoto Noriaki Hashimoto Kousaku Sakaguchi Tatsuro Sakata Masaharu Ando Yasuhiro Makino Shuji Matsumura Hiroki Takayama Hiroyuki Seki Shintarou Nanba Yuki Moritou Tetsuya Yasunaka Hideki Ohnishi Akinobu Takaki Kazuhiro Nouso Yoshiaki Iwasaki Kazuhide Yamamoto Department of Gastroenterology and Hepatology Okayama University Graduate School of Medicine Dentistry and Pharma- ceutical Sciences Department of Molecular Hepatology Okayama University Graduate School of Medicine Dentistry and Pharma- ceutical Sciences Department of Internal Medicine Okayama Saiseikai General Hospital Department of Internal Medicine Hiroshima City Hospital Department of Internal Medicine Kagawa Prefectural Central Hospital Department of Internal Medicine Kurashiki Central Hospital Department of Internal Medicine Mihara Red Cross hospital Department of Internal Medicine Fukuyama City Hospital Department of Internal Medicine National Hospital Organization Fukuyama Clinical Center Department of Internal Medicine Mitoyo General Hospital Department of Gastroenterology National Hospital Organization Iwakuni Clinical Center Department of Internal Medicine Sumitomo Besshi Hospital Department of Gastroenterology Tsuyama Central Hospital Health Service Center Okayama University

AIM: To investigate factors that accurately predict hepatocellular carcinoma(HCC) development after antiviral therapy in chronic hepatitis C(CHC) patients. METHODS: CHC patients who received pegylated interferon and ribavirin were enrolled in this cohort study that investigated the ability of alpha-fetoprotein(AFP) to predict HCC development after interferon(IFN) therapy. RESULTS: Of 1255 patients enrolled, 665 developed sustained virological response(SVR) during mean follow-up period of 5.4 years. HCC was occurred in 89 patients, and 20 SVR patients were included. Proportional hazard models showed that HCC occurred in SVR patients showing AFP ≥ 5 ng/m L before therapy and in non-SVR patients showing AFP ≥ 5 ng/m L before and 1 year after therapy besides older age, and low platelet counts. SVR patients showing AFP ≥ 5 ng/m L before therapy and no decrease in AFP to < 5 ng/m L 1 year after therapy had significantly higher HCC incidence than non-SVR patients showing AFP ≥ 5 ng/m L before therapy and decreased AFP(P = 0.043). AFP ≥ 5 ng/m L before therapy was significantly associated with low platelet counts and high values of alanine aminotransferase(ALT) in stepwise logistic regression analysis. After age, gender, platelet count, and ALT was matched by propensity score, significantly lower HCC incidence was shown in SVR patients showing AFP < 5 ng/m L before therapy than in those showing AFP ≥ 5 ng/m ***: The criteria of AFP < 5 ng/m L before and 1 year after IFN therapy is a benefical predictor for HCC development in CHC patients.

关键词： Hepatitis C virus Interferon Hepatocellular carcin

Optimal surveillance program for hepatocellular carcinoma- getting ready, but not yet

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World Journal of Hepatology 2015年第18期7卷 2133-2135页

作者： Grace Lai-Hung Wong Department of Medicine and Thera- peutics 9/F Prince of Wales Hospital the Chinese University of Hong Kong Institute of Digestive Disease the Chinese University of Hong Kong State Key Laboratory of Digestive Disease the Chinese University of Hong Kong

Hepatocellular carcinoma(HCC) secondary to chronic viral hepatitis is a major health problem in AsianPacific regions due to the endemics of chronic hepatitis B and C virus infection. HCC surveillance has been recommended to patients who are at risk to develop HCC. Unfortunately, a significant proportion of patients still died in long run due to tumor recurrence. The key components of an optimal surveillance program include an accurate tumor biomarker and optimal surveillance interval. Serum alpha-fetoprotein(AFP), despite of being the most widely used biomarker for HCC surveillance, it was criticized as neither sensitive nor specific. Other HCC biomarkers, including lectin-reactive AFP(AFP-L3), des-gamma carboxyprothrombin, are still under investigations. Recent study showed cancerassociated genome-wide hypomethylation and copy number aberrations by plasma DNA bisulfite sequencing to be accurate with both sensitivity and specificity close to 90% in detecting HCC in a case-control study. Concerning the optimal surveillance interval, we believe one size does not fit all patients. Accurate risk prediction to assist prognostication with well-validated HCC risk scores would be useful to decide the need for HCC surveillance. These key components of an optimal HCC surveillance program should be further validated at a surveillance setting.

关键词： Antiviral therapy Biomarkers Hepatocellular carcin

Pathogenesis of hepatocarcinogenesis in non-cirrhotic nonalcoholic fatty liver disease:Potential mechanistic pathways

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World Journal of Hepatology 2015年第22期7卷 2384-2388页

作者： Ryan B Perumpail Andy Liu Robert J Wong Aijaz Ahmed Stephen A Harrison Division of Gastroenterology and Hepatology Liver Transplant ProgramStanford University School of Medicine Albert Einstein College of Medicine Division of Gastroenterology and Hepatology Alameda Health SystemHighland Hospital Campus Division of Gastroenterology San Antonio Military Medical Center

Although hepatocellular carcinoma(HCC) primarily arises in the background of liver cirrhosis,the development of HCC in nonalcoholic fatty liver disease(NAFLD) without cirrhosis is increasingly recognized. The pathogenesis of NAFLD associated non-cirrhotic HCC is distinct from that of cirrhotic HCC because the metabolic syndrome(MS) along with obesity and insulin resistance(IR) underlie several unique mechanisms that promote tumorigenesis. IR associated with MS,NAFLD,and type 2 diabetes mellitus lead to the release of multiple pro-inflammatory cytokines,including tumor necrosis factor alpha,interleukin-6,leptin and resistin,as well as decreased amounts of adiponectin. These processes favor the development of hepatic steatosis and inflammation within the liver,which precede HCC development. Nevertheless,further investigation is necessary to elucidate the determinants for development of HCC in patients with NAFLD in the absence of cirrhosis.

关键词： Nonalcoholic steatohepatitis Hepatocellular carcin

Gastrointestinal neuroendocrine tumors treated with high dose octreotide-LAR:A systematic literature review

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World Journal of Gastroenterology 2015年第6期21卷 1945-1955页

作者： Michael S Broder David Beenhouwer Jonathan R Strosberg Maureen P Neary Dasha Cherepanov Partnership for Health Analytic Research LLC Beverly Hills H. Lee Moffitt Cancer Center and Research Institute Novartis Pharmaceuticals Corporation

AIM:To review literature on efficacy and safety of octreotide-long-acting repeatable(LAR)used at doses higher than the Food and Drug Administration(FDA)-approved 30 mg/mo for treatment of neuroendocrine tumors(NETs).METHODS:We searched Pub Med and Cochrane Library from 1998-2012,5 conferences(American Society of Clinical Oncology,Endocrine Society,European Neuroendocrine Tumor Society,European Society for Medical Oncology,North American Neuroendocrine Tumor Society)from 2000-2013 using Me SH and keyterms including neuroendocrine tumors,carcinoid tumor,carcinoma,neuroendocrine,and *** of accepted articles were also *** reviewers reviewed titles,abstracts,and full-length *** that reported data on efficacy and safety of≥30 mg/mo octreotide-LAR for NETs in human subjects,published in any language were included in the ***:The search identified 1086 publications,of which 238 underwent full-text review(20 were translated into English);17 were included in the *** varied in designs,subjects,octreotide-LAR regimens,and definition of *** studies reported use of higher doses to control symptoms and tumor progression,although symptom severity and formal quality-of-life analysis were not quantitatively *** studies reported efficacy,describing 260 subjects with doses ranging from 40 mg/mo or 30 mg/3 wk up to 120 mg/*** studies reported expert clinical opinion that supported dose escalation of octreotide-LAR up to 60 mg/mo for symptom control and suggested increased doses may be effective at preventing tumor *** studies reported safety;there was no evidence of increased toxicity associated with doses of octreotide-LAR>30 mg/***:As reported in this review,octreotide-LAR at doses>30 mg/mo is being prescribed for symptom and tumor control in NET ***,expert clinical opinion provided support for escalation of somatostatin analogs for refractory hormonal sy

关键词： carcinoma Neuroendocrine carcinoid syndrome carcin

A plant sesquiterpene lactone and its derivative reduce cutaneous side effect of vemurafenib,a BRAF inhibitor drug to treat late stage melanoma

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中国药理学与毒理学杂志 2015年第S1期29卷 90-91页

作者： Meng-ting CHANG Jia-hua FENG Kyoko NAKAGAWA-GOTO Kuo-Hsiung LEE Lie-Fen SHYUR Agricultural Biotechnology Research Center Academia Sinica Chinese Taipei 115 Institute of Plant Biology College of Life Science National Taiwan University Chinese Taipei 106 College of Medical Pharmaceutical and Health Sciences Kanazawa University Kakuma-machi Kanazawa 920-1192 Japan Natural Products Research Laboratories Eshelamn School of Phamacy University of North Carclina Chape Hill North Carolina 27599 USA

OBJECTIVE To investigate the pharmacological effect of a plant sesquiterpene lactone(designated D)and its semi-organically synthesized novel derivative(designated S)and the role of lipid mediators,viz.,oxylipins in attenuating vemurafenib-induced cutaneous side *** A DMBA/TPAinduced skin carcinogenesis mouse model mimicking cutaneous side effect caused by vemurafenib was established to evaluate the efficacy of compound D and S in reversal of vemurafenib side *** oxylipin metabolomics platform using UPLC-TQD mass spectrometry coupled with partial least squares-discriminant analysis(PLS-DA)analysis,cell-based assays,and immunochemistry analysis were performed to elucidate the mechanism insights of DET and S compounds and the role of specific oxylipins in skin cancer *** Vemurafenib treatment expedited the skin papillomas formation in DMBA-TPA treated mouse from week 6 to week *** D and S compounds could suppress the vemurafenib side effect and also decrease total papillomas numbers(55% to 72%)and average sizes(66% to 89%).Oxylipins metabolome analysis shows that specific arachidonic acid metabolites may play a role in vemurafenib-induced squamous cell carcinoma or keratoacanthomas formation in mouse skin that can be deregulated by D or S compound ***,S compound can inhibit vemurafenib-induced paradoxical activation of MAP kinases in mouse skin or in NRAS mutant melanoma *** Our results indicate that plant sesquiterpene lactone D and its novel analog can reduce cutaneous side effect of vemurafenib through novel modes of action by inhibiting paradoxical activation of MAP kinases and de-regulating pro-inflammation mediators COX-2 and specific ecosanoid-type of *** study may suggest a novel adjuvant therapy approach in treatment of BRAFV600 Emutant melanoma.

关键词： vemurafenib sesquiterpene lactone two-stage carcin