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Hepatocellular Carcinoma: Current Management

CURRENT PROBLEMS IN SURGERY 2010年第1期47卷 10-67页

作者： Cha, Charles H. Saif, M. Wasif Yamane, Brett H. Weber, Sharon M. Yale Univ Sch Med Dept Surg New Haven CT USA Yale Univ Sch Med Dept Med Yale Canc CtrGI Canc Program New Haven CT USA Univ Wisconsin Madison WI USA

The age-adjusted incidence of hepatocellular carcinoma (HCC) has tripled in the United States over the past 2 decades, fueled by the dramatic increase of hepatitis C during that same time period. Currently, there are an estimated 3 million people with chronic hepatitis C and 1.2 million with chronic hepatitis B in the United States. These patients are estimated to develop HCC at a rate of 0.5% to 5% per year.1 The incidence of HCC in the United States still lags behind many parts of the world where hepatitis B is endemic, such as China, Southeast Asia, and southern Africa. Worldwide, HCC is the third most common cause of cancer death and there are an estimated 1 million cases worldwide. The median survival in unresectable cases is less than 4 months and under a year for untreated patients with less advanced ***, the long-term survival rates from HCC in the United States have doubled over the past 2 decades, and a part of this increase is likely due to advances in surgical therapy for HCC, particularly as cancers are being detected earlier and therefore are still localized.8 Both surgical resection and transplantation are highly effective in the treatment of patients with localized HCC. Typically these surgical modalities complement each other, as patients with preserved liver function are candidates for resection and those with poor underlying liver function would be directed toward transplantation. However, their relative roles in the treatment of HCC have generated quite a bit of debate. Ultimately, as the multitude of treatment modalities proliferate, HCC must be treated in a multidisci-plinary fashion, involving hepatologists, oncologists, surgeons, radiologists, and pathologists, to come up with the best treatment plan for any individual patient.

关键词： United States treatment planning Transplantation ectomy Hepatitis B human-centered computing Hepatitis C liver function

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Dynamic changes of the inflammation-based index predict mortality following chemoembolisation for hepatocellular carcinoma: a prospective study

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ALIMENTARY PHARMACOLOGY & THERAPEUTICS 2014年第11-12期40卷 1270-1281页

作者： Pinato, D. J. Karamanakos, G. Arizumi, T. Adjogatse, D. Kim, Y. W. Stebbing, J. Kudo, M. Jang, J. W. Sharma, R. Univ London Imperial Coll Sci Technol & Med Hammersmith Hosp Div Expt Med London W12 0HS England Kinki Univ Sch Med Dept Gastroenterol & Hepatol Osaka 589 Japan Univ London Imperial Coll Sci Technol & Med Hammersmith Hosp Dept Oncol London W12 0HS England Catholic Univ Korea Incheon St Marys Hosp Dept Internal Med Seoul South Korea

BackgroundTransarterial chemoembolisation (TACE) is a standard treatment for unresectable, intermediate stage hepatocellular carcinoma (HCC). Survival after TACE, however, can be highly variable, with no suitable biomarker predicting therapeutic outcome. The inflammation-based index (IBI) has previously been shown to independently predict overall survival (OS) in all stages of HCC. AimTo explore the prognostic ability of IBI as a predictor of survival after TACE. MethodsBaseline staging, biochemical and clinicopathological features including IBI were studied in a derivation set of 64 patients undergoing TACE for intermediate stage HCC. Dynamic changes in IBI before and after TACE were studied as predictors of survival using both a univariate and multivariate Cox regression model and further validated in two independent patient cohorts from Korea (n=76) and Japan (n=577). ResultsPre-treatment IBI predicted for OS in the derivation set (P=0.001). Other univariate predictors of OS included radiological response to TACE (P<0.001), pre-TACE CLIP score (P<0.01), tumour diameter >5cm (P=0.05) and AFP 400 (P<0.001). Normalisation of IBI post-TACE was associated with radiological response by mRECIST criteria and improved OS (P<0.001). Normalisation of IBI remained a significant multivariate predictor of OS in both the derivation and validation sets (P<0.001). ConclusionsNormalisation of IBI after TACE is shown to be an independent predictor of survival and may be integrated into the retreatment criteria for repeat TACE in intermediate stage HCC. IBI and its dynamic changes after treatment are validated as a biomarker allowing the stratification of patients with a significant survival advantage following initial TACE.

关键词： Prospective Studies Hepatocellular Cancer Mortality chemoembolization human-centered computing

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Segment-oriented hepatic resection in the management of malignant neoplasms of the liver

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JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS 1998年第5期187卷 471-481页

作者： Billingsley, KG Jarnagin, WR Fong, Y Blumgart, LH Mem Sloan Kettering Canc Ctr Dept Surg Hepatobiliary Serv New York NY 10021 USA

Background: Improvements in the understanding of intrahepatic anatomy and radiographic technology have facilitated a segment-oriented approach to ii-ver resection. This approach involves the resection of isolated anatomic segments or sectors of the liver as dictated by the extent of the;intrahepatic pathology. Segment-oriented resection allows maximal conservation of normal liver parenchyma while clearing tumor. This report describes the technical features and the results of a prospective evaluation of segmental and sectoral resections in the treatment of malignant hepatic neoplasms. Study Design: Patients with malignant hepatic neoplasms that were treated with a segment-oriented hepatic resection were identified from a prospective clinical data base. After undergoing segment-oriented liver resection, the patients were followed at regular intervals. Recurrent disease was the end point of the study. Followup is reported at a median of 12 months. This review outlines the technique of resection, intraoperative events, operating time, blood loss, and the ability to obtain negative resection margins. Results: During the 5-year period between July 1992 and July 1997, 400 patients underwent liver resection for metastatic neoplasms and hepatocellular carcinoma (HCC). During this period, 79 patients (20%) were treated with a segment-oriented resection. These patients represent the study group for this report. The overall mortality rate was 2.5%;all postoperative deaths occurred in patients with HCC and cirrhosis. Overall morbidity was 26%, The median hospital stay was 8 days. Mean transfusion requirements were 1.0 +/- 0.3 U of packed red blood cells. Patients with HCC showed a greater transfusion requirement than did patients without HCC: 2.7 +/- 1.2 U versus 0.6 +/- 0.2 U (p < 0.05). Of the patients without HCC, 17% required transfusion. During the 12-month median followup period, the overall disease recurrence rate was 23%. Disease recurred at the hepatic-resection margin

关键词： Hepatectomy Liver Neoplasms 肝切除术肝肿瘤 End Point Malignancy ectomy Mortality Hepatectomy liver parenchyma Liver Liver Neoplasms human-centered computing Patients technical features

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The combination of sorafenib with transarterial chemoembolisation for hepatocellular carcinoma

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ALIMENTARY PHARMACOLOGY & THERAPEUTICS 2011年第2期34卷 205-213页

作者： Cabrera, R. Pannu, D. S. Caridi, J. Firpi, R. J. Soldevila-Pico, C. Morelli, G. Clark, V. Suman, A. George, T. J., Jr. Nelson, D. R. Univ Florida Dept Med Div Gastroenterol Hepatol & Nutr Sect Hepatobiliary Dis Gainesville FL 32610 USA Univ Florida Dept Med Div Internal Med Gainesville FL 32610 USA Univ Florida Dept Radiol Div Intervent Radiol Gainesville FL 32610 USA Univ Florida Dept Med Div Oncol Gainesville FL 32610 USA

Background Standard of practice involves using transarterial therapy for multifocal hepatocellular carcinoma (HCC) alone and sorafenib only for more advanced HCC, but the sorafenib and transarterial therapy combination may provide greater efficacy. Aim To evaluate the safety and efficacy of concurrent sorafenib and transarterial therapy in HCC. Methods Consecutive cases of HCC were treated with sorafenib and transarterial therapy, receiving sorafenib 2 to 4 weeks before transarterial therapy. Baseline clinical parameters, adverse events (AEs) and survival were collected. Results A total of 47 patients received sorafenib and transarterial therapy. The majority of the patients were male (70%) with HCV (60%), median age of 60 years, good performance status (0-1), stable cirrhosis (Child: A 72%;B 28%), unresectable tumour (stage: B 81%;C 19%) and median AFP of 24 ng/mL. Median follow-up was 12 months and median time on sorafenib was 6 months. LC Bead TACE was used with a median frequency of 3. The majority of the patients (89%) experienced AEs. The most common AEs were fatigue (51%), hand-foot skin reaction (51%) and diarrhoea (43%). Grade 3 and 4 AEs included fatigue (13%) and hand-foot skin reaction (26%). Most patients required a dose reduction (66%). The main AE related to transarterial therapy was post-TACE syndrome (23%). The disease control rate was 68% at 6 months. Overall median survival rate was 18.5 months (95% CI 16.1-20.9 months). Conclusion Concurrent sorafenib and transarterial therapy is overall safe with no unexpected side effects and encouraging efficacy that warrants further study.

关键词： sorafenib Medicine Side Effect Hepatocellular Cancer Median human-centered computing

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Prognostic significance of preoperative prognostic nutritional index in hepatocellular carcinoma: a meta-analysis

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HPB 2018年第10期20卷 888-895页

作者： Man, Zhongran Pang, Qing Zhou, Lei Wang, Yong Hu, Xiaosi Yang, Song Jin, Hao Liu, Huichun Bengbu Med Coll Affiliated Hosp 1 Dept Hepatobiliary Surg 287 Changhuai Rd Bengbu 233000 Anhui Peoples R China

Background: To date, epidemiological evidence of the association between preoperative prognostic nutritional index (PNI) and the prognosis of hepatocellular carcinoma (HCC) remains controversial. Methods: A literature search was performed in the databases of PubMed, Embase, and Web of Science. Hazard ratio (HR), odds ratio (OR), and 95% confidence interval (CI) were extracted to estimate the association of preoperative PNI with overall survival (OS), disease-free survival (DFS), and postoperative recurrence of HCC, respectively. A random-effects model was used to calculate the pooled effect size. Results: Thirteen studies with a total of 3,738 patients with HCC met inclusion criteria for this metaanalysis. It indicated that a lower level of preoperative PNI was a significant predictor of worse OS (HR = 1.82, 95% CI: 1.44-2.31) and DFS (HR = 1.49, 95% CI: 1.06-2.07). In addition, risk of postoperative recurrence was significantly higher in patients with a lower preoperative PNI (OR = 1.92, 95% CI: 1.33-2.76). Subgroup analysis based on therapeutic intent demonstrated a significant positive association between preoperative low PNI and worse OS for those patients undergoing surgical resection and for those undergoing TACE or non-surgical treatment. Conclusion: The current meta-analysis demonstrates that preoperative PNI is a prognostic marker in HCC.

关键词： Meta-Analysis Heart Rate SERPINE2 gene Confidence intervals Positive Association human-centered computing osmium Association (Psychology) ectomy

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Allosteric MEK1/2 Inhibitor Refametinib (BAY 86-9766) in Combination with Sorafenib Exhibits Antitumor Activity in Preclinical Murine and Rat Models of Hepatocellular Carcinoma

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NEOPLASIA 2013年第10期15卷 1147-1157页

作者： Schmieder, Roberta Puehler, Florian Neuhaus, Roland Kissel, Maria Adjei, Alex A. Miner, Jeffrey N. Mumberg, Dominik Ziegelbauer, Karl Scholz, Arne Bayer HealthCare Global Drug Discovery Berlin Germany Roswell Pk Canc Inst Buffalo NY 14263 USA Ardea Biosci Inc San Diego CA USA

OBJECTIVE: The objectives of the study were to evaluate the allosteric mitogen-activated protein kinase kinase (MEK) inhibitor BAY 86-9766 in monotherapy and in combination with sorafenib in orthotopic and subcutaneous hepatocellular carcinoma (HCC) models with different underlying etiologies in two species. DESIGN: Antiproliferative potential of BAY 86-9766 and synergistic effects with sorafenib were studied in several HCC cell lines. Relevant pathway signaling was studied in MH3924a cells. For in vivo testing, the HCC cells were implanted subcutaneously or orthotopically. Survival and mode of action (MoA) were analyzed. RESULTS: BAY 86-9766 exhibited potent antiproliferative activity in HCC cell lines with half-maximal inhibitory concentration values ranging from 33 to 762 nM. BAY 86-9766 was strongly synergistic with sorafenib in suppressing tumor cell proliferation and inhibiting phosphorylation of the extracellular signal-regulated kinase (ERK). BAY 86-9766 prolonged survival in Hep3B xenografts, murine Hepa129 allografts, and MH3924A rat allografts. Additionally, tumor growth, ascites formation, and serum alpha-fetoprotein levels were reduced. Synergistic effects in combination with sorafenib were shown in Huh-7, Hep3B xenografts, and MH3924A allografts. On the signaling pathway level, the combination of BAY 86-9766 and sorafenib led to inhibition of the upregulatory feedback loop toward MEK phosphorylation observed after BAY 86-9766 monotreatment. With regard to the underlying MoA, inhibition of ERK phosphorylation, tumor cell proliferation, and microvessel density was observed in vivo. CONCLUSION: BAY 86-9766 shows potent single-agent antitumor activity and acts synergistically in combination with sorafenib in preclinical HCC models. These results support the ongoing clinical development of BAY 86-9766 and sorafenib in advanced HCC.

关键词： Hepatocellular Cancer bays sorafenib Synergism human-centered computing Cell Line

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Safety of Liver Resection for Hepatocellular Carcinoma After Sorafenib Therapy: A Multicenter Case-Matched Study

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ANNALS OF SURGICAL ONCOLOGY 2013年第11期20卷 3603-3609页

作者： Barbier, Louise Fuks, David Pessaux, Patrick Muscari, Fabrice Le Treut, Yves-Patrice Faivre, Sandrine Belghiti, Jacques Beaujon Hosp Dept HPB Surg Clichy France Hautepierre Hosp Dept HPB Surg Strasbourg France Hop Rangueil Dept HPB Surg Toulouse France La Concept Hosp Dept HPB Surg Marseille France Beaujon Hosp Dept Oncol Clichy France

Liver resection can be considered in some hepatocellular carcinoma (HCC) patients who received sorafenib. The lack of clinical data about safety of resection after sorafenib treatment led us to assess its potential impact on perioperative course in a multicentric study. From 2008 to 2011, a total of 23 HCC patients who underwent liver resection after treatment with sorafenib (sorafenib group) were compared with 46 HCC patients (control group) matched for age, gender, underlying liver disease, tumor characteristics and type of resection. Patients received sorafenib for a median duration of 1 (range 0.2-11) months and drug was interrupted at least 7 days before surgery. End points were intraoperative (operative time, vascular clamping, blood loss and transfusion), and postoperative outcomes focusing on recovery of liver function. In the sorafenib group, HCC was developed on F4 cirrhosis in 48 % and the rate of major resection was 44 %. Surgical procedure duration (280 vs. 240 min), transfusion rate (26 vs. 15 %), blood loss (400 vs. 300 mL) and vascular clamping (70 vs. 74 %) were similar in the two groups. Mortality was zero in the sorafenib group and one (2.1 %) in the control group (p = 1.000). The incidence of postoperative complications was 44 % in the sorafenib group and 59 % in the control group (p = 0.307). Recovery of liver function was similar in the two groups in terms of prothrombin time (90 vs. 81 %, p = 0.429) and bilirubin level (16 vs. 24 mu mol/L, p = 102) at postoperative day 5. No adverse effect of preoperative administration of sorafenib was observed during and immediately after liver resection for HCC.

关键词： Hepatocellular Cancer ectomy Hemorrhage sorafenib Hepatectomy Blood Transfusion human-centered computing liver function bilirubin measurement

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Effects of Metallothionein-1 Genetic Polymorphism and Cigarette Smoking on the Development of Hepatocellular Carcinoma

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ANNALS OF SURGICAL ONCOLOGY 2013年第6期20卷 2088-2095页

作者： Wong, Ruey-Hong Huang, Chun-Huang Yeh, Chao-Bin Lee, Hong-Shen Chien, Ming-Hsien Yang, Shun-Fa Chung Shan Med Univ Dept Publ Hlth Taichung Taiwan Chung Shan Med Univ Hosp Dept Family & Community Med Taichung Taiwan Chung Shan Med Univ Inst Med Taichung Taiwan Chung Shan Med Univ Sch Med Dept Emergency Med Taichung Taiwan Chung Shan Med Univ Hosp Dept Emergency Med Taichung Taiwan Taipei Med Univ Wan Fang Hosp Taipei Taiwan Taipei Med Univ Coll Med Grad Inst Clin Med Taipei Taiwan Chung Shan Med Univ Hosp Dept Med Res Taichung Taiwan

A low expression of metallothionein (MT) has been observed in liver cancer. Such a phenomenon might be influenced by oxidative stress, thus resulting in the cells being more susceptible to DNA damage and apoptotic death. In particular, oxidative stress induced by cigarette smoking might affect MT-1 expression. We designed a hospital-based case-control study to evaluate the effects of MT-1 genotypes and smoking on hepatocellular carcinoma (HCC) occurrence. A total of 102 HCC patients and 191 matched healthy control subjects were recruited, and epidemiological information was collected. Six genotypes of MT-1 were determined with TaqMan single-nucleotide polymorphism genotyping assays. Individuals possessing MT-1 rs8052394 A, rs964372 G, and rs8052334 T alleles as well as engaging in cigarette smoking had increased risks of HCC;these alleles also had higher linkage disequilibrium. Carriers with MT-1 rs8052394, rs964372, and rs8052334 A-G-T haplotype had a 2.25-fold (95 % confidence interval [CI] 1.46-3.26) risk for HCC development than the control group (A-C-T, the most common haplotype). Compared to nonsmokers with other haplotypes (A-C-T, G-G-C, A-G-C, G-G-T, G-C-T, and G-C-C), nonsmokers with A-G-T haplotype had a 1.93-fold (95 % CI 1.01-3.71) increased risk, and smokers with other haplotypes had a 3.66-fold (95 % CI 1.78-7.54) increased risk, whereas smokers carrying the A-G-T haplotype had the highest risk (matched relative risk 6.72;95 % CI 2.86-15.79) of developing HCC. The MT-1 A-G-T haplotypes are associated with increased risk of HCC, especially in those who smoke.

关键词： Cancer of Liver Hepatocellular Cancer Confidence intervals Cigarette Smoking Haplotypes human-centered computing Current smoker

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Gas chromatography/time-of-flight mass spectrometry-based metabonomics of hepatocarcinoma in rats with lung metastasis: elucidation of the metabolic characteristics of hepatocarcinoma at formation and metastasis

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RAPID COMMUNICATIONS IN MASS SPECTROMETRY 2010年第18期24卷 2765-2775页

作者： Li, Zong-Fang Wang, Juan Huang, Chen Zhang, Shu Yang, Jun Jiang, An Zhou, Rui Pan, Dun Xi An Jiao Tong Univ Sch Med Dept Gen Surg Affiliated Hosp 2 Xian 710004 Shaanxi Prov Peoples R China Xi An Jiao Tong Univ Sch Med Lab Environm & Genes Related Dis Educ Minist Xian 710061 Peoples R China Xi An Jiao Tong Univ Sch Med Affiliated Hosp 2 Dept Pathol Xian 710004 Peoples R China

Hepatocarcinoma (HCC) has a very high mortality rate and the high recurrence and metastasis rates contribute to the poor prognosis of HCC patients. To understand HCC formation and metastasis, we assessed the metabonomics of rat HCC and HCC with lung metastasis (HLM). The HLM rat model was established by exposure to diethylnitrosamine (DEN). Levels of serum and urine metabolites were quantified with gas chromatography/time-of-flight mass spectrometry (GC/TOFMS), and data were analyzed with partial least-squares discrimination analysis (PLS-DA). Serum and urine levels of some metabolites differed significantly between the control, HCC, and HLM groups. The products and intermediates from glycolysis and glutamate metabolism were elevated, while the tricarboxylic acid (TCA) cycle was inhibited, in both HCC and HLM. HLM samples revealed enhanced metabolism of nucleic acids, amino acids and glucuronic acid. PLS-DA indicated that principal component weighting was greatest for serum serine, phenylalanine, lactic acid, tyrosine and glucuronic acid, and urine glycine, serine, 5-oxyproline, malate, hippuric acid and uric acid. These data provide novel information that will improve understanding of the pathophysiological processes involved in HCC and HLM, and revealed potential metabolic markers for HCC invasion and metastasis. Copyright (c) 2010 John Wiley & Sons, Ltd.

关键词： Metabolomics lung metastasis Hepatocellular Cancer Glucuronic Acids Mortality Mass spectroscopy human-centered computing metastasis Rats

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An independent shopping experience for wheelchair users through augmented reality and RFID

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ASSISTIVE TECHNOLOGY 2019年第1期31卷 9-18页

作者： Rashid, Zulqarnain Pous, Rafael Norrie, Christopher S. Univ Dundee Sch Sci & Engn Dundee DD1 4HN Scotland Univ Pompeu Fabra Barcelona Dept Informat & Commun Technol Barcelona Spain

People with physical and mobility impairments continue to struggle to attain independence in the performance of routine activities and tasks. For example, browsing in a store and interacting with products located beyond an arm's length may be impossible without the enabling intervention of a human assistant. This research article describes a study undertaken to design, develop, and evaluate potential interaction methods for motor-impaired individuals, specifically those who use wheelchairs. Our study includes a user-centered approach, and a categorization of wheelchair users based upon the severity of their disability and their individual needs. We designed and developed access solutions that utilize radio frequency identification (RFID), augmented reality (AR), and touchscreen technologies in order to help people who use wheelchairs to carry out certain tasks autonomously. In this way, they have been empowered to go shopping independently, free from reliance upon the assistance of others. A total of 18 wheelchair users participated in the completed study.

关键词： accessibility augmented reality (AR) human-centered computing radio frequency identification (RFID) wheelchair users

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