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Cirrhosis and pre-neoplastic lesions

ABDOMINAL IMAGING 2012年第2期37卷 188-214页

作者： Grazioli, Luigi Olivetti, Lucio Orlando, Emanuela Spedali Civili Brescia Dipartimento Diagnost Immagini I-25100 Brescia Italy Ist Ospitalieri Cremona UO Radiol Dipartimento Lab Diagnost Immagini & Alte Tecnol I-26100 Cremona Italy

Cirrhotic livers are characterized by irreversible remodeling of architecture with bridging fibrosis, vascular reorganization and formation of hepatocellular nodules, which are classified histologically as either regenerative or dysplastic lesions. The differentiation of these lesions is important because regenerative nodules (RNs) are benign, whereas dysplastic nodules (DNs) are premalig-nant. Pathologically, hepatocarcinoma (HCC) develops in a multistep fashion in the following sequence: from low-grade dysplastic nodule (LGDN) to high-grade dysplastic nodule (HGDN), small HCC and, finally, large HCC. Differentiation between DN and early HCC is the most important issue in the clinical *** article reviews the current concepts regarding the multistep process of hepatocarcinogenesis, along with the associated histologic and MRI manifestations.

关键词： Bridging fibrosis Lesions Hepatocarcinogenesis Dysplastic human-centered computing dwarf novae Regenerative

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Comparative Assessment of the Safety and Effectiveness of Radiofrequency Ablation Among Elderly Medicare Beneficiaries with Hepatocellular Carcinoma

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ANNALS OF SURGICAL ONCOLOGY 2012年第4期19卷 1058-1065页

作者： Massarweh, Nader N. Park, James O. Yeung, Raymond S. W. Flum, David R. Univ Washington Dept Surg Seattle WA 98195 USA Univ Washington Dept Hlth Serv Seattle WA 98195 USA Univ Washington Surg Outcomes Res Ctr Seattle WA 98195 USA

Background. Radiofrequency ablation (RFA) use among patients with hepatocellular carcinoma (HCC) has increased dramatically over the last decade, but assessments outside specialized centers are lacking. This population-based study was intended to evaluate the safety and effectiveness of RFA when used to treat HCC. Methods. A cohort study of HCC patients (diagnosed 2002-2005) was performed using linked Surveillance, Epidemiology, and End Results (SEER)-Medicare data. Early (<= 90-day) mortality and readmission as well as survival among patients undergoing RFA, resection, or no treatment were compared using multivariate and propensity score adjusted Poisson and Cox regression models. Results. Of 2631 patients (mean age 76.1 +/- 6.1 years, 65.9% male), 16% underwent RFA (49.6%) or resection (50.4%). Early mortality (13.6 vs. 18.7%, P = .16) and readmission (34.5 vs. 32.1%, P = .60) rates were similar among RFA and resection patients. The 1-year survival after RFA and resection was similar (72.2 vs. 79.7%, P = .18), but beyond 3 years there was a survival benefit among patients undergoing resection (39.2 vs. 58.0%, P < .001). Patients treated with RFA as a sole therapeutic intervention in the 1st year had a similar hazard of death compared with untreated patients (hazard ratio [HR] 0.84, 95% confidence interval [95% CI] 0.54-1.33). Conclusions. In the general community, patients treated with RFA have a similar risk of early adverse events compared with those treated with resection with no clear survival benefit when used as a sole intervention. Although RFA has been described as a safe and effective treatment for HCC at specialized centers, this experience may not extrapolate to the general community and requires further evaluation.

关键词： Patients Hepatocellular Cancer RCRA FACILITY ASSESSMENT radiofrequency ablation human-centered computing ectomy

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Living donor liver transplantation versus deceased donor liver transplantation for hepatocellular carcinoma: A meta-analysis

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LIVER TRANSPLANTATION 2012年第10期18卷 1226-1236页

作者： Liang, Wenhua Wu, Linwei Ling, Xiaoting Schroder, Paul M. Ju, Weiqiang Wang, Dongping Shang, Yushu Kong, Yuan Guo, Zhiyong He, Xiaoshun Sun Yat Sen Univ Affiliated Hosp 1 Organ Transplant Ctr Guangzhou 510080 Guangdong Peoples R China Univ Toledo Coll Med Dept Med Microbiol & Immunol Toledo OH 43606 USA

Because of the severe organ shortage, living donor liver transplantation (LDLT) offers a timely alternative to deceased donor liver transplantation (DDLT) for patients with hepatocellular carcinoma (HCC). However, the higher recurrence rate of HCC after LDLT and the indication criteria remain controversial. By conducting a quantitative meta-analysis, we sought to compare the survival outcomes and recurrence rates with LDLT and DDLT for patients with HCC. Comparative studies of LDLT and DDLT for HCC, which were identified by a comprehensive literature search, were included in this study. The evaluated outcomes included patient survival, recurrence-free survival (RFS), and recurrence rates at defined time points. Seven studies with a total of 1310 participants were included in this study. For LDLT and DDLT recipients, we found comparable patient survival rates [1 year, odds ratio (OR) = 1.03, 95% confidence interval (CI) = 0.62-1.73;3 years, OR = 1.07, 95% CI = 0.77-1.48;and 5 years, OR = 0.64, 95% CI = 0.33-1.24] and RFS rates (1 year, OR = 0.86, 95% CI = 0.54-1.38;3 years, OR = 1.04, 95% CI = 0.69-1.58;and 5 years, OR = 1.11, 95% CI = 0.70-1.77). Moreover, we found no significant differences in the 1-, 3-, or 5-year recurrence rates between LDLT and DDLT recipients (1 year, OR = 1.55, 95% CI = 0.36-6.58;3 years, OR = 2.57, 95% CI = 0.53-12.41;and 5 years, OR = 1.21, 95% CI = 0.44-3.32). A subgroup analysis revealed similar outcomes for patients with HCC meeting the Milan criteria. These findings demonstrate that for HCC patients (especially those within the Milan criteria), LDLT represents an acceptable option that does not compromise patient survival or increase HCC recurrence in comparison with DDLT. Liver Transpl 18:1226-1236, 2012. (c) 2012 AASLD.

关键词： Patients Chlorine human-centered computing Repetition rate

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Can long term therapy with oral nucleos(t)ide analogs influence the prognosis of chronic hepatitis B-related complications?

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JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY 2012年第10期27卷 1541-1543页

作者： Ooi, Marie Teoh, Narci C. Canberra Hosp Gastroenterol & Hepatol Unit Garran ACT 2604 Australia Canberra Hosp Australian Natl Univ Med Sch Garran ACT 2604 Australia

The authors reflect on the study by Kim and colleagues which investigated patients with chronic hepatitis B virus (CHB) who were treated with second line nucleos(t)ide analogs or lamivudine. They mention the conclusion that the Child-Pugh scoring system was suboptimal at forecasting poorer survival in patients with HBV-liver cirrhosis. They note that the study contributes to the literature by stressing the oral antiviral agents' effectiveness in mitigating development of CHB complications.

关键词： Prognosis Newborn Infant Parturition Hepatitis B vaccination Hepatitis B human-centered computing Chronic Hepatitis Complication Long-term oxygen therapy birth

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Sorafenib Use in Hepatocellular Carcinoma in Japan: Early Experience and Impact on Clinical Practice

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CLINICAL DRUG INVESTIGATION 2012年第2-Sup期32卷 1-2页

作者： Zhu, Andrew X. Harvard Univ Massachusetts Gen Hosp Ctr Canc Sch Med Boston MA 02114 USA

Hepatocellular carcinoma (HCC) is the most common form of primary hepatic cancer in adults, and accounts for 95% of cancers of the liver in Japan.W The leading risk factors for liver cancer in Japan are hepatitis C and hepatitis B viral infections, with 80-90% of Japanese patients with river cancer having hepatitis C viral infection Japanese investigators have made many contributions to the screening, early diagnosis and treatment of HCC, and have greatly enriched our knowledge of strategies used in patients with this disease. Many key areas in HCC research including the pathological diagnosis, diagnostic imaging techniques, liver transplantation, segment resection, percutaneous local therapy, transarterial che-moembolization (TACE) and hepatic arterial infusion chemotherapy have been extensively studied in Japan and are now used worldwide.

关键词： field focus Cancer of Liver Japan local therapy human-centered computing Hepatitis C Hepatitis B

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Younger Age and Presence of Macrovascular Invasion Were Independent Significant Factors Associated With Poor Disease-Free Survival in Hepatocellular Carcinoma Patients Undergoing Living Donor Liver Transplantation

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TRANSPLANTATION PROCEEDINGS 2012年第2期44卷 516-519页

作者： Wai, C. -T. Woon, W. -A. Tan, Y. -M. Lee, K. -H. Tan, K. -C. Gleneagles Hosp Asian Ctr Liver Dis & Transplantat Singapore Singapore

Objective. Patients with hepatocellular carcinoma (HCC) exceeding the University of California, San Francisco (UCSF) criteria are normally rejected for cadaveric liver transplants. However, whether they should be allowed to undergo living donor liver transplantation (LDLT) has been controversial. We reviewed the outcome of patients with advanced HCC who underwent LDLT at our center. Methods. From April 2002 to May 2011, 176 patients underwent LDLT at our center;of these, 77 (44%) had HCC at the explant liver. Patient overall survival and recurrence-free survival (RFS) was analyzed using Kaplan-Meier method. Multivariate analysis was performed by Cox analysis. Results. Age was 56 +/- 1 (56, 29-71) years;62 (80.5%) were male;Model for End-stage Liver Disease Score was 11 +/- 1 (9, 6-36), alpha fetoprotein (AFP) was 3683 +/- 2019 (69, 3-139,591) ng/L;maximum tumor size was 4.5 (0.5-15) cm. Number or tumor nodules was 5 (1-10), and 32 (42%) had macrovascular invasion diagnosed pretransplant. Eleven (14%) were within UCSF criteria. After follow-up of 953 +/- 90 (744, 2-2989) days, 53 (69%) were alive and 48 (62%) were recurrence-free. One-, 3and 5-year overall survival (OS) and recurrence-free survival (RFS) were 80%, 70%, and 57% and 80%, 65%, and 48%, respectively. Five-year OS and RFS for those within UCSF criteria were both 78% versus 55% and 46% outside UCSF criteria (P = not significant). At multivariate analysis, high AFP, younger age, and macrovascular invasion were associated with both poor RFS. Conclusion. In HCC patients exceeding UCSF criteria, a reasonable 5-year overall survival of 55% post-LDLT can be obtained. Patients with HCC exceeding the UCSF criteria, especially in the older age group with no portal vein invasion and lower APP level, should be actively considered for LDLT.

关键词： overall survival Patients cell invasion Hepatocellular Cancer Disease-Free Survival human-centered computing Living Donors Liver Transplantation Portal Vein

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Hepatocellular carcinoma: Towards personalized medicine

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CANCER SCIENCE 2012年第5期103卷 846-850页

作者： Miki, Daiki Ochi, Hidenori Hayes, C. Nelson Aikata, Hiroshi Chayama, Kazuaki RIKEN Ctr Genom Med Lab Digest Dis Hiroshima Japan Hiroshima Univ Grad Sch Biomed Sci Programs Biomed Res Dept Med & Mol SciDiv Frontier Med Sci Hiroshima Japan

Over the past several years, the success of genome-wide association studies (GWAS) and pharmacogenomics has gradually begun to enable personalized medicine in some fields. In the field of liver diseases, host genetic factors are now very useful in clinical practice for predicting treatment outcome and adverse reactions for pegylated interferon plus ribavirin combination therapy against chronic hepatitis C virus (HCV) infection. Recently, three virus-related hepatocellular carcinoma (HCC) GWAS were reported from Asia. One study examined hepatitis B virus-related HCC in China, where hepatitis B is very prevalent, and the other two examined HCV-related HCC in Japan. We identified a common variant in the DEPDC5 locus associated with HCV-related HCC, and another group identified an association involving the MICA locus. In this review, we compare the results of these GWAS and earlier candidate gene studies. Further research is needed to determine the role of these single nucleotide polymorphisms on HCC risk, but identification of these markers could make it possible to assess the magnitude of the risk of cancer based on each patient's genetic background. Consideration of the genetic background of the patients will likely play a role in personalized medicine for HCC, and understanding the mechanism underlying the association could suggest novel promising therapeutic targets in the future. (Cancer Sci 2012;103: 846850)

关键词： Pharmacogenomics Genetic Background Genome-Wide Association Study Genetic factors Liver Diseases Precision Medicine DEPDC5 gene human-centered computing Treatment Outcome Combined Modality Therapy Association (Psychology) Hepatitis B

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c-Jun NH2-terminal kinase may predict hepatocellular carcinoma recurrence

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HEPATOLOGY RESEARCH 2012年第4期42卷 349-350页

作者： Maeda, Shin Yokohama City Univ Grad Sch Med Dept Gastroenterol Yokohama Kanagawa 232 Japan

Hepatocellular carcinoma (HCC) is one of the most common causes of cancer death worldwide, particularly in eastern Asia. HCC shows extremely frequent intrahe-patic recurrence after apparently successful curative treatments. Although factors for such recurrence have been investigated, it is still difficult to predict or to find predictive *** this issue, Hagiwawa et al. report the possible prediction of HCC recurrence by c-Jun NH_2-terminal kinase (JNK) activation in non-cancerous liver tissue. The JNKs (JNK1, 2, 3) belong to a family of mitogen-activated protein kinases (MAPK), together with extracellular-regulated kinases (ERK) and p38. JNKs are activated by stress signals and pro-inflammatory stimuli, and activated JNKs phosphorylate c-Jun, JunD, and other transcription factors that are involved in the formation of the AP-1 complex. In addition, JNKs phosphorylate other proteins that induce apoptosis, cell proliferation or transformation.

关键词： East Asia Transcription Factors MAPK8 gene Cause of Death PHOSPHONATION Transcription Factor AP-1 jun Oncogene liver tissue human-centered computing Relapse

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Potentially curative treatment in patients with hepatocellular cancer - results from the liver cancer research network

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ALIMENTARY PHARMACOLOGY & THERAPEUTICS 2012年第3期36卷 257-265页

作者： Kanwal, F. Befeler, A. Chari, R. S. Marrero, J. Kahn, J. Afdhal, N. Morgan, T. Roberts, L. Mohanty, S. R. Schwartz, J. VanThiel, D. Li, J. Zeringue, A. Di Bisceglie, A. John Cochran VA Med Ctr St Louis MO USA St Louis Univ Sch Med Div Gastroenterol & Hepatol St Louis MO USA Vanderbilt Univ Med Ctr Div Liver Transplantat & Hepatobiliary Surg Nashville TN USA Univ Michigan Div Gastroenterol & Hepatol Ann Arbor MI 48109 USA Univ So Calif Keck Sch Med Div Gastrointestinal & Liver Dis Los Angeles CA 90033 USA Beth Israel Deaconess Med Ctr Boston MA 02215 USA Harvard Univ Sch Med Boston MA USA Univ Calif Irvine Div Gastroenterol Irvine CA USA VA Long Beach Healthcare Syst Gastroenterol Serv Long Beach CA USA Mayo Clin Coll Med Div Gastroenterol & Hepatol Rochester MN USA Univ Chicago Gastroenterol Sect Chicago IL 60637 USA Univ Chicago Ctr Liver Dis Chicago IL 60637 USA Oregon Hlth & Sci Univ Portland OR 97201 USA Rush Univ Med Ctr Chicago IL 60612 USA

Background The extent to which potentially curative therapies are used in patients with hepatocellular cancer (HCC) and their related outcomes are unknown in the US. Aim To determine the rate and outcomes of potentially curative treatment in patients with HCC. Methods Eleven US centers followed patients with HCC between 2001 and 2007. We determined rates of liver transplantation, surgical resection, or tumour ablation during follow-up, examined differences in adjusted survival of patients receiving these treatments, and determined the factors associated with receipt of potentially curative treatment. Results Of the 267 patients, 76 (28%) patients had early HCC, defined as Child A or B cirrhosis, with a solitary HCC or <= 3 nodules, each <= 3 cm. Of these, 53 (69.7%) received curative treatment. Thirty six percent of patients with non-early HCC received curative treatment. Compared to patients with non-early HCC who did not receive curative treatment, patients with early HCC and curative treatment had the best survival [hazard ratio, HR = 0.19 (95% CI, 0.080.42)] followed by patients with advanced HCC who received curative treatment [HR = 0.37 (95% CI, 0.220.64)]. Baseline performance status was significantly associated with receipt of curative treatment as well as survival after adjusting for demographics, clinical characteristics, and HCC stage. Conclusions In this multicenter database, most of the patients with early HCC received potentially curative treatment. However, only 28% of patients had early HCC. One-third of patients with non-early HCC also underwent curative therapy. Potentially curative treatment improved survival and this effect was seen in patients with early as well as non-early HCC.

关键词： curative treatment patient treatment human-centered computing Patients

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Primary Versus Salvage Living Donor Liver Transplantation for Patients With Hepatocellular Carcinoma: Impact of Microvascular Invasion on Survival

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TRANSPLANTATION PROCEEDINGS 2012年第2期44卷 487-493页

作者： Moon, J. I. Kwon, C. H. D. Joh, J. W. Choi, G. S. Jung, G. O. Kim, J. M. Shin, M. Choi, S. J. Kim, S. J. Lee, S. -K. Sungkyunkwan Univ Sch Med Dept Surg Samsung Med Ctr Seoul 135710 South Korea Sungkyunkwan Univ Sch Med Dept Anesthesiol & Pain Med Samsung Med Ctr Seoul 135710 South Korea Soonchunhyang Univ Hosp Bucheon Dept Surg Puchon South Korea Konyang Univ Sch Med Konyang Univ Hosp Dept Surg Taejon South Korea

Objective. Salvage liver transplantation (LT) has been proposed for patients with a small hepatocellular carcinoma (HCC) and preserved liver function. Few reports have been issued on salvage LT in a living-donor (LD) LT setting. Therefore, we performed this study to evaluate differences in tumor invasiveness and other risk factors on survival after salvage versus primary LDLT. Methods. Between September 1996 and December 2008, 324 patients with HCC underwent LT. We excluded 138 patient from the analysis, leaving 186 HCC patients for analysis, including 17 (9.1%) who had undergone earlier resection, the salvage LDLT cohort. The other 169 patients underwent primary LDLT. Results. Intrahepatic metastasis, Edmonson-Steiner histologic grade, microscopic vascular invasion, and preoperative serum alpha-fetoprotein levels significantly influenced tumor recurrence. Microscopic vascular invasion, intrahepatic metastasis, Edmonson-Steiner histologic grade, and treatment by salvage LDLT were significantly associated with poor patient survival univariate analysis. However, only microscopic vascular invasion was significant on multivariate analysis. The treatment modality (primary or salvage LDLT) was not observed to affect overall or disease-free survival significantly on multivariate analysis. Disease-free survival was significantly better in the primary than in the salvage LDLT group. Furthermore, patients in the primary LDLT group tended to show better survival. However, when stratified by the presence or absence of microscopic vascular invasion, no significant group difference was found for overall or disease-free survival among those without versus with microscopic vascular invasion. Conclusions. Five-year overall survival after primary versus salvage LDLT were similar when differences in tumor pathologic features, such as microscopic vascular invasion, were taken into account. Multivariate analysis showed that the treatment itself was not a significant prognostic factor fo

关键词： Patients cell invasion Disease-Free Survival Survival human-centered computing Level Trigger Liver Transplantation Invasions

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