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Hepatocellular Carcinoma (hepatocellular + carcinoma)
Kinds of Hepatocellular Carcinoma Terms modified by Hepatocellular Carcinoma Selected AbstractsThe Impact of Interferon Gamma Receptor Expression on the Mechanism of Escape From Host Immune Surveillance in Hepatocellular CarcinomaHEPATOLOGY, Issue 3 2000Mitsuo Nagao M.D. Interferon gamma (IFN-,) plays an important role in host defense mechanism and participates in the progression of chronic liver disease. IFN-, exerts its pleiotrophic effects by transcriptional regulation of expression of numerous genes, such as major histocompatibility complex (MHC) class I and Fas, through interaction with IFN-, receptor (IFN-,-R). Although hepatocytes in normal liver express weak or no IFN-,-R, those in acute and chronic liver disease up-regulate its expression. A study using IFN-,-R ,-chain knock-out mice revealed the actions of IFN-, on tumor cells as an extrinsic tumor-suppressor mechanism. However, it is unclear whether or how hepatocellular carcinoma (HCC) blocks the signal transduction of IFN-, to evade host immune surveillance. We examined the expression of IFN-,-R and IFN-,,inducible genes in 44 cases with HCC using real-time reverse-transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry. In noncancerous liver tissues (n = 38), IFN-,-R expression on the cell surface was up-regulated in 27 cases. In IFN-,-R,negative cases (n = 15), tumor size was larger (P = .032), serum ,-fetoprotein (AFP) level was higher (P = .001), intrahepatic and extrahepatic metastasis was more common (P = .044 and .013, respectively), and Ki-67 labeling index (LI) was higher (P = .041), compared with IFN-,-R,positive cases. Accordingly, the evasion mechanism may play an important role in progression, especially metastasis, in HCC. The significant correlation between the status of IFN-,-R and the expression of Fas and MHC implies that the loss of IFN-,-R might contribute to the mechanism of escape from host immune rejection in HCC. [source] The committee for revision of the Clinical Practice Guidelines for Hepatocellular CarcinomaHEPATOLOGY RESEARCH, Issue 2010Article first published online: 19 MAY 2010 No abstract is available for this article. [source] AHPBA/SSO/SSAT Sponsored Consensus Conference on Multidisciplinary Treatment of Hepatocellular CarcinomaHPB, Issue 5 2010Elijah Dixon No abstract is available for this article. [source] Cerebral Embolism of Iodized Oil (Lipiodol) after Transcatheter Arterial Chemoembolization for Hepatocellular CarcinomaJOURNAL OF NEUROIMAGING, Issue 4 2009Joon-Tae Kim MD ABSTRACT Cerebral lipiodol embolism is a rare complication of transcatheter arterial chemoembolization (TACE). Its pathological mechanism remains ambiguous despite several investigations. In Case 1, a 67-year-old man with hepatocellular carcinoma (HCC) experienced neurological deficits soon after undergoing a fourth session of TACE. Computed tomography (CT) scan showed multiple hyperdense lesions along the gyrus of frontal lobes and in the subcortical white matter. Transcranial Doppler (TCD) and transesophageal echocardiogram performed during the intravenous injection of agitated saline documented the presence of a right-to-left shunt (RLS) by demonstrating microbubbles in the left middle cerebral artery and left atrium. In Case 2, a 63-year-old woman underwent a third TACE due to a large HCC. After the procedure, her mental status deteriorated. Brain CT showed multiple hyperdense lesions on the cerebral and cerebellar cortex. TCD with agitated saline showed multiple microembolic signals shortly after the injection of agitated saline. The risk of cerebral lipiodol embolism may increase with recurrence and progression of HCC in patients who have a pre-existing RLS in the heart or lung. A test for the detection of an RLS may be necessary to identify patients with a heightened risk of cerebral embolism when multiple TACE procedures are required. TACE for HCC can cause pulmonary embolism or infarction.1,2 However, cerebral lipiodol embolism is rare after TACE. There have been several reports of cerebral embolism after TACE, but their exact mechanism has not yet been fully elucidated. We report herein 2 patients who developed cerebral lipiodol embolism after undergoing multiple TACE procedures for remnant HCC through a pre-existing RLS. [source] Is hepatic transplantation justified for primary liver cancer?JOURNAL OF SURGICAL ONCOLOGY, Issue 8 2007FACS, Robert A. Fisher MD Abstract A concise, yet objective overview of Hepatocellular Carcinoma (HCC) treatment in 2006 with an intent to transplant is presented. The most significant variables impacting on the use of hepatic transplantation as therapy for primary liver cancer are developed under the headings of: Staging Criteria; Organ allocation; Transplant dropout minimization therapies; and Effects on the HCC general population. The pertinent medical literature and update of an ongoing intent-to-treat HCC with transplant single center randomized control trial are reviewed. J. Surg. Oncol. 2007;95:674,679. © 2007 Wiley-Liss, Inc. [source] A Variant of Des-,-Carboxy Prothrombin Was Increased in Alcoholic Liver Disease Without Hepatocellular CarcinomaALCOHOLISM, Issue 2001Motoyuki Ohhira Serum variants of des-,-carboxy prothrombin (DCP) recognized by two different monoclonal antibodies, 19B7 and MU-3, were measured in patients with alcoholic liver disease (ALD), and the values were compared with those of viral liver disease (VLD) and hepatocellular carcinoma (HCC). In the assay that used 19B7 antibody, DCP levels in ALD and HCC were significantly higher than that of VLD, although there was no significant difference in the values between ALD and HCC. In the assay that used MU-3 antibody, DCP level of HCC was significantly higher than those of ALD and VLD, although there was no significant difference in values between ALD and VLD. The ratio of 19B7/MU-3 assay values was significantly higher for ALD than the ratios for VLD and HCC. It is suggested that ALD has a different DCP variant pattern compared with VLD and HCC, which suggests that ALD has a different mechanism of DCP production. [source] Expression of KiSS-1 Gene and its Role in Invasion and Metastasis of Human Hepatocellular CarcinomaTHE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 8 2009Zang Shengbing Abstract KiSS-1 has been identified as a putative metastasis-suppressor gene in human melanomas and breast cancer cell lines. Although loss of KiSS-1 expression has been associated with progression and poor prognosis of various cancers, the exact role of KiSS-1 expression in HCC is not well-defined. Our study investigated KiSS-1 expression levels in HCC and its role in invasion and metastasis of human HCC. The expression levels of KiSS-1 and MMP-9 protein were determined by tissue microarray (TMA) serial sections, immunohistochemistry and semi-quantitative image analysis. All clinical and histological data obtained were subjected to statistical analysis. The expression of KiSS-1 protein in HCC and intrahepatic metastasis lesions was significantly lower (P < 0.01) when compared with non-tumor liver tissue and normal liver tissue. Multivariate analysis revealed a significant inverse correlation between KiSS-1 expression and ,1 TNM stage, (F = 7.113, P < 0.01) and ,2intrahepatic metastasis (t = 2.898, P < 0.01). Loss of KiSS-1 in intrahepatic metastasis versus primary carcinomas was statistically significant (P<0.01). We also found a negative correlation between KiSS-1 and MMP-9 expression in HCC (r = -0.506, P < 0.01). We conclude that loss of KiSS-1 during HCC metastasis, along with a concomitant upregulation of MMP-9 suggests a possible mechanism for cell motility and invasion during HCC metastasis, with KiSS-1 emerging as a possible therapeutic target during HCC metastasis. Anat Rec, 292:1128,1134, 2009. © 2009 Wiley-Liss, Inc. [source] Vascular Changes in Hepatocellular CarcinomaTHE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 6 2008Zhen Fan Yang Abstract Hepatocellular carcinoma (HCC) is one of the most vascular solid tumors, in which angiogenesis plays an important role. The status of angiogenesis in HCC correlates with the disease progression and prognosis, and thus provides a potential therapeutic target. This review summarizes the vascular changes and molecular and cellular basis of angiogenesis in HCC. Development of HCC is characterized by arterialization of its blood supply and sinusoidal capillarization. Vascular endothelial growth factor (VEGF) is a potent angiogenic factor that plays a critical role in mediating angiogenesis in HCC. The VEGF can function on various types of cells, such as endothelial cells, hepatic stellate cells, endothelial progenitor cells and hemangiocytes, to induce vascular changes in HCC. Therefore, blockade of VEGF-mediated pathways, either by anti-VEGF neutralizing antibody or tyrosine kinase inhibitors that target VEGF receptors, suppresses carcinogenesis and angiogenesis in HCC. In addition to VEGF, several other angiogenic factors in HCC have recently been identified. These factors can also regulate angiogenic processes through interaction with VEGF or VEGF-independent pathways. Despite the fact that treatment of HCC remains a tough task due to lack of effective systemic therapy, antiangiogenic therapy has already entered clinical trials in HCC patients and sheds light on a promising novel treatment for this disease. Anat Rec, 291:721,734, 2008. © 2008 Wiley-Liss, Inc. [source] Harm and Benefits of Primary Liver Resection and Salvage Transplantation for Hepatocellular CarcinomaAMERICAN JOURNAL OF TRANSPLANTATION, Issue 3 2010A. Cucchetti Primary transplantation offers longer life-expectancy in comparison to hepatic resection (HR) for hepatocellular carcinoma (HCC) followed by salvage transplantation; however, livers not used for primary transplantation can be reallocated to the remaining waiting-list patients, thus, the harm caused to resected patients could be balanced, or outweighed, by the benefit obtained from reallocation of livers originating from HCC patients first being resected. A Markov model was developed to investigate this issue based on literature data or estimated from the United Network for Organ Sharing database. Markov model shows that primary transplantation offers longer life-expectancy in comparison to HR and salvage transplantation if 5-year posttransplant survival remains higher than 60%. The balance between the harm for resected patients and the benefit for the remaining waiting list depends on (a) the proportion of HCC candidates, (b) the percentage shifted to HR and (c) the median expected time-to-transplant. Faced with a low proportion of HCC candidates, the harm caused to resected patients was higher than the benefit that could be obtained for the waiting-list population from re-allocation of extra livers. An increased proportion of HCC candidates and/or an increased median time-to-transplant could lead to a benefit for waiting-list patients that outweighs this harm. [source] Progression of Alphafetoprotein Before Liver Transplantation for Hepatocellular Carcinoma in Cirrhotic Patients: A Critical FactorAMERICAN JOURNAL OF TRANSPLANTATION, Issue 1 2010E. Vibert Liver transplantation (LT) for cirrhotic/Hepatocellular carcinoma (HCC) is associated with reduced survival in patients with poor histological features. Preoperative levels of alphafetoprotein (AFP) could predict negative biological features. AFP progression could be more relevant than static AFP levels in predicting LT outcomes. A total of 252 cirrhotic/HCC patients transplanted between 1985 and 2005 were reviewed. One hundred fifty-three patients were analyzed, 99 excluded (for nonsecreting tumors and/or salvage transplantation). Using receiver operating characteristics analysis for recurrence after LT, ,progression' of AFP was defined by >15 ,g/L per month before LT. A total of 127 (83%) were transplanted under and 26(16%) over this threshold. After 45 months of follow-up (median), 5-year overall survival (OS) and recurrence free-survival (RFS) were 72% and 69%, respectively. Five-year survival in the progression group was lower than the nonprogression group (OS 54% vs. 77%; RFS 47% vs. 74%). Multivariate analysis showed progression of AFP >15 ,g/L per month and preoperative nodules >3 were associated with decreased OS. Progression group and age >60 years were associated with decreased RFS. Male gender, progression of AFP and size of tumor >30 mm were associated with satellite nodules and/or vascular invasion. In conclusion, increasing AFP >15 ,g/L/month while waiting for LT is the most relevant preoperative prognostic factor for low OS/DFS. AFP progression could be a pathological preoperative marker of tumor aggressiveness. [source] Significance of Des-Gamma-Carboxy Prothrombin in Selection Criteria for Living Donor Liver Transplantation for Hepatocellular CarcinomaAMERICAN JOURNAL OF TRANSPLANTATION, Issue 10 2009M. Fujiki Des-gamma-carboxy prothrombin (DCP) levels reportedly correlate with histological features of hepatocellular carcinoma (HCC). We examined serum DCP as a predictor of HCC recurrence in 144 patients who underwent living donor liver transplantation. Receiver operating characteristics (ROC) analysis revealed superiority of DCP and AFP over preoperative tumor size or number for predicting recurrence. Multivariate analysis revealed tumor size >5 cm, ,11 nodules, and DCP >400 mAU/mL as significant independent risk factors for recurrence. Incidence of microvascular invasion (62% vs. 27%, p = 0.0003) and poor differentiation (38% vs. 16%, p = 0.0087) were significantly higher for patients with DCP >400 mAU/mL than for patients with DCP ,400 mAU/mL. In ROC analysis for patients with ,10 nodules all ,5 cm to predict recurrence, area under the curve was much higher for DCP than for AFP (0.84 vs. 0.69). Kyoto criteria were thus defined as ,10 nodules all ,5 cm, and DCP ,400 mAU/mL. The 5-year recurrence rate for 28 patients beyond-Milan but within-Kyoto criteria was as excellent as that for 78 patients within-Milan criteria (3% vs. 7%). The preoperative DCP level offers additional information regarding histological features, and thus can greatly improve patient selection criteria when used with tumor bulk information. [source] Is Downstaging Prior to Liver Transplantation Important in Hepatocellular Carcinoma?AMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2009P. Lee Downstaging hepatocellular carcinoma for liver transplantation is a procedure in evolution, but the results presented in this article for Yttrium-90 radioembolization are encouraging. See Article by Lewandowski et al on page 1920,1928. [source] A Comparative Analysis of Transarterial Downstaging for Hepatocellular Carcinoma: Chemoembolization Versus RadioembolizationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2009R. J. Lewandowski Chemoembolization and other ablative therapies are routinely utilized in downstaging from United Network for Organ Sharing (UNOS) T3 to T2, thus potentially making patients transplant candidates under the UNOS model for end-stage liver disease (MELD) upgrade for hepatocellular carcinoma (HCC). This study was undertaken to compare the downstaging efficacy of transarterial chemoembolization (TACE) versus transarterial radioembolization. Eighty-six patients were treated with either TACE (n = 43) or transarterial radioembolization with Yttrium-90 microspheres (TARE-Y90; n = 43). Median tumor size was similar (TACE: 5.7 cm, TARE-Y90: 5.6 cm). Partial response rates favored TARE-Y90 versus TACE (61% vs. 37%). Downstaging to UNOS T2 was achieved in 31% of TACE and 58% of TARE-Y90 patients. Time to progression according to UNOS criteria was similar for both groups (18.2 months for TACE vs. 33.3 months for TARE-Y90, p = 0.098). Event-free survival was significantly greater for TARE-Y90 than TACE (17.7 vs. 7.1 months, p = 0.0017). Overall survival favored TARE-Y90 compared to TACE (censored 35.7/18.7 months; p = 0.18; uncensored 41.6/19.2 months; p = 0.008). In conclusion, TARE-Y90 appears to outperform TACE for downstaging HCC from UNOS T3 to T2. [source] Transarterial Chemoinfusion for Hepatocellular Carcinoma as Downstaging Therapy and a Bridge toward Liver TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 5 2009W. De Luna Favorable outcomes after liver transplantation (LT) in patients with hepatocellular carcinoma (HCC) are well described for patients who fall within defined tumor criteria. The effectiveness of tumor therapies to maintain tumor characteristics within these criteria or to downstage more advanced tumors to fall within these criteria is not well understood. The aim of this study was to examine the response to transcatheter arterial chemoinfusion (TACI) in HCC patients awaiting LT and its efficacy for downstaging or bridging to transplantation. We performed a retrospective study of 248 consecutive TACI cases in 122 HCC patients at a single U.S. medical center. Patients were divided into two groups: those who met the Milan criteria on initial HCC diagnosis (n = 95) and those with more advanced disease (n = 27). With TACI treatment, 87% of the Milan criteria group remained within the Milan criteria and 63% of patients with more advanced disease were successfully downstaged to fall within the Milan criteria. In conclusion, TACI appears to be an effective treatment as a bridge to LT for nearly 90% patients presenting within the Milan criteria and an effective downstaging modality for over half of those whose tumor burden was initially beyond the Milan criteria. [source] 18F-FDG-Uptake of Hepatocellular Carcinoma on PET Predicts Microvascular Tumor Invasion in Liver Transplant PatientsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 3 2009A. Kornberg Vascular invasion of hepatocellular carcinoma (HCC) is a major risk factor for poor outcome after liver transplantation (LT). The aim of this retrospective analysis was to assess the value of preoperative positron emission tomography (PET) using 18F-fluorodeoxyglucose (18F-FDG) in liver transplant candidates with HCC for predicting microvascular tumor invasion (MVI) and posttransplant tumor recurrence. Forty-two patients underwent LT for HCC after PET evaluation. Sixteen patients had an increased 18F-FDG tumor uptake on preoperative PET scans (PET +), while 26 recipients revealed negative PET findings (PET,) pre-LT. PET, recipients demonstrated a significantly better 3-year recurrence-free survival (93%) than PET + patients (35%, p < 0.001). HCC recurrence rate was 50% in the PET + group, and 3.8% in the PET,population (p < 0.001). PET + status was identified as independent predictor of MVI [hazard ratio: 13.4]. Patients with advanced PET negative tumors and patients with HCC meeting the Milan criteria had a comparable 3-year-recurrence-free survival (80% vs. 94%, p = 0.6). Increased 18F-FDG uptake on PET is predictive for MVI and tumor recurrence after LT for HCC. Its application may identify eligible liver transplant candidates with tumors beyond the Milan criteria. [source] Liver Transplantation for Recurrent Hepatocellular Carcinoma on Cirrhosis After Liver Resection: University of Bologna ExperienceAMERICAN JOURNAL OF TRANSPLANTATION, Issue 6 2008M. Del Gaudio Liver resection (LR) for patients with small hepatocellular carcinoma (HCC) with preserved liver function, employing liver transplantation (LT) as a salvage procedure (SLT) in the event of HCC recurrence, is a debated strategy. From 1996 to 2005, we treated 227 cirrhotic patients with HCC transplantable: 80 LRs and 147 LTs of 293 listed for transplantation. Among 80 patients eligible for transplantation who underwent LR, 39 (49%) developed HCC recurrence and 12/39 (31%) of these patients presented HCC recurrence outside Milan criteria. Only 10 of the 39 patients underwent LT, a transplantation rate of 26% of patients with HCC recurrence. According to intention-to-treat analysis of transplantable HCC patients who underwent LR (n = 80), compared to all those listed for transplantation (n = 293), 5-year overall survival was 66% in the LR group versus 58% in patients listed for LT, respectively (p = NS); 5-year disease-free survival was 41% in the LR group versus 54% in patients listed for LT (p = NS). Comparable 5-year overall (62% vs. 73%, p = NS) and disease-free (48% vs. 71%, p = NS) survival rates were obtained for SLT and primary LT for HCC, respectively. LR is a valid treatment for small HCC and in the event of recurrence, SLT is a safe and effective procedure. [source] Hepatitis B and C Viruses Infection, Lifestyle and Genetic Polymorphisms as Risk Factors for Hepatocellular Carcinoma in Haimen, ChinaCANCER SCIENCE, Issue 12 2002Shun-Zhang Yu A case-control study was carried out to investigate the impact of factors including virus infection, aflatoxin B1, microcystins, smoking/drinking and dietary habits as well as genetic polymorphisms of aldehyde dehydrogenase 2 (ALDH2) and cytochrome P4502E1 (CYP2E1), on susceptibility to hepatocellular carcinoma (HCC) in Haimen, China. A total of 248 patients with HCC and 248 sex-, age- and residence-matched population-based controls were recruited into the study. Virus infection, and ALDH2 and CYP2E1 gene polymorphisms were assessed in 134 paired cases and controls. By univariate analysis, hepatitis B virus (HBV) infection (odds ratio [OR]=9.75; 95% confidence interval [CI] =4.71,20.2), history of intravenous injection (OR=1.50; 95%CI=1.02,2.22), average income (OR=0.63; 95% CI=0.43,0.92), frequent intake of foods rich in protein, e.g., egg (OR=0.6; 95% CI=0.42,0.87), chicken (OR=0.53; 95% CI=0.35,0.79), pork (OR=0.67; 95% CI=0.46,0.98) and fresh fish (OR=0.58; 95% CI=0.39,0.87) significantly differed between cases and controls. However, peanut intake (OR=0.66; 95% CI=0.43,1.01), source of drinking water, including tap (OR=1.33; 95% CI=0.81,2.20), deep well (OR=0.94; 95% CI=0.56,1.55), shallow well (OR=0.85; 95% CI=0.55-,1.30), river (OR=0.95; 95% CI=0.65,1.38), ditch (OR=1.09; 95% CI=0.76,1.55) and pond water (OR=1.0; 95% CI=0.14,7.10) were not significantly associated with risk. Univariate analysis also indicated that the 1,1 genotype of ALDH2 (OR=1.38; 95% CI=0.86,2.23) as well as the Pst1- and Rsa1-digested c1/c1 genotype of CYP2E1 (OR=1.36; 95% CI=0.81,2.28), was slightly more frequent in the case group. On multivariate analysis, HBV infection (OR=13.9; 95% CI=5.78,33.6) and history of intravenous injection (OR=2.72; 95% CI=1.24,6.00) were still associated with significantly increased risk of HCC, while frequent intake of fresh fish (OR=0.32; 95% CI=0.12,0.86) decreased this risk. These findings suggest that whereas peanut intake, water sources as well as genetic polymorphisms in ALDH2 and CYP2E1 do not significantly correlate with the risk of HCC, HBV infection is a main risk factor, and dietary items rich in protein, especially fresh fish, might protect against the risk of HCC in Haimen, China. [source] Autologous Fixed Tumor Vaccine: A Formulation with Cytokine-microparticles for Protective Immunity against Recurrence of Human Hepatocellular CarcinomaCANCER SCIENCE, Issue 4 2002Bao Gang Peng We developed a tumor vaccine consisting of fixed hepatocellular carcinoma (HCC) cells/tissue fragments, biodegradable microparticles encapsulating granulocyte-macrophage-colony stimulating factor and interleukin-2, and an adjuvant. The vaccine protected 33% of syngeneic mice from HCC cell challenge. The vaccine containing human autologous HCC fragments showed essentially no adverse effect in a phase I/IIa clinical trial and 8/12 patients developed a delayed-type hyper-sensitivity (DTH) response against the fragments. Although 2 of 4 DTH-response-negative patients had recurrence after curative resection, the DTH-response-positive patients had no recurrence. The time before the first recurrence in the vaccinated patients was significantly longer than that in 24 historical control patients operated in the same department (P<0.05). This formulation is a promising candidate to prevent recurrence of human HCC. [source] Therapeutic and Analysis Model of Intrahepatic Metastasis Reflects Clinical Behavior of Hepatocellular CarcinomaCANCER SCIENCE, Issue 2 2002Shigeaki Sawada This study was designed to establish an intrahepatic metastasis model to investigate the biology and therapy of hepatocellular carcinoma (HCC) in mice. A fragment of mouse HCC tumor CBO140C12 was orthotopically implanted into the mouse liver. The number of intrahepatic metastatic colonies and the volume of the implanted tumor increased in a time-dependent manner. At 28 days after fragment implantation, all mice showed intrahepatic metastasis. Intravenous administrations of cisplatin and doxorubicin at 7 and 21 days after the implantation significantly sup- pressed the growth of the primary tumor nodule, but tended to inhibit intrahepatic metastasis. However, a marked decrease of body weight was observed during the experiment. On the other hand, an inhibitor of matrix metalloproteinases (MMPs), ONO,4817, decreased the gelatinase activity of MMP,9 secreted by CBO140C12 cells, and significantly reduced the number of colonies of intrahepatic metastasis when administered orally. Our established model, which is focused on intrahepatic metastasis, is suitable for evaluating the therapeutic effect of HCC and for analyzing intrahepatic metastasis, because this model reflects the clinical features of HCC and all the steps of tumor metastasis. [source] Metastatic hepatocellular carcinoma presenting as a pancreatic mass by computed tomography scan and mimicking a primary neuroendocrine tumor: A potential pitfall in aspiration cytologyDIAGNOSTIC CYTOPATHOLOGY, Issue 12 2009Valerie A. Fitzhugh M.D. Abstract Hepatocellular carcinoma (HCC) is a highly malignant neoplasm, often presenting at late stage and portending a poor prognosis for the patient. The peripancreatic fat is a rare site of extrahepatic metastasis, and metastatic HCC can mimic primary pancreatic neoplasms, even in this location. It is crucial to be aware of this pitfall in the evaluation of aspiration cytology of pancreatic neoplasms and to develop a strategy to reach the correct diagnosis. We present an endoscopic ultrasound fine-needle aspiration diagnosis of metastatic HCC presenting as a pancreatic mass radiologically that had neuroendocrine features on various cytological and histological preparations. The metastatic lesions were located surgically in the peripancreatic adipose tissue with involvement of one peripancreatic lymph node. This case illustrates the utility of FNA for diagnosing uncommon presentations of HCC and the importance of clinical history, cell block, and an immunocytochemical panel in determining the origin of the tumor. Diagn. Cytopathol. 2009. © 2009 Wiley-Liss, Inc. [source] Evaluation of aspiration cytology of the liver space occupying lesions by simultaneous examination of smears and cell blocksDIAGNOSTIC CYTOPATHOLOGY, Issue 8 2009Ujjawal Khurana M.D. Abstract This study was undertaken to compare the efficacy of cytologic smears and histological sections from cell blocks in diagnosis of space occupying lesions (SOLs) of the liver and to classify the lesions on the basis of combined cytohistologic diagnosis. The study was conducted on 50 patients who had radiologically detected SOL/SOLs in the liver and ultrasound-guided fine needle aspiration of liver was done. In all the cases, both smears and cell blocks were made. Forty-seven cases were diagnosed as malignant and three as benign on both cytologic smears and cell blocks. Hepatocellular carcinoma was diagnosed in 8 (16%) cases and metastasis in 39 (78%) cases. The subtyping of malignancy could not be done on 11 (22%) cytologic smears and 8 (16%) cell block sections. However, on combined cytohistologic correlation, 17 (34%) out of these 19 (38%) cases could be subtyped. Sensitivity of cytologic smears and cell blocks in subtyping of malignancy was 72.3% and 82.9%, respectively. Combined cytohistologic diagnosis was found to be significantly better than isolated cytologic and cell block diagnosis (P , 0.05). To conclude, FNA of the SOLs of the liver is an effective procedure for diagnosing malignancy. However, cytological examination alone may fail to pinpoint the type of the tumor. Concomitant examination of cell block not only confirms the malignancy but also helps in subtyping it. Diagn. Cytopathol. 2009. © 2009 Wiley-Liss, Inc. [source] Proteome analysis of human liver tumor tissue by two-dimensional gel electrophoresis and matrixassisted laser desorption/ionization-mass spectrometry for identification of disease-related proteinsELECTROPHORESIS, Issue 24 2002Jina Kim Abstract Hepatocellular carcinoma (HCC) is a common malignancy worldwide and is a leading cause of death. To contribute to the development and improvement of molecular markers for diagnostics and prognostics and of therapeutic targets for the disease, we have largely expanded the currently available human liver tissue maps and studied the differential expression of proteins in normal and cancer tissues. Reference two-dimensional electrophoresis (2-DE) maps of human liver tumor tissue include labeled 2-DE images for total homogenate and soluble fraction separated on pH 3,10 gels, and also images for soluble fraction separated on pH 4,7 and pH 6,9 gels for a more detailed map. Proteins were separated in the first dimension by isoelectric focusing on immobilized pH gradient (IPG) strips, and by 7.5,17.5% gradient sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) gels in the second dimension. Protein identification was done by peptide mass fingerprinting with delayed extraction-matrix assisted laser desorption/ionization-time of flight-mass spectrometry (DE-MALDI-TOF-MS). In total, 212 protein spots (117 spots in pH 4,7 map and 95 spots in pH 6,9) corresponding to 127 different polypeptide chains were identified. In the next step, we analyzed the differential protein expression of liver tumor samples, to find out candidates for liver cancer-associated proteins. Matched pairs of tissues from 11 liver cancer patients were analyzed for their 2-DE profiles. Protein expression was comparatively analyzed by use of image analysis software. Proteins whose expression levels were different by more than three-fold in at least 30% (four) of the patients were further analyzed. Numbers of protein spots overexpressed or underexpressed in tumor tissues as compared with nontumorous regions were 9 and 28, respectively. Among these 37 spots, 1 overexpressed and 15 underexpressed spots, corresponding to 11 proteins, were identified. The physiological significance of the differential expressions is discussed. [source] A randomized controlled trial of transcatheter arterial chemoembolization with lipiodol, doxorubicin and cisplatin versus intravenous doxorubicin for patients with unresectable hepatocellular carcinomaEUROPEAN JOURNAL OF CANCER CARE, Issue 5 2009M. MABED md, professor Hepatocellular carcinoma (HCC) is a major and often therapeutically frustrating oncological problem. A total of 100 patients with unresectable HCC were recruited and randomized to be treated with either transcatheter arterial chemoembolization (TACE) or systemic chemotherapy. Fifty patients were treated with TACE using lipiodol, doxorubicin and cisplatin, while 50 patients were treated with systemic doxorubicin alone. Patients treated with TACE achieved a significantly higher response rate, with partial response achieved in 16 patients (32%) versus five patients (10%) in the chemotherapy arm (P = 0.007). A significantly more favourable tumour response to chemoembolization was found in patients with single lesions (P = 0.02), Child class A (P = 0.007), Okuda stage 1 (P = 0.005) and ,-feto protein less than 400 ng/mL (P < 0.001). The probability of tumour progression was significantly lower in cases treated with TACE where the median progression free survival was 32 weeks (range, 16,70 weeks) versus 26 weeks (range, 14,54 weeks) for patients treated with systemic chemotherapy (P = 0.03). However, the median overall survival did not differ significantly in cases treated with TACE (38 weeks) compared with those treated with chemotherapy (32 weeks) (P = 0.08), except for patients with serum albumin >3.3 g/dL (60 vs. 36 weeks; P = 0.003). Multivariate Cox regression analysis showed that a rise of serum albumin by 1 g/dL is associated with a decrease in the risk of death by 33% (95% confidence interval: 0.12,0.94, P = 0.038). Mortality in the chemoembolization arm was due to tumour progression in 18 patients (53%), liver failure in 11 patients (32%) and gastro intestinal tract (GIT) bleeding in 5 patients (15%). Mortality in the chemotherapy arm was due to tumour progression in 23 patients (64%), liver failure in 9 patients (25%) and GIT bleeding in 4 patients (11%). Treatment-related mortality was 4% in the TACE arm versus 0% in the chemotherapy arm. In conclusion, the overall survival benefits of TACE and systemic doxorubicin are similar for patients with unresectable HCC amenable to either treatment. It is crucial to optimize the benefit,risk ratio of TACE. In this setting, serum albumin level is a candidate marker for selection of cases who may benefit from this procedure. [source] Hepatocellular carcinoma: Sorafenib before liver transplantation?,HEPATOLOGY, Issue 6 2010Alain Braillon No abstract is available for this article. [source] Inhibition of poly adenosine diphosphate-ribose polymerase decreases hepatocellular carcinoma growth by modulation of tumor-related gene expression,HEPATOLOGY, Issue 1 2010Rosa Quiles-Perez Hepatocellular carcinoma (HCC) is associated with a poor prognosis due to a lack of effective treatment options. In HCC a significant role is played by DNA damage and the inflammatory response. Poly (ADP-ribose) polymerase-1 (PARP-1) is an important protein that regulates both these mechanisms. The objective of this study was to examine the effect of pharmacology PARP-1 inhibition on the reduction of tumor volume of HCC xenograft and on the hepatocarcinogenesis induced by diethyl-nitrosamine (DEN). Pharmacologic PARP-1 inhibition with DPQ greatly reduces tumor xenograft volume with regard to a nontreated xenograft (394 mm3 versus 2,942 mm3, P < 0.05). This observation was paralleled by reductions in xenograft mitosis (P = 0.02) and tumor vasculogenesis (P = 0.007, confirmed by in vitro angiogenesis study), as well as by an increase in the number of apoptotic cells in DPQ-treated mice (P = 0.04). A substantial difference in key tumor-related gene expression (transformed 3T3 cell double minute 2 [MDM2], FLT1 [vascular endothelial growth factor receptor-1, VEGFR1], epidermal growth factor receptor [EPAS1]/hypoxia-inducible factor 2 [HIF2A], EGLN1 [PHD2], epidermal growth factor receptor [EGFR], MYC, JUND, SPP1 [OPN], hepatocyte growth factor [HGF]) was found between the control tumor xenografts and the PARP inhibitor-treated xenografts (data confirmed in HCC cell lines using PARP inhibitors and PARP-1 small interfering RNA [siRNA]). Furthermore, the results obtained in mice treated with DEN to induce hepatocarcinogenesis showed, after treatment with a PARP inhibitor (DPQ), a significant reduction both in preneoplastic foci and in the expression of preneoplastic markers and proinflammatory genes (Gstm3, Vegf, Spp1 [Opn], IL6, IL1b, and Tnf), bromodeoxyuridine incorporation, and NF-,B activation in the initial steps of carcinogenesis (P < 0.05). Conclusion: This study shows that PARP inhibition is capable of controlling HCC growth and preventing tumor vasculogenesis by regulating the activation of different genes involved in tumor progression. (HEPATOLOGY 2010;51:255,266.) [source] Molecular mechanisms of hepatocellular carcinoma,HEPATOLOGY, Issue 6 2008Rajagopal N. Aravalli Hepatocellular carcinoma (HCC) typically has poor prognosis, because it is often diagnosed at an advanced stage. Heterogeneous phenotypic and genetic traits of affected individuals and a wide range of risk factors have classified it a complex disease. HCC is not amenable to standard chemotherapy and is resistant to radiotherapy. In most cases, surgical resection and liver transplantation remain the only curative treatment options. Therefore, development of novel, effective therapies is of prime importance. Extensive research over the past decade has identified a number of molecular biomarkers as well as cellular networks and signaling pathways affected in liver cancer. Recent studies using a combination of "omics" technologies, microRNA studies, combinatorial chemistry, and bioinformatics are providing new insights into the gene expression and protein profiles during various stages of the disease. In this review, we discuss the contribution of these newer approaches toward an understanding of molecular mechanisms of HCC and for the development of novel cancer therapeutics. (HEPATOLOGY 2008;48:2047-2063.) [source] Expression of X-linked inhibitor-of-apoptosis protein in hepatocellular carcinoma promotes metastasis and tumor recurrence,HEPATOLOGY, Issue 2 2008Ying-Hong Shi Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. Despite significantly improved diagnosis and treatment in recent years, the long-term therapeutic effect is compromised by the frequent recurrence and metastasis, of which the molecular mechanisms are not fully understood. Our initial studies in established HCC cell lines with different metastatic capabilities indicated a correlation of metastasis with the resistance to apoptosis and therefore the ability to survive in stressed conditions. Subsequent investigation revealed that increased expression of X-linked inhibitor-of-apoptosis protein (XIAP) was correlated with the resistance to apoptosis and enhanced invasiveness in vitro, which could contribute to increased metastatic foci in vivo. Furthermore, we found that nearly 90% of clinical samples from advanced HCC patients expressed high levels of XIAP. Patients with XIAP-positive tumors had a significantly increased risk of relapse, which resulted from metastasis after total liver resection and orthotopic liver transplantation. Indeed, XIAP expression could be an independent prognostic factor for predicting disease-free survival rate and overall survival rate of these patients. XIAP expression was also highly correlated with advanced cases that exceeded the Milan criteria and could be a prognostic factor for disease-free survival in these patients as well. Conclusion: Our studies have shown an important molecule in controlling HCC metastasis, defined a biomarker that can be used to predict HCC recurrence and patient survival after treatment, and suggest that XIAP can be a molecular target subject to intervention to reduce metastasis and recurrence. (HEPATOLOGY 2008;48:497,507.) [source] Hepatitis C virus replication is inhibited by 22,-methoxyolean-12-ene-3,, 24(4,)-diol (ME3738) through enhancing interferon-,,HEPATOLOGY, Issue 1 2008Yoichi Hiasa A derivative of soyasapogenol, 22,-methoxyolean-12-ene-3,, 24(4,)-diol (ME3738), ameliorates liver injury induced by Concanavalin A in mice. We examined whether ME3738 has independent antiviral effects against hepatitis C virus (HCV) using an established HCV replication model that expresses the full-length genotype 1a HCV complementary DNA plasmid (pT7-flHCV-Rz) under the control of a replication-defective adenoviral vector expressing T7 polymerase. Hepatocellular carcinoma (HepG2) cells, human hepatoma (Huh7) cells, or monkey kidney (CV-1) cells were transfected with pT7-flHCV-Rz, and infected with adenoviral vector expressing T7 polymerase. ME3738 or interferon-, (IFN-,) was added thereafter and then protein and RNA were harvested from the cells at 9 days after infection. HCV-positive and HCV-negative strands were measured by real-time reverse-transcription polymerase chain reaction and HCV core protein expression was measured using an enzyme-linked immunosorbent assay. The messenger RNA levels of innate antiviral response-related genes were assessed using real-time reverse-transcription polymerase chain reaction. ME3738 dose-dependently reduced HCV-RNA and core protein in hepatocyte-derived cell lines. The antiviral effect was more pronounced in HepG2 than in Huh7 cells. ME3738 increased messenger RNA levels of interferon-, (IFN-,) and of IFN-stimulated genes (2,-5, oligoadenylate synthetase, myxovirus resistance protein A [MxA]). Interferon-, knockdown by small interfering RNA abrogated the anti-HCV effect of ME3738. Moreover, the anti-HCV effects were synergistic when ME3738 was combined with IFN-,. Conclusion: ME3738 has antiviral effects against HCV. The enhancement of autocrine IFN-, suggests that ME3738 exerts antiviral action along the type I IFN pathway. This anti-HCV action by ME3738 was synergistically enhanced when combined with IFN-,. ME3738 might be a useful anti-HCV drug either with or without IFN-,. (HEPATOLOGY 2008.) [source] Laminin-5 stimulates hepatocellular carcinoma growth through a different function of ,6,4 and ,3,1 integrins,HEPATOLOGY, Issue 6 2007Carlo Bergamini Hepatocellular carcinoma (HCC) growth severely affects prognosis. Ki-67, a known marker of cell proliferation, is a negative prognostic factor in HCC. Growth factors such as the epidermal growth factor (EGF) induce HCC cell proliferation but do not explain the great heterogeneity of HCC growth. Laminin-5 (Ln-5) is an extracellular matrix protein (ECM) present in the tissue microenvironment of HCC. The two main receptors for Ln-5, integrins ,3,1 and ,6,4, are expressed on the cell surface of HCC cells. The aim of this study is to investigate an alternative mechanism of HCC growth whereby Ln-5 promotes HCC cell proliferation through ,3,1 and ,6,4. HCC tissues containing Ln-5 display a larger diameter and higher number of positive cells for Ki-67, a well known proliferative index, as determined by double immunofluorescence staining and real-time PCR on microdissected tissues. In vitro, Ln-5, but not collagen I, collagen IV or fibronectin, induces proliferation as much as EGF does, via Erk phosphorylation as a consequence of ,4 integrin phosphorylation. However, the two HCC cell lines do not proliferate in presence of Ln-5 despite ,4 integrin and Erk1/2 activation. After transfection with ,3 integrin, in the presence of Ln-5 one of these HCC cell lines acquires a proliferative activity whereas one of the proliferative HCC cell lines, knocked-down for ,3 integrin, loses its proliferative activity. Conclusions: Our study suggests a new mechanism of HCC growth whereby Ln-5 stimulates proliferation via a different function of ,6,4 and ,3,1. (HEPATOLOGY 2007.) [source] Hepatocellular carcinoma in ten children under five years of age with bile salt export pump deficiency,HEPATOLOGY, Issue 2 2006A. S. Knisely Hepatocellular carcinoma (HCC) is rare in young children. We attempted to see if immunohistochemical and mutational-analysis studies could demonstrate that deficiency of the canalicular bile acid transporter bile salt export pump (BSEP) and mutation in ABCB11, encoding BSEP, underlay progressive familial intrahepatic cholestasis (PFIC),or "neonatal hepatitis" suggesting PFIC,that was associated with HCC in young children. We studied 11 cases of pediatric HCC in the setting of PFIC or "neonatal hepatitis" suggesting PFIC. Archival liver were retrieved and immunostained for BSEP. Mutational analysis of ABCB11 was performed in leukocyte DNA from available patients and parents. Among the 11 nonrelated children studied aged 13-52 months at diagnosis of HCC, 9 (and a full sibling, with neonatal hepatitis suggesting PFIC, of a tenth from whom liver was not available) had immunohistochemical evidence of BSEP deficiency; the eleventh child did not. Mutations in ABCB11 were demonstrated in all patients with BSEP deficiency in whom leukocyte DNA could be studied (n = 7). These mutations were confirmed in the parents (n = 14). With respect to the other 3 children with BSEP deficiency, mutations in ABCB11 were demonstrated in all 5 parents in whom leukocyte DNA could be studied. Thirteen different mutations were found. In conclusion, PFIC associated with BSEP deficiency represents a previously unrecognized risk for HCC in young children. Immunohistochemical evidence of BSEP deficiency correlates well with demonstrable mutation in ABCB11. (HEPATOLOGY 2006;44:478,486.) [source] | ||||||||||||||||||||||||||||||||||||||||||||||