National Cancer Institute®
Last Modified: June 1, 2002
UI - 11878776
AU - Toretsky JA; Zitomersky NL; Eskenazi AE; Voigt RW; Strauch ED; Sun CC;
TI - Huber R; Meltzer SJ; Schlessinger D Glypican-3 expression in Wilms tumor and hepatoblastoma.
SO - J Pediatr Hematol Oncol 2001 Nov;23(8):496-9
AD - Department of Pediatrics, and Greenebaum Cancer Center, University of Maryland School of Medicine and Baltimore VA Medical Center, USA.
BACKGROUND: Glypican-3 (GPC3) is a heparan sulfate proteoglycan. When it is disrupted, it causes the X-linked gigantism-overgrowth Simpson-Golabi-Behmel syndrome. Its involvement in growth control is consistent with recent reports that it can bind to growth factors, possibly including insulin-like growth factor 2. Further, it has been hypothesized that it may function as a tumor suppressor gene in breast and ovarian carcinomas and mesotheliomas. PATIENTS AND METHODS: RNA and protein were extracted from Wilms tumor and hepatoblastoma tissue samples and GPC3 levels were measured in these extracts by Northern blotting, reverse transcription polymerase chain reaction, and immunoblotting. RESULTS: In contrast to published results with carcinomas, high levels of GPC3 expression were found in Wilms tumor and hepatoblastoma. Low or undetectable expressions of this gene were found in normal tissue surrounding the tumor. CONCLUSIONS: Increased expression of GPC3 in Wilms tumor and hepatoblastoma suggests a growth-promoting or neutral activity for this gene product rather than a growth-suppressive effect.
UI - 11916628
AU - Deladoey J; Gex G; Vuissoz JM; Strasburger CJ; Wajnrajch MP; Mullis PE
TI - Effect of different growth hormone (GH) mutants on the regulation of GH-receptor gene transcription in a human hepatoma cell line.
SO - Eur J Endocrinol 2002 Apr;146(4):573-81
AD - Department of Paediatrics, Division of Paediatric Endocrinology, Inselspital, CH-3010 Bern, Switzerland.
OBJECTIVE: G to A transition at position 6664 of the growth hormone (GH-1) gene results in the substitution of Arg183 by His (R183H) in the GH protein and causes a new form of autosomal dominant isolated GH deficiency (IGHD type II). The aim of this study was to assess the bioactivity of this R183H mutant GH in comparison with both other GH variants and the 22-kDa GH in terms of GH-receptor gene regulation. DESIGN AND METHODS: The regulation of the GH-receptor gene (GH-receptor/GH binding protein, GHR/GHBP) transcription following the addition of variable concentrations (0, 12.5, 25, 50 and 500 ng/ml) of R183H mutant GH was studied in a human hepatoma cell line (HuH7) cultured in a serum-free hormonally defined medium. In addition, identical experiments were performed using either recombinant human GH (22-kDa GH) as a positive control or two GH-receptor antagonists (R77C mutant GH and pegvisomant (B-2036-PEG)) as negative controls. GHR/GHBP mRNA expression was quantitatively assessed by RT-PCR amplification after 0, 1, 3 and 6 h incubation. RESULTS: Following the addition of R183H mutant GH, GHR/GHBP mRNA changed at a similar rate to that seen in experiments where 22-kDa GH was added, indicating equal bioactivity. At all times and concentrations studied, the addition of R77C mutant GH, however, resulted in a significantly lower increase (P<0.001) of GHR/GHBP mRNA concentration compared with that caused by the addition of either 22-kDa GH or R183H mutant GH. Furthermore, in additional experiments, pegvisomant resulted in an absolute block of GHR/GHBP mRNA expression identical to that seen in control experiments where no 22-kDa GH was added at all. CONCLUSIONS: These data indicate that the R183H mutant GH, although causing an autosomal dominant form of IGHD has an identical effect on GHR/GHBP transcription as its wild-type, the 22-kDa GH. This implies that the IGHD caused by the R183H heterozygous mutation of the GH-1 gene is mainly due to a block of its regulated GH secretion. In addition, the R77C-GH variant and pegvisomant have an antagonistic effect at the level of GHR/GHBP transcription. All these data were confirmed by run-on experiments. In addition, these data highlight, as far as the GH variants are concerned, that a mutational alteration within the GH-1 gene might cause short stature also on the basis of an altered secretory pathway. This fact has to be taken into consideration when growth retardation is clinically diagnosed and studied at the molecular level. Secretory pathways and, therefore, cell-biological mechanisms are of importance and have to be considered in future not only at the scientific but also at the clinical level.
UI - 11441549
AU - Catalano O; Lobianco R; Esposito M; Siani A
TI - Hepatocellular carcinoma recurrence after percutaneous ablation therapy: helical CT patterns.
SO - Abdom Imaging 2001 Jul-Aug;26(4):375-83
AD - Department of Radiology, S. Maria delle Grazie Hospital, via Domitiana Loc. La Schiana, Pozzuoli, Naples I-80078, Italy.
BACKGROUND: To categorize the helical computed tomographic (CT) intrahepatic recurrence patterns of hepatocellular carcinoma (HCC) after treatment with percutaneous ablation procedures. METHODS: Double-phase helical CT studies of 67 patients with HCC recurrence were reviewed. The study population had undergone percutaneous ablation therapy procedures (multisession or single-session ethanol injection therapy, radiofrequency thermal ablation therapy, and interstitial laser photocoagulation therapy) for 120 HCC nodules. RESULTS: Four patterns were defined. (A) Enhancing tissue within the edge of the ablated nodule on arterial phase images (ingrowth): this pattern was seen in five treated lesions (4.2% of all treated nodules) in five patients (7.5% of all patients with recurrence) 3-7 months after treatment (mean = 4 months). (B) Enhancing tissue around the treated nodule but continuously to its border on arterial-phase images (outgrowth): this pattern was found in 12 (10%) treated lesions in 12 patients (18%) 3-6 months after ablation (mean = 4 months). (C) Enhancing tissue within the same segment of the treated nodule on arterial phase images (spread): this pattern was detected in 10 (8%) treated lesions in 10 patients (15%) 3-6 months after treatment (mean = 5 months). (D) Enhancing tissue within different segments from the treated nodule on arterial phase images (progression): this pattern was identified in 34 patients (51%) with 53 (44%) treated tumors 5-22 months after ablation (mean = 8 months). A mixed pattern was found in six subjects (9%) with seven (6%) treated nodules. Among the 61 patients with a nonmixed pattern, there were 85 treated nodules with persistent necrosis, 17 treated nodules with local recurrence (pattern A or B), and 107 new nodules due to nonlocal recurrence (pattern C or D). Portal phase enhanced images and especially unenhanced images showed a lower detection rate and a lower lesion-to-liver conspicuity score (for all patterns but mainly for pattern C). CONCLUSION: Four patterns of recurrence after percutaneous ablation procedures can be categorized on double-phase helical CT and are best depicted on arterial phase images. Knowledge of these patterns is relevant for early detection and may be helpful in understanding the recurrence mechanism.
UI - 11441550
AU - Gabata T; Kadoya M; Matsui O; Ueda K; Kawamori Y; Terayama N; Sanada J;
TI - Kobayashi S Peritumoral spared area in fatty liver: correlation between opposed-phase gradient-echo MR imaging and CT arteriography.
SO - Abdom Imaging 2001 Jul-Aug;26(4):384-9
AD - Department of Radiology, Kanazawa University, School of Medicine, 13-1 Takara-machi, Kanazawa City, Ishikawa, Japan 920-8641.
BACKGROUND: The purpose of the present study was to evaluate the magnetic resonance findings of a spared area of fatty liver caused by hepatic tumors and clarify the etiology of this phenomenon by computed tomographic (CT) arteriography. METHODS: Six patients with hepatic tumors (metastases from colon cancer, n = 3; breast cancer, n = 2; hepatocellular carcinoma, n = 1) were examined. In-phase (IP) and opposed-phase (OP) T1-weighted spoiled gradient-echo images were obtained. CT during arterial portography (CTAP) and CT during hepatic arteriography (CTHA) were also performed. Pathologic confirmation was obtained in three patients with metastases from colon cancer. RESULTS: In all six patients, peritumoral ringlike or wedge-shaped hyperintense areas in relation to the tumor and the surrounding steatotic liver parenchyma were clearly visualized on OP images alone. This area appeared as a perfusion defect on CTAP and ringlike or wedge-shaped enhancement on CTHA. Pathologically, the peritumoral hyperintense areas on OP images were compatible with the spared area of fatty liver. CONCLUSION: A peritumoral spared area can be demonstrated with OP images. The etiology of the phenomenon is correlated with decreased portal flow and increased arterial flow in the peritumoral hepatic parenchyma.
UI - 11906615
AU - Herold C; Reck T; Fischler P; Ott R; Radespiel-Troeger M; Ganslmayer M;
TI - Hohenberger W; Hahn EG; Schuppan D Prognosis of a large cohort of patients with hepatocellular carcinoma in a single European centre.
SO - Liver 2002 Feb;22(1):23-8
AD - Department of Medicine I, Department of Surgery, Institute for Medical Statistics, Biometry and Epidemiology, University of Erlangen-Nuernberg, Germany. email@example.com
BACKGROUND/AIM: Only a few follow up data are available for patients with hepatocellular carcinoma (HCC) in Europe and the USA. Therefore, we analysed all HCC patients admitted to our hospital between 1988 and 1999. METHODS: We documented aetiology, stage (HCC: Okuda and UICC classifications, liver cirrhosis: Child-Pugh score), and diagnostic and therapeutic measures of 281 consecutive HCC patients. Survival time was calculated as a function of staging and therapy. RESULTS: Cirrhosis was diagnosed in all patients. Seventy-two patients underwent liver resection, 28 liver transplantation, 31 transarterial chemoembolization and 14 percutaneous ethanol injection. One hundred and thirty-six patients received no treatment. The Okuda and the Child-Pugh classification predicted a significant decrease of median survival time, whereas the UICC classification was less powerful. CONCLUSIONS: HCC occurred only in patients with liver cirrhosis. Survival time correlated with therapy (or no therapy) and with the Child-Pugh Score. In European patients the Okuda classification is superior to the UICC classification and should be compared to novel classification systems.
UI - 11906619
AU - Verhoef C; Valkema R; de Man RA; Krenning EP; Yzermans JN
TI - Fluorine-18 FDG imaging in hepatocellular carcinoma using positron coincidence detection and single photon emission computed tomography.
SO - Liver 2002 Feb;22(1):51-6
AD - Department of Surgery, University Hospital Dijkzigt, Rotterdam, The Netherlands.
BACKGROUND/AIMS: We prospectively evaluated whether fluorine-18 deoxyglucose (FDG) positron coincidence detection (PCD) or FDG single-photon emission computed tomography (SPECT) provides additional benefits to our conventional preoperative evaluation of lesion detection in patients suspected to have hepatocellular carcinoma (HCC). METHODS: Thirteen consecutive patients with a suspected HCC underwent conventional preoperative evaluation with ultrasonography (US), triple-phase helical computed tomography (CT), superparamagnetic iron oxides (SPIO) enhanced magnetic resonance imaging (MRI) and serum alpha-fetoprotein (AFP) level. All 13 patients had an FDG-PCD and SPECT. These results were evaluated to assess the value of FDG-PCD and SPECT in addition to US, SPIO-enhanced MRI and triple-phase helical CT. RESULTS: Ten of the 13 (77%) patients had at least one histologically confirmed HCC without extrahepatic abdominal spread. The tumors ranged in size from 1 to 8 cm and the serum AFP ranged from 3 to 30 000 microg/l. Of these 10 patients, two patients had an increased tumor F-FDG uptake (sensitivity of 20%); one patient with an AFP of 5 microg/l and a tumor size of maximum 4.5 cm and one patient with an AFP of 249 microg/l and a tumor size of maximum 2 cm. In three patients with a benign liver mass, FDG imaging with either PCD or SPECT was negative. There was no false positive finding. CONCLUSIONS: We found poor sensitivity of FDG-PCD and FDG-SPECT for the detection of HCC. There were no clear relations between AFP or tumor size and FDG uptake. Therefore, we conclude that FDG imaging with PCD or SPECT has no value in the preoperative work-up for HCC in patients with cirrhosis.
UI - 11906621
AU - Makhlouf HR; Ishak KG
TI - Sclerosed hemangioma and sclerosing cavernous hemangioma of the liver: a comparative clinicopathologic and immunohistochemical study with emphasis on the role of mast cells in their histogenesis.
SO - Liver 2002 Feb;22(1):70-8
AD - Department of Hepatic and Gastrointestinal Pathology, Armed Forces Institute of Pathology, Washington, DC 20306-6000, USA.
BACKGROUND/AIMS: Sclerosed hemangiomas of the liver are rare. To date, their histopathology, immunohistochemistry, and the role of mast cells (MC) in their histogenesis have not been systematically studied. PATIENTS/METHODS: Clinical, histopathologic and immunohistochemical features of 20 sclerosed hemangiomas were compared with those of 18 sclerosing cavernous hemangiomas. The number of MC was quantified and compared in all cases, using a tryptase immunostain. RESULTS: Compared to patients with sclerosed hemangiomas, those with sclerosing hemangiomas were younger (mean age, 63 versus 71 years); had larger tumors (mean 6 +/- 4.73 versus 3 +/- 2.2 cm); presented with a mass more frequently, and epigastric pain less frequently. Sclerosing hemangiomas, but not sclerosed hemangiomas, were more frequent in males than in females. Sclerosing hemangiomas occurred much more frequently in the right lobe than sclerosed hemangiomas. Sclerosing hemangiomas had less fibrosis, hyalinization, and elastic fibers than sclerosed hemangiomas (p = 0.00004). Numerous thick-walled blood vessels were a feature of sclerosed hemangiomas but not of sclerosing hemangiomas. Collagen IV, and laminin were more uniformly positive in sclerosing hemangiomas than in sclerosed hemangiomas. Increased immunoreactivity for smooth muscle actin was present in sclerosed hemangiomas more often than in sclerosing hemangiomas. FVIII-R Ag, CD34, and CD31 were more diffusely positive in sclerosing hemangiomas than in sclerosed hemangiomas. In sclerosing hemangiomas, the mean number of tryptase-positive MC per high power field (MC/HPF) varied from 8.25 +/- 6.23 in vascular areas to 1.6 +/- 4.01 in sclerotic areas. In comparison, the mean number of MC in sclerosed hemangiomas, was 4.3 +/- 5.01 in vascular areas, and 0.86 +/- 0.58 in sclerotic areas (p = 0.0095). The number of MC was significantly correlated with vascular proliferation and inversely related to the degree of fibrosis (p < 0.0001). CONCLUSIONS: This study demonstrates certain distinct clinical and histopathologic differences between sclerosing cavernous hemangiomas and sclerosed hemangiomas of the liver. We have established the presence of MC in those tumors, and suggest possible involvement of the MC in angiogenesis, and the regression process and development of fibrosis.
UI - 11930075
AU - Dromain C; de Baere T; Elias D; Kuoch V; Ducreux M; Boige V; Petrow P;
TI - Roche A; Sigal R Hepatic tumors treated with percutaneous radio-frequency ablation: CT and MR imaging follow-up.
SO - Radiology 2002 Apr;223(1):255-62
AD - Department of Radiology, Institut Gustave-Roussy, 39 rue Camille Desmoulins, 94805 Villejuif, France. firstname.lastname@example.org
PURPOSE: To describe the appearance of hepatic tumors treated with radio-frequency (RF) ablation on computed tomographic (CT) and magnetic resonance (MR) images and the pattern of residual tumor at the site of RF ablation and to assess prospectively the sensitivity, specificity, and positive and negative predictive CT and MR imaging values in the evaluation of RF treatment. MATERIALS AND METHODS: Thirty-one patients with 50 tumors (nine hepatocellular carcinomas and 41 metastases) treated with RF ablation underwent CT and MR imaging on the same day at 2, 4, and 6 months; CT was performed every 3 months thereafter. CT and MR findings were interpreted separately and prospectively by two reviewers with consensus. For both imaging techniques, appearance of the treated area, treatment efficacy, and complications were assessed at each time. Sensitivity and specificity were determined by using the McNemar test. RESULTS: After a mean follow-up of 19 months, nine tumors showed local regrowth. At 2 months, MR imaging depicted more local regrowths (eight of nine; sensitivity, 89%) than did CT (four of nine; sensitivity, 44%) but without significant differences (P =.12). In two cases, only T2-weighted imaging depicted local regrowth. All nine lesions became conspicuous at 4-month follow-up with both techniques. At 2 months, thin peripheral rim enhancement and arterioportal shunting were found in 24% and 12%, respectively, of the treated tumors. These findings disappeared thereafter and are not linked to tumor regrowth. CONCLUSION: Despite the small number of patients, CT and MR imaging may depicted all local regrowth at 4 months or sooner. MR imaging may have an edge over CT in the early detection of local regrowth.
UI - 12003382
AU - Lauret E; Rodriguez M; Gonzalez S; Linares A; Lopez-Vazquez A;
TI - Martinez-Borra J; Rodrigo L; Lopez-Larrea C HFE gene mutations in alcoholic and virus-related cirrhotic patients with hepatocellular carcinoma.
SO - Am J Gastroenterol 2002 Apr;97(4):1016-21
AD - Department of Gastroenterology, Hospital Central de Asturias, Spain.
OBJECTIVE: The increased risk of developing hepatocellular carcinoma in hereditary hemochromatosis has been associated with cirrhosis and hepatic iron overload. The aim of this study was to investigate the association between HFE gene mutations (C282Y, H63D) and hepatocellular carcinoma in patients with alcoholic and virus-related cirrhosis. METHODS: Serum markers of iron status and HFE mutations were determined in 179 patients with alcoholic cirrhosis and 98 patients with hepatitis B and/or hepatitis C virus-related cirrhosis. A total of 43 patients with alcoholic cirrhosis and 34 patients with virus-related cirrhosis had hepatocellular carcinoma. The control group consisted of 159 healthy bone marrow donors. RESULTS: No differences were found in the frequencies of mutations among patients with alcoholic cirrhosis, those with virus-related cirrhosis, and the control subjects. However, nine (20.9%) of the 43 patients with alcoholic cirrhosis and hepatocellular carcinoma were heterozygous for the C282Y mutation, compared with six (4.4%) of the 136 patients without tumor (p = 0.002). This difference was not found in patients with virus-related cirrhosis, with or without hepatocellular carcinoma, or the H63D mutation. The transferrin saturation was the only serum iron marker the value of which was significantly higher among C282Y heterozygotes with alcoholic cirrhosis compared to those without mutation. CONCLUSIONS: The high frequency of heterozygosity for the C282Y mutation in patients with alcoholic cirrhosis plus hepatocellular carcinoma suggests that the presence of this mutation could be associated with an increased risk of developing hepatocellular carcinoma in these patients.
UI - 11950223
AU - Blanquicett C; Johnson MR; Heslin M; Diasio RB
TI - Housekeeping gene variability in normal and carcinomatous colorectal and liver tissues: applications in pharmacogenomic gene expression studies.
SO - Anal Biochem 2002 Apr 15;303(2):209-14
AD - Division of Clinical Pharmacology, Department of Pharmacology and Toxicology, Comprehensive Cancer Center, University of Alabama at Birmingham, 35294, USA.
UI - 12000734
AU - Liu SH; Lin CY; Peng SY; Jeng YM; Pan HW; Lai PL; Liu CL; Hsu HC
TI - Down-regulation of annexin A10 in hepatocellular carcinoma is associated with vascular invasion, early recurrence, and poor prognosis in synergy with p53 mutation.
SO - Am J Pathol 2002 May;160(5):1831-7
AD - Graduate Institute of Pathology, College of Medicine, National Taiwan University, Taipei.
Annexins (ANXs) are a large group of calcium-binding proteins participating in diverse important biological processes. ANXA10 is the least expressed new member of unknown function. We showed that ANXA10 mRNA was expressed in adult liver and hepatocellular carcinoma (HCC), but not in multiple adult and fetal tissues, cholangiocarcinoma, and several other common carcinomas. Of 182 unifocal primary HCCs, ANXA10 mRNA was dramatically reduced in 121 (66%), and the down-regulation correlated with p53 mutation (P = 0.024), early intrahepatic tumor recurrence (P = 0.0007), and lower 4-year survival (P = 0.0014). Down-regulation of ANXA10 was twofold more frequent in large than small HCCs (P = 0.0012), in grade II to III than grade I HCC (P < 0.00001), and in stage IIIA to IV than stage I to II HCC (P < 0.00001). Moreover, ANXA10 down-regulation and p53 mutation acted synergistically toward high-grade (P < 0.00001), high-stage HCC (P < 0.00001), and poorer prognosis (P = 0.0025). Our results indicate that the expression of the tissue- and tumor-restricted ANXA10 is a marker of liver cell differentiation and growth arrest, and its down-regulation associated with malignant phenotype of hepatocytes, vascular invasion, and progression of HCC, leading to poor prognosis. Thus, ANXA10 might serve as a new potential target of gene therapy for HCC.
UI - 11783914
AU - Dominguez-Malagon H; Gaytan-Graham S
TI - Hepatocellular carcinoma: an update.
SO - Ultrastruct Pathol 2001 Nov-Dec;25(6):497-516
AD - Department of Surgical Pathology, Instituto Nacional de Cancerologia, Tlalpan, Mexico. email@example.com
Hepatocellular carcinoma (HCC) is the most common malignant tumor of males in the world, with an incidence of 1,000,000 new cases a year. It is endemic in Southeast Asia and Sub-Saharan Africa. Risk factors include chronic infection with hepatitis B virus (HBV) and hepatitis C virus (HCV), Aflatoxin B1 uptake, hemochromatosis, and alpha1 -antitripsin deficiency. Epidemiological studies provide evidence for the association of HCC with HBV infection. The incidence of HCC is high in regions hyperendemic for HBV. Chronic carrier state and maternal-infant transmission are important factors in the development of HCC. Evidence of direct oncogenic effect of H BV is well established, HCCs contain viral DNA sequences integrated into hepatocyte DNA that act as random insertional mutagens, and these sites are near genes involved in the control of proliferation and differentiation. The mechanism of hepatitis C virus in hepatocarcinogenesis is still imprecise but a high percentage of cases are related to this virus. Chronic alcohol consumption and cirrhosis are cofactors that increase the development of HCC in patients with chronic viral infection. In experimental carcinogenesis a multipotential element called oval cell proliferates in the early stages. The cellular events are accompanied by increased expression of several growth factors that enhance the survival of carcinogen-activated cells by suppressing apoptosis and increasing elements entering the cell cycle. Hepatic carcinogenesis is a complex process associated with accumulation of genetic and epigenetic changes that run through steps of initiation, promotion and progression. Activation of oncogenes of the "ras" family and others has been detected during chemically-induced HCC in rodents, but there is little evidence of such activation in human tumors. The role of tumor supressor genes such as retinoblastoma (RB) and P53 genes has been documented. Aflatoxin B1 that contaminates foods in endemic areas has a clear role in hepatocarcinogenesis. Metabolites of this toxin promote apurinic sites and G to T mutations in chromosomal DNA, the third base of codon 249 of the P53 gene is preferentially targeted to form aducts with aflatoxin B1, and this mutation has been specifically identified in HBV infection. Histological and cytological criteria for the diagnosis of HCC are well established and are based in architectural and cytological changes. An important issue is the diagnosis of liver "nodules" detected by image, from which small biopsies or aspiration material is obtained. Special studies such as reticulin, CD34, cytokeratin profile, and MOC-31 can be very useful for the differential diagnosis of primary and metastatic tumors. Telomerase activity has been found in HCC and negative in pericancerous tissue. It is more pronounced in poorly differentiated tumors and correlates with factors of clinical importance, such as prognosis and recurrences. Cells of well-differentiated HCC have an ultrastructural appearance similar to normal hepatocytes. During the process of dedifferentiation, there is progressive loss of organization of intracellular organelles. The cell cohesion is lost, intercellular gaps with microvilli appear, the sinusoids become capillarized, and reparative changes are seen in the spaces of Disse. A variety of inclusions, such as Mallory bodies, granular material, secondary lysosomes, and Dubin-Johnson pigment, have been described. Fibrolamellar carcinoma has a characteristic histological picture and ultrastructurally oncocytic features. Neuroendocrine granules and combination of HCC with bile duct carcinoma are seen by electron microscopy.
UI - 11899824
AU - Lopatkina TN; Tanashchuk EL; Siutkin VE; Popova IV
TI - [Assessment of survival and risk of hepatocellular carcinoma in patients with cirrhosis of mixed (viral, alcoholic) etiology]
SO - Ter Arkh 2002;74(2):44-6
AIM: To determine factors affecting overall survival and risk to develop hepatocellular carcinoma (HCC) in patients with hepatic cirrhosis (HC) of mixed (viral, alcoholic) etiology. MATERIAL AND METHODS: Mono- and multi-variance analysis of prognostic effects of such factors as age of the patients, mixed infection VHB/VHC, markers of HBV replication, antibodies to nuclear antigen of HBV (HBcAb) without HBs-system in the serum ("isolated" HBcAb), duration of viral infection, alcohol intake and abuse, dilatation of the esophageal veins, some laboratory parameters were studied in 55 HC patients having at least one marker of hepatitis B virus (HBV) and/or hepatitis C virus (HCV), long history of alcohol abuse. RESULTS: It was found that risk of HCC was associated with duration of alcohol abuse and infection, mixed HBV/HCV infection, age 60 and older. Of independent significance was only duration of alcohol abuse. Lethal outcomes in HC patients in the mixed infection were due to development of HCC (36%) and HC complications (64%). Survival of the patients was less in severe dilatation of the esophageal veins, high clinicolaboratory index, low level of serum albumin, presence of "isolated" BcAb and mixed viral infection. CONCLUSION: Of the greatest prognostic efficacy in respect of survival was the model combining "isolated" HBcAb, the degree of esophageal veins dilatation and hepatitis activity.
UI - 11955389
AU - Cao Z; Cheng X; Wu Z
TI - [Changes of immune function in liver cirrhosis patients after splenectomy combined with resection of hepatocellular carcinoma]
SO - Zhonghua Wai Ke Za Zhi 2002 Feb;40(2):97-9
AD - Department of Hepatic Surgery Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
OBJECTIVE: To study the changes of immune function in liver cirrhosis patients after splenectomy combined with resection of hepatocellular carcinoma (HCC). METHODS: Sixteen patients with HCC associated with liver cirrhosis were divided into two groups: splenectomy combined with hepatectomy (n = 7) and hepatectomy (n = 9). T-lymphocyte subsets such as CD4, CD8, CD4/CD8 and Th-lymphocyte cytokines such as IFN-gamma, IL2, IL10 in 7 ml peripheral venous blood before operation and two months after operation were examined and compared between the two groups. RESULTS: There was no significant difference in pre-operative CD4, CD4/CD8, IL2, IFN-gamma, IL10 levels in the two group. Two months after operation, the levels of CD4 (38.2% +/- 3.7%), CD4/CD8 (1.7 +/- 0.3), IFN-gamma [(104.4 +/- 14.9) pg/ml], IL2 [(98.6 +/- 18.6) pg/ml] were increased and those of CD8 (23.7 +/- 13.7) pg/ml and IL10 [(55.5 +/- 11.2) pn/ml] were decreased in the two groups, but the changes in the group of splenectomy combined with hepatectomy were more obvious than those in the hepatectomy group. The levels of CD4 (32.5% +/- 4.0%), CD4/CD8 (1.1 +/- 0.1), IFN-gamma [(70.5 +/- 12.6) pg/ml], IL2 [(80.9 +/- 13.5) pg/ml] in the group of splenectomy combined with hepatectomy, were much higher than those in the hepatectomy group; those of CD8 (29.4% +/- 4.0%), IL10 [(89.4 +/- 10.0) pg/ml] level were significantly lower than those in the hepatectomy (P < 0.05). CONCLUSION: Splenectomy combined with hepatectomy for HCC associated with liver cirrhosis donor decrease but promote the recover T-lymphocyte subsets and Th1/Th2 cytokines from imbalance and improve the patient's antitumor immune function.
UI - 11819825
AU - Cui J; Zhou XD; Liu YK; Tang ZY; Zile MH
TI - Abnormal beta-catenin gene expression with invasiveness of primary hepatocellular carcinoma in China.
SO - World J Gastroenterol 2001 Aug;7(4):542-6
AD - Department of Food Science and Human Nutrition, Michigan State University, East Lansing, MI 48824, USA. firstname.lastname@example.org
AIM: To study the abnormal expression of beta-catenin gene and its relationship ith invasiveness of primary hepatocellular carcinoma among Chinese people. METHODS: Thirty-four hepatocellular carcinoma (HCC) specimens and adjacent para-cancerous tissues, 4 normal liver tissues were immunohistochemically stained to study subcellular distribution of beta-catenin. Semiquantitive analysis of expression of beta-catenin gene exon 3 mRNA was examined by RT-PCR and in situ hybridization. The relationship between expressions of both beta-catenin protein, mRNA and clinicopathological characteristics of HCC was also analyzed. RESULTS: Immuno-histochemistry showed that all normal liver tissues and para-cancerous tissues examined displayed membranous type staining for beta-catenin protein, occasionally with weak expression in the cytoplasm. While 21 cases (61.8%) of HCC examined showed accumulated type in cytoplasms or nuclei. The accumulated type Labling Index (LI) of cancer tissue and para-cancerous tissue was (59.9 +/- 26.3) and (18.3 +/- 9.7) respectively (P<0.01). Higher accumulated type LI was closely related with invasiveness of HCC. Results of RT-PCR showed the beta-catenin gene exon 3 mRNA Expression Index (EI) of 34 HCCs was higher than that of para-cancerous tissue and normal liver tissue. Using in situ hybridization, the signal corresponding to beta-catenin gene exon 3 mRNA was particularly strong in cytoplasm of HCC when compared with those of para-cancerous and normal liver tissues. Over expression of beta-catenin exon 3 was also found to be correlated with high metastatic potential of HCC. CONCLUSION: Abnormal expression of beta-catenin gene may contribute importantly to the invasiveness of HCC among Chinese people.
UI - 11819835
AU - Cao XY; Liu J; Lian ZR; Clayton M; Hu JL; Zhu MH; Fan DM; Feitelson M
TI - Cloning of differentially expressed genes in human hepatocellular carcinoma and nontumor liver.
SO - World J Gastroenterol 2001 Aug;7(4):579-82
AD - Institute of Digestive Diseases, Xijing Hospital, Xi'an 710033, Shaanxi Province, China. email@example.com
UI - 11895095
AU - Dickinson JA; Wun YT; Wong SL
TI - Modelling death rates for carriers of hepatitis B.
SO - Epidemiol Infect 2002 Feb;128(1):83-92
AD - Department of Community and Family Medicine, The Chinese University of Hong Kong, 4/F School of Public Health, Prince of Wales Hospital, Shatin, NT.
Hepatitis B carriers who acquired the infection perinatally die from hepatocellular carcinoma (HCC) and cirrhosis at high rates. Published cohort studies are largely limited to males and are too small to estimate the age-specific risk of death. We therefore used routinely collected Hong Kong data to estimate the risks. Deaths were partitioned between carriers and non-carriers, then current life table calculations determined life expectancy and probability of dying from HCC or cirrhosis. HCC is the dominant cause of death for male carriers in middle adulthood with a lifetime risk of 27% for HCC compared to 4% for females. Predicted life expectancy is 72 years for male carriers, compared to 79 years for non-carriers. Female carriers have a life expectancy of 81 years and non-carriers 83 years. This model probably applies to all southern Chinese populations and emigrants with similar life history, and other populations that acquired infection early in life.
UI - 12016426
AU - Befeler AS; Di Bisceglie AM
TI - Hepatocellular carcinoma: diagnosis and treatment.
SO - Gastroenterology 2002 May;122(6):1609-19
AD - Division of Gastroenterology and Hepatology, Department of Internal Medicine, Saint Louis University School of Medicine, 3635 Vista Avenue, St. Louis, MO 63110, USA.
Hepatocellular carcinoma is the most frequent primary malignancy of the liver and appears to be rising in incidence in the United States and other developed western countries. Imaging studies play a key role in diagnosis of hepatocellular carcinoma, and more and more commonly, patients are being diagnosed at an asymptomatic stage. The use of triphasic computed tomography scanning and improved magnetic resonance imaging equipment and protocols has led to greater sensitivity and specificity for these techniques in diagnosis of hepatocellular carcinoma. Accurate staging of hepatocellular carcinoma is important in determining prognosis and in helping decide the best treatment for each patient. No one staging system appears optimal, but important factors to be considered are the size of the tumor, severity of underlying liver disease, and the functional status of the patient. Liver transplantation has grown in importance as a treatment for hepatocellular carcinoma but may be limited by availability of donor organs and long waiting times. This situation may be improved by greater use of living donor liver transplantation. Hepatic resection remains an important treatment modality for hepatocellular carcinoma, particularly in the absence of cirrhosis. Tumor ablation by alcohol injection or radiofrequency ablation is associated with favorable outcomes and may be considered a potentially curative treatment. Early diagnosis of hepatocellular carcinoma remains a key goal in improving the poor prognosis of this form of liver cancer. Identifying hepatocellular carcinoma at an early stage is often associated with having better treatment options for patients with small, asymptomatic tumors.
UI - 11808943
AU - Nair S; Shiva Kumar K; Thuluvath PJ; Shivakumar KS
TI - Mortality from hepatocellular and biliary cancers: changing epidemiological trends.
SO - Am J Gastroenterol 2002 Jan;97(1):167-71
AD - Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
OBJECTIVES: The incidence of hepatocellular carcinoma may be rising in the United States. The aim of this study was to determine the epidemiological trends in mortality from hepatocellular carcinoma (HCC) and biliary cancers (BCs) in Maryland during the last 3 decades. METHODS: The number of deaths due to HCC and BCs from 1970 to 1997 were obtained from the Maryland State Department of Health & Hygiene vital statistics database. Malignant neoplasms of the gallbladder and intrahepatic and extrahepatic bile ducts were grouped together as biliary cancers. To determine the trend in mortality, the total time period was divided into seven 4-yr periods. RESULTS: Mortality from HCC increased from 0.94 to 1.84 per 100,000 population (rate ratio = 1.94, CI = 1.87-2.03) and that from BCs increased from 1.28 to 1.7 per 100,000 population (rate ratio = 1.31, CI = 1.26-1.36) over the study period. Although mortality due to HCC doubled in men (1.34 to 2.7 per 100,000) during this period, only a modest increase was observed among women (0.59 to 1.06 per 100,000). Because of a marked increase in the number of deaths among white Americans, the difference in HCC-related mortality between white Americans and African Americans decreased considerably during this period. Mean age at death increased steadily for BCs from 67 to 73 yr, whereas there was no real trend for HCC. Among African Americans, the death from HCC remained stable, but there was a 2-fold increase in BC-related death. CONCLUSIONS: There was a marked increase in deaths from HCC over the past 3 decades in Maryland. This increase was more evident among men and white Americans. Deaths due to BCs increased modestly during the same period of observation. The marked rise in BC-related deaths among African Americans remains unexplained.
UI - 11854908
AU - Xie Q; Liu KD; Hu MY; Zhou K
TI - SF/HGF-c-Met autocrine and paracrine promote metastasis of hepatocellular carcinoma.
SO - World J Gastroenterol 2001 Dec;7(6):816-20
AD - Experimental Research Center of Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
AIM: To explore the role of SF/HGF-Met autocrine and paracrine in metastasis of hepatocellular carcinoma (HCC). METHODS: SF/HGF and c-met transcription and protein expression in HCC were examined by RT-PCR and Western Blot in 4 HCC cell lines, including HepG2, Hep3B, SMMC7721 and MHCC-1, the last cell line had a higher potential of metastasis. sf/hgf cDNA was transfected by the method of Lipofectin into SMMC7721. SF/HGF and c-met antibody were used to stimulate and block SF/HGF-c-met signal transduction. Cell morphology, mobility, and proliferation were respectively compared by microscopic observation, wound healing assay and cell growth curve. RESULTS: HCC malignancy appeared to be relative to its met-SF/HGF expression. In MHCC-1, c-met expression was much stronger than that in other cell lines with lower potential of metastasis and only SF/HGF autocrine existed in MHCC-1. After sf/hgf cDNA transfection or conditioned medium of MHCC-1 stimulation, SMMC7721 changed into elongated morphology, and the abilities of proliferation (P < 0.05) and mobility increased. Such bio-activity could be blocked by c-met antibody (P < 0.05). CONCLUSION: The system of SF/HGF-c-met autocrine and paracrine played an important role in development and metastasis potential of HCC. Inhibition of SF/HGF-c-met signal transduction system may reduce the growth and metastasis of HCC.
UI - 11854909
AU - Wang ZX; Hu GF; Wang HY; Wu MC
TI - Expression of liver cancer associated gene HCCA3.
SO - World J Gastroenterol 2001 Dec;7(6):821-5
AD - Department of General Surgery, Chinese PLA General Hospital of Lanzhou Military Command, Gansu Province, China. firstname.lastname@example.org
AIM: To study and clone a novel liver cancer related gene, and to explore the molecular basis of liver cancer genesis. METHODS: Using mRNA differential display polymerase chain reaction (DDPCR), we investigated the difference of mRNA in human hepatocellular carcinoma (HCC) and paired surrounding liver tissues, and got a gene probe. By screening a human placenta cDNA library and genomic homologous extend, we obtained a full-length cDNA named HCCA3. We analyzed the expression of this novel gene in 42 pairs of HCC and the surrounding liver tissues, and distribution in human normal tissues by means of Northern blot assay. RESULTS: A full-length cDNA of liver cancer associated gene HCCA3 has been submitted to the GeneBank nucleotide sequence databases (Accession No. AF276707). The positive expression rate of this gene was 78.6% (33/42) in HCC tissues, and the clinical pathological data showed that the HCCA3 was closely associated with the invasion of tumor capsule (P=0.023) and adjacant small metastasis satellite nodules lesions (P=0.041). The HCCA3 was widely distributed in the human normal tissues, which was intensively expressed in lungs, brain and colon tissues, while lowly expressed in the liver tissues. CONCLUSION: A novel full-length cDNA was cloned and differentiated, which was highly expressed in liver cancer tissues. The high expression was closely related to the tumor invasiveness and metastasis,that may be the late heredited change in HCC genesis.
UI - 11997564
AU - Blachar A; Federle MP; Ferris JV; Lacomis JM; Waltz JS; Armfield DR; Chu
TI - G; Almusa O; Grazioli L; Balzano E; Li W Radiologists' performance in the diagnosis of liver tumors with central scars by using specific CT criteria.
SO - Radiology 2002 May;223(2):532-9
AD - Department of Radiology, University of Pittsburgh Medical Center, 200 Lothrop St, Pittsburgh, PA 15213, USA.
PURPOSE: To determine the performance of radiologists with differing levels of expertise in the diagnosis of the most common types of liver tumors with central scars (ie, focal nodular hyperplasia [FNH], fibrolamellar hepatocellular carcinoma [HCC], and large hepatic hemangioma) by using specific computed tomographic (CT) findings. MATERIALS AND METHODS: Review of medical records at the University of Pittsburgh Medical Center identified patients with a total of 64 liver tumors that had central scars-including 29 cases of FNH, 20 fibrolamellar HCCs, and 15 large (>3.5 cm in diameter) hemangiomas-and with CT scans available for review. Retrospective review of these scans was performed individually by six radiologists who were blinded to the diagnosis, including two faculty abdominal radiologists, one abdominal imaging fellow, and three radiology residents. Individual performance was evaluated by means of receiver operating characteristic analysis, and interobserver agreement was measured by using the Cronbach alpha. Individual CT findings that may allow differentiation of tumor types were identified with the Kruskal-Wallis test. RESULTS: CT allowed good to excellent interobserver agreement in the diagnosis of tumor type and in recognition of differential findings among the three types. The individual accuracy of diagnosis was very good, with the average area under the receiver operating characteristic curve ranging from 0.81 to 0.90. Although the faculty radiologists performed the best, the differences in performance between the subgroups of readers and the levels of confidence in diagnosis were not statistically significant. The diagnosis of fibrolamellar HCC was the most accurate and had the highest sensitivity, followed by FNH and large hemangioma. Clinical and CT findings that were found to be statistically significant in differentiating tumor types were patient age and sex, tumor size larger than 10 cm, width of tumor scars, invasion of vessels, nodular centripetal enhancement, marked hyperattenuation on arterial phase images, lymphadenopathy, heterogeneity, extrahepatic metastases, surface lobulation, calcification, and isoattenuation with liver tissue on portal venous phase images. CONCLUSION: CT allows accurate differentiation of the most common types of liver tumors with central scars, including FNH, fibrolamellar HCC, and large hemangioma. Copyright RSNA, 2002
UI - 11710692
AU - Morcos M; Dubois S; Bralet MP; Belghiti J; Degott C; Terris B
TI - Primary liver carcinoma in genetic hemochromatosis reveals a broad histologic spectrum.
SO - Am J Clin Pathol 2001 Nov;116(5):738-43
AD - Department of Pathology, Hopital Beaujon, Clichy, France.
Hepatocellular carcinoma (HCC) is a well-known complication of genetic hemochromatosis (GH). However, the frequency of primary liver carcinoma (PLC) with biliary differentiation, such as cholangiocarcinoma (CC) and combined hepatocholangiocarcinoma (CHCC), in GH remains unclear We analyzed the histologic type of 20 PLCs occurring in the background of GH; all patients were homozygotic for the C282Y mutation. Ten were depleted of iron by successive phlebotomies, while the remaining 10 were untreated. Histologically, 13 cases were classified as HCC, 3 as CC, and 4 as CHCC. Immunohistochemical detection of Hep Par 1, cytokeratin 19 (CK19), and MUC1 supported this classification; PLC with biliary differentiation was immunoreactive for MUC1 in 86% (6/7) of cases and for CK19 in 100% (7/7) of cases. The nontumoral liver exhibited no cirrhosis or extensive fibrosis in 6 cases. Von Meyenburg complexes were present in 11 cases and intraparenchymal bile duct adenomas in 3. These data suggest that PLCs in patients with GH present a wide histologic spectrum, with tumors showing frequent biliary differentiation; may arise on a nonfibrotic or a cirrhotic liver; and often are associated with Von Meyenburg complexes and to a lesser extent with bile duct adenomas.
UI - 11896411
AU - Nita ME; Alves VA; Carrilho FJ; Ono-Nita SK; Mello ES; Gama-Rodrigues JJ
TI - Molecular aspects of hepatic carcinogenesis.
SO - Rev Inst Med Trop Sao Paulo 2002 Jan-Feb;44(1):39-48
AD - Discipline of Clinical Gastroenterology, Department of Gastroenterology, School of Medicine, University of Sao Paulo, Sao Paulo, SP, Brazil. email@example.com
Exogenous agents correlated with hepatocellular carcinoma (HCC) have been identified and well characterized. These agents, including the different viruses that cause chronic hepatitis and cirrhosis, can lead to regenerative nodules and dysplastic nodules/adenomatous hyperplasia. These conditions associated with several molecular alterations of hepatocyte ultimately culminate in hepatocellular carcinoma. Recently, there has been a great progress in the identification of somatic and germinative mutations that may be correlated with the development of HCC, justifying a review on the subject. Hence, the factors involved in the process of hepatic carcinogenesis, such as infection by the hepatitis B and C viruses, with a special focus in the molecular alterations described in recent years are discussed herein, pointing out areas potentially relevant for clinical development.
UI - 12011430
AU - Smela ME; Hamm ML; Henderson PT; Harris CM; Harris TM; Essigmann JM
TI - The aflatoxin B(1) formamidopyrimidine adduct plays a major role in causing the types of mutations observed in human hepatocellular carcinoma.
SO - Proc Natl Acad Sci U S A 2002 May 14;99(10):6655-60
AD - Biological Engineering Division and Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Building 56, Room 669, Cambridge, MA 02139, USA.
A G to T mutation has been observed at the third position of codon 249 of the p53 tumor-suppressor gene in over 50% of the hepatocellular carcinoma cases associated with high exposure to aflatoxin B(1) (AFB(1)). Hypotheses have been put fo