Table of Contents
CancerMail from the National Cancer Institute
UI - 20333154
AU - Kratzer W; Kachele V; Merkle E; Mason RA; Buchner M; von Tirpitz C; Pfeiffer M
TI - [Contrast enhanced power Doppler sonography: comparison of various administration forms of the ultrasound contrast agent Levovist]
SO - Rofo Fortschr Geb Rontgenstr Neuen Bildgeb Verfahr 2000 May;172(5):443-8
AD - Abt. Innere Medizin I, Universitatsklinikum Ulm. email@example.com
PURPOSE: Objective of the present study was the comparison of various administration forms of the ultrasound contrast medium Levovist with regard to duration and intensity of contrast enhancement in patients with tumors of the liver or pancreas. PATIENTS AND METHODS: Seven patients with tumors of the liver or pancreas were examined prospectively using power Doppler sonography. Ultrasound contrast enhancement was achieved using Levovist (8 ml, 400 mg/ml) in three different administration forms: 1st as a bolus injection through the main channel, 2nd through the injection valve of an intravenous cannula, or 3rd as a continuous infusion. Semiquantitative evaluation of the degree of contrast enhancement over the course of the examination was conducted by three independent examiners. RESULTS: Levovist, administered by continuous infusion, resulted in a significantly longer average period of contrast enhancement (9:43 min (extratumoral), 7:34 min (intratumoral)) than did the same dosage administered as a bolus injection through the main channel (6:01 min (extratumoral), 4:54 min (intratumoral), p = 0.0156 (extratumoral); p = 0.0313 (intratumoral), but contrast intensity was decreased. Bolus injection through the injection valve of the i.v. cannula was associated with decreased duration and intensity of contrast enhancement compared with injection through the main channel. CONCLUSION: Compared with bolus injection, the continuous infusion of Levovist resulted in a significant prolongation of the duration but in a decreased intensity of contrast enhancement. Administration of Levovist through the injection valve does not result in optimal contrast enhancement and is therefore not recommended.
UI - 21200176
AU - Zissin R
TI - Liver capsular retraction--not a specific sign of malignancy: a reminder.
SO - Eur Radiol 2000;10(12):1993
UI - 21261126
AU - Zocchetti C
TI - [Liver angiosarcoma in humans: epidemiologic considerations]
SO - Med Lav 2001 Jan-Feb;92(1):39-53
AD - Regione Lombardia, Osservatorio Epidemiologico e Flussi Informativi, Via Pola, 9-20124 Milano. Carlo_Zocchetti@regione.lombardia.it
A review of the available literature on angiosarcoma of the liver in an epidemiologic perspective shows that this cancer is rare (0.5-2.5 cases every 10,000,000 persons). It escapes current mortality statistics; it presents peculiar diagnostic difficulties even when histologic material is scrutinized by panels of pathologists; it occurs in both gender at every age (also in children); estimated latency is long (10-40 years, in occupational cases) or very long (60 years and above, in non-occupational cases). Thorotrast, arsenic, and vinyl chloride monomer are frequently listed as risk factors but, along with other substances (steroids, hemochromatosis, diethylstilbestrol, phenelzine, urethane, cyclophosphamide, oral contraceptives) they contribute to explaining the occurrence of no more than 20% of the published cases. Focussing on subjects exposed to vinyl chloride monomer, the published cases were all males aged 35-75 years, with an average latency of 22 years (range 10-40), in jobs with a potential for a high, or very high exposure to VCM (mainly as autoclave cleaner) started before 1970, and limited to a small number of factories. No evidence of a relationship between environmental (non occupational) exposure to VCM and angiosarcoma of the liver emerges from the available literature. We conclude that in more than 25 years of research, apart from the case of vinyl chloride, the etiology of this type of cancer has remained unchanged and largely unknown.
UI - 21365402
AU - Stauss HJ
TI - Benign autoimmunity to combat malignancy.
SO - Clin Exp Immunol 2001 Jul;125(1):1-2
UI - 21385725
AU - Kim MY; Park E; Park JH; Park DH; Moon WS; Cho BH; Shin HS; Kim DG
TI - Expression profile of nine novel genes differentially expressed in hepatitis B virus-associated hepatocellular carcinomas.
SO - Oncogene 2001 Jul 27;20(33):4568-75
AD - Department of Internal Medicine, Division of GI and Hepatology, Research Institute of Clinical Medicine, Chonbuk National University Medical School and Hospital, Chonju, Chonbuk 561-712, Republic of Korea.
Chronic hepatitis B virus (HBV) infection is known to be one of the major causes in the development of hepatocellular carcinoma (HCC), although the biomolecular mechanism(s) involved remain unclear. To identify the cellular gene(s) involved in HBV-associated hepatocarcinogenesis, we used the mRNA differential display method and examined three paired tumor and nontumor tissues, all of which had chromosomally integrated HBV-DNA through chronic infection. Using 240 different combinations of three one-base anchored oligo-dT primers and 80 arbitrary 13-mers, genes decreased or increased in expression more than twofold between each tumor tissue and its paired nontumor tissue were identified. Twenty-nine known genes and four novel genes were differentially over-expressed in the HCC tumor tissues. In contrast, 27 known genes and five novel genes were under-expressed in those tumor tissues. The nucleotide sequences of the nine novel gene fragments were determined and their expression patterns were examined in 40 HCC samples. HA61T2, PT18, HG63T1, and HG57T1 were preferentially over-expressed in 32 cases (80%, P<0.001), 24 cases (60%), 23 cases (57.5%) and 22 cases (55%) of the 40 tumor tissues, respectively. There was an increased frequency of HG57T1 over-expression in HCC patients with HBV-positive serology and low serum alpha-feto protein (AFP) levels (P<0.05). DNT10, PT8, PT19, ENT25 and HA6T4 were under-expressed in 26 cases (65%), 23 cases (57.5%), 21 cases (53%), 20 cases (50%) and 18 cases (45%) of the 40 tumor samples, respectively. There was a strong correlation of DNT10 under-expression with high serum AFP level in HCC patients, irrespective of HBV serology (P<0.01). HA6T4 was preferentially under-expressed in HCC tumors in patients with HBV-positive serology and high serum AFP levels (P<0.05). Thus, the functional analyses of the known and novel genes identified in this study should prove valuable to further understand the mechanism(s) of hepatocarcinogenesis.
UI - 21378003
AU - Wong N; Lam WC; Lai PB; Pang E; Lau WY; Johnson PJ
TI - Hypomethylation of chromosome 1 heterochromatin DNA correlates with q-arm copy gain in human hepatocellular carcinoma.
SO - Am J Pathol 2001 Aug;159(2):465-71
AD - Department of Clinical Oncology, Sir Y. K. Pao Centre for Cancer, The Chinese University of Hong Kong, Shatin, Hong Kong, China. firstname.lastname@example.org
Using comparative genomic hybridization (CGH) analysis, we, and others, have shown that there is a high and consistent incidence of chromosome 1q copy gain in human hepatocellular carcinoma (HCC). Chromosome 1 rearrangements, that involved peri-centromeric breakpoints, have also been frequently reported in karyotypic studies of HCC. Satellite DNA hypomethylation has been postulated as the mechanism underlying the induction of chromosome 1 peri-centromeric instability in many human cancers and in individuals with the rare recessive disorder ICF (immunodeficiency, centromeric heterochromatin instability, facial anomalies). In this study, we have investigated the role of DNA hypomethylation in 1q copy gain in HCC by examining the methylation status of chromosome 1 heterochromatin DNA (band 1q12). Thirty-six histologically confirmed samples of HCC were studied (24 paired tumor and adjacent nontumorous liver tissues, and 12 tumor only). Hypomethylation of satellite 2 (Sat2) DNA in 1q12 was analyzed by Southern blotting using methyl-sensitive enzyme digestion. In parallel, all cases were analyzed by CGH. A strong correlation between hypomethylated Sat2 sequences and 1q copy gain with a 1q12 breakpoint was found (P < 0.001). We postulate that such hypomethylation alters the interaction between the CpG-rich satellite DNA and chromatin proteins, resulting in heterochromatin decondensation, breakage and aberrant 1q formation. Spectral karyotyping further supported the presence of fragile 1q12 in HCC. Of particular interest was the finding of Sat2 DNA hypomethylation in 5 of 24 adjacent nontumorous liver tissues examined. These tissues showed no evidence of malignancy on histological examination nor did they display any CGH abnormalities. Our findings suggest a role for Sat2 demethylation in the early stages of the stepwise progression of liver carcinogenesis.
UI - 21399406
AU - Kashyap R; Jain A; Nalesnik M; Carr B; Barnes J; Vargas HE; Rakela J; Fung J
TI - Clinical significance of elevated alpha-fetoprotein in adults and children.
SO - Dig Dis Sci 2001 Aug;46(8):1709-13
AD - Thomas E. Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh Medical Center, Pennsylvania, USA.
The aim of the current study is to identify underlying pathology associated with elevated serum alpha-fetoprotein (AFP; >20 ng/ml) among patients referred to a tertiary-care academic medical center with emphasis in liver diseases, hepatobiliary surgery, and liver transplantation. From May 1992 to April 1997, 386 patients (320 adults and 66 children) with elevated AFP (>20 ng/ml) were identified from the Medical Archival System (MARS) database at the University of Pittsburgh Medical Center. The medical records from all these patients were retrospectively reviewed. Radiological, pathological, and biochemical profiles were obtained at the time of documented elevated AFP. These patients included: 218 adults with malignancies, 102 adults without malignancies, 18 children and infants with malignancies, and 48 children and infants without malignancies. Thirty-two percent of adults were found to have raised AFP with liver disease and without hepatocellular carcinoma and 78% had some type of malignancy, predominantly hepatocellular carcinoma. Seventy-three percent of infants and children had elevated AFP without malignancy. Based on our findings, we recommend that all patients (adults, infants and children) with raised AFP of >20 ng/ml should undergo thorough evaluation to rule out malignant disease.
UI - 21412526
AU - Chih HW; Chiu HF; Tang KS; Chang FR; Wu YC
TI - Bullatacin, a potent antitumor annonaceous acetogenin, inhibits proliferation of human hepatocarcinoma cell line 2.2.15 by apoptosis induction.
SO - Life Sci 2001 Aug 3;69(11):1321-31
AD - Fooyin Institute of Technology, Kaohsiung County, Taiwan, ROC.
Bullatacin, isolated from the fruit of Annona atemoya, is one of the most potentially effective antitumor annonaceous acetogenins. Bullatacin was studied here for its ability to inhibit the proliferation of 2.2.15 cells, hepatitis B virus (HBV) DNA transfected human hepatocarcinoma cell line. It was found that bullatacin induced cytotoxicity of 2.2.15 cells in a time- and dose-dependent manner. Fifty percent effective dose (ED50) on day 1 of exposure to bullatacin were 7.8 +/- 2.5 nM for 2.2.15 cells. [3H]-Thymidine incorporation assays showed almost the same results. Bullatacin-treatment also reduced concentrations of hepatitis B surface antigen (HBsAg) in the cultured medium released from 2.2.15 cells, coincident with the decrease in the cell proliferation. Analysis of mophological changes of bullatacin-treated 2.2.15 by inverted phase-contrast microscope and eletron microscopy revealed a possible model of action for bullatacin to inhibit proliferation of 2.2.15 cells by inducing apoptosis. Most of the bullatacin-induced cell death was found to be due to apoptosis, as determined by double staining with fluorescein-isothiocyanate (FITC)-labeled annexin V and propidium iodide (PI).
UI - 21193589
AU - Hussain SA; Ferry DR; El-Gazzaz G; Mirza DF; James ND; McMaster P; Kerr DJ
TI - Hepatocellular carcinoma.
SO - Ann Oncol 2001 Feb;12(2):161-72
AD - CRC Institute for Cancer Studies, University Hospital Birmingham, Edgbaston, UK.
Hepatocellular carcinoma (HCC) is the sixth most common cancer of men and eleventh most common cancer of women world-wide. However, because almost every individual who develops liver cancer dies of the disease, HCC is the third most common cause of the cancer deaths in men and seventh most common in women. The treatment of choice for hepatocellular carcinoma remains surgical resection or liver transplantation, in carefully selected cases. In patients with hepatocellular carcinoma not amenable to surgical intervention a variety of different therapeutic interventions have been investigated. These include direct ablation of the tumour using agents such as ethanol or acetic acid, transcatheter arterial chemoembolization, or systemic chemotherapy. The evaluation of their efficacy is compromised by the paucity of adequately powered randomised clinical trials. The main challenge facing the research community over the next decade is to prioritise the most promising treatments and take these forward into multicentre controlled trials. Even if these fail to improve results, they will help reduce the variation in clinical practice by eliminating anecdotal treatment.
UI - 21301533
AU - Kawate S; Ohwada S; Hamada K; Koyama T; Takenoshita S; Morishita Y; Hagiwara K
TI - Mutational analysis of the Smad6 and Smad7 genes in hepatocellular carcinoma.
SO - Int J Mol Med 2001 Jul;8(1):49-52
AD - Second Department of Surgery, Gunma University Faculty of Medicine, Maebashi, Gunma 371-8511, Japan.
Resistance to the transforming growth factor-beta (TGF-beta) is a frequently found phenotype in human malignancies. The recent identification of Smad6 and Smad7, both anti-Smads which inhibit TGF-beta signaling, raises a possibility that constitutive activation of the anti-Smads by a somatic mutation may impair the TGF-beta signaling pathway. We tested this hypothesis by screening the entire coding sequences of these anti-Smads for mutations in 52 hepatocellular carcinoma (HCC) samples using polymerase chain reaction - single strand conformation polymorphism analysis. We detected no mutations, but found 3 single nucleotide polymorphisms (SNPs) in the Smad6 gene and 2 SNPs in the Smad7 gene. These results suggest that mutations of the Smad6 and Smad7 genes are not the main cause of the TGF-beta resistance in human HCC.
UI - 21306803
AU - Cui J; Yang D
TI - [Methylation status of c-fms oncogene in hepatocellular carcinoma and its relation with clinical pathology]
SO - Zhonghua Gan Zang Bing Za Zhi 2001 Jun;9(3):137-8
AD - Department of Gastroenterology, Zhujiang Hospital, First Military Medical University, Guangzhou 510282, China.
OBJECTIVE: To study the methylation status change of c-fms oncogene in hepatocellular carcinogenesis, and to clarify the abnormal highly expressing mechanism of c-fms/CSF-1R in hepatocellular carcinoma (HCC). METHODS: Genome DNA of 30 cases of HCC tissue and matching surrounding-cancer tissue were digested with restrictive endonucleases Hpa II/Msp I. Methylation status of c-fms oncogene was tested with Southern blot. Methylation status of c-fms oncogene in the HCC tissue and the matching surrounding-cancer tissue was compared. The relation between methylation status of c-fms oncogene and clinical pathology of HCC was determined. RESULTS: Methylation status of c-fms oncogene decreased in 36.7% (11/30) HCC tissue and 13.3% (4/30) matching surrounding-cancer tissue. The hypomethylation rate of c-fms oncogene in the HCC tissue was higher than that in the matching surrounding-cancer tissue. There was significant correlation between Edmondson scale of HCC and hypomethylation of c-fms oncogene. The hypomethylation rate of HCC in Edmondson III-IV was higher than that in Edmondson I-II. CONCLUSIONS: Hypomethylation of c-fms oncogene may be an important molecular mechanism leading to abnormally high expressing of CSF-1R, which contributes to occurrence and deterioration of HCC.
UI - 21306804
AU - Yan F; Zhou K; Wu D; Yang J; Gong J; Shen J
TI - [Evaluation of dynamic enhanced fast multiplanar spoiling gradient recalled(FMPSPGR) in the diagnosis of small hepatocellular carcinoma]
SO - Zhonghua Gan Zang Bing Za Zhi 2001 Jun;9(3):139-41
AD - Department of Radiology, Zhongshan Hospital, Shanghai Medical University, Shanghai 200032, China.
OBJECTIVE: To analyze the features of small hepotocellular carcinoma (SHCC) by spin echo (SE) sequence and dynamic enhanced FMPSPGR, and to compare the sensitivity for detecting and the accuracy for characterization, further to discuss the value of FMPSPGR in the diagnosis of SHCC. METHODS: SE T(1)WI, T(2)WI and FMPSPGR dynamic imaging of the liver were performed for 58 patients with SHCC. The sensitivity for detecting and accuracy for characterization were statistically compared. RESULTS: Seventy-two lesions were found in 58 patients. In the detection of SHCC, the order of the sensitivity was dynamic enhanced FMPSPGR>SE T(2)WI>no-enhanced FMPSPGR>SE T(1)WI. Dynamic enhanced FMPSPGR was significantly higher than any of the others. There was significant difference between no-enhanced FMPSPGR and SE T(2)WI, but not significant difference between T(2)WI and no-enhanced FMPSPGR. In the characterization of SHCC, the accuracy of pre- and post-contrast FMPSPGR was significantly higher than that of SE (T(1)WI+T(2)WI) with remarkable statistical difference. CONCLUSIONS: FMPSPGR dynamic imaging is superior to SE in the detection and characterization of SHCC. The sensitivity for detecting and the accuracy for characterization will be improved when both FMPSPGR and SE are used.
UI - 21306805
AU - Shen W; Wu X
TI - [Clinical significance of differential display cDNA fragment MRG98.2 expression in hepatocellular carcinoma]
SO - Zhonghua Gan Zang Bing Za Zhi 2001 Jun;9(3):142-4
AD - Department of Digestive Diseases, Second Affiliated Hospital of Chongqing University of Medical Sciences, Chongqing 400010, China.
OBJECTIVE: To search for the gene related to hepatocellular carcinoma (HCC), and to study its potential significance in liver oncogenesis. METHODS: The difference in mRNA expression among HCC, nontumorous liver tissue, and normal liver tissue was investigated by differential display technique. Ten hepatic tissues of hepatoma versus surrounding noncancerous liver tissues were examined with MRG98.2 as a probe in Dot blot analysis. Expression of vascular endothelial growth factor (VEGF) mRNA in above-mentioned samples was examined with reverse transcription-polymerease chain reaction (RT-PCR). RESULTS: Differential display cDNA fragment MRG98.2 was isolated from hepatoma samples. Dot blot analysis showed that MRG98.2 was expressed in 7 cases of HCC samples (7/10) but only in 2 of the surrounding noncancerous hepatic tissues (2/10). The expression of VEGF mRNA was upregulated in 6/7 of HCC samples expressed MRG98.2. CONCLUSIONS: MRG98.2 may be a gene related to HCC. Its expression in HCC correlates with VEGF mRNA. MRG98.2 expression is helpful in predicting a tendency toward invasion and metastasis of HCC or a poor prognosis.
UI - 20198153
AU - Roncalli M; Bianchi P; Grimaldi GC; Ricci D; Laghi L; Maggioni M; Opocher E; Borzio M; Coggi G
TI - Fractional allelic loss in non-end-stage cirrhosis: correlations with hepatocellular carcinoma development during follow-up.
SO - Hepatology 2000 Apr;31(4):846-50
AD - Departments of Pathology and Research Laboratories, Humanitas Clinical Institute of Rozzano, Milan, Italy. email@example.com
Hepatocellular carcinoma (HCC) is usually preceded by cirrhosis whose genetic background is still poorly understood. The aim of this study was to evaluate, in non-end-stage cirrhosis, the fractional allelic loss (FAL) at loci mostly reported to be altered in HCC and the microsatellite instability (MSI). Twenty cases of cirrhosis were retrospectively selected. Eleven had developed an HCC during the follow-up (HCC-prone group), while 9 remained HCC-free (HCC-free group). Microdissected hepatocellular cirrhotic nodules from basal liver biopsies, were studied at 20 loci (on the chromosomal arms 1p and 1q, 3p, 4q, 6q, 7q, 8p, 13q, and 18q) and with the mononucleotide repeats BAT26 and TGFbIIR. Genetic changes were detected in both groups. Overall, the FAL index was statistically increased in the HCC-prone group (0.213) as compared to the HCC-free group (0.094; P =.044). Allelic loss at chromosomal arms 1p, 4q, 13q, 18q, and concurrent losses at more than 3 loci were confined to the HCC-prone group. In both groups, MSI was never ascertained using BAT26 and TGFbIIR. In conclusion, an increased FAL index and the lack of MSI characterize the non-end-stage cirrhosis of patients undergoing HCC during follow-up. These data emphasize the role of early clonal changes in chronic liver disease, and their potential predictive significance for clinical use.
UI - 20257975
AU - Okabe H; Ikai I; Matsuo K; Satoh S; Momoi H; Kamikawa T; Katsura N; Nishitai R; Takeyama O; Fukumoto M; Yamaoka Y
TI - Comprehensive allelotype study of hepatocellular carcinoma: potential differences in pathways to hepatocellular carcinoma between hepatitis B virus-positive and -negative tumors.
SO - Hepatology 2000 May;31(5):1073-9
AD - Department of Gastroenterological Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan. firstname.lastname@example.org
To examine the role of the loss of heterozygosity (LOH) in hepatitis-related carcinogenesis, we performed a genome-wide scan of LOH in 44 tumors of hepatocellular carcinoma (HCC) using 216 microsatellite markers throughout all human chromosomes. A high frequency of LOH (>30% of informative cases) was observed at 33 loci on chromosome arms 4q, 6q, 8p, 8q, 9p, 9q, 13q, 16p, 16q, 17p, and 19p. LOH on 19p has not yet been reported, and that appears to be a new candidate in the search for tumor suppressor genes. High rates of LOH are correlated with hepatitis B virus (HBV) positivity, poorly differentiated tumors, vascular invasion, and intrahepatic metastasis (P <.0001). LOH on 13q and 16q occurred more frequently in HBV(+) patients (P <.0001), and LOH on 6q occurred more frequently in virus-negative patients (P <.001). The frequency of LOH on 4q and 13q was significantly lower in well-differentiated tumors than in moderately and poorly differentiated tumors (P <.01). In contrast, LOH on 6q was frequently detected in well-differentiated tumors compared with other histological subclasses (P <.001). Our results suggest that LOH on 6q may play an important role in the early stage of hepatocarcinogenesis in virus-negative patients, but different mechanisms might underlie the initial step to carcinogenesis in HBV(+) patients. LOH on 13q and 16q may play an essential role in the progression of HBV(+) tumors. Further studies of fine deletion mapping on chromosomes 13q and 16q are required to define the genomic segments on which putative tumor suppressor genes responsible for HBV(+) tumors exist.
UI - 20287453
AU - Kawai H; Suda T; Aoyagi Y; Isokawa O; Mita Y; Waguri N; Kuroiwa T; Igarashi M; Tsukada K; Mori S; Shimizu T; Suzuki Y; Abe Y; Takahashi T; Nomoto M; Asakura H
TI - Quantitative evaluation of genomic instability as a possible predictor for development of hepatocellular carcinoma: comparison of loss of heterozygosity and replication error.
SO - Hepatology 2000 Jun;31(6):1246-50
AD - The Third Division, Department of Internal Medicine, Department of Surgery, Niigata University School of Medicine, Niigata, Japan.
Both loss of heterozygosity (LOH) and replication error (RER) are considered to be phenotypes of genomic instability. To unveil the role of the genomic instability in hepatocarcinogenesis, frequencies of LOH and RER were simultaneously determined in 15 hepatocellular carcinomas (HCCs), surrounding nontumorous liver tissues (SL), and 13 liver tissues with chronic viral hepatitis void of cancer (NC) by referencing peripheral blood leukocytes (PBLs) from the corresponding donor using 18 microsatellite markers spread throughout the genome. LOH was significantly frequent in HCC compared with that in SL or NC (P =.005, P =.0003, respectively) and observed preferentially at particular microsatellite loci, D1S204, D2S123, D8S1106, D9S266, D16S748, and D19S601. Although the higher prevalence of RER was also significant in HCC compared with that in NC (P =.03), in most cases the errors were detected at very low frequencies and random loci. Both LOH and RER tended to appear more prevalently in SL than in NC. The occurrence rate of LOH was higher in the tissues associated with hepatitis B virus (HBV) than with hepatitis C virus (HCV) infection especially in HCC (P =.03). When referencing SL instead of PBLs, the prevalence of LOH and RER in HCC significantly decreased (P =.02 and P =.03, respectively). These results suggest that LOH is closely associated with multistep hepatocarcinogenesis especially under HBV infection, but RER is imperceptibly associated. The quantitative evaluation of the frequency of LOH by referencing PBLs may be a useful predictor for HCC development in chronic liver diseases.
UI - 20494429
AU - Roncalli M; Borzio M; Bianchi P; Laghi L
TI - Comprehensive allelotype study of hepatocellular carcinoma.
SO - Hepatology 2000 Oct;32(4 Pt 1):876
UI - 21220191
AU - Berdon WE
TI - Hepatoblastoma.
SO - Pediatr Radiol 2001 Apr;31(4):306
UI - 21236669
AU - Jung SE; Kim KH; Kim MY; Kim DY; Lee SC; Park KW; Kim WK
TI - Clinical characteristics and prognosis of patients with hepatoblastoma.
SO - World J Surg 2001 Feb;25(2):126-30
AD - Department of Pediatric Surgery, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-ku, Seoul 110-744, Korea.
Hepatoblastoma is a rare pediatric malignancy that frequently appears in an advanced unresectable stage. Improved resectability and survival rate have been reported with the help of neoadjuvant chemotherapy. Between January 1987 and June 1995 a series of 20 patients were managed with a diagnosis of hepatoblastoma. The median age at diagnosis was 13 months (2 months to 7 years 10 months) with a male/female ratio of 13:7. Chemotherapy effectively reduced the tumor volume (with statistical significance: p = 0.008) and was able to convert seven of nine initially unresectable tumors (78%) to resectable ones. Altogether, 14 operations were done, 12 radical and 2 palliative, with or without adjuvant chemotherapy. The whole population was followed for a median duration of 33 months; and the median survival for the whole group was 26 months. The curative resection group displayed a 5-year survival rate of 61.1%, but none in the noncurative group survived more than 13 months (p = 0.0001). In the univariate analysis for prognostic factors, large tumor size at diagnosis and the absence of thrombocytopenia were associated with poor survival, but these differences were not statistically significant. Pure fetal histology was not associated with better prognosis. In this new era of neoadjuvant chemotherapy, the optimal management strategy for hepatoblastoma is still debated, with radical surgical resection at the earliest possible time being the final goal. For now an individualized approach appears to be the protocol of choice.
UI - 21244962
AU - Balkau B; Kahn HS; Courbon D; Eschwege E; Ducimetiere P; Paris Prospective Study
TI - Hyperinsulinemia predicts fatal liver cancer but is inversely associated with fatal cancer at some other sites: the Paris Prospective Study.
SO - Diabetes Care 2001 May;24(5):843-9
AD - Institut National de la Sante et de la Recherche Medicale Unite 258 and the Faculty of Medicine, University Paris-Sud, Villejuif, France. email@example.com
OBJECTIVE: To investigate whether insulin is a risk factor for death by site-specific cancers. RESEARCH DESIGN AND METHODS: This was a prospective cohort study of 6,237 nondiabetic French working men between ages 44 and 55 years at baseline from the Paris Prospective Study cohort. Death by site-specific cancers was investigated in relation to baseline insulin concentrations during fasting and 2 h after a 75-g oral glucose tolerance test. RESULTS: Of the original 6,237 men in the cohort, 1.739 died over the 23.8 years of follow-up. 778 (45%) from cancer. Baseline hyperinsulinemia, both fasting and 2-h, was significantly associated with fatal liver cancer, with age-adjusted standardized hazards ratios of 2.72 (95% CI 1.87-3.94) and 3.41 (2.23-5.21). In contrast, fasting hyperinsulinemia was inversely associated with fatal lip, oral cavity, and pharynx cancer and larynx cancer, with hazards ratios of 0.55 (0.41-0.75) and 0.63 (0.47-0.83), respectively; 2-h insulin concentrations were inversely associated with stomach and larynx cancers (hazards ratios 0.62 [0.43-0.90] and 0.66 [0.50-0.891, rcspectively). These relationships were stable after adjusting for other risk factors. Insulin concentrations remained negatively associated with deaths from these cancers in analyses restricted to men who smoked and in those who were not chronic alcohol consumers.
UI - 21404097
AU - El-Serag HB; Richardson PA; Everhart JE
TI - The role of diabetes in hepatocellular carcinoma: a case-control study among United States Veterans.
SO - Am J Gastroenterol 2001 Aug;96(8):2462-7
AD - Sections of Gastroenterology and Health Services Research, The Houston Veterans Affairs Medical Center and Baylor College of Medicine, Texas 77030, USA.
OBJECTIVE: Diabetes mellitus (DM) has been reported to increase the risk of hepatocellular carcinoma (HCC). We carried out a case-control study to examine the role of DM while controlling for several known risk factors of HCC. METHODS: All hospitalized patients with primary liver cancer (PLC) during 1997-1999 were identified in the computerized database of the Department of Veterans Affairs, the Patient Treatment File. Controls without cancer were randomly assigned from the Patient Treatment File during the same time period. The inpatient and outpatient files were searched for several conditions including DM, hepatitis C virus (HCV), hepatitis B virus (HBV), alcoholic cirrhosis, autoimmune hepatitis, hemochromatosis, and nonspecific cirrhosis. Adjusted odds ratios (OR) were calculated in a multivariable logistic regression model. RESULTS: We identified 823 patients with PLC and 3459 controls. The case group was older (62 yr [+/-10] vs 60 [+/-11], p < 0.0001), had more men (99% vs 97%, 0.0004), and a greater frequency of nonwhites (66% vs 71%, 0.0009) compared with controls. However, HCV- and HBV-infected patients were younger among cases than controls. Risk factors that were significantly more frequent among PLC cases included HCV (34% vs 5%, p < 0.0001), HBV (11% vs 2%, p < 0.0001), alcoholic cirrhosis (47% vs 6%, p < 0.0001), hemochromatosis (2% vs 0.3%, p < 0.0001), autoimmune hepatitis (5% vs 0.5%, p < 0.0001), and diabetes (33% vs 30%, p = 0.059). In the multivariable logistic regression, diabetes was associated with a significant increase in the adjusted OR of PLC (1.57, 1.08-2.28, p = 0.02) in the presence of HCV, HBV, or alcoholic cirrhosis. Without markers of chronic liver disease, the adjusted OR for diabetes and PLC was not significantly increased (1.08, 0.86-1.18, p = 0.4). There was an increase in the HCV adjusted OR (17.27, 95% Cl = 11.98-24.89) and HBV (9.22, 95% CI = 4.52-18.80) after adjusting for the younger age of HCV- and HBV-infected cases. The combined presence of HCV and alcoholic cirrhosis further increases the risk with an adjusted OR of 79.21 (60.29-103.41). The population attributable fraction for HCV among hospitalized veterans was 44.8%, whereas that of alcoholic cirrhosis was 51%. CONCLUSION: DM increased the risk of PLC only in the presence of other risk factors such as hepatitis C or B or alcoholic cirrhosis. Hepatitis C infection and alcoholic cirrhosis account for most of PLC among veterans.
UI - 21417678
AU - Yakicier MC; Legoix P; Vaury C; Gressin L; Tubacher E; Capron F; Bayer J; Degott C; Balabaud C; Zucman-Rossi J
TI - Identification of homozygous deletions at chromosome 16q23 in aflatoxin B1 exposed hepatocellular carcinoma.
SO - Oncogene 2001 Aug 23;20(37):5232-8
AD - INSERM U434, CEPH 27 Rue Juliette Dodu 75010 Paris, France.
Loss of heterozygosity (LOH) represents the most frequent genetic alteration observed in hepatocellular carcinoma (HCC). Chromosome 16q is of particular interest as it exhibits LOH in 29% of HCC tumors and is frequently lost in breast, prostate, ovarian and gastric carcinomas. We genotyped 157 HCC tumors for 17 microsatellite markers distributed on chromosome 16q and determined a common region of LOH localized between the markers D16S518 and D16S504. By refining the boundaries of two interstitial LOH and two homozygous deletions, the critical region was delimited to 180 kb between D16S3096 and D16S3029. This region is located in intron 8 of the WWOX/FOR gene, but a search for mutations in all coding exons of this gene in 27 HCC tumors and cell lines did not reveal any tumor somatic alterations. Furthermore, by RT-PCR, no abnormal transcripts of this WWOX/FOR gene was detected in nine HCC cell lines. Finally, analysis of the p53 gene mutations with the clinical parameters of all tumors revealed that the two homozygous deletions have occurred in tumors presenting a R249S mutation. Our data revealed a relationship between chromosome 16q homozygous deletions and R249S p53 mutations in tumors where the patient had been exposed to aflatoxin B1 (P=0.002). These results are consistent with a role of aflatoxin B1 in the instability of chromosome 16q at the fragile site FRA16D. However, the nature of the specific gene that is altered during hepatocarcinogenesis remains to be elucidated.
UI - 21413778
AU - Yeh SH; Chen PJ; Shau WY; Chen YW; Lee PH; Chen JT; Chen DS
TI - Chromosomal allelic imbalance evolving from liver cirrhosis to hepatocellular carcinoma.
SO - Gastroenterology 2001 Sep;121(3):699-709
AD - Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan.
BACKGROUND & AIMS: Cirrhotic nodules have long been assumed to be the precancerous lesions of hepatocellular carcinoma (HCC). We thus investigated the allelic imbalance (AI) in cirrhotic nodules to define the genetic aberrations in early hepatocarcinogenesis. METHODS: One hundred eighty cirrhotic nodules from 7 female patients with HCC were collected by microdissection. Their clonality nature was assessed by examining the X chromosome methylation pattern. AI in monoclonal cirrhotic nodules and the corresponding HCCs were analyzed with microsatellite polymorphic markers. RESULTS: One hundred one out of 180 nodules (56.1%) were monoclonal and the average fractional AI (FAI) was 21%, lower than the 40% in HCC. Their overall AI patterns differed significantly from that in HCC (P < 0.001) with FAI on 2q, 4q, 8p, and Xq higher than the mean value. Comparison of FAI in nodules (stratified by increasing total AI events) further revealed a progressive increase of FAI on 4q, 8p, and Xq. In contrast, FAI on 1p, 13q, 16q, and 17p were low in nodules but rose above the mean only in HCC. CONCLUSIONS: About half of the cirrhotic nodules are monoclonal and already have chromosome aberrations. AI on 4q, 8p, and Xq may be the earlier mutations, whereas AI on 1p, 13q, 16q, and 17p occurs late in hepatocarcinogenesis.
UI - 21417316
AU - Kirimlioglu H; Dvorchick I; Ruppert K; Finkelstein S; Marsh JW; Iwatsuki S; Bonham A; Carr B; Nalesnik M; Michalopoulos G; Starzl T; Fung J; Demetris A
TI - Hepatocellular carcinomas in native livers from patients treated with orthotopic liver transplantation: biologic and therapeutic implications.
SO - Hepatology 2001 Sep;34(3):502-10
AD - Thomas E. Starzl Transplantation Institute, University of Pittsburgh Medical Center, Pittsburgh, PA 15261, USA.
The gross and histopathologic characteristics of 212 nonfibrolamellar hepatocellular carcinomas (HCCs) discovered in native livers removed at the time of liver transplantation were correlated with features of invasive growth and tumor-free survival. The results show that most HCCs begin as small well-differentiated tumors that have an increased proliferation rate and induce neovascularization, compared with the surrounding liver. But at this stage, they maintain a near-normal apoptosis/mitosis ratio and uncommonly show vascular invasion. As tumors enlarge, foci of dedifferentiation appear within the neoplastic nodules, which have a higher proliferation rate and show more pleomorphism than surrounding better-differentiated areas. Vascular invasion, which is the strongest predictor of disease recurrence, correlates significantly with tumor number and size, tumor giant cells and necrosis, the predominant and worst degree of differentiation, and the apoptosis/mitosis ratio. In the absence of macroscopic or large vessel invasion, largest tumor size (P <.006), apoptosis/mitosis ratio (P <.03), and number of tumors (P <.04) were independent predictors of tumor-free survival and none of 24 patients with tumors having an apoptosis/mitosis ratio greater than 7.2 had recurrence. A minority of HCCs (<15%) quickly develop aggressive features (moderate or poor differentiation, low apoptosis/mitosis ratio, and vascular invasion) while still small, similar to flat carcinomas of the bladder and colon. In conclusion, hepatic carcinogenesis in humans is a multistep and multifocal process. As in experimental animal studies, aggressive biologic behavior (vascular invasion and recurrence) correlates significantly with profound alterations in the apoptosis/mitosis ratio and with architectural and cytologic alterations that suggest a progressive accumulation of multiple genetic abnormalities.
UI - 21417319
AU - Donato MF; Arosio E; Del Ninno E; Ronchi G; Lampertico P; Morabito A; Balestrieri MR; Colombo M
TI - High rates of hepatocellular carcinoma in cirrhotic patients with high liver cell proliferative activity.
SO - Hepatology 2001 Sep;34(3):523-8
AD - Division of Hepatology, IRCCS Maggiore Hospital, Milan, Italy.
The prevalence, risk factors, and clinical significance of high liver cell proliferative activity were investigated in 208 well-compensated cirrhotic patients (150 men; 50 years; 135 with chronic hepatitis C) who had been under prospective surveillance for hepatocellular carcinoma (HCC) with annual abdominal ultrasound (US) and serum alpha-fetoprotein (AFP) determination. Immunostaining for proliferating cell nuclear antigen (PCNA) was employed to assess liver cell proliferative activity in formalin-fixed, paraffin-embedded liver specimens. The percentage of reactive nuclei was calculated by a computer-assisted image analysis system. The overall PCNA labeling index (LI) ranged from 0.1% to 12.5% (mean, 2.1%), being significantly higher in the 50 patients who developed HCC during 88 +/- 42 months of follow-up than in the 158 patients who remained cancer-free (3.6% +/- 2.4% vs. 1.6% +/- 1.5%; P <.0001). By receiver operating curve (ROC), a 2.0% cut-off value of PCNA-LI discriminated between patients at high and low risk for developing cancer. By multivariate analysis, high histologic grading scores and gender were associated to PCNA LI >2.0%. The yearly incidence of HCC was 5.2% for the 80 patients with PCNA-LI >2.0% compared with 1.1% for the 128 with low PCNA-LI (relative risk, 4.90; 95% CI, 2.63-9.55). By multivariate analysis, PCNA-LI >2.0% was the strongest independent predictor of cancer (hazard ratio, 5.49; 95% CI, 2.90-10.37). Overall, survival was significantly lower in patients with high liver cell proliferative activity rates than in those with low proliferative rates (10% vs. 75%; P <.0001). In conclusion, development of HCC in patients with compensated cirrhosis seems to be reliably predicted by liver cell proliferation status.
UI - 21417814
AU - Lim JH; Choi D; Cho SK; Kim SH; Lee WJ; Lim HK; Park CK; Paik SW; Kim YI
TI - Conspicuity of hepatocellular nodular lesions in cirrhotic livers at ferumoxides-enhanced MR imaging: importance of Kupffer cell number.
SO - Radiology 2001 Sep;220(3):669-76
AD - Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Ilwon-dong, Kangnam-ku, Seoul 135-710, Korea.
PURPOSE: To correlate the conspicuity of hepatocellular carcinomas and dysplastic nodules on ferumoxides-enhanced magnetic resonance (MR) images with the number of Kupffer cells in the hepatic lesions, as compared with that in background liver in histopathologic findings. MATERIALS AND METHODS: Sixty-nine histopathologically proved moderately or poorly differentiated hepatocellular carcinomas, 10 well-differentiated hepatocellular carcinomas, and 19 dysplastic nodules were retrospectively studied in 68 patients with cirrhosis who underwent ferumoxides-enhanced MR imaging. The contrast-to-noise ratio between the nodules and surrounding parenchyma was calculated at T2-weighted fast spin-echo imaging, and the difference in the number of Kupffer cells between the nodules and surrounding hepatic tissue was calculated histopathologically. The results of MR imaging and histopathologic examination were correlated. RESULTS: All 69 moderately or poorly differentiated hepatocellular carcinomas had high contrast-to-noise ratios at MR imaging and large differences in the number of Kupffer cells. Six of the 10 well-differentiated hepatocellular carcinomas had contrast-to-noise ratios of zero or nearly zero, and five of these had little difference in the number of Kupffer cells. All 19 dysplastic nodules had contrast-to-noise ratios of zero or nearly zero, and there were virtually no differences in the number of Kupffer cells. CONCLUSION: Hepatocellular nodule conspicuity at ferumoxides-enhanced MR imaging depends on differences in the number of Kupffer cells within a nodule and the surrounding cirrhotic liver; moderately or poorly differentiated hepatocellular carcinomas can be distinguished from well-differentiated hepatocellular carcinomas and dysplastic nodules.
UI - 21063757
AU - Emile JF; Adam R; Sebagh M; Marchadier E; Falissard B; Dussaix E; Bismuth H; Reynes M
TI - Hepatocellular carcinoma with lymphoid stroma: a tumour with good prognosis after liver transplantation.
SO - Histopathology 2000 Dec;37(6):523-9
AD - Service d'Anatomopathologie,Centre Hepatobiliaire, Hopital Paul Brousse and UPRES 1596 'Virus Hepatotropes et Cancer', Universite Paris Sud, France. firstname.lastname@example.org
AIMS: Carcinomas with lymphoid stroma arising in non-liver-organs have a better prognosis than other carcinomas and may be associated with Epstein-Barr virus. We determined the frequency, characteristics and prognosis of hepatocellular carcinomas with lymphoid stroma. METHODS AND RESULTS: Histology of the livers of 162 patients with hepatocellular carcinoma, who underwent an orthotopic liver transplantation, was reviewed independently by three pathologists. Hepatocellular carcinoma with lymphoid stroma was diagnosed when all tumour samples contained more lymphocytes than tumour cells. Epstein-Barr virus was detected by in-situ hybridization and by polymerase chain reaction. Five patients (3.6%) were classified as hepatocellular carcinomas with lymphoid stroma. All patients were males. Cirrhosis was present in four/five patients. Serum alpha-fetoprotein levels were normal. Inter-observer histological reproducibility was good. Tumour cells did not contain Epstein-Barr virus. The five patients were alive without tumour at three years, although two of them had adverse prognostic factors at the time of transplantation (more than one tumour with a diameter > or = 40 mm). Only one patient had tumour recurrence, but he survived 7.6 years post-transplantation. The 5-year survival of patients with hepatocellular carcinoma with lymphoid stroma was better than that of the patients with other types of hepatocellular carcinomas (P = 0.04). CONCLUSIONS: Hepatocellular carcinoma with lymphoid stroma should be considered as a distinct clinicopathological and prognostic entity.
UI - 21157388
AU - Quaglia A; Bhattacharjya S; Dhillon AP
TI - Limitations of the histopathological diagnosis and prognostic assessment of hepatocellular carcinoma.
SO - Histopathology 2001 Feb;38(2):167-74
AD - Department of Histopathology, Royal Free and University College Medical School, Royal Free Campus, London, UK.
UI - 20564938
AU - Stringer MD
TI - Liver tumors.
SO - Semin Pediatr Surg 2000 Nov;9(4):196-208
AD - Children's Liver Centre, St James University Hospital, Leeds, UK.
Liver tumors in children are rare, potentially complex, and encompass a broad spectrum of disease processes. Any age group may be affected, including the fetus. Most present with abdominal distension and/or a mass. Accurate preoperative diagnosis is usually possible using a combination of ultrasound scanning and cross-sectional imaging techniques (CT and/or MR), supplemented by liver biopsy and measurement of tumor markers. The most common benign tumors are hemangiomas, but mesenchymal hamartoma, focal nodular hyperplasia, and adenoma also are found. In Western countries, hepatoblastoma is the most common primary malignant liver tumor; disease-free survival is now possible in more than 80% of affected patients because of advances in combination chemotherapy, improved techniques of surgical resection, and the selective use of liver transplantation. In contrast, there has been less progress in the management of hepatocellular cancer, which still poses many therapeutic challenges. Copyright 2000 by W.B. Saunders Company
UI - 21241365
AU - Wang JH; Lu SN; Changchien CS; Lee CM; Tung HD; Chen TM
TI - Flash echo gray scale imaging with subtraction in assessment of small hepatocellular carcinoma treated with percutaneous ethanol injection: preliminary report.
SO - J Ultrasound Med 2001 May;20(5):539-44
AD - Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Taiwan, Republic of China.
OBJECTIVE: To assess the therapeutic effect of percutaneous ethanol injection on small hepatocellular carcinoma by using a flash echo imaging system, a newly developed technique for detecting echoes from microbubble contrast agents more efficiently. METHODS: Six patients with 7 small nodular hepatocellular carcinomas, proved by fine-needle aspiration cytologic or pathologic examination, were included. Percutaneous ethanol injection was performed until there was no intratumoral color signal on conventional color and power Doppler ultrasonography. A bubble contrast agent was then injected, and flash echo imaging in the subtraction mode was performed for assessment of the therapeutic effect. Dynamic computed tomography, magnetic resonance imaging, and hepatic angiography were also used for evaluation of the therapeutic effect. RESULTS: Five tumors had perfusion defects that were equal in size to or larger than the tumors. No tumor stain was shown on hepatic angiography. Two tumors had partial perfusion defects. Viable tumors were confirmed by tumor resection in 1 case and cytologic examination in the other. CONCLUSIONS: Our preliminary results show that flash echo imaging with subtraction has potential value in evaluation of the therapeutic effect of percutaneous ethanol injection on small hepatocellular carcinoma.
UI - 21243578
AU - Kao CH; Tsai SC; Wang JJ; Ho YJ; Ho ST
TI - Evaluation of hepatobiliary function by hepatobiliary scintigraphy in hepatoma patients after transcatheter arterial embolization.
SO - Scand J Gastroenterol 2001 May;36(5):553-7
AD - Dept. of Nuclear Medicine, Taichung Veterans General Hospital, Taiwan. email@example.com
BACKGROUND: Transcatheter arterial embolization (TAE) is the treatment of choice for inoperable hepatocellular carcinoma. However, altered and impaired gallbladder function due to gallbladder infarction and bile duct necrosis following TAE have been reported. METHODS: Hepatobiliary function was evaluated using quantitative Tc-99m DISIDA hepatobiliary scintigraphy in 40 hepatoma patients before and after TAE. The patients were separated into two groups: group 1 (20 patients), who received pre-cystic artery TAE, and group 2 (also 20 patients), who received post-cystic artery TAE. RESULTS: After TAE, there were no significant changes in liver or bile duct function in the patients of either group. However, for group I patients, significantly decreased gallbladder function was found after TAE. CONCLUSIONS: Altered and impaired gallbladder function is common in hepatoma patients who receive pre-cystic artery TAE, and Tc-99m DISIDA cholescintigraphy may be useful for evaluating hepatobiliary function in hepatoma patients who receive TAE.
UI - 21407974
AU - Balter JM; Dawson LA; Kazanjian S; McGinn C; Brock KK; Lawrence T; Ten Haken R
TI - Determination of ventilatory liver movement via radiographic evaluation of diaphragm position.
SO - Int J Radiat Oncol Biol Phys 2001 Sep 1;51(1):267-70
AD - Department of Radiation Oncology, University of Michigan Health Systems, Ann Arbor, MI 48109-0010, USA. firstname.lastname@example.org
PURPOSE: To determine the accuracy of estimation of liver movement inferred by observing diaphragm excursion on radiographic images. METHODS AND MATERIALS: Eight patients with focal liver cancer had platinum embolization microcoils implanted in their livers during catheterization of the hepatic artery for delivery of regional chemotherapy. These patients underwent fluoroscopy, during which normal breathing movement was recorded on videotape. Movies of breathing movement were digitized, and the relative proj