National Cancer Institute®
Last Modified: November 21, 2001
UI - 21243501
AU - Tabor E
TI - Hepatocellular carcinoma: global epidemiology.
SO - Dig Liver Dis 2001 Mar;33(2):115-7
AD - Office of Blood Research and Review, Food and Drug Administration, Rockville, MD 20852-1448, USA. email@example.com
UI - 21280254
AU - Aguayo A; Patt YZ
TI - Liver cancer.
SO - Clin Liver Dis 2001 May;5(2):479-507
AD - Department of Gastrointestinal Medical Oncology, Division of Medicine, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
The prognosis of patients with HCC remains dismal. Even in the subgroups of patients who have the most favorable characteristics and are eligible for surgical resection, the 5-year survival rate is less than 25%. For patients with more advanced disease, the median survival time is less than 1 year. The good news in HCC research is that the disease can be prevented. In Taiwan, the rate of HCC in children aged 6 to 9 years decreased from 5.2 per million population before the neonatal vaccination program began in 1984 to 1.3 per million population in the first vaccinated cohort. Treatment of viral hepatitis with IFN may decrease the rates of long-term development of HCC. Other agents that may prevent second primary tumors following resection of HCC, such as polyprenoic acid and acylic retinoid, are also being investigated.
UI - 21338543
AU - Okano H; Shiraki K; Inoue H; Ito T; Yamanaka T; Deguchi M; Sugimoto K;
TI - Sakai T; Ohmori S; Fujikawa K; Murata K; Takase K; Nakano T "Variable echo sign" (ultrasonographical alteration of echogenicity) in cavernous hepatic hemangioma.
SO - Int J Oncol 2001 Aug;19(2):337-40
AD - First Department of Internal Medicine, Mie University School of Medicine, 2-175 Edobashi, Tsu, Mie 514-8507, Japan.
There are few reports describing cavernous hepatic hemangiomas with alteration of ultrasonographical imaging during examinations. We performed ultrasonographic examination of 64 cavernous hepatic hemangiomas and recognized 26 cases (41%) with an alteration of echogenicity during the examinations. We refer to this alteration of echogenicity of cavernous hepatic hemangioma as a "variable echo sign". We performed angiography of the cavernous hepatic hemangiomas with variable echo sign. Most of these imaging patterns showed mild or moderate pooling, suggesting that the alteration of echogenicity might be based on a slow blood flow exchange. We suggest that a variable echo sign is specific to ultrasonographic imaging with cavernous hepatic hemangioma and may be useful to differentiate cavernous hepatic hemangioma from other tumors.
UI - 21383860
AU - Beissert M; Jenett M; Kessler C
TI - [Diagnosis of space-occupying lesions of the liver. What is the value of diagnostic imaging?]
SO - MMW Fortschr Med 2001 Apr 26;143(17):29-33
AD - Institut fur Rontgendiagnostik der Universitat Wurzburg. firstname.lastname@example.org
Ultrasound in B-mode or tissue harmonic imaging is the procedure of first choice for investigating the liver. If US is employed to screen for metastatic disease, B-mode contrast harmonic imaging should be used in addition to conventional ultrasound. For the diagnosis "space-consuming liver lesion", the echogenicity and clinical aspects determine the further diagnostic procedure. Echogenic liver lesions in patients with known malignant disease, and echo-poor or "echo-complex" lesions always indicate a need for further spiral CT or MRT investigations. In tumour patients, spiral CT offers the advantage of enabling simultaneous evaluation of the parenchyma, and abdominal staging. Primary SPIO-amplified MRT is indicated whenever the primary interest is the detection of space-consuming liver lesions. In the case of echogenic lesions in the absence of underlying malignant disease, US follow-up suffices. Here, differential diagnostic information can be gained from the vascular distribution patterns of a lesion obtained with color-coded duplex US. Hepatic lesions that, after exhausting all diagnostic imaging procedures remain suspicious, require biopsy.
UI - 21375989
AU - Sugihara S; Suto Y; Kamba M; Ogawa T
TI - Comparison of various techniques of iron oxide-enhanced breath-hold MR imaging of hepatocellular carcinoma.
SO - Clin Imaging 2001 Mar-Apr;25(2):104-9
AD - Department of Radiology, Faculty of Medicine, Tottori University, Nishicho, Yonago 683, Japan.
The purpose of our study is to compare qualitatively and quantitatively the abilities of various superparamagnetic iron oxide (SPIO)-enhanced breath-hold magnetic resonance imaging (MRI) techniques to detect hepatocellular carcinoma (HCC). Eight patients with HCCs were imaged. The images were obtained with conventional T2-weighted spin-echo imaging (CSE), half-Fourier single-shot turbo spin-echo (HASTE), single-shot gradient-echo type echo planar imaging (GE-EPI), and single-shot spin-echo type echo planar imaging (SE-EPI) before and after SPIO administration. The liver signal-to-noise ratios (SNRs) in CSE and each EPI sequence were significantly decreased after SPIO administration. GE-EPI had the highest decrease ratio (DR) of liver SNR, followed by SE-EPI (TE=98), SE-EPI (TE=28), CSE, and HASTE in this order. The relative contrasts with GE-EPI and SE-EPI (TE=98) were significantly higher than that with CSE after SPIO administration. On receiver operating characteristic (ROC) analysis, diagnostic accuracy did not differ significantly among the pulse sequences after SPIO administration. GE-EPI and SE-EPI (longer TE) were useful for SPIO-enhanced breath-hold MRI performed to detect HCC.
UI - 21385138
AU - Yang EB; Zhao YN; Zhang K; Mack P
TI - Microsatellite alterations in human hepatocellular carcinoma infected with hepatitis B virus: associated with the elevation of serum alpha-fetoprotein.
SO - Int J Oncol 2001 Sep;19(3):513-8
AD - Department of Experimental Surgery, Singapore General Hospital, Outram Road, Singapore 169608. email@example.com
Identification of the basic genetic changes in human hepatocellular carcinoma (HCC) is very important for the understanding of this cancer. In this study, genomic DNA from 29 pairs of HCC and corresponding non-tumour tissues infected with hepatitis B virus (HBV) was prepared. Five CA-repeated microsatellite markers, including D8S277, D3S1029, D5S409, D2S123, and TP53, were used to analyse microsatellite alterations and their subtypes in these patients by polymerase chain reaction (PCR) amplification and denatured polyacrylamide gel electrophoresis. Microsatellite alterations were found in 15 of the 29 HCC patients (51.72%), implying that microsatellites are unstable in genomic DNA of HBV-infected HCC. It was found that frequency of microsatellite alterations in these HCC patients was not associated with patients' age, sex, status of tumour differentiation, and tumour size. Frequency of microsatellite alterations in HCC patients with cirrhosis tended to be less than that in patients without cirrhosis, but Fisher's exact test, 2-tailed, showed that this difference was not significant. Significantly more microsatellite alterations in serum alpha-fetoprotein (AFP)-positive cases were observed than those in serum AFP-negative ones, implying that the elevation of AFP in HBV-infected HCC may be associated with microsatellite stability.
UI - 21398001
AU - Nishiguchi S; Shiomi S; Ofuji S; Ishizu H; Iwata Y; Sasaki N; Minamitani
TI - S; Ochi H Leiomyosarcoma of the liver detected by high F-18 fluorodeoxyglucose positron emission tomographic uptake.
SO - Clin Nucl Med 2001 Sep;26(9):798-9
AD - Third Department of Internal Medicine, Osaka City University Medical School, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan.
UI - 21423017
AU - Niketeghad F; Decker HJ; Caselmann WH; Lund P; Geissler F; Dienes HP;
TI - Schirmacher P Frequent genomic imbalances suggest commonly altered tumour genes in human hepatocarcinogenesis.
SO - Br J Cancer 2001 Sep 1;85(5):697-704
AD - Institute of Pathology, University of Cologne, Joseph Stelzmann Str. 9, Cologne, D-50931, Germany.
Hepatocellular carcinoma (HCC) is one of the most frequent-occurring malignant tumours worldwide, but molecular changes of tumour DNA, with the exception of viral integrations and p53 mutations, are poorly understood. In order to search for common macro-imbalances of genomic tumour DNA, 21 HCCs and 3 HCC-cell lines were characterized by comparative genomic hybridization (CGH), subsequent database analyses and in selected cases by fluorescence in situ hybridization (FISH). Chromosomal subregions of 1q, 8q, 17q and 20q showed frequent gains of genomic material, while losses were most prevalent in subregions of 4q, 6q, 13q and 16q. Deleted regions encompass tumour suppressor genes, like RB-1 and the cadherin gene cluster, some of them previously identified as potential target genes in HCC development. Several potential growth- or transformation-promoting genes located in chromosomal subregions showed frequent gains of genomic material. The present study provides a basis for further genomic and expression analyses in HCCs and in addition suggests chromosome 4q to carry a so far unidentified tumour suppressor gene relevant for HCC development. Copyright 2001 Cancer Research Campaign.
UI - 21190916
AU - Matsumura T; Makino R; Mitamura K
TI - Frequent down-regulation of E-cadherin by genetic and epigenetic changes in the malignant progression of hepatocellular carcinomas.
SO - Clin Cancer Res 2001 Mar;7(3):594-9
AD - Second Department of Internal Medicine, Showa University School of Medicine, Tokyo, Japan.
E-cadherin mediates cell-cell adhesion by associating with catenins. Loss of E-cadherin function by genetic or epigenetic alteration of the E-cadherin gene (CDH1) leads to tumorigenesis. To study the involvement of E-cadherin dysfunction in liver tumorigenesis, we examined the allelic loss and methylation of 5'-CpG sites of CDH1 in hepatocellular carcinomas (HCCs). Loss of heterozygosity (LOH) of CDH1 and adjacent 16q22-23 loci was observed in 13 of 30 (43%) HCCs. Methylation of the 5'-CpG of CDH1 was analyzed by Southern blot hybridization, and hypermethylation was observed in 8 of the 24 (33%) HCCs examined. The amount of E-cadherin mRNA was analyzed by RNase protection assay, and a decrease in E-cadherin mRNA was observed in 10 of the 23 cases examined. A reduction in E-cadherin was found in 10 of 21 HCCs using immunoblot analysis. The amount of E-cadherin was comparable to that of E-cadherin mRNA. Down-regulation of E-cadherin was common in cases with LOH but rare in cases with methylated promoter. These results suggest that hypermethylation of the CDH1 promoter is present in a small cell population in the tumor, thus the methylation status is liable to vary according to individual cell condition. Hypermethylation was observed in early stage HCCs, whereas LOH was found frequently in more malignant tumors. Down-regulation of E-cadherin is closely related to the progression of HCCs and is stably induced by LOH of CDH1.
UI - 21271452
AU - Lau WY; Ho S; Leung WT; Chan M; Lee WY; Johnson PJ
TI - What determines survival duration in hepatocellular carcinoma treated with intraarterial Yttrium-90 microspheres?
SO - Hepatogastroenterology 2001 Mar-Apr;48(38):338-40
AD - Department of Surgery, Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong.
BACKGROUND/AIMS: The survival duration of patients with nonresectable hepatocellular carcinoma confined to the liver and treated with intraarterial yttrium-90 microspheres was highly variable. METHODOLOGY: Eighty-two patients treated by this method were analyzed. Thirty-one patients who lived for one year or longer from the date of first treatment were classified as 'long survivors' and 51 patients who died within 1 year were classified as 'short survivors'. RESULTS: Comparison between the 2 categories suggested that lower pretreatment level of alpha-fetoprotein and higher tumor-to-normal uptake ratio of yttrium-90 microspheres favored longer survival. Results also indicated that the treatment was effective even for large tumors and for postoperative recurrence. Repeated treatment of viable residual or recurrent tumors offered further palliation and prolongation of survival. CONCLUSIONS: Pretreatment alpha-fetoprotein level, tumor-to-normal uptake ratio of yttrium-90 microspheres and the number of treatments determine survival duration.
UI - 21271489
AU - Hara M; Mori M; Hara T; Yamamoto K; Honda M; Nishizumi M
TI - Risk of developing hepatocellular carcinoma according to the titer of antibody to hepatitis C virus.
SO - Hepatogastroenterology 2001 Mar-Apr;48(38):498-501
AD - Department of Community Health Science, Saga Medical School, Nabeshima 5-1-1, Saga 849-8501, Japan. firstname.lastname@example.org
BACKGROUND/AIMS: Hepatitis C virus infection has been reported to be one of the main risk factor for developing hepatocellular carcinoma in Japan. The aim of the study was to examine the differences in the risk of developing hepatocellular carcinoma according to the titer of antibody to HCV. METHODOLOGY: A total of 13,173 inhabitants had their titers of anti-HCV examined based on a second generation passive hemagglutination assay, and we thus found 1,758 inhabitants whose anti-HCV titers were equal to or above 2(5). After carefully comparing our findings with the list of hepatocellular carcinoma in the Saga Prefectural Cancer Registry, we ascertained 45 cases of hepatocellular carcinoma (males 37, females 8). The logistic regression model was used to estimate the Odds ratio of risk factors for hepatocellular carcinoma. RESULTS: The risk of hepatocellular carcinoma in the subjects from 60-69 years of age was significantly higher than in the other age groups (Odds ratio = 3.88, P < 0.01). The risk of hepatocellular carcinoma in the males was also significantly higher than in the females (Odds ratio = 8.96, P < 0.001). The risk of hepatocellular carcinoma in the subjects with a titer of anti-HCV equal to or above 2(12) was significantly higher than in the subjects with a titer of less than 2(12) (Odds ratio = 33.46, P < 0.001). Furthermore, the age- and sex-adjusted risk for developing hepatocellular carcinoma for the subjects with a titer equal to or above 2(12) was significantly higher than that for subjects with a titer of less than 2(12) (Odds ratio = 32.56, P < 0.001). CONCLUSIONS: The risk of developing hepatocellular carcinoma was significantly high in the subjects with a titer equal to or above 2(12). To measure the titer of anti-HCV is thus considered to be useful for effectively detecting infection in a mass screening program.
UI - 21271493
AU - Yoshidome S; Tanabe G; Yoshida A; Ueno S; Hamanoue M; Mitue S; Aikou T
TI - Risk prediction using histology of noncancerous liver before hepatic resection for hepatocellular carcinoma.
SO - Hepatogastroenterology 2001 Mar-Apr;48(38):518-22
AD - First Department of Surgery, Kagoshima University School of Medicine, 8-35-1 Sakuragaoka, Kagoshima, 890-8520 Japan. email@example.com
BACKGROUND/AIMS: The aim of this study is to elucidate the feasibility of the risk assessment of hepatic resection by histological evaluation of noncancerous liver in patients with hepatocellular carcinoma. METHODOLOGY: The study involved 78 patients with hepatocellular carcinoma who had undergone a needle biopsy of noncancerous liver before hepatic resection. The histological activity index score which consists of four categories indicating the inflammatory activity and the degree of fibrosis was determined, and its association with complications after hepatic resection was examined. RESULTS: Postoperative complications occurred in 26 of the first 52 patients that underwent hepatic resection. A logistic analysis selected histological activity index score as an independent factor related to postoperative complications (Odds ratio 1.31, P < 0.02). Postoperative complications occurred more frequently in patients with a histological activity index score > or = 6 that had undergone resection of two or more segments (P < 0.05), and also in those with histological activity index score > or = 10 that had undergone segmentectomy or subsegmentectomy (P < 0.05). When the histological activity index score was taken into consideration in deciding operative procedures for a further 20 patients, the incidence of postoperative complications reduced considerably to 10%. CONCLUSIONS: Preoperative histological evaluation of noncancerous liver by a needle biopsy may be helpful in deciding the operative procedure to avoid complications after hepatic resection for hepatocellular carcinoma.
UI - 21287869
AU - Trevisani F; D'Intino PE; Morselli-Labate AM; Mazzella G; Accogli E;
TI - Caraceni P; Domenicali M; De Notariis S; Roda E; Bernardi M Serum alpha-fetoprotein for diagnosis of hepatocellular carcinoma in patients with chronic liver disease: influence of HBsAg and anti-HCV status.
SO - J Hepatol 2001 Apr;34(4):570-5
AD - Dipartimento di Medicina Interna, Cardioangiologia, Epatologia, University of Bologna, Italy. firstname.lastname@example.org
BACKGROUND: It is not established whether virological status affects the efficiency of alpha-fetoprotein (AFP) as a hepatocellular carcinoma (HCC) marker among patients with chronic liver disease (CLD). METHODS: We enrolled in a case-control study 170 HCC and 170 CLD patients, matched for age, sex, CLD and HBsAg/anti-HCV status. The AFP sensitivity, specificity, positive (PPV) and negative (NPV) predictive values were calculated. PPV and NPV were evaluated for three additional HCC prevalences (5, 10, and 20%). RESULTS: The best discriminating AFP value was 16 ng/ml. A value of 20 ng/ml (above which investigations for HCC are recommended) had equivalent sensitivity (60.0 vs. 62.4%) and specificity (90.6 vs. 89.4%). PPV of 20 ng/ml was 84.6% but decreased to 25.1% at 5% tumor prevalence. NPV was 69.4% and rose to 97.7% at 5% prevalence. In the different groups of infected patients PPV ranged from 80.0 to 90.9%, falling to 17.4-34.5% at 5% prevalence. In noninfected patients PPV was 100% at any HCC prevalence. NPV ranged from 59.0 to 73.0%, reaching 96.5-98.1% at 5% prevalence. CONCLUSIONS: In CLD patients, AFP monitoring misses many HCCs and inappropriately arouses suspicion of malignancy in many patients. Its usefulness is barely affected by the infection responsible for CLD. An AFP elevation could be more indicative of HCC in non-infected patients.
UI - 21393542
AU - Hung CH; Changchien CS; Lu SN; Eng HL; Wang JH; Lee CM; Hsu CC; Tung HD
TI - Sonographic features of hepatic adenomas with pathologic correlation.
SO - Abdom Imaging 2001 Sep-Oct;26(5):500-6
AD - Division of Gastroenterology, Department of Internal Medicine, Chang Gung Memorial Hospital, 123 Ta Pei Road, Niao Sung 833, Kaohsiung, Taiwan, ROC.
BACKGROUND: We compared the sonographic characteristics of hepatic adenomas with pathologic findings. METHODS: Information over 10 years was collected on 12 patients (six men, six women; mean age = 47 years) with surgically proven hepatic adenomas. Clinical data, sonographic features, and histopathologic findings were reviewed. RESULTS: The tumors in males were smaller and simpler than those in women (p < 0.05, Fisher's exact test). Four of the six larger tumors (>5 cm) showed mixed-echoic patterns corresponding with pathologically intratumoral hemorrhage and necrosis. Four homogeneously hypoechoic tumors had less change in tumor composition. Three homogeneously hyperechoic tumors had evident fatty changes inside. One isoechoic tumor had a hypoechoic rim, that correlated mostly to the tumor itself and compressed liver parenchyma. Seven of the 12 tumors had thin fibrous capsules that were not seen on sonography. CONCLUSION: Hepatic adenomas have variable sonographic appearances depending on changes in the tumor. Hypoechoic, hyperechoic, and mixed-echoic patterns represent simple adenoma, adenoma with fatty metamorphosis, and hemorrhagic necrosis, respectively, in tumors.
UI - 21420001
AU - Poovorawan Y; Chongsrisawat V; Tangkijvanich P
TI - Problems and prevention of viral hepatitis in Thailand.
SO - J Med Assoc Thai 2001 Jun;84 Suppl 1():S18-25
AD - Department of Paediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
To this day, viral hepatitis remains a major public health problem in Thailand. Chronic infection with hepatitis B and C viruses are the leading causes of chronic liver diseases, including cirrhosis and hepatocellular carcinoma (HCC). Outbreaks of hepatitis A virus continue to occur in Thailand, even after several years of consistently declining prevalence rates. Also, the reduction in prevalence of hepatitis D virus infection has been observed among intravenous drug users over the past decade. Hepatitis E virus constitutes a rather unusual cause of sporadic acute hepatitis in Thailand. Highly effective vaccines are currently available for prevention of hepatitis A and B, however, as yet no effective vaccine for hepatitis C is imminent. Following rapid progress in the development of molecular techniques, several new hepatitis viruses have been identified. Among these, Hepatitis G, TT and SEN viruses have recently been described but their significance as to causation of human liver disease has yet to be established. This article reviews the current epidemiology, molecular biology, and strategies aimed at prevention and control of hepatitis virus infection in Thailand emphasizing new developments and recent data obtained from our research studies.
UI - 21295255
AU - Hemming AW; Gallinger S; Greig PD; Cattral MS; Langer B; Taylor BR;
TI - Verjee Z; Giesbrecht E; Nakamachi Y; Furuya KN The hippurate ratio as an indicator of functional hepatic reserve for resection of hepatocellular carcinoma in cirrhotic patients.
SO - J Gastrointest Surg 2001 May-Jun;5(3):316-21
AD - Department of Surgery, University of Florida, Gainesville 32610, USA. email@example.com
Predicting the ability of the cirrhotic liver to withstand resection remains a challenge for the surgeon. This study evaluates the use of the hippurate ratio, a novel assessment of glycine conjugation of para-aminobenzoic acid by the liver, as a preoperative indicator of functional hepatic reserve. Between 1998 and 2000, sixty-one cirrhotic patients were prospectively assessed for hepatic resection using the hippurate ratio, indocyanine green retention at 15 minutes (ICG R-15), and other standard measures of liver function. Twenty-six patients were excluded as candidates for resection on the basis of inadequate functional hepatic reserve. Patients excluded from resection had significantly higher ICG R-15 values (29% +/- 9% vs. 16% +/- 12%, P = 0.001), higher Child-Pugh scores (5.9 +/- 0.9 vs. 5.3 +/- 0.4, P = 0.01), and lower hippurate ratios (30% +/- 14% vs. 45% +/- 15%, P = 0.005). There was a significant correlation between the hippurate ratio and ICG R-15. Other indicators of liver function such as factor V, factor VII, albumin, bilirubin, prothrombin time, and transaminases were no different between patients who did and those who did not undergo resection. Of the 35 patients resected, there were seven (20%) who developed varying degrees of liver failure with three perioperative deaths (8.5%). Patients who had some degree of liver failure had significantly lower hippurate ratios than patients who had no liver failure (29% +/- 10% vs. 48% +/- 14%, P = 0.002). There was no difference in ICG R-15 values between patients who had liver failure and those who did not. The hippurate ratio offers information on hepatocellular reserve that is not provided by other measures of liver function and may allow better selection of cirrhotic patients for liver resection.
UI - 21419010
AU - Shuto T; Hirohashi K; Kubo S; Tanaka H; Yamamoto T; Higaki I; Takemura
TI - S; Kinoshita H Treatment of adrenal metastases after hepatic resection of a hepatocellular carcinoma.
SO - Dig Surg 2001;18(4):294-7
AD - Second Department of Surgery, Osaka City University Medical School, Osaka, Japan. firstname.lastname@example.org
BACKGROUND: The adrenal gland is a common site of extrahepatic metastases from a hepatocellular carcinoma (HCC). However, treatment of adrenal metastases has not been well characterized. METHODS: Of 562 patients who underwent hepatic resection for a HCC, 91 developed extrahepatic metastases. We reviewed the medical records of 10 patients with adrenal metastases (9 males and 1 female; mean age 63 years at the time of hepatic resection). RESULTS: The mean diameter of the primary tumors was 5 cm, and all were located in the right lobe of the liver. The mean interval from hepatic resection to recurrence was 18 months. Seven patients underwent treatment of intrahepatic recurrence. To treat the adrenal metastases, surgical resection was performed in 4 patients, and transcatheter arterial embolization was performed in 1 patient. The patients treated had no other extrahepatic metastases. The mean diameter of the resected adrenal tumors was 6 cm. There was no hospital mortality. With surgical resection, 1 patient has been alive 63 months after recurrence. CONCLUSIONS: Adrenal metastases from a HCC were often large at the time of diagnosis. Since surgical resection was a safe procedure, and some patients could be alive for a long time, it should be performed whenever possible. Copyright 2001 S. Karger AG, Basel
UI - 21438126
AU - Mazure NM; Nguyen TL; Danan JL
TI - Severe hypoxia specifically downregulates hepatocyte nuclear factor-4 gene expression in HepG2 human hepatoma cells.
SO - Tumour Biol 2001 Sep-Oct;22(5):310-7
AD - Centre de Recherche sur l'Endocrinologie Moleculaire et le Developpement CNRS-UPR 9078, Meudon-Bellevue, France.
The liver is one of the organs in which hypoxia helps to regulate gene expression under normal physiological conditions and in diseases such as cirrhosis and cancer. We postulated that the expression/activity of some of the 'liver-enriched' transcription factors, which control liver-specific genes, was sensitive to hypoxia. We tested hepatocyte nuclear factor-1 (HNF-1), HNF-3 and HNF-4, which play key roles in differentiation, development and hepatic gene expression, using HepG2 human hepatoma cells cultured under hypoxic conditions. Severe hypoxia/anoxia downregulated HNF-4 DNA-binding activity while DNA-binding activity of HNF-1 and HNF-3 remained unaffected. These hypoxic conditions also strongly and specifically decreased cell contents of HNF-4 protein, indicating that the decrease in HNF-4 DNA-binding activity was due to the lower amount of protein and not to decreased DNA-binding affinity. Northern analysis indicated that the expression of the hnf-4 gene was also downregulated in HepG2 cells cultured under hypoxic conditions. These results provide evidence that hypoxic stress triggers a cascade of events that inhibits the transactivation potential of HNF-4 in HepG2 cells. This step may be crucial in modulating the expression of a subset of liver genes that are targets for this nuclear receptor. This relationship provides a new route for the investigation of the effects of hypoxia on the liver cell. Copyright 2001 S. Karger AG, Basel
UI - 21468155
AU - Choi D; Kim SH; Lim JH; Cho JM; Lee WJ; Lee SJ; Lim HK
TI - Detection of hepatocellular carcinoma: combined T2-weighted and dynamic gadolinium-enhanced MRI versus combined CT during arterial portography and CT hepatic arteriography.
SO - J Comput Assist Tomogr 2001 Sep-Oct;25(5):777-85
AD - Department of Radiology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
PURPOSE: The purpose of this study was to compare the preoperative detectability of hepatocellular carcinomas (HCCs) using combined T2-weighted and dynamic gadolinium-enhanced MRI and combined CT during arterial portography (CTAP) and CT hepatic arteriography (CTHA). METHOD: Thirty-three patients with 43 HCCs underwent T2-weighted and dynamic gadolinium-enhanced MRI and combined CTAP and CTHA. The diagnosis was established by pathologic examination following surgical resection in 26 patients and by biopsy in 7 patients. The MR protocol included fast SE with two TEs (including T2-weighted imaging) and precontrast and gadolinium-enhanced T1-weighted fast multiplanar spoiled gradient-recalled echo images with dynamic study. The MR images of all sequences and the paired CTAP and CTHA images were independently reviewed by three radiologists. Image review was conducted on a segment-by-segment basis. Diagnostic accuracy was evaluated with receiver operating characteristic analysis. RESULTS: The accuracies (Az values) of MRI of all sequences and combined CTAP and CTHA for all observers were 0.960 and 0.959, respectively. The mean sensitivities of MRI and CT were 90 and 94%, respectively. The differences were not statistically significant. The mean specificity of MRI (99%) was significantly higher than that of combined CTAP and CTHA (92%). CONCLUSION: Combined T2-weighted and dynamic gadolinium-enhanced MRI is as accurate as combined CTAP and CTHA for preoperative detection of HCCs.
UI - 21467321
AU - Huang BJ; Huang TJ; Liang QW; Huang CW; Fang Y
TI - [Quantitative detection of HER-2 oncogene amplification in primary hepatocellular carcinoma using dual FISH technique and its clinical significance]
SO - Yi Chuan Xue Bao 2001;28(9):793-800
AD - Department of Etiology, Cancer Institute, Sun Yat-sen University of Medical Sciences, Guangzhou 510060, China.
To investigate the frequency of HER-2 oncogene amplification in primary hepatocellular carcinoma (HCCs) and its relationships with clinicopathological parameters and prognosis, 42 surgical samples from patients with primary HCCs were detected for their HER-2 oncogene amplification by dual FISH technique, and then the correlations between HER-2 amplification and clinicopathological characteristics and prognosis were analyzed statistically. HER-2 oncogene amplification was detected in 9 of 42 (21.4%) primary HCCs, including 4 (9.5%) cases with high copy (HC) and 5 (11.9%) ones with low copy (LC). HER-2 amplification was associated significantly with postoperative survival time of HCC patients examined (P = 0.046) and the presence of HER-2 gene amplification showed a trend toward a correlation with tumor size (P = 0.085), but wasn't relative to sex, age, AFP level, HBV infection, postoperative relapse and clinical staging of HCC patients tested (P > 0.05). On the other hand, gain of the HER-2 oncogene copy was examined in 31 of 42(73.8%) primary HCCs, consisting of 9 (21.4%) cases with HER-2 amplification and 22(52.4%) ones with aneusomy 17/polysomy 17. There weren't significant relationships between gain of HER-2 oncogene copy and, HCC patient's sex, tumor size, clinical staging, postoperative relapse and survival time (P > 0.05), but gain of HER-2 oncogene copy correlated significantly to patients' age, AFP level and HBV infection (P < 0.05). The study indicated that there were a lower frequency of HER-2 oncogene amplification and a higher frequency of aneusomy 17/polysomy 17 in primary HCCs and that HER-2 oncogene amplification activation might be involved in the development and progression of a subset of HCCs, and seemed to be a valuably independent prognosis factor predicting postoperative poorer survival for patients with HCC.
UI - 21463360
AU - Kato A; Miyazaki M; Ambiru S; Yoshitomi H; Ito H; Nakagawa K; Shimizu H;
TI - Yokosuka O; Nakajima N Multidrug resistance gene (MDR-1) expression as a useful prognostic factor in patients with human hepatocellular carcinoma after surgical resection.
SO - J Surg Oncol 2001 Oct;78(2):110-5
AD - First Department of Surgery, School of Medicine, Chiba University, Chuo-Ku, Chiba, Japan.
BACKGROUND: Multidrug resistance gene (MDR-1) overexpression has been correlated with tumor aggressiveness and worse prognosis in some human neoplasms. The aim of this study is to evaluate the clinical value of MDR-1 mRNA expression as a prognostic factor after surgical resection in human hepatocellular carcinoma (HCC). METHODS: MDR-1 mRNA levels in tissue samples from 34 patients with HCC, who underwent surgical resection, were measured by quantitative northern blot analysis. We stratified these patients into two groups according to a ratio of MDR-1 mRNA levels of HCC to nontumorous tissue; MDR-1 mRNA ratio > or = 1.0 and < 1.0. The overall and disease-free survival rates were analyzed using multivariate regression analysis. RESULTS: The median survival periods were 10.3 and 35.8 months for patients with the MDR-1 mRNA ratio > or = 1.0 and < 1.0, respectively, and the corresponding 5-year survival rates were 33 and 54%, respectively, P < 0.05. The multivariate analysis revealed that TNM stage and MDR-1 mRNA ratio were independent factors for predicting overall survival after surgical resection. CONCLUSION: This study suggested that the measurement of the MDR-1 mRNA levels in HCC and nontumorous liver tissue might be a useful prognostic factor after surgical resection in patients with HCC. Copyright 2001 Wiley-Liss, Inc.
UI - 21467975
AU - Chen TC; Nakanuma Y; Zen Y; Chen MF; Jan YY; Yeh TS; Chiu CT; Kuo TT;
TI - Kamiya J; Oda K; Hamaguchi M; Ohno Y; Hsieh LL; Nimura Y Intraductal papillary neoplasia of the liver associated with hepatolithiasis.
SO - Hepatology 2001 Oct;34(4 Pt 1):651-8
AD - Department of Pathology, Chang Gung Memorial Hospital, Chang Gung University School of Medicine, Tao Yuan, Taipei, Taiwan.
Intraductal papillary growth of neoplastic biliary epithelia with a fine fibrovascular stalk (intraductal papillary neoplasia of liver [IPN-L]) resembling intraductal papillary mucinous neoplasm of pancreas is occasionally associated with hepatolithiasis. In this study, 136 cases histologically. IPN-L was found in 41 of 136 hepatolithiasis cases (30.1%). Sixty-two IPN-L cases (42 women and 20 men; age range, 59.8 +/- 10 years) were divided into 4 types (type 1, IPN-L with low-grade dysplasia, 23 cases; type 2, IPN-L with high grade dysplasia, 11 cases; type 3, IPN-L with in situ and microinvasive carcinoma, 13 cases; and type 4, IPN-L of types 2 and 3 with distinct invasive carcinoma, 15 cases). Intraductal spreading and glandular involvement were commonly observed in all types. About half of types 3 and 4 cases had mucobilia, and mucinous carcinoma was variably found in two thirds of group 4 patients. IPN-L frequently showed variable gastroenteric differentiation such as goblet cells and foveolar and colon-like metaplasia. IPN-L with goblet cells and colon-like metaplasia was frequently associated with overproduction of mucin and mucobilia (P <.01). In Japan, IPN-L was not frequent in hepatolithiasis (12 of 135 cases). In conclusion, IPN-L forms a spectrum of biliary neoplasm in hepatolithiasis. It often displays variable gastroenteric metaplasia and significant intraductal spread. IPN-L tends to progress to mucinous carcinoma. Formerly reported "mucin-producing intrahepatic cholangiocarcinoma" with a favorable prognosis is included in IPN-L.
UI - 21467983
AU - Kuper H; Ye W; Broome U; Romelsjo A; Mucci LA; Ekbom A; Adami HO;
TI - Trichopoulos D; Nyren O The risk of liver and bile duct cancer in patients with chronic viral hepatitis, alcoholism, or cirrhosis.
SO - Hepatology 2001 Oct;34(4 Pt 1):714-8
AD - Department of Epidemiology and Public Health, University College London, London, UK. email@example.com
No prospective study has analyzed simultaneously chronic viral hepatitis and alcoholism as risk factors for liver carcinogenesis, while taking into consideration the role of cirrhosis. Nor has the risk for hepatocellular carcinoma among patients with chronic viral hepatitis been prospectively evaluated in a low-risk Western population. Last, the relationship between hepatocellular carcinoma risk factors and bile duct cancer remains to be clarified. We analyzed prospectively the risk for primary liver and extrahepatic biliary tract cancer among 186,395 patients hospitalized with either chronic viral hepatitis, alcoholism, cirrhosis, or any combination of these conditions through linkages between national Swedish registers. Compared with the general population, the relative risk of hepatocellular carcinoma was 34.4 for chronic viral hepatitis alone, 2.4 for alcoholism alone, and 40.7 for cirrhosis alone. Among patients with combinations of these risk conditions, the relative risk of hepatocellular carcinoma was 27.3 for chronic viral hepatitis and alcoholism, 118.5 for chronic viral hepatitis and cirrhosis, 22.4 for alcoholism and cirrhosis, and 171.4 for all 3 conditions. We found limited evidence for an excess risk of intrahepatic, but not for extrahepatic, biliary duct cancer. Cirrhosis amplifies the risk of hepatocellular carcinoma among patients with chronic viral hepatitis, but it is not a prerequisite for liver carcinogenesis. In contrast, cirrhosis may be a necessary intermediate for the development of hepatocellular carcinoma among alcoholics.
UI - 94363628
AU - Melchiorri C; Bolondi L; Chieco P; Pagnoni M; Gramantieri L; Barbara L
TI - Diagnostic and prognostic value of DNA ploidy and cell nuclearity in ultrasound-guided liver biopsies.
SO - Cancer 1994 Sep 15;74(6):1713-9
AD - Institute of Oncology, S. Orsola Hospital, Bologna, Italy.
BACKGROUND. Focal nodule lesions in patients with cirrhotic livers may be visualized by using imaging techniques; however, the diagnostic and prognostic judgment of biopsies from borderline lesions may be difficult using conventional histologic criteria. METHODS. The diagnostic and prognostic value of DNA ploidy analysis determined by image cytometry of Feulgen-stained isolated hepatocytes was investigated in ultrasound-guided biopsies from 50 nodular lesions found in patients with cirrhotic livers (39 hepatocellular carcinomas [HCCs] and 11 macroregenerative nodules) and from 10 patients with livers affected by viral chronic hepatitis. Of the 11 macroregenerative nodules, 7 presented a subsequent neoplastic behavior. Specimens from the morphologically normal livers of five patients who underwent liver surgery served as control tissues. Image cytometry was performed on Feulgen-stained cytologic preparations, obtained by enzymatic digestion of formalin fixed biopsies. The DNA ploidy of the main stem line and the distribution of mononucleated and binucleated hepatocytes (nuclearity) were compared using histologic diagnosis, Edmondson's grade, tumor size, and patient follow-up. RESULTS. The main stem line was peridiploid in all benign specimens and in 31 clinically confirmed HCCs, peritetraploid in 11 HCCs, perioctaploid in 1 HCC, and aneuploid in 3 HCCs. The fraction of mononucleated polyploid hepatocytes was found to be the best diagnostic parameter in euploid HCCs and was significantly correlated with the Edmondson grade and the nodular size. Survival information was available for 43 patients, with a median observation period of 350 days. A DNA ploidy value of the main stem line greater than 3c was an important determinant of survival as a single parameter and in association with histologic grade and greatest dimension of tumor. CONCLUSIONS. This study suggests that the ploidy distribution analysis of mononucleated and binucleated hepatocytes can provide valuable information for making correct diagnoses and for predicting survival outcome for patients with HCCs.
UI - 21342882
AU - Akhter J; Lu Y; Finlay I; Pourgholami MH; Morris DL
TI - 1alpha,25-Dihydroxyvitamin D3 and its analogues, EB1089 and CB1093, profoundly inhibit the in vitro proliferation of the human hepatoblastoma cell line HepG2.
SO - ANZ J Surg 2001 Jul;71(7):414-7
AD - University of New South Wales, Department of Surgery, St George Hospital, Sydney, Australia.
BACKGROUND: 1alpha,25-dihydroxyvitamin D3 (1,25[OH]2D3) has been shown to inhibit the proliferation of various cancer cells including colon, prostate, melanoma, osteosarcoma and breast cancer. METHODS: The human hepatoma cell line (HepG2) was cultured with 1,25(OH)2D3 or one of two analogues EB1089 or CB1093 for various durations. Cellular proliferation was measured by uptake of [3H]thymidine, and cell numbers were determined by trypan blue exclusion counting. RESULTS: 1,25(OH)2D3, EB1089 and CB1093 all inhibited proliferation of HepG2 by up to 90% after 5 days of treatment, compared to the untreated controls. Decreased proliferation was associated with an approximately 50% reduction in cell numbers at concentrations of up to 10(-10) mol/L after 5 days of treatment with 1,25(OH)2D3. Cell proliferation rapidly recovered in cultures treated with lower concentrations of 1,25(OH)2D3 (10(-10) and 10(-11) mol/L) when 1,25(OH)2D3 was removed from the cultures by placing cells in serum containing medium without 1,25(OH)2D3. When HepG2 cells were treated with 10(-8) mol/L 1,25(OH)2D3 for 5 weeks, there was still significant inhibition of proliferation, although at week 5 there was 66% inhibition compared to 93% at the end of week 1. CONCLUSIONS: 1,25(OH)2D3, EB1089 and CB1093 all significantly inhibit the proliferation of HepG2 hepatoblastoma cells, with EB1089 being the most potent at lower concentrations. Inhibition can be maintained for at least 4 weeks, but is reversed after removal of vitamin D3.
UI - 21345332
AU - Grazioli L; Federle MP; Brancatelli G; Ichikawa T; Olivetti L; Blachar A
TI - Hepatic adenomas: imaging and pathologic findings.
SO - Radiographics 2001 Jul-Aug;21(4):877-92; discussion 892-4
AD - Department of Radiology, University of Brescia, Brescia, Italy.
Hepatocellular adenoma is a rare benign lesion that is most often seen in young women with a history of oral contraceptive use. It is typically solitary, although multiple lesions have been reported, particularly in patients with glycogen storage disease and liver adenomatosis. Because of the risk of hemorrhage and malignant transformation, hepatocellular adenomas must be identified and treated promptly. At pathologic analysis, hepatocellular adenoma is usually a well-circumscribed, nonlobulated lesion, and at gross examination, resected adenomas frequently demonstrate areas of hemorrhage and infarction. Most adenomas are not specifically diagnosed at ultrasonography (US) and are usually further evaluated with computed tomography (CT) or other imaging modalities. Color Doppler US may help differentiate hepatocellular adenoma from focal nodular hyperplasia. Multiphasic helical CT allows more accurate detection and characterization of focal hepatic lesions. Hepatocellular adenomas are typically bright on T1-weighted magnetic resonance images and predominantly hyperintense relative to liver on T2-weighted images. The prognosis of hepatic adenoma is not well established. Criteria that guide treatment include the number and size of the lesions, the presence of symptoms, and the surgical risk incurred by the patient. Understanding the imaging appearance of hepatocellular adenoma can help avoid misdiagnosis and facilitate prompt, effective treatment.
UI - 21403105
AU - Choi YL; Park SH; Jang JJ; Park CK
TI - Expression of the G1-S modulators in hepatitis B virus-related hepatocellular carcinoma and dysplastic nodule: association of cyclin D1 and p53 proteins with the progression of hepatocellular carcinoma.
SO - J Korean Med Sci 2001 Aug;16(4):424-32
AD - Department of Diagnostic Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Deranged expression of cell cycle modulators has been reported to contribute to the development and progression of hepatocellular carcinoma (HCC). However, their expression patterns remain poorly understood in hepatitis B virus (HBV)-related HCC, which constitutes about 65-70% of HCC in Korea. The aims of this study were to evaluate the expressions of G1-S modulators in HBV-related HCCs and dysplastic nodules (DNs), and to correlate with the histopathologic features of HCCs. Immunohistochemical expressions of cyclin D1, cyclin E, p53, p27, p21, p16, Rb, and PCNA proteins were investigated in 80 HCCs and 22 DNs. Cyclin D1 overexpression showed positive relationships with advanced tumor stage, poor differentiation, larger tumor size, microvascular invasion, intrahepatic meta-stasis, no tumor capsule formation, infiltrative growth, aberrant p53 expression, and high PCNA labeling index (LI) of HCC (p<0.05). Aberrant p53 expression showed positive relationship with poor differentiation of HCC (p<0.01). Expression of cyclin D1 or p53 was not observed in DNs. The p27 LI and p16 LI were lower in HCCs with intrahepatic metastasis (p<0.05). Cyclin D1 overexpression and aberrant p53 expression could be associated with the progression of HBV-related HCC, and might have a less crucial role in the DN-HCC sequence. In addition, elevated expression of p27 and p16 proteins might have inhibitory action to the intrahepatic metastasis of HBV-related HCC.
UI - 21230505
AU - Moehler M; Blechacz B; Weiskopf N; Zeidler M; Stremmel W; Rommelaere J;
TI - Galle PR; Cornelis JJ Effective infection, apoptotic cell killing and gene transfer of human hepatoma cells but not primary hepatocytes by parvovirus H1 and derived vectors.
SO - Cancer Gene Ther 2001 Mar;8(3):158-67
AD - Department of Internal Medicine, University of Mainz, Germany. firstname.lastname@example.org
Autonomous parvoviruses preferentially replicate in and kill in vitro-transformed cells and reduce the incidence of spontaneous and implanted tumors in animals. Because of these natural oncotropic and oncolytic properties, parvoviruses deserve to be considered as potential antitumor vectors. Here, we assessed whether parvovirus H1 is able to kill human hepatoma cells by induction of apoptosis but spares primary human liver cells, and whether the former cells can efficiently be transduced by H1 virus-based vectors. Cell death, infectivity, and transgene transduction were investigated in Hep3B, HepG2, and Huh7 cells and in primary human hepatocytes with natural and recombinant H1 virus. All hepatoma cells were susceptible to H1 virus-induced cytolyis. Cell death correlated with H1 virus DNA repli