National Cancer Institute®
Last Modified: July 1, 2002
UI - 11350553
AU - Tong MJ; Blatt LM; Kao VW
TI - Surveillance for hepatocellular carcinoma in patients with chronic viral hepatitis in the United States of America.
SO - J Gastroenterol Hepatol 2001 May;16(5):553-9
AD - Liver Center, Huntington Medical Research Institutes in Pasadena, California 91105, USA. firstname.lastname@example.org
BACKGROUND: Measurement of serum alpha-fetoprotein (AFP) and abdominal ultrasound (US) examination are used for the early detection of hepatocellular carcinoma (HCC) in chronic liver disease patients. However, the accuracy and usefulness of these tests in a clinical setting in the United States of America have not been clarified. METHODS: We conducted a 7-year prospective surveillance study by using both AFP and US to detect HCC in 602 patients with chronic viral hepatitis. Our main goal was to determine the optimal test for detection of early HCC. We also assessed the clinical outcome of HCC patients identified during this time period. RESULTS: Thirty-one cases of HCC were detected. Serum AFP levels were elevated in 74% of HCC patients, but was also high in 10% of patients who did not develop HCC. The positive predictive value for AFP to detect HCC was only 12% or less for all AFP cut-off values, and the maximum joint sensitivity and specificity as determined by receiver operator characteristic analysis was approximately 65 and 90%, respectively. Abdominal US identified all 31 cases of HCC. The positive predictive value for US examinations to detect HCC was 78%, while the sensitivity and specificity was 100 and 98%, respectively. After detection of HCC, 24 (77%) patients died within a mean of 16.7 +/- 19.4 months. CONCLUSIONS: Our study indicates that US examination was more accurate in detecting HCC. Because of its poor predictive value and low sensitivity, serum AFP should not be used as the only test for screening and surveillance for HCC.
UI - 11914642
AU - Okano H; Shiraki K; Inoue H; Yamanaka T; Deguchi M; Sugimoto K; Sakai T;
TI - Ohmori S; Fujikawa K; Murata K; Nakano T Peroxisome proliferator-activated receptor gamma augments tumor necrosis factor family-induced apoptosis in hepatocellular carcinoma.
SO - Anticancer Drugs 2002 Jan;13(1):59-65
AD - First Department of Internal Medicine, Mie University School of Medicine, Tsu 514-8507, Japan.
Proliferator-activated receptor gamma (PPARgamma) is a nuclear receptor, which mainly associates with adipogenesis, but also appears to facilitate cell differentiation or apoptosis in certain malignant cells. This apoptosis induction by PPARgamma is increased by co-stimulation with tumor necrosis factor (TNF)-alpha-related apoptosis-inducing ligand (TRAIL), a member of the TNF family. In this study, we investigated the effect of PPARgamma on Fas-mediated apoptosis in hepatocellular carcinoma (HCC) cell lines. PPARgamma was expressed on all seven HCC cell lines and located in their nuclei. 15-Deoxy-Delta-12,14-prostaglandin J2 (15d- PGJ2), a PPARgamma ligand, inhibited cellular proliferation in HepG2, SK-Hep1 or HLE cells, unlike pioglitazone, another PPARgamma ligand, which did not have a significant influence on proliferation of these cells. However, 15d-PGJ2 facilitated Fas-mediated HCC apoptosis that could not be induced by Fas alone. These results suggest that PPARgamma can augment TNF-family-induced apoptosis.
UI - 12034592
AU - Jeong YY; Mitchell DG; Kamishima T
TI - Small (<20 mm) enhancing hepatic nodules seen on arterial phase MR imaging of the cirrhotic liver: clinical implications.
SO - AJR Am J Roentgenol 2002 Jun;178(6):1327-34
AD - Department of Radiology, Thomas Jefferson University Hospital, 132 S. 10th St., 1096 Main Bldg., Philadelphia, PA 19107, USA.
OBJECTIVE: To determine the significance in patients with cirrhosis of small (<20 mm) hepatic nodules that show no hyperintensity on T2-weighted MR images but that enhance during arterial phase MR imaging, we reviewed the cases of patients with such nodules. MATERIALS AND METHODS: Our review of radiology reports yielded 68 nodules in 40 patients with cirrhosis that showed no hyperintensity on T2-weighted MR images but had rapid enhancement during arterial phase MR imaging after administration of a gadolinium contrast agent. Thirty-four patients (60 nodules) had multiple follow-up MR imaging examinations (range of length of follow-up, 1-72 months; average length of follow-up, 15 months 2 weeks). The final diagnosis of the nodule was determined by pathology reports or after at least 2 years of follow-up to ensure nodule stability and, therefore, benignity. Two radiologists independently reviewed MR images of the nodules, noting the size, signal intensity on T1- or T2-weighted images, and homogeneity of contrast enhancement. RESULTS: Nine (13%) of the 68 nodules were hepatocellular carcinomas (HCCs). The size of nodules on the first MR examination was between 4 and 20 mm (mean size, 9.5 mm). No significant correlation between the diagnosis of HCC and nodule signal intensity (p = 0.48) or contrast enhancement homogeneity (p = 0.56) on first MR examination was found. Positive predictive value (PPV) and negative predictive value (NPV) for diagnosing HCC on the basis of nodule growth were 100% and 98%, respectively. For diagnosing HCC on the basis of a change in nodule signal intensity, the PPV was 60% and the NPV was 91%. For diagnosing HCC on the basis of a change of enhancement homogeneity, the PPV was 63%, and the NPV was 94%. CONCLUSION: A finding of growth in small, early-enhancing nodules in patients with cirrhosis is highly predictive of HCC. When small nodules are observed on a single examination, close follow-up of the patient appears appropriate.
UI - 12027987
AU - Ohlsson B; Nilsson J; Stenram U; Akerman M; Tranberg KG
TI - Percutaneous fine-needle aspiration cytology in the diagnosis and management of liver tumours.
SO - Br J Surg 2002 Jun;89(6):757-62
AD - Department of Surgery, University of Lund, SE-22185 Lund, Sweden.
BACKGROUND: The aim of the study was to investigate the value of percutaneous fine-needle aspiration cytology (FNAC) in the diagnosis and management of liver tumours. METHODS: FNAC followed by histopathological examination was carried out in 216 patients with suspected liver tumours. The final diagnosis was primary liver cancer in 106, colorectal metastases in 51, non-colorectal metastases in 46, benign tumour in nine and no tumour in four patients. RESULTS: Cytology resulted in correct classification of the lesion as benign or malignant in 87 per cent of patients, correct discrimination between primary and secondary malignancy in half of the patients, and a correct diagnosis of tumour type in one-third of patients. The tumour was erroneously classified as benign or malignant in 22 patients (11 per cent) and four patients (2 per cent) respectively. When FNAC showed malignancy, the predictive value was 98 per cent, whereas the predictive value was 27 per cent when it did not. FNAC guided investigations and treatment in one-quarter of patients. Implantation metastases were recorded in seven patients (3 per cent), including five (10 per cent) of 51 patients with colorectal liver metastases, and caused major local problems and death in four patients. CONCLUSION: FNAC was valuable in about a quarter of patients with liver tumour. The risks of implantation metastases and a false-negative finding do not justify its use in candidates for curative therapy of liver tumours.
UI - 12089170
AU - Poon TC; Mok TS; Chan AT; Chan CM; Leong V; Tsui SH; Leung TW; Wong HT;
TI - Ho SK; Johnson PJ Quantification and utility of monosialylated alpha-fetoprotein in the diagnosis of hepatocellular carcinoma with nondiagnostic serum total alpha-fetoprotein.
SO - Clin Chem 2002 Jul;48(7):1021-7
AD - Department of Clinical Oncology, the Sir Y.K. Pao Centre for Cancer, The Chinese University of Hong Kong, Shatin, Hong Kong.
BACKGROUND: At concentrations <500 microg/L, serum alpha-fetoprotein (AFP) has low specificity in the diagnosis of hepatocellular carcinoma (HCC), but monosialylated AFP (msAFP) is more specific for HCC. We describe two strategies for quantitative analysis of msAFP and explore their diagnostic accuracy in cases of HCC with nondiagnostic serum total AFP concentrations. METHODS: We first used isoelectric focusing, Western blot, and densitometry (IEF-Western blot assay). We then developed a second assay, a novel glycosylation immunosorbent assay (GISA), based on the specificity of sialyltransferase and immunosorbent technology. Both assays were used to measure msAFP and msAFP percentage relative to total AFP in sera with nondiagnostic AFP concentrations from 36 patients with newly diagnosed HCC and from 18 patients with liver cirrhosis. RESULTS: The msAFP percentages and concentrations were significantly higher in the HCC patient group regardless of the quantification methods. The msAFP concentrations and msAFP percentages obtained by the two assays were highly correlated (r = 0.70 and 0.49, respectively). For discrimination of HCC with nondiagnostic serum total AFP from liver cirrhosis, the areas under the ROC curves were 0.81 (95% confidence interval, 0.70-0.92) for msAFP by IEF-Western blot assay, 0.73 (0.58-0.87) for msAFP by GISA, 0.89 (0.80-0.97) for msAFP percentage by IEF-Western blot assay, and 0.74 (0.59-0.89) for msAFP percentage by GISA. CONCLUSIONS: Both the serum concentration and percentage of msAFP are potential diagnostic markers for HCC with nondiagnostic AFP. GISA can quantify a specific glycoform of a serologic marker.
UI - 11798820
AU - Li S; Wang H; Zhang C
TI - [Genome-wide loss of heterozygosity analyses in primary hepatocellular carcinoma]
SO - Zhonghua Yi Xue Za Zhi 2000 Aug;80(8):577-81
AD - Cancer Center, Sun Yat-Sen University of Medical Sciences, Guangzhou 510060, China.
OBJECTIVE: To investigate genome-wide loss of heterozygosity (LOH) and its clinical significance in primary hepatocellular carcinoma (HCC) in southern China. METHODS: LOH on 22 autosomes was investigated with 382 sets of microsatellite markers in 65 cases of HCC. RESULTS: The average rate of informative loci was 68.1%. More than 30% LOH was detected in loci on 17p (54.1%), 4q (48.1%), 16q (43.8%), 1q (38.3%), 8p (37.2%), 13q (33.7%), and 3p (30.8%). The frequency of LOH on D4S2964 (4q13-21) in HBsAg-positive cases was significantly higher than that in HBsAg-negative cases (P < 0.05). Cases with LOH on loci both D3S3681 (3p14-21) and D17S938 (17p13) had significantly higher rates of postoporative recurrence than those without LOH on these two loci (91% and 83% vs 52% and 65%, respectively). The 3-year survival rate was significantly lower in cases with LOH than in those without LOH on D17S938 (P < 0.05). CONCLUSIONS: LOH status in HCC patients in southern China is similar to that reported in other countries and areas. However, we first identified the high frequency of LOH on chromosome 3p in HCC. Furthermore, the infection of hepatitis B virus (HBV) may be correlated with the loss of some tumor suppressor genes on D4S2964 (4q12-13), and some tumor suppressor genes may reside on loci D3S3681 (3p12) and D17S938 (17p13), relating with tumor recurrence and prognosis.
UI - 12062996
AU - Vento S; Cainelli F
TI - Does hepatitis C virus cause severe liver disease only in people who drink alcohol?
SO - Lancet Infect Dis 2002 May;2(5):303-9
AD - Section of Infectious Diseases, Department of Pathology, University of Verona, Verona, Italy. email@example.com
Hepatitis C virus (HCV) infects about 170 million people worldwide, and has been portrayed in the media as a silent killer, incorrectly implying that cirrhosis and hepatocellular carcinoma are the certain final outcomes of infection. Results of numerous population-based surveys indicate that chronic HCV infection is highly prevalent in elderly people who, in most instances, do not develop end-stage liver disease. In individuals who do progress to cirrhosis and hepatocellular carcinoma alcohol plays a fundamental part, via mechanisms that result in increased viral replication, enhanced HCV quasispecies complexity, increased liver-cell death, suppression of immune responses, and iron overload. Although overlaps are present in the histological appearance of the liver in patients with hepatitis C who do and do not drink alcohol, histology could be of some help in revealing the role of alcohol in HCV disease progression even in people who deny drinking. Interventions and high-impact, continuous public-health campaigns are needed to persuade doctors and patients infected with HCV of the importance of abstaining from alcohol if risk of progression towards cirrhosis and hepatocellular carcinoma is to be reduced.
UI - 12010894
AU - Levy I; Sherman M; the Liver Cancer Study Group of the University of
TI - Toronto Staging of hepatocellular carcinoma: assessment of the CLIP, Okuda, and Child-Pugh staging systems in a cohort of 257 patients in Toronto.
SO - Gut 2002 Jun;50(6):881-5
AD - Department of Medicine, Toronto General Hospital and the University of Toronto, Toronto Canada.
BACKGROUND: A new staging system for hepatocellular carcinoma (HCC) has recently been reported from Italy (CLIP classification). It combines Child-Pugh staging with tumour criteria: tumour morphology, portal invasion, and alpha fetoprotein levels. AIMS: To validate the use of the CLIP staging in a cohort of HCC patients and compare it with Okuda staging. PATIENTS AND METHODS: A retrospective analysis of patients with patient with insufficient data and 37 transplant patients were excluded. Hence 257 patients in whom complete data for clinical staging were available were included in the study. The median survival of the cohort was 22.8 months. The CLIP stage 0 group (23.1% of the cohort) and the Okuda stage 1 group (50.7% of the cohort) had a five year survival rate of 67% and 35%, respectively (p<0.02). The CLIP stage 0 criteria more accurately defined patients with a good prognosis. The Okuda classification failed to identify two thirds of the 37 patients with a poor prognosis, who were identified by the CLIP criteria. Patients with a CLIP score > or =4 shared a very poor prognosis (median survival 1-3 months). Further classification above stage 4 was unnecessary. SUMMARY: The CLIP classification for HCC is easy to implement and more accurate than the Okuda classification. Our cohort was different from the CLIP cohort (more hepatitis B) but the results were still consistent.
UI - 12049008
AU - Olah A; Issekutz A; Toth-G B; Haulik L; Banga P
TI - [Surgical treatment of giant hemangiomas of the liver]
SO - Magy Seb 2002 Apr;55(2):57-62
AD - Petz Aladar Megyei Oktato Korhaz, Sebeszeti Osztaly, 9002 Gyor, Pf. 92. firstname.lastname@example.org
Spontaneous rupture of liver hemangiomas is exceptional, they rarely increase in size. Elective surgery of liver hemangiomas is safe and effective. In our teaching hospital during a 5-year period 9 patients underwent elective surgery for giant liver hemangiomas, one more patient required urgent operation for spontaneous rupture. Indications for elective surgery were: abdominal pain in 5 patients, enlargement in 1 patient, and 3 patients were worried about the risk of rupture or having a tumor left in situ. The average age of our four male and six female patients was 44.5 years (30-58). The median largest dimension of the lesions was 8.5 cm (5.5-14); six of them located in the right, four in the left lobe. Enucleation was performed in most patients (8, mostly of them in the right lobe); anatomical resections were performed only in two cases (left lobectomy). There was no postoperative mortality, the only complication was mild pneumonia in one patient. Elective surgery is indicated only in a small number of patients with hemangiomas, it should be limited to giant, symptomatic tumors or those with a documented tendency to increase in size. The type of resection depends on the site and the size of the lesion. Enucleation can be performed rapidly and safely in most patients and as such it is preferable to anatomical resection.
UI - 11976616
AU - Tonolini M; Solbiati L; Ierace T; Kirn V; Croce F
TI - Extrahepatic recurrence and second malignancies after treatment of hepatocellular carcinoma: spectrum of imaging findings.
SO - Radiol Med (Torino) 2002 Mar;103(3):196-205
AD - Servizio di Radiologia, Ospedale di Circolo, Busto Arsizio (Varese), Italy. email@example.com
PURPOSE: To describe diagnostic imaging features (with a focus on CT findings) of extrahepatic relapses of treated hepatocellular carcinoma and to propose a post-treatment follow-up protocol. MATERIAL AND METHODS: During a six-year span, 226 patients (aged 32-88 years) with chronic hepatitis/cirrhosis were diagnosed as having hepatocellular carcinoma confined to the liver and treated percutaneously with radiofrequency (RF) ablation. A total of 313 treatment sessions were performed. Post-therapeutic follow-up is based upon clinical evaluation, laboratory and imaging (with CT holding the key role) studies. RESULTS: Mean duration of follow-up was 17 months. After successful treatment, actuarial probability of neoplastic relapse is 30.7% after 1 year and 58.5% after 2 years. Eighty-eight patients had recurrence of hepatocellular carcinoma after a variable time interval (mean 7.3 months). Extrahepatic neoplastic relapse was observed in 14 patients, half of these without active hepatic disease. Distribution of extrahepatic sites of recurrence was as follows: abdominal lymph nodes (6 cases), bone (3), peritoneum (2), adrenal (2), lung (1). Five patients (2.2%) had a second primary neoplasm. CONCLUSIONS: Extrahepatic hepatocellular carcinoma is uncommon and occurs in advanced stages, but may represent a pattern of post-treatment relapse. The distinctive hypervascularity of this tumour histology may be observed in adenopathies and adrenal metastases. Second primary neoplasms should be considered in the differential diagnosis of lesions observed during follow-up.
UI - 12010300
AU - Halavaara J; Tervahartiala P; Isoniemi H; Hockerstedt K
TI - Efficacy of sequential use of superparamagnetic iron oxide and gadolinium in liver MR imaging.
SO - Acta Radiol 2002 Mar;43(2):180-5
AD - Department of Radiology, Helsinki University Central Hospital, Finland.
PURPOSE: To evaluate the efficacy of combined (double contrast) use of superparamagnetic iron particles (SPIOs) and gadolinium (Gd) in liver MR imaging. MATERIAL AND METHODS: Unenhanced, Gd-enhanced, SPIO-enhanced, and both SPIO- and Gd-enhanced images were acquired at 1.5 T. Twenty patients with previously detected liver lesions were included. Fast SE-STIR, and breath-hold true FISP, fat-suppressed T1- and T2-weighted sequences were obtained with all techniques. Lesion count was assessed by consensus reading. RESULTS: Collective evaluation of all MR sequences revealed 61 lesions in 16 patients; SPIO-enhanced MR detected lesions with a sensitivity of 95% (n=58). The sensitivity of unenhanced MR imaging was 90% (n=55). There was no statistical difference between SPIO-enhanced and unenhanced MR images. From single sequences, the greatest number of lesions was detected with the SPIO-enhanced fast SE-STIR sequence (n=56, sensitivity 92%). By using the fat-suppressed T1-weighted sequence, Gd-enhanced and both SPIO- and Gd-enhanced MR images demonstrated sensitivities of 77% (n=47) and 80% (n=49), respectively. Despite the combined use of both contrast media, this sequence was significantly less sensitive in lesion detection when compared to SPIO-enhanced imaging. CONCLUSION: SPIO-enhanced MR imaging was the most sensitive method in lesion detection. The benefit of the combined use of SPIO and Gd was negligible.
UI - 12076913
AU - Katayama K; Ooka Y; Uemura A; Shinzaki S; Egawa S; Naito M; Ishibashi K;
TI - Kamoi R Saline injection into the pleural cavity to detect tumors of the hepatic dome with sonography: a new approach for treatment of hepatocellular carcinoma.
SO - AJR Am J Roentgenol 2002 Jul;179(1):102-4
AD - Department of Internal Medicine, Osaka Koseinenkin Hospital, 4-2-78 Fukushima, Fukushima-ku, Osaka 553-0003, Japan.
UI - 12076905
AU - Sahani D; Saini S; Pena C; Nichols S; Prasad SR; Hahn PF; Halpern EF;
TI - Tanabe KK; Mueller PR Using multidetector CT for preoperative vascular evaluation of liver neoplasms: technique and results.
SO - AJR Am J Roentgenol 2002 Jul;179(1):53-9
AD - Department of Radiology, Division of Abdominal Imaging and Intervention, Massachusetts General Hospital, Ellison 234-E, 55 Fruit St., Boston, MA 02114, USA.
OBJECTIVE: The purpose of our study was to evaluate the performance of CT angiography using multidetector CT (MDCT) for preoperative vascular evaluation in candidates who were scheduled for liver neoplasm resection. SUBJECTS AND METHODS: Forty-two consecutive subjects with malignant liver tumors scheduled for resection were studied with multiphase MDCT. The first 22 subjects underwent both multiphase MDCT angiography and catheter angiography before surgery. The subsequent 20 subjects underwent only preoperative CT angiography. Postprocessing was performed, and the images were analyzed for the depiction of arterial, portal vein, and hepatic vein anatomy and for the identification of important vascular variants. The postprocessing findings were compared and correlated with the findings from catheter angiography (22/42) or intraoperative sonography (42/42) and surgery (42/42). RESULTS: Arterial anomalies were detected on the images of 17 of 42 patients, including a replaced right hepatic artery in five, replaced left hepatic artery in six, accessory right and left hepatic arteries in two, common trunk for the celiac and superior mesenteric arteries in one, and early bifurcation of the celiac artery in one. In 22 patients in whom catheter angiography confirmation was available, the number of arteries and almost all the significant anomalies were correctly identified on CT angiography (accuracy, 97%; sensitivity, 94%; specificity, 100%). In the subset of 20 patients who underwent MDCT angiography without catheter angiography confirmation, all clinically relevant information was provided by CT angiography. The portal and hepatic vein anatomy and the relationships of the liver tumors to the neighboring venous structures were shown on CT. CONCLUSION: Multidetector CT provides valuable preoperative information about hepatic vascular architecture and can be used as a noninvasive alternative to catheter angiography before oncologic liver surgery.
UI - 12076906
AU - Kawata S; Murakami T; Kim T; Hori M; Federle MP; Kumano S; Sugihara E;
TI - Makino S; Nakamura H; Kudo M Multidetector CT: diagnostic impact of slice thickness on detection of hypervascular hepatocellular carcinoma.
SO - AJR Am J Roentgenol 2002 Jul;179(1):61-6
AD - Department of Radiology, Osaka University Graduate School of Medicine D1, 2-2 Yamadaoka, Suita City, Osaka, 565-0871 Japan.
OBJECTIVE: The objective of our study was to evaluate the diagnostic impact of varying slice thickness on multidetector CT to optimize detection of hypervascular hepatocellular carcinoma. MATERIALS AND METHODS: Forty-three patients with 87 hypervascular hepatocellular carcinomas (diameter: range, 3-80 mm; mean, 22 mm) and 19 patients with either chronic hepatitis or liver cirrhosis and without hepatocellular carcinoma who had undergone early arterial and late arterial phase imaging of the entire liver on multidetector CT were retrospectively enrolled in this study. The detector row configuration was 2.5 x 4 mm, the pitch was 6, and the scanning time was 10.5 sec for each phase. All patients received contrast medium (2 mL/kg of body weight) at a rate of 5 mL/sec; the mean scanning delay for the early arterial phase was 19.0 sec, and the mean delay for the late arterial phase was 34.5 sec. Eighty 2.5-mm-thick reconstruction images, forty 5-mm-thick reconstruction images, and twenty-six 7.5-mm-thick reconstruction images were obtained for each phase. Each image set was interpreted separately by three observers to detect hypervascular hepatocellular carcinoma by viewing images on a workstation monitor. Sensitivity, positive predictive value, and area under the receiver operating characteristic curve (A(z)) were calculated. We used retrospectively excellent follow-up and imaging or pathologic proof as the gold standard. RESULTS: The mean sensitivity and positive predictive value for hypervascular hepatocellular carcinoma were 76% and 69% on 2.5-mm images, 73% and 69% on 5-mm images, and 67% and 76% on 7.5-mm images, respectively. No significant difference in sensitivity among the images was detected, except by one observer who reported a significant difference in the sensitivity between 2.5- and 7.5-mm images (p < 0.05) and between 5- and 7.5-mm images (p < 0.05). The mean A(z) values were 0.79, 0.80, and 0.78 for 2.5-, 5-, and 7.5-mm images, respectively. No significant difference in A(z) values among the images obtained with different slice thicknesses was detected. CONCLUSION: For multidetector CT identification of hypervascular hepatocellular carcinoma, we found little or no advantage in reducing slice thickness to less than 5 mm.
UI - 12076907
AU - Lim JH; Choi D; Kim SH; Lee SJ; Lee WJ; Lim HK; Kim S
TI - Detection of hepatocellular carcinoma: value of adding delayed phase imaging to dual-phase helical CT.
SO - AJR Am J Roentgenol 2002 Jul;179(1):67-73
AD - Department of Radiology, Samsung Medical Center, 50 Ilwon-dong, Kangnam-ku, Seoul, Korea 135-710.
OBJECTIVE: The purpose of our study was to determine the value of adding delayed phase imaging to dual-phase helical CT for the detection of hepatocellular carcinoma. SUBJECTS AND METHODS: One hundred thirteen patients with 131 hepatocellular carcinomas underwent triple-phase helical CT. The diagnosis was established by pathologic examination after surgical resection in all patients. For triple-phase helical CT, hepatic arterial, portal venous, and delayed phase scanning began 30, 60, and 180 sec, respectively, after the injection of 120 mL of iodinated contrast material. Dual-phase helical CT excluding delayed phase and triple-phase helical CT images were reviewed independently by three radiologists on a segment-by-segment basis. Diagnostic accuracy was assessed using receiver operating characteristic analysis in 330 resected segments. Sensitivities and specificities were calculated. The value of the delayed phase images in the characterization of hepatocellular carcinoma was also assessed. RESULTS: The diagnostic accuracy of triple-phase helical CT including delayed phase (area under the curve [A(z)], 0.973) was significantly higher than that of dual-phase helical CT (A(z), 0.954). The mean sensitivity of triple-phase CT (89%) was also significantly higher than that of dual-phase CT (86%). The mean specificities of triple-phase CT (99%) and dual-phase CT (99%) were equal. Delayed phase images were helpful in the characterization of hepatocellular carcinoma in 14% of patients. CONCLUSION: The addition of delayed phase imaging to dual-phase helical CT is valuable for the detection and characterization of hepatocellular carcinoma.
UI - 12076908
AU - Bennett GL; Krinsky GA; Abitbol RJ; Kim SY; Theise ND; Teperman LW
TI - Sonographic detection of hepatocellular carcinoma and dysplastic nodules in cirrhosis: correlation of pretransplantation sonography and liver explant pathology in 200 patients.
SO - AJR Am J Roentgenol 2002 Jul;179(1):75-80
AD - Department of Abdominal Radiology, New York University Medical Center, 560 First Avenue, New York, NY 10016, USA.
OBJECTIVE: The objective of this study was to determine the sensitivity and specificity of sonography as an aid in detecting hepatocellular carcinomas and dysplastic nodules using explantation correlation in patients with cirrhosis and no known hepatocellular carcinomas. MATERIALS AND METHODS: The sonography reports of 200 patients with cirrhosis who underwent sonography and then underwent liver transplantation within 90 days were retrospectively reviewed for focal solid liver lesions. All focal solid masses detected on sonography were considered possible hepatocellular carcinomas. The sonographic findings were compared with thin-section explanted liver pathologic results. RESULTS: Twenty-seven patients (13.5%) had hepatocellular carcinoma at explantation, including four patients with diffuse, multifocal tumors. Eight of the 39 lesions were detected on sonography for a patient sensitivity of 29.6% and a lesion sensitivity of 20.5%. Sonography revealed three (75%) of four hepatocellular carcinomas larger than 5 cm in diameter, one (50%) of two hepatocellular carcinomas with diameters of 3.1-5.0 cm, one (20%) of five hepatocellular carcinomas with diameters of 2.1-3.0 cm, three (13.6%) of 22 hepatocellular carcinomas with diameters of 1-2 cm, and no lesions with diameters smaller than 1 cm. Forty-two patients (21%) had a total of 126 dysplastic nodules including two patients with innumerable lesions. Sonography depicted only two dysplastic nodules, for a patient sensitivity of 4.8% and a lesion sensitivity of 1.6%. The overall specificity of sonography for either hepatocellular carcinomas or dysplastic nodules was 96%. CONCLUSION: Sonography has low sensitivity but high specificity in revealing hepatocellular carcinomas and dysplastic nodules in patients with a cirrhotic liver requiring liver transplantation. In these patients, sonography should not be the sole imaging modality used for lesion detection before transplantation.
UI - 12057093
AU - Yao F; Terrault N
TI - Hepatitis C and hepatocellular carcinoma.
SO - Curr Treat Options Oncol 2001 Dec;2(6):473-83
AD - Division of Gastroenterology, University of California, San Francisco, S357, 513 Parnassus Avenue, San Francisco, CA 94143-0538, USA. firstname.lastname@example.org
Chronic hepatitis C infection (HCV) accounts for approximately 50% of the cases of hepatocellular carcinoma (HCC) in the United States. Cirrhosis or an advanced stage of fibrosis is the major risk factor of HCC; patients with cirrhosis are recommended to undergo surveillance with alpha-fetoprotein and ultrasound. Alpha interferon (IFN-alpha) is associated with a reduced risk of HCC in patients with chronic infection but insufficient data exist to recommend treatment of patients with cirrhosis and HCV for this reason alone. Resection and liver transplantation are the only "curative" therapies available. Advanced fibrosis or cirrhosis in patients with HCC limits the number of patients for whom resection is applicable. Moreover, the remaining liver is at high risk of developing a second primary tumor. Partial hepatic resection for hepatocellular carcinoma should be restricted to patients with well-compensated cirrhosis (Child's A class). Acceptable parameters include a single lesion not exceeding 5 cm, normal levels of bilirubin, and absence of portal hypertension. Liver transplantation is the best definitive treatment for HCV-infected patients who have small, localized HCC (solitary lesion not greater than 5 cm, or no more than 3 lesions, none of which are greater than 3 cm). Limitations of liver transplantation as a therapy for HCC are the scarcity of donor organs and the prolonged waiting time during which continued tumor growth occurs. Living donors can reduce waiting time and increase the number of patients treatable by transplantation. Chemoembolization and local ablation therapies have not been shown to confer survival benefits as primary treatments for HCC. The potential benefit of these procedures in controlling tumor growth to "bridge" patients to liver transplantation must be further investigated. Similarly, systemic chemotherapy and hormonal therapy do not generally produce a survival advantage. However, recent studies that used octreotide and combination doxorubicin/cisplatin/5-FU/interferon appear to be promising.
UI - 12094698
AU - Takeda S; Nakao A
TI - [Genetic detection and clinical applications in patients with hepatocellular carcinoma]
SO - Nippon Geka Gakkai Zasshi 2002 Jun;103(6):472-5
AD - Department of Gastroenterological Surgery (Surgery II), Nagoya University Graduate School of Medicine, Nagoya, Japan.
This paper provides a review of the known genetic diagnostic indicators of liver cancer. The correlation between the genetic diagnosis and clinical outcome in patients with hepatocellular carcinoma (HCC) has been widely reported, based on the detection of liver-specific mRNA or tumor DNA in the blood. Our results suggest that an alteration of alpha-fetoprotein (AFP) mRNA in peripheral blood from HCC patients during the perioperative period might permit the prediction of early recurrence after surgery. The presence of circulating HCC cells may be indicative of metastasis if liver-specific AFP mRNA is detected in the peripheral blood. However, some studies showed that sensitive RT-PCR might possibly give rise to false positivity because nontumor hepatocytes would also express low levels of AFP mRNA. Recently, quantification of AFP mRNA for HCC cell detection using real-time PCR or semiquantitative RT-PCR has proven useful in the prediction of metastasis/recurrence. On the other hand, circulating liver tumor DNA such as p16 and p15 methylation and mitochondrial mutations in the plasma and serum of liver cancer patients might be useful for monitoring, similar to the tumor markers. In future, HCC-specific genes and genes sensitive to radiation and chemotherapy are expected to have wide-spread clinical applications.
UI - 11891535
AU - Arima T; Nakao K; Nakata K; Ishikawa H; Ichikawa T; Hamasaki K; Ishii N;
TI - Eguchi K Transactivation of human alpha-fetoprotein gene by X-gene product of hepatitis B virus in human hepatoma cells.
SO - Int J Mol Med 2002 Apr;9(4):397-400
AD - First Department of Internal Medicine, Nagasaki University School of Medicine, Sakamoto, Nagasaki, Japan.
The X-gene product of hepatitis B virus (HBX) modulates a variety of viral and cellular genes relevant to hepatocarcinogenesis, where alpha-fetoprotein (AFP) is produced by hepatoma cells. In the present study, the possible mechanism by which HBX regulates AFP expression was investigated using three human hepatoma cells, HepG2, HuH-7 and Hep3B, which are known to contain the wild-type, the mutant-type and the deletion of p53, respectively. Transfection with the HBX expression vector stimulated the co-transfected AFP reporter gene expression in HepG2 cells and HuH-7 cells, but not in Hep3B cells. Transfection with the p53 expression vector repressed the AFP reporter gene expression in all three hepatoma cells, while overexpression of HBX counteracted the p53-induced repression. In addition, a G-->A substitution at nucleotide -119 in the AFP promoter sequence abrogated the stimulatory effect of HBX on the AFP promoter in HepG2 cells. These results suggest that HBX interacts with p53 to up-regulate AFP gene transcription probably by restoration of the p53-mediated repression of the AFP promotor activity.
UI - 12053291
AU - Rabe C; Caselmann WH
TI - [Is MRI reliable for screening for hepatocellular carcinoma?]
SO - Dtsch Med Wochenschr 2002 Jun 7;127(23):1275-6
UI - 12101859
AU - Kao JH; Chen DS
TI - Recent research progress in hepatocellular carcinoma.
SO - J Formos Med Assoc 2002 Apr;101(4):239-48
AD - Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, National Taiwan University Hospital, Taipei,Taiwan.
Hepatocellular carcinoma (HCC) is responsible for significant morbidity and mortality throughout the world, and is clearly linked to viral infections. Mass vaccination programs against hepatitis B virus have reduced the incidence of HCC in Taiwanese children, and are likely to yield similar benefits elsewhere. In many countries, a definite increase in the incidence of HCC has been reported, largely attributable to the increasing incidence of hepatitis C virus infection. Although the major viral and environmental risk factors for the development of HCC have been determined, the oncogenic pathways leading to malignant transformation of liver cells have long remained obscure. HCC is also extremely difficult to manage. Although patients at risk can be identified and early detection of HCC is feasible, the current management of HCC is confusing due to the lack of well-designed, randomized clinical trials comparing various treatment modalities. New surgical techniques and postoperative therapies may improve the outcome in some resectable cancers; however, the vast majority of patients have unresectable tumors. Local ablation treatments may shrink or necrose tumors, but the clear benefit of such therapies remains to be seen. Further elucidation of the genetic and molecular features of HCC may lend insight that will lead to the development of innovative strategies to manage this cancer. In this article, the current understanding of HCC with respect to etiologic factors, genetic mechanisms responsible for hepatocarcinogenesis, diagnosis, therapy, and prevention are reviewed.
UI - 12095924
AU - Montalto G; Cervello M; Giannitrapani L; Dantona F; Terranova A;
TI - Castagnetta LA Epidemiology, risk factors, and natural history of hepatocellular carcinoma.
SO - Ann N Y Acad Sci 2002 Jun;963():13-20
AD - Institute of Internal Medicine, Institute of Development Biology, CNR, University of Palermo, Palermo, Italy. email@example.com
The incidence of hepatocellular carcinoma is increasing in many countries. The estimated number of new cases annually is over 500,000, and the yearly incidence comprises between 2.5 and 7% of patients with liver cirrhosis. The incidence varies between different geographic areas, being higher in developing areas; males are predominantly affected, with a 2:3 male/female ratio. The heterogeneous geographic distribution reflects the epidemiologic impact of the main etiologic factors and environmental risk, which are the hepatitis B (HBV) and hepatitis C (HCV) viruses. The percentage of cases of hepatocellular carcinoma attributable to HBV worldwide is 52.3% and is higher in Asia where the seroprevalence of HBsAg in the population is high. However, the vaccination campaign against this virus in some eastern countries has tended to lower the incidence of new cases of hepatocellular carcinoma. The percentage of cases of hepatocellular carcinoma attributable to HCV is 25%, and it is more prevalent in Japan, Spain, and Italy where the association between hepatocellular carcinoma and antibodies to HCV ranges between 50 and 70%. In most cases hepatocellular carcinoma develops in cirrhotic livers, where the persistent proliferation of liver cells represents the key factor of progression to hepatocellular carcinoma independent of the etiology. Another minor risk factor is aflatoxin B1 consumption, which is responsible for most cases of hepatocellular carcinoma in Africa, where the consumption of contaminated foods is common. Other known risk factors are some hereditary diseases, such as hemochromatosis, porphyria cutanea tarda, hereditary tyrosinemia, and alpha1 anti-trypsin deficiency. The natural history of hepatocellular carcinoma is heterogeneous and is influenced by nodule dimension, the mono- or plurifocality of lesions at diagnosis, the growth rate of the tumor, and the stage of the underlying cirrhosis. Available data to date suggest that tumor growth in a cirrhotic liver is variable and that the time in which a lesion in undetectable until it becomes 2 cm is between 4 and 12 months. Therefore, the suggested interval for surveillance screening with ultrasound in patients with liver cirrhosis has been set at 6 months. Patients who should benefit from screening programs are those who would be treated with curative therapy if diagnosed with hepatocellular carcinoma. Thus, the ideal target population should be limited to Child-Pugh's class A cirrhotic patients without significant comorbidity.
UI - 12095925
AU - Levy L; Renard CA; Wei Y; Buendia MA
TI - Genetic alterations and oncogenic pathways in hepatocellular carcinoma.
SO - Ann N Y Acad Sci 2002 Jun;963():21-36
AD - Unite de Recombinaison et Expression Genetique, INSERM U163, Departement des Retrovirus, Institut Pasteur, 75015 Paris, France.
Hepatocellular carcinoma (HCC) is a major type of primary liver cancer and one of the rare human neoplasms etiologically linked to viral factors. Chronic infections with the hepatitis B virus (HBV) and the hepatitis C virus (HCV) have been implicated in about 80% of cases worldwide, and other known environmental risk factors, including alcohol abuse and dietary intake of aflatoxin B1, might synergize with viral infections. Recent insight into the molecular mechanisms leading to HCC development has been provided by the identification of major genetic abnormalities revealed by genomewide allelotype studies and molecular cytogenetic analysis. Moreover, several oncogenic pathways have been implicated in malignant transformation of liver cells. Inactivation of the p53 tumor suppressor gene by mutations and allelic deletions in about 30% of HCC cases has been associated predominantly with exposure to aflatoxin B1 and HBV infection. By contrast, a mutation in the beta-catenin gene in around 22% of HCCs is more rare in HBV-associated tumors. Activation of cyclin D1 and disruption of the Rb pathway are also commonly involved in liver tumorigenesis. New major challenges include the identification of candidate genes located in frequently altered chromosomal regions and that of oncogenic pathways driven by different risk factors. This search might shed some light on the tumorigenic role of HBV and HCV. It might also permit accurate evaluation of major targets for prognostic and therapeutic intervention.
UI - 12095927
AU - Giannitrapani L; Cervello M; Soresi M; Notarbartolo M; La Rosa M;
TI - Virruso L; D'Alessandro N; Montalto G Circulating IL-6 and sIL-6R in patients with hepatocellular carcinoma.
SO - Ann N Y Acad Sci 2002 Jun;963():46-52
AD - Istituto di Medicina Interna e Geriatria, Universita di Palermo, Palermo, Italy.
Interleukin-6 plays a central role in regulating the immune system, hematopoiesis, and acute phase reaction. It interacts with a receptor complex consisting of a specific ligand-binding protein (IL-6R, gp80) and a signal transduction protein (gp130). In this report, serum levels of IL-6 and a soluble form of the interleukin-6 receptor (sIL-6R) were evaluated in patients with hepatocellular carcinoma. The correlation between IL-6 and sIL-6R values, the stage of hepatocellular carcinoma, and main liver function tests was also studied.
UI - 11833870
AU - Kim JH; Kim TK; Kim BS; Eun HW; Kim PN; Lee MG; Ha HK
TI - Enhancement of hepatic hemangiomas with levovist on coded harmonic angiographic ultrasonography.
SO - J Ultrasound Med 2002 Feb;21(2):141-8
AD - Department of Diagnostic Radiology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
OBJECTIVE: To evaluate the pattern of contrast enhancement with Levovist on coded harmonic angiographic ultrasonography of hepatic hemangiomas. METHODS: Twenty hemangiomas were evaluated with coded harmonic angiographic ultrasonography and a microbubble contrast agent. Verification of the diagnosis of a hemangioma was made by means of dynamic computed tomography (n = 8), dynamic magnetic resonance imaging (n = 1), radionuclide scanning (n = 6), or follow-up ultrasonography (n = 5). Ultrasonographic images were obtained before contrast agent administration and with a bolus injection of 2.5 g of a microbubble contrast agent (300 mg/mL Levovist; Schering AG, Berlin, Germany) every 10 to 15 seconds for 5 minutes. The contrast enhancement patterns of the 20 hemangiomas were assessed. RESULTS: The tumor diameters as measured on ultrasonography were 7 to 97 mm (mean, 26.7 mm). Of the 20 hemangiomas, peripheral globular enhancement with progressive centripetal fill-in was shown in 15 (75%), rimlike enhancement with progressive centripetal fill-in was shown in 2 (10%), and homogeneous enhancement was shown in 1 (5%). In the remaining 2 lesions (10%), the enhancement patterns could not be seen, because they were not found on coded harmonic angiographic ultrasonography. CONCLUSIONS: Coded harmonic angiographic ultrasonography with a microbubble contrast agent can depict the typical enhancement pattern in most hepatic hemangiomas.
UI - 11982701
AU - Herath NI; Kew MC; Walsh MD; Young J; Powell LW; Leggett BA; MacDonald
TI - GA Reciprocal relationship between methylation status and loss of heterozygosity at the p14(ARF) locus in Australian and South African hepatocellular carcinomas.
SO - J Gastroenterol Hepatol 2002 Mar;17(3):301-7
AD - Conjoint Gastroenterology Laboratory, Clinical Research Center, Royal Brisbane Hospital Research Foundation, The Queensland Institute of Medical Research, Queesland, Australia. nirmithH@qimr.edu.au
Chromosome 9p21, a locus comprising the tumor suppressor genes (TSG) p16(INK4a) and p14(ARF), is a common region of loss of heterozygosity (LOH) in hepatocellular carcinoma (HCC). p14(ARF) shares exon 2 with p16