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Abramson Cancer CenterNCI CANCERLIT® Search: Diagnosis-Histopathology-Pathogenesis of Liver Cancer - July 2002
National Cancer Institute®
Last Modified: July 1, 2002
- Surveillance for hepatocellular carcinoma in patients with chronic viral hepatitis in the United States of America.
- Peroxisome proliferator-activated receptor gamma augments tumor necrosis factor family-induced apoptosis in hepatocellular carcinoma.
- Small (<20 mm) enhancing hepatic nodules seen on arterial phase MR imaging of the cirrhotic liver: clinical implications.
- Percutaneous fine-needle aspiration cytology in the diagnosis and management of liver tumours.
- Quantification and utility of monosialylated alpha-fetoprotein in the diagnosis of hepatocellular carcinoma with nondiagnostic serum total
- [Genome-wide loss of heterozygosity analyses in primary hepatocellular carcinoma]
- Does hepatitis C virus cause severe liver disease only in people who drink alcohol?
- HCC: what's the score.
- Staging of hepatocellular carcinoma: assessment of the CLIP, Okuda, and Child-Pugh staging systems in a cohort of 257 patients in Toronto.
- [Surgical treatment of giant hemangiomas of the liver]
- Extrahepatic recurrence and second malignancies after treatment of hepatocellular carcinoma: spectrum of imaging findings.
- Efficacy of sequential use of superparamagnetic iron oxide and gadolinium in liver MR imaging.
- Saline injection into the pleural cavity to detect tumors of the hepatic dome with sonography: a new approach for treatment of hepatocellular
- Using multidetector CT for preoperative vascular evaluation of liver neoplasms: technique and results.
- Multidetector CT: diagnostic impact of slice thickness on detection of hypervascular hepatocellular carcinoma.
- Detection of hepatocellular carcinoma: value of adding delayed phase imaging to dual-phase helical CT.
- Sonographic detection of hepatocellular carcinoma and dysplastic nodules in cirrhosis: correlation of pretransplantation sonography and liver
- Hepatitis C and hepatocellular carcinoma.
- [Genetic detection and clinical applications in patients with hepatocellular carcinoma]
- Transactivation of human alpha-fetoprotein gene by X-gene product of hepatitis B virus in human hepatoma cells.
- [Is MRI reliable for screening for hepatocellular carcinoma?]
- Recent research progress in hepatocellular carcinoma.
- Epidemiology, risk factors, and natural history of hepatocellular carcinoma.
- Genetic alterations and oncogenic pathways in hepatocellular carcinoma.
- Circulating IL-6 and sIL-6R in patients with hepatocellular carcinoma.
- Enhancement of hepatic hemangiomas with levovist on coded harmonic angiographic ultrasonography.
- Reciprocal relationship between methylation status and loss of heterozygosity at the p14(ARF) locus in Australian and South African
- Is obesity an independent risk factor for hepatocellular carcinoma in cirrhosis?
- Androgen receptor exon 1 CAG repeat length and risk of hepatocellular carcinoma in women.
- Hepatitis B e antigen and the risk of hepatocellular carcinoma.
- Hepatitis B e Antigen--the dangerous endgame of hepatitis B.
- An increased standardised mortality ratio for liver cancer among polyvinyl chloride workers in Taiwan.
- Establishment and characterization of human metastatic hepatocellular carcinoma cell line.
- Role of reactive oxygen species in apoptosis induced by N-ethylmaleimide in HepG2 human hepatoblastoma cells.
- Hepatic and extrahepatic malignancies in primary sclerosing cholangitis.
- Natural history of hepatocellular carcinoma including fibrolamellar and hepato-cholangiocarcinoma variants.
- [Arguments for surgical resection of hepatocellular carcinoma greater than 20 cm]
- Accumulation of iodized oil within the nonneoplastic liver adjacent to hepatocellular carcinoma via the drainage routes of the tumor after
- N-acetyltransferase 2 polymorphism is not related to the risk of advanced alcoholic liver disease.
- Mutational spectrum of beta-catenin, AXIN1, and AXIN2 in hepatocellular carcinomas and hepatoblastomas.
- Mapping of a minimal deleted region in human hepatocellular carcinoma to 1p36.13-p36.23 and mutational analysis of the RIZ (PRDM2) gene localized
- Preferential loss of a polymorphic RIZ allele in human hepatocellular carcinoma.
- NS-398, a selective cyclooxygenase 2 inhibitor, inhibited cell growth and induced cell cycle arrest in human hepatocellular carcinoma cell
- Resection of hepatocellular carcinoma with out preoperative tumor biopsy.
- [Expression and clinical significance of MAGE-4 gene in human hepatocellular carcinoma]
- [CT, MR and DSA imaging in the follow-up of patients with hepatocellular carcinoma well filled with lipiodol after transcatheter arterial
- [The expression of bcl-xL mRNA in the tissues of normal liver and hepatocarcinoma]
- Peripheral endothelial cells are not reliable in differentiating primary benign and malignant hepatocellular lesions in fine needle aspirates of
- Carcinogenicity of trichloroethylene.
- High-density allelotyping of chromosome 8p in hepatocellular carcinoma and clinicopathologic correlation.
- [Loss of heterozygosity on chromosomes 17 and 16 in primary hepatocellular carcinomas]
- Molecular cloning and characterization of a novel gene which is highly expressed in hepatocellular carcinoma.
Table of Contents
1
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. myron.tong@schs.com
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.
2
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.
3
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.
4
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.
5
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.
6
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.
7
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. ventosandro@yahoo.it
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.
8
UI - 12010872
AU - Shouval D
TI -
HCC: what's the score.
SO - Gut 2002 Jun;50(6):749-50
AD - The Liver Unit, Hadassah University Hospital, Jerusalem, Israel.
9
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.
10
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.
olah.seb@arrabonet.gyor.hu
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.
11
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. tonolini@tin.it
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.
12
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.
13
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.
14
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.
15
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.
16
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.
17
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.
18
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.
fykyao@itsa.ucsf.edu
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.
19
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.
20
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.
21
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
22
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.
23
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. gmontal@unipa.it
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.
24
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.
25
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.
26
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.
27
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
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