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NCI CANCERLIT® Search: Diagnosis-Histopathology-Pathogenesis of Liver Cancer - October 2001
National Cancer Institute®
Ultima Vez Modificado: 21 de noviembre del 2001
Table of Contents
1
UI - 21243501
AU - Tabor E
TI -
Hepatocellular carcinoma: global epidemiology.
SO - Dig Liver Dis 2001 Mar;33(2):115-7
AD - Office of Blood Research and Review, Food and Drug Administration,
Rockville, MD 20852-1448, USA. tabor@cber.fda.gov
2
UI - 21280254
AU - Aguayo A; Patt YZ
TI -
Liver cancer.
SO - Clin Liver Dis 2001 May;5(2):479-507
AD - Department of Gastrointestinal Medical Oncology, Division of Medicine,
University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
The prognosis of patients with HCC remains dismal. Even in the subgroups
of patients who have the most favorable characteristics and are eligible
for surgical resection, the 5-year survival rate is less than 25%. For
patients with more advanced disease, the median survival time is less
than 1 year. The good news in HCC research is that the disease can be
prevented. In Taiwan, the rate of HCC in children aged 6 to 9 years
decreased from 5.2 per million population before the neonatal
vaccination program began in 1984 to 1.3 per million population in the
first vaccinated cohort. Treatment of viral hepatitis with IFN may
decrease the rates of long-term development of HCC. Other agents that
may prevent second primary tumors following resection of HCC, such as
polyprenoic acid and acylic retinoid, are also being investigated.
3
UI - 21338543
AU - Okano H; Shiraki K; Inoue H; Ito T; Yamanaka T; Deguchi M; Sugimoto K;
TI -
Sakai T; Ohmori S; Fujikawa K; Murata K; Takase K; Nakano T
"Variable echo sign" (ultrasonographical alteration of echogenicity) in
cavernous hepatic hemangioma.
SO - Int J Oncol 2001 Aug;19(2):337-40
AD - First Department of Internal Medicine, Mie University School of
Medicine, 2-175 Edobashi, Tsu, Mie 514-8507, Japan.
There are few reports describing cavernous hepatic hemangiomas with
alteration of ultrasonographical imaging during examinations. We
performed ultrasonographic examination of 64 cavernous hepatic
hemangiomas and recognized 26 cases (41%) with an alteration of
echogenicity during the examinations. We refer to this alteration of
echogenicity of cavernous hepatic hemangioma as a "variable echo sign".
We performed angiography of the cavernous hepatic hemangiomas with
variable echo sign. Most of these imaging patterns showed mild or
moderate pooling, suggesting that the alteration of echogenicity might
be based on a slow blood flow exchange. We suggest that a variable echo
sign is specific to ultrasonographic imaging with cavernous hepatic
hemangioma and may be useful to differentiate cavernous hepatic
hemangioma from other tumors.
4
UI - 21383860
AU - Beissert M; Jenett M; Kessler C
TI -
[Diagnosis of space-occupying lesions of the liver. What is the value of
diagnostic imaging?]
SO - MMW Fortschr Med 2001 Apr 26;143(17):29-33
AD - Institut fur Rontgendiagnostik der Universitat Wurzburg.
beissert@roentgen.uni-wuerzburg.de
Ultrasound in B-mode or tissue harmonic imaging is the procedure of
first choice for investigating the liver. If US is employed to screen
for metastatic disease, B-mode contrast harmonic imaging should be used
in addition to conventional ultrasound. For the diagnosis
"space-consuming liver lesion", the echogenicity and clinical aspects
determine the further diagnostic procedure. Echogenic liver lesions in
patients with known malignant disease, and echo-poor or "echo-complex"
lesions always indicate a need for further spiral CT or MRT
investigations. In tumour patients, spiral CT offers the advantage of
enabling simultaneous evaluation of the parenchyma, and abdominal
staging. Primary SPIO-amplified MRT is indicated whenever the primary
interest is the detection of space-consuming liver lesions. In the case
of echogenic lesions in the absence of underlying malignant disease, US
follow-up suffices. Here, differential diagnostic information can be
gained from the vascular distribution patterns of a lesion obtained with
color-coded duplex US. Hepatic lesions that, after exhausting all
diagnostic imaging procedures remain suspicious, require biopsy.
5
UI - 21375989
AU - Sugihara S; Suto Y; Kamba M; Ogawa T
TI -
Comparison of various techniques of iron oxide-enhanced breath-hold MR
imaging of hepatocellular carcinoma.
SO - Clin Imaging 2001 Mar-Apr;25(2):104-9
AD - Department of Radiology, Faculty of Medicine, Tottori University,
Nishicho, Yonago 683, Japan.
The purpose of our study is to compare qualitatively and quantitatively
the abilities of various superparamagnetic iron oxide (SPIO)-enhanced
breath-hold magnetic resonance imaging (MRI) techniques to detect
hepatocellular carcinoma (HCC). Eight patients with HCCs were imaged.
The images were obtained with conventional T2-weighted spin-echo imaging
(CSE), half-Fourier single-shot turbo spin-echo (HASTE), single-shot
gradient-echo type echo planar imaging (GE-EPI), and single-shot
spin-echo type echo planar imaging (SE-EPI) before and after SPIO
administration. The liver signal-to-noise ratios (SNRs) in CSE and each
EPI sequence were significantly decreased after SPIO administration.
GE-EPI had the highest decrease ratio (DR) of liver SNR, followed by
SE-EPI (TE=98), SE-EPI (TE=28), CSE, and HASTE in this order. The
relative contrasts with GE-EPI and SE-EPI (TE=98) were significantly
higher than that with CSE after SPIO administration. On receiver
operating characteristic (ROC) analysis, diagnostic accuracy did not
differ significantly among the pulse sequences after SPIO
administration. GE-EPI and SE-EPI (longer TE) were useful for
SPIO-enhanced breath-hold MRI performed to detect HCC.
6
UI - 21385138
AU - Yang EB; Zhao YN; Zhang K; Mack P
TI -
Microsatellite alterations in human hepatocellular carcinoma infected
with hepatitis B virus: associated with the elevation of serum
alpha-fetoprotein.
SO - Int J Oncol 2001 Sep;19(3):513-8
AD - Department of Experimental Surgery, Singapore General Hospital, Outram
Road, Singapore 169608. gesyeb@sgh.gov.sg
Identification of the basic genetic changes in human hepatocellular
carcinoma (HCC) is very important for the understanding of this cancer.
In this study, genomic DNA from 29 pairs of HCC and corresponding
non-tumour tissues infected with hepatitis B virus (HBV) was prepared.
Five CA-repeated microsatellite markers, including D8S277, D3S1029,
D5S409, D2S123, and TP53, were used to analyse microsatellite
alterations and their subtypes in these patients by polymerase chain
reaction (PCR) amplification and denatured polyacrylamide gel
electrophoresis. Microsatellite alterations were found in 15 of the 29
HCC patients (51.72%), implying that microsatellites are unstable in
genomic DNA of HBV-infected HCC. It was found that frequency of
microsatellite alterations in these HCC patients was not associated with
patients' age, sex, status of tumour differentiation, and tumour size.
Frequency of microsatellite alterations in HCC patients with cirrhosis
tended to be less than that in patients without cirrhosis, but Fisher's
exact test, 2-tailed, showed that this difference was not significant.
Significantly more microsatellite alterations in serum alpha-fetoprotein
(AFP)-positive cases were observed than those in serum AFP-negative
ones, implying that the elevation of AFP in HBV-infected HCC may be
associated with microsatellite stability.
7
UI - 21398001
AU - Nishiguchi S; Shiomi S; Ofuji S; Ishizu H; Iwata Y; Sasaki N; Minamitani
TI -
S; Ochi H
Leiomyosarcoma of the liver detected by high F-18 fluorodeoxyglucose
positron emission tomographic uptake.
SO - Clin Nucl Med 2001 Sep;26(9):798-9
AD - Third Department of Internal Medicine, Osaka City University Medical
School, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan.
8
UI - 21423017
AU - Niketeghad F; Decker HJ; Caselmann WH; Lund P; Geissler F; Dienes HP;
TI -
Schirmacher P
Frequent genomic imbalances suggest commonly altered tumour genes in
human hepatocarcinogenesis.
SO - Br J Cancer 2001 Sep 1;85(5):697-704
AD - Institute of Pathology, University of Cologne, Joseph Stelzmann Str. 9,
Cologne, D-50931, Germany.
Hepatocellular carcinoma (HCC) is one of the most frequent-occurring
malignant tumours worldwide, but molecular changes of tumour DNA, with
the exception of viral integrations and p53 mutations, are poorly
understood. In order to search for common macro-imbalances of genomic
tumour DNA, 21 HCCs and 3 HCC-cell lines were characterized by
comparative genomic hybridization (CGH), subsequent database analyses
and in selected cases by fluorescence in situ hybridization (FISH).
Chromosomal subregions of 1q, 8q, 17q and 20q showed frequent gains of
genomic material, while losses were most prevalent in subregions of 4q,
6q, 13q and 16q. Deleted regions encompass tumour suppressor genes, like
RB-1 and the cadherin gene cluster, some of them previously identified
as potential target genes in HCC development. Several potential growth-
or transformation-promoting genes located in chromosomal subregions
showed frequent gains of genomic material. The present study provides a
basis for further genomic and expression analyses in HCCs and in
addition suggests chromosome 4q to carry a so far unidentified tumour
suppressor gene relevant for HCC development. Copyright 2001 Cancer
Research Campaign.
9
UI - 21190916
AU - Matsumura T; Makino R; Mitamura K
TI -
Frequent down-regulation of E-cadherin by genetic and epigenetic changes
in the malignant progression of hepatocellular carcinomas.
SO - Clin Cancer Res 2001 Mar;7(3):594-9
AD - Second Department of Internal Medicine, Showa University School of
Medicine, Tokyo, Japan.
E-cadherin mediates cell-cell adhesion by associating with catenins.
Loss of E-cadherin function by genetic or epigenetic alteration of the
E-cadherin gene (CDH1) leads to tumorigenesis. To study the involvement
of E-cadherin dysfunction in liver tumorigenesis, we examined the
allelic loss and methylation of 5'-CpG sites of CDH1 in hepatocellular
carcinomas (HCCs). Loss of heterozygosity (LOH) of CDH1 and adjacent
16q22-23 loci was observed in 13 of 30 (43%) HCCs. Methylation of the
5'-CpG of CDH1 was analyzed by Southern blot hybridization, and
hypermethylation was observed in 8 of the 24 (33%) HCCs examined. The
amount of E-cadherin mRNA was analyzed by RNase protection assay, and a
decrease in E-cadherin mRNA was observed in 10 of the 23 cases examined.
A reduction in E-cadherin was found in 10 of 21 HCCs using immunoblot
analysis. The amount of E-cadherin was comparable to that of E-cadherin
mRNA. Down-regulation of E-cadherin was common in cases with LOH but
rare in cases with methylated promoter. These results suggest that
hypermethylation of the CDH1 promoter is present in a small cell
population in the tumor, thus the methylation status is liable to vary
according to individual cell condition. Hypermethylation was observed in
early stage HCCs, whereas LOH was found frequently in more malignant
tumors. Down-regulation of E-cadherin is closely related to the
progression of HCCs and is stably induced by LOH of CDH1.
10
UI - 21271452
AU - Lau WY; Ho S; Leung WT; Chan M; Lee WY; Johnson PJ
TI -
What determines survival duration in hepatocellular carcinoma treated
with intraarterial Yttrium-90 microspheres?
SO - Hepatogastroenterology 2001 Mar-Apr;48(38):338-40
AD - Department of Surgery, Chinese University of Hong Kong, Prince of Wales
Hospital, Shatin, Hong Kong.
BACKGROUND/AIMS: The survival duration of patients with nonresectable
hepatocellular carcinoma confined to the liver and treated with
intraarterial yttrium-90 microspheres was highly variable. METHODOLOGY:
Eighty-two patients treated by this method were analyzed. Thirty-one
patients who lived for one year or longer from the date of first
treatment were classified as 'long survivors' and 51 patients who died
within 1 year were classified as 'short survivors'. RESULTS: Comparison
between the 2 categories suggested that lower pretreatment level of
alpha-fetoprotein and higher tumor-to-normal uptake ratio of yttrium-90
microspheres favored longer survival. Results also indicated that the
treatment was effective even for large tumors and for postoperative
recurrence. Repeated treatment of viable residual or recurrent tumors
offered further palliation and prolongation of survival. CONCLUSIONS:
Pretreatment alpha-fetoprotein level, tumor-to-normal uptake ratio of
yttrium-90 microspheres and the number of treatments determine survival
duration.
11
UI - 21271489
AU - Hara M; Mori M; Hara T; Yamamoto K; Honda M; Nishizumi M
TI -
Risk of developing hepatocellular carcinoma according to the titer of
antibody to hepatitis C virus.
SO - Hepatogastroenterology 2001 Mar-Apr;48(38):498-501
AD - Department of Community Health Science, Saga Medical School, Nabeshima
5-1-1, Saga 849-8501, Japan. g9713@post.saga-med.ac.jp
BACKGROUND/AIMS: Hepatitis C virus infection has been reported to be one
of the main risk factor for developing hepatocellular carcinoma in
Japan. The aim of the study was to examine the differences in the risk
of developing hepatocellular carcinoma according to the titer of
antibody to HCV. METHODOLOGY: A total of 13,173 inhabitants had their
titers of anti-HCV examined based on a second generation passive
hemagglutination assay, and we thus found 1,758 inhabitants whose
anti-HCV titers were equal to or above 2(5). After carefully comparing
our findings with the list of hepatocellular carcinoma in the Saga
Prefectural Cancer Registry, we ascertained 45 cases of hepatocellular
carcinoma (males 37, females 8). The logistic regression model was used
to estimate the Odds ratio of risk factors for hepatocellular carcinoma.
RESULTS: The risk of hepatocellular carcinoma in the subjects from 60-69
years of age was significantly higher than in the other age groups (Odds
ratio = 3.88, P < 0.01). The risk of hepatocellular carcinoma in the
males was also significantly higher than in the females (Odds ratio =
8.96, P < 0.001). The risk of hepatocellular carcinoma in the subjects
with a titer of anti-HCV equal to or above 2(12) was significantly
higher than in the subjects with a titer of less than 2(12) (Odds ratio
= 33.46, P < 0.001). Furthermore, the age- and sex-adjusted risk for
developing hepatocellular carcinoma for the subjects with a titer equal
to or above 2(12) was significantly higher than that for subjects with a
titer of less than 2(12) (Odds ratio = 32.56, P < 0.001). CONCLUSIONS:
The risk of developing hepatocellular carcinoma was significantly high
in the subjects with a titer equal to or above 2(12). To measure the
titer of anti-HCV is thus considered to be useful for effectively
detecting infection in a mass screening program.
12
UI - 21271493
AU - Yoshidome S; Tanabe G; Yoshida A; Ueno S; Hamanoue M; Mitue S; Aikou T
TI -
Risk prediction using histology of noncancerous liver before hepatic
resection for hepatocellular carcinoma.
SO - Hepatogastroenterology 2001 Mar-Apr;48(38):518-22
AD - First Department of Surgery, Kagoshima University School of Medicine,
8-35-1 Sakuragaoka, Kagoshima, 890-8520 Japan. shinro@po.synapse.ne.jp
BACKGROUND/AIMS: The aim of this study is to elucidate the feasibility
of the risk assessment of hepatic resection by histological evaluation
of noncancerous liver in patients with hepatocellular carcinoma.
METHODOLOGY: The study involved 78 patients with hepatocellular
carcinoma who had undergone a needle biopsy of noncancerous liver before
hepatic resection. The histological activity index score which consists
of four categories indicating the inflammatory activity and the degree
of fibrosis was determined, and its association with complications after
hepatic resection was examined. RESULTS: Postoperative complications
occurred in 26 of the first 52 patients that underwent hepatic
resection. A logistic analysis selected histological activity index
score as an independent factor related to postoperative complications
(Odds ratio 1.31, P < 0.02). Postoperative complications occurred more
frequently in patients with a histological activity index score > or = 6
that had undergone resection of two or more segments (P < 0.05), and
also in those with histological activity index score > or = 10 that had
undergone segmentectomy or subsegmentectomy (P < 0.05). When the
histological activity index score was taken into consideration in
deciding operative procedures for a further 20 patients, the incidence
of postoperative complications reduced considerably to 10%. CONCLUSIONS:
Preoperative histological evaluation of noncancerous liver by a needle
biopsy may be helpful in deciding the operative procedure to avoid
complications after hepatic resection for hepatocellular carcinoma.
13
UI - 21287869
AU - Trevisani F; D'Intino PE; Morselli-Labate AM; Mazzella G; Accogli E;
TI -
Caraceni P; Domenicali M; De Notariis S; Roda E; Bernardi M
Serum alpha-fetoprotein for diagnosis of hepatocellular carcinoma in
patients with chronic liver disease: influence of HBsAg and anti-HCV
status.
SO - J Hepatol 2001 Apr;34(4):570-5
AD - Dipartimento di Medicina Interna, Cardioangiologia, Epatologia,
University of Bologna, Italy. trevi@unibo.it
BACKGROUND: It is not established whether virological status affects the
efficiency of alpha-fetoprotein (AFP) as a hepatocellular carcinoma
(HCC) marker among patients with chronic liver disease (CLD). METHODS:
We enrolled in a case-control study 170 HCC and 170 CLD patients,
matched for age, sex, CLD and HBsAg/anti-HCV status. The AFP
sensitivity, specificity, positive (PPV) and negative (NPV) predictive
values were calculated. PPV and NPV were evaluated for three additional
HCC prevalences (5, 10, and 20%). RESULTS: The best discriminating AFP
value was 16 ng/ml. A value of 20 ng/ml (above which investigations for
HCC are recommended) had equivalent sensitivity (60.0 vs. 62.4%) and
specificity (90.6 vs. 89.4%). PPV of 20 ng/ml was 84.6% but decreased to
25.1% at 5% tumor prevalence. NPV was 69.4% and rose to 97.7% at 5%
prevalence. In the different groups of infected patients PPV ranged from
80.0 to 90.9%, falling to 17.4-34.5% at 5% prevalence. In noninfected
patients PPV was 100% at any HCC prevalence. NPV ranged from 59.0 to
73.0%, reaching 96.5-98.1% at 5% prevalence. CONCLUSIONS: In CLD
patients, AFP monitoring misses many HCCs and inappropriately arouses
suspicion of malignancy in many patients. Its usefulness is barely
affected by the infection responsible for CLD. An AFP elevation could be
more indicative of HCC in non-infected patients.
14
UI - 21287874
AU - Sherman M
TI -
Alphafetoprotein: an obituary.
SO - J Hepatol 2001 Apr;34(4):603-5
15
UI - 21393542
AU - Hung CH; Changchien CS; Lu SN; Eng HL; Wang JH; Lee CM; Hsu CC; Tung HD
TI -
Sonographic features of hepatic adenomas with pathologic correlation.
SO - Abdom Imaging 2001 Sep-Oct;26(5):500-6
AD - Division of Gastroenterology, Department of Internal Medicine, Chang
Gung Memorial Hospital, 123 Ta Pei Road, Niao Sung 833, Kaohsiung,
Taiwan, ROC.
BACKGROUND: We compared the sonographic characteristics of hepatic
adenomas with pathologic findings. METHODS: Information over 10 years
was collected on 12 patients (six men, six women; mean age = 47 years)
with surgically proven hepatic adenomas. Clinical data, sonographic
features, and histopathologic findings were reviewed. RESULTS: The
tumors in males were smaller and simpler than those in women (p < 0.05,
Fisher's exact test). Four of the six larger tumors (>5 cm) showed
mixed-echoic patterns corresponding with pathologically intratumoral
hemorrhage and necrosis. Four homogeneously hypoechoic tumors had less
change in tumor composition. Three homogeneously hyperechoic tumors had
evident fatty changes inside. One isoechoic tumor had a hypoechoic rim,
that correlated mostly to the tumor itself and compressed liver
parenchyma. Seven of the 12 tumors had thin fibrous capsules that were
not seen on sonography. CONCLUSION: Hepatic adenomas have variable
sonographic appearances depending on changes in the tumor. Hypoechoic,
hyperechoic, and mixed-echoic patterns represent simple adenoma, adenoma
with fatty metamorphosis, and hemorrhagic necrosis, respectively, in
tumors.
16
UI - 21420001
AU - Poovorawan Y; Chongsrisawat V; Tangkijvanich P
TI -
Problems and prevention of viral hepatitis in Thailand.
SO - J Med Assoc Thai 2001 Jun;84 Suppl 1():S18-25
AD - Department of Paediatrics, Faculty of Medicine, Chulalongkorn
University, Bangkok, Thailand.
To this day, viral hepatitis remains a major public health problem in
Thailand. Chronic infection with hepatitis B and C viruses are the
leading causes of chronic liver diseases, including cirrhosis and
hepatocellular carcinoma (HCC). Outbreaks of hepatitis A virus continue
to occur in Thailand, even after several years of consistently declining
prevalence rates. Also, the reduction in prevalence of hepatitis D virus
infection has been observed among intravenous drug users over the past
decade. Hepatitis E virus constitutes a rather unusual cause of sporadic
acute hepatitis in Thailand. Highly effective vaccines are currently
available for prevention of hepatitis A and B, however, as yet no
effective vaccine for hepatitis C is imminent. Following rapid progress
in the development of molecular techniques, several new hepatitis
viruses have been identified. Among these, Hepatitis G, TT and SEN
viruses have recently been described but their significance as to
causation of human liver disease has yet to be established. This article
reviews the current epidemiology, molecular biology, and strategies
aimed at prevention and control of hepatitis virus infection in Thailand
emphasizing new developments and recent data obtained from our research
studies.
17
UI - 21295255
AU - Hemming AW; Gallinger S; Greig PD; Cattral MS; Langer B; Taylor BR;
TI -
Verjee Z; Giesbrecht E; Nakamachi Y; Furuya KN
The hippurate ratio as an indicator of functional hepatic reserve for
resection of hepatocellular carcinoma in cirrhotic patients.
SO - J Gastrointest Surg 2001 May-Jun;5(3):316-21
AD - Department of Surgery, University of Florida, Gainesville 32610, USA.
hemmiaw@mail.surgery.ufl.edu
Predicting the ability of the cirrhotic liver to withstand resection
remains a challenge for the surgeon. This study evaluates the use of the
hippurate ratio, a novel assessment of glycine conjugation of
para-aminobenzoic acid by the liver, as a preoperative indicator of
functional hepatic reserve. Between 1998 and 2000, sixty-one cirrhotic
patients were prospectively assessed for hepatic resection using the
hippurate ratio, indocyanine green retention at 15 minutes (ICG R-15),
and other standard measures of liver function. Twenty-six patients were
excluded as candidates for resection on the basis of inadequate
functional hepatic reserve. Patients excluded from resection had
significantly higher ICG R-15 values (29% +/- 9% vs. 16% +/- 12%, P =
0.001), higher Child-Pugh scores (5.9 +/- 0.9 vs. 5.3 +/- 0.4, P =
0.01), and lower hippurate ratios (30% +/- 14% vs. 45% +/- 15%, P =
0.005). There was a significant correlation between the hippurate ratio
and ICG R-15. Other indicators of liver function such as factor V,
factor VII, albumin, bilirubin, prothrombin time, and transaminases were
no different between patients who did and those who did not undergo
resection. Of the 35 patients resected, there were seven (20%) who
developed varying degrees of liver failure with three perioperative
deaths (8.5%). Patients who had some degree of liver failure had
significantly lower hippurate ratios than patients who had no liver
failure (29% +/- 10% vs. 48% +/- 14%, P = 0.002). There was no
difference in ICG R-15 values between patients who had liver failure and
those who did not. The hippurate ratio offers information on
hepatocellular reserve that is not provided by other measures of liver
function and may allow better selection of cirrhotic patients for liver
resection.
18
UI - 21419010
AU - Shuto T; Hirohashi K; Kubo S; Tanaka H; Yamamoto T; Higaki I; Takemura
TI -
S; Kinoshita H
Treatment of adrenal metastases after hepatic resection of a
hepatocellular carcinoma.
SO - Dig Surg 2001;18(4):294-7
AD - Second Department of Surgery, Osaka City University Medical School,
Osaka, Japan. shutou@med.osaka-cu.ac.jp
BACKGROUND: The adrenal gland is a common site of extrahepatic
metastases from a hepatocellular carcinoma (HCC). However, treatment of
adrenal metastases has not been well characterized. METHODS: Of 562
patients who underwent hepatic resection for a HCC, 91 developed
extrahepatic metastases. We reviewed the medical records of 10 patients
with adrenal metastases (9 males and 1 female; mean age 63 years at the
time of hepatic resection). RESULTS: The mean diameter of the primary
tumors was 5 cm, and all were located in the right lobe of the liver.
The mean interval from hepatic resection to recurrence was 18 months.
Seven patients underwent treatment of intrahepatic recurrence. To treat
the adrenal metastases, surgical resection was performed in 4 patients,
and transcatheter arterial embolization was performed in 1 patient. The
patients treated had no other extrahepatic metastases. The mean diameter
of the resected adrenal tumors was 6 cm. There was no hospital
mortality. With surgical resection, 1 patient has been alive 63 months
after recurrence. CONCLUSIONS: Adrenal metastases from a HCC were often
large at the time of diagnosis. Since surgical resection was a safe
procedure, and some patients could be alive for a long time, it should
be performed whenever possible. Copyright 2001 S. Karger AG, Basel
19
UI - 21438126
AU - Mazure NM; Nguyen TL; Danan JL
TI -
Severe hypoxia specifically downregulates hepatocyte nuclear factor-4
gene expression in HepG2 human hepatoma cells.
SO - Tumour Biol 2001 Sep-Oct;22(5):310-7
AD - Centre de Recherche sur l'Endocrinologie Moleculaire et le Developpement
CNRS-UPR 9078, Meudon-Bellevue, France.
The liver is one of the organs in which hypoxia helps to regulate gene
expression under normal physiological conditions and in diseases such as
cirrhosis and cancer. We postulated that the expression/activity of some
of the 'liver-enriched' transcription factors, which control
liver-specific genes, was sensitive to hypoxia. We tested hepatocyte
nuclear factor-1 (HNF-1), HNF-3 and HNF-4, which play key roles in
differentiation, development and hepatic gene expression, using HepG2
human hepatoma cells cultured under hypoxic conditions. Severe
hypoxia/anoxia downregulated HNF-4 DNA-binding activity while
DNA-binding activity of HNF-1 and HNF-3 remained unaffected. These
hypoxic conditions also strongly and specifically decreased cell
contents of HNF-4 protein, indicating that the decrease in HNF-4
DNA-binding activity was due to the lower amount of protein and not to
decreased DNA-binding affinity. Northern analysis indicated that the
expression of the hnf-4 gene was also downregulated in HepG2 cells
cultured under hypoxic conditions. These results provide evidence that
hypoxic stress triggers a cascade of events that inhibits the
transactivation potential of HNF-4 in HepG2 cells. This step may be
crucial in modulating the expression of a subset of liver genes that are
targets for this nuclear receptor. This relationship provides a new
route for the investigation of the effects of hypoxia on the liver cell.
Copyright 2001 S. Karger AG, Basel
20
UI - 21468155
AU - Choi D; Kim SH; Lim JH; Cho JM; Lee WJ; Lee SJ; Lim HK
TI -
Detection of hepatocellular carcinoma: combined T2-weighted and dynamic
gadolinium-enhanced MRI versus combined CT during arterial portography
and CT hepatic arteriography.
SO - J Comput Assist Tomogr 2001 Sep-Oct;25(5):777-85
AD - Department of Radiology, Samsung Medical Center, Sungkyunkwan University
School of Medicine, Seoul, Korea.
PURPOSE: The purpose of this study was to compare the preoperative
detectability of hepatocellular carcinomas (HCCs) using combined
T2-weighted and dynamic gadolinium-enhanced MRI and combined CT during
arterial portography (CTAP) and CT hepatic arteriography (CTHA). METHOD:
Thirty-three patients with 43 HCCs underwent T2-weighted and dynamic
gadolinium-enhanced MRI and combined CTAP and CTHA. The diagnosis was
established by pathologic examination following surgical resection in 26
patients and by biopsy in 7 patients. The MR protocol included fast SE
with two TEs (including T2-weighted imaging) and precontrast and
gadolinium-enhanced T1-weighted fast multiplanar spoiled
gradient-recalled echo images with dynamic study. The MR images of all
sequences and the paired CTAP and CTHA images were independently
reviewed by three radiologists. Image review was conducted on a
segment-by-segment basis. Diagnostic accuracy was evaluated with
receiver operating characteristic analysis. RESULTS: The accuracies (Az
values) of MRI of all sequences and combined CTAP and CTHA for all
observers were 0.960 and 0.959, respectively. The mean sensitivities of
MRI and CT were 90 and 94%, respectively. The differences were not
statistically significant. The mean specificity of MRI (99%) was
significantly higher than that of combined CTAP and CTHA (92%).
CONCLUSION: Combined T2-weighted and dynamic gadolinium-enhanced MRI is
as accurate as combined CTAP and CTHA for preoperative detection of
HCCs.
21
UI - 21467321
AU - Huang BJ; Huang TJ; Liang QW; Huang CW; Fang Y
TI -
[Quantitative detection of HER-2 oncogene amplification in primary
hepatocellular carcinoma using dual FISH technique and its clinical
significance]
SO - Yi Chuan Xue Bao 2001;28(9):793-800
AD - Department of Etiology, Cancer Institute, Sun Yat-sen University of
Medical Sciences, Guangzhou 510060, China.
To investigate the frequency of HER-2 oncogene amplification in primary
hepatocellular carcinoma (HCCs) and its relationships with
clinicopathological parameters and prognosis, 42 surgical samples from
patients with primary HCCs were detected for their HER-2 oncogene
amplification by dual FISH technique, and then the correlations between
HER-2 amplification and clinicopathological characteristics and
prognosis were analyzed statistically. HER-2 oncogene amplification was
detected in 9 of 42 (21.4%) primary HCCs, including 4 (9.5%) cases with
high copy (HC) and 5 (11.9%) ones with low copy (LC). HER-2
amplification was associated significantly with postoperative survival
time of HCC patients examined (P = 0.046) and the presence of HER-2 gene
amplification showed a trend toward a correlation with tumor size (P =
0.085), but wasn't relative to sex, age, AFP level, HBV infection,
postoperative relapse and clinical staging of HCC patients tested (P >
0.05). On the other hand, gain of the HER-2 oncogene copy was examined
in 31 of 42(73.8%) primary HCCs, consisting of 9 (21.4%) cases with
HER-2 amplification and 22(52.4%) ones with aneusomy 17/polysomy 17.
There weren't significant relationships between gain of HER-2 oncogene
copy and, HCC patient's sex, tumor size, clinical staging, postoperative
relapse and survival time (P > 0.05), but gain of HER-2 oncogene copy
correlated significantly to patients' age, AFP level and HBV infection
(P < 0.05). The study indicated that there were a lower frequency of
HER-2 oncogene amplification and a higher frequency of aneusomy
17/polysomy 17 in primary HCCs and that HER-2 oncogene amplification
activation might be involved in the development and progression of a
subset of HCCs, and seemed to be a valuably independent prognosis factor
predicting postoperative poorer survival for patients with HCC.
22
UI - 21463360
AU - Kato A; Miyazaki M; Ambiru S; Yoshitomi H; Ito H; Nakagawa K; Shimizu H;
TI -
Yokosuka O; Nakajima N
Multidrug resistance gene (MDR-1) expression as a useful prognostic
factor in patients with human hepatocellular carcinoma after surgical
resection.
SO - J Surg Oncol 2001 Oct;78(2):110-5
AD - First Department of Surgery, School of Medicine, Chiba University,
Chuo-Ku, Chiba, Japan.
BACKGROUND: Multidrug resistance gene (MDR-1) overexpression has been
correlated with tumor aggressiveness and worse prognosis in some human
neoplasms. The aim of this study is to evaluate the clinical value of
MDR-1 mRNA expression as a prognostic factor after surgical resection in
human hepatocellular carcinoma (HCC). METHODS: MDR-1 mRNA levels in
tissue samples from 34 patients with HCC, who underwent surgical
resection, were measured by quantitative northern blot analysis. We
stratified these patients into two groups according to a ratio of MDR-1
mRNA levels of HCC to nontumorous tissue; MDR-1 mRNA ratio > or = 1.0
and < 1.0. The overall and disease-free survival rates were analyzed
using multivariate regression analysis. RESULTS: The median survival
periods were 10.3 and 35.8 months for patients with the MDR-1 mRNA ratio
> or = 1.0 and < 1.0, respectively, and the corresponding 5-year
survival rates were 33 and 54%, respectively, P < 0.05. The multivariate
analysis revealed that TNM stage and MDR-1 mRNA ratio were independent
factors for predicting overall survival after surgical resection.
CONCLUSION: This study suggested that the measurement of the MDR-1 mRNA
levels in HCC and nontumorous liver tissue might be a useful prognostic
factor after surgical resection in patients with HCC. Copyright 2001
Wiley-Liss, Inc.
23
UI - 21467975
AU - Chen TC; Nakanuma Y; Zen Y; Chen MF; Jan YY; Yeh TS; Chiu CT; Kuo TT;
TI -
Kamiya J; Oda K; Hamaguchi M; Ohno Y; Hsieh LL; Nimura Y
Intraductal papillary neoplasia of the liver associated with
hepatolithiasis.
SO - Hepatology 2001 Oct;34(4 Pt 1):651-8
AD - Department of Pathology, Chang Gung Memorial Hospital, Chang Gung
University School of Medicine, Tao Yuan, Taipei, Taiwan.
Intraductal papillary growth of neoplastic biliary epithelia with a fine
fibrovascular stalk (intraductal papillary neoplasia of liver [IPN-L])
resembling intraductal papillary mucinous neoplasm of pancreas is
occasionally associated with hepatolithiasis. In this study, 136 cases
histologically. IPN-L was found in 41 of 136 hepatolithiasis cases
(30.1%). Sixty-two IPN-L cases (42 women and 20 men; age range, 59.8 +/-
10 years) were divided into 4 types (type 1, IPN-L with low-grade
dysplasia, 23 cases; type 2, IPN-L with high grade dysplasia, 11 cases;
type 3, IPN-L with in situ and microinvasive carcinoma, 13 cases; and
type 4, IPN-L of types 2 and 3 with distinct invasive carcinoma, 15
cases). Intraductal spreading and glandular involvement were commonly
observed in all types. About half of types 3 and 4 cases had mucobilia,
and mucinous carcinoma was variably found in two thirds of group 4
patients. IPN-L frequently showed variable gastroenteric differentiation
such as goblet cells and foveolar and colon-like metaplasia. IPN-L with
goblet cells and colon-like metaplasia was frequently associated with
overproduction of mucin and mucobilia (P <.01). In Japan, IPN-L was not
frequent in hepatolithiasis (12 of 135 cases). In conclusion, IPN-L
forms a spectrum of biliary neoplasm in hepatolithiasis. It often
displays variable gastroenteric metaplasia and significant intraductal
spread. IPN-L tends to progress to mucinous carcinoma. Formerly reported
"mucin-producing intrahepatic cholangiocarcinoma" with a favorable
prognosis is included in IPN-L.
24
UI - 21467983
AU - Kuper H; Ye W; Broome U; Romelsjo A; Mucci LA; Ekbom A; Adami HO;
TI -
Trichopoulos D; Nyren O
The risk of liver and bile duct cancer in patients with chronic viral
hepatitis, alcoholism, or cirrhosis.
SO - Hepatology 2001 Oct;34(4 Pt 1):714-8
AD - Department of Epidemiology and Public Health, University College London,
London, UK. hannahk@public-health.ucl.ac.uk
No prospective study has analyzed simultaneously chronic viral hepatitis
and alcoholism as risk factors for liver carcinogenesis, while taking
into consideration the role of cirrhosis. Nor has the risk for
hepatocellular carcinoma among patients with chronic viral hepatitis
been prospectively evaluated in a low-risk Western population. Last, the
relationship between hepatocellular carcinoma risk factors and bile duct
cancer remains to be clarified. We analyzed prospectively the risk for
primary liver and extrahepatic biliary tract cancer among 186,395
patients hospitalized with either chronic viral hepatitis, alcoholism,
cirrhosis, or any combination of these conditions through linkages
between national Swedish registers. Compared with the general
population, the relative risk of hepatocellular carcinoma was 34.4 for
chronic viral hepatitis alone, 2.4 for alcoholism alone, and 40.7 for
cirrhosis alone. Among patients with combinations of these risk
conditions, the relative risk of hepatocellular carcinoma was 27.3 for
chronic viral hepatitis and alcoholism, 118.5 for chronic viral
hepatitis and cirrhosis, 22.4 for alcoholism and cirrhosis, and 171.4
for all 3 conditions. We found limited evidence for an excess risk of
intrahepatic, but not for extrahepatic, biliary duct cancer. Cirrhosis
amplifies the risk of hepatocellular carcinoma among patients with
chronic viral hepatitis, but it is not a prerequisite for liver
carcinogenesis. In contrast, cirrhosis may be a necessary intermediate
for the development of hepatocellular carcinoma among alcoholics.
25
UI - 94363628
AU - Melchiorri C; Bolondi L; Chieco P; Pagnoni M; Gramantieri L; Barbara L
TI -
Diagnostic and prognostic value of DNA ploidy and cell nuclearity in
ultrasound-guided liver biopsies.
SO - Cancer 1994 Sep 15;74(6):1713-9
AD - Institute of Oncology, S. Orsola Hospital, Bologna, Italy.
BACKGROUND. Focal nodule lesions in patients with cirrhotic livers may
be visualized by using imaging techniques; however, the diagnostic and
prognostic judgment of biopsies from borderline lesions may be difficult
using conventional histologic criteria. METHODS. The diagnostic and
prognostic value of DNA ploidy analysis determined by image cytometry of
Feulgen-stained isolated hepatocytes was investigated in
ultrasound-guided biopsies from 50 nodular lesions found in patients
with cirrhotic livers (39 hepatocellular carcinomas [HCCs] and 11
macroregenerative nodules) and from 10 patients with livers affected by
viral chronic hepatitis. Of the 11 macroregenerative nodules, 7
presented a subsequent neoplastic behavior. Specimens from the
morphologically normal livers of five patients who underwent liver
surgery served as control tissues. Image cytometry was performed on
Feulgen-stained cytologic preparations, obtained by enzymatic digestion
of formalin fixed biopsies. The DNA ploidy of the main stem line and the
distribution of mononucleated and binucleated hepatocytes (nuclearity)
were compared using histologic diagnosis, Edmondson's grade, tumor size,
and patient follow-up. RESULTS. The main stem line was peridiploid in
all benign specimens and in 31 clinically confirmed HCCs, peritetraploid
in 11 HCCs, perioctaploid in 1 HCC, and aneuploid in 3 HCCs. The
fraction of mononucleated polyploid hepatocytes was found to be the best
diagnostic parameter in euploid HCCs and was significantly correlated
with the Edmondson grade and the nodular size. Survival information was
available for 43 patients, with a median observation period of 350 days.
A DNA ploidy value of the main stem line greater than 3c was an
important determinant of survival as a single parameter and in
association with histologic grade and greatest dimension of tumor.
CONCLUSIONS. This study suggests that the ploidy distribution analysis
of mononucleated and binucleated hepatocytes can provide valuable
information for making correct diagnoses and for predicting survival
outcome for patients with HCCs.
26
UI - 21342882
AU - Akhter J; Lu Y; Finlay I; Pourgholami MH; Morris DL
TI -
1alpha,25-Dihydroxyvitamin D3 and its analogues, EB1089 and CB1093,
profoundly inhibit the in vitro proliferation of the human
hepatoblastoma cell line HepG2.
SO - ANZ J Surg 2001 Jul;71(7):414-7
AD - University of New South Wales, Department of Surgery, St George
Hospital, Sydney, Australia.
BACKGROUND: 1alpha,25-dihydroxyvitamin D3 (1,25[OH]2D3) has been shown
to inhibit the proliferation of various cancer cells including colon,
prostate, melanoma, osteosarcoma and breast cancer. METHODS: The human
hepatoma cell line (HepG2) was cultured with 1,25(OH)2D3 or one of two
analogues EB1089 or CB1093 for various durations. Cellular proliferation
was measured by uptake of [3H]thymidine, and cell numbers were
determined by trypan blue exclusion counting. RESULTS: 1,25(OH)2D3,
EB1089 and CB1093 all inhibited proliferation of HepG2 by up to 90%
after 5 days of treatment, compared to the untreated controls. Decreased
proliferation was associated with an approximately 50% reduction in cell
numbers at concentrations of up to 10(-10) mol/L after 5 days of
treatment with 1,25(OH)2D3. Cell proliferation rapidly recovered in
cultures treated with lower concentrations of 1,25(OH)2D3 (10(-10) and
10(-11) mol/L) when 1,25(OH)2D3 was removed from the cultures by placing
cells in serum containing medium without 1,25(OH)2D3. When HepG2 cells
were treated with 10(-8) mol/L 1,25(OH)2D3 for 5 weeks, there was still
significant inhibition of proliferation, although at week 5 there was
66% inhibition compared to 93% at the end of week 1. CONCLUSIONS:
1,25(OH)2D3, EB1089 and CB1093 all significantly inhibit the
proliferation of HepG2 hepatoblastoma cells, with EB1089 being the most
potent at lower concentrations. Inhibition can be maintained for at
least 4 weeks, but is reversed after removal of vitamin D3.
27
UI - 21345332
AU - Grazioli L; Federle MP; Brancatelli G; Ichikawa T; Olivetti L; Blachar A
TI -
Hepatic adenomas: imaging and pathologic findings.
SO - Radiographics 2001 Jul-Aug;21(4):877-92; discussion 892-4
AD - Department of Radiology, University of Brescia, Brescia, Italy.
Hepatocellular adenoma is a rare benign lesion that is most often seen
in young women with a history of oral contraceptive use. It is typically
solitary, although multiple lesions have been reported, particularly in
patients with glycogen storage disease and liver adenomatosis. Because
of the risk of hemorrhage and malignant transformation, hepatocellular
adenomas must be identified and treated promptly. At pathologic
analysis, hepatocellular adenoma is usually a well-circumscribed,
nonlobulated lesion, and at gross examination, resected adenomas
frequently demonstrate areas of hemorrhage and infarction. Most adenomas
are not specifically diagnosed at ultrasonography (US) and are usually
further evaluated with computed tomography (CT) or other imaging
modalities. Color Doppler US may help differentiate hepatocellular
adenoma from focal nodular hyperplasia. Multiphasic helical CT allows
more accurate detection and characterization of focal hepatic lesions.
Hepatocellular adenomas are typically bright on T1-weighted magnetic
resonance images and predominantly hyperintense relative to liver on
T2-weighted images. The prognosis of hepatic adenoma is not well
established. Criteria that guide treatment include the number and size
of the lesions, the presence of symptoms, and the surgical risk incurred
by the patient. Understanding the imaging appearance of hepatocellular
adenoma can help avoid misdiagnosis and facilitate prompt, effective
treatment.
28
UI - 21403105
AU - Choi YL; Park SH; Jang JJ; Park CK
TI -
Expression of the G1-S modulators in hepatitis B virus-related
hepatocellular carcinoma and dysplastic nodule: association of cyclin D1
and p53 proteins with the progression of hepatocellular carcinoma.
SO - J Korean Med Sci 2001 Aug;16(4):424-32
AD - Department of Diagnostic Pathology, Samsung Medical Center, Sungkyunkwan
University School of Medicine, Seoul, Korea.
Deranged expression of cell cycle modulators has been reported to
contribute to the development and progression of hepatocellular
carcinoma (HCC). However, their expression patterns remain poorly
understood in hepatitis B virus (HBV)-related HCC, which constitutes
about 65-70% of HCC in Korea. The aims of this study were to evaluate
the expressions of G1-S modulators in HBV-related HCCs and dysplastic
nodules (DNs), and to correlate with the histopathologic features of
HCCs. Immunohistochemical expressions of cyclin D1, cyclin E, p53, p27,
p21, p16, Rb, and PCNA proteins were investigated in 80 HCCs and 22 DNs.
Cyclin D1 overexpression showed positive relationships with advanced
tumor stage, poor differentiation, larger tumor size, microvascular
invasion, intrahepatic meta-stasis, no tumor capsule formation,
infiltrative growth, aberrant p53 expression, and high PCNA labeling
index (LI) of HCC (p<0.05). Aberrant p53 expression showed positive
relationship with poor differentiation of HCC (p<0.01). Expression of
cyclin D1 or p53 was not observed in DNs. The p27 LI and p16 LI were
lower in HCCs with intrahepatic metastasis (p<0.05). Cyclin D1
overexpression and aberrant p53 expression could be associated with the
progression of HBV-related HCC, and might have a less crucial role in
the DN-HCC sequence. In addition, elevated expression of p27 and p16
proteins might have inhibitory action to the intrahepatic metastasis of
HBV-related HCC.
29
UI - 21230505
AU - Moehler M; Blechacz B; Weiskopf N; Zeidler M; Stremmel W; Rommelaere J;
TI -
Galle PR; Cornelis JJ
Effective infection, apoptotic cell killing and gene transfer of human
hepatoma cells but not primary hepatocytes by parvovirus H1 and derived
vectors.
SO - Cancer Gene Ther 2001 Mar;8(3):158-67
AD - Department of Internal Medicine, University of Mainz, Germany.
moehler@1-med.klinik.uni-mainz.de
Autonomous parvoviruses preferentially replicate in and kill in
vitro-transformed cells and reduce the incidence of spontaneous and
implanted tumors in animals. Because of these natural oncotropic and
oncolytic properties, parvoviruses deserve to be considered as potential
antitumor vectors. Here, we assessed whether parvovirus H1 is able to
kill human hepatoma cells by induction of apoptosis but spares primary
human liver cells, and whether the former cells can efficiently be
transduced by H1 virus-based vectors. Cell death, infectivity, and
transgene transduction were investigated in Hep3B, HepG2, and Huh7 cells
and in primary human hepatocytes with natural and recombinant H1 virus.
All hepatoma cells were susceptible to H1 virus-induced cytolyis. Cell
death correlated with H1 virus DNA repli
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