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Abramson Cancer CenterNCI CANCERLIT® Search: Diagnosis-Histopathology-Pathogenesis of Liver Cancer - April 2002
National Cancer Institute®
Last Modified: April 1, 2002
Table of Contents
1
UI - 11686032
AU - Stevenson JP; O'Dwyer PJ
TI -
Cancers of the large bowel and hepatobiliary tract.
SO - Cancer Chemother Biol Response Modif 2001;19():547-71
AD - University of Pennsylvania Cancer Center, Presbyterian Medical Center,
51 North 39th Street, Medical Arts Building, Suite 103, Philadelphia, PA
19104, USA.
2
UI - 11122434
AU - Emile JF; Adam R; Sebagh M; Marchadier E; Falissard B; Dussaix E;
TI -
Bismuth H; Reynes M
Hepatocellular carcinoma with lymphoid stroma: a tumour with good
prognosis after liver transplantation.
SO - Histopathology 2000 Dec;37(6):523-9
AD - Service d'Anatomopathologie,Centre Hepatobiliaire, Hopital Paul Brousse
and UPRES 1596 'Virus Hepatotropes et Cancer', Universite Paris Sud,
France. jean-francois.emile@pbr.ap-hop-paris.fr
AIMS: Carcinomas with lymphoid stroma arising in non-liver-organs have a
better prognosis than other carcinomas and may be associated with
Epstein-Barr virus. We determined the frequency, characteristics and
prognosis of hepatocellular carcinomas with lymphoid stroma. METHODS AND
RESULTS: Histology of the livers of 162 patients with hepatocellular
carcinoma, who underwent an orthotopic liver transplantation, was
reviewed independently by three pathologists. Hepatocellular carcinoma
with lymphoid stroma was diagnosed when all tumour samples contained
more lymphocytes than tumour cells. Epstein-Barr virus was detected by
in-situ hybridization and by polymerase chain reaction. Five patients
(3.6%) were classified as hepatocellular carcinomas with lymphoid
stroma. All patients were males. Cirrhosis was present in four/five
patients. Serum alpha-fetoprotein levels were normal. Inter-observer
histological reproducibility was good. Tumour cells did not contain
Epstein-Barr virus. The five patients were alive without tumour at three
years, although two of them had adverse prognostic factors at the time
of transplantation (more than one tumour with a diameter > or = 40 mm).
Only one patient had tumour recurrence, but he survived 7.6 years
post-transplantation. The 5-year survival of patients with
hepatocellular carcinoma with lymphoid stroma was better than that of
the patients with other types of hepatocellular carcinomas (P = 0.04).
CONCLUSIONS: Hepatocellular carcinoma with lymphoid stroma should be
considered as a distinct clinicopathological and prognostic entity.
3
UI - 11737314
AU - Szekely E
TI -
Hepatocellular carcinoma with lymphoid stroma: 'lymphoepithelioma-like
carcinoma'?
SO - Histopathology 2001 Nov;39(5):540
4
UI - 11750150
AU - Koushima Y; Ebara M; Fukuda H; Morimoto N; Sugiura N; Yoshikawa M;
TI -
Sanada M; Saisho H; Matsumoto T; Yukawa M
Small hepatocellular carcinoma: assessment with T1-weighted spin-echo
magnetic resonance imaging with and without fat suppression.
SO - Eur J Radiol 2002 Jan;41(1):34-41
AD - The First Department of Medicine, School of Medicine, Chiba University
Hospital, 1-8-1 Inohana, 1254-9-306 Miyako-cho, Chuou-ku, Chiba-shi,
Chiba 260, Japan. ko-san@gb3.so-net.ne.jp
OBJECTIVE: We examined the detectability of small hepatocellular
carcinomas (HCCs) and the factors that affect hyperintensity of small
HCC on T1-weighted images (T1W) by using T1-weighted fat-suppressed
images (T1FS). METHODS: Thirty-nine HCCs (29 patients) measuring 30 mm
or less were enrolled. The mean size of HCCs was 21.0+/-4.9 mm.
Spin-echo T1W, T2-weighted images (T2W), and T1FS were obtained using a
1.5 T system. We evaluated the detectability in each sequence by
receiver-operating-characteristic (ROC) analysis and the
tumor-to-hepatic parenchyma contrast-to-noise ratio (CNR), the variance
in the detectability among all interpreters with each sequence, and the
presence or absence of improvement in the detectability by interpreting
T1FS in addition to conventional T1W plus T2W. The contents of fat,
copper, and iron in histologically diagnosed HCCs showing hyperintensity
on both T1W and T1FS were measured. For determination of heavy metals,
we used a particle induced X-ray emission analytical instrument.
RESULTS: ROC analyses revealed that T1FS were superior to T1W and T2W in
detecting small HCCs (0.900+/-0.017 for T1FS, 0.859+/-0.019 for T1W, and
0.745+/-0.030 for T2W). The detectability by interpreting T1FS in
addition to conventional T1W plus T2W was improved (0.931+/-0.013 for
the conventional images and 0.973+/-0.008 for the conventional images
plus T1FS, P<0.001). The detected lesions on T1FS demonstrated favorable
CNR values. The copper content in the cancer and the ratio of the copper
content in the cancer to that in the non-cancerous tissue were
275.4+/-219.0 microg/g dry weight, 6.9+/-5.5 in HCCs showing
hyperintensity on both T1W and T1FS. Both were significantly higher
(P<0.05). CONCLUSION: T1FS showed excellent sensitivity and specificity
in detecting small HCCS irrespective of the experience of interpreters.
The use of T1FS suggested the involvement of copper might be one of the
factors in hyperintensity of HCCs on T1W.
5
UI - 11247062
AU - Krastev N; Grigorov N; Dinkov L; Genov Y; Mitova R; Donov M
TI -
[The role of laparoscopy and laparoscopic ultrasonography in the
diagnosis and differential diagnosis of nodular hepatocellular lesions]
SO - Khirurgiia (Sofiia) 1998;53(6):14-8
AD - *University Hospital "Queen Joanna," Clinical Center of
Gastroenterology, Sofia, Bulgaria.
The diagnostic relevance of laparoscopy (LS) and laparoscopic echography
(LE) in nodular hepatocellular lesions is studied. LS is done using a R.
Wolf laparoscope, and LE--with a 7.5 MHz linear transducer, obtained
from the Aloka Company. A total of 250 patients presenting 288 nodular
hepatocellular lesions are investigated over 15 years (1983-1998),
including: focal nodular hyperplasia (FNH)--1, nodular regenerative
hyperplasia (NRH)--1, hepatocellular adenoma (HCA)--1, adenomatous
hyperplasia (AH)--38, hepatocellular carcinoma (HCC)--58, Budd-Chiari
syndrome--2, primary sclerosing cholangitis (PSCh)--2, and cirrhosis of
liver--185. The lesions are distributed according to the updated
classification of the International Working Party, published in 1995. In
addition to the latter, a case of cholangiocellular adenoma undergoing
malignant degeneration and a case presenting carcinoma, giving rise to
differential diagnostic difficulties are also described. Some of the
aforementioned diseases are reported for the first time in the Bulgarian
literature. Emphasis is laid on the practicability of combining
endoscopic with imaging diagnostics, attributable to laparoscopic
echography and to the advantages of echolaparoscopic biopsy. Almost half
of the foci (46.1%) are morphologically verified. The aim of cytological
assessment is to establish the malignant character of the lesion, first
and foremost, while the histological finding is essential for making a
correct diagnosis.
6
UI - 11852387
AU - Bioulac-Sage P; Lepreux S; Laurent C; Balabaud C
TI -
[Adenoma or focal nodular hyperplasia of the liver? A difficult
pathological diagnosis]
SO - Gastroenterol Clin Biol 2001 Oct;25(10):866-8
AD - Service d'Anatomie-Pathologique, Hopital Pellegrin, CHU, Bordeaux,
France. paulette.bioulac-sage@gref.u-bordeaux2.fr
7
UI - 11917867
AU - Yotsuyanagi H
TI -
[Progression of HBV and HCV hepatitis into the chronic stage and cancer]
SO - Nippon Naika Gakkai Zasshi 2001 Dec 10;90(12):2426-30
8
UI - 11865373
AU - Liu CL; Fan ST; Lo CM; Ng IO; Poon RT; Wong J
TI -
Intraoperative iatrogenic rupture of hepatocellular carcinoma.
SO - World J Surg 2002 Mar;26(3):348-52
AD - Department of Surgery, Centre of Liver Diseases, University of Hong Kong
Medical Centre, Queen Mary Hospital, 102 Pokfulam Road, Hong Kong,
China. clliu@hkucc.hku.hk
Intraoperative iatrogenic rupture of hepatocellular carcinoma (HCC),
which can occur during hepatic resection when large tumors are being
mobilized, may adversely affect the operative outcome. Little
information is available in the literature on this serious
intraoperative complication. The aim of the present study is to document
iatrogenic rupture of HCC as a serious complication during hepatic
resection and its effects on the operative and long-term outcomes of
patients with this complication. A retrospective study was performed on
all patients with intraoperative iatrogenic rupture of HCC during
hepatic resection from 1989 to 1997, and the operative and long-term
survival outcomes were compared with those of patients without the
complication. Among 194 patients who underwent hepatic resection for a
large HCC (> or =5 cm) during the study period, 8 (4.1%) had
intraoperative iatrogenic rupture of the tumor. When compared with 186
patients with similar clinical parameters but without intraoperative
rupture, patients with intraoperative rupture had significantly more
intraoperative blood loss (median 5.7 vs. 2.0 L;p = 0.01) and blood
transfusion requirement (median 3.1 vs 0.9 L; p = 0.02). On follow-up,
patients in the intraoperative rupture group had a significantly higher
intraperitoneal extrahepatic recurrence rate (33.3% vs. 2.9%; p =0.02)
and significantly shorter survival (median 11.5 vs. 37.9 months,p =
0.04) when compared with patients without the complication.
Intraoperative iatrogenic rupture is a serious complication of hepatic
resection for HCC because it is associated with increased intraoperative
blood loss, increased incidence of intraperitoneal extrahepatic
recurrence, and short survival. Extreme care should be taken during
mobilization of the tumor, and an alternative operative approach in the
presence of a difficult hepatic resection of a large HCC may be required
to avoid the complication.
9
UI - 11897617
AU - Han C; Demetris AJ; Michalopoulos G; Shelhamer JH; Wu T
TI -
85-kDa cPLA(2) plays a critical role in PPAR-mediated gene transcription
in human hepatoma cells.
SO - Am J Physiol Gastrointest Liver Physiol 2002 Apr;282(4):G586-97
AD - Department of Pathology, University of Pittsburgh School of Medicine,
Pittsburgh, Pennsylvania 15213, USA.
In an effort to understand the role of key eicosanoid-forming enzymes in
the activation of peroxisome proliferator-activated receptor (PPAR),
this study was designed to evaluate the possible contributions of
cytosolic phospholipase A(2) (cPLA(2)) and group IIA secretory
phospholipase A(2) (sPLA(2)) in the regulation of PPAR-mediated gene
transcription in a human hepatoma cell line (HepG2). The HepG2 cells
express both PPAR-alpha and -gamma but not PPAR-beta. Overexpression of
cPLA(2), but not group IIA sPLA(2) in the HepG2 cells, caused a
significantly increased PPAR-alpha/gamma-mediated reporter activity.
Antisense inhibition of cPLA(2) resulted in a significantly decreased
PPAR-alpha/gamma activity. The PPAR-alpha/gamma-induced gene
transcription in the HepG2 cells was inhibited by the cPLA(2) inhibitors
methyl arachidonyl fluorophosphonate and arachidonyltrifluoromethyl
ketone, but not by the sPLA(2) inhibitor LY311727. The expression of
PPAR-alpha-mediated endogenous gene apolipoprotein A-II was increased in
cells with overexpression of cPLA(2), decreased in cells with antisense
inhibition of cPLA(2), but unaltered in cells with overexpression of
group IIA sPLA(2). The above results demonstrated an important role of
cPLA(2), but not group IIA sPLA(2) in the control of PPAR activation.
The cPLA(2)-mediated PPAR activation was likely mediated by arachidonic
acid and prostaglandin E(2). This study reveals a novel intracellular
function of cPLA(2) in PPAR activation in HepG2 cells. The cPLA(2) thus
may represent a potential therapeutic target for the control of
PPAR-related liver and metabolic disorders such as obesity, lipid
metabolic disorders, diabetes mellitus, and atherosclerosis.
10
UI - 11565794
AU - Yu LR; Shao XX; Jiang WL; Xu D; Chang YC; Xu YH; Xia QC
TI -
Proteome alterations in human hepatoma cells transfected with antisense
epidermal growth factor receptor sequence.
SO - Electrophoresis 2001 Aug;22(14):3001-8
AD - Research Center for Proteome, Shanghai Institutes for Biological
Sciences, Chinese Academy of Sciences, PR China.
The epidermal growth factor (EGF) is a member of the growth factor
superfamily that can stimulate the proliferation of many types of cells.
Overexpression of EGF receptor (EGFR) was observed in many types of
cancer cells. Anti-EGFR antibodies or antisense nucleic acid sequences
of EGFR can suppress the growth of hepatoma cells. In order to further
investigate the proteome alterations associated with malignant growth of
the human hepatoma cells and the influence of EGFR signal pathway on the
cellular proteome, we have comparatively analyzed the proteomes of human
hepatoma cells transfected with antisense EGFR sequence (cell strain
JX-1) and its control cells (cell strain JX-0) by two-dimensional (2-D)
gel electrophoresis and mass spectrometry. Image analysis of
silver-stained 2-D gels revealed that 40 protein spots showed
significant expression changes in JX-1 cells compared to JX-0 cells.
Three of them, including the tumor suppressor protein maspin, changed
with tendency to the normal levels. Two protein spots were identified as
HSP27 in the same gel, and one of them had a reduced level in JX-1
cells. The apparent alterations of HSP27 in expression level might be
the results from their differential chemical modifications, suggesting
the effect of dynamic post-translational modifications of proteins on
the growth of hepatoma cells. Other proteins such as glutathione
peroxidase (GPX-1) and 14-3-3-sigma also exhibited altered expression in
JX-1 cells, and their functional implications are discussed.
11
UI - 11807374
AU - Strasberg SM; Siegal BA
TI -
Survival of patients staged by FDG-PET before resection of hepatic
metastases from colorectal cancer.
SO - Ann Surg 2002 Feb;235(2):308; discussion 310
12
UI - 11920539
AU - Leung TW; Tang AM; Zee B; Lau WY; Lai PB; Leung KL; Lau JT; Yu SC;
TI -
Johnson PJ
Construction of the Chinese University Prognostic Index for
hepatocellular carcinoma and comparison with the TNM staging system, the
Okuda staging system, and the Cancer of the Liver Italian Program
staging system: a study based on 926 patients.
SO - Cancer 2002 Mar 15;94(6):1760-9
AD - Department of Clinical Oncology, The Chinese University of Hong Kong,
Hong Kong SAR, China. waitongleung@cuhk.edu.hk
BACKGROUND: The current TNM staging system for patients with
hepatocellular carcinoma (HCC) does not include liver function
parameters and does not provide a precise prognosis for patients in
different risk groups. The objectives of this study were to construct a
new prognostic index for patients with hepatocellular carcinoma, the
Chinese University Prognostic Index (CUPI), and to compare it with
existing staging systems in terms of their ability to classify patients
into different risk group. METHODS: From 1996 to 1998, 926 ethnic
Chinese patients who were diagnosed with HCC (mainly hepatitis
B-associated) at a single institution were recruited prospectively into
this study. A multivariate analysis on 19 patient characteristics was
performed using a Cox regression model to identify independent
prognostic factors. Weights were derived from the regression
coefficients of various factors to construct the CUPI. Patients were
classified according to different staging systems. Survival curves were
plotted with the Kaplan-Meier method and were compared by using a
log-rank test. RESULTS: Both the TNM staging system and the Okuda
staging system had prognostic significance, but the significance was
lower for the Cancer of the Liver Italian Program (CLIP) prognostic
score among the patients in the study population. The CUPI was
constructed by adding the following factors into the TNM staging system:
total bilirubin, ascites, alkaline phosphatase, alpha fetoprotein, and
asymptomatic disease on presentation. The new CUPI characterized three
risk groups with highly significant differences in survival during the
whole period of follow-up (P < 0.00001) and was more discriminant than
the other systems. CONCLUSIONS: In the study population of patients with
mainly hepatitis B-associated HCC, the CUPI was more discriminant than
the TNM staging system, the Okuda staging systems, or the CLIP
prognostic score in classifying patients into different risk groups and
was better at predicting survival. The CUPI needs to be validated by
different cohorts of patients before it can be recommended for general
use. Copyright 2002 American Cancer Society.
13
UI - 11920541
AU - Sasaki Y; Yamamura H; Kawakami Y; Yamada T; Hiratsuka M; Kameyama M;
TI -
Ohigashi H; Ishikawa O; Imaoka S; Ishiguro S; Takahashi K
Expression of smooth muscle calponin in tumor vessels of human
hepatocellular carcinoma and its possible association with prognosis.
SO - Cancer 2002 Mar 15;94(6):1777-86
AD - Department of Surgery, Osaka Medical Center for Cancer and
Cardiovascular Diseases, Osaka City, Japan. sasaki-yo@mc.pref.osaka.jp
BACKGROUND: Hepatocellular carcinoma (HCC) is a vascular-rich tumor. The
tumor vessels in HCC were demonstrated to have alpha-smooth muscle actin
positive smooth muscle cells (SMCs). However, it is unclear whether the
SMCs in the wall of the tumor vessels are differentiated or
undifferentiated. Basic calponin is an actin-, tropomyosin-, and
calmodulin-binding protein, and expression of the calponin gene in SMCs
has been recognized as one of the late stage differentiation markers of
SMCs. The authors investigated the differentiation state of SMCs in
tumor vessels by immunohistochemical examination of calponin in patients
with HCC, and whether it is associated with the patients' prognosis.
METHODS: Tumor and nontumor tissues were obtained from 75 patients with
HCC who underwent radical hepatic resection. The differentiation state
of the smooth muscle cells were evaluated based on the expression level
of calponin, an actin-binding protein, using immunohistochemistry and
reverse transcription-polymerase chain reaction analysis. The disease
free survival (DFS) rates were estimated according to the Kaplan-Meier
method comparing groups of patients with calponin positive and negative
tumor vessels. A multivariate analysis based on the Cox proportional
hazards regression model was performed to estimate whether the
expression of calponin is an independent prognostic factor. RESULTS: In
the 75 patients with HCC examined, 36 patients (48%) possessed calponin
positive SMCs, and the remaining 39 (52%) did not. There were no
significant differences in either clinical or pathologic factors between
the two groups of patients. The 5- and 8-year DFS rate of the patients
with calponin positive vessels were 37% and 26%, respectively. These
values were significantly higher (11% and 5%) than those of patients
with calponin negative vessels. Gender, TNM classification,
perioperative transfusion, and calponin expression were found to be
independent prognostic factors for DFS. CONCLUSIONS: Immunohistochemical
examination of the calponin expression in the tumor vessels is a new and
useful means to predict the prognosis of HCC patients after hepatic
resection. Copyright 2002 American Cancer Society.
14
UI - 11920542
AU - Tarao K; Rino Y; Ohkawa S; Tamai S; Miyakawa K; Takakura H; Endo O;
TI -
Yoshitsugu M; Watanabe N; Matsuzaki S
Close association between high serum alanine aminotransferase levels and
multicentric hepatocarcinogenesis in patients with hepatitis C
virus-associated cirrhosis.
SO - Cancer 2002 Mar 15;94(6):1787-95
AD - Department of Gastroenterology, Kanagawa Cancer Center, Yokohama, Japan.
BACKGROUND: Multicentric development of hepatocellular carcinoma (HCC)
is a characteristic feature of hepatitis C virus (HCV)-associated
cirrhosis (HCV-LC). In this study, the objective was to determine
whether the persistent elevation of the serum alanine aminotransferase
(ALT) level, which represents the inflammatory necrosis of hepatocytes,
is correlated with the multicentric development of hepatocellular
carcinoma (HCC) in patients with early-stage HCV-LC. METHODS:
Ninety-three consecutive patients with biopsy proven HCV-LC (Child Stage
A) who had been followed for > 5 years for the development of HCC were
studied. They were subdivided into three groups according to their serum
ALT level: Group A included 33 patients with annual average serum ALT
levels that were persistently high (> or = 80 IU; high ALT group), Group
B included 41 patients with annual average serum ALT levels that were
persistently low (< 80 IU; low ALT group), and Group C included 19
unclassified patients. The patients had been studied prospectively with
frequent ultrasonography and magnetic resonance imaging or computed
tomography (CT) scans for > 5 years. When the development of HCC was
suspected, angiography, infusion of lipiodol into the hepatic artery,
and lipiodol-CT scans were performed in all patients to determine the
number of HCC nodules. RESULTS: In Group A, 27 patients (81.8%)
developed HCC. Seventeen of 27 patients (63.0%) had multiple nodules. In
contrast, in Group B, only 12 patients (29.3%) developed HCC, and only 1
of these 12 patients (8.3%) had multiple nodules. There was a
significant difference between Groups A and B in the incidence of
developing HCC (P < 0.001) and developing multiple nodules (P = 0.006).
In addition, among the male patients, the incidence of developing
multiple HCC nodules in Group A (12 of 19 patients; 63.2%) was
significantly higher (P < 0.05) compared with the incidence in Group B
(0 of 6 patients; 0%). The same tendency was observed among the female
patients. CONCLUSIONS: These results showed a close correlation between
multicentric hepatocarcinogenesis and sustained necroinflammation of the
liver in patients with HCV-LC. Copyright 2002 American Cancer Society.
15
UI - 11100351
AU - Okano A; Hajiro K; Takakuwa H; Nishio A; Matsusue S; Sano A; Kobashi Y
TI -
Diffuse intrahepatic recurrence after resection of hepatocellular
carcinoma.
SO - Hepatogastroenterology 2000 Sep-Oct;47(35):1356-9
AD - Department of Gastroenterology, Tenri Hospital, Nara, Japan.
BACKGROUND/AIMS: An early diffuse type in the pattern of the
postoperative intrahepatic recurrence of hepatocellular carcinoma has
been recognized. The purpose of this study was to elucidate risk factors
for diffuse recurrence of hepatocellular carcinoma. METHODOLOGY: The
subjects involved in the present study were 114 patients with
hepatocellular carcinomas resected in Tenri Hospital during the past 12
years. Univariate analysis was used for retrospective determination of
the factors related to diffuse recurrences after surgery in 10 cases
among 114 patients. RESULTS: The risk factors linked to diffuse
recurrence were microscopical portal infiltration (P < 0.01), elevated
alpha-fetoprotein (more than 1000 ng/mL) (P < 0.05), the absence of
preoperative transcatheter arterial embolization (P < 0.01), and two or
more segmentectomies of the liver (P < 0.01). Six of 10 patients with
microscopical portal infiltration and elevated alpha-fetoprotein (more
than 1000 ng/mL) had diffuse recurrence (P < 0.01). Six of 8 patients
with two or more segmentectomies without preoperative TAE had diffuse
recurrence (P < 0.01). CONCLUSIONS: When patients with the diagnosis of
operable hepatocellular carcinoma have portal infiltration and elevated
alpha-fetoprotein (more than 1000 ng/mL), two or more segmentectomies of
the liver without preoperative transcatheter arterial embolization
should be avoided.
16
UI - 11798894
AU - Wang Z; Wang H; Chen Z
TI -
[Cloning of liver cancer-related gene HCCA2 and association of that gene
with liver cancer]
SO - Zhonghua Yi Xue Za Zhi 2001 Mar 25;81(6):332-5
AD - International Co-operation Lab on Cellular Signal Transduction, The East
Hospital of Hepatobiliary Surgery, The Second Military Medical
University, Shanghai 200438, China.
OBJECTIVE: To study and clone novel liver cancer-related genes and to
explore the molecular basis of hepatocarcinogenesis. METHODS: mRNA
differential display polymerase chain reaction (DDPCR) was used to clone
several gene fractions that were highly expressed in hepatocarcinoma
tissues and not expressed or lowly expressed in paracarcinoma tissue. A
full-length cDNA of one of such genes was obtained by screening the
placenta cDNA library. The expression of this novel gene in 43 pairs of
human hepatocellular carcinoma and paracarcinoma tissue was analyzed by
Northern blotting. RESULTS: A full-length cDNA of liver cancer-related
gene HCCA2 that was widely distributed in normal tissues and not
expressed in liver tissue. The positive expression rate of this gene was
79% (34/43) in hepatocellular carcinoma tissue. Its expression was
associated with the completeness of the tumor envelop and the expression
of KI-67 PROTEIN (P < 0.01). CONCLUSION: The novel gene HCCA2 may be
related with the infiltration and proliferation of liver cancer.
17
UI - 11850539
AU - Itoh T; Orba Y; Takei H; Ishida Y; Saitoh M; Nakamura H; Meguro T;
TI -
Horita S; Fujita M; Nagashima K
Immunohistochemical detection of hepatocellular carcinoma in the setting
of ongoing necrosis after radiofrequency ablation.
SO - Mod Pathol 2002 Feb;15(2):110-5
AD - Laboratory of Molecular and Cellular Pathology, Hokkaido University
School of Medicine, Hokkaido, Japan.
After radiofrequency ablation (RFA), hepatocellular carcinoma undergoes
complete necrosis and an ongoing necrosis that is irreversible and
characterized histologically by disrupted cell outlines, homogenous
cytoplasmic eosinophilia, and preserved nuclear staining, with the cells
appearing quite distinct from viable cancer cells. Antibody to detect
single-stranded DNA (ssDNA) specifically labeled nuclei in the setting
of ongoing necrosis, but not viable tumor cells, whereas human
mitochondrial antibody labeled the cytoplasm of viable cells but not
cells of ongoing necrosis. The results demonstrate that RFA causes
denaturation of both DNA and proteins and that the immunohistochemistry
of ssDNA and mitochondrial protein is useful in detection of ongoing
necrosis after RFA and provides pathological information on the validity
of this procedure.
18
UI - 11870467
AU - Quaia E; Bertolotto M; Dalla Palma L
TI -
Characterization of liver hemangiomas with pulse inversion harmonic
imaging.
SO - Eur Radiol 2002 Mar;12(3):537-44
AD - Department of Radiology, Cattinara Hospital, University of Trieste,
Strada di Fiume 447, 34149 Trieste, Italy. equaia@yahoo.com
The purpose of this study was to determine if pulse inversion harmonic
imaging (PIHI) can characterize liver hemangiomas. We retrospectively
evaluated 39 consecutive patients with liver hemangiomas, 20 typical on
conventional US (hyperechoic, homogeneous, or slightly inhomogeneous and
with sharp margins) and 19 atypical (11 inhomogeneous with different
echogenicity larger than 3 cm, 6 hypoechoic, and 2 isoechoic smaller
than 3 cm). Each liver hemangioma was firstly evaluated by PIHI and then
confirmed by dynamic helical CT (28 patients) or by 6 months of US
follow-up (11 patients). The PIHI was performed by two distinct sweeps
on a marker lesion, 30 s (vascular phase) and from 3 to 5 min (late
phase) after bolus injection of Levovist (2.5 g, 300 mg/ml). Scans were
digitally stored and reviewed using a dedicated software. Contrast
enhancement features of marker lesion were subjectively evaluated.
Typical hemangiomas on conventional US revealed on PIHI a characteristic
rim-like or peripheral globular enhancement on 30-s scan in 4 of 20
cases (20%) and a characteristic isoechoic pattern on late phase in 16
of 20 cases (80%). On PIHI, all (11 of 11) atypical hemangiomas larger
than 3 cm and 4 of 8 atypical liver hemangiomas smaller than 3 cm
revealed a characteristic rim-like or peripheral globular enhancement on
vascular phase with a characteristic centripetal fill-in on late phase.
In 4 of 8 atypical liver hemangiomas smaller than 3 cm no characteristic
pattern was revealed by PIHI. Pulse inversion harmonic imaging revealed
a typical pattern in the majority of liver hemangiomas typical and
atypical on conventional US. In few liver hemangiomas atypical on
conventional US PIHI did not identify a characteristic pattern and
helical CT was necessary for final characterization.
19
UI - 11882759
AU - Poon RT; Fan ST; Lo CM; Liu CL; Wong J
TI -
Long-term survival and pattern of recurrence after resection of small
hepatocellular carcinoma in patients with preserved liver function:
implications for a strategy of salvage transplantation.
SO - Ann Surg 2002 Mar;235(3):373-82
AD - Centre for the Study of Liver Disease & Department of Surgery,
University of Hong Kong Medical Centre, Queen Mary Hospital, Hong Kong,
China. poontp@hkucc.hku.hk
OBJECTIVE: To evaluate the survival results and pattern of recurrence
after resection of potentially transplantable small hepatocellular
carcinomas (HCC) in patients with preserved liver function, with special
reference to the implications for a strategy of salvage transplantation.
SUMMARY BACKGROUND DATA: Primary resection followed by transplantation
for recurrence or deterioration of liver function has been recently
suggested as a rational strategy for patients with HCC 5 cm or smaller
and preserved liver function. However, there are no published data on
transplantability after HCC recurrence or long-term deterioration of
liver function after resection of small HCC in Child-Pugh class A
patients. Such data are critical in determining the feasibility of
salvage transplantation. METHODS: From a prospective database of 473
patients with resection of HCC between 1989 and 1999, 135 patients age
65 years or younger had Child-Pugh class A chronic liver disease
(chronic hepatitis or cirrhosis) and transplantable small HCC (solitary
< or =5 cm or two or three tumors < or = 3 cm). Survival results were
analyzed and the pattern of recurrence was examined for eligibility for
salvage transplantation based on the same criteria as those of primary
transplantation for HCC. RESULTS: Overall survival rates at 1, 3, 5, and
10 years were 90%, 76%, 70%, and 35%, respectively, and the
corresponding disease-free survival rates were 74%, 50%, 36%, and 22%.
Cirrhosis and oligonodular tumors were predictive of worse disease-free
survival. Patients with concomitant oligonodular tumors and cirrhosis
had a 5-year overall survival rate of 48% and a disease-free survival
rate of 0%, which were significantly worse compared with other
subgroups. At a median follow-up of 48 months, 67 patients had
recurrence and 53 (79%) of them were considered eligible for salvage
transplantation. Decompensation from Child-Pugh class A to B or C
without recurrence occurred in only six patients. CONCLUSIONS: For
Child-Pugh class A patients with small HCC, hepatic resection is a
reasonable first-line treatment associated with a favorable 5-year
overall survival rate. A considerable proportion of patients may survive
without recurrence for 5 or even 10 years; among those with recurrence,
the majority may be eligible for salvage transplantation. These data
suggest that primary resection and salvage transplantation may be a
feasible and rational strategy for patients with small HCC and preserved
liver function. Primary transplantation may be a preferable option for
the subset of patients with oligonodular tumors in cirrhotic liver in
view of the poor survival results after resection.
20
UI - 11895493
AU - Aishima SI; Taguchi KI; Sugimachi K; Shimada M; Sugimachi K; Tsuneyoshi
TI -
M
c-erbB-2 and c-Met expression relates to cholangiocarcinogenesis and
progression of intrahepatic cholangiocarcinoma.
SO - Histopathology 2002 Mar;40(3):269-78
AD - Department of Anatomic Pathology, Graduate School of Medical Sciences,
Kyushu University, Fukuoka, Japan.
AIMS: The c-erbB-2 and c-Met proto-oncogenes are important for tumour
invasiveness and metastasis in many types of malignant tumours. Previous
studies have indicated that these proteins are associated with
carcinogenesis in intrahepatic cholangiocarcinoma. In this study, we
examined c-erbB-2 and c-Met expression by immunohistochemistry in
hepatolithiasis, intrahepatic cholangiocarcinoma and metastatic lymph
node, in order to clarify whether these proteins play a role in
carcinogenesis and tumour metastasis in intrahepatic cholangiocarcinoma.
METHODS AND RESULTS: In hepatolithiasis, the staining for c-erbB-2 was
positive in 14 of the 23 (61%) cases, while staining for c-Met was
positive in eight of the 23 (35%) cases. In intrahepatic
cholangiocarcinoma, staining for c-erbB-2 was positive in 45 of the 81
(55%) cases, while staining for c-Met was positive in 28 (35%) cases.
The positivity of c-Met staining in intrahepatic cholangiocarcinoma was
significantly higher in the differentiated type of cholangiocarcinoma
than in the undifferentiated type. In addition, c-Met-positive staining
had an inverted correlation with tumour size, the presence of perineural
invasion and the presence of lymph node metastasis. c-Met staining had a
significantly higher positivity in cases at an early stage of
intrahepatic cholangiocarcinoma. In contrast, the positivity of c-erbB-2
staining in intrahepatic cholangiocarcinoma was significantly higher in
cases with lymph node metastasis than in cases without. In metastatic
lymph nodes, the staining for c-erbB-2 was positive in 20 of the 25
(80%) cases, while staining for c-Met was positive in six of the 25
(24%) cases. There was no difference in survival between
c-erbB-2-positive and negative patients. However, the patients with
c-Met-positive tumours had a significantly longer survival than those
with c-Met-negative tumours in the medium survival term. The
multivariate analysis showed the presence of lymph node metastasis,
lymphatic permeation and histological differentiation to be independent
prognostic factors. CONCLUSION: These results indicate that increased
c-Met expression participates in cholangiocarcinogenesis and in the
early developmental stages of intrahepatic cholangiocarcinoma, while
increased c-erbB-2 expression contributes to the development of
cholangiocarcinogenesis into an advanced stage associated with tumour
metastasis.
21
UI - 11798850
AU - Li X; Ding M; Lai B
TI -
[Frequent loss of heterozygosity on chromosome 4 in human hepatocellular
carcinoma]
SO - Zhonghua Yi Xue Za Zhi 2001 Jan 10;81(1):37-40
AD - Department of Anatomical and Cellular Pathology and Surgery, The Chinese
University of Hong Kong, Hong Kong, China.
OBJECTIVE: Few previous studies have shown high frequency of loss of
heterozygosity (LOH) on chromosome 4q in hepatocellular carcinoma (HCC).
We define more clearly the deletion regions that may harbor the putative
tumor suppressor genes in HCC. METHODS: Forty-eight cases of HCC and
their corresponding non-tumor liver tissues were investigated with 12
microsatellite polymorphic markers for LOH. RESULTS: Twenty-one of 48
(44%) and 30 of 48 (63%) tumors showed LOH on at least one locus on the
short and the long arms respectively. Two distinct common deleted
regions (CDR) with different patterns of deletion were identified. The
first CDR was located on 4q22-q25, between loci D4S392 and D4S1625. In
addition, 17 of 27 (63%) of the informative tumors showed LOH on this
region with locus D4S406 and constituted the highest rate of LOH on
chromosome 4. The second CDR was located at 4q27-q31, between loci
D4S1625 and D4S1652. CONCLUSION: There are at least two tumor suppressor
loci on 4q.
22
UI - 11906869
AU - Kim T; Murakami T; Hori M; Takamura M; Takahashi S; Okada A; Kawata S;
TI -
Cruz M; Federle MP; Nakamura H
Small hypervascular hepatocellular carcinoma revealed by double arterial
phase CT performed with single breath-hold scanning and automatic bolus
tracking.
SO - AJR Am J Roentgenol 2002 Apr;178(4):899-904
AD - Department of Radiology, D1 Osaka University Medical School, 2-2
Yamadaoka, Suita City, Osaka 565-0871, Japan.
OBJECTIVE: The purpose of this study was to evaluate the usefulness of
double arterial phase CT for the detection of small hypervascular
hepatocellular carcinomas, using an automated bolus-tracking technique
to initiate the hepatic arterial phase CT. MATERIALS AND METHODS: Double
arterial and late phase contrast-enhanced helical CT scans were obtained
on 287 consecutive patients suspected of having hepatocellular
carcinoma. These included 56 patients with 90 small (< or 3 cm)
hepatocellular carcinomas and 50 patients with no hepatocellular
carcinomas. CT scans of these patients were interpreted by three
reviewers. The first arterial phase scan was initiated automatically 10
sec after the bolus-tracking program detected the threshold enhancement
of 50 H in the abdominal aorta. Three reviewers interpreted the late
phase CT scans in combination with the first, second, or both hepatic
arterial phases. Measures of the reviewers' detection of hepatocellular
carcinoma included analysis of interobserver variation, sensitivity,
specificity, and area under receiver operating characteristic curve
(A(z)). RESULTS: The time elapsed from bolus initiation to threshold
aortic enhancement ranged from 10 to 24 sec (mean, 13 sec), resulting in
initiation of the first arterial phase CT scan from 20 to 34 sec (mean,
23 sec). The combination of late phase CT and both first and second
arterial phase images showed significantly better performance than the
combination of the late phase and either the first or second arterial
phases, although the difference was most evident in comparison with the
combination of second arterial and late phases. CONCLUSION: An automated
bolus-tracking program can be used to optimize the timing of hepatic
arterial phase CT. Multiphasic CT performed using this technique is
useful in detection of small hepatocellular carcinoma.
23
UI - 11673833
AU - Enomoto A; Esumi M; Yamashita K; Takagi K; Takano S; Iwai S
TI -
Abnormal nucleotide repeat sequence in the TGF-betaRII gene in
hepatocellular carcinoma and in uninvolved liver tissue.
SO - J Pathol 2001 Oct;195(3):349-54
AD - Department of Pathology, Nihon University School of Medicine, Tokyo
173-8610, Japan.
Replication error (RER)-related genetic alterations are associated with
a subset of hepatocellular carcinomas (HCCs) with multiple primary
cancers. This study investigated whether mutations in the nucleotide
repeats of three putative target genes of RER are associated with
hepatocarcinogenesis. The genes examined were those encoding
transforming growth factor beta type II receptor (TGF-betaRII),
BCL-2-associated X protein (BAX), and insulin-like growth factor II
receptor (IGF-IIR). Tumour and non-tumour hepatic tissues were examined
in 48 HCC patients, 34 with solitary HCC and 14 who had double cancer
with gastric cancer. Four double-cancer cases showed an abnormal signal
in the single nucleotide repeat (A)10 of the TGF-betaRII gene. These
four were among the six RER-positive cases in this series. The genotypes
of the poly A tract of the TGF-betaRII gene in the liver tumour tissue
of the four cases with an abnormal signal were (A)9/10, (A)9/10,
(A)9/10, and (A)9/9. Five uninvolved liver tissue specimens from these
four patients showed (A)9/10 and (A)9/9, (A)9/10, (A)10/10 and (A)9/9,
respectively. The genotype in the stomach cancer specimens of these four
patients was (A)10/10, indicating no germline mutation of the
TGF-betaRII gene. There were no mutations in the nucleotide repeats of
the BAX and IGF-IIR genes in any of the liver tissue specimens.
Abnormality of the nucleotide repeat in the TGF-betaRII gene occurred in
the uninvolved liver tissue as well as the HCC tissue in some HCC
patients. Such genetic instability may be gene-specific and
tissue-specific in carcinogenesis. Copyright 2001 John Wiley & Sons,
Ltd.
24
UI - 11866444
AU - Kito M; Akao Y; Ohishi N; Yagi K; Nozawa Y
TI -
Arsenic trioxide-induced apoptosis and its enhancement by buthionine
sulfoximine in hepatocellular carcinoma cell lines.
SO - Biochem Biophys Res Commun 2002 Mar 8;291(4):861-7
AD - Institute of Applied Biochemistry, Yagi Memorial Park, Mitake, Gifu
505-0116, Japan.
We treated four hepatocellular carcinoma cell lines, HLE, HLF, HuH7, and
HepG2 with ATO and demonstrated that arsenic trioxide (ATO) at low doses
(1--3 muM) induced a concentration-dependent suppression of cell growth
in HLE, HLF, and HuH7. HLE cells underwent apoptosis at 2 microM ATO,
which was executed by the activation of caspase-3 through the
mitochondrial pathway mediated by caspase-8 activation and Bid
truncation. When these cell lines were exposed to ATO in combination
with l-S,R-buthionine sulfoximine (BSO) which inhibits GSH synthesis, a
synergistic growth suppression was induced, even in HepG2 showing a
lower sensitivity to ATO than other cell lines tested. The intracellular
GSH levels after the treatment with ATO plus BSO were considerably
decreased in HLE cells compared with those after the treatment with ATO
or BSO alone. The production of reactive oxygen species (ROS) which was
examined by 2' ,7' -dichlorodihydrofluorescein diacetate, increased
significantly after the treatment with ATO plus BSO in HLE cells. These
findings indicate that ATO at low concentrations induces growth
inhibition and apoptosis, and furthermore that the ATO-BSO combination
treatment enhances apoptosis through increased production of ROS in
hepatocellular carcinoma cells.
25
UI - 11895095
AU - Dickinson J A; Wun Y T; Wong S L
TI -
Modelling death rates for carriers of hepatitis B.
SO - Epidemiol Infect 2002 Feb;128(1):83-92
AD - Department of Community and Family Medicine, The Chinese University of
Hong Kong, 4/F School of Public Health, Prince of Wales Hospital,
Shatin, NT.
Hepatitis B carriers who acquired the infection perinatally die from
hepatocellular carcinoma (HCC) and cirrhosis at high rates. Published
cohort studies are largely limited to males and are too small to
estimate the age-specific risk of death. We therefore used routinely
collected Hong Kong data to estimate the risks. Deaths were partitioned
between carriers and non-carriers, then current life table calculations
determined life expectancy and probability of dying from HCC or
cirrhosis. HCC is the dominant cause of death for male carriers in
middle adulthood with a lifetime risk of 27% for HCC compared to 4% for
females. Predicted life expectancy is 72 years for male carriers,
compared to 79 years for non-carriers. Female carriers have a life
expectancy of 81 years and non-carriers 83 years. This model probably
applies to all southern Chinese populations and emigrants with similar
life history, and other populations that acquired infection early in
life.
26
UI - 11861987
AU - Chan KL; Fan ST; Tam PK; Chiang AK; Chan GC; Ha SY
TI -
Paediatric hepatoblastoma and hepatocellular carcinoma: retrospective
study.
SO - Hong Kong Med J 2002 Feb;8(1):13-7
AD - Centre for the Study of Liver Disease, The University of Hong Kong,
Queen Mary Hospital, 102 Pokfulam Road, Hong Kong.
OBJECTIVES: To compare and contrast clinical characteristics and
outcomes of hepatoblastoma or hepatocellular carcinoma in paediatric
patients. DESIGN: Retrospective study. SETTING: University teaching
hospital, Hong Kong. PATIENTS AND METHODS: Medical records of 22
paediatric patients with hepatoblastoma (n=11) or hepatocellular
carcinoma (n=11) admitted to Queen Mary Hospital between 1989 and 2000
were reviewed. Data gathered included demographic data, results of liver
function tests, hepatitis A, B, and C titres, and alpha-foetoprotein
levels, and imaging studies including chest X-ray, ultrasound study,
computed tomography scan, and magnetic resonance imaging/hepatic
angiogram for tumour staging and resectability. RESULTS: The mean age of
patients with hepatoblastoma was 18 months (range, 5 months to 3 years),
while that of patients with hepatocellular carcinoma was 10.2 years
(range, 2 to 16 years). Females predominated in the hepatoblastoma group
(female:male, 8:3) and males in the hepatocellular carcinoma group
(male:female, 10:1). None of the patients with hepatoblastoma were
hepatitis B surface antigen positive, in contrast to 64% of the
hepatocellular carcinoma group. Only 45% of the hepatocellular
carcinomas were resectable at presentation and this figure remained
u
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