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Abramson Cancer CenterNCI CANCERLIT® Search: Therapy of Primary Liver Cancer - March 2002
National Cancer Institute®
Last Modified: March 1, 2002
Table of Contents
1
UI - 11591936
AU - Shimada M; Hashizume M; Maehara S; Tsujita E; Rikimaru T; Yamashita Y;
TI -
Tanaka S; Adachi E; Sugimachi K
Laparoscopic hepatectomy for hepatocellular carcinoma.
SO - Surg Endosc 2001 Jun;15(6):541-4
AD - Department of Surgery and Science, Graduate School of Medical Sciences,
Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
mshimada@surg2.med.kyushu-u.ac.jp
BACKGROUND: No reports exist on the role of laparoscopic hepatectomy in
the short- and long-term outcomes of patients with hepatocellular
carcinoma (HCC). We present our results from using laparoscopic
hepatectomy for HCC and discuss the importance of this procedure.
METHODS: To investigate the role of laparoscopic hepatectomy in the
short- and long-term outcomes, 17 patients with HCC who underwent
laparoscopic hepatectomy (laparoscopic hepatectomy group) were compared
with 38 patients who underwent conventional open hepatectomy (open
hepatectomy group) during the same period. RESULTS: No differences in
operation time, blood loss, rate of blood transfusion, or incidence of
postoperative complications were found between the two groups. The
postoperative hospital stay for the laparoscopic hepatectomy group was
significantly shorter than for the open hepatectomy group. With
long-term prognosis, no difference was found in survival rate and
disease-free survival rate between the two groups. No recurrence was
found in the stump of the remaining liver after laparoscopic
hepatectomy. CONCLUSIONS: Laparoscopic hepatectomy has resulted in a
better short-term outcome after surgery than conventional open
hepatectomy. The long-term prognosis in the laparoscopic hepatectomy
group was similar to that in the open hepatectomy group. Therefore,
laparoscopic hepatectomy can be a new alternative for treatment of
cirrhotic patients with HCC when patients are strictly selected.
2
UI - 11686533
AU - Berger WK; Poledna J
TI -
New strategies for the placement of cryoprobes in malignant tumors of
the liver for reducing the probability of recurrences after hepatic
cryosurgery.
SO - Int J Colorectal Dis 2001 Sep;16(5):331-9
AD - I. Physiologisches Institut, Universitat des Saarlandes, Homburg,
Germany. phwber@krzsun.med-rz.uni-sb.de
We examined modifications in the conventional techniques of cryosurgery
for reducing the relatively large number of recurrences after hepatic
cryosurgery. Since recurrences are likely to develop in tumor regions
which are not frozen to lethal temperatures, the temperature
distribution in frozen livers was studied by thermocouple techniques and
by calculating the spatial and temporal alterations in the thermal
fields for detecting, if present, nonlethally frozen sectors in a frozen
tumor tissue. Misplacement of the cryoprobes and the presence of blood
vessels in the vicinity of the target tissue were found to be the main
sources for nonoptimal freezing of the tumor. Furthermore an
overestimation of the size of the lethally frozen tumor regions is
possible because of the slow fusion and long-lasting shape alterations
in the lethally frozen regions growing together from several cryoprobes.
The placement of cryoprobe was optimized by aiming for positions of the
cryoprobes by which the tumor is totally enclosed by the calculated -50
degrees C isotherm. The effect of blood vessels could be compensated by
thermally shielding the target tissue with an additional cryoprobe
between tumor and vessel. In irregularly shaped tumors the placement of
cryoprobes was improved by calculating the temperature distribution for
cryoprobes in positions thought to be optimal and examining whether this
selected placement of cryoprobes cooled all regions of the tumor to
lethal temperatures. This procedure was performed before actual
cryosurgery on a digitized image of the tumor displayed on the PC
screen, and, if required, positions of the cryoprobes were altered until
calculations showed that all of the target tissue was frozen to lethal
temperatures. For small tumors the placement of the cryoprobes outside
the target was found to be advantageous. Under such conditions the tumor
was so rapidly cooled to lethal temperatures by synergistic effects
between the cryoprobes that excessive cryodamage in normal liver tissue
was avoided.
3
UI - 11748380
AU - The Ginseng-HCC Chemopreventive Study Osaka Group.
TI -
Study on chemoprevention of hepatocellular carcinoma by ginseng: an
introduction to the protocol.
SO - J Korean Med Sci 2001 Dec;16 Suppl():S70-4
In patients with chronic hepatitis C virus disease, there is a high
incidence of development of hepatocellular carcinoma (HCC) in the
process of transition from chronic hepatitis to hepatic cirrhosis.
Although ginseng traditionally has been used mainly as a nutritional
supplement in Asian countries, a case-control study found that it may
inhibit the development of HCC. We therefore planned a clinical study of
HCC prevention by medicinal ginseng. The subjects are patients with
chronic C virus disease (chronic hepatitis and hepatic cirrhosis), who
are high risk group for HCC. This intervention study is a multi-center,
double-blind, randomized controlled trial. The participants will be
randomly divided into two groups. The test sample (1 g of red ginseng
powder per day) will be administered for 5 yr, and ginseng intake will
be prohibited during the administration period. The primary endpoint of
this study is the development of HCC. Target number of recruiting
subjects are 300. The participants should be registered from February
4
UI - 11821801
AU - Tanaka S; Sugimachi K; Maehara S; Harimoto N; Shirabe K; Wands JR;
TI -
Sugimachi K
Oncogenic signal transduction and therapeutic strategy for
hepatocellular carcinoma.
SO - Surgery 2002 Jan;131(1 Suppl):S142-7
AD - Department of Surgery and Science, Graduate School of Medical Sciences
and Station for Collaborative Research, Kyushu University, Fukuoka,
Japan.
Discoveries of oncogenic signaling molecules lead to the comprehension
of molecular mechanisms of tumor progression, as well as to the
development of novel therapeutic tools for hepatocellular carcinoma. We
have identified critical functions of intracellular signals transmitted
from insulin-like growth factor and Wnt oncoprotein in carcinogenesis.
The insulin-like growth factor system activates a number of signaling
cascades resulting not only in hepatic mitogenesis, but also in cell
survival. The secreted oncoprotein Wnt transforms beta-catenin
potentials as a component of cell adhesion complexes with cadherins,
into a transcription factor in the nucleus. Here, the important role of
such signal transduction is reviewed, and we emphasize its control as a
promising approach for the treatment of hepatocellular carcinoma.
5
UI - 11821802
AU - Adachi E; Maehara S; Tsujita E; Taguchi K; Aishima S; Rikimaru T;
TI -
Yamashita Y; Tanaka S
Clinicopathologic risk factors for recurrence after a curative hepatic
resection for hepatocellular carcinoma.
SO - Surgery 2002 Jan;131(1 Suppl):S148-52
AD - Department of Surgery and Science, Graduate School of Medical Sciences,
Kyushu University, Fukuoka, Japan.
BACKGROUND: The long-term prognosis after resection for patients with
hepatocellular carcinoma is still unsatisfactory because of the high
recurrence rate. The survival of patients with multiple intrahepatic or
extrahepatic recurrence is especially poor. METHODS: Among the patients
who underwent hepatic resection for hepatocellular carcinoma between
1981 and 2000, 216 patients with 3 or less than 3 intrahepatic
recurrences (group B); 156 patients with more than 3 intrahepatic
recurrences, extrahepatic recurrences, or both (group C); and 51
patients who survived more than 5 years without recurrence (group A)
were clinicopathologically studied. RESULTS: The period to recurrence of
group C was significantly earlier than that of group B and also showed a
significantly poor prognosis after recurrence. Tumor factors, including
size, portal venous invasion, intrahepatic metastasis, histologic grade,
or the number of tumors at resection in group C was significantly worse
than in groups A and B. Although no differences are recognized in the
tumor factors between groups A and B, except for the alpha-fetoprotein
level, liver function in group B was significantly worse than that in
group A. In addition, the frequency of hepatitis B surface antigen in
group B and that of hepatitis C virus in group B was significantly less
and higher than that in group A, respectively. CONCLUSION: Similar to
extrahepatic metastasis, multinodular recurrences are also mainly caused
by metastatic recurrence from the main tumor by means of the portal
system, and recurrences with up to 3 intrahepatic nodules are mainly
caused by metachronous multicentric hepatocarcinogenesis. Because the
mechanisms of recurrence differed, determining the patterns of
recurrence on the basis of the clinicopathologic findings is important
for selecting the optimal postoperative therapy for each individual
patient.
6
UI - 11821803
AU - Kanematsu T; Furui J; Yanaga K; Okudaira S; Shimada M; Shirabe K
TI -
A 16-year experience in performing hepatic resection in 303 patients
with hepatocellular carcinoma: 1985-2000.
SO - Surgery 2002 Jan;131(1 Suppl):S153-8
AD - Department of Surgery II, Nagasaki University School of Medicine,
Nagasaki, Japan.
BACKGROUND: Hepatic resection is an accepted therapeutic modality for
hepatocellular carcinoma (HCC). Over the past 2 decades, liver surgery
has evolved to a refined and deliberate operation. In the present study
surgical results are analyzed with an aim toward further improving the
treatment of HCC. METHODS: We studied 303 patients with HCC who
underwent a hepatic resection at 2 university hospitals from 1985
through 2000. Living-related liver transplantation was a procedure of
choice in 1 patient with early staged HCC. Fifty-five percent of the
patients had associated cirrhosis. Before the operation, the liver
function was mainly evaluated with the indocyanine green retention test.
RESULTS: The mortality rate within 30 days after the operation was 1.6%.
One-, 3-, 5-, 10-, and 15-year cumulative survival rates were 84%, 67%,
51%, 20%, and 11%, respectively. The tumor stage I and II groups showed
superior survival rates to those of the tumor stage III and IV groups,
respectively, and the difference was statistically significant. The
disease-free survival curves, however, showed the rate to be 27% at 5
years and 11% at 10 years. CONCLUSIONS: Although the surgical results
have greatly improved in the treatment of HCC, the recurrence rate is
still high. In carefully screened patients with poor liver function and
small HCC, liver transplantation enhances the possibility of cure.
7
UI - 11821809
AU - Suehiro T; Terashi T; Shiotani S; Soejima Y; Sugimachi K
TI -
Liver transplantation for hepatocellular carcinoma.
SO - Surgery 2002 Jan;131(1 Suppl):S190-4
AD - Department of Surgery and Science, Graduate School of Medical Sciences,
Kyushu University, Fukuoka, Japan.
The surgical management for hepatocellular carcinoma (HCC) is
multiplicity. In Japan, liver resection has generally been considered to
be the only curative treatment for HCC. The resectability of a tumor in
cirrhotic patients, however, is limited by the diminished functional
reserve of the cirrhotic liver and the attendant risk for intraoperative
bleeding and postoperative liver failure. In cirrhotic patients, liver
transplantation has been considered as the indication for HCC in many
countries except Japan. Although the survival rate of patients with HCC
who received liver transplants was poor in the early period, it later
moved to the same level as for patients with other liver diseases. In
1993, living donor adult liver transplantation was started in Japan and
it became an additional option for the treatment of HCC. A shortage of
liver donors means that new methods of liver procurement must be
explored. Domino liver transplantation using the livers of patients with
familial amyloid polyneuropathy was also another option for advanced
HCC. For the prevention of a recurrence of HCC, pre-, intra-, and
postoperative chemotherapy have been performed after both liver
resection and liver transplantation. We should also try to minimize
intraoperative dissemination by surgical manipulation. Recently,
potential gene therapies for HCC have been studied.
Electroporation-mediated IL-12 gene therapy for HCC was found to be
effective for both mIL-12-transferred HCC and for distant HCC. For
patients with HCC accompanied by liver cirrhosis, liver transplantation
remains the ultimate curative therapy. Immunologic and oncologic
approaches to HCC can help prevent tumor recurrence and also help us to
obtain better results after liver transplantation.
8
UI - 11865632
AU - Hasegawa I; Hirashima N
TI -
[Styrene maleic acid neocarzinostatin-transcatheter embolization for
hepatocellular carcinoma--third report]
SO - Gan To Kagaku Ryoho 2002 Feb;29(2):253-9
AD - Dept. of Gastroenterology, Chukyo Hospital.
To evaluate the effect of styrene maleic neocarzinostatin-transcatheter
arterial embolization (SMANCS-TAE), 40 patients with unresectable
hepatocellular carcinoma (HCC) of hypervascular radiological feature,
associated with liver cirrhosis (LC), 18 in clinical stage 2 and 20 in
stage 3, were treated by SMANCS-TAE. SMANCS with Lipiodol and then
gelatin sponge particles were injected into the artery branch supplying
HCC using selective catheterization, and its effect was evaluated by
computed tomography (CT) Grade. In patients with Grade III or less
(Lipiodol accumulation < 99% in the entire tumor) after the first course
of therapy, SMANCS-TAE or arterial injection of SMANCS-Lipiodol was
performed once or twice more. Consequently, 32 of 40 patients (80%)
obtained Grade IV (100% Lipiodol accumulation in the entire tumor) after
from once to thrice (median, 1.6 courses). Grade IV was maintained in 26
of 32 patients, and non-recurrence was found 16 of 40 (40%) at the
primary tumor to the time at last of follow up. Severe side effects were
not noted except in 10 cases with narrowness of hepatic artery and cases
of 2 biloma in patients undergoing therapy two or more times. The 1-,
2-, 3-, and 5-year survival rate was 85, 64, 35, and 26%, respectively.
No significant difference was noted in the survival rate between
clinical stage 2 and 3 liver cirrhosis (LC). But the survival rate of
patients who continued to exhibit Grade IV at the primary tumor was
significantly better than in those exhibiting Grade III or less (96, 68,
56, and 43% vs 64, 29, 0, and 0%, respectively; p < 0.01). In
conclusion, the HCC patients, even those with decompensated LC, who
obtained and maintained Grade IV after SMANCS-TAE could reduce the
courses of treatment without severe side effects and survived longer.
SMANCS-TAE might be useful for the good quality of life of HCC patients.
9
UI - 11868788
AU - Shiina S; Teratani T; Obi S; Hamamura K; Koike Y; Omata M
TI -
Nonsurgical treatment of hepatocellular carcinoma: from percutaneous
ethanol injection therapy and percutaneous microwave coagulation therapy
to radiofrequency ablation.
SO - Oncology 2002;62 Suppl 1():64-8
AD - Department of Gastroenterology, University of Tokyo, Japan.
sshiina-tky@umin.ac.jp
Treatment of hepatocellular carcinoma (HCC) is different from that of
other solid tumors, in that surgery plays a limited role while
nonsurgical therapies are very instrumental. At our institute, 90% of
previously untreated patients have received image-guided percutaneous
tumor ablations, such as percutaneous ethanol injection therapy (PEIT),
percutaneous microwave coagulation therapy (PMCT) and radiofrequency
ablation (RFA). We performed PEIT in 756 patients with HCC. Their
survival rates were 89% at 1 year, 64% at 3 years, 39% at 5 years, and
18% at 10 years. With PMCT, survival rates of 122 new patients with HCC
were 90% at 1 year, 87% at 2 years, and 68% at 3 years. We performed RFA
in 324 patients. RFA required fewer treatment sessions and a shorter
hospital stay than PEIT or PMCT to achieve complete necrosis of the
lesions. By virtue of their local curability, minimal effect on liver
function, and easy repeatability for recurrence, image-guided
percutaneous tumor ablations, especially RFA, will be increasingly
important in the treatment of HCC.
10
UI - 11868789
AU - Kaneko S; Urabe T; Kobayashi K
TI -
Combination chemotherapy for advanced hepatocellular carcinoma
complicated by major portal vein thrombosis.
SO - Oncology 2002;62 Suppl 1():69-73
AD - Gastroenterology, Kanazawa University Hospital, Kanazawa Graduate School
of Medical Science, Japan. skaneko@medf.m.kanazawau.ac.jp
Patients with advanced hepatocellular carcinoma (HCC) have a poor
prognosis, and the development of new therapeutic strategies is
necessary. Here we report the efficacy of combination chemotherapy in
our biochemical modulation. Synergistic effects of interferon-alpha-2b
on 5-fluorouracil or cisplatin were demonstrated in Huh7 cells. The
efficacy of methotrexate-5-fluorouracil, cisplatin, and
interferon-alpha-2b combination therapy was demonstrated in 34 patients
with HCC complicated by major portal vein thrombosis. Among the 29
patients eligible for the study, there were 3 complete responders and 10
partial responders with an overall response rate of 45%. The 2-year
survival of the 34 patients was 15%, and the median survival of complete
and partial responders was 11 months. There was severe transient
hematological toxicity. Eight patients suffered from renal
insufficiency, and 4 of them underwent hemodialysis. Although a control
study is clearly necessary, our combination therapy induced a good
response in the patients with advanced HCC. On the basis of our results,
intensive chemotherapy should be attempted in advanced HCC complicated
by major portal vein invasion.
11
UI - 11868790
AU - Makuuchi M; Imamura H; Sugawara Y; Takayama T
TI -
Progress in surgical treatment of hepatocellular carcinoma.
SO - Oncology 2002;62 Suppl 1():74-81
AD - Department of Surgery, Graduate School of Medicine, University of Tokyo,
Japan. makuuchi-tky@umin.ac.jp
Surgery for hepatocellular carcinoma has improved dramatically during
the last two decades, and the improvement is mainly attributable to the
development of intraoperative ultrasound-guided operative procedures
such as Makuuchi's segmentectomy, introduction of the intermittent
vascular occlusion technique, and establishment of the precise criteria
for indications of various hepatectomy procedures. The use of
preoperative portal vein embolization for inducing compensatory
hypertrophy of remnant liver in the future has increased the safety and
extended indications of hepatectomy for hepatocellular carcinoma.
Operative mortality has fallen below 2% in the 1990s, with the 5-year
survival rate reaching nearly 50% in a recent nationwide survey in
Japan. More than 90% of hepatectomies at our institution are performed
without red blood cell transfusions, and the mean hospital stay is
shortened to approximately 23 days. Moreover, not a single case of
operative death has been recorded since 1993.
12
UI - 11868792
AU - Matsunami H; Shimizu Y; Lynch SV; Balderson GA; Ando Y; Strong RW
TI -
Liver transplantation as a therapeutic option for hepatocellular
carcinoma.
SO - Oncology 2002;62 Suppl 1():82-6
AD - Department of Surgery, Matsunami General Hospital, Gifu, Japan.
mahide@he.mirai.ne.jp
Better outcomes of the patients receiving liver transplantation for
viral hepatitis and hepatocellular carcinoma (HCC) are achieved by
improved patient selection and perioperative treatment with antiviral
agents including lamivudine, ribavirin and interferon. Patient selection
is accomplished by high-quality imaging as well as exclusion of patients
with large tumors, obvious extrahepatic disease or macroscopic vascular
invasion. Using such criteria, a 5-year survival of 92% has been reached
in the Queensland Liver Transplant Service on a small number of highly
selected patients with HCC. The treatment algorithm of Makuuchi has
guided us in recommending resection, estimating to what extent the liver
resection can be performed safely, and timing liver transplantation when
it is the only option. Adult-to-adult living-donor liver transplantation
is being performed safely in many centers worldwide. The transplantation
of liver from living donors to HCC patients, when standard criteria for
the likelihood of good outcomes are fulfilled, will increase in Japan in
the near future.
13
UI - 11868794
AU - Kumada H
TI -
Long-term treatment of chronic hepatitis C with glycyrrhizin [stronger
neo-minophagen C (SNMC)] for preventing liver cirrhosis and
hepatocellular carcinoma.
SO - Oncology 2002;62 Suppl 1():94-100
AD - Department of Gastroenterology, Toranomon Hospital, Tokyo, Japan.
In Japan, hepatitis C virus (HCV) is the single most frequent cause of
hepatocellular carcinoma (HCC), resulting in yearly deaths of over
30,000. Although the mechanism of how HCV induces HCC is not clear,
persistent HCV infection and necro-inflammatory changes in chronic
hepatitis C accelerate the development of liver cirrhosis and can
eventuate in HCC. Hence, means of eradicating HCV as well as suppressing
inflammation in the liver, even if patients stay infected with HCV,
would decrease the incidence of HCC with chronic hepatitis C. For more
than 40 years, a preparation of glycyrrhizin [Stronger Neo-Minophagen C
(SNMC)] has been used for the treatment of 'allergic' hepatitis in
Japan. In 1977, intravenous injection with SNMC was started in patients
with chronic hepatitis or liver cirrhosis, most of whom have turned out
to be infected with hepatitis viruses. In a multicenter double-blind
study, alanine aminotransferase (ALT) levels decreased in the patients
who received 40 ml/day of SNMC for 4 weeks at a rate significantly
higher (p < 0.001) than controls receiving placebo. Furthermore, SNMC
100 ml/day for 8 weeks improved liver histology in 40 patients with
chronic hepatitis, in correlation with improved ALT levels in serum.
Liver cirrhosis occurred less frequently in 178 patients on long-term
SNMC than in 100 controls (28 vs. 40% at year 13, p < 0.002). Finally,
HCC developed less frequently in the 84 patients on long-term SNMC than
in the 109 controls (13 vs. 25% at year 15, p < 0.002). Combined, these
results indicate that a long-term treatment with SNMC prevents the
development of HCC in the patients with chronic hepatitis. SNMC is
particularly helpful in the patients with chronic hepatitis C who fail
to respond to interferon and in those who cannot be treated with it for
various reasons.
14
UI - 11435538
AU - Shetty SK; Rosen MP; Raptopoulos V; Goldberg SN
TI -
Cost-effectiveness of percutaneous radiofrequency ablation for malignant
hepatic neoplasms.
SO - J Vasc Interv Radiol 2001 Jul;12(7):823-33
AD - Harvard Medical School and Department of Radiology, Beth Israel
Deaconess Medical Center, 330 Brookline Avenue, E/AN-248, Boston,
Massachusetts 02215, USA.
PURPOSE: Percutaneous radiofrequency (RF) ablation is a promising
technique for the treatment of hepatic malignancies. However, its
cost-effectiveness has not been established. The purpose of this study
is to determine the cost-effectiveness of RF ablation compared to
palliative care in the treatment of hepatocellular cancer and colorectal
liver metastases. This study also seeks to evaluate the effects of
transition from traditional to newly implemented prospective outpatient
reimbursement mechanisms on RF ablation cost-effectiveness. MATERIALS
AND METHODS: The marginal direct costs of a percutaneous RF ablation
treatment strategy were compared to palliative care over a range of
survival benefits with use of a cost-effectiveness model built from the
perspective of the payer. Variables used in the model, including
complication rates and procedure efficacy, were obtained from the
literature and the authors' experience with 46 consecutive patients.
RESULTS: The cost-effectiveness of a standardized percutaneous RF
ablation treatment strategy compared to palliative care was $20,424,
$11,407, $5,034, and $3,492, respectively, per life-year (LY) gained
when marginal median survival conferred by RF ablation is 6 months, 1
year, 3 years, and 5 years. The RF ablation treatment strategy would be
required to generate 6.14, 2.26, and 1.10 months of marginal median
survival benefit to achieve strict ($20,000/LY gained), moderate
($50,000/LY gained), and generous ($100,000/LY gained)
cost-effectiveness thresholds. Cost-effectiveness was sensitive to the
number of lifetime treatments, hours of observation time, frequency of
follow-up evaluations, cost of abdominal computed tomography, and
decision to perform RF ablation as an inpatient or outpatient.
CONCLUSION: Percutaneous RF ablation is a cost-effective treatment
strategy compared to palliative care and has likely already achieved the
survival benefit required to meet even a strict cost-effectiveness
criterion. Dependence on reimbursement mechanism highlights the
importance of concordance between policy and RF ablation technology. The
results of this study allow flexible application of cost-effectiveness
data despite current uncertainties in treatment and survival data and
heterogeneity in treatment populations.
15
UI - 11776603
AU - Li H; Ou Q; Chen J
TI -
[Combined hepatic artery chemoembolization and portal vein chemotherapy
after radical resection of hepatocellular carcinoma to prevent
recurrence]
SO - Zhonghua Zhong Liu Za Zhi 2000 Jan;22(1):61-3
AD - Department of Surgery, Memorial Hospital, Sun Yat-sen University of
Medical Sciences, Guangzhou 510120, China.
OBJECTIVE: To study the value of combined hepatic artery
chemoembolization (HACE) and portal vein chemotherapy (PVC) after
radical resection of hepatocellular carcinoma (HCC) to prevent
undergone radical tumor resection. After operation, combined treatment
with HACE and PVC was given in group I (28 cases), HACE alone in group
II (30 cases), nothing in group III (28 cases). All patients were
followed up over 3 years. RESULTS: Recurrence rate at one year after
surgery was significantly lower in group I and II than in group III; at
two years, it was lower in group I than in group II and III. Survival
rate at one year was notably higher in group I and II than in group III;
at 2 years, it was higher in group I than in group II and III.
Recurrence rate and survival rate were similar in group I and group II
at 3 and 5 years after surgery. Tumor larger than 5 cm, no capsule,
multiple foci, AFP > 400 micrograms/L were high risk factors of
postoperative recurrence. CONCLUSION: After radical resection of HCC,
combined use of HACE and PVC is superior to HACE alone to reduce
recurrence rate and to increase survival rate within 2 years after
operation. Such remarkable difference no more exists at 3 and 5 years
following operation.
16
UI - 11810776
AU - Rui J; Wang S; Chen S
TI -
[A surgery oriented serial treatments of 191 patients with large primary
liver cancer]
SO - Zhonghua Zhong Liu Za Zhi 2001 Sep;23(5):417-9
AD - Liver Cancer Institute, Post & Telecommunications General Hospital,
Department of Hepatic Surgery, Eighth Clinical College, Beijing
University, Beijing 100032, China.
OBJECTIVE: To discuss the methods and effects of a series of surgery
oriented therapies in the treatment of large primary liver cancers.
cancer were treated chiefly by operation. The size of the primary cancer
varied from 5.2 to 19.7 cm (median 9.4 cm). Various kinds of liver
resections were performed in 121 patients and, as a supplement, deep
cryosurgery was carried for out the rest 70 patients. Importable drug
delivery system (IDDS) was instituted intraoperatively. Transcatheter
arterial chemo-embolization (TACE, THP 30-60 mg, E-ADM 20-40 mg, CDDP
40-80 mg, MMC 10-20 mg, iodine oil 5-30 ml), percutaneous ethanol
injection (PEI), bioimmunotherapy and the traditional Chinese medicine
were used pre- and post-operatively. CT angiography (CTA) and CT during
arterial portography (CTAP) were used to find satellite nodules. Early
recurrence was diagnosed by AFPmRNA monitor in peripheral blood. Child's
classification plus branch chain amino acid/aromatic amino acid
(BCAA/AAA) were adopted in evaluating the pre-operative liver functions.
RESULTS: Remarkable results were observed after this surgery oriented
serial treatment. The 1-, 3- and 5-year survival rates in the resection
group were 75.8%, 45.6% and 30.4%, respectively. The 1- and 3-year
survival rates in the cryosurgery group were 63.2% and 37.0%. The
operative mortality was 1.6%. Recurrence rates were 69.2% in AFPmRNA
positive group and 33.3% in AFPmRNA negative group. Comparing this two
groups, significant difference was observed (P < 0.05). BCAA/AAA were
lower than 1.5 in two patients died after resection. CONCLUSION: A
serial treatment with surgery as the chief modality gives satisfactory
results in large primary liver cancers. This regimen should be adhered
to as a main strategy in dealing with large liver cancers. AFPmRNA in
the peripheral blood, signifying a recurrence, may become a hope of a
new clinical parameter. BCAA/AAA plus Child's classification is able to
evaluate more accurately the hepatic functional reserve before surgery.
17
UI - 11779412
AU - Harvey BG; Maroni J; O'Donoghue KA; Chu KW; Muscat JC; Pippo AL; Wright
TI -
CE; Hollmann C; Wisnivesky JP; Kessler PD; Rasmussen HS; Rosengart TK;
Crystal RG
Safety of local delivery of low- and intermediate-dose adenovirus gene
transfer vectors to individuals with a spectrum of morbid conditions.
SO - Hum Gene Ther 2002 Jan 1;13(1):15-63
AD - Division of Pulmonary and Critical Care Medicine, Weill Medical College
of Cornell University, New York, NY 10021, USA.
To help define the safety profile of the use of adenovirus (Ad) gene
transfer vectors in humans, this report summarizes our experience since
humans using low (<10(9) particle units) or intermediate (10(9)-10(11)
particle units) doses. Included in the study are 90 individuals and 12
controls, with diverse comorbid conditions, including cystic fibrosis,
colon cancer metastatic to liver, severe coronary artery disease, and
peripheral vascular disease, as well as normals. These individuals
received 140 different administrations of vector, with up to seven
administrations to a single individual. The vectors used include three
different transgenes (human cystic fibrosis transmembrane conductance
regulator cDNA, E. coli cytosine deaminase gene, and the human vascular
endothelial growth factor 121 cDNA) administered by six different routes
(nasal epithelium, bronchial epithelium, percutaneous to solid tumor,
intradermal, epicardial injection of the myocardium, and skeletal
muscle). The total population was followed for 130.4 patient-years. The
study assesses adverse events, common laboratory tests, and long-term
follow-up, including incidence of death or development of malignancy.
The total group incidence of major adverse events linked to an Ad vector
was 0.7%. There were no deaths attributable to the Ad vectors per se,
and the incidence of malignancy was within that expected for the
population. Overall, the observations are consistent with the concept
that local administration of low and intermediate doses of Ad vectors
appears to be well tolerated.
18
UI - 11851828
AU - Okuno M; Kojima S; Moriwaki H
TI -
Chemoprevention of hepatocellular carcinoma: concept, progress and
perspectives.
SO - J Gastroenterol Hepatol 2001 Dec;16(12):1329-35
AD - First Department of Internal Medicine, Gifu University School of
Medicine, Gifu, Japan. mokuno@cc.gifu-u.ac.jp
Hepatocellular carcinoma (HCC) often develops in patients with chronic
liver diseases associated with hepatitis B (HBV) and hepatitis C (HCV)
virus infections with high incidences. Particularly, post-therapeutic
recurrence encountered after the curative treatment of the preceding HCC
may limit the prognosis. Thus, prevention of HCC is of great
significance. In the present review, immunopreventions with
alpha-interferon and glycyrrhizin, as well as chemoprevention with
acyclic retinoid, are discussed. alpha-Interferon prevents the
development of HCC not only in patients with a long-term elimination of
HCV (sustained virological responders), but in ones with normalized
serum aminotransferases (sustained biochemical responders). Glycyrrhizin
also suppresses serum aminotransferases and thereby prevents the tumor
development, even though the compound does not have antiviral activity
for HBV or HCV by itself. Therefore, suppression of hepatic
necroinflammation by these drugs may serve to prevent
hepatocarcinogenesis. In contrast, acyclic retinoid suppresses the
post-therapeutic recurrence in cirrhotic patients who underwent curative
treatment of preceding tumors. The retinoid induces the disappearance of
serum lectin-reactive alpha-fetoprotein (AFP-L3), a tumor marker
indicating the presence of unrecognizable tumors in the remnant liver,
suggesting a deletion of such minute (pre)malignant clones (clonal
deletion). As a molecular mechanism of the clonal deletion, a novel
mechanism of apoptosis induction by the retinoid via tissue
transglutaminase is implicated. In future, a combination of
immunopreventive and chemopreventive therapies may give a clue to the
further advances of cancer prevention, and thereby to the improvement of
the prognosis of cirrhotic patients.
19
UI - 11837720
AU - Takimoto M; Ohkoshi S; Ichida T; Takeda Y; Nomoto M; Asakura H; Naito A;
TI -
Mori S; Hata K; Igarashi K; Hara H; Ohta H; Soga K; Watanabe T; Kamimura
T
Interferon inhibits progression of liver fibrosis and reduces the risk
of hepatocarcinogenesis in patients with chronic hepatitis C: a
retrospective multicenter analysis of 652 patients.
SO - Dig Dis Sci 2002 Jan;47(1):170-6
AD - Department of the Internal Medicine III, School of Medicine, Niigata
University, Niigata-City, Japan.
A retrospective multicenter analysis of 652 patients with chronic
hepatitis C who have been treated with interferon (IFN) was performed to
assess the effects of IFN on the clinical course and development of HCC.
During a mean follow-up of 54.8 months, hepatocellular carcinoma (HCC)
developed in 7.0% of the patients. The rate was significantly higher in
the patients who did not respond to IFN treatment than in those with
sustained virological response and those who obtained a normalization of
alanine aminotransferase levels despite the presence of HCV RNA
(incomplete response) (P < 0.01). Using multivariate Cox's proportional
hazard model, alcohol abuse (P < 0.05) and a higher level of fibrosis (P
< 0.05) before treatment were the significant background factors
associated with HCC development in the patients who did not respond to
IFN. Interestingly, a significant increase in the rate of HCC
development occurred in patients who had a histological finding of
progressive fibrosis (F3). In addition, patients with low histological
staging scores were likely to have an incomplete response, even if a
sustained virological response was not obtained. IFN produced an
improvement in histological activity and fibrosis stage in the second
biopsy specimens irrespective of the clinical outcome when compared
against untreated subjects.
20
UI - 11848540
AU - Kitagawa K; Taniguchi H; Mugitani T; Koh T; Obayashi T; Kunishima S;
TI -
Yamaguchi A; Yamagishi H
Safety and advantage of perioperative autologous blood transfusion in
hepatic resection for hepatocellular carcinoma.
SO - Anticancer Res 2001 Sep-Oct;21(5):3663-7
AD - Digestive Surgery, Kyoto Kujo Hospital, Japan. Kskitagawa@aol.com
BACKGROUND: The safety and advantages of perioperative autologous blood
transfusion (ABT) were evaluated on hepatectomy for hepatocellular
carcinoma (HCC). MATERIALS AND METHODS: Blood samples were obtained and
stored from 30 patients with HCC. HCC cells were investigated by the
presence of AFPmRNA using RT-PCR after storage. We also reviewed
postoperative liver function and the long-term outcomes of 138 patients
who underwent hepatectomy receiving ABT compared with patients receiving
homologous blood transfusion (HBT) and patients without blood
transfusion. RESULTS: AFPmRNA was not detected in all samples stored for
more than 14 days. Postoperative ALT, AST and total bilirubin in the HBT
group were significantly higher than those of other groups. Patients in
the HBT group had significantly lower survival rates than patients in
the ABT group. CONCLUSION: ABT was safe after storage and it had
advantages compared with HBT with regard to postoperative liver function
and survival rate after the hepatectomy for HCC.
21
UI - 11869011
AU - Achenbach T; Seifert JK; Pitton MB; Schunk K; Junginger T
TI -
Chemoembolization for primary liver cancer.
SO - Eur J Surg Oncol 2002 Feb;28(1):37-41
AD - Klinik fur Radiologie, Johannes Gutenberg-Universitat, Mainz, Germany.
AIMS: For most patients with primary liver cancer surgical treatment is
not feasible and prognosis without treatment is poor. We aimed to assess
the morbidity and efficacy of transarterial chemoembolization (TACE)
with lipiodol and mitomycin C in these patients in a prospective
with non-resectable hepatocellular carcinoma were treated with TACE. In
case of radiological or tumour-marker response, treatment was repeated
after 4--6 weeks, up to seven times per patient. RESULTS: Morbidity was
23% and usually minor, no patient died within 30 days of treatment. A
decrease in size of the reference tumour or constant tumour-size in
CT-scan were observed in 14 of 20 patients (70%) and of the 19 patients
with elevated AFP-serum levels 12 (63%) had an AFP reduction following
treatment. The median survival time was 14 months with a 1- and 2-year
survival rate of 69% and 29%, respectively. Survival was not different
in radiological or AFP responders vs non-responders. CONCLUSION: While
TACE with lipiodol and mitomycin C for primary liver cancer is
associated with considerable antitumoural efficacy, as demonstrated by
tumour marker and radiological response, an effect on patient survival
is not evident. New treatment options with an impact on survival are
needed for these patients. Copyright Harcourt Publishers Limited.
22
UI - 11286465
AU - Villa E; Ferretti I; Grottola A; Buttafoco P; Buono MG; Giannini F;
TI -
Manno M; Bertani H; Dugani A; Manenti F
Hormonal therapy with megestrol in inoperable hepatocellular carcinoma
characterized by variant oestrogen receptors.
SO - Br J Cancer 2001 Apr 6;84(7):881-5
AD - Department of Internal Medicine, University of Modena, Italy.
Variant liver oestrogen receptor transcripts in hepatocellular carcinoma
are associated with aggressive clinical course and unresponsiveness to
tamoxifen. To evaluate the impact on survival and on tumour growth of
megestrol (progestin drug acting at post-receptorial level) we enrolled
45 patients with HCC characterized by variant liver oestrogen receptors
in a prospective, randomized study with megestrol vs. placebo. Presence
of variant oestrogen receptors was determined by RT/PCR. 24 patients
were randomized to no treatment and 21 to therapy with megestrol 160 mg
day(-1). Results were analysed by Kaplan-Meier and Cox methods. Survival
of hepatocellular carcinoma characterized by variant oestrogen receptors
was extremely poor (median survival 7 months); megestrol significantly
improved survival (18 months) (P = 0.0090). Tumour growth at one year
was significantly slowed down in megestrol-treated patients (P =
0.0212). Bilirubin levels, presence of portal thrombosis, HBV aetiology
and treatment were identified at univariate analysis as factors
significantly associated with survival; at multivariate analysis, only
megestrol therapy (P = 0.0003), presence of HBV infection (P = 0.0009)
and presence of portal vein thrombosis (P = 0.0051) were factors
independently related with survival. (1) Megestrol slows down the
aggressive tumour growth of patients with hepatocellular carcinoma
characterized by variant estrogen receptors and (2) is also able to
favourably influence the course of disease, more than doubling median
survival. Copyright 2001 Cancer Research Campaign.
23
UI - 11604987
AU - Okano H; Shiraki K; Inoue H; Ito T; Yamanaka T; Deguchi M; Sugimoto K;
TI -
Sakai T; Ohmori S; Murata K; Takase K; Nakano T
Combining transcatheter arterial chemoembolization with percutaneous
ethanol injection therapy for small size hepatocellular carcinoma.
SO - Int J Oncol 2001 Nov;19(5):909-12
AD - First Department of Internal Medicine, Mie University School of
Medicine, Tsu 514-8507, Japan.
For patients with unresectable small size HCC, percutaneous ethanol
injection therapy (PEIT) is used as a non-surgical treatment because it
is difficult to achieve complete tumor necrosis by transcatheter
arterial chemoembolization (TAE) alone. However, some small HCCs (<21 mm
in diameter) are resistant to PEIT with incomplete tumor necrosis, which
is associated with insufficient ethanol injection to the tumor. For more
effective treatment for HCC, we performed a combination of TAE and PEIT
on patients with small size HCC and evaluated the cumulative recurrence
and survival rates. The recurrence rate in patients treated with the
combination was less than that of TAE or PEIT alone. There were five
patients without tumor recurrence during the follow-up period and three
out of these underwent the combination treatment. The period of no
recurrence was 33.4 months on average. In conclusion, we recommend
combination therapy with TAE and PEIT for patients to accomplish more
effective treatment of small size HCC.
24
UI - 11720452
AU - Farinati F; Gianni S; De Giorgio M; Fiorentini S
TI -
Megestrol treatment in patients with hepatocellular carcinoma.
SO - Br J Cancer 2001 Nov 16;85(10):1606-8
25
UI - 11603004
AU - Brans B; De Winter F; Defreyne L; Troisi R; Vanlangenhove P; Van
TI -
Vlierberghe H; Lambert B; Praet M; de Hemptinne B; Dierckx RA
The anti-tumoral activity of neoadjuvant intra-arterial 131I-lipiodol
treatment for hepatocellular carcinoma: a pilot study.
SO - Cancer Biother Radiopharm 2001 Aug;16(4):333-8
AD - Division of Nuclear Medicine, Ghent University Hospital, De Pintelaan
185, B-9000 Ghent, Belgium. boudewijn.brans@rug.ac.be
BACKGROUND: The high recurrence rate after curative resection has
stimulated the development of adjuvant treatment modalities, such as
local embolization. This study was set up to investigate the
anti-tumoral potential of neo-adjuvant 131I-lipiodol administration
before liver transplantation. METHODS: In this preliminary, prospective
study we treated 10 consecutive HCC patients by intra-arterial injection
of 131I-lipiodol into the hepatic artery followed by liver
transplantation within 1-9 months (mean 3.4). After hepatic
catheterization, 1332-2146 MBq (mean 1887 MBq) or 36-58 mCi (mean 51
mCi) was instilled as selective as possible, depending on the
distribution of the tumors: non-selectively in the hepatic artery
propria (n = 4), selectively in the right and/or left hepatic artery (n
= 3) or super-selectively in segmental arteries (n = 3). RESULTS:
Anti-tumoral activity was regarded as obvious with 1) a strong decrease
of alfa-fetoprotein (AFP), comparing the highest recorded value before
and after 131I-lipiodol and/or 2) a downstaging in TNM classification on
the posttherapy MRI as compared to the pre-therapy MRI and/or 3) tumors
with > 50% necrosis on histo-pathology of the explanted liver, without
previous chemoembolization. Either of these criteria were met by 5/10
(50%) of patients. A 4) downstaging in pTNM classification on
histopathology compared to the TNM classification of the MRI and/or a 5)
tumor necrosis of only 10-50% were regarded as possibly tumor-related
but were not accepted as a single criteria of anti-tumoral activity.
This was seen in 3/10 (30%) of patients. Clinical side-effects of the
131I-lipiodol therapy were generally mild with a temperature rise in two
cases, nausea without vomiting in another two and upper back pain in one
patient. In one patient progressive liver failure developed one week
after 131I-lipiodol therapy necessitating premature liver
transplantation after 4 weeks. CONCLUSION: With the use of stringent
anti-tumoral criteria, this study shows evidence of an anti-tumoral
effect in 50% of patients. Our data support the evaluation on larger
patient numbers to confirm the promising anti-tumoral activity of
131I-lipiodol in HCC patients candidated for liver transplantation.
26
UI - 11854960
AU - Melliza DM; Woodall M
TI -
Radiofrequency ablation of liver tumors: the complementary roles of the
clinic and research nurse.
SO - Gastroenterol Nurs 2000 Sep-Oct;23(5):210-4
AD - Ambulatory Treatment Center, University of Texas, M. D. Anderson Cancer
Center, Houston, Texas, USA.
This article describes a clinical research protocol designed to
determine the value of Radiofrequency Ablation (RFA) for the treatment
of histologically proven primary or metastatic liver cancer. RFA is a
localized thermal technique that destroys tumor tissue. The research
protocol is described, including enrollment criteria, performance of
RFA, and the follow-up necessary to ascertain protocol success or
failure. The complementary and collaborative roles of the research nurse
and clinic nurse in carrying out the RFA protocol are described.
27
UI - 11707647
AU - Favoulet P; Cercueil JP; Faure P; Osmak L; Isambert N; Beltramo JL;
TI -
Cognet F; Krause D; Bedenne L; Chauffert B
Increased cytotoxicity and stability of Lipiodol-pirarubicin emulsion
compared to classical doxorubicin-Lipiodol: potential advantage for
chemoembolization of unresectable hepatocellular carcinoma.
SO - Anticancer Drugs 2001 Nov;12(10):801-6
AD - Faculty of Medicine, Unite INSERM 517, 21000 Dijon, France.
There is no well-defined curative treatment for advanced and
unresectable hepatocellular carcinoma. The widely used transarterial
chemoembolization (TACE) with a doxorubicin-Lipiodol emulsion has not
been shown to improve survival in randomized studies. Further,
obstruction of the hepatic artery used in the procedure is badly
tolerated in patients with cirrhosis. Drugs with a more rapid
penetration into the cancer cells are likely to eliminate the need for
obstruction of the hepatic artery. We therefore compared the
cytotoxicity of another anthracycline pirarubicin with that of the
commonly used doxorubicin. In this report, we show that pirarubicin has
a greater in vitro cytotoxic effect than doxorubicin on the HepG2 and
Hu-H7 human hepatoma cell lines. Pirarubicin emulsion with Lipiodol is
more stable at 37 degrees C
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