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NCI CANCERLIT® Search: Therapy of Primary Liver Cancer - April 2002
National Cancer Institute®
Last Modified: April 1, 2002
Table of Contents
1
UI - 11593513
AU - Cao X; He N; Sun J; Tan J; Zhang C; Yang J; Lu T; Li J
TI -
Hepatic radioembolization with Yttrium-90 glass microspheres for
treatment of primary liver cancer.
SO - Chin Med J (Engl) 1999 May;112(5):430-2
AD - Department of Radiology, General Hospital, Tianjin Medical University,
Tianjin 300052, China.
OBJECTIVE: To study the clinical results of hepatic radioembolization
with Yttrium-90 (90Y) glass microspheres in the treatment of primary
liver cancer. METHODS: Seventeen patients with liver cancer were treated
radioembolization with 90Y and lipiodol-ultrafluid was used.
Percutaneous port-catheter system (PCS) implantations via femoral artery
were performed in 12 patients. RESULTS: In the 17 patients, their mean
ratio of absorbed doses between tumor and normal liver was 2.4:1. CT
showed a significant reduction in tumor size in 11 of the 17 patients.
Average survival was 19.5 months. The indwelling catheters of all the 12
patients were patent and no catheter tip locations were found.
CONCLUSIONS: 90Y glass microsphere is one of the best radioisotopes. Not
only good responses to the therapy of 90Y glass microspheres can be
achieved in patients with metastatic liver cancer, but also in those
with primary liver cancer, specially the localized or hypervascular
mass. The patients with massive arterioportal shunt should not be
limited to this form of radiation therapy. The percutaneous PCS
implantation via the femoral artery is a new passageway for the
treatment of primary liver cancer with 90Y glass microspheres and other
interventional therapy.
2
UI - 11780473
AU - Ho S; Lau WY; Leung WT
TI -
Comments on "Hepatic radioembolization with yttrium-90 glass
microspheres for treatment of primary liver cancer" by Cao et al, Chin
Med J 1999; 112: 430-432.
SO - Chin Med J (Engl) 2001 Apr;114(4):433-4
3
UI - 11862430
AU - Ueno H; Okada S; Okusaka T; Ikeda M; Kuriyama H
TI -
Phase I and pharmacokinetic study of 5-fluorouracil administered by
5-day continuous infusion in patients with hepatocellular carcinoma.
SO - Cancer Chemother Pharmacol 2002 Feb;49(2):155-60
AD - Hepatobiliary and Pancreatic Oncology Division, National Cancer Center
Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
hiueno@ncc.go.jp
PURPOSE: In this study the maximum tolerated dose of 5-fluorouracil
administered by 5-day (120-h) continuous infusion every 4 weeks was
investigated and the pharmacokinetics in patients with hepatocellular
carcinoma were evaluated. METHODS: Patients with hepatocellular
carcinoma no longer amenable to established forms of treatment were
eligible for the study. The starting dose of 5-fluorouracil was 300
mg/m(2) per day and doses were escalated in 50 mg/m(2) per day
increments in successive cohorts of three new patients if tolerated.
Pharmacokinetic studies were performed at the time of the first course
of therapy. RESULTS: Enrolled in the study were 20 patients. The maximum
tolerated dose was 500 mg/m(2) per day and the dose-limiting toxicity
was stomatitis. Other toxicities were mild and well tolerated. Age,
gender and associated liver cirrhosis were significant factors
influencing 5-fluorouracil clearance. With regard to biochemical
parameters, serum alanine aminotransferase and cholesterol levels were
correlated with 5-fluorouracil clearance. CONCLUSIONS: The maximum
tolerated dose for 5-day continuous infusion of 5-fluorouracil in
hepatocellular carcinoma patients was 500 mg/m(2) per day. The
recommended dose for phase II studies using this schedule is 450 mg/m(2)
per day. Furthermore, the pharmacokinetic data obtained in this study
may be useful in determining chemotherapy dosage adjustments for
reduction of toxicity.
4
UI - 11247073
AU - Penchev R
TI -
[Two-year experience with the jet dissector "Parenchymotome 01" in
clinical practice]
SO - Khirurgiia (Sofiia) 1998;53(6):52-6
AD - Military Medical Academy, Clinic of General Surgery, Sofia, Bulgaria.
5
UI - 11672831
AU - Colombo M
TI -
Treatment of hepatocellular carcinoma.
SO - Antiviral Res 2001 Nov;52(2):209-15
AD - Department of Hepatology, IRCCS Maggiore Hospital, University of Milan,
Via Pace No. 9, 20122 Milan, Italy. massimo.colombo@unimi.it
Treatment options have largely been selected according to empirical
criteria, such as the presence or absence of cirrhosis, number and size
of tumors, and degree of hepatic deterioration and taking into account
the local technological and economic resources. There are virtually no
controlled studies comparing the efficacy of the available treatments,
and the substantial heterogeneity of survival between control groups
does not allow us to obtain therapeutic evaluation by comparing results
of separate trials. The reassessment of treatment outcomes on the basis
of intention-to-treat analysis yielded less encouraging figures. Hepatic
resection is the primary option for the few patients with a
hepatocellular carcinoma arising in a normal liver with well-preserved
hepatic function and for patients with a single tumor, compensated
cirrhosis and low portal hypertension who are not candidable to liver
transplantation. The latter is the best treatment modality for patients
with a solitary tumor <5 cm in diameter or patients with less than three
tumors <3 cm, resulting in a 5-year survival of 75%. Locoregional
ablative treatments are curative options for patients with a
"resectable" tumor who cannot be offered transplantation or hepatic
resection. The 5-year survival is approximately 50% but it copes with a
high risk of tumor recurrence. Patients with advanced tumor disease
cannot be offered curative treatments but only symptomatic treatments.
6
UI - 11905412
AU - Leung TW; Tang AM; Zee B; Yu SC; Lai PB; Lau WY; Johnson PJ
TI -
Factors predicting response and survival in 149 patients with
unresectable hepatocellular carcinoma treated by combination cisplatin,
interferon-alpha, doxorubicin and 5-fluorouracil chemotherapy.
SO - Cancer 2002 Jan 15;94(2):421-7
AD - Department of Clinical Oncology, The Chinese University of Hong Kong,
SAR. waitongleung@cuhk.edu.hk
BACKGROUND: The objective of the current study was to identify patient
and disease related factors that influence response and survival for
patients with unresectable hepatocellular carcinoma (HCC) who received a
systemic combination chemotherapy consisting of cisplatin,
alpha-interferon, doxorubicin, and 5-fluorouracil (PIAF). METHODS: From
treated with PIAF: cisplatin (20mg/m2 intravenously, Days 1-4),
doxorubicin (40mg/m2 intravenously, Day 1), 5-fluorouracil (400mg/m2
intravenously, Days 1-4), and alpha-interferon (5MU/m2 subcutaneously,
Days 1-4), once every 3 weeks up to a maximum of six cycles. Univariate
and multivariate analyses of patient and disease characteristics were
used to identify factors predicting response and survival. RESULTS: The
objective response rate according to conventional criteria was 16.8%
(complete response in 3 out of 149 patients, or 2%, 95% confidence
interval [CI] 0-4.3%; partial response in 22 out of 149 patients, or
14.8%, 95% CI 9-20%). The median survival time was 30.9 weeks (95% CI
22.1 to 40). Significant independent predictors of an objective response
were: absence of cirrhosis (P = 0.006), low bilirubin level (P = 0.006),
and positive hepatitis C serology (P = 0.025). The following factors
were related to a shorter survival time: high Okuda stage (P = 0.001),
vascular involvement (P = 0.018), and cirrhosis (P = 0.008). Good risk
patients (absence of cirrhosis and total bilirubin < or = 0.6mg/dL) had
an objective response rate of 50%. CONCLUSIONS. Patients with
unresectable HCC who also have normal total bilirubin and non-cirrhotic
livers have a better chance of response and prolonged survival after
treatment with systemic PIAF.
7
UI - 11900230
AU - Wood BJ; Ramkaransingh JR; Fojo T; Walther MM; Libutti SK
TI -
Percutaneous tumor ablation with radiofrequency.
SO - Cancer 2002 Jan 15;94(2):443-51
AD - Diagnostic Radiology Department, Special Procedures Division, National
Institutes of Health Clinical Center, Bethesda, Maryland 20892, USA.
bwood@nih.gov
BACKGROUND: Radiofrequency thermal ablation (RFA) is a new minimally
invasive treatment for localized cancer. Minimally invasive surgical
options require less resources, time, recovery, and cost, and often
offer reduced morbidity and mortality, compared with more invasive
methods. To be useful, image-guided, minimally invasive, local
treatments will have to meet those expectations without sacrificing
efficacy. METHODS: Image-guided, local cancer treatment relies on the
assumption that local disease control may improve survival. Recent
developments in ablative techniques are being applied to patients with
inoperable, small, or solitary liver tumors, recurrent metachronous
hereditary renal cell carcinoma, and neoplasms in the bone, lung,
breast, and adrenal gland. RESULTS: Recent refinements in ablation
technology enable large tumor volumes to be treated with image-guided
needle placement, either percutaneously, laparoscopically, or with open
surgery. Local disease control potentially could result in improved
survival, or enhanced operability. CONCLUSIONS: Consensus indications in
oncology are ill-defined, despite widespread proliferation of the
technology. A brief review is presented of the current status of
image-guided tumor ablation therapy. More rigorous scientific review,
long-term follow-up, and randomized prospective trials are needed to
help define the role of RFA in oncology.
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 - 11920537
AU - Chan AO; Yuen MF; Hui CK; Tso WK; Lai CL
TI -
A prospective study regarding the complications of transcatheter
intraarterial lipiodol chemoembolization in patients with hepatocellular
carcinoma.
SO - Cancer 2002 Mar 15;94(6):1747-52
AD - Department of Medicine, Queen Mary Hospital, the University of Hong
Kong, Hong Kong.
BACKGROUND: Hepatocellular carcinoma (HCC) is a common cause of cancer
death throughout the world. The majority of patients are not suitable
for curative resection either because of the advanced stage of the
disease at the time of presentation or because of underlying cirrhosis.
Transcatheter intraarterial lipiodol chemoembolization (TACE) has been
reported to be one of the most effective palliative measures for HCC.
However, its severe side effects continue to make its use controversial.
METHODS: In the current study, the authors prospectively evaluated 197
sessions of TACE performed in 59 patients with HCC. RESULTS: Acute
hepatic decompensation occurred in 20% of the 197 sessions with 3% of
cases being irreversible. Significant elevation of bilirubin was
associated with the dosage of cisplatin used (P = 0.0001), basal
bilirubin level (P = 0.0001), basal prothrombin time (P =0.004), basal
aspartate aminotransferase (AST) level (P = 0.013), and stage of
cirrhosis (P < 0.0001). Patients with irreversible hepatic
decompensation were more likely to have higher pre-TACE bilirubin levels
(P = 0.009), more prolonged prothrombin time (P = 0.015), received a
higher dose of cisplatin (P = 0.033), and more advanced cirrhosis (P <
0.0001). The majority of the other side effects were self-limiting with
the exception of one patient who died of liver and splenic abscesses.
Approximately 36% of the patients achieved a tumor response, 39%
achieved stable disease, and 29% developed progressive disease.
CONCLUSIONS: The results of the current study identified factors that
appeared to predispose patients to irreversible hepatic decompensation
after TACE. Despite the high percentage of patients who developed
hepatic decompensation after TACE, irreversible damage occurred in only
a minority. Copyright 2002 American Cancer Society.
10
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.
11
UI - 11343266
AU - Kato T; Reddy KR
TI -
Radiofrequency ablation for hepatocellular carcinoma: help or hazard?
SO - Hepatology 2001 May;33(5):1336-7
12
UI - 11767865
AU - Harris M; Gibbs P; Cebon J; Jones R; Sewell R; Schelleman T; Angus P
TI -
Hepatocellular carcinoma and chemoembolization.
SO - Intern Med J 2001 Dec;31(9):517-22
AD - Department of Medical Oncology, Austin & Repatriation Medical Centre,
Melbourne, Victoria, Australia. marion.harris@ludwig.edu.au
BACKGROUND: Chemoembolization is often used in the treatment of
hepatocellular carcinoma; however, there are limited data on its
efficacy in an Australian setting. AIMS: To review retrospectively the
experience of 21 patients with hepatocellular carcinoma who collectively
1999 in a teaching hospital and liver transplant centre in Victoria.
METHODS: Selective catheterization of the right or left hepatic arteries
was performed. A mixture of cisplatin 50 mg, epirubicin 50 mg, mitomycin
C 10 mg, Lipiodol and gelfoam was injected. Computed tomography (CT)
scans were performed at baseline and at 1-3 months after
chemoembolization. Outcome measures included response rates, toxicity,
progression-free and overall survival. RESULTS: CT response rates:
partial response 19% (n = 7), median duration 11 months (range 2+ to
37+); minor response 17% (n = 6), median duration 7 months (1+ to 12+);
stable disease 42% (n = 15), median duration 3 months (1+ to 15 months);
and progressive disease 22% (n = 8). Major toxicities included one case
each of acute renal failure, contrast encephalopathy, gastric ulceration
and hepatorenal failure. Median progression-free survival was 3 months
(range 0-37+). Median overall survival was 15 months (range 6-50+).
CONCLUSION: Chemoembolization has a role in the palliative treatment of
hepatocellular carcinoma. Our response rates and toxicity data are
consistent with those in the published literature. However, new
treatments are needed and prevention of disease by reduction in the
prevalence of chronic hepatitis B and C will be required to
significantly reduce mortality from this tumour.
13
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.
14
UI - 11920482
AU - Schnater JM; Aronson DC; Plaschkes J; Perilongo G; Brown J; Otte JB;
TI -
Brugieres L; Czauderna P; MacKinlay G; Vos A
Surgical view of the treatment of patients with hepatoblastoma: results
from the first prospective trial of the International Society of
Pediatric Oncology Liver Tumor Study Group.
SO - Cancer 2002 Feb 15;94(4):1111-20
AD - Pediatric Surgical Center Amsterdam (EKZ-AMC/VUmc), Amsterdam, The
Netherlands.
BACKGROUND: Surgical resection is the cornerstone of treatment for
patients with hepatoblastoma (HB). The Society of Pediatric Oncology
Liver Tumor Study Group launched its first prospective trial (SIOPEL-1)
with the intention to treat all patients with preoperative chemotherapy
and delayed surgical resection. The objective of this article was to
assess the assumed surgical advantages of primary chemotherapy. METHODS:
Between 1990 and 1994, 154 patients age < 16 years with HB were
registered on SIOPEL-1. The pretreatment extent of disease was assessed,
and, after undergoing biopsy, patients were treated with cisplatin 80
mg/m(2) intravenously over 24 hours and doxorubicin 60 mg/m(2)
intravenously over 48 hours by continuous infusion (PLADO). Generally,
tumors were resected after four of a total of six courses of PLADO.
RESULTS: One hundred twenty eight patients underwent surgical resection
(13 patients underwent primary surgery, and 115 patients underwent
delayed surgery after PLADO). A pretreatment surgical biopsy was
performed in 96 of 128 patients (75%). Biopsy complications occurred in
7 of 96 patients (7%). Twenty-two patients showed pulmonary metastases
at the time of diagnosis, and 7 patients underwent thoracotomy.
Operative morbidity and mortality were 18% and 5%, respectively.
Complete macroscopic surgical resection was achieved in 106 patients
(92%), including 6 patients who underwent orthotopic liver
transplantation. The actuarial 5-year event free survival (EFS) rate for
all 154 patients in the study was 66%, and the overall survival (OS)
rate was 75%. For the 115 patients who were included in the surgical
analysis that followed the exact protocol, the EFS and OS rates were 75%
and 85%, respectively. CONCLUSIONS: Biopsy is a safe procedure and
should be performed routinely. Preoperative chemotherapy seems to make
tumor resection easier. Reresection of a positive resection margin does
not necessarily have to be performed, because postoperative chemotherapy
showed good results. Resection of lung metastases can be curative if
there is local control of the primary tumor; however, results showed
that the patient's prognosis was worse. Surgical morbidity or mortality
rates were not necessarily higher in large multicenter studies. More
importantly, countries of lesser economic status also can contribute
effectively to these trials. Copyright 2002 American Cancer Society. DOI
10.1002/cncr.10282
15
UI - 11872055
AU - Lee WC; Jeng LB; Chen MF
TI -
Estimation of prognosis after hepatectomy for hepatocellular carcinoma.
SO - Br J Surg 2002 Mar;89(3):311-6
AD - Department of General Surgery, Chang-Gung Memorial Hospital, 5 Fu Hsing
Street, Kwei-Shan Hsiang, Taoyuan Hsien, Taiwan. weichen@cgmh.org.tw
BACKGROUND: The preferred means of treatment for hepatocellular
carcinoma is surgical resection. However, the tumour recurrence rate is
high. Accurate estimation of the risk of tumour recurrence after
hepatectomy may facilitate the administration of adjuvant therapy after
hepatectomy to patients with a high likelihood of tumour recurrence.
METHODS: The clinical and pathological profiles of 176 patients
were used to analyse univariate prognostic factors. The Cox proportional
hazard model was used for multivariate analysis. Disease-free and
overall cumulative survival rates were estimated with respect to the
number of prognostic factors. RESULTS: Independent factors associated
with a lower disease-free survival included the presence of venous
infiltration, presence of daughter tumours, absence of tumour
encapsulation and tumour size exceeding 5 cm. Factors decreasing the
overall survival rate included the presence of venous infiltration,
absence of tumour encapsulation and surgical resection margin less than
1 cm. The 1-year disease-free survival rate decreased from 77.5(s.e.
5.6) to 14.0(8.5) per cent when the number of risk factors present
increased from zero to three. The 5-year survival rate decreased from
60.2(11.7) per cent to zero when the number of risk factors increased
from zero to three. CONCLUSION: The deterioration of disease-free or
overall survival of patients with hepatocellular carcinoma after
hepatectomy correlates with increasing number of risk factors. The
number of risk factors can be employed to accurately estimate
disease-free and overall survival.
16
UI - 11896118
AU - Seymour LW; Ferry DR; Anderson D; Hesslewood S; Julyan PJ; Poyner R;
TI -
Doran J; Young AM; Burtles S; Kerr DJ; Cancer Research Campaign Phase
I/II Clinical Trials committee
Hepatic drug targeting: phase I evaluation of polymer-bound doxorubicin.
SO - J Clin Oncol 2002 Mar 15;20(6):1668-76
AD - Cancer Research UK Institute for Cancer Studies, University of
Birmingham, United Kingdom.
PURPOSE: Preclinical studies have shown good anticancer activity
following targeting of a polymer bearing doxorubicin with galactosamine
(PK2) to the liver. The present phase I study was devised to determine
the toxicity, pharmacokinetic profile, and targeting capability of PK2.
PATIENTS AND METHODS: Doxorubicin was linked via a lysosomally
degradable tetrapeptide sequence to N-(2-hydroxypropyl)methacrylamide
copolymers bearing galactosamine. Targeting, toxicity, and efficacy were
evaluated in 31 patients with primary (n = 25) or metastatic (n = 6)
liver cancer. Body distribution of the radiolabelled polymer conjugate
was assessed using gamma-camera imaging and single-photon emission
computed tomography. RESULTS: The polymer was administered by
intravenous (i.v.) infusion over 1 hour, repeated every 3 weeks. Dose
escalation proceeded from 20 to 160 mg/m(2) (doxorubicin equivalents),
the maximum-tolerated dose, which was associated with severe fatigue,
grade 4 neutropenia, and grade 3 mucositis. Twenty-four hours after
administration, 16.9% +/- 3.9% of the administered dose of doxorubicin
targeted to the liver and 3.3% +/- 5.6% of dose was delivered to tumor.
Doxorubicin-polymer conjugate without galactosamine showed no targeting.
Three hepatoma patients showed partial responses, with one in continuing
partial remission 47 months after therapy. CONCLUSION: The recommended
PK2 dose is 120 mg/m(2), administered every 3 weeks by IV infusion.
Liver-specific doxorubicin delivery is achievable using
galactosamine-modified polymers, and targeting is also seen in primary
hepatocellular tumors.
17
UI - 11896125
AU - Tan SB; Machin D; Cheung YB; Chung YF; Tai BC; Machin D
TI -
Following a trial that stopped early: what next for adjuvant hepatic
intra-arterial iodine-131 lipiodol in resectable hepatocellular
carcinoma?
SO - J Clin Oncol 2002 Mar 15;20(6):1709
18
UI - 11915031
AU - Ijichi M; Takayama T; Matsumura M; Shiratori Y; Omata M; Makuuchi M
TI -
alpha-Fetoprotein mRNA in the circulation as a predictor of postsurgical
recurrence of hepatocellular carcinoma: a prospective study.
SO - Hepatology 2002 Apr;35(4):853-60
AD - Hepato-Biliary-Pancreatic Surgery Division, Artificial Organ and
Transplantation Division, Department of Surgery, University of Tokyo,
Tokyo, Japan.
alpha-fetoprotein (AFP) messenger RNA (mRNA) has been proposed as a
marker of hepatocellular carcinoma (HCC) cells disseminated into the
circulation, but its clinical significance remains controversial. We
prospectively assessed the prognostic value of AFP mRNA in patients
undergoing curative hepatic resection for HCC. Peripheral blood samples
were taken from 87 patients before and after surgery to determine the
presence of AFP mRNA by use of a reverse-transcription polymerase chain
reaction. A primary endpoint was recurrence-free interval. AFP mRNA was
detectable preoperatively in 31 patients (36%) and postoperatively in 30
patients (34%). With a median follow-up period of 28 months (range, 3-41
months), HCC recurred in 46 patients (53%). Among 4 groups separated
according to preoperative and postoperative AFP mRNA status, patients
with consistent positivity of AFP mRNA showed the highest recurrence
rate (85%) and trend to distant or multiple recurrence. The
recurrence-free interval was significantly shorter in patients with
postoperative positivity of AFP mRNA than in those without (53% [95% CI,
36-71] vs. 88% [95% CI, 79-96] at 1 year, 37% [95% CI, 17-57] vs. 60%
[95% CI, 46-75] at 2 years; P =.014), whereas the preoperative
positivity of AFP mRNA provided no significance (P =.100). Cox's
proportional-hazards model identified the postoperative positivity of
AFP mRNA as an independent prognostic factor for HCC recurrence
(relative risk, 2.33; 95% CI, 1.26-4.34; P =.007). In conclusion,
postsurgical recurrence of HCC can be predicted by detecting AFP
mRNA-expressing cells in peripheral blood.
19
UI - 11894035
AU - Fukuda S; Okuda K; Imamura M; Imamura I; Eriguchi N; Aoyagi S
TI -
Surgical resection combined with chemotherapy for advanced
hepatocellular carcinoma with tumor thrombus: report of 19 cases.
SO - Surgery 2002 Mar;131(3):300-10
AD - Department of Surgery, Kurume University School of Medicine, Fukuoka,
Japan.
BACKGROUND: Prognosis of hepatocellular carcinoma (HCC) with tumor
thrombus in the main portal vein (MPV), inferior vena cava (IVC), or
extrahepatic bile duct (EBD) treated by conventional therapies has been
considered poor. This study aimed to evaluate the efficacy of hepatic
arterial infusion chemotherapy after surgical resection as an adjuvant
therapy or as a treatment for intrahepatic recurrence of HCC with tumor
thrombus in MPV, IVC, or EBD. METHODS: Nineteen patients with HCC and
tumor thrombus in the MPV, IVC, or EBD who underwent hepatectomy with
thrombectomy were reviewed retrospectively. RESULTS: The overall 3-year
survival rate was 48.5%. Two patients with postoperative residual tumor
thrombus died within 6 months owing to rapid progression of the residual
tumor thrombus. Five patients survived more than 5 years after their
operations. Tumors disappeared completely in 3 patients after hepatic
arterial infusion chemotherapy with a combination of cisplatinum and
5-fluorouracil, and the longest survival period was 17 years and 11
months in a patient with EBD thrombus. CONCLUSIONS: If hepatic reserve
is satisfactory, an aggressive surgical approach combined with
chemotherapy seems to be of benefit for patients having HCC with tumor
thrombus in the MPV, IVC, or EBD.
20
UI - 11894036
AU - Regimbeau JM; Kianmanesh R; Farges O; Dondero F; Sauvanet A; Belghiti J
TI -
Extent of liver resection influences the outcome in patients with
cirrhosis and small hepatocellular carcinoma.
SO - Surgery 2002 Mar;131(3):311-7
AD - Department of Hepatobiliary and Digestive Surgery, Beaujon Hospital,
University of Paris VII, Clichy, France.
BACKGROUND: The long-term outcome after resection of hepatocellular
carcinoma (HCC) is influenced by parameters related to the tumor and the
underlying liver disease. However, the extent of the resection, which
can be limited or anatomical (including the tumor and its portal
territory), is controversial. METHODS: Among 64 Child-Pugh A patients
with cirrhosis who underwent curative liver resection for small HCC (<
or = 4 cm) between 1990 and 1996, 34 patients underwent limited
resection with a margin width of at least 1 cm, and 30 patients
underwent anatomic resection of at least 1 liver segment with complete
removal of the portal area containing the tumor. The 2 groups were
comparable in terms of epidemiologic and pathologic parameters. The
major end points were: (1) in-hospital mortality and morbidity; (2)
overall and disease-free survival; and (3) rate and topography of
recurrence. RESULTS: The 30-day mortality (6% vs 7%) and morbidity (52%
vs 47%) rates after limited and anatomic liver resection were not
statistically different. The 5- and 8-year overall survival rates after
limited versus anatomic resection were, respectively, 35% versus 54% (P
<.05) and 6% versus 45% (P <.05). The 5- and 8-year disease-free
survival rates were, respectively, 26% versus 45% and 0% versus 21% (P
<.05). Local recurrence was more frequently observed after limited
resections than after anatomic resections (50% vs 10%, P <.05).
CONCLUSIONS: In patients with cirrhosis and a small HCC, anatomic
resection achieves better disease-free survival than limited resection
without increasing the postoperative risk. Therefore, anatomical
resection should be the treatment of choice and considered as the
reference surgical treatment compared with other treatments.
21
UI - 9679583
AU - Beppu T; Ogawa M; Yamanaka T; Egami H; Ohara C; Masuda Y; Kudo S;
TI -
Kuramoto M; Doi K; Matsuda T
[Clinical evaluation of Azasetron Hydrochloride: a new selective 5-HT3
receptor antagonist--antiemetic profile and plasma concentration in
transcatheter arterial chemoembolization using CDDP for unresectable
hepatocellular carcinoma]
SO - Gan To Kagaku Ryoho 1998 Jul;25(8):1197-202
AD - Dept. of Surgery II, Kumamoto University Medical School.
We performed a clinical evaluation on the antiemetic profile and the
plasma concentration of Azasetron Hydrochloride (a new selective 5-HT3
receptor antagonist), in transcatheter arterial chemoembolization using
CDDP for unresectable hepatocellular carcinoma. Antiemetic effects were
examined in 32 patients in the serotone group (administration of
serotone 10 mg + methylprednisolone 125 mg) and in 77 patients of the
control group (administration of metoclopramide 20-30 mg +
methylprednisolone 500 mg). The response rate and the CR ratio in
serotone group was 97% and 66%, respectively. These results were
statistically higher than in the control group. Although all patients
had chronic liver diseases, no side effects and complications related to
administration of serotone were observed. The average area under the
concentration (AUC) curve of plasma serotone in five patients with liver
cirrhosis was 531 ng.h/ml, which was greater than that of a healthy
volunteer. In conclusion, serotone is a new, safe and useful antiemetic
drug in TACE therapy for hepatocellular carcinoma.
22
UI - 11408926
AU - De Ledinghen V; Monvoisin A; Neaud V; Krisa S; Payrastre B; Bedin C;
TI -
Desmouliere A; Bioulac-Sage P; Rosenbaum J
Trans-resveratrol, a grapevine-derived polyphenol, blocks hepatocyte
growth factor-induced invasion of hepatocellular carcinoma cells.
SO - Int J Oncol 2001 Jul;19(1):83-8
AD - Groupe de Recherches pour l'Etude du Foie, INSERM E9917, Universite
Victor Segalen Bordeaux 2, 33076 Bordeaux cedex, France.
We have shown that liver myofibroblasts stimulate in vitro invasion of
hepatocellular carcinoma cell lines through a hepatocyte growth
factor/urokinase-dependent mechanism. Resveratrol, a grapevine-derived
polyphenol, has been shown to inhibit cellular events associated with
tumor initiation, promotion and progression. The aim of this study was
to evaluate the effects of trans-resveratrol on invasion of the human
hepatoma cell line HepG2. Cell invasion was assessed using a Boyden
chamber assay. Activation of the HGF signal transduction pathways was
evaluated by Western blot with phospho-specific antibodies. Urokinase
expression was measured by RT-PCR and zymography. Trans-resveratrol
decreased hepatocyte growth factor-induced cell scattering and invasion.
It also decreased cell proliferation without evidence for cytotoxicity
or apoptosis. Trans-resveratrol did not decrease the level of the
hepatocyte growth factor receptor c-met and did not impede the
hepatocyte growth factor-induced increase in c-met precursor synthesis.
Moreover, trans-resveratrol did not decrease hepatocyte growth
factor-induced c-met autophosphorylation, or Akt-1 or
extracellular-regulated kinases-1 and -2 activation. Finally, it did not
decrease urokinase expression and did not block the catalytic activity
of urokinase. In conclusion, our results demonstrate that
trans-resveratrol decreases hepatocyte growth factor-induced HepG2 cell
invasion by an as yet unidentified post-receptor mechanism.
23
UI - 11926943
AU - Antonetti MC; Killelea B; Orlando R 3rd
TI -
Hand-assisted laparoscopic liver surgery.
SO - Arch Surg 2002 Apr;137(4):407-11; discussion 412
AD - Department of Surgery, Hartford Hospital and University of Connecticut
School of Medicine, Hartford, CT, USA.
HYPOTHESIS: The hand-assisted laparoscopic technique may be applied to
the treatment of liver tumors. DESIGN: A case series with mean follow-up
of 13 months. SETTING: University-affiliated tertiary care center.
PATIENTS: A total of 15 patients with hepatic neoplasms underwent
screening tests, including appropriate tumor marker analyses, abdominal
sonography, and computed tomographic scan and, in most cases, magnetic
resonance imaging to determine operability. Contraindications included
extrahepatic disease, more than 5 liver lesions, coagulopathy, and
ascites. INTERVENTION: Between March 1, 1998, and April 30, 2001, 15
patients underwent 16 hand-assisted diagnostic laparoscopic operations
to rule out extrahepatic disease. Four patients had extrahepatic
disease. In the 11 patients without evidence of extrahepatic disease,
intraoperative ultrasound was used to establish the number and location
of liver lesions. Operative strategies included resection, cryoablation,
or both. MAIN OUTCOME MEASURES: Operative time, conversion to open
procedure, length of stay, complications, and recurrence of disease.
RESULTS: Of the 15 patients with liver tumors, 6 patients had more
extensive disease than was detected by either preoperative imaging or
laparoscopic exploration They included extrahepatic disease (3),
additional liver lesion (2), or both (1). Hand-assisted management
included resection only (3), cryoablation only (5), and a combination of
the 2 (3). A total of 9 lesions were resected and 10 lesions were
cryoablated. The mean operative time was 197 minutes with a mean length
of stay of 4.5 days. There were no conversions to open procedures. One
patient experienced minor postoperative bleeding but required no
treatment. All treated patients are alive, and 5 have had recurrence of
disease. CONCLUSIONS: Hand-assisted technique can be applied safely and
effectively to laparoscopic liver surgery and may identify presence of
otherwise undetectable disease.
24
UI - 11926946
AU - Iannitti DA; Dupuy DE; Mayo-Smith WW; Murphy B
TI -
Hepatic radiofrequency ablation.
SO - Arch Surg 2002 Apr;137(4):422-6; discussion 427
AD - Department of Surgery, Brown University School of Medicine, Rhode Island
Hospital, Providence, RI, USA. Diannitti@usasurg.org
HYPOTHESIS: Hepatic radiofrequency ablation (RFA) is effective in
treating patients with unresectable hepatic malignancies. DESIGN: Case
series of 123 patients with unresectable hepatic tumors or tumors with
histological findings not traditionally treated by means of hepatic
resection were considered for hepatic RFA. Median follow-up was 20
months. SETTING: Tertiary referral center. PATIENTS: The 123 patents
underwent 168 RFA sessions from January 1, 1998, through September 30,
2001. Sixty-nine patients were male and 54, female; average age was 65
years (range, 1-89 years). Fifty-two patients had metastatic colorectal
cancer; 30, hepatocellular carcinoma; and 41, cancers with other
histological findings. INTERVENTIONS: A 200-W, cooled-tip RF probe
system was used for all cases. Probe placement and ablation were
monitored by means of real-time ultrasonography or fluoroscopic computed
tomography. Final tissue temperature of greater than 50 degrees C was
achieved in all cases. RESULTS: Initial treatment sessions were
percutaneous in 87 patients, open operations in 33, and laparoscopic in
3. Repeated sessions were percutaneous in all but 2 patients. The mean
number of lesions treated per session was 2.7 (range, 1-24). Mean tumor
size was 5.2 cm (range, 0.5-15.0 cm). One death occurred within 30 days
of a procedure. No hepatic bleeds, bile leaks, or adult respiratory
distress syndrome occurred. Overall morbidity was 7.1%. Complications
included hepatic abscesses in 4 patients, transient liver insufficiency
in 3, segmental hepatic infarcts in 2, diaphragm paralysis in 1, hepatic
artery-to-portal vein fistula in 1, and systemic hemolysis in 1.
CONCLUSIONS: Hepatic RFA is an effective treatment option for patients
with unresectable hepatic malignancies. Careful patient selection based
on tumor size, location, and number and on patient clinical status
should determine the choice of treatment. Further controlled trials are
needed to determine the effect of hepatic RFA on long-term survival.
25
UI - 11819207
AU - Pimpalwar AP; Sharif K; Ramani P; Stevens M; Grundy R; Morland B; Lloyd
TI -
C; Kelly DA; Buckles JA; de Ville De Goyet J
Strategy for hepatoblastoma management: Transplant versus nontransplant
surgery.
SO - J Pediatr Surg 2002 Feb;37(2):240-5
AD - Birmingham, England.
BACKGROUND: Liver transplantation now is proposed for managing selected
hepatoblastoma cases. Indications are not yet well defined. METHODS: The
case records of 34 children with hepatoblastoma treated over a period of
10 years (1991 to 2000) were reviewed retrospectively. RESULTS: All
patients benefited from preoperative chemotherapy. Twenty patients
underwent major hepatic resections. Twelve patients, in absence of
residual metastasis, underwent liver transplant because the tumour
remained unresectable after chemotherapy. Two patients who presented
with recurrence after a right hepatectomy, benefited from transplant as
a second option. Two other patients did not undergo surgery because of
widespread disease or resistance to chemotherapy. Disease-free survival
rates were 95% after surgical resection, 100% when primary transplant
was performed in patients with good response to chemotherapy, 60% after
transplantation in patients with poor response to chemotherapy, 50% in
patients with transplant as second option, and 0% in patients not
undergoing surgery. CONCLUSIONS: Transplantation is a potentially
curative option for unresectable hepatoblastoma when chemosensitive
(decrease in alpha-fetoprotein and decrease in tumour size). In this
context, also favourable cases with good response but difficult
resections with doubtful margins of resection may best be proposed for
primary transplantation. Patients with recurrent or resistant disease
are not good candidates.
26
UI - 11933628
AU - Biertho L; Waage A; Gagner M
TI -
[Laparoscopic hepatectomy]
SO - Ann Chir 2002 Mar;127(3):164-70
AD - Mount Sinai School of Medicine, Department of Surgery, Minimally
Invasive Surgery Center, New York, NY, USA.
AIM: To report the current indications and techniques of laparoscopic
liver resections, and assess the results of this technique by reviewing
international literature. REVIEW OF THE LITERATURE: About 200
laparoscopic hepatectomies have been reported from 1991 to 2001. 102
resections were performed for malignant tumours, and 84 for benign
tumours. Global conversion rate was 7% (13/186). Morbidity rate was
16.1% with two cases of possible gas embolisms (1.1%). Mortality rate
was 0.54% (1/186 patients). Mean hospital stay was 7.7 days. CONCLUSION:
Laparoscopic hepatectomy is feasible, with a morbidity and mortality
rate comparable to open procedures according to a careful selection of
patients. However, prospective randomized trials are still needed to
confirm those results, especially for resection of metastasis or
malignant tumors. Evolution of laparoscopic hepatectomies will probably
depend on the development of new techniques and instrumentations.
27
UI - 11037997
AU - Dancey JE; Shepherd FA; Paul K; Sniderman KW; Houle S; Gabrys J; Hendler
TI -
AL; Goin JE
Treatment of nonresectable hepatocellular carcinoma with intrahepatic
90Y-microspheres.
SO - J Nucl Med 2000 Oct;41(10):1673-81
AD - Department of Radiology, The Toronto General Hospital, University of
Toronto, Ontario, Canada.
Treatment for nonresectable hepatocellular carcinoma (HCC) is
palliative. The relatively greater arteriolar density of hepatic tumors
compared with normal liver suggests that intrahepatic arterial
administration of 90Y-microspheres can be selectively deposited in tumor
nodules and results in significantly greater radiation exposure to the
tumor than external irradiation. The purpose of this study was to
determine the proportion (frequency) and duration of response, survival,
and toxicity after intrahepatic arterial injection of 90Y-microspheres
in patients with HCC. METHODS: Patients with documented HCC, Eastern
Cooperative Oncology Group performance status 0-3, adequate bone marrow,
and hepatic and pulmonary function were eligible for study. Patients who
had significant shunting of blood to the lungs or gastrointestinal (GI)
tract or who could not undergo cannulation of the hepatic artery were
excluded. Patients received a planned dose of 100 Gy through a catheter
placed into the hepatic artery. RESULTS: Twenty-two patients were
treated with 90Y-microspheres; 20 of the treated patients (median age,
62.5 y) were evaluated for treatment efficacy. Nine patients were Okuda
stage I, and 11 were Okuda stage II. The median dose delivered was 104
Gy (range, 46-145 Gy). All 22 treated patients experienced at least 1
adverse event. Of the 31 (15%) serious adverse events, the most common
were elevations in liver enzymes and bilirubin and upper GI ulceration.
The response rate was 20%. The median duration of response was 127 wk;
the median survival was 54 wk. Multivariable analysis suggested that a
dose >104 Gy (P = 0.06), tumor-to-liver activity uptake ratio >2 (P =
0.06), and Okuda stage I (P = 0.07) were associated with longer
survival. CONCLUSION: Significantly higher doses of radiation can be
delivered to a HCC tumor by intrahepatic arterial administration of
90Y-microspheres than by external beam radiation. This treatment appears
to be beneficial in nonresectable HCC with acceptable toxicity.
28
UI - 11585877
AU - Ho S; Lau JW; Leung TW
TI -
Intrahepatic (90)Y-microspheres for hepatocellular carcinoma.
SO - J Nucl Med 2001 Oct;42(10):1587-9
29
UI - 11847576
AU - Lim HK; Han JK
TI -
Hepatocellular carcinoma: evaluation of therapeutic response to
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