OncoLink
NCI CANCERLIT® Search: Therapy of Primary Liver Cancer - September 2001
Last Modified: November 1, 2001

Table of Contents

CancerMail from the National Cancer Institute

1
UI - 21341884
AU - Chagnon S; Qanadli S; Lacombe P
TI - [Percutaneous radiofrequency ablation of liver tumors]
SO - Gastroenterol Clin Biol 2001 Apr;25(4 Suppl):B85-99
AD - Radiologie, Hopital Ambroise-Pare, 9, avenue Charles-de-Gaulle, 92104 Boulogne-Billancourt Cedex.

2
UI - 21394554
AU - Order SE; Court WS
TI - Intra-arterial cisplatin more effective than intravenous.
SO - Int J Radiat Oncol Biol Phys 2001 Aug 1;50(5):1377

3
UI - 21406455
AU - Dalla Valle R; Borie D; Hannoun L; Botta GC
TI - Surgical treatment of hepatocellular carcinoma in cirrhosis.
SO - Dig Liver Dis 2000 May;32(4):346-56
AD - Department of Surgery and Transplantation, University of Parma, Italy. r.dalval@unipr.it
Hepatocellular carcinoma is one of the most frequent forms of cancer worldwide and its diagnosis and treatment have changed substantially during the last few years. Recent advances in ultrasonography, spiral computed tomography scan and nuclear magnetic resonance have further simplified the diagnostic approach to hepatocellular carcinoma. Ultrasonography is the reference examination, giving a wide variety of information on tumour size, location, relationship with portal and hepatic veins and splanchnic haemodynamics. Surgical resection and liver transplantation can both be defined as curative treatment while other techniques such as percutaneous ethanol injection and chemoembolization must be considered as palliative. Therapeutic strategies for hepatocellular carcinoma are based upon data concerning the characteristics of the tumour the functional status of non-tumoural liver parenchyma and patients' general conditions. Surgery of hepatocellular carcinoma in cirrhotic liver is mainly restricted by lack of functional hepatic reserve and by the limited capacity of hepatic regeneration. The best surgical results are obtained in early tumoural stages which generally need limited resection. Nevertheless, major liver resections have a specific role in selected cases. Recurrence rate after surgical resection is high and is related to a large number of factors. For this reason, liver transplantation, removing at the same time, the tumour and the underlying disease, is considered, theoretically, the best treatment for hepatocellular carcinoma, but its role is still debated and limited by difficult organ sharing. Integration of present therapeutic schemes are under evaluation with promising preliminary results.

4
UI - 21410089
AU - Takayama T; Makuuchi M
TI - Ablation of hepatocellular carcinoma.
SO - Jpn J Clin Oncol 2001 Jul;31(7):297-8

5
UI - 21410094
AU - Ikeda M; Okada S; Ueno H; Okusaka T; Kuriyama H
TI - Radiofrequency ablation and percutaneous ethanol injection in patients with small hepatocellular carcinoma: a comparative study.
SO - Jpn J Clin Oncol 2001 Jul;31(7):322-6
AD - Hepatobiliary and Pancreatic Oncology Division, National Cancer Center Hospital, Tokyo, Japan.
BACKGROUND: Radiofrequency ablation (RFA) is a novel thermal ablation technique to achieve coagulative necrosis of hepatocellular carcinoma. A study was conducted to compare the antitumor effect and adverse effect of RFA with those of percutaneous ethanol injection (PEI) in patients with solitary small hepatocellular carcinoma. METHODS: The study population consisted of 119 consecutive patients with solitary hepatocellular carcinoma smaller than 3 cm in diameter. Among these, 23 patients were treated with RFA and the remaining 96 patients were treated with PEI. The antitumor effects of both treatments were assessed by contrast-enhanced computed tomography 1 month after treatment. RESULTS: Complete tumor necrosis was achieved in 23 patients (100%) of the RFA group and 90 patients (94%) of the PEI group (p = 0.48) and local recurrence rates at 1 year were 15% in the RFA group and 14% in the PEI group (p = 0.80). RFA required an average of 1.5 sessions to achieve complete necrosis, whereas PEI required an average of 4.0 sessions. As a consequence, the hospital stay in the RFA group (median 10 days) was significantly shorter than that in the PEI group (median 17 days). There were no serious adverse effects or complications except for one case of cholangitis in the PEI group, although deterioration of serum transaminase after RFA was significantly more severe than that after PEI. CONCLUSION: RFA achieved complete tumor necrosis for small hepatocellular carcinoma with fewer treatment sessions compared with PEI. There were no serious complications.

6
UI - 21193589
AU - Hussain SA; Ferry DR; El-Gazzaz G; Mirza DF; James ND; McMaster P; Kerr DJ
TI - Hepatocellular carcinoma.
SO - Ann Oncol 2001 Feb;12(2):161-72
AD - CRC Institute for Cancer Studies, University Hospital Birmingham, Edgbaston, UK.
Hepatocellular carcinoma (HCC) is the sixth most common cancer of men and eleventh most common cancer of women world-wide. However, because almost every individual who develops liver cancer dies of the disease, HCC is the third most common cause of the cancer deaths in men and seventh most common in women. The treatment of choice for hepatocellular carcinoma remains surgical resection or liver transplantation, in carefully selected cases. In patients with hepatocellular carcinoma not amenable to surgical intervention a variety of different therapeutic interventions have been investigated. These include direct ablation of the tumour using agents such as ethanol or acetic acid, transcatheter arterial chemoembolization, or systemic chemotherapy. The evaluation of their efficacy is compromised by the paucity of adequately powered randomised clinical trials. The main challenge facing the research community over the next decade is to prioritise the most promising treatments and take these forward into multicentre controlled trials. Even if these fail to improve results, they will help reduce the variation in clinical practice by eliminating anecdotal treatment.

7
UI - 21329407
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.

8
UI - 21329410
AU - Kamada K; Nakanishi T; Kitamoto M; Aikata H; Kawakami Y; Ito K; Asahara T; Kajiyama G
TI - Long-term prognosis of patients undergoing transcatheter arterial chemoembolization for unresectable hepatocellular carcinoma: comparison of cisplatin lipiodol suspension and doxorubicin hydrochloride emulsion.
SO - J Vasc Interv Radiol 2001 Jul;12(7):847-54
AD - First Department of Internal Medicine, Hiroshima University School of Medicine, Hiroshima, Japan. kkamada@mcai.med.hiroshima-u.ac.jp
PURPOSE: To evaluate long-term prognosis of transcatheter arterial chemoembolization (TACE) with use of cisplatin (CDDP) lipiodol (LPD) suspension (CDDP/LPD) compared with that with use of doxorubicin hydrochloride (ADM) LPD emulsion (ADM/LPD) in patients with unresectable hepatocellular carcinoma (HCC). MATERIALS AND METHODS: One hundred eight patients were treated with use of CDDP/LPD and 26 were treated with use of ADM/LPD. Survival rates and frequency of side effects and complications in the CDDP/LPD group were compared with those in the ADM/LPD group. RESULTS: CDDP/LPD was given at a dose of 15-70 mg (mean dose, 41 mg), whereas ADM/LPD was given at a dose of 20-100 mg (mean dose, 57 mg) throughout the study period. The survival rates in the CDDP/LPD group were 81% at 1 year, 41% at 3 years, 19% at 5 years, and 13% at 7 years, whereas those in the ADM/LPD group were 67% at 1 year, 18% at 3 years, and 0% at 5 years. The CDDP/LPD group showed significantly better survival than the ADM/LPD group (P <.05). In the CDDP/LPD group, there was a significant prolongation of survival in patients with monofocal HCC (P <.05) and patients with HCC assessed as an almost complete LPD accumulation (P <.05). There were no significant differences in survival rates in the ADM/LPD group according to tumor size and number of tumors. Hepatic failure was observed in 8% of all procedures and was not different between the two therapeutic groups. Renal dysfunction was observed in 2% of all treatments involving CDDP/LPD, and it resolved spontaneously with appropriate medications. CONCLUSIONS: TACE with use of low-dose CDDP was efficacious for unresectable HCC and had few complications. TACE with use of CDDP may contribute to prolongation of the life span of patients with HCC versus TACE with use of ADM.

9
UI - 21340754
AU - Dawson LA; Ten Haken RK; Lawrence TS
TI - Partial irradiation of the liver.
SO - Semin Radiat Oncol 2001 Jul;11(3):240-6
AD - Department of Radiation Oncology, University of Michigan, 1500 E. Medical Center Dr., Ann Arbor, MI 48109-0010, USA. dawson@umich.edu
The use of three-dimensional radiotherapy (RT) and the prospective follow-up of patients for radiation-induced liver disease (RILD) have led to a more quantitative understanding of the partial organ tolerance of the liver compared with previous estimates based on clinical judgment alone. Parameters of both the Lyman normal tissue complication probability (NTCP) model and a local damage-organ injury (D-I) NTCP model have been fit to clinical data from patients who have received hepatic radiation. Based on analyses of over 180 patients, the liver exhibits a large volume effect and a low threshold volume for RILD. Mean liver dose is associated with RILD, and no cases of RILD have been reported in patients with a mean liver dose of less than 31 Gy. Most recent estimates of the partial liver tolerance to RT suggest that if less than 25% of the normal liver is treated with RT, then there may be no upper limit on dose associated with RILD. Estimates of the liver doses associated with a 5% risk of RILD for uniform irradiation of one third, two thirds, and the whole liver are 90 Gy, 47 Gy, and 31 Gy, respectively. Copyright 2001 by W.B. Saunders Company

10
UI - 21367100
AU - Mazzolini G; Prieto J
TI - [Genetic therapy for the hepatic tumors]
SO - Medicina (B Aires) 2001;61(3):364-8

11
UI - 21402378
AU - Yamazaki H; Oi H; Matsushita M; Kim T; Tanaka E; Inoue T; Nakamura H; Teshima T; Inoue T
TI - Renal cortical retention on delayed CT and nephropathy following transcatheter arterial chemoembolisation.
SO - Br J Radiol 2001 Aug;74(884):695-700
AD - Department of Radiology, Toyonaka Municipal Hospital, 4-14-1 Shibahara, Toyonaka, Osaka 560-8565, Japan.
The aim of this study was to examine the relationship between renal cortical retention on delayed CT and contrast medium-associated and/or transarterial chemoembolisation (TACE)-associated nephropathy following TACE. The authors reviewed the findings on 180 treatments in 121 patients with normal serum creatinine levels who underwent TACE for liver tumours. Nephropathy was defined as an increase in the creatinine level of greater than 0.5 mg x dl(-1) (44 micromol x l(-1)) and greater than 25% on days 1, 3, 7 or 14 post TACE. Renal cortical retention was recognized when CT values for the renal cortex showed either mild renal cortical retention (CT value >50) or severe renal cortical retention (CT value >100). There was evidence of renal cortical retention in 81 (45%) cases and of nephropathy in 11 (6%) cases. Only 2% of patients without renal cortical retention showed nephropathy, whereas 11% of those with renal cortical retention showed nephropathy (p=0.02). Stepwise selection using a multivariate logistic regression model showed renal cortical retention and gender to be significant factors for nephropathy following TACE. In conclusion, renal cortical retention is a useful predicator for nephropathy following TACE. Delayed CT could be used not only for assessment of lipiodol retention but also for predicting nephropathy.

12
UI - 21236669
AU - Jung SE; Kim KH; Kim MY; Kim DY; Lee SC; Park KW; Kim WK
TI - Clinical characteristics and prognosis of patients with hepatoblastoma.
SO - World J Surg 2001 Feb;25(2):126-30
AD - Department of Pediatric Surgery, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-ku, Seoul 110-744, Korea.
Hepatoblastoma is a rare pediatric malignancy that frequently appears in an advanced unresectable stage. Improved resectability and survival rate have been reported with the help of neoadjuvant chemotherapy. Between January 1987 and June 1995 a series of 20 patients were managed with a diagnosis of hepatoblastoma. The median age at diagnosis was 13 months (2 months to 7 years 10 months) with a male/female ratio of 13:7. Chemotherapy effectively reduced the tumor volume (with statistical significance: p = 0.008) and was able to convert seven of nine initially unresectable tumors (78%) to resectable ones. Altogether, 14 operations were done, 12 radical and 2 palliative, with or without adjuvant chemotherapy. The whole population was followed for a median duration of 33 months; and the median survival for the whole group was 26 months. The curative resection group displayed a 5-year survival rate of 61.1%, but none in the noncurative group survived more than 13 months (p = 0.0001). In the univariate analysis for prognostic factors, large tumor size at diagnosis and the absence of thrombocytopenia were associated with poor survival, but these differences were not statistically significant. Pure fetal histology was not associated with better prognosis. In this new era of neoadjuvant chemotherapy, the optimal management strategy for hepatoblastoma is still debated, with radical surgical resection at the earliest possible time being the final goal. For now an individualized approach appears to be the protocol of choice.

13
UI - 21249656
AU - Machi J
TI - Radiofrequency ablation for multiple hepatic metastases.
SO - Ann Surg Oncol 2001 May;8(4):379-80

14
UI - 21253462
AU - Tanikawa K
TI - Chemotherapy for highly advanced hepatocellular carcinoma.
SO - J Gastroenterol Hepatol 2001 Apr;16(4):361-2

15
UI - 21253470
AU - Ikeda K; Saitoh S; Kobayashi M; Suzuki Y; Suzuki F; Tsubota A; Arase Y; Murashima N; Chayama K; Kumada H
TI - Long-term interferon therapy for 1 year or longer reduces the hepatocellular carcinogenesis rate in patients with liver cirrhosis caused by hepatitis C virus: a pilot study.
SO - J Gastroenterol Hepatol 2001 Apr;16(4):406-15
AD - Department of Gastroenterology, Toranomon Hospital and Okinaka Memorial Institute for Medical Research, Tokyo, Japan. ikedakenji@tora.email.ne.jp
BACKGROUND AND METHODS: In order to elucidate the influence of a long-term administration of interferon on the appearance rates of hepatocellular carcinoma (HCC) in hepatitis C virus (HCV)-related cirrhosis, we retrospectively analyzed 694 patients with cirrhosis. A total of 113 patients underwent interferon therapy, including 25 patients with a long-term administration of interferon for 1 year or more, and the other 581 patients received no antiviral drugs. RESULTS: Crude cumulative appearance rates of HCC in the interferon and the untreated groups were 14.1, and 28.4% at the end of the 5th year, and 36.7 and 52.5% at the end of the 10th year, respectively (P = 0.0028). As there was a waiting time between diagnosis and treatment (median 2.0 months, average 21.3 months) in the treated group, Cox proportional hazard analysis using a time-dependent covariate was introduced to evaluate the anticarcinogenic effect of interferon. Although male sex, higher alpha-fetoprotein, older age, lower albumin concentration, and lower platelet count significantly increased the carcinogenesis rate, interferon was not a significant contributing factor to the carcinogenesis rate as a whole (hazard ratio = 0.83, P= 0.32). When the patients with interferon were divided into two groups according to therapy duration, long-term interferon therapy significantly decreased the hepatocellular carcinogenesis rate after an adjustment by significant covariates (hazard ratio = 0.28, P= 0.0048). CONCLUSION: When interferon is administered for 12 months or longer, effective cancer prevention will be achieved, even in patients with HCV-related cirrhosis.

16
UI - 21253475
AU - Minata M; Nishida N; Komeda T; Azechi H; Katsuma H; Nishimura T; Kuno M; Ito T; Yamamoto Y; Ikai I; Yamaoka Y; Fukuda Y; Nakao K
TI - Postoperative detection of alpha-fetoprotein mRNA in blood as a predictor for metastatic recurrence of hepatocellular carcinoma.
SO - J Gastroenterol Hepatol 2001 Apr;16(4):445-51
AD - Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, Japan.
BACKGROUND: We tested for the presence of alpha-fetoprotein (AFP) mRNA by using nested RT-PCR in the peripheral blood of hepatocellular carcinoma (HCC) patients who had undergone curative surgery, and investigated the occurrence of intrahepatic and/or extrahepatic metastasis thereafter, to reveal the optimal timing of blood sampling for the prediction of metastatic recurrence. METHODS: Twenty-nine patients with HCC, who had been operated on were analyzed with RT-PCR at several points during the clinical course, and examined for metastatic recurrence for 3-28 months (mean = 18.7 months) after surgery. RESULTS: The presence of AFP mRNA before surgery was significantly correlated with the tumor size (P = 0.017). Metastatic recurrence was associated with the postoperative detection of AFP mRNA (P < 0.001), but not with the preoperative and/or perioperative detection. Furthermore, AFP mRNA was detected in some cases that showed low serum AFP levels at recurrence. The recurrence-free period after the detection of AFP mRNA varied from 1 to 12 months. CONCLUSIONS: The postoperative detection of AFP mRNA is useful for the prediction of metastatic recurrence, and long-term follow up with this method should be conducted.

17
UI - 21253476
AU - Ishikawa T; Ichida T; Sugitani S; Tsuboi Y; Genda T; Sugahara S; Uehara K; Inayoshi J; Yokoyama J; Ishimoto Y; Asakura H
TI - Improved survival with oral administration of enteric-coated tegafur/uracil for advanced stage IV-A hepatocellular carcinoma.
SO - J Gastroenterol Hepatol 2001 Apr;16(4):452-9
AD - Department of Internal Medicine III, Niigata University School of Medicine, Japan.
BACKGROUND AND AIMS: There is currently no proven chemotherapy regimen for hepatocellular carcinoma (HCC). The principal chemotherapeutic approach in most cases is infusion therapy into the hepatic arteries feeding the tumors. However, the clinical effects of chemotherapy are extremely poor. Therefore, in the present study, we conducted a prospective randomized trial of the efficacy of oral administration of enteric-coated tegafur/uracil for advanced HCC. METHODS: From 1994 to 1999, a total of 56 consecutive patients with unresectable stage IV-A HCC were studied prospectively to examine the efficacy of enteric-coated tegafur/uracil in HCC and to determine the significant prognostic factors. Twenty-eight patients were treated only with enteric-coated tegafur/uracil without other anticancer treatment. Another 20 patients were given conservative management only. The remaining eight patients withdrew from the study. RESULTS: In the group treated only with enteric-coated tegafur/uracil, the median survival time and 1 and 2 year survival rates were 12.13 months and 55.3 and 36.9%, respectively. In the control group, the median survival time and 1 year survival rate were 6.20 months and 5.5%, respectively. By both univariate analysis and multivariate analysis using Cox's proportional hazards model, treatment with enteric-coated tegafur/uracil was shown to be the factor most significantly favoring a better prognosis. CONCLUSIONS: Although the prognosis of most patients with stage IV-A HCC is poor, administration of enteric-coated tegafur/uracil induces long-term survival and is an effective treatment for stage IV-A HCC.

18
UI - 21253477
AU - Shiraga K; Sakaguchi K; Senoh T; Ohta T; Ogawa S; Sawayama T; Mouri H; Fujiwara A; Tsuji T
TI - Modulation of doxorubicin sensitivity by cyclosporine A in hepatocellular carcinoma cells and their doxorubicin-resistant sublines.
SO - J Gastroenterol Hepatol 2001 Apr;16(4):460-6
AD - First Department of Internal Medicine, Okayama University Medical School, Japan.
BACKGROUND AND AIMS: Cyclosporine A (Cys) and verapamil (Ver) sensitize multidrug-resistant (MDR) cells to various anticancer drugs by interacting with membrane glycoproteins involved in the drug efflux. In the present study, we assessed the effect of Cys on the modulation of doxorubicin (DOR) sensitivity in hepatocellular carcinoma (HCC) cell lines, and their DOR-resistant sublines. METHODS: The sensitivity to DOR and the chemosensitizing effects of Cys were assessed by using two human HCC cell lines, PLC/PRF/5 and Hep-3B, and their DOR-resistant sublines, PLC/DOR and 3B/DOR. The expression of multidrug resistance 1 (MDR1) and multidrug resistance-associated protein (MRP) mRNA in these cells were detected by using a RT-PCR. The HCC cell lines grown in individual wells of 24-well plates were incubated with DOR that were sequentially diluted in culture medium in combination with 5 micromol/L Cys for 24 h. The cell viability in each well was measured by using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. RESULTS: The mRNA of MDR1 and that of MRP were readily detectable in the HCC cell lines by RT-PCR. When 5 micromol/L Cys was added to the culture, the 50% inhibiting concentration (IC50) of DOR was reduced from 0.93 +/- 0.29 microg/mL to 0.32 +/- 0.10 microg/mL in PLC/PRF/5, and from 0.25 +/- 0.07 microg/mL to 0.09 +/- 0.04 microg/mL in Hep-3B. Furthermore, in the presence of 5 micromol/L Cys, the IC50 of DOR was reduced from 48.63 +/- 17.04 microg/mL to 0.49 +/- 0.14 microg/mL in PLC/DOR, and from 4.60 +/- 1.22 microg/mL to 0.15 +/- 0.06 microg/mL in 3B/DOR. The amounts of PCR products of MDR1 mRNA in PLC/DOR and 3B/DOR were greater than those in PLC/PRF/5 and Hep-3B, respectively. CONCLUSIONS: In HCC, the amplification of MDR1 mRNA is probably the main mechanism underlying acquired DOR resistance. Cyclosporine is also indicated to be highly active in potentiating the anticancer activity of DOR in HCC cells and their DOR-resistant sublines.

19
UI - 21390938
AU - Zhao H; Wu X; Liu Z
TI - Effect of Gan Fu Le on 24 cases of primary hepatocarcinoma.
SO - J Tradit Chin Med 2001 Jun;21(2):134-5
AD - Shangdong Provincial Hospital, Ji'nan, Shandong Province 250021.

20
UI - 21417317
AU - Krohne TU; Shankara S; Geissler M; Roberts BL; Wands JR; Blum HE; Mohr L
TI - Mechanisms of cell death induced by suicide genes encoding purine nucleoside phosphorylase and thymidine kinase in human hepatocellular carcinoma cells in vitro.
SO - Hepatology 2001 Sep;34(3):511-8
AD - Department of Medicine II, University Hospital Freiburg, Germany.
For gene therapy of hepatocellular carcinoma (HCC), the Escherichia coli purine nucleoside phosphorylase (PNP)/fludarabine suicide gene system may be more useful than the herpes simplex virus thymidine kinase/ganciclovir (HSV-tk/GCV) system as a result of a stronger bystander effect. To analyze the molecular mechanisms involved in PNP/fludarabine-mediated cell death in human HCC cells in comparison with HSV-tk/GCV, we transduced human HCC cells of the cell lines, HepG2 and Hep3B, with PNP or HSV-tk using adenoviral vectors, followed by prodrug incubation. Both systems predominantly induced apoptosis in HepG2 and Hep3B cells. PNP/fludarabine induced strong p53 accumulation and a more rapid onset of apoptosis in p53-positive HepG2 cells as compared with p53-negative Hep3B cells, but efficiency of tumor cell killing was similar in both cell lines. In contrast, HSV-tk/GCV-induced apoptosis was reduced in p53-negative Hep3B cells as compared with p53-positive HepG2 cells. HSV-tk/GCV, but not PNP/fludarabine, caused up-regulation of Fas in p53-positive HepG2 cells and of Fas ligand (FasL) in both HCC cell lines. These results demonstrate cell line-specific differences in response to treatment with PNP/fludarabine and HSV-tk/GCV, respectively, and indicate that PNP/fludarabine may be superior to HSV-tk/GCV for the treatment of human HCC because of its independence from p53 and the Fas/FasL system.

21
UI - 21423151
AU - Salizzoni M; Zamboni F; Lupo F; Franchello A; David E; Rizzetto M
TI - Liver transplantation for early-detected, multifocal hepatocellular carcinoma.
SO - Br J Surg 2001 Sep;88(9):1194-5
AD - Liver Transplantation Centre, San Giovanni Battista Hospital, University of Torino, Turin, Italy.

22
UI - 21424060
AU - Liu CL; Fan ST; Lo CM; Tso WK; Poon RT; Lam CM; Wong J
TI - Management of spontaneous rupture of hepatocellular carcinoma: single-center experience.
SO - J Clin Oncol 2001 Sep 1;19(17):3725-32
AD - Center for the Study of Liver Disease, University of Hong Kong Medical Center, Queen Mary Hospital, Hong Kong, China.
PURPOSE: To report the management of patients with spontaneous rupture of hepatocellular carcinoma (HCC) in a single center over a 10-year period and to evaluate a two-stage therapeutic approach. PATIENTS AND METHODS: A retrospective study was performed on all 1,716 patients with HCC who presented from 1989 to 1998. The two-stage therapeutic approach to manage ruptured HCC consisted of initial management by conservative method, hemostasis by transarterial embolization (TAE) or surgical means, followed by second-stage hepatic resection or transarterial oily chemoembolization (TOCE). Results of definitive treatment were compared with patients with no history of rupture during the same study period. RESULTS: During the study period, 154 patients (9%) had spontaneous HCC rupture. Initial intervention to control bleeding included TAE in 42 patients, surgical hemostasis in 35 patients, and conservative management only in 53 patients. The 30-day mortality rate was 38%. Independent factors on presentation affecting 30-day mortality were shock on admission, hemoglobin, serum total bilirubin, and known diagnosis of inoperable tumor. After initial stabilization and clinical evaluation, 33 patients underwent hepatic resection and 30 patients received TOCE. Median survival of the hepatectomy patients was 25.7 months; that of the TOCE patients was 9.7 months. Compared with patients with no rupture, survival after hepatectomy (25.7 months v 49.2 months, P =.003) was inferior but still substantially long, whereas survival after TOCE was comparable (9.7 months v 8.7 months, P =.904). CONCLUSION: Early mortality of spontaneous rupture of HCC was dependent on prerupture disease state, liver function, and severity of bleeding. Although it was a catastrophic presentation, prolonged survival could be achieved in selected patients with second-stage hepatic resection or TOCE.

23
UI - 20218308
AU - Sugawara Y; Yamamoto J; Shimada K; Yamasaki S; Kosuge T; Takayama T; Makuuchi M
TI - Splenectomy in patients with hepatocellular carcinoma and hypersplenism.
SO - J Am Coll Surg 2000 Apr;190(4):446-50
AD - Department of Hepatobiliary Pancreatic Surgery, National Cancer Center Hospital, Tokyo, Japan.
BACKGROUND: Hypersplenism secondary to portal hypertension is common in hepatocellular carcinoma (HCC), but surgeons still face the unresolved problem of how to manage HCC patients with hypersplenism. STUDY DESIGN: The records of 48 patients with HCC and hypersplenism were retrospectively examined and postoperative changes in platelet counts, serum total bilirubin levels, and dinical staging scores were analyzed to evaluate the clinical value of combined splenectomy and liver resection. Hepatectomy and splenectomy were performed as a two-stage operation in 13 patients and synchronously in 35. RESULTS: Postoperative platelet counts were significantly increased, and serum total bilirubin levels were significantly decreased. Clinical staging scores were also reduced after splenectomy in patients who underwent splenectomy before hepatectomy. CONCLUSIONS: Synchronous or metachronous splenectomy can increase the safety of hepatectomy in selected patients with HCC by reducing both the likelihood of bleeding complications and bilirubin overload.

24
UI - 20443318
AU - Hanazaki K; Kajikawa S; Adachi W; Amano J
TI - Portal vein thrombosis may be a fatal complication after synchronous splenectomy in patients with hepatocellular carcinoma and hypersplenism.
SO - J Am Coll Surg 2000 Sep;191(3):341-2

25
UI - 20564938
AU - Stringer MD
TI - Liver tumors.
SO - Semin Pediatr Surg 2000 Nov;9(4):196-208
AD - Children's Liver Centre, St James University Hospital, Leeds, UK.
Liver tumors in children are rare, potentially complex, and encompass a broad spectrum of disease processes. Any age group may be affected, including the fetus. Most present with abdominal distension and/or a mass. Accurate preoperative diagnosis is usually possible using a combination of ultrasound scanning and cross-sectional imaging techniques (CT and/or MR), supplemented by liver biopsy and measurement of tumor markers. The most common benign tumors are hemangiomas, but mesenchymal hamartoma, focal nodular hyperplasia, and adenoma also are found. In Western countries, hepatoblastoma is the most common primary malignant liver tumor; disease-free survival is now possible in more than 80% of affected patients because of advances in combination chemotherapy, improved techniques of surgical resection, and the selective use of liver transplantation. In contrast, there has been less progress in the management of hepatocellular cancer, which still poses many therapeutic challenges. Copyright 2000 by W.B. Saunders Company

26
UI - 21234301
AU - Noie T; Sugawara Y; Harihara Y; Takayama T; Kubota K; Ohashi Y; Makuuchi M
TI - Kinetics of urinary trypsin inhibitor in patients undergoing partial hepatectomy.
SO - Scand J Gastroenterol 2001 Apr;36(4):410-6
AD - Dept. of Surgery, Graduate School of Medicine, University of Tokyo, Japan.
BACKGROUND: The kinetics and role of urinary trypsin inhibitor (UTI) in liver surgery are unclear. We investigated the effects of preoperative liver function and the extent of liver resection on postoperative UTI synthesis in the liver after partial hepatectomy. METHODS: Sixty-one consecutive patients who underwent liver resection were the subjects of the study. Plasma and urine UTI, plasma C reactive protein (CRP) and plasma and urine creatinine were measured perioperatively. RESULTS: Although the average plasma UTI level did not change significantly, the average urine UTI level per day showed a change similar to that of the average plasma CRP level, reaching a maximum of approximately eight times the preoperative level on the second postoperative day (86,610 +/- 53,109 U/day). The maximum postoperative increase in urine UTI excretion per day (delta-uUTImax) correlated significantly with the maximum increase in CRP and the increase in creatinine clearance. Multiple regression analysis revealed that delta-uUTImax was significantly and positively correlated with the indocyanine green plasma disappearance rate and operation duration, and negatively correlated with the resection rate. CONCLUSIONS: The postoperative urine UTI level may reflect preoperative liver function and the extent of liver resection after partial hepatectomy.

27
UI - 21243578
AU - Kao CH; Tsai SC; Wang JJ; Ho YJ; Ho ST
TI - Evaluation of hepatobiliary function by hepatobiliary scintigraphy in hepatoma patients after transcatheter arterial embolization.
SO - Scand J Gastroenterol 2001 May;36(5):553-7
AD - Dept. of Nuclear Medicine, Taichung Veterans General Hospital, Taiwan. kaoch@vghtc.vghtc.gov.tw
BACKGROUND: Transcatheter arterial embolization (TAE) is the treatment of choice for inoperable hepatocellular carcinoma. However, altered and impaired gallbladder function due to gallbladder infarction and bile duct necrosis following TAE have been reported. METHODS: Hepatobiliary function was evaluated using quantitative Tc-99m DISIDA hepatobiliary scintigraphy in 40 hepatoma patients before and after TAE. The patients were separated into two groups: group 1 (20 patients), who received pre-cystic artery TAE, and group 2 (also 20 patients), who received post-cystic artery TAE. RESULTS: After TAE, there were no significant changes in liver or bile duct function in the patients of either group. However, for group I patients, significantly decreased gallbladder function was found after TAE. CONCLUSIONS: Altered and impaired gallbladder function is common in hepatoma patients who receive pre-cystic artery TAE, and Tc-99m DISIDA cholescintigraphy may be useful for evaluating hepatobiliary function in hepatoma patients who receive TAE.

28
UI - 21333693
AU - Ohtani Y; Tanaka Y; Makuuchi H
TI - [Pre and post operative nutritional management for the patients with hepatoma]
SO - Nippon Rinsho 2001 May;59 Suppl 5():597-600
AD - Department of Surgery, School of Medicine, Tokai University.

29
UI - 21340483
AU - Miyakawa Y; Iino S
TI - Toward prevention of hepatocellular carcinoma developing in chronic hepatitis C.
SO - J Gastroenterol Hepatol 2001 Jul;16(7):711-4

30
UI - 21354003
AU - Herrero JI; Sangro B; Quiroga J; Pardo F; Herraiz M; Cienfuegos JA; Prieto J
TI - Influence of tumor characteristics on the outcome of liver transplantation among patients with liver cirrhosis and hepatocellular carcinoma.
SO - Liver Transpl 2001 Jul;7(7):631-6
AD - Liver Unit, Clinica Universitaria, Pamplona, Spain. iherrero@unav.es
Hepatocellular carcinoma (HCC) may recur after liver transplantation (LT), mainly in patients with multinodular and large tumors. However, factors predictive of outcome after LT in patients with small tumors remain ill defined. We investigated which factors were related to mortality or tumor recurrence among 47 liver transplant recipients with liver cirrhosis and HCC and compared them with 107 patients with liver cirrhosis without tumor who underwent LT in the same period. Patients with HCC were older (P <.001), more frequently had cirrhosis of a viral origin (P <.001), and had lower Child-Pugh scores (P <.001) than patients without tumor. Survival of patients with and without tumor was not significantly different (P =.20). Among patients with HCC, those with lower recurrence-free survival rates had liver cirrhosis of a viral origin, vascular invasion, bilobar disease, and tumor-node-metastasis (TNM) stage IV. At multivariate analysis, the only factor associated with mortality or recurrence was TNM stage IV (P =.02). Our results suggest that in patients with HCC and TNM stage IV, LT might be contraindicated.

31
UI - 21369493
AU - Zhao J; Wang H; Wei L; Habib NA; Lu X; Wu M; Guo Y
TI - The cytotoxic effect of E1B 55-kDa mutant adenovirus on human hepatocellular carcinoma cell lines.
SO - Cancer Gene Ther 2001 May;8(5):333-41
AD - International Cancer Institute and Eastern Hospital of Hepatobiliary Surgery, the Second Military Medical University, Shanghai 200433, People's Republic of China.
It has been suggested the E1B 55 kDa mutant adenovirus dl1520 can selectively kill p53-deficient human tumor cells. In this study, we examined the cytotoxic effect of dl1520 on nine human hepatocellular carcinoma (HCC) cell lines with different p53 genetic and functional status. The results showed that HCC cell lines with deleted or mutant p53 gene and reduced p53 transcriptional activities were more susceptible to dl1520-induced cytolysis. Hep3B (p53-null) and HepG2 (p53-wt) cells were arrested at G2/M phase when cytolysis occurred. Cyclin-dependent kinase inhibitor (CDKI) p21(Waf-1/Cip-1) was downregulated 24 hours after dl1520 infection in HepG2 cells and increased when cytolysis occurred. No p21 expression was detected in Hep3B cells. DNA fragmentation was found in both Hep3B and HepG2 cells after dl1520 infection. Bax expression increased in dl1520-infected HepG2 cells but not in Hep3B cells. Notably, three Bax-like proteins, molecular mass around 40 to 80 kDa, accumulated 48 hours after adenovirus infection in Hep3B cells but not in HepG2 cells. These results suggest that the susceptibility of HCC cells to dl1520-induced cytolysis is related to both p53 genotype and functional status, and is mediated by both cell cycle disturbance and apoptosis.

32
UI - 21392101
AU - Levy AE; Kowdley KV
TI - Unresectable hepatocellular carcinoma: the need for an individualized multidisciplinary approach.
SO - J Clin Gastroenterol 2001 Sep;33(3):180-2

33
UI - 21421064
AU - Terkivatan T; de Wilt JH; de Man RA; van Rijn RR; Zondervan PE; Tilanus HW; IJzermans JN
TI - Indications and long-term outcome of treatment for benign hepatic tumors: a critical appraisal.
SO - Arch Surg 2001 Sep;136(9):1033-8
AD - Department of Surgery, University Hospital Rotterdam-Dijkzigt, Dr Molewaterplein 40, 3015 GD Rotterdam, the Netherlands. ijzermans@hlkd.azr.nl
HYPOTHESIS: The natural history and clinical behavior of benign hepatic tumors during long-term follow-up may not justify primary surgical treatment. DESIGN: Retrospective study. SETTING: Tertiary referral center. PATIENTS: Two hundred eight patients diagnosed as having a benign liver tumor between January 1, 1979, and December 31, 1999. INTERVENTION: Seventy-four patients underwent hepatic surgery and 134 were managed conservatively by radiological follow-up. MAIN OUTCOME MEASURES: Symptoms and complications were assessed during management and follow-up. RESULTS: In the surgically treated population, the liver lesion was symptomatic in 47 patients (64%) and an incidental finding in 27 (36%). The operative morbidity and mortality were 27% (20 of 74 patients) and 3% (2 of 74 patients), respectively. Overall, 28 (80%) of 35 patients with complaints were asymptomatic after surgery. During observation of the tumor in the conservatively managed group, 39 (87%) of 45 patients who presented with complaints were asymptomatic during a mean follow-up of 45 months; 6 patients had mild abdominal pain considered to be unrelated to the tumor. CONCLUSIONS: Conservative management of solid benign liver lesions such as focal nodular hyperplasia and hemangioma can be performed safely, irrespective of their size. We only advise surgery for liver lesions when there is an inability to exclude malignancy or in the case of severe complaints related to the tumor. Resection is always advocated in the case of a large hepatocellular adenoma (>5 cm) to reduce the risk of rupture and malignant degeneration.

34
UI - 21429799
AU - Shaked A; Lucey MR
TI - Transplantation of liver grafts from living donors into adults.
SO - N Engl J Med 2001 Sep 20;345(12):923-4

About OncoLink  Contact OncoLink  Privacy statement   Disclaimer  Link to OncoLink  Home
For assistance please visit our HELP section
© Trustees of the University of Pennsylvania