National Cancer Institute®
Last Modified: August 1, 2002
UI - 10430248
AU - Stuart K; Tessitore J; Rudy J; Clendennin N; Johnston A
TI - A Phase II trial of nolatrexed dihydrochloride in patients with advanced hepatocellular carcinoma.
SO - Cancer 1999 Aug 1;86(3):410-4
AD - Boston Center for Liver Cancer, Beth Israel Deaconess Medical Center, Harvard Medical School, Massachusetts 02215, USA.
BACKGROUND: Inoperable hepatocellular carcinoma is an incurable malignancy with no accepted standard therapy. Chemotherapy has demonstrated occasional responses and the need is great for a new and effective agent. Therefore the authors conducted this Phase II trial of a novel thymidylate synthase inhibitor, nolatrexed dihydrochloride (designed using structure-based computer modeling), in patients with advanced hepatocellular carcinoma. METHODS: Forty-one patients with unresectable or metastatic hepatocellular carcinoma were treated with nolatrexed, which was administered as a 24-hour outpatient intravenous infusion for 5 days at a dose of 795 mg/m2/day as free base (1000 mg/m2/day as salt) during each 21-day cycle. Prophylactic treatment was given for emesis and rash. RESULTS: Twenty-eight patients received at least 2 courses of treatment and 26 patients were evaluable. Two patients (8%) achieved a partial response and 2 additional patients achieved a minor response that was significant enough to allow surgical resection with curative intent. Fourteen patients (54%) achieved stable disease. The overall median survival was 7 months (10 months among patients who completed 2 cycles) and 1 patient remained free of disease at last follow-up, 37 months after surgery. Toxicity was modest and generally was comprised of stomatitis, nausea, malaise, and rash. CONCLUSIONS: Nolatrexed appears to have modest biologic activity in hepatocellular carcinoma. Due to the lack of alternative treatments, further study of this drug or an oral equivalent may be warranted.
UI - 10447578
AU - Mok TS; Leung TW; Lee SD; Chao Y; Chan AT; Huang A; Lui MC; Yeo W; Chak
TI - K; Johnston A; Johnson P A multi-centre randomized phase II study of nolatrexed versus doxorubicin in treatment of Chinese patients with advanced hepatocellular carcinoma.
SO - Cancer Chemother Pharmacol 1999;44(4):307-11
AD - Department of Clinical Oncology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong, China. firstname.lastname@example.org
PURPOSE: A multi-centre randomized phase II study of single agent nolatrexed dihydrochloride versus doxorubicin was undertaken in Chinese patients with advanced hepatocellular carcinoma (HCC) to study and compare the clinical efficacy of the two drugs. METHODS: Fifty-four patients with clinical or histological diagnosis of HCC were randomized in a 2:1 ratio to receive nolatrexed or doxorubicin. Nolatrexed 725 mg/m(2)/day was given by continuous infusion via a central venous device for 5 days and doxorubicin 60 mg/m(2) was given as a rapid intravenous infusion every 3 weeks. RESULTS: No objective responses were observed in either treatment arm. Two patients in the nolatrexed arm and none in the doxorubicin arm had >50% decline in serum alpha-fetoprotein. The median survival for the patients in the nolatrexed and doxorubicin arms was 139 days and 104 days, respectively. Moderate toxicities including leukopenia, thrombocytopenia, mucositis and skin rash were observed in both treatment arms. CONCLUSION: Nolatrexed and doxorubicin are minimally active in the treatment of advanced HCC. Given the small sample size, no difference is observed between the two drugs.
UI - 12046075
AU - Tian G; Yu JP; Luo HS; Yu BP; Yue H; Li JY; Mei Q
TI - Effect of nimesulide on proliferation and apoptosis of human hepatoma SMMC-7721 cells.
SO - World J Gastroenterol 2002 Jun;8(3):483-7
AD - Gastroenterology department. Renmin hospital of Wuhan university, 238 Jie-fang Road,Wuhan 430060,Hubei Province,China.
AIM: Cyclooxygenase-2 (COX-2) has been suggested to be associated with carcinogenesis. We sought to investigate the effect of the selective COX-2 inhibitor, Nimesulide on proliferation and apoptosis of SMMC-7721 human hepatoma cells.METHODS: This study was carried out on the culture of hepatic carcinoma SMMC-7721 cell line. Various concentrations of Nimesulide (0, 200 micromol/L, 300 micromol/L, 400 micromol/L) were added and incubated. Cell proliferation was detected with MTT colorimetric assay, cell apoptosis by electron microscopy, flow cytometry and TUNEL.RESULTS: Nimesulide could significantly inhibit SMMC-7721 cells proliferation dose-dependent and in a dependent manner compared with that of the control group. The duration lowest inhibition rate produced by Nimesulide in SMMC-7721 cells was 19.06%, the highest inhibition rate was 58.49%. After incubation with Nimesulide for 72 h, the most highest apoptosis rate and apoptosis index of SMMC-7721 cells comparing with those of the control were 21.20%+/-1.62% vs 2.24%+/-0.26% and 21.23+/-1.78 vs 2.01+/-0.23 (P<0.05). CONCLUSION:The selective COX-2 inhibitor, Nimesulide can inhibit the proliferation of SMMC-7721 cells and increase apoptosis rate and apoptosis index of SMMC-7721 cells. The apoptosis rate and the apoptosis index are dose-dependent. Under electron microscope SMMC-7721 cells incubated with 300 micromol and 400 micromol Nimesulide show apoptotic characteristics. With the clarification of the mechanism of selective COX-2 inhibitors, These COX-2 selective inhibitors can become the choice of prevention and treatment of cancers.
UI - 12115564
AU - Chen YN; Chen JC; Yin SC; Wang GS; Tsauer W; Hsu SF; Hsu SL
TI - Effector mechanisms of norcantharidin-induced mitotic arrest and apoptosis in human hepatoma cells.
SO - Int J Cancer 2002 Jul 10;100(2):158-65
AD - School of Chinese Medicine, China Medical College, Taichung, Taiwan.
NCTD is a demethylated form of cantharidin with antitumor properties, which is now in use as a routine anticancer drug against hepatoma. However, there is limited information on the effect of NCTD on human cancer cells. In the present study, NCTD inhibited proliferation, caused mitotic arrest, then progressed to apoptosis within 96 hr in 3 human hepatoma cell lines: HepG2, Hep3B and Huh-7. NCTD treatment (5 microg/ml) enhanced the expression of Cdc25C and p21(Cip1/Waf1), increasing the phosphorylation of these 2 proteins. In addition, NCTD treatment induced an earlier increase in cyclin B1-associated histone H1 kinase activity within 48 hr, but an approximately 70% reduction of both protein level and kinase activity of cyclin B1 was observed at 72 hr. Treatment with NCTD significantly decreased the expression of p53 protein but did not affect the expression of Cdk1 and p27(Kip1). Moreover, NCTD treatment also increased the phosphorylation of Bcl-2 and Bcl-X(L) but did not affect the expression of Bax or Bad. Bcl-2 phosphorylation appears to inhibit its binding to Bax since less Bax was detected in immunocomplex with Bcl-2 in NCTD-treated HepG2 cells. In addition, NCTD treatment caused activation of caspase-9 and caspase-3, preceding DNA fragmentation and morphologic features of apoptosis. Pretreatment with the broad-spectrum caspase inhibitor z-VAD-fmk markedly inhibited NCTD-induced caspase-3 activity and cell death. These results suggest that phosphorylation of p21(Cip1/Waf1) and Cdc25C and biphasic regulation of cyclin B1-associated kinase activity may contribute to NCTD-induced M-phase cell-cycle arrest. Furthermore, the increase of p21(Cip1/Waf1), phosphorylation of Bcl-2 and Bcl-X(L), activation of caspase-9 and caspase-3 may be the molecular mechanism through which NCTD induces apoptosis. Copyright 2002 Wiley-Liss, Inc.
UI - 11798803
AU - Cheng J; Leng X; Peng J
TI - [Construction of a hepatoma-targeting vector of adeno-associated virus containing human alpha-fetoprotein promoter and wild p53 gene in gene therapy of liver cancer]
SO - Zhonghua Yi Xue Za Zhi 2000 Jun;80(6):461-3
AD - Department of Surgery, People's Hospital, Beijng Medical University, Beijing 100044, China.
OBJECTIVE: To construct plasmids that express target genes in hepatoma cell line using adeno-associated virus (AAV) vectors containing human AFP promoter. METHODS: Primers containing specific enzyme-cutting sites were designed to amplify the alpha-fetoprotein promoter (AFP promoter) from human genome. The promoter was cloned into pTR-UF5, a plasmid containing GFP reporter gene, resulting in the recombinant AAV plasmid containing the reporter gene (rAAV-AFP-GFP). Blunted ligation was used to construct the recombinant AAV vector plasmid containing human wild p53 gene (rAAV-AFP-53). The plasmid rAAV-AFP-GFP was used to transfect the AFP-expressing Hep G(2) and non-AFP-expressing 293 cell lines, respectively, to measure the function of the cloned AFP promoter. Flow cytometry was used to measure the effect of rAAV-AFP-53 on hepatoma cell line HLE. RESULTS: rAAV-AFP-53 and rAAV-AFP-GFP were verified by DNA sequencing and enzyme digestion to carry human AFP promoter. Cell transfection of rAAV-AFP-GFP showed selective expression in AFP-positive hepatoma cell lines with a transfection rate of 36.5%; rAAV-AFP-53 induced apoptosis rate was 73.88%. CONCLUSION: Two adeno-associated virus plasmids are successfully constructed that carry p53 gene and reporter gene, respectively, guided by AFP promoter. The former one shows a hepatoma-specific apoptosis-inducing effect.
UI - 11937079
AU - Popat A; Shear NH; Malkiewicz I; Thomson S; Neuman MG
TI - Mechanism of Impila (Callilepis laureola)-induced cytotoxicity in Hep G2 cells.
SO - Clin Biochem 2002 Feb;35(1):57-64
AD - Division of Clinical Pharmacology, Sunnybrook and Women's College Health Sciences Centre, Toronto, Ontario, Canada.
OBJECTIVES: To determine the mechanism(s) of Impila (Callilepis laureola)-induced toxicity in human hepatoblastoma Hep G2 cells in vitro and the possible prevention of this toxicity by N-acetylcysteine (NAC). DESIGN AND METHODS: Cells were treated with an aqueous extract of Impila (10 mg/mL) for up to 24 h. NAC (5 mM) was administered either concomitantly with Impila or one hour post Impila treatment. Cytotoxicity was quantitated spectrophotometrically by the metabolism of the tetrazolium dye MTT. Total glutathione (GSH) was measured using the Tietze assay. RESULTS: Impila produced cytotoxicity and depleted GSH in a concentration- and time-dependent manner. A significant depletion in GSH was observed after 15 min (p < 0.0001 vs. control), whereas significant cytotoxicity was only observed after at least 3 h (p < 0.0001 vs. control). Both concomitant and posttreatment with NAC prevented Impila-induced GSH depletion and resulted in a significant decrease in Impila-induced cytotoxicity (p < 0.001 vs. NAC-untreated cells). CONCLUSION: Our results suggest the mechanism of Impila-induced cytotoxicity in Hep G2 cells in vitro involves depletion of cellular GSH. Preventing GSH depletion by supplementing cells with NAC reduces cytotoxicity.
UI - 12087720
AU - Khlebnikov EP; Elagina LV; Vishnevskii VA; Kybyshkin VA; Izotova GN;
TI - Pavlova MV; Ikramov RZ [Perioperative management of focal liver diseases by ofloxacin]
SO - Antibiot Khimioter 2002;47(2):24-8
AD - A.V. Vishnevsky Institute of Surgery, Russian Academy of Medical Sciences, Moscow.
Perioperative use of ofloxacin for prophylaxis was investigated in 20 patients with focal hepatic formations (hemangioma, adenocarcinoma, echinococcosis). First dose of ofloxacin (200 mg) was given intravenously 15 min before operation. After operation ofloxacin was used intravenously (400 mg daily) for 5 days. Pharmacokinetic investigation demonstrated that perioperative intravenous use of ofloxacin provided concentrations in blood and hepatic tissue satisfactory for potential microflore inhibition. Immunological monitoring demonstrated positive dynamics on 5-7 days after operation. dynamics depended on nosology of the focal hepatic formation. Ofloxacin use for prophylaxis in the operated patients with focal hepatic formations was efficient for profilaxy of postoperation infective complications.
UI - 12133355
AU - Liang L; Li S; Huang J
TI - [The protective effect and mechanism of ischemic preconditioning for hepatic resection under hepatic blood inflow occlusion in hepatocellular carcinoma patients with cirrhosis]
SO - Zhonghua Wai Ke Za Zhi 2002 Apr;40(4):265-7
AD - Department of Hepatobiliary Surgery, First Affiliated Hospital, Sun Yet-sen University of Medical Sciences, Guangzhou 510080, China.
OBJECTIVE: To investigate the protective effect of ischemic preconditioning (IPC) for hepatic resection under hepatic blood inflow occlusion (HBIO) in hepatocellular carcinoma patients with cirrhosis and its possible mechanism. METHODS: 29 consecutive patients resectable HCC were randomized into two groups. IPC group: before HBIO, IPC with 5 min of ischemia and 5 min of reperfusion was given; control group: simple HBIO. The liver function, hepatic caspase-3 activity, and apoptotic cell were compared between the two groups. RESULTS: The AST, ALT levels of POD 1, POD 3 and POD 7 in the IPC group were significantly higher than those of the control group, respectively (t = 4.238, P < 0.05). The TBIL levels of POD 3 and POD 7 in the IPC group were significantly higher than those of the control group, respectively (t = 2.296, P < 0.05). The ALB of POD 1 in the IPC group was higher than in the control group (t = 2.029, P > 0.05). After 1 h of reperfusion, the hepatic caspase-3 activity and apoptotic sinusoidal endothelial cell were significantly higher than those of in the control group (t = 2.349, P < 0.05). CONCLUSIONS: IPC has the a protective effect in hepatic resection under HBIO in HCC patients with cirrhosis. Its mechanism is that sinusoidal endothelial cell apoptosis is inhibited by inhibiting caspase-3 activity.
UI - 12133356
AU - Wang Y; Chen H; Wu M; Jian X; Wei G; Sun Y
TI - [Resection of right or total hepatic caudate lobe including paracaval portion]
SO - Zhonghua Wai Ke Za Zhi 2002 Apr;40(4):268-70
AD - Eastern Hepatobiliary Hospital, Second Military Medical University, Shanghai 200438, China.
OBJECTIVES: To evaluate the surgical techniques and feasibility for resecting the hepatic caudate lobe including the paracaval portion. METHODS: Right posterior approach for right caudate lobectomy and left lateral approach for total caudate lobectomy were taken with or without some kinds of preparatory segmentectomies. RESULTS: Seven right and 6 total caudate lobectomies, all including paracaval portion, ware accomplished without operative death. The mean intraoperative blood loss was 896.15 (250 - 2 000) ml and the mean portal triad clamping time was 25.4 (10 - 83) min. The postoperative course was uneventful for all the cases, and the mean hospital stay was 12 (9 - 22) days. CONCLUSIONS: Although being complicated anatomically, resection of the hepatic caudate lobe including the paracaval portion is feasible with a high safety.
UI - 11909699
AU - Sekhar KR; Spitz DR; Harris S; Nguyen TT; Meredith MJ; Holt JT; Guis D;
TI - Marnett LJ; Summar ML; Freeman ML Redox-sensitive interaction between KIAA0132 and Nrf2 mediates indomethacin-induced expression of gamma-glutamylcysteine synthetase.
SO - Free Radic Biol Med 2002 Apr 1;32(7):650-62
AD - Dept of Radiation Oncology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Exposure of HepG2 cells to nonsteroidal anti-inflammatory drugs (i.e., indomethacin and ibuprofen; NSAIDs) as well as resveratrol, caused increased expression of the mRNAs coding for the catalytic (Gclc) and modifier (Gclm) subunits of the glutathione synthetic enzyme, gamma-glutamylcysteine synthetase. In addition, indomethacin exposure increased intracellular glutathione content as well as inhibited glutathione depletion and cytotoxicity caused by diethyl maleate. Indomethacin-induced increases in the expression of gamma-glutamylcysteine synthetase mRNA were preceded by increases in steady state levels of intracellular pro-oxidants and glutathione disulfide accumulation. Simultaneous incubation with the thiol antioxidant N-acetylcysteine (NAC) inhibited indomethacin-mediated increases in GCLC mRNA, suggesting that increases in GCLC message were triggered by changes in intracellular oxidation/reduction (redox) reactions. Indirect immunofluorescence using intact cells demonstrated that indomethacin induced the nuclear translocation of Nrf2, a transcription factor believed to regulate GCLC expression. Immunoprecipitation studies showed that indomethacin treatment also inhibited Nrf2 tethering to KIAA0132 (the human homolog of Keap1 accession #D50922), which is believed to be a negative regulator of Nrf2. Consistent with this idea, over-expression of Nrf2 increased GCLC reporter gene expression and over-expression of KIAA0132 inhibited GCLC reporter gene activity as well as inhibited indomethacin-induced increases in the expression of GCLC. Finally, simultaneous treatment with NAC inhibited both indomethacin-induced release of Nrf2 from KIAA0132 and indomethacin-induced nuclear translocation of Nrf2. These results demonstrate that NSAIDs and resveratrol cause increases in the expression of gamma-glutamylcysteine synthetase mRNA and identify these agents as being capable of stimulating glutathione metabolism. These results also support the hypothesis that indomethacin-induced transcriptional activation of GCLC involves the redox-dependent release of KIAA0132 from Nrf2 followed by the nuclear translocation of Nrf2.
UI - 12086903
AU - Medina-Franco H; Sellers MT; Eckhoff DE; Bynon JS; Urist MM; Heslin MJ
TI - Multimodality treatment for patients with hepatocellular carcinoma: analysis of prognostic factors in a single Western institution series.
SO - J Gastrointest Surg 2001 Nov-Dec;5(6):638-45
AD - Department of Surgery, Section of Surgical Oncology, University of Alabama at Birmingham, USA.
There are few Western studies evaluating prognostic factors for survival in patients with hepatocellular carcinoma (HCC) and the influence on survival of various therapeutic options including orthotopic liver transplantation (OLT). A retrospective analysis was performed of 122 patients with HCC treated at the University of Alabama at Birmingham factors were analyzed with overall survival as the main outcome variable. Median age was 62 years. Most patients were male (74%) and white (79%). Eighty patients (66%) had associated cirrhosis. Sixty-three percent of patients presented with American Joint Committee on Cancer (AJCC) stage III or IV tumors. The median follow-up for survivors was 22 months. The 1-, 3-, and 5-year actuarial survival rates for the entire cohort were 46%, 24%, and 17%, respectively. On multivariate analysis, ablative surgery (P = 0.003), AJCC stages I and II (P = 0.0012), and absence of vascular invasion (P = 0.0001) were found to be independent favorable characteristics. Forty-four patients underwent surgical resection (including OLT, n = 20) or a surgical ablative procedure. All but two nonsurgical patients died of disease. The actuarial 1-, 3-, and 5-year survival rates for this group were 80%, 71%, and 61%, respectively. On multivariate analysis of the surgical group, only vascular invasion was associated with poor prognosis (P = 0.001). OLT was associated with a favorable prognosis on univariate analysis (P = 0.02). Forty percent of patients who received transplants underwent local/regional treatment before transplantation and the outcome in these patients was no different from that in other transplant patients. Surgical treatment is the only potential curative option for HCC, and qualifying for liver transplantation may be a favorable prognostic factor in surgical patients. Local/regional therapy prior to transplantation may provide a bridge to OLT without an increase in tumor-related mortality.
UI - 12168494
AU - Huang CJ; Lian SL; Chen SC; Wu DK; Wei SY; Huang MY; Ho YH
TI - External beam radiation therapy for inoperable hepatocellular carcinoma with portal vein thrombosis.
SO - Kaohsiung J Med Sci 2001 Dec;17(12):610-4
AD - Department of Radiotherapy, Kaohsiung Medical University Hospital, No. 100, Shih-Chuan 1st Rd., Kaohsiung 807, Taiwan.
Portal vein thrombosis (PVT) in patients with hepatocellular carcinoma (HCC) has a poor impact on prognosis. Many of these tumors may cause 1996, 41 unresectable HCC patients with PVT underwent transcatheter arterial chemoembolization (TACE) and external beam radiation therapy (EBRT) to the portion of PVT. The irradiated field, with a mean equivalent field size of 6.6 x 7.1 cm2, was localized and simulated by abdominal sonography, angiography and computed tomography. Radiation dose ranged from 36 to 66 Gy (mean dose: 51.4 Gy), in a daily fraction of 1.8 to 2 Gy. The response of EBRT was evaluated by abdominal sonography within 3 months of completion of EBRT. The response rates of the PVT after treatment were 39% for complete response (CR), 41% for partial response (PR), and 19% for no response (NR), respectively. The median overall survival time from start of radiotherapy was 10 months for all patients, 17 months for CR patients, 8 months for PR patients and 4 months for NR patients. By multivariate analysis, response of PVT resulted in a significant improvement in survival. (P = 0.001) There was no occurrence of severe complication of radiation-induced liver disease. The results obtained with combined treatment modality of EBRT and TACE in the treatment of HCC patients with PVT are encouraging.
UI - 12081752
AU - Esnaola N; Vauthey JN; Lauwers G
TI - Liver fibrosis increases the risk of intrahepatic recurrence after hepatectomy for hepatocellular carcinoma (Br J Surg 2002; 89: 57-62).
SO - Br J Surg 2002 Jul;89(7):939-40; discussion 940
UI - 12118934
AU - Srivastava DN; Thulkar S; Sharma S; Pandey GK; Sahni P; Julka PK;
TI - Acharya SK Therapeutic radiological interventional procedures in hepatocellular carcinoma.
SO - Indian J Gastroenterol 2002 May-Jun;21(3):96-8
AD - Department of Radiodiagnosis, All India Institute of Medical Sciences, Ansari Nagar, New Delhi. email@example.com
BACKGROUND: To improve the survival rate of patients with hepatocellular carcinoma (HCC) in whom surgery is not possible, various methods have been developed employing angiographic and percutaneous techniques. We analyzed our experience with various percutaneous therapeutic interventional techniques done for HCC in our center. METHODS: Sixty-one patients with inoperable HCC (mean age 48.9 [SD 13.8] y; 47 men) were chemoembolization (TACE) alone (22), TACE with percutaneous alcohol injection (PEI) (20), transcatheter arterial embolization (TAE) with steel coils and gel foam for gastrointestinal bleed (7), percutaneous radiofrequency ablation (1), percutaneous preoperative right portal vein embolization (3) and percutaneous preoperative tumor embolization to reduce blood loss at surgery (8). RESULTS: In 42 patients treated by TACE and PEI and TACE alone, tumor necrosis was scored; over 50% necrosis was seen only after six and nine months in both treatment groups. The survival rates after six and nine months and the median survival were similar in the two groups. Of 7 cases treated with TAE with steel coils and gel foam, the gastrointestinal bleeding stopped in four; in the other three, bleeding did not stop completely although less transfusion was required. In the patient treated by radiofrequency ablation, follow-up contrast-enhanced CT did not show enhancing tumor mass. We noted left lobe enlargement after percutaneous preoperative right portal vein embolization, prior to right hepatectomy. CONCLUSION: In patients with HCC not amenable to surgical intervention, a variety of percutaneous therapeutic interventional techniques may be used.
UI - 12013692
AU - Wildi S; Kadry Z; Clavien PA
TI - Neoadjuvant and adjuvant therapies for resectable hepatocellular carcinoma (HCC) and palliation strategies.
SO - Swiss Surg 2002;8(2):61-6
AD - Department of Visceral and Transplantation Surgery, University Hospital of Zurich, Switzerland.
Hepatocellular carcinoma (HCC) is the most common primary malignancy in the liver worldwide. The incidence of the tumor varies geographically. Thus, in the eastern area (China, Taiwan, and Japan) there are more than 20 cases per year per 100'000 population compared to less than 5 cases per 100'000 in most western countries . The etiology of HCC is multifactorial. The two most important factors are the presence of cirrhosis and chronic hepatitis . Early detection of HCC still remains a challenge. At the time of diagnosis, only 20-30% of all patients have tumors that are surgically resectable. Survival after curative resection is 30%-50% at five years. The poor outcome of the disease led to the development of different adjuvant and neoadjuvant therapies. There are numerous studies dealing with the treatment of HCC. Unfortunately, only few randomized controlled trials exist. In addition, there is no consensus on staging of HCC and no standardization of the outcome in the literature, which makes it difficult to compare the different procedures. This paper summarizes the current strategies in the treatment of HCC.
UI - 12013693
AU - Herfarth C; Lamade W; Fischer L; Chiu P; Cardenas C; Thorn M; Vetter M;
TI - Grenacher L; Meinzer HP The effect of virtual reality and training on liver operation planning.
SO - Swiss Surg 2002;8(2):67-73
AD - Department of Surgery, University of Heidelberg, Germany.
OBJECTIVE: The three-dimensional relation of a liver tumour to the intrahepatic vascular trees is basis of operation planning in liver surgery. Yet it has not been proven whether 3D reconstruction and further computerised processing will enhance precision of operation planning in liver surgery which has been based on the liver segment classification of Couinaud up to now. DESIGN: Our interdisciplinary group (department of Surgery, German Cancer Research Center and Department of Radiology) has developed a new interactive computer-based quantitative 3D operation planning system for liver surgery which is being introduced into the clinical routine. The system quantifies the organ structures semiautomatically, defines resection planes depending on safety margins and the vascular trees, and presents the data in digital movies as well as in quantitative reports. We conducted a clinical trial to evaluate whether 3D reconstruction will lead to an improved operation planning. Data of 7 virtual patients were presented to a total of 81 surgeons in different levels of training. The tumours had to be assigned to a liver segment and subsequently drawn together with the operation proposals into a liver model. The precision of both was measured quantitatively for each surgeon and stratified concerning 2D and different types of 3D presentations. RESULTS: The 3D anatomy can be visualised in high quality which results in good perception of the third dimension (depth). Tumour assignment to liver segments was significantly correlated to the level of training (p < 0.05). There was a significant increase (p < 0.001) in the precision of tumour localisation by 51% and resection proposal from 2D through 3D reconstructions by 13%-21%. Quantitative differences of the simplified Couinaud's classification of the liver segments compared to the true vascular anatomy of up to 40% were found. CONCLUSION: The impact of individual 3D-reconstruction on surgical planning has been proven to be significant and increases precision quantitatively. The merit of Couinaud's classification may be enhanced by individualisation of the segment borders in future.
UI - 11916199
AU - Huo TI; Huang YH; Wu JC; Lee PC; Chang FY; Lee SD
TI - Survival benefit of cirrhotic patients with hepatocellular carcinoma treated by percutaneous ethanol injection as a salvage therapy.
SO - Scand J Gastroenterol 2002 Mar;37(3):350-5
AD - Dept. of Medicine, Taipei Veterans General Hospital and National Yang-Ming University School of Medicine, Taiwan, Republic of China. firstname.lastname@example.org
BACKGROUND: The therapeutic strategy for cirrhotic patients with hepatocellular carcinoma (HCC) who cannot tolerate surgery or transcatheter arterial chemoembolization (TACE) is uncertain. The safety and efficacy of percutaneous ethanol injection (PEI) as a salvage therapy in such patients is not clear. METHODS: A total of 63 (49 men) HCC patients (mean age 67 +/- 11 years), for whom surgery or TACE was not indicated because of the coexistence of various medical conditions, were enrolled and prospectively studied. Fifty-six (89%) were treated with PEI and 7 were treated with conservative measures. The outcome and the factors that may affect survival were evaluated. RESULTS: During a mean follow-up period of 16 +/- 9 months, 17 (30%) of the patients treated with PEI and 5 (71%) of those treated with conservative measures died (P = 0.045). A total of 16 patient-related and tumor-related variables that may influence the outcome were analyzed. Survival analysis showed that female gender, small (< or = 3 cm) solitary tumor and PEI were associated with a better prognosis (P < 0.05). When using the Cox proportional hazard model, PEI was the only significant independent factor predicting survival (relative risk: 0.3, 95% confidence interval: 0.11-0.86, P = 0.024). The 1- and 2-year survival rates were 85% and 65% for patients treated with PEI compared to 57% and 29% for conservative measures (P = 0.016). CONCLUSIONS: PEI may be a treatment option for cirrhotic patients who have HCC and coexisting contraindications that preclude surgery and TACE. Careful pre-treatment patient selection may effectively prolong the survival.
UI - 12053220
AU - Suzuki S; Sakaguchi T; Yokoi Y; Okamoto K; Kurachi K; Tsuchiya Y;
TI - Okumura T; Konno H; Baba S; Nakamura S Clinicopathological prognostic factors and impact of surgical treatment of mass-forming intrahepatic cholangiocarcinoma.
SO - World J Surg 2002 Jun;26(6):687-93
AD - Department of Surgery II, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu 431-3192, Japan. email@example.com
The clinicopathological characteristics relevant to prognosis after surgical treatment of intrahepatic cholangiocarcinoma (ICC) remain unclear. In this study, the clinicopathological features of 19 patients with mass-forming ICC, the most common form of the disease, were reviewed to analyze prognostic determinants. Two or more segmentectomies of the liver with systematic lymphadenectomy were performed in 18 patients. Resection of the extrahepatic bile duct was performed in 14 patients, and reconstruction of the portal vein was accomplished in 5 patients. Stage IVA or IVB tumors were seen in 13 patients, and lymph node (LN) metastasis was present in 14 patients. The estimated 5-year survival rate after surgery for mass-forming ICC was 28%, with median survival time of 18 months. In univariate analysis, five variables were determined to be significantly correlated with poor survival of patients with mass-forming ICC after surgery. These variables include mass-forming ICC with periductal infiltration, perineural invasion, portal vein invasion, presence of intrahepatic metastasis, and two or more LN metastases. Survival rates of 5 patients without LN metastasis and 6 patients with a single LN metastasis were 80% and 33% at 5 years, respectively, while 8 patients with two or more LN metastasis failed to survive beyond 2 years. Multivariate analysis revealed the presence of intrahepatic metastasis to be an independent prognostic factor of poor survival. Hepatectomy with resection of the extrahepatic bile duct and systematic lymphadenectomy yields a good chance for prolonged survival for patients with mass-forming ICC when the lesion is singular and LN metastasis is limited to a regional LN. Because the presence of intrahepatic metastasis was closely related to a poor prognosis in patients with mass-forming ICC, efficacious chemotherapy would be needed to control development of the lesion.
UI - 12053231
AU - Chen MF; Jeng LB; Lee WC
TI - Surgical results in patients with hepatitis virus-related hepatocellular carcinoma in Taiwan.
SO - World J Surg 2002 Jun;26(6):742-7
AD - Department of General Surgery, Chang Gung Memorial Hospital, 5 Fu-Hsing Street, Kwei-Shan, Taoyuan, Taiwan. firstname.lastname@example.org
To investigate the surgical results of hepatectomy for hepatocellular carcinoma in relation to hepatitis virus status in Taiwan, 252 patients patients were divided into four groups: 30 patients (11.9%) seronegative for both hepatitis B surface antigen (HBsAg) and antihepatitis C antibody (HCVAb) (N-HCC group); 133 patients (52.8%) seropositive for HBsAg and seronegative for HCVAb (B-HCC group); 66 patients (26.2%) seronegative for HBsAg and seropositive for HCVAb (C-HCC group); and 23 patients (9.1%) seropositive for both HBsAg and HCVAb (BC-HCC group). Patients in group C-HCC were older (p = 0.001) and had a higher incidence of diabetes mellitus (p = 0.004). Also, they had a higher indocyanine green retention rate at 15 minutes (p = 0.021), longer international normalization ratio for the prothrombin time (p = 0.049), and smaller tumor (p = 0.006). Postoperative complications and hospital mortality were significantly higher in patients in the C-HCC and BC-HCC groups (p = 0.046, 0.021). All patients were followed 12 to 76 months after hepatectomy (mean 23.5 +/- 16.3 months). The 1-, 3-, and 5-year overall cumulative survival rates of the 252 patients in this series were 80%, 54.3%, and 34.2%, respectively. The cumulative intrahepatic recurrence rates were 46.5%, 64.9%, and 72.9% at 1, 3, and 5 years, respectively. The mean disease-free survival time was longest in group C-HCC and shortest in group BC-HCC (p = 0.020). The overall survival time and cumulative survival rates in the four groups were not significantly different (p = 0.146).
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