• Laparoscopic-assisted liver resection.

• Percutaneous radiofrequency thermoablation as an alternative to surgery for treatment of liver tumour recurrence after hepatectomy.

• [Liver transplantation for patients with hepatitis B/C virus cirrhosis or hepato cellular carcinoma]

• Hepatocellular carcinoma in children and adolescents: results from the Pediatric Oncology Group and the Children's Cancer Group intergroup

• [Surgical treatment of giant hemangiomas of the liver]

• Comparison of transarterial chemoembolization in patients with unresectable, diffuse vs focal hepatocellular carcinoma.

• Saline injection into the pleural cavity to detect tumors of the hepatic dome with sonography: a new approach for treatment of hepatocellular

• Radiofrequency ablation of hepatic tumors: increased tumor destruction with adjuvant liposomal doxorubicin therapy.

• Treatment of hepatocellular carcinoma by interventional methods.

• Radiofrequency ablation of unresectable primary liver cancer.

• Does diabetes mellitus influence the perioperative outcome or long term prognosis after resection of hepatocellular carcinoma?

• Protein kinase inhibitors modulate time-dependent effects of UV and ionizing irradiation on ICAM-1 expression on human hepatoma cells.

• Gene therapy of hepatocellular carcinoma and gastrointestinal tumors.

• [Surgical treatment of hepatocellular carcinoma: resection or transplantation? Results of a multivariate analysis]

• Transcatheter arterial embolization with zinostatin stimalamer for hepatocellular carcinoma.

• Hepatitis B leading to hepatocellular carcinoma: calculating the risk.

• Transarterial chemoembolization for unresectable hepatocellular carcinoma: meta-analysis of randomized controlled trials.

• Treatment of ruptured hepatocellular carcinoma.

• Hepatocellular carcinoma.

• [Laparoscopic cryoablation of liver tumors]

• [Arguments for surgical resection of hepatocellular carcinoma greater than 20 cm]

• Intraarterial lidocaine administration for relief of pain resulting from transarterial chemoembolization of hepatocellular carcinoma: its

• Accumulation of iodized oil within the nonneoplastic liver adjacent to hepatocellular carcinoma via the drainage routes of the tumor after

• [Liver transplant in hepatocellular carcinoma: would the organ shortage and good outcome justify the expansion of indication or of new surgical

• [Results of liver transplantation in patients with hepatocellular carcinoma]

• Resection of hepatocellular carcinoma with out preoperative tumor biopsy.

• Pretreatment prognostic factors and treatment results in children with hepatoblastoma: a report from the German Cooperative Pediatric Liver

• [Advanced age as risk factor in liver resection surgery]

• A phase II trial of gemcitabine in patients with advanced hepatocellular carcinoma.

1
UI - 12021904
AU - Tang CN; Li MK
TI - Laparoscopic-assisted liver resection.
SO - J Hepatobiliary Pancreat Surg 2002;9(1):105-10
AD - Department of Surgery, Pamela Youde Nethersole Eastern Hospital, 3, Lok Man Road, Chai Wan, Hong Kong.
BACKGROUND/PURPOSE: The recent rapid development of innovative laparoscopic instruments and improvements in surgical skill have made laparoscopic-assisted liver resection possible. Obviously, extensive experience in laparoscopic and hepatobiliary surgery is mandatory in carrying out liver resection through the minimal access approach. Here, we describe and evaluate our results during the period 1998-2001.METHODS: During this period we attempted laparoscopic-assisted liver resection in 11 patients. There were 8 female and 3 male patients, of mean age 57.2 years (range, 28-68 years).RESULTS: In all but 1 patient, the laparoscopic operation was successfully performed. Indications included recurrent pyogenic cholangitis (RPC; n = 6), hepatocellular carcinoma ( n = 3), colorectal liver secondary ( n = 1), and hemangioma ( n = 1). The mean +/- SD operating time was 190 +/- 62.4 min (range, 60-290 min), and mean +/- SD blood loss was 394 +/- 241 cc (range, 200-1000 cc). All patients but 1 were discharged within 2 weeks after the operation, and in this 1 patient, the prolonged hospital stay was due to postoperative bile leak, which was managed by combined percutaneous and endoscopic biliary drainage. With a mean follow-up of 10 months, there was no significant long-term complication.CONCLUSION: In summary, laparoscopic-assisted liver resection is a feasible and safe treatment option for various liver pathologies, such as RPC and primary and secondary liver tumors.

2
UI - 12027986
AU - Elias D; De Baere T; Smayra T; Ouellet JF; Roche A; Lasser P
TI - Percutaneous radiofrequency thermoablation as an alternative to surgery for treatment of liver tumour recurrence after hepatectomy.
SO - Br J Surg 2002 Jun;89(6):752-6
AD - Department of Surgical Oncolog, Comprehensive Cancer Centre, Institut Gustave Roussy, Rue Camille Desmoulins, 94805 Villejuif Cedex, France. elias@igr.fr
BACKGROUND: Radiofrequency (RF) current, converted into heat through ion agitation and friction, can destroy liver tumours by means of coagulation necrosis. This study assessed whether percutaneous RF ablation is a useful and safe technique for the treatment of liver tumour recurrence after hepatectomy. METHODS: Forty-seven patients presenting with local recurrence after hepatectomy for malignant tumours (29 with colorectal secondaries) were treated with percutaneous RF ablation instead of repeat hepatectomy. RF thermal ablation was performed under image guidance for 12-15 min. This group represented 63 per cent of 75 patients treated with curative intent for liver recurrence in the same time interval. The other 28 patients underwent repeat hepatectomy. RESULTS: The mean(s.d.) number of liver metastases destroyed was 1.4(0.7) (range 1-3) and their diameter was 21(8) (range 9-35) mm. Twenty-six patients presented with liver recurrence at least once but up to three times after the initial RF application. Incomplete local RF treatment was observed in six of 47 patients. Fifteen patients developed extrahepatic recurrence. The mean(s.d.) interval between RF ablation and the last follow-up visit was 14.4(10.1) (range 5.5-40) months. One death and three major complications occurred. Survival rates at 1 and 2 years were 88 and 55 per cent respectively. A retrospective study of the authors' database over two similar consecutive periods showed that RF ablation increased the percentage of curative local treatments for liver recurrence after hepatectomy from 17 to 26 per cent and decreased the proportion of repeat hepatectomies from 100 to to 39 per cent. CONCLUSION: Percutaneous RF treatment increases the number of patients eligible for curative treatment. It should be preferred to repeat hepatectomy when feasible and safe because it is less invasive. Repeat hepatectomy is indicated only when percutaneous RF ablation is contraindicated or fails.

3
UI - 12048876
AU - Todo S; Furukawa H; Matsushita M; Shimamura T; Jin MB; Suzuki T;
TI - Taniguchi M [Liver transplantation for patients with hepatitis B/C virus cirrhosis or hepato cellular carcinoma]
SO - Nippon Geka Gakkai Zasshi 2002 May;103(5):408-13
AD - Hokkaido University School of Medicine, Department of General Surgery.
The outcome of liver transplantation for patients with hepatitis B/C virus (HBV/HBC) cirrhosis or with hepatocellular carcinoma(HCC) was deemed pessimistic until the early 1990s due to the high rate of recurrence and mortality. However, with the advent of new antiviral agents and strict adherence transplant indications, the results of liver transplantation in patients with these disease have improved progressively. Coadministration of lamivudine and anti-HBV immunoglobulin, and of interferon and ribavirin inhibits the recurrence of hepatitis B and hepatitis C, respectively. Excluding HCC patients with extrahepatic or lymph node metastasis, vascular invasion, a single lesion more than 5 cm in diameter, or multiple lesions more than 3 cm in diameter, the 5-year patient survival rate has improved from 30% to 85%, with a disease-free survival rate of more than 90%. However, the development of lamivudineresistant mutants after prolonged use of the agent needs to be overcome, possibly by new antiviral agents such as adefovir. In addition, to expand the current limited transplant indications for HCC, the efficacy of perioperative anticancer treatment and the importance of molecular diagnosis of circulating hepatoma cells must be determined in future.

4
UI - 12065555
AU - Katzenstein HM; Krailo MD; Malogolowkin MH; Ortega JA; Liu-Mares W;
TI - Douglass EC; Feusner JH; Reynolds M; Quinn JJ; Newman K; Finegold MJ; Haas JE; Sensel MG; Castleberry RP; Bowman LC Hepatocellular carcinoma in children and adolescents: results from the Pediatric Oncology Group and the Children's Cancer Group intergroup study.
SO - J Clin Oncol 2002 Jun 15;20(12):2789-97
AD - Department of Pediatrics and Surgery, Northwestern University and Children's Memorial Hospital, Chicago, IL, USA. hmk476@northwestern.edu
PURPOSE: To determine surgical resectability, event-free survival (EFS), and toxicity in children with hepatocellular carcinoma (HCC) randomized to treatment with either cisplatin (CDDP), vincristine, and fluorouracil (regimen A) or CDDP and continuous-infusion doxorubicin (regimen B). PATIENTS AND METHODS: Forty-six patients were enrolled onto Pediatric Intergroup Hepatoma Protocol INT-0098 (Pediatric Oncology Group (POG) 8945/Children's Cancer Group (CCG) 8881). After initial surgery or biopsy, children with stage I (n = 8), stage III (n = 25), and stage IV (n = 13) HCC were randomly assigned to receive regimen A (n = 20) or regimen B (n = 26). RESULTS: For the entire cohort, the 5-year EFS estimate was 19% (SD = 6%). Patients with stage I, III, and IV had 5-year EFS estimates of 88% (SD = 12%), 8% (SD = 5%), and 0%, respectively. Five-year EFS estimates were 20% (SD = 9%) and 19% (SD = 8%) for patients on regimens A and B, respectively (P =.78), with a relative risk of 1.2 (95% confidence interval, 0.60 to 2.3) for regimen B when compared with regimen A. Outcome was similar for either regimen within disease stages. Events occurred before postinduction surgery I in 18 (47%) of 38 patients with stage III or IV disease, and tumor resection was possible in two (10%) of the remaining 20 children with advanced-stage disease after chemotherapy. CONCLUSION: Children with initially resectable HCC have a good prognosis and may benefit from the use of adjuvant chemotherapy. Outcome was uniformly poor for children with advanced-stage disease treated with either regimen. New therapeutic strategies are needed for the treatment of advanced-stage pediatric HCC.

5
UI - 12049008
AU - Olah A; Issekutz A; Toth-G B; Haulik L; Banga P
TI - [Surgical treatment of giant hemangiomas of the liver]
SO - Magy Seb 2002 Apr;55(2):57-62
AD - Petz Aladar Megyei Oktato Korhaz, Sebeszeti Osztaly, 9002 Gyor, Pf. 92. olah.seb@arrabonet.gyor.hu
Spontaneous rupture of liver hemangiomas is exceptional, they rarely increase in size. Elective surgery of liver hemangiomas is safe and effective. In our teaching hospital during a 5-year period 9 patients underwent elective surgery for giant liver hemangiomas, one more patient required urgent operation for spontaneous rupture. Indications for elective surgery were: abdominal pain in 5 patients, enlargement in 1 patient, and 3 patients were worried about the risk of rupture or having a tumor left in situ. The average age of our four male and six female patients was 44.5 years (30-58). The median largest dimension of the lesions was 8.5 cm (5.5-14); six of them located in the right, four in the left lobe. Enucleation was performed in most patients (8, mostly of them in the right lobe); anatomical resections were performed only in two cases (left lobectomy). There was no postoperative mortality, the only complication was mild pneumonia in one patient. Elective surgery is indicated only in a small number of patients with hemangiomas, it should be limited to giant, symptomatic tumors or those with a documented tendency to increase in size. The type of resection depends on the site and the size of the lesion. Enucleation can be performed rapidly and safely in most patients and as such it is preferable to anatomical resection.

6
UI - 12049535
AU - Lopez RR Jr; Pan SH; Hoffman AL; Ramirez C; Rojter SE; Ramos H;
TI - McMonigle M; Lois J Comparison of transarterial chemoembolization in patients with unresectable, diffuse vs focal hepatocellular carcinoma.
SO - Arch Surg 2002 Jun;137(6):653-7; discussion 657-8
AD - Comprehensive Liver Disease Center, St Vincent Medical Center, Los Angeles, CA 90057, USA.
HYPOTHESIS: Transarterial chemoembolization (TACE) is beneficial for selected patients with unresectable hepatocellular carcinoma (HCC). DESIGN AND SETTING: A prospective comparison study in a tertiary hospital. STUDY PERIOD: November 21, 1995, to May 2, 2001, with a mean follow-up of 939 days. PATIENTS: A total of 157 TACE treatments were performed in 88 patients with unresectable HCC: 132 treatments in 69 patients with focal HCC (F-HCC) and 25 treatments in 19 patients with diffuse HCC (D-HCC). INTERVENTIONS: Transarterial chemoembolization consisted of selective catheterization and intra-arterial infusion of a mixture of doxorubicin hydrochloride, cisplatin, and mitomycin followed by embolization. Sequential treatments were performed for bilobar HCC. MAIN OUTCOME MEASURES: Child-Pugh classification and clinical outcomes, including alpha-fetoprotein (AFP) response, length of hospital stay, readmission rate, and survival, were compared between patients with F-HCC and D-HCC following TACE using the chi(2) test, Fisher exact test, or t test (2-tailed, unpaired). RESULTS: Fifty-eight patients (84%) in the F-HCC group and 18 patients (95%) in the D-HCC group had cirrhosis. For those patients with cirrhosis, 58 (100%) in the F-HCC group and 14 (78%) in the D-HCC group had a Child-Pugh score of A or B (P =.002). The mean baseline AFP was higher in the D-HCC group: 55 577 vs 7815 ng/mL in the F-HCC group (P =.001). Of the patients secreting AFP, 4 (29%) of 14 in the D-HCC group and 30 (68%) of 44 in the F-HCC group had a significant decrease in AFP 1 month following TACE (P =.01). The mean hospital stay was longer (3 vs 1.9 days; P =.001), and readmissions occurred more frequently (44% vs 9%; P<.001) in the D-HCC group. The mean survival rate was significantly higher in the F-HCC group: 425 vs 103 days (P<.001). CONCLUSIONS: In patients with F-HCC, TACE is well tolerated and provides a survival benefit. However, there is no apparent benefit for patients with D-HCC. Importantly, tumor characteristics and hepatic reserve are essential criteria for successful TACE.

7
UI - 12076913
AU - Katayama K; Ooka Y; Uemura A; Shinzaki S; Egawa S; Naito M; Ishibashi K;
TI - Kamoi R Saline injection into the pleural cavity to detect tumors of the hepatic dome with sonography: a new approach for treatment of hepatocellular carcinoma.
SO - AJR Am J Roentgenol 2002 Jul;179(1):102-4
AD - Department of Internal Medicine, Osaka Koseinenkin Hospital, 4-2-78 Fukushima, Fukushima-ku, Osaka 553-0003, Japan.

8
UI - 12076912
AU - Goldberg SN; Kamel IR; Kruskal JB; Reynolds K; Monsky WL; Stuart KE;
TI - Ahmed M; Raptopoulos V Radiofrequency ablation of hepatic tumors: increased tumor destruction with adjuvant liposomal doxorubicin therapy.
SO - AJR Am J Roentgenol 2002 Jul;179(1):93-101
AD - Department of Radiology, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Ave, Boston, MA 02215, USA.
OBJECTIVE: The purpose of this study was to determine whether the administration of liposomal doxorubicin before radiofrequency ablation increases coagulation more than radiofrequency alone in focal hepatic tumors. SUBJECTS AND METHODS: Fourteen focal hepatic tumors (diameter: mean +/- SD, 4.0+/-1.8 cm) in 10 patients (colorectal cancer, n = 3 patients; hepatocellular carcinoma, n = 4; neuroendocrine tumor, n = 2; breast cancer, n = 1) were treated with internally cooled radiofrequency ablation. In addition to undergoing radiofrequency, five patients (n = 7 lesions) were randomly assigned to receive 20 mg of IV doxorubicin in a long-circulating stealth liposome carrier (Doxil) 24 hr before ablation. Contrast-enhanced helical CT was performed immediately (within 30 min) after radiofrequency ablation (baseline) and 2-4 weeks after ablation. The volume of induced coagulation was measured by three-dimensional reconstruction techniques, and the measurements were compared. RESULTS: For tumors treated with radiofrequency alone, the volume of the thermal lesion had decreased 12-24% (mean +/- SD, 82.5% +/- 4.4% of initial volume) at 2-4 weeks after ablation. By comparison, increased tumor destruction at 2-4 weeks after ablation was observed for all lesions treated with combined Doxil and radiofrequency (p<0.001). Six lesions increased 24-36% in volume, and coagulation surrounding a small colorectal metastasis increased 342%. No coagulation was identified in four unablated control lesions in the two patients receiving Doxil alone. CONCLUSION: Our pilot clinical study suggests that adjuvant Doxil chemotherapy increases tumor destruction compared with radiofrequency ablation therapy alone in a variety of focal hepatic tumors. Optimization of this synergistic strategy may ultimately allow improved clinical efficacy and outcome.

9
UI - 11702161
AU - Livraghi T
TI - Treatment of hepatocellular carcinoma by interventional methods.
SO - Eur Radiol 2001;11(11):2207-19
AD - Department of Radiology, Ospedale Civile, via Cereda 23, 20059 Vimercate (Milan), Italy. lalivra@tin.it
In the treatment of early and intermediate hepatocellular carcinoma the range of indications for percutaneous ablation techniques is becoming wider than surgery or intra-arterial therapies. Indeed, whereas for some years only patients with up to three small tumours were treated, with the introduction of the single-session technique performed under general anaesthesia, even patients with more advanced disease are now being treated. Although it is understood that partial resection assures the highest local control, the survival rates after surgery are roughly comparable with percutaneous ethanol injection (PEI). The explanation is due to a balance among advantages and disadvantages of the two therapies. PEI survival curves are better than curves of resected patients who present adverse prognostic factors, and this means that surgery needs a better selection of the patients. Indications for both of therapies are reported. An unanswered question remains the choice between PEI and other new ablation procedures. In our department we currently use radio-frequency ablation in the majority of patients but consider PEI and segmental transarterial chemoembolisation complementary, and use them according to the features of the disease and the response. Evaluation of therapeutic efficacy, technique and results of them are reported.

10
UI - 12081073
AU - Seidenfeld J; Korn A; Aronson N
TI - Radiofrequency ablation of unresectable primary liver cancer.
SO - J Am Coll Surg 2002 Jun;194(6):813-28; discussion 828
AD - Technology Evaluation Center, Blue Cross and Blue Shield Association, Chicago, IL 60601-7680, USA.

11
UI - 12094870
AU - Poon RT; Fan ST; Wong J
TI - Does diabetes mellitus influence the perioperative outcome or long term prognosis after resection of hepatocellular carcinoma?
SO - Am J Gastroenterol 2002 Jun;97(6):1480-8
AD - Centre for the Study of Liver Disease and Department of Surgery, University of Hong Kong Medical Centre, Queen Mary Hospital, China.
OBJECTIVE: This study aims to evaluate whether diabetes mellitus has a significant influence on the perioperative outcome or long term prognosis after resection of hepatocellular carcinoma (HCC). METHODS: The clinicopathological data and postoperative morbidity and mortality of 62 diabetic and 463 nondiabetic patients who underwent resection of HCC between 1989 and 2000 were compared. The long term overall and disease-free survival results were also compared, and the prognostic impact of diabetes mellitus was assessed by multivariate analysis. RESULTS: The diabetic and nondiabetic groups were comparable in terms of the frequency of cirrhosis, liver function, type of resection, and tumor factors such as size and pTNM stage. Overall complication rate (38.7% vs 37.1%, p = 0.820), 30-day mortality (3.2% vs 3.0%, p = 0.583), and hospital mortality (6.4% vs 6.0%, p = 0.782) were similar in diabetic and nondiabetic patients. There was no significant difference in the overall survival (median = 43.5 vs 43.2 months, p = 0.438) or disease-free survival (median = 18.2 vs 15.0 months, p = 0.418). On multivariate analysis, only tumor pTNM stage, operative blood loss, and preoperative indocyanine green retention at 15 min were significant predictors of overall survival. Tumor pTNM stage, size, and operative blood loss were significant predictors of disease-free survival. CONCLUSIONS: This study indicates that diabetes mellitus does not increase the perioperative morbidity or mortality after resection of HCC, nor does it significantly influence the long term prognosis. Based on the current study data, diabetes mellitus should not be considered an unfavorable factor in the selection of patients for resection of HCC.

12
UI - 12079536
AU - Meineke V; Moede T; Gilbertz KP; Mayerhofer A; Ring J; Kohn FM; Van
TI - Beuningen D Protein kinase inhibitors modulate time-dependent effects of UV and ionizing irradiation on ICAM-1 expression on human hepatoma cells.
SO - Int J Radiat Biol 2002 Jul;78(7):577-83
AD - Institute of Radiobiology, Federal Armed Forces Medical Academy, D-80937 Munich, Germany. Viktor.Meineke@t-online.de
PURPOSE: To investigate modulation of the expression of the adhesion protein ICAM-1 by UV and ionizing irradiation. MATERIALS AND METHODS: HepG2 hepatoma cells were irradiated in vitro with UVB (20 mJ cm(-2)) or X-rays (5 Gy), respectively. Gene expression of ICAM-1 after irradiation was quantified by RT-PCR. Cell surface density of ICAM-1 was determined by flow cytometry. Protein or lipid kinase inhibitors were used to clarify radiation-induced transduction pathways that control ICAM-1 expression. Immuno-electron microscopy and dot-blot analysis were used to examine localization of ICAM-1. RESULTS: The study showed time-dependent effects of ionizing and UV irradiation on ICAM-1 expression of HepG2 cells. After an immediate transient decrease of ICAM-1 cell surface expression within minutes to hours, ICAM-1 expression increased up to 1.35-fold over normal level at 48 h post-irradiation. Irradiation caused ICAM-1 to become internalized into lysosomes. Additionally, ICAM-1 together with parts of the cell were pinched off. Finally, ICAM-1 levels were down- and up-regulated by decreased or increased gene expression. The early decrease of ICAM-1 expression could be blocked by a potent PKC inhibitor (BisX), whereas the increase of ICAM-1 after 24 h was prevented by addition of the p38 MAP kinase inhibitor SB 203580. CONCLUSION: The data suggest that ICAM-1 expression is modulated by UV, as well as ionizing radiation, in a time-dependent way involving PKC and p38 MAP kinase pathways.

13
UI - 12095923
AU - Sangro B; Qian C; Schmitz V; Prieto J
TI - Gene therapy of hepatocellular carcinoma and gastrointestinal tumors.
SO - Ann N Y Acad Sci 2002 Jun;963():6-12
AD - Gene Therapy Unit, Department of Internal Medicine, Clinica Universitaria, Universidad de Navarra, Pamplona, Spain.
Primary liver cancer and liver metastases from gastrointestinal tumors lack effective therapy. Gene therapy is a promising therapeutic approach and is based on the introduction of genetic material into cells to generate a curative biological effect. Adenoviral vectors can very efficiently transduce a wide variety of malignant epithelial cells both in vitro and in vivo. A variety of gene therapy-based anticancer strategies have been effective in animal tumor models, including replacement of tumor suppressor genes, selective activation of prodrugs, genetic immunotherapy, and antiangiogenic actions. Enzymes used for genetic activation include viral thymidine kinase (tk), which may activate nucleoside analogs such as ganciclovir. We and others have demonstrated the efficacy of the tk/ganciclovir system in the treatment of hepatocellular carcinoma and metastatic colorectal cancer in experimental models. Also, this strategy can be safely applied to patients with liver tumors. Interleukin-12 (IL-12) is among the most potent cytokines in stimulating antitumor immunity. In models of primary and metastatic liver cancer we showed that intratumoral administration of recombinant adenovirus encoding IL-12 activates natural killer cells, induces specific antitumor immunity, and displays a powerful antiangiogenic effect, resulting in tumor regression. There is a synergistic effect with the gene transfer of the chemokine IP-10. Also, intratumoral injection of either dendritic cells transfected ex vivo with recombinant adenovirus encoding IL-12 (Ad.IL-12) or an adenovirus coding for the CD40 ligand have shown an intense antitumor effect against experimental colorectal cancer. In summary, a variety of gene therapy strategies have been effective against animal models of gastrointestinal tumors. Clinical trials should determine whether human patients can be treated safely and effectively by such strategies.

14
UI - 11723888
AU - De Carlis L; Sammartino C; Giacomoni A; Lautiero A; Slim AO; Pirotta V;
TI - Colella G; Forti D [Surgical treatment of hepatocellular carcinoma: resection or transplantation? Results of a multivariate analysis]
SO - Chir Ital 2001 Sep-Oct;53(5):579-86
AD - Divisione di Chirurgia Generale e dei Trapianti Addominali Pizzamiglio 2o, A.O. Niguarda Ca' Granda, 20162 Milano.
This retrospectively study presents the results of a large series of transplanted or resected patients, with the aim of defining the characteristics of those patients who may benefit from resection or transplantation in an era in which these two surgical options can both be offered with low risks and extremely satisfactory results. Two hundred and seventy-five patients (154 resected and 121 transplanted) with hepatocellular carcinoma were submitted to surgical treatment in of cirrhosis, aetiology of liver disease, Child-Pugh classification, and alpha-fetoprotein levels were considered. Twenty-two of the 121 (18.1%) transplanted patients and 7 of the 154 (4.5%) resected patients died within 3 months of surgery. All curves show an evident trend towards increased mortality or recurrence rates in the resected group after prolonged follow-up. Liver transplantation appears to offer better survival and recurrence-free rates than liver resection in patients with hepatocellular carcinoma. Liver resection should be considered a good therapeutic alternative in patients who do not fulfill the transplant criteria.

15
UI - 12065870
AU - Okusaka T; Okada S; Ueno H; Ikeda M; Iwata R; Furukawa H; Takayasu K;
TI - Moriyama N; Sato T; Sato K Transcatheter arterial embolization with zinostatin stimalamer for hepatocellular carcinoma.
SO - Oncology 2002;62(3):228-33
AD - Hepatobiliary and Pancreatic Oncology Division, National Cancer Center Hospital, Tokyo, Japan. tokusaka@ncc.go.jp
Zinostatin stimalamer (SMANCS) is a lipophilic intra-arterial chemotherapeutic agent for hepatocellular carcinoma (HCC). In our previous study, transcatheter arterial infusion chemotherapy using SMANCS for HCC showed a response rate of 20%. In an effort to obtain a superior anti-tumor effect against HCC, we conducted a phase II study of transcatheter arterial embolization (TAE) using SMANCS and gelatin sponge in 50 chemotherapy-naive patients with HCC. Four milligrams SMANCS plus 4 ml lipiodol emulsion was injected into the hepatic artery, followed by an injection of gelatin sponge. The responses were evaluated by computed tomography (CT) 1 month after treatment and thereafter every 3-4 months. One patient (2%) showed complete response and 15 patients (30%) had partial response resulting in an overall response rate of 32% (16/50; 95% confidence interval 19-45%). In 33 patients (66%), the disease remained stable, and 1 patient (2%) showed progressive disease. In 35 patients (70%), the rate of necrotic area to whole tumor was more than 50% according to the evaluation method using lipiodol accumulation in CT. The 1-, 3- and 5-year survival rates were 90, 55 and 19%, respectively. Grade 3 hematological toxicity was observed as thrombocytopenia in 2 patients (4%). Grade 3 and 4 non-hematological toxicity (liver dysfunction) occurred in 17 (34%) and 7 patients (14%), respectively. TAE using SMANCS, which was well tolerated, may be an effective treatment for advanced HCC. Copyright 2002 S. Karger AG, Basel

16
UI - 11817790
AU - Puliyel JM; Taneja V; Jindal K; Thomas N
TI - Hepatitis B leading to hepatocellular carcinoma: calculating the risk.
SO - Indian J Gastroenterol 2001 Nov-Dec;20(6):251-2

17
UI - 12091661
AU - Camma C; Schepis F; Orlando A; Albanese M; Shahied L; Trevisani F;
TI - Andreone P; Craxi A; Cottone M Transarterial chemoembolization for unresectable hepatocellular carcinoma: meta-analysis of randomized controlled trials.
SO - Radiology 2002 Jul;224(1):47-54
AD - National Council of Research, Istituto Metodologie Diagnostiche Avanzate, Palermo, Italy. camma@ismeda.pa.cnr.it
PURPOSE: To review the available evidence of chemoembolization for unresectable hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Computerized bibliographic searches with MEDLINE and CANCERLIT databases from 1980 through 2000 were supplemented with manual searches, with the keywords "hepatocellular carcinoma," "liver cell carcinoma," "randomized controlled trial [RCT]," and "chemoembolization." Studies were included if patients with unresectable HCC were enrolled and if they were RCTs in which chemoembolization was compared with nonactive treatment (five RCTs) or if different transarterial modalities of therapy (13 RCTs) were compared. Data were extracted from each RCT according to the intention-to-treat method. Five of the RCTs with a nonactive treatment arm were combined by using the random-effects model, whereas all 18 RCTs were pooled from meta-regression analysis. RESULTS: Chemoembolization significantly reduced the overall 2-year mortality rate (odds ratio, 0.54; 95% CI: 0.33, 0.89; P =.015) compared with nonactive treatment. Analysis of comparative RCTs helped to predict that overall mortality was significantly lower in patients treated with transarterial embolization (TAE) than in those treated with transarterial chemotherapy (odds ratio, 0.72; 95% CI: 0.53, 0.98; P =.039) and that there is no evidence that transarterial chemoembolization is more effective than TAE (odds ratio, 1.007; 95% CI: 0.79, 1.27; P =.95), which suggests that the addition of an anticancer drug did not improve the therapeutic benefit. CONCLUSION: In patients with unresectable HCC, chemoembolization significantly improved the overall 2-year survival compared with nonactive treatment, but the magnitude of the benefit is relatively small.

18
UI - 11828948
AU - Tanaka A; Takeda R; Mukaihara S; Hayakawa K; Shibata T; Itoh K; Nishida
TI - N; Nakao K; Fukuda Y; Chiba T; Yamaoka Y Treatment of ruptured hepatocellular carcinoma.
SO - Int J Clin Oncol 2001 Dec;6(6):291-5
AD - Department of Emergency Medicine, Kyoto University Hospital, 54-1 Kawaracho Shogoin, Sakyo-ku, Kyoto 606-8507, Japan. er1akira@kuhp.kyoto-u.ac.jp
BACKGROUND: The problem of whether surgical or conservative treatment is indicated for ruptured hepatocellular carcinoma (HCC) has not been analyzed from the viewpoint of long-term development of hepatitis viral infection from liver fibrosis to liver cirrhosis. Although transcatheter arterial embolization (TAE) for hemostasis followed by two-stage hepatectomy has been established as the best treatment for ruptured HCC, there still remain difficulties in the treatment of some patients. METHODS: Twelve patients with ruptured HCC who were surgically or conservatively treated were retrospectively analyzed in terms of modality of treatment, liver function, extension of HCC, complications, survival rate, and cause of death. RESULTS: Tumor rupture can occur either in the early phase or in the terminal phase during the development from liver fibrosis to liver cirrhosis, while tumor rupture occurs at the advanced stage in terms of HCC extension. TAE for emergent hemostasis or prevention of re-bleeding was performed in ten patients, while TAE was contraindicated in one patient and emergent laparotomy for hemostasis was performed in one patient. In four patients, elective extended surgical resection was performed, because liver function was evaluated as clinical stage 1 according to the General rules for the clinical and pathological study of primary liver cancer of the Liver Cancer Study Group of Japan. In seven patients, conservative or medical treatment was selected, because liver function was evaluated as poor. The surgically treated group, who could tolerate extensive operation, survived longer than the conservatively treated group. CONCLUSIONS: While TAE remains the best method to employ for hemostasis, it still has limitations. Hence, we should be mindful of other possible modalities for hemostasis and their outcomes. Rupture of HCC at an early phase in the development of liver fibrosis is a good indication for elective surgical treatment and should be distinguished from rupture in the terminal phase of liver cirrhosis, which should be treated conservatively. Although elective surgical treatment can be performed in selected patients, tumor size and location of HCC, in addition to liver function, should be taken into consideration.

19
UI - 12057148
AU - Venook AP
TI - Hepatocellular carcinoma.
SO - Curr Treat Options Oncol 2000 Dec;1(5):407-15
AD - Division of Hematology and Oncology, University of California, San Francisco, 400 Parnassus Avenue, Suite 502, San Francisco, CA 94143, USA.
Early detection of hepatocellular carcinoma (HCC) is feasible, particularly in patients known to be at risk from chronic hepatitis and chronic liver disease. The optimal surveillance strategy is unknown. HCC usually presents as an incurable disease even when detected on surveillance. Surgical resection is the treatment of choice, but the coexistence of chronic liver disease and the insidious nature of HCC make it unresectable in most patients. Orthotopic liver transplantation for selected patients or ablative techniques may offer an opportunity to render patients disease-free even if the tumor is unresectable. There are numerous therapies offered to patients with unresectable HCC, including chemotherapy, hormonal therapy, and regional intra-arterial treatments. While potentially palliative, none of these approaches has been demonstrated to prolong survival in these patients. If possible, the treatment of patients with HCC should be done on clinical trials.

20
UI - 12073516
AU - Shimonov M; Shechter P; Victoria F; Ada R; Henri H; Czerniak A
TI - [Laparoscopic cryoablation of liver tumors]
SO - Harefuah 2002 May;141(5):414-7, 500
AD - Department of Surgery, Wolfson Medical Center, Holon Israel.
BACKGROUND: Hepatic resection remains the gold standard form of treatment for patients with liver metastases. However, only a small percentage of patients are suitable for resection. Local ablation techniques such as cryotherapy have been used with some success in patients with hepatic tumors. We reviewed our experience with cryotherapy via the laparoscopic approach. METHODS: Eighteen patients suffering from unresectable liver tumor were treated at our department. Ten patients suffered from colorectal liver metastases, eight patients suffered from hepatocellular carcinoma. Laparoscopic treatment was performed under general anesthesia commencing with laparoscopy and laparoscopic ultrasound (LAPUS) for accurate disease staging. Patients having extrahepatic liver spread were excluded. Patients with unresectable liver tumor with no evidence of extrahepatic disease were then treated with laparoscopic cryoablation. The laparoscopic cryoablation system consisted of two integrated parts: The cryoablation system (Cryo-hit, Galil Medical, Israel; employing Argon/Helium gases using 5 mm needles) combined with Laparoscopic ultrasound system using a 10 mm US probe (Sharplan U-sight system, Israel). Cryoablation treatment (two cycles of 10 minutes each) starts with the insertion of the cryo-needle under US guidance. Two or more needles are inserted according to tumor configuration. Treatment is continuously monitored by LAPUS. RESULTS: Morbidity consisted mostly of fever (4/18, 22%) due to atelectasis. Two patients bled and were treated conservatively. One patient died following the development of myocardial infarction 3 days after treatment. FOLLOW-UP: After 13-40 months, mean period of 16 months. Eight patients are alive (17, 18, and 29 months, hepatocellular carcinoma; 13-32 months, metastatic disease). It is important to note that 2 patients have had repeat LC and one patient had 3 LC treatments for recurrent metastatic disease. CONCLUSIONS: LC of irresectable liver tumors is feasible, well tolerated and carries relatively low morbidity with no procedure-related mortality. Repeat treatment is possible. Long term survival may be achieved.

21
UI - 12094427
AU - Ruso L; Laurini M; Balboa O
TI - [Arguments for surgical resection of hepatocellular carcinoma greater than 20 cm]
SO - Ann Chir 2002 May;127(5):402-3

22
UI - 11907741
AU - Lee SH; Hahn ST; Park SH
TI - Intraarterial lidocaine administration for relief of pain resulting from transarterial chemoembolization of hepatocellular carcinoma: its effectiveness and optimal timing of administration.
SO - Cardiovasc Intervent Radiol 2001 Nov-Dec;24(6):368-71
AD - Department of Radiology, St. Mary's Hospital, The Catholic University of Korea, Seoul, South Korea.
PURPOSE: Patients undergoing transarterial chemoembolization (TACE) for hepatocellular carcinoma (HCC) commonly have significant post-procedural abdominal pain necessitating narcotic administration. It is known that intraarterial administration of lidocaine is effective in controlling the pain during the procedure. However, optimum timing of the lidocaine administration is not precisely known. The purpose of this study was to assess the efficacy of intraarterial lidocaine administration for control of pain resulting from TACE and to evaluate the optimal timing of administration. METHODS: In a prospective trial, 113 consecutive patients with HCC who underwent TACE were classified into three groups: those who received a lidocaine bolus intraarterially immediately prior to TACE (group A, n = 30), those who received lidocaine immediately after TACE (group B, n = 46), and those who did not received lidocaine (group C, n = 37). Incidence and degree of post-procedural pain was assessed using a subjective method (visual analogue scales scored from 0 to 10) and an objective method (amount of post-procedural analgesics). RESULTS: The incidence of post-procedural pain in group A (16.7%) was significantly lower than that of group B (38.3%; p = 0.005). The mean pain score was 3.0 in group A and 4.8 and 3.1 in groups B and C, respectively. The mean dose of analgesic used after the procedure in group A (25.0 mg) was significantly lower than those in group B (52.9 mg) and group C (41.0 mg; p = 0.002). CONCLUSIONS: Pre-TACE intraarterial administration of lidocaine is much more effective than post-TACE administration in reducing the incidence and the severity of post-procedural pain. Furthermore, in order to reduce the incidence of post-procedural pain and dose of post-procedural analgesics, we recommend routine pre-TACE administration of lidocaine because post-procedural pain might developed even in patients who did not feel any pain during the TACE.

23
UI - 11907744
AU - Terayama N; Matsui O; Gabata T; Kobayashi S; Sanada J; Ueda K; Kadoya M;
TI - Kawamori Y Accumulation of iodized oil within the nonneoplastic liver adjacent to hepatocellular carcinoma via the drainage routes of the tumor after transcatheter arterial embolization.
SO - Cardiovasc Intervent Radiol 2001 Nov-Dec;24(6):383-7
AD - Department of Radiology, Kanazawa University School of Medicine, Japan. tera@rad.m.kanazawa-u.ac.jp
PURPOSE: After transcatheter arterial embolization (TAE) with iodized oil (Lipiodol), a relatively dense accumulation of Lipiodol is often seen in the nontumorous liver adjacent to a hypervascular hepatocellular carcinoma (HCC) nodule. We compared this phenomenon with the findings obtained with single-level dynamic CT during hepatic arteriography (SLDCTHA) and presumed its possible mechanism. METHODS: Fifty-six patients with HCC underwent hepatic angiography including SLDCTHA followed by segmental or subsegmental TAE with a mixture of an anticancer drug and Lipiodol. We compared the drainage area of the HCC depicted on SLDCTHA with the Lipiodol accumulation in the nontumorous liver adjacent to the HCC on CT after TAE (LpCT). RESULTS: In 26 of the 56 patients, a definite corona enhancement around the HCC, suggesting the drainage of blood from the tumor into the surrounding liver parenchyma, was seen on the late phase of SLDCTHA. In 17 of these 26 patients (65.4%), LpCT showed a more intense accumulation of Lipiodol in the nontumorous liver adjacent to the HCC that corresponded to the drainage area revealed on SLDCTHA. CONCLUSION: The drainage of blood from the HCC was considered to be a possible mechanism of the accumulation of Lipiodol in the nontumorous liver adjacent to the HCC.

24
UI - 12068529
AU - D'Albuquerque LA; de Oliveira e Silva A; Garcia CE
TI - [Liver transplant in hepatocellular carcinoma: would the organ shortage and good outcome justify the expansion of indication or of new surgical techniques?]
SO - Arq Gastroenterol 2001 Oct-Dec;38(4):213-5

25
UI - 12068530
AU - Parolin MB; Coelho JC; Matias JE; Puccinelli V; Jarabiza R; Ioshii SO
TI - [Results of liver transplantation in patients with hepatocellular carcinoma]
SO - Arq Gastroenterol 2001 Oct-Dec;38(4):216-20
AD - Servico de Transplante Hepatico, Servico de Anatomia Patologica, Hospital de Clinicas, Universidade Federal do Parana (HC-UFPR), Curitiba, PR. mbparolin@hotmail.com
BACKGROUND: Hepatocellular carcinoma is one of the most common malignancies worldwide. Liver transplantation has emerged as a good option for early-stage hepatocellular carcinoma yielding survival rates as good as for recipients without this type of tumor. OBJECTIVE: To assess the outcome of cirrhotic patients with hepatocellular carcinoma undergoing liver transplantation at the Liver Transplantation Service of the "Hospital de Clinicas", Federal University of Parana, Curitiba, PR, Brazil. METHODS: Retrospective study of cirrhotic patients with hepatocellular carcinoma undergoing orthotopic liver transplantation at diagnosis of hepatocellular carcinoma was established during the pretransplant workup in five patients and the tumor was an incidental finding in the native liver in three. The indication for liver transplantation was restricted to solitary tumor equal to or less than 5 cm or up to 3 nodules, with each nodule measuring less than 3 cm, and no evidence of vascular invasion or extrahepatic spread. Patient survival and evidence of tumoral recurrence posttransplant were evaluated. RESULTS: The most common cause for pretransplantation liver disease was hepatitis C virus (50%). On examination of the explanted liver, the majority of patients (6/8, 75%) had a single lesion; one patient had two nodules and one had a multifocal hepatocellular carcinoma found incidentally in the native liver. Tumor size ranged from 0.2 to 5.0 cm. All cases had neither vascular invasion nor linfonodal envolvement. All patients remained alive and free of tumor recurrence at the time of the study with a mean follow-up of 18.5 months (range, 5-29 months). CONCLUSION: Liver transplantation is a good therapeutic option for early stage hepatocellular carcinoma arising in cirrhotic patients. With proper selection, liver transplantation can offer excellent survival rates free of tumor recurrence.

26
UI - 11923620
AU - Frilling A; Broelsch CE
TI - Resection of hepatocellular carcinoma with out preoperative tumor biopsy.
SO - Ann Surg 2002 Apr;235(4):604; discussion 604-5

27
UI - 12115331
AU - Fuchs J; Rydzynski J; Von Schweinitz D; Bode U; Hecker H; Weinel P;
TI - Burger D; Harms D; Erttmann R; Oldhafer K; Mildenberger H; Study Committee of the Cooperative Pediatric Liver Tumor Study Hb 94 for the German Society for Pediatric Oncology and Hematology Pretreatment prognostic factors and treatment results in children with hepatoblastoma: a report from the German Cooperative Pediatric Liver Tumor Study HB 94.
SO - Cancer 2002 Jul 1;95(1):172-82
AD - Department of Pediatric Surgery, University of Tuebingen, Tuebingen, Germany. joerg.fuchs@med.uni-tuebingen.de
BACKGROUND: In the past 20 years, a dramatic improvement in the prognosis of patients with hepatoblastoma (HB) has been achieved by combining surgery with chemotherapy in several national and international trials. A worldwide, unsolved problem remains the treatment of patients with advanced or metastatic HB. METHODS: The German Cooperative Pediatric Liver Tumor Study HB 94 was a prospective, consisting of cisplatin, ifosfamide, and doxorubicin (CDDP/IFO/DOXO) and/or etoposide and carboplatin (VP16/CARBO). The prognostic significance of the surgical strategy, pretreatment factors, and tumor characteristics for disease free survival (DFS) were analyzed. RESULTS: Sixty-nine children with HB were treated in the HB 94 study. The median follow-up of survivors was 58 months (range, 32-93 months). Fifty-three of 69 patients (77%) remained alive, and 16 of 69 patients (23%) died. Long-term DFS was as follows: 26 of 27 patients had Stage I HB, 3 of 3 patients had Stage II HB, 19 of 25 patients had Stage III HB, and 5 of 14 patients had Stage IV. A complete resection of the primary tumor was achieved in 54 of 63 patients (86%). Six children (8%) had no surgical treatment. Twenty-two tumors were resected primarily, and 41 children underwent surgery after initial chemotherapy. Two children underwent liver transplantation. There was no perioperative death. Forty-eight children received primary chemotherapy with CDDP/IFO/DOXO. Forty-one of 48 children achieved partial remission after CDDP/IFO/DOXO. Eighteen children with advanced or recurrent HB underwent VP16/CARBO chemotherapy, with a response achieved by 12 children. The relevant pretreatment prognostic factors were growth pattern of the liver tumor (P = 0.0135), vascular tumor invasion (P = 0.0039), occurrence of distant metastases (P = 0.0001), initial alpha-fetoprotein level (P = 0.0034), and surgical radicality (P < 0.0001). CONCLUSIONS: The current results underline the necessity of preoperative chemotherapy in all children with HB. Complete tumor resection is one of the main prognostic factors. Copyright 2002 American Cancer Society.

28
UI - 11824052
AU - Aldrighetti L; Arru M; Calori G; Moiraghi L; Caterini R; Mukenge S;
TI - Ferla G [Advanced age as risk factor in liver resection surgery]
SO - Chir Ital 2001 Nov-Dec;53(6):773-82
AD - Divisione di Chirurgia I, Istituto Scientifico, Ospedale San Raffaele, Via Olgettina 60, 20132 Milano.
To evaluate the influence of age on the outcome of liver resections, 105 consecutive patients undergoing hepatic resection were divided into two groups: age > or = 65 years [Old Group (O-Group)] and age < 65 years [Young Group (Y-Group)]. O-Group and Y-Group patients were analyzed comparatively in terms of primary diagnosis, concomitant diseases, previous surgery, type of operation (major or minor resection), associated procedures, presence and length of portal clamping, intraoperative blood losses and transfusions, and length of operation. The end points of the study were postoperative mortality, morbidity, transfusions, and length of post-operative hospitalization. The Y-Group included 61 resections in 60 patients, with a mean age of 52 +/- 10 years (mean +/- SD), range 23-64 years, and the O-Group 44 resections in 43 patients, with a mean age of 71 +/- 4 years, range 65-82 years. The O-Group included more cases of hepatoma (45.4% vs 18%, p = 0.002) and cirrhosis (40.9% vs 18.7%, p = 0.017). Median length of operation was slightly higher in the Y-Group (330 vs 270 minutes, p = 0.003). The O- and Y-Groups were comparable (p = n.s.) when evaluated for all other variables listed. As regards the end points of the study, length of post-operative hospitalization was identical in both groups (median 9 days, range 5-60 days) and neither PRBC transfusions (O-Group vs Y-Group: 16% vs 25%) nor FFP transfusions (O-Group vs Y-Group: 13.6% vs 6.5%) showed any statistically significant difference. Postoperative mortality consisted in 1 death among the younger patients while no deaths were recorded among the older patients. Postoperative morbidity was higher in the Y-Group than in the O-Group (31.1% vs 20.5%, p = 0.59). Advanced age does not negatively affect the outcome of liver resections.

29
UI - 12115351
AU - Fuchs CS; Clark JW; Ryan DP; Kulke MH; Kim H; Earle CC; Vincitore M;
TI - Mayer RJ; Stuart KE A phase II trial of gemcitabine in patients with advanced hepatocellular carcinoma.
SO - Cancer 2002 Jun 15;94(12):3186-91
AD - Department of Adult Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA. Charles_Fuchs@dfci.harvard.edu
BACKGROUND: There is no effective systemic therapy for patients with hepatocellular carcinoma. A recent trial reported a moderate antitumor activity for gemcitabine among Asian patients with advanced hepatocellular carcinoma. This led to our examination of the efficacy and tolerability of the drug in a population of U.S. patients. METHODS: Thirty patients with measurable, unresectable, or metastatic hepatocellular carcinoma who had received at least one previous form of systemic therapy were enrolled. All patients were required to have adequate major organ function and performance status. Patients received gemcitabine (1000 mg/m(2) intravenously over 30 minutes weekly) for 3 consecutive weeks followed

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