Percutaneous intraarterial techniques for treatment of liver tumors are continuously under development. New therapeutic methods are available (such as microsphere-encapsulated chemotherapy or yttrium 90 microspheres) and presently under evaluation. These methods enlarge the field of indications, i.e. in metastasis from colorectal cancer. Hepatocellular carcinoma and metastasis from neuroendocrine tumours are the main pathologies favourably responding to "conventional" chemoembolization. Thank to controlled studies and meta-analysis performed along the last ten years, curative-palliative-as well as adjuvant-indications for chemoembolization in hepatocellular carcinoma are now wellestablished.

Hepatocellular carcinoma (HCC) is increasing in many countries as a result of an increase in hepatitis C virus (HCV) infection since World War II. The epidemiology of HCC varies with the global region. There have been conflicting observations from different parts of the world concerning the frequency of HCC in patients who in the distant past had post-transfusion non-A, non-B hepatitis. The genetic basis of hepatocarcinogenesis is still poorly understood. In hepatitis B virus (HVB) associated HCC, codon 249 mutation in the p 53 gene seems more related to exposure to aflatoxin B1 than to hepatocarcinogenesis itself. HCC that occurs in children in high HBV endemic regions could be associated with germ-line mutations, but little information is available; not much is known about chemical hepatocarcinogens in the environment other than aflatoxins. The X gene of HBV seems to play an important role in HBV-associated hepatocarcinogenesis. There are preliminary observations on the molecular mechanism of HCV-associated HCC, such as HCV core protein inducing HCC in transgenic mice and the NS3 genome transforming NIH 3T3 cells. Pathological distinction between preneoplastic and very early transformed lesions still depends on classical morphology, and a more genetically oriented differential diagnosis is required. Clinical diagnosis based on modern imaging has improved greatly, but is still unsatisfactory in the differential diagnosis of preneoplastic and early transformed nodules, because the vasculature changes that occur within the nodule are not accurately discerned with the current imaging. Use of sensitive des-gamma-carboxy prothrombin (PIVKA II) assay, and lectin affinity chromatography separating HCC specific subspecies of AFP molecules with a more practical biochemical technique will further improve diagnosis. Early diagnosis and transplantation are the best treatment at the moment, but transplantation is not widely available because of the donor shortage. Despite successful resection, the remnant cirrhotic liver frequently develops new HCC lesions, seriously curtailing long-term survival. All-out efforts should be directed to the prevention of HCC, through prevention of viral hepatitis, prevention of acute hepatitis from becoming chronic, prevention of chronic hepatitis from progressing to cirrhosis, and prevention of the cirrhotic liver from developing HCC (chemoprevention). At the moment, very few such studies exist.

PURPOSE: To study local therapeutic efficacy, side effects, and complications of radio-frequency (RF) ablation in the treatment of medium and large hepatocellular carcinoma (HCC) lesions in patients with cirrhosis or chronic hepatitis. MATERIALS AND METHODS: One-hundred fourteen patients who were under conscious sedation or general anesthesia had 126 HCCs greater than 3.0 cm in diameter treated with RF by using an internally cooled electrode. Eighty tumors were medium (3.1-5.0 cm), and 46 were large (5.1-9.5 cm). The mean diameter for all tumors was 5.4 cm. At imaging, 75 tumors were considered noninfiltrating, and 51 were considered infiltrating. RESULTS: Complete necrosis was attained in 60 lesions (47.6%), nearly complete (90%-99%) necrosis in 40 lesions (31.7%), and partial (50%-89%) necrosis in the remaining 26 lesions (20.6%). Medium and/or noninfiltrating tumors were treated successfully significantly more often than large and/or infiltrating tumors. Two major complications (death, hemorrhage requiring laparotomy) and five minor complications (self-limited hemorrhage, persistent pain) were observed. The single death was due to a break in sterile technique rather than to the RF procedure itself. CONCLUSION: RF ablation appears to be an effective, safe, and relatively simple procedure for the treatment of medium and large HCCs.

PURPOSE: To compare the effectiveness of radio-frequency (RF) thermal ablation with that of percutaneous ethanol injection (PEI) for the treatment of small hepatocellular carcinoma (HCC) in patients with cirrhosis. MATERIALS AND METHODS: A series of 102 patients with hepatic cirrhosis and either single HCC 5 cm in diameter or smaller or as many as three HCCs each 3 cm or smaller (overall number of lesions, 142) randomly received either RF ablation (n = 52) or PEI (n = 50) as the sole first-line anticancer treatment. Mean follow-up was 22.9 months +/- 9.4 (SD) in the RF group and 22.4 months +/- 8.6 in the PEI group. Prognostic value of treatment techniques was assessed with univariate and multivariate Cox proportional hazards regression models. RESULTS: One- and 2-year survival rates were 100% and 98% in the RF group and 96% and 88% in the PEI group, respectively (univariate relative risk [RR]= 0.20; 95% CI: 0.02, 1.69; P =.138). One- and 2-year local recurrence-free survival rates were 98% and 96% in the RF group and 83% and 62% in the PEI group, respectively (univariate RR = 0.17; 95% CI: 0.06, 0.51; P =.002). One- and 2-year event-free survival rates were 86% and 64% for the RF group and 77% and 43% for the PEI group, respectively (univariate RR = 0.48; 95% CI: 0.27, 0.85; P =.012). RF treatment was confirmed as an independent prognostic factor for local recurrence-free survival rates with multivariate analysis (adjusted RR = 0.20; 95% CI: 0.05, 0.73; P =.015). CONCLUSION: RF ablation is superior to PEI with respect to local recurrence-free survival rates.

BACKGROUND: Radiofrequency (RF)-induced tissue coagulation represents a new approach for the thermal destruction of tumors within the liver. The purpose of the current study was to 1) assess technique safety; 2) determine the extent and evolution of induced cellular damage; and 3) correlate the observed pathologic effects with radiologic studies. METHODS: Twenty-three tumors measuring </= 8 cm (19 colorectal metastases and 4 hepatomas) in 22 patients were treated with RF (range, 500-1550 milliamperes) using internally cooled electrodes. All treated tumors were resected to allow pathologic analysis. Eleven tumors were treated intraoperatively under ultrasonographic guidance and excised immediately. Twelve tumors were treated percutaneously using ultrasound or computed tomography (CT) guidance and subsequently were excised 3-7 days after ablation. Contrast-enhanced CT (n = 12) and magnetic resonance imaging (MRI)(n = 2) were performed after ablation of all percutaneously treated patients. RESULTS: Tumors treated intraoperatively did not demonstrate definitive coagulative necrosis. However, pathologic abnormalities suggestive of tissue injury were observed with hematoxylin and eosin staining, and absent cytosolic and mitochondrial enzyme activity suggested irreversible cellular damage. In contrast, specimens removed > 3 days after ablation showed definite, contiguous coagulative necrosis without intervening areas of viable tumor. CT and MRI scans demonstrated circumscribed hypodense, nonenhancing regions surrounding the electrode tract as early as 15 minutes after ablation. These corresponded within 2 mm to measurements of coagulation at pathology. CONCLUSIONS: RF ablation is a minimally invasive and safe approach to the treatment of tumors in the liver. Tumors treated with RF energy do not immediately demonstrate coagulative necrosis, but do show evidence of irreversible cellular damage. The extent of tumor necrosis correlates closely with findings at contrast-enhanced imaging.

This study analyzed the natural history and prognostic factors of patients with nonsurgical hepatocellular carcinoma (HCC). Twenty variables from 102 cirrhotic patients with HCC who were not treated within prospective randomized controlled trials (RCT) were investigated through uni- and multivariate analyses. None of them was suitable for radical therapies (surgical resection, liver transplantation, or ethanol injection) or presented end-stage disease as reflected by an Okuda stage 3 or a Performance Status >/=3. Sixty-five patients were Child-Pugh A, 34 were B, and 3 were C. Most of them exhibited a preserved Performance Status Test (PST)(0 = 56; 1 = 38; 2 = 8). Tumor was solitary in 26 (</=5 cm in 16) and multinodular/massive in 76. After a median follow-up of 17 months, 79 patients died, the 1-, 2-, and 3-year survival being 54%, 40%, and 28%. The multivariate study identified PST (P =.01), constitutional syndrome (P =.04), vascular invasion (P =.001), and extrahepatic spread (P =.04) as independent predictors for mortality. The 1-, 2-, and 3-year survival for the 48 patients without adverse factors (Stage 0) was 80%, 65%, and 50%, respectively, and 29%, 16%, and 8% in the 54 patients with at least one adverse parameter (Stage I). Therefore, Stage 0 would correspond to an intermediate stage, while Stage I would represent an advanced status, before reaching an end-stage phase. In conclusion, the outcome of nonsurgical HCC is not homogeneously grim and may be predicted by assessing the presence of symptoms and of an invasive tumoral pattern. Therapeutic trials should be designed and evaluated considering these characteristics.

A randomized trial of hepatic arterial chemoembolization was conducted in 42 patients with unresectable hepatocellular carcinoma. These patients represented 41% of patients with hepatocellular carcinoma seen during the inclusion period. In the remaining 59%, 9% had resectable tumours and 50% had unresectable tumours with contraindication for chemoembolization. Patients received either repeated chemoembolization with gelfoam powder and doxorubicin (group 1) or symptomatic treatment (group 2). There was no difference in age, prevalence of cirrhosis or staging according to Okuda between the two groups of patients. A complete tumour response (assessed by arteriography, ultrasonography and serum alphafetoprotein) was observed in four patients, and a partial response in three other patients from group 1. Actuarial survival rates were 33 and 24% in group 1 and 52 and 31% in group 2 at 6 and 12 months, respectively (differences were not significant--logrank test). With the treatment used in our study, chemoembolization did not prolong the survival time of patients with unresectable hepatocellular carcinoma. There were, however, some complete or partial responses. The high spontaneous 1-year survival rate of untreated patients was probably due to the exclusion of the most severely ill patients. Our results do not support the use of this method of chemoembolization in the treatment of hepatocellular carcinoma.

Hepatocellular carcinoma is the most frequent primary malignancy of the liver and appears to be rising in incidence in the United States and other developed western countries. Imaging studies play a key role in diagnosis of hepatocellular carcinoma, and more and more commonly, patients are being diagnosed at an asymptomatic stage. The use of triphasic computed tomography scanning and improved magnetic resonance imaging equipment and protocols has led to greater sensitivity and specificity for these techniques in diagnosis of hepatocellular carcinoma. Accurate staging of hepatocellular carcinoma is important in determining prognosis and in helping decide the best treatment for each patient. No one staging system appears optimal, but important factors to be considered are the size of the tumor, severity of underlying liver disease, and the functional status of the patient. Liver transplantation has grown in importance as a treatment for hepatocellular carcinoma but may be limited by availability of donor organs and long waiting times. This situation may be improved by greater use of living donor liver transplantation. Hepatic resection remains an important treatment modality for hepatocellular carcinoma, particularly in the absence of cirrhosis. Tumor ablation by alcohol injection or radiofrequency ablation is associated with favorable outcomes and may be considered a potentially curative treatment. Early diagnosis of hepatocellular carcinoma remains a key goal in improving the poor prognosis of this form of liver cancer. Identifying hepatocellular carcinoma at an early stage is often associated with having better treatment options for patients with small, asymptomatic tumors.

Hepatocellular carcinoma (HCC) has ranked second in cancer mortality in China since the 1990s and is increasing in frequency among males in many countries. Hepatitis B and C viruses, aflatoxin and algal toxin in the contaminated drinking water remain major aetiological factors and hepatitis G virus and transfusion-transmitted virus can not be excluded. A prospective randomized control trial screening for HCC in a high-risk population using alpha fetoprotein (AFP) and ultrasonography has demonstrated a decrease in HCC mortality. Rapidly progressing medical imaging has continuously contributed to the improving treatment results. Surgical resection still plays a major role in influencing prognosis of HCC. Studies on recurrence and metastasis after curative resection have become a key issue for further improvement of the surgical outcome. Regional cancer therapies are progressing rapidly, based on the advances in early diagnosis. The advantages and disadvantages of these are noted. Multimodality combination and sequential treatment has been accepted as an important approach for unresectable HCC and cytoreduction and sequential resection have attracted attention. Conformal radiotherapy has shown important potential for HCC treatment. Intra-arterial chemotherapy has been repeatedly proved effective; however, systemic chemotherapy for HCC remains disappointing. The effects of tamoxifen are questionable, whereas alpha-interferon has been shown to have significant potential, particularly in prevention of recurrence. All of these treatments have resulted in continuing improvement of HCC prognosis in some centres.

This study was intended to compare the survival rates of two contemporary cohorts of patients with solitary hepatocellular carcinomas < or = 4 cm subjected to surgical resection (n = 33) or percutaneous ethanol injection (n = 30). Outcomes in a third cohort, 21 patients with hepatocellular carcinoma who underwent orthotopic liver transplantation, were also assessed. Surgical and ethanol-treated patients were similar with regard to age and tumor stage, differing only in liver function; 30 of the 33 surgical patients were of Child-Pugh class A, whereas only 7 of the 30 ethanol-treated patients were of class A (p < 0.05). Surgical resection was successful in 30 cases; ethanol injection achieved initial success in 23 patients. Tumor recurrence rate at 2 yr was 45% in the surgical group and 66% in the ethanol group. The difference was significant only for cases with tumors between 3 and 4 cm. Despite poorer liver function, the 1-, 2-, 3- and 4-yr survival rates of ethanol-treated patients (83%, 66%, 55% and 34%, respectively) were not different from those of surgically treated patients (81%, 73%, 44% and 44%, respectively). The 1- and 2-yr survival rates of patients given liver transplants were 81% and 66%, without tumor recurrence, after 16-mo follow-up. These data confirm that ethanol injection is a useful treatment for patients with solitary small hepatocellular carcinomas and suggest that surgical resection and liver transplantation may achieve better results only after strict candidate selection to reduce mortality and tumor recurrence during follow-up.