Tumour biopsy is usually considered mandatory for patient management by oncologists. Currently percutaneous ablation is used therapeutically for cirrhotic patients with small hepatocellular carcinoma (HCC), not suitable for resection or waiting for liver transplantation. However malignant seeding is a recognized complication of both diagnostic and therapeutic procedures in patients with HCC. Although percutaneous therapy whether with or without biopsy of a suspected HCC nodule may minimize the risk of seeding, this has not been confirmed.

To evaluate the risk of seeding, defined as new neoplastic disease occurring outside the liver capsule, either in the subcutaneous tissue or peritoneal cavity following needle biopsy and/or local ablation therapy (LAT).

A literature search resulted in 179 events in 99 articles between January 1983 and February 2007: 66 seedings followed liver biopsy, 26 percutaneous ethanol injection (PEI), 1 microwave, 22 radiofrequency ablation (RFA), and 64 after combined biopsy and percutaneous treatment (5 microwave; 33 PEI; 26 RFA).

In 41 papers specifying the total number of patients biopsied and/or treated, the median risk of seeding was 2.29% (range 0-11%) for biopsy group; 1.4% (1.15-1.85%) for PEI when used with biopsy and 0.61% (0-5.56%) for RFA without biopsy, 0.95% (0-12.5%) for RFA with biopsy and 0.72% (0-10%) for liver nodules (including non-HCC nodules) biopsied and ablated.

Risk of seeding with HCC is substantial and appears greater with using diagnostic biopsy alone compared to therapeutic percutaneous procedures. This risk is particularly relevant for patients being considered for liver transplantation.

The prognosis of hepatocellular carcinoma (HCC) with tumor thrombosis of the main trunk or major branches of the portal vein (mPVTT) is extremely poor, even if it is curatively resected. Uncontrollable multiple metastases to the residual liver are often observed within several months after the operation. We report here the results of a pilot study, showing the efficacy of adjuvant arterial infusion chemotherapy after the resection of HCC with mPVTT.

Twelve patients had curative resection of HCC with mPVTT. Six of the patients were treated by the arterial infusion of a chemotherapeutic agent via a subcutaneously implanted injection port after curative resection of HCC with mPVTT. The initial course consisted of the daily administration of cisplatin (CDDP) and continuous infusion of 5-fluorouracil (5-FU). This was followed by the weekly or biweekly administration of CDDP and subsequent infusion of 5-FU until the cumulative dose of 5-FU reached 15 g.

The median overall survival time was 58.0 months with adjuvant chemotherapy and 8.0 months without adjuvant chemotherapy. The median disease-free interval was 15.0 months with adjuvant chemotherapy and 4.0 months without adjuvant chemotherapy. Adverse reactions were tolerable nausea and loss of appetite.

This chemotherapeutic regimen achieved favorable results and may be useful as adjuvant chemotherapy in treating patients after curative resection of HCC with mPVTT.

Hepatocellular carcinoma caused by hepatitis B and hepatitis C are global scourges but are likely to peak in incidence in the next 2 decades and then decline. Universal vaccination has been effective in stemming the incidence of chronic hepatitis B and early-onset HCC in regions of high endemicity where implemented, but preventive measures in HCV are not yet available. After the attrition of older affected generations, the incidence of HCC will likely decline rapidly. While no vaccine is currently available for hepatitis C, cases are projected to peak and decline because of a marked reduction in transmission as a result of behavioral modification and safeguarding of blood supplies. Until these epidemiologic projections come to pass, management of hepatocellular carcinoma will continue to become a progressively more frequently encountered clinical challenge. Therapy for chronic hepatitis may ameliorate but will not eliminate the development of tumors. The demand for orthotopic liver transplantation will continue to climb, and palliative therapies for non-resectable cases will require studies aimed at optimization of benefit. LDLT may remain an option for high-risk patients affording tumor-free survival for some otherwise terminal patients.

Cutaneous seeding is a rare complication of interventional ultrasound procedures. We describe a case of needle-track cutaneous seeding of hepatocellular carcinoma (HCC) after sonographically guided percutaneous ethanol injection (PEI). In our case, the seeding might have been related to the type of needle used and the multiple passes required to treat the liver lesion. Despite the risk of needle-track seeding, PEI remains useful in the treatment of HCC.

Since hematogenous spread of tumor cells may adversely affect the prognosis of patients with hepatocellular carcinoma, we prospectively analyzed whether the presence of alpha-fetoprotein (AFP) messenger RNA (mRNA) in blood, used as a marker of circulating hepatocellular carcinoma cells, correlates with outcome.

Eighty-eight patients were enrolled between December 1993 and August 1995, and 81 were followed until the end of 1997. All patients were treated with percutaneous ethanol injection therapy and/or transarterial embolization during follow-up. The status of AFP mRNA in blood was serially determined. Cumulative metastasis-free survival and overall survival were analyzed in relation to AFP mRNA and other clinical and laboratory variables.

Among 81 patients followed, 54 were positive for AFP mRNA at entry and 27 were negative. Extrahepatic metastasis developed more frequently among the AFP mRNA-positive patients (13 of 54) than among the AFP mRNA-negative patients (2 of 27) (p=0.0296). After treatment, AFP mRNA became negative in 24 of 54 patients (44%). Cumulative metastasis-free survival and overall survival were significantly better in the 24 patients whose AFP mRNA became negative after treatment than in the 30 patients with persistently positive AFP mRNA (p= 0.0001 and p<0.0001, respectively).

The presence or absence of AFP mRNA in blood is a predictor of outcome in patients with hepatocellular carcinoma.

The treatment of patients with compensated liver cirrhosis and small hepatocarcinomas remains controversial. Whereas partial hepatectomy (PH) is currently recommended, the role of orthotopic liver transplantation (OLT) has become progressively accepted. We used the techniques of decision analysis to measure the clinical benefits and the economic consequences of immediate resection versus transplantation in patients with compensated cirrhosis and who were diagnosed with small hepatocellular carcinoma (HCC). We restricted our analysis to patients with resectable carcinomas, which is either solitary tumor (< or = 5 cm in diameter), or multiple tumors (up to 3), none being > 3 cm in diameter and, in both cases, no tumor invasion of blood vessels. We took into account the risks of tumor spreading and dissemination and/or development of decompensated cirrhosis while waiting for donor organs because organ shortage is presented as the main obstacle to transplantation in these patients. Our analysis suggests that orthotopic liver transplantation (OLT) offers a substantial survival benefit compared with resection, ranging from a minimum of 1 year to a maximum of 4.7 years depending on treatment-related survival rates. However, the magnitude of this benefit relies on the availability of an organ donor; therefore, if the waiting period exceeds 6 to 10 months, depending on tumor growth pattern, the increase in life expectancy provided by transplantation is overwhelmed by the risks that patients face while waiting for transplantation. Consequently, partial resection becomes the preferred strategy. The predicted marginal cost-effectiveness ratios of transplantation compared with resection would range between $44,454 and $183,840 per additional year gained mainly influenced by the time delay before getting a transplant. We conclude that compared with partial hepatectomy (PH), OLT for resectable hepatocarcinoma(s) offers substantial survival benefit among well-targeted subgroups of patients as long as an organ donor is available within a maximal 6 to 10 months time delay, which is a plausible scenario in most centers with a liver transplant program. However, the marginal cost-effectiveness ratios incurred by this strategy are higher than that of many other current medical interventions.

Percutaneous ethanol injection (PEI) has become a widely used procedure in the treatment of hepatocellular carcinoma (HCC). However, the criteria for selecting patients are not standardized, and little information is available about the complications of the procedure.

A questionnaire was sent to 11 experienced Italian centers. It investigated: the size and the number of HCC nodules suitable for treatment and the Child-Pugh risk class of the associated cirrhosis; the performance of the procedure; the number and characteristics of the patients treated; and, finally, any complications.

Most of the centers performed PEI in single HCC nodules less than 5 cm in diameter or in multiple nodules if fewer than three, the larger being less than 3 cm. Patients in Child-Pugh's classes A, B, and C with single nodules were generally considered for PEI. A prothrombin time of less than 40% and a platelet count of less than 40,000/mm3 contraindicated PEI in most of the centers. PEI was generally performed on outpatients, using Chiba or spinal needles. One thousand and sixty-six patients (8118 sessions) were enrolled; 74% had a single HCC nodule and 26% multiple nodules. All except four had cirrhosis; 53% were in Child class A, 38% in class B, and 9% in class C. The mean number of sessions needed to destroy an HCC nodule was 6.7 (range, 2-14), with a mean alcohol injection volume of 5.0 ml per session (range, 2-20 ml). One death (0.09%) and 34 complications (3.2%) were reported. Among the complications we call attention to the hemorrhagic ones (eight cases) and tumoral seeding (seven cases). Severe pain experienced during the maneuver led to discontinuation of the procedure in 3.7% of the patients; 13.5% of the patients required analgesics and 24% had fever after PEI.

Some procedural aspects of PEI treatment differ among the various centers a standardization is advisable. In the present survey PEI is a low-risk technique.

Hepatocellular carcinoma (HCC) with tumor thrombosis of the main trunk of the portal vein (PVTT) has a poor prognosis. This study was designed to evaluate the efficacy of arterial infusion chemotherapy for advanced HCC of this type.

Nine patients with HCC were treated by arterial infusion of a chemotherapeutic agent via a subcutaneously implanted injection port. One course consisted of the daily administration of cisplatin (10 mg for 1 hour on Days 1-5) and the subsequent infusion of 5-fluorouracil (250 mg for 5 hours on Days 1-5). In principle, patients were to receive four serial courses of chemotherapy.

The mean course of chemotherapy was 4.6 (range, 2.6-7.6) months. The serum total concentrations of alpha-fetoprotein and des-gamma-carboxyprothrombin were reduced after chemotherapy in most of the patients. Two patients showed complete response (CR) with disappearance of HCC and PVTT after treatment, and the other two showed partial response (PR) (response rate [CR + PR/All cases], 44.4%). The 3-year survival rate was 40%. The mean survival after the therapy was 14.9 (range, 4.1-48.9) months. The 50% survival was 9.2 months. Adverse reactions were tolerable nausea and loss of appetite.

This chemotherapeutic regimen achieved favorable results and may be useful in treating patients with HCC with tumor thrombosis of the main trunk of the portal vein.

The incidence of hepatocellular carcinoma is increased in patients with cirrhosis. Therefore, surveillance for detection of small tumors has been proposed. The aim of this study was to determine the clinical and economical effects of screening for small hepatocellular carcinoma in Western patients with Child-Pugh class A cirrhosis.

Based on a decision analysis model representing the natural history of cirrhosis and the continuing risk of developing cancer, we compared a strategy of performing ultrasound and alpha-fetoprotein dosage every 6 months with a strategy of seeking tumors only if they are clinically suspected. In both strategies, partial hepatectomy was performed for patients with compensated cirrhosis and diagnosed with resectable tumors. We did not consider orthotopic liver transplantation as a therapeutic option. Data were drawn from MEDLINE search.

For most patients seen in the daily practice, screening provides negligible benefits in life expectancy (< 3 months), even when the incidence of cancer is high (6% per year), and despite our choice of consistent biases in favor of screening. The cost-effectiveness ratios of systematic surveillance range between $48,000 and $284,000 for each additional life-year gained, more than other common medical practices. However, for a minority of patients with a predicted cirrhosis-related survival rate above 80% at 5 years (the "ideal" candidates) screening may increase mean life expectancy by 3 to 9 months depending on age, cancer incidence (1.5% to 6% per year), and survival rate after surgery (40% to 60% at 3 years). In this clinical setting, the cost-effectiveness ratios range between $26,000 and $55,000 for each additional life-year gained.

For most patients with cirrhosis seen in the daily practice, biannual screening to detect symptomless tumors accessible to surgical resection provides negligible benefit in life expectancy. In addition, the cost-effectiveness ratios incurred by this strategy is more important than that of many current medical practices. On the other hand, for well-targeted patients with the longest reported cirrhosis-related survival rate, screening may substantially increase mean life expectancy, at lower costs. Careful selection of these patients with a favorable cirrhosis-related prognosis requires further studies.