Laura Crocetti

Local-Regional Treatment of Hepatocellular Carcinoma

Local-regional treatments play a key role in the management of hepatocellular carcinoma (HCC). Image-guided tumor ablation is recommended in patients with early-stage HCC when surgical options are precluded and can replace resection in selected patients. Radiofrequency (RF) ablation has shown superior anticancer effects and greater survival benefit with respect to the seminal percutaneous technique, ethanol injection, in meta-analyses of randomized controlled trials and is currently established as the standard method for local tumor treatment. Novel thermal and nonthermal techniques for tumor ablation, including microwave ablation and irreversible electroporation, seem to have potential to overcome the limitations of RF ablation and warrant further clinical investigation. Transcatheter arterial chemoembolization (TACE) is the standard of care for patients with asymptomatic noninvasive multinodular tumors in intermediate-stage disease. Embolic microspheres that have the ability to release a drug in a controlled and sustained fashion have been shown to substantially increase the safety and efficacy of TACE in comparison to conventional ethiodized oil-based regimens. The available data for radioembolization with yttrium 90 suggest that this is a potential new option for patients with HCC, and future studies should be devoted to assessments of the role of radioembolization in the treatment algorithm for HCC.

Quality Improvement Guidelines for Radiofrequency Ablation of Liver Tumours

The development of image-guided percutaneous techniques for local tumour ablation has been one of the major advances in the treatment of liver malignancies. Among these methods, radiofrequency ablation (RFA) is currently established as the primary ablative modality at most institutions. RFA is accepted as the best therapeutic choice for patients with early-stage hepatocellular carcinoma (HCC) when liver transplantation or surgical resection are not suitable options [1, 2]. In addition, RFA is considered a viable alternate to surgery (1) for inoperable patients with limited hepatic metastatic disease, especially from colorectal cancer, and (2) for patients deemed ineligible for surgical resection because of extent and location of the disease or concurrent medical conditions [3]. These guidelines were written to be used in quality-improvement programs to assess RFA of HCC and liver metastases. The most important processes of care are (1) patient selection, (2) performing the procedure, and (3) monitoring the patient. The outcome measures or indicators for these processes are indications, success rates, and complication rates.

Percutaneous radiofrequency ablation of hepatic colorectal metastases: Technique, indications, results, and new promises

Surgical resection is the standard of care for colorectal metastases isolated to the liver. However, only 10–25% of the patients are eligible for resection because of extent and location of the disease in the liver or concurrent medical conditions. Image-guided radiofrequency (RF) ablation is a minimally invasive technique that is emerging as a viable alternate treatment of nonsurgical patients with limited hepatic metastatic disease. Several series have shown that RF ablation can result in complete tumor eradication in properly selected candidates and have provided indirect evidence that the treatment improves survival. In a recent multicenter trial including 423 patients, overall survival of RF-ablation treated patients reached 47% at 3 years and 24% at 5 years. RF ablation technology is undergoing continuous improvement, and its clinical application has been successfully expanded to the treatment of colorectal metastases to the lung. Randomized trials comparing RF ablation with either surgical resection or chemotherapy protocols, however, are still missing. In this article, we review technique, indications, clinical results, and future prospects of RF ablation in the therapeutic management of metastatic colorectal cancer patients.

Targeting Liver Lesions for Radiofrequency Ablation : An Experimental Feasibility Study Using a CT-US Fusion Imaging System

Purpose:To investigate the feasibility and validity of real-time guidance using a fusion imaging system that combines ultrasound (US) and computed tomography (CT) in the targeting and subsequent radiofrequency (RF) ablation of a liver target inconspicuous on US. Methods and Materials:The study was designed as an experimental ex vivo study in calf livers with radiopaque internal targets, inconspicuous at US, simulating a focal liver lesion. The study included 2 phases. The initial phase was to examine the feasibility of matching preprocedural volumetric CT data of the calf livers with real-time US using a commercially available multimodality fusion imaging system (Virtual Navigator System, Esaote SpA, Genoa, Italy), and to assess the accuracy of targeting using a 22 gauge cytologic needle. The second phase of the study was to validate such a technique using a 15 gauge RF multitined expandable needle (RITA Medical Systems, Mountain View, CA) and to examine the accuracy of the needle placement relative to the target. The tip of the trocar of the RF needle had to be placed 1 cm from the target and then the hooks had to be deployed to 3 cm. Unenhanced CT of the liver and multiplanar reconstructions were performed to calculate accuracy of positioning, ie, the lateral distance between the needle and the target, the distance between the tip of the trocar of the RF electrode and the target, and the lateral distance between the central tine of the RF electrode and the target. Results:All calf livers underwent successful CT-US registration with a mean registration error of 3.0 ± 0.1 mm and 2.9 ± 0.1 mm in the initial and second phase of the study, respectively. In the initial phase an overall number of 24 insertions were performed after the US-CT guidance. The mean needle to target distance was 1.9 ± 0.7 mm (range, 0.8–3.0 mm). In the second phase an overall number of 12 ablations were performed. The mean target–trocar distance was 10.3 ± 2.6 mm. The mean target-central tine lateral distance was 3.9 ± 0.7 mm (range, 2.9–5.1 mm). After the dissection of the specimen the target was found unchanged in the center of the ablation zone in all cases. Conclusion:Real-time registration and fusion of preprocedure CT volume images with intraprocedure US is feasible and accurate. The study was however conducted in an ideal experimental setting, without patient movements and breathing, and further studies are warranted to validate the system under clinical conditions.

Percutaneous ablation of hepatocellular carcinoma: State‐of‐the‐art

Percutaneous ablation is considered the best treatment option for patients with early‐stage hepatocellular carcinoma (HCC) who are not candidates for surgical resection or liver transplantation. Several methods have been developed, including intratumoral injection of ethanol or acetic acid, and thermal ablation with radiofrequency, laser, microwaves, or cryosurgery. Percutaneous ethanol injection (PEI) has been the most widely used technique. Several series have provided indirect evidence that PEI improves the natural history of HCC. Patients with Child‐Pugh class A cirrhosis and either a single tumor smaller than 5 cm or as many as three lesions each smaller than 3 cm may achieve a 5‐year survival of 50%. The major limitation of PEI is the high local recurrence rate, which may reach 33–43%. Radiofrequency (RF) ablation has emerged as the most powerful alternate method for percutaneous ablation. Recent studies have shown that RF ablation can achieve more effective local tumor control than PEI with fewer treatment sessions. In a randomized trial, local recurrence‐free survival rates were significantly higher in patients who received RF ablation than in those treated by PEI, and treatment allocation was confirmed as an independent prognostic factor by multivariate analysis. RF ablation could therefore be considered as the percutaneous treatment of choice for patients with early‐stage tumors. Further investigation is warranted to clarify whether current RF technology could offer improved results in patients with intermediate‐stage HCC. (Liver Transpl 2004;10:S91–S97.)

Doxorubicin-eluting bead-enhanced radiofrequency ablation of hepatocellular carcinoma: a pilot clinical study

BACKGROUND/AIMS Experimental studies have shown synergy between radiofrequency (RF) ablation and adjuvant chemotherapy in animal tumour models. We aimed to assess safety and efficacy of doxorubicin-eluting bead (DEB)-enhanced RF ablation in the treatment of human hepatocellular carcinoma (HCC). METHODS Twenty patients with single HCC ranging 3.3-7.0 cm (mean, 5.0 cm+/-1.4) showing evidence of residual viable tumour after standard RF ablation underwent intraarterial DEB administration (50-125 mg doxorubicin; mean, 60.2 mg+/-21.8). Follow-up period ranged 6-20 months (mean, 12 months+/-5). RESULTS No major complication occurred. No deterioration of liver function was observed. The volume of treatment-induced necrosis--as measured on imaging--increased from 48.1 cm3+/-35.7 after RF ablation to 75.5 cm3+/-52.4 after DEB administration, with an increase of 60.9%+/-39.0. The enhanced effect resulted in confirmed complete response (CR) of the target lesion in 12 (60%) of 20 patients. Incomplete response with persistence of <10% of initial tumour volume was observed in 6 (30%) of 20 patients, and local tumour progression in 2 (10%) of 20. CONCLUSIONS Intraarterial DEB administration substantially enhances the effect of RF ablation. DEB-enhanced RF ablation is safe and results in a high rate of CR in patients refractory to standard RF treatment.

Biliary and reticuloendothelial impairment in hepatocarcinogenesis: the diagnostic role of tissue-specific MR contrast media.

The development and progression of a hepatocellular carcinoma (HCC) in a chronically diseased liver, i.e., the carcinogenesis, comprise a multistep and long-term process. Morphologically, this process is associated with the presence of distinct nodular lesions in the liver that are called ‘preneoplastic lesions.’ These preneoplastic lesions are associated with and can precede the growth and progression of well-differentiated HCCs . The characterization of nodular lesions and demonstration of the multistep development of HCC in the cirrhotic liver by imaging modalities represent a challenging issue. The arterial hypervascular supply, depicted by different dynamic studies, represents a fundamental radiological criterion for the diagnosis of HCC in cirrhosis. Magnetic resonance (MR) imaging performed with tissue-specific contrast media can help to investigate the “grey area” of carcinogenesis, in which significant histological changes are already present without any imaging evidence of neoangiogenesis. The purpose of this review is to provide information on the properties of tissue-specific MR contrast agents and on their usefulness in the demonstration of the pathologic changes that take place at the level of the biliary and reticuloendothelial systems during the carcinogenetic process in liver cirrhosis.

Chemoembolization of Hepatocellular Carcinoma

Transarterial chemoembolization (TACE) is the current standard of care for patients with intermediate-stage hepatocellular carcinoma (HCC) and relatively preserved liver function. In a meta-analysis of randomized controlled trials comparing conventional TACE regimens-including the administration of an anticancer-in-oil emulsion followed by embolic agents-versus best supportive care, TACE was shown to improve median survival from 16 to 20 months. Various strategies to improve outcomes for this patient group have become the subject of much ongoing clinical research. The introduction of an embolic drug-eluting bead (DEB) has been shown to substantially improve the pharmacokinetic profile of TACE, providing levels of consistency and repeatability not available with conventional regimens while concomitantly significantly diminishing systemic drug exposure. In randomized trials, DEB-TACE significantly reduced liver toxicity and drug-related adverse events compared with conventional TACE. In this article, technique, indications and contraindications, and clinical outcomes of conventional and DEB-TACE in the management of HCC are reviewed. In addition, scientific background and early clinical experience with the use of combination regimens including TACE and systemically active molecular-targeted agents with antiangiogenic properties are discussed. The combination of DEB-TACE and antiangiogenic therapy represents a potentially powerful approach that is currently undergoing clinical investigation in a phase 3 setting.

Radiofrequency Ablation of Lung Malignancies: Where Do We Stand?

Percutaneous radiofrequency (RF) ablation is a minimally invasive technique used to treat solid tumors. Because of its ability to produce large volumes of coagulation necrosis in a controlled fashion, this technique has gained acceptance as a viable therapeutic option for unresectable liver malignancies. Recently, investigation has been focused on the clinical application of RF ablation in the treatment of lung malignancies. In theory, lung tumors are well suited to RF ablation because the surrounding air in adjacent normal parenchyma provides an insulating effect, thus facilitating energy concentration within the tumor tissue. Experimental studies in rabbits have confirmed that lung RF ablation can be safely and effectively performed via a percutaneous, transthoracic approach, and have prompted the start of clinical investigation. Pilot clinical studies have shown that RF ablation enables successful treatment of relatively small lung malignancies with a high rate of complete response and acceptable morbidity, and have suggested that the technique could represent a viable alternate or complementary treatment method for patients with non-small cell lung cancer or lung metastases of favorable histotypes who are not candidates for surgical resection. This article gives an overview of lung RF ablation, discussing experimental animal findings, rationale for clinical application, technique and methodology, clinical results, and complications.

MnDPDP-enhanced MRI vs dual-phase spiral CT in the detection of hepatocellular carcinoma in cirrhosis

Abstract. The objectives of this study were twofold: (a) to assess safety and tolerability of the hepatobiliary MR contrast agent MnDPDP; and (b) to investigate the sensitivity of MnDPDP-enhanced MRI, in comparison with dual-phase spiral CT, in the detection of hepatocellular carcinoma (HCC) in cirrhosis. Fifty patients with liver cirrhosis and histologically proven HCC were enrolled in a prospective phase-IIIB clinical trial. All patients underwent evaluation with dual-phase spiral CT and pre-contrast and post-contrast MRI at 1.5 T. The MR examination protocol included spin-echo (SE) and gradient-recalled-echo (GRE) T1-weighted images acquired before and 60–120 min after administration of 0.5 μmol/kg (0.5 ml/kg) MnDPDP (Teslascan, Nycomed Amersham, Oslo, Norway); and fast T2-weighted SE images obtained solely before contrast injection. Gold standard was provided by findings at Lipiodol CT in combination with follow-up spiral CT studies, which were repeated at 4-month intervals over a 10- to 27-month (mean ± SD 20.1 ± 5.1 months) follow-up period. No serious adverse event occurred. Eighty tumors ranging 0.8–9.1 cm in diameter (mean ± SD 3.2 ± 2.4 cm) were detected by Lipiodol CT or confirmed as cancerous foci by follow-up CT studies. Pre-contrast MRI detected 38 of 80 lesions (48 %); MnDPDP-enhanced MRI, 65 of 80 lesions (81 %); pre-contrast plus post-contrast MRI, 69 of 80 lesions (86 %); and dual-phase spiral CT, 64 of 80 lesions (80 %). The difference between unenhanced and MnDPDP-enhanced MRI was statistically significant (p < 0.001). The difference between MRI (pre-contrast plus post-contrast) and dual-phase spiral CT was not statistically significant (p = 0.33). The confidence in the final diagnosis, however, was significantly higher for MRI as compared with spiral CT (p < 0.001). MnDPDP is a safe and well-tolerated hepatobiliary MR contrast agent. Magnetic resonance imaging with use of MnDPDP is significantly more sensitive than unenhanced MRI and as good as dual-phase spiral CT for detection of HCC in cirrhosis.