Clotilde Della Pina

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.

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.

Hepatocellular carcinoma: new options for image-guided ablation

Image-guided percutaneous ablation is currently accepted as the best therapeutic choice for patients with early-stage hepatocellular carcinoma (HCC) when transplantation and resection are precluded. Several methods for chemical or thermal tumor destruction have been developed and tested clinically during the past two decades. The seminal technique used for local treatment of HCC has been percutaneous ethanol injection (PEI). Several studies have provided indirect evidence that PEI improves the natural history of nonsurgical patients with early-stage HCC. Its major limitation is the high rate of local recurrence. Radiofrequency (RF) ablation has been the most widely assessed alternative to PEI. Five randomized controlled trials have shown that RF ablation achieves more effective and reproducible tumor destruction than PEI, leading to a better local control of the disease. As a result, RF ablation has been established as the primary ablative modality. The value of newer thermal and non-thermal methods for local tumor treatment, such as microwave ablation, irreversible electroporation (IRE), and light activated drug therapy, should be investigated in the setting of randomized controlled trials.

Single-session percutaneous ethanol ablation of early-stage hepatocellular carcinoma with a multipronged injection needle: results of a pilot clinical study

PURPOSE To investigate the feasibility, safety, and efficacy of single-session ethanol ablation with multipronged needles in the treatment of early-stage hepatocellular carcinoma (HCC). MATERIALS AND METHODS A pilot clinical study enrolled 20 patients with Child-Pugh A-B cirrhosis (15 men and 5 women 53-84 years old [mean 70.3 years old ± 8.3, median 72 years old]) and with 25 HCC tumors 1.2-3.8 cm in longest diameter (mean 2.3 cm ± 0.6) located in unfavorable locations for radiofrequency (RF) ablation. Ethanol ablation was performed under moderate sedation using a multipronged injection needle (Quadra-Fuse; REX Medical, Conshohocken, Pennsylvania) and ultrasound guidance. Follow-up period ranged from 12-24 months (mean 15.9 months ± 4.6, median 16 months) and included contrast-enhanced computed tomography (CT) or magnetic resonance (MR) imaging performed 1 month after treatment and at 3-month intervals thereafter. RESULTS The treatment protocol was successfully completed in all patients (technical success rate 100%). No major complications were observed. A single treatment session with injection of 5-26 mL of ethanol (mean 9.5 mL ± 5.5) resulted in complete tumor ablation at 1 month CT or MR imaging in 21 (84%) of 25 tumors. A second treatment session increased the number of tumors with complete response (CR) to 23 of 25 (primary effectiveness rate 92%). Tumor progression was observed in three cases during the follow-up period, for a rate of confirmed CR of 80% (20 of 25). CONCLUSIONS Ethanol ablation performed with a multipronged injection needle was not associated with any major complications and resulted in a high rate of confirmed CR. This technique offers an alternative to RF ablation for single-session treatment of early-stage HCC.

Clinical management of hepatic malignancies: ferucarbotran-enhanced magnetic resonance imaging versus contrast-enhanced spiral computed tomography

This study compares ferucarbotran-enhanced magnetic resonance (MR) imaging with spiral computed tomography (CT) in the clinical management of patients with suspected hepatic malignancy. One hundred fifty-nine patients with suspected liver malignancy were included in a prospective, multicenter, phase IIIB clinical trial. Patients were examined with baseline plus contrast-enhanced spiral CT and with baseline plus ferucarbotran-enhanced MR imaging. For each patient, four maps of liver lesions were constructed by a trusted blind party on the basis of (a) baseline plus contrast-enhanced spiral CT, (b) baseline MR imaging, (c) baseline plus ferucarbotran-enhanced MR imaging, and (d) final diagnosis. Three blinded experts evaluated the treatment options for each map. The concordance of the treatment choice based on imaging with the treatment choice based on final diagnosis was verified. The final therapeutic decision was radical therapy for 85 patients, palliative therapy for 49 patients, and no treatment for 25 patients who had a final diagnosis of benign lesion. Proper treatment allocation was achieved in 121 (76%) of 159 patients when the evaluation was based on liver maps obtained from spiral CT, in 97 (61%) of 159 patients when the evaluation was based on liver maps obtained from baseline MR imaging, and in 136 (85%) of 159 patients when the evaluation was based on liver maps obtained from baseline plus ferucarbotran-enhanced MR imaging. MR imaging with ferucabotran was significantly superior to spiral CT for correct treatment allocation (P = 0.0167). Ferucarbotran-enhanced MR imaging is superior to spiral CT in clinical management of patients with suspected hepatic malignancy.

Peri-intraprocedural imaging: US, CT, and MRI

Imaging in liver interventional oncology plays a key role in the entire process starting from patient selection, leading to patient treatment and continuing with patient follow-up. Pre-procedural imaging evaluation is aimed to determine the indication for interventional therapies according to the size, number, and location of hepatic lesions, to the presence of major vascular invasion, nodal disease, and distant metastases, and to choose the most suitable approach according to tumor histology. Ideal qualities of a targeting technique include clear delineation of the tumor tissue and the surrounding anatomy, coupled with real-time imaging, multiplanar, and interactive capabilities. Moreover, the modality of image guidance should visualize therapy effects during the intervention to assess coverage of the targeted tissue and to prevent unintended thermal injury to critical structures in the surroundings of the target. Post-treatment imaging is then imperative to evaluate response to therapy by assessing for residual or recurrent disease, revising prognosis, and guiding future therapy. In this article, the role of imaging in patient selection and treatment planning will be discussed. Recently amended RECIST (mRECIST) for evaluation of tumor response in hepatocellular carcinoma and specific treatment-related findings after thermal ablation, trans-arterial chemoembolization, and radioembolization will be reviewed.

European Guidelines in Liver Contrast Ultrasound

Despite the improvement in detection and characterization of focal liver lesions that can be achieved using contrast-enhanced US, several issues are still open. First, contrast US will hardly replace CT or MR imaging for preoperative assessment of patients with liver tumors, as these techniques still offer a more comprehensive assessment of the liver parenchyma, which is mandatory to properly plan any kind of surgical or interventional procedure. Second, the daily schedule of each US laboratory doing liver examinations will have to be reformulated, and many US laboratories will have to update their equipment and to provide proper training for their doctors. Last but not least, the cost of the introduction of contrastenhanced US into daily practice will have to be taken into account. It can be argued that cost saving associated with patients who will no longer need a CT or MR imaging of the liver after contrast-enhanced US could largely counterbalance the cost of the examination. However, an optimal use of contrast-enhanced US will require the definition of precise diagnostic flow charts for each clinical situation. Nevertheless, contrast-enhanced US has the potential to become the primary liver imaging modality for early detection and characterization of focal lesions. Early diagnosis of primary and secondary liver malignancies greatly enhances the possibility of curative surgical resection or successful percutaneous ablation, resulting in better patient care and eventually in improved patient survival.

Advances in diagnostic imaging: The value of contrast-enhanced ultrasound for liver

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