Carlo Bartolozzi

Radio-frequency thermal ablation of liver metastases with a cooled-tip electrode needle: results of a pilot clinical trial

Abstract. The aim of this study was to evaluate feasibility, safety, and effectiveness of radio-frequency (RF) thermal ablation, performed by using a cooled-tip electrode needle, in the treatment of liver metastases. Twenty-nine patients (20 males and 9 females; age range 43–77 years) with one to four hepatic metastases 1.1–4.8 cm in diameter (mean 2.9 ± 0.8 cm) from previously resected intra-abdominal primary malignancies were treated. All patients were excluded from surgery and had partial or no response to chemotherapy. Radio-frequency ablation was performed by using a 100-W generator and 17-gauge, dual-lumen, cooled-tip electrode needles with a 2- to 3-cm exposed tip. Exposure time was 12 min for each needle insertion. Findings at spiral CT were used to assess the therapeutic response. A total of 127 insertions were performed (mean 2.4 ± 1.7 insertions/lesion) during 84 treatment sessions (mean 1.6 ± 0.7 sessions/lesion) in absence of major complications. Complete tumor response (i. e., unenhancing area of thermal necrosis larger than the treated tumor) was seen in 41 (77 %) of 53 lesions, including 33 (87 %) of 38 lesions 3 cm or less in diameter. After a mean follow-up period of 6.5 ± 2.1 months (range 3–9 months), recurrence of the treated lesion was seen in 5 (12 %) of the 41 cases. New metastatic lesions appeared in 7 patients. Two patients died after 6 and 8 months, respectively. Of the 27 patients still in follow-up, 14 are currently free of disease. Radio-frequency thermal ablation with a cooled-tip electrode needle is a safe and effective local treatment for hepatic metastases 3 cm or less in greatest dimension.

Long-term results of percutaneous ethanol injection therapy for hepatocellular carcinoma in cirrhosis: a European experience

Abstract. The objective of our work was to evaluate the long-term results of percutaneous ethanol injection (PEI) for the treatment of hepatocellular carcinoma (HCC) in patients with liver cirrhosis. A total of 184 cirrhotic patients with HCC underwent PEI as the only anticancer treatment over an 8-year period. Patients were followed after therapy by means of clinical examinations, laboratory tests, and US and CT studies performed at regular time intervals. Survival rates were determined according to the Kaplan-Meier method. The overall survival was 67 % at 3 years, 41 % at 5 years, and 19 % at 7 years. The 3-, 5-, and 7-year survival rates of patients with single HCC ≤ 3 cm (78, 54, and 28 %, respectively) were significantly higher (p < 0.01) than those of patients with single HCC of 3.1–5 cm (61, 32, and 16, respectively) or multiple HCCs (51, 21, and 0 %, respectively). Survival of Child-Pugh A patients (79 % at 3 years, 53 % at 5 years, and 32 % at 7 years) was significantly longer (p < 0.01) than that of Child-Pugh B patients (50 % at 3 years, 28 % at 5 years, and 8 % at 7 years). A selected group of 70 patients with Child-Pugh A cirrhosis and single HCC ≤ 3 cm had a 7-year survival of 42 %. Long-term survival of cirrhotic patients with HCC treated with PEI is comparable to that reported in published series of matched patients submitted to surgical resection.

Tissue harmonic and contrast-specific imaging: back to gray scale in ultrasound

The development of new US techniques that produce images based on nonlinear acoustic effects of US interaction with matter or microbubble contrast agents has opened new prospects for gray-scale US in native tissue and contrast imaging. Tissue harmonic imaging uses higher frequencies generated on propagation of the US beam through matter to improve image quality and resolve small anatomic structures and details, and is becoming a routine approach in US examination of many abdominal districts. Contrast-specific imaging techniques display enhancement of US agents in gray-scale with optimal contrast and spatial resolution, and offer high sensitivity either to microbubble movement or to microbubble destruction in dependence of the level of the applied acoustic peak pressure. Owing to the ability to exploit the microcirculation, contrast-specific techniques have enabled the evolution of contrast US from vascular imaging to the imaging of perfused tissues. Several studies have shown that these methods can substantially improve US detection and characterization of focal liver lesions, and promising results have been reported in other areas of investigation. This article reviews physical principles, technical issues, and clinical applications of tissue harmonic and contrast-specific imaging. It is foreseen that the new gray-scale US techniques will rapidly become a tool in numerous clinical scenarios.

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.

Small hepatocellular carcinoma - Detection with US, CT, MR imaging, DSA, and Lipiodol-CT

Twenty-two patients with 37 small (3 cm or less) nodular lesions of hepatocellular carcinoma (HCC) were examined with ultrasonography (US), CT, MR imaging, digital subtraction angiography (DSA), and CT following intraarterial injection of Lipiodol (Lipiodol-CT). All patients subsequently underwent surgery, and the gold standard was provided by intraoperative US. The detection rate was 70% for US, 65% for CT, 62% for MR imaging, 73% for DSA, and 86% for Lipiodol-CT. A significant difference (p<0.05) was observed between the detection rate of Lipiodol-CT and the detection rates of all the other imaging modalities. The difference was even more manifest (p<0.02) when only lesions smaller than or equal to 1 cm were considered. It is concluded that Lipiodol-CT is the single most sensitive examination to detect small nodules of HCC. It should therefore be considered a mandatory step in the preoperative evaluation of patients with HCC considered to be surgical candidates after noninvasive imaging studies.

Thyroid blood flow evaluation by color-flow doppler sonography distinguishes Graves’ disease from Hashimoto’s thyroiditis

Thyroid hypoechogenicity at ultrasound is a characteristic of autoimmune thyroid diseases, with an overlap of this echographic pattern in patients affected by Graves’ disease or Hashimoto’s thyroiditis. Aim of the present paper was to study the thyroid blood flow (TBF) by color-flow doppler (CFD) and peak systolic velocity (PSV) at the inferior thyroid artery in 37 Graves’ and 45 goitrous Hashimoto’s thyroiditis patients. CFD pattern was defined as normal (or type 0): TBF limited to peripheral thyroid arteries (PSV = 17.7±3 cm/sec, mean±SD); type I: TBF mildly increased; type II: TBF clearly increased; type III: TBF markedly increased. The CFD was in direct relationship to the PSV. Out of 18 patients with Graves’ disease and untreated active hyperthyroidism CFD pattern was type III in 17 and type II in 1. The PSV was 42.1±15 cm/sec. In 17 patients euthyroid under methimazole, the CFD pattern was type 0 in 3 (17%) type I in 5 (30%), type II in 5 (30%), type III in 4 (23%). In this group of Graves’ patients the PSV was 36±14 cm/sec. In two patients, hypothyroid after radioiodine treatment, the CFD pattern was type 0 in 1 and type I in 1. In the group of Hashimoto’s patients TBF was in no relationship with thyroid status or treatment and was type 0 in 22 (49%), type I in 20 (44%), type II in 3 (7%), while none had type III CFD pattern. Thyroid hypoechogenicity at ultrasound was present in 32/37 (86%) Graves’ and 41/45 (91%) Hashimoto’s patients. All the four patients with Hashimoto’s thyroiditis and normal thyroid ultrasound pattern had also a normal CFD pattern, while 4/5 patients with Graves’ disease and normal echographic pattern had an increased TBF. In conclusion, a diffusely increased thyroid blood flow is pathognomonic of untreated Graves’ disease and an abnormal CFD pattern identifies the majority of Graves’ patients with a normal thyroid ultrasound pattern. Thus, CFD sonography may be useful in distinguishing patients with Graves’ disease and Hashimoto’s thyroiditis having a similar thyroid echographic pattern at ultrasound.

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.

Focal liver lesions: MR imaging–pathologic correlation

Abstract. Magnetic resonance signal intensity of focal liver lesions is affected by numerous pathologic factors. Lesion histologic features, such as cellularity, vascularity, stromal component, and intratumoral necrosis or hemorrhage, strongly affect T1 and T2 relaxation times. Additionally, intracellular content of certain substances, such as glycogen, fat, melanin, iron, and copper, may also have a substantial role in determining MR signal behavior. In this review we discuss the correlations between MR imaging features and pathologic findings in benign and malignant focal liver lesions. Knowledge of imaging–pathology correlations greatly assist in characterizing focal lesions. Moreover, in certain tumor histotypes, such as hepatocellular carcinoma, careful analysis of lesion signal intensity may help predict the degree of tumor differentiation.

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.)

Conventional versus Doxorubicin-eluting Bead Transarterial Chemoembolization for Hepatocellular Carcinoma

PURPOSE To compare short- and long-term clinical outcomes after conventional transarterial chemoembolization and drug-eluting bead (DEB) transarterial chemoembolization in hepatocellular carcinoma (HCC). MATERIALS AND METHODS Patients with unresectable HCC unsuitable for ablative therapies were randomly assigned to undergo conventional or DEB chemoembolization. The primary endpoints of the study were safety, toxicity, and tumor response at 1 month. Secondary endpoints were number of repeated chemoembolization cycles, time to recurrence and local recurrence, time to radiologic progression, and survival. RESULTS In total, 67 patients (mean age, 70 y ± 7.7) were evaluated. Mean follow-up was 816 days ± 361. Two periprocedural major complications occurred (2.9%) that were treated by medical therapy without the need for other interventions. A significant increase in alanine aminotransferase levels 24 hours after treatment was reported, which was significantly greater after conventional chemoembolization (n = 34) than after DEB chemoembolization (n = 33; preprocedure, 60 IU ± 44 vs 74 IU ± 62, respectively; at 24 h, 216 IU ± 201 vs 101 IU ± 89, respectively; P = 0.007). No other differences were observed in liver toxicity between groups. At 1 month, complete and partial tumor response rates were 70.6% and 29.4%, respectively, in the conventional chemoembolization group and 51.5% and 48.5%, respectively, in the DEB chemoembolization group. No differences were observed between groups in time to recurrence and local recurrence, radiologic progression, and survival. CONCLUSIONS Conventional chemoembolization and DEB chemoembolization have a limited impact on liver function on short- and long-term follow-up and are associated with favorable clinical outcomes.