Franz Poch

The vascular cooling effect in hepatic multipolar radiofrequency ablation leads to incomplete ablation ex vivo

Abstract Purpose: Major limitations of conventional RFA are vascular cooling effects. However, vascular cooling effects are supposed to be less pronounced in multipolar RFA. The objective of this ex vivo study was a systematic evaluation of the vascular cooling effects in multipolar RFA. Materials and methods: Multipolar RFA with three bipolar RFA applicators was performed ex vivo in porcine liver (applicator distance 20 mm, energy input 40 kJ). A saline-perfused glass tube (‘vessel’) was placed parallel to the applicators in order to simulate a natural liver vessel. Five applicator-to-vessel geometries were tested. A liquid-filled glass tube without perfusion was used as a dry run. Ablations were orthogonally cut to the applicators at a defined height. Cooling effects were analysed qualitatively and quantitatively along these cross sectional areas. Results: Thirty-six ablations were performed. A cooling effect could be seen in all ablations with perfused vessels compared to the dry run. While this cooling effect did not have any influence on the ablation areas (859–1072 mm2 versus 958 mm2 in the dry run, p > 0.05), it had a distinctive impact on ablation shape. A vascular cooling effect could be observed in all ablations with perfusion directly around the vessel independent of the applicator position compared to the dry run (p < 0.01). Conclusions: A vascular cooling effect occurred in all multipolar RFA with simulated liver vessels ex vivo independent of the applicator-to-vessel geometry. While the cooling effect did not influence the total ablation area, it had a distinctive impact on the ablation shape.

Minimal vascular flows cause strong heat sink effects in hepatic radiofrequency ablation ex vivo.

The present paper aims to assess the lower threshold of vascular flow rate on the heat sink effect in bipolar radiofrequency ablation (RFA) ex vivo.

Comparison of bipolar radiofrequency ablation zones in an in vivo porcine model: Correlation of histology and gross pathological findings

BACKGROUND Continuing research ex vivo and in vivo with animal models is performed to advance the oncological safety of radiofrequency ablation (RFA) of liver tumors. In these experiments, frequently imaging modalities (e.g. MRI or CT) or macro-morphological measurements are used to determine the full extent of the different ablation zones inside of RFA lesions. However, no systematic study has been performed so far, which verified the accuracy of the macro-morphological findings. Therefore, the present study aimed to correlate histological and gross pathological findings of bipolar radiofrequency ablation zones of porcine livers with regard to cell viability in vivo. METHODS Bipolar RFA was performed in the liver of anaesthetized female domestic pigs under CT-guidance using an internally cooled 20 mm RFA applicator. Afterwards RFA cross sections of the liver were made in a perpendicular orientation to the applicator. Ablation zones were initially documented by photography and thereafter prepared for histological analysis. Latter was based on HE-staining and NADH-diaphorase cell viability staining. Micro- and macro-morphological sections were digitally analyzed along the cross-section area for statistical correlation. RESULTS Three different RF ablation zones could be differentiated. A central zone showing no cell viability (white zone) was surrounded by a red zone. The red zone could be divided into an inner zone of viable and non-viable cells (red zone 1), followed by a zone of edema with mostly viable cells (red zone 2).Micro- and macro-morphological data showed a strong correlation for the white zone (r = 0.95, p < 0.01), the red zone 1 (r = 0.85, p < 0.01), and the red zone 2 (r = 0.89, p < 0.01). CONCLUSION White zone and red zone could clearly be distinguished in gross pathology and histology after bipolar RFA of porcine liver tissue in vivo. The red zone could be differentiated into an inner zone of viable and non-viable cells and an outer zone with high cell viability and intercellular edema. A strong correlation of micro- and macro-morphology could be shown for all three ablation zones. With this knowledge, gross pathological examination can be used as a reliable indicator of lethally damaged tissue in bipolar RFA of in vivo porcine liver.

Measuring and optimizing results in multipolar RFA: Techniques and early findings in an experimental setting

Radiofrequency ablation (RFA) has shown to be a reasonable alternative for the treatment of hepatic tumors and metastases although multiple limitations remain. Cooling effects due to larger vessels can prevent complete coverage and may lead to early tumor relapse. This preliminary in vivo pig study combines the use of multipolar RFA with three applicators (six electrodes) and interrupted liver perfusion using Pringles maneuver to overcome the most serious limitations. Furthermore, immediate detection of incomplete RFA is important to revise ablation. We used contrast enhanced computed tomography (CECT) to evaluate post ablation results in comparison to macroscopic images in healthy pig liver. We found significantly (p = 0.001) larger ablation zones and no affection by larger vessels with interrupted liver perfusion. This allows effective RFA for larger tumors. Immediate postinterventional CECT provided comparable results (r = 0.985) to macroscopic evaluation.

Determination of the electrical conductivity of human liver metastases: impact on therapy planning in the radiofrequency ablation of liver tumors.

Background Radiofrequency ablation is used to induce thermal necrosis in the treatment of liver metastases. The specific electrical conductivity of a liver metastasis has a distinct influence on the heat formation and resulting tumor ablation within the tissue. Purpose To examine the electrical conductivity σ of human colorectal liver metastases and of tumor-free liver tissue in surgical specimens. Material and Methods Surgical specimens from patients with resectable colorectal liver metastases were used for measurements (size of metastases <30 mm). A four-needle measuring probe was used to determine the electrical conductivity σ of human colorectal liver metastasis (n = 8) and tumor-free liver tissue (n = 5) in a total of five patients. All measurements were performed at 470 kHz, which is the relevant frequency for radiofrequency ablation. The tissue temperature was also measured. Hepatic resections were performed in accordance with common surgical standards. Measurements were performed in the operating theater immediately after resection. Results The median electrical conductivity σ was 0.57 S/m in human colorectal liver metastases at a median temperature of 35.1℃ and 0.35 S/m in tumor-free liver tissue at a median temperature of 34.9℃. The electrical conductivity was significantly higher in tumor tissue than in tumor-free liver tissue (P = 0.005). There were no differences in tissue temperature between the two groups (P = 0.883). Conclusion The electrical conductivity is significantly higher in human colorectal liver metastases than in tumor-free liver tissue at a frequency of 470 kHz.

Intermittent Pringle maneuver may be beneficial for radiofrequency ablations in situations with tumor-vessel proximity

Abstract Background Radiofrequency ablation (RFA) represents a treatment option for non-resectable liver malignancies. Larger ablations can be achieved with a temporary hepatic inflow occlusion (Pringle maneuver – PM). However, a PM can induce dehydration and carbonization of the target tissue. The objective of this study was to evaluate the impact of an intermittent PM on the ablation size. Methods Twenty-five multipolar RFAs were performed in porcine livers ex vivo. A perfused glass tube was used to simulate a natural vessel. The following five test series (each n=5) were conducted: (1) continuous PM, (2–4) intermittent PM, and (5) no PM. Ablations were cut into half. Ablation area, minimal radius, and maximal radius were compared. Results No change in complete ablation size could be measured between the test series (p>0.05). A small rim of native liver tissue was observed around the glass tube in the test series without PM. A significant increase of ablation area could be measured on the margin of the ablations with an intermittent PM, starting without hepatic inflow occlusion (p<0.05). Conclusion An intermittent PM did not lead to smaller ablations compared to a continuous or no PM ex vivo. Furthermore, an intermittent PM can increase the ablation area when initial hepatic inflow is succeeded by a PM.

Finding Optimal Ablation Parameters for Multipolar Radiofrequency Ablation

Purpose. Radiofrequency ablation (RFA) for primary liver tumors and liver metastases is restricted by a limited ablation size. Multipolar RFA is a technical advancement of RFA, which is able to achieve larger ablations. The aim of this ex vivo study was to determine optimal ablation parameters for multipolar RFA depending on applicator distance and energy input. Methods. RFA was carried out ex vivo in porcine livers with three internally cooled, bipolar applicators in multipolar ablation mode. Three different applicator distances were used and five different energy inputs were examined. Ablation zones were sliced along the cross-sectional area at the largest ablation diameter, orthogonally to the applicators. These slices were digitally measured and analyzed. Results. Sixty RFA were carried out. A limited growth of ablation area was seen in all test series. This increase was dependent on ablation time, but not on applicator distance. A steady state between energy input and energy loss was not observed. A saturation of the minimum radius of the ablation zone was reached. Differences in ablation radius between the three test series were seen for lowest and highest energy input (P < .05). No differences were seen for medium amounts of energy (P > .05). Conclusions. The ablation parameters applicator distance and energy input can be chosen in such a way, that minor deviations of the preplanned ablation parameters have no influence on the size of the ablation area.

Characterization of benign periablational enhancement following multipolar radiofrequency ablation using perfusion CT in an in-vivo porcine liver model

PURPOSE: Thermal ablation is an important interventional option in the management of liver tumors. Immediate postablational imaging regularly shows periablational enhancement. This peripheral hyperperfusion may induce heat-sink effects which could contribute to incomplete tumor ablation. To reduce the effect of hyperperfusion the feeding vessels source must be known. The aim of this study was to dynamically characterize the type of blood supply of the periablational enhancement zone immediately after hepatic radiofrequency ablation (RFA) using perfusion CT. METHODS: We used an in-vivo porcine liver model. Multipolar RFA was performed in healthy pig livers. Immediate postablational perfusion CT was acquired. The contrast enhancement over time of the peripheral ablation zone, the aorta and the portal vein were recorded. Time differences of the peak periablational enhancement to the peak arterial perfusion and to the peak portalvenous perfusion were calculated and analyzed. RESULTS: The perfusion peak of the periablational enhancement zone always occurred in mean 8.1 s after the arterial peak in the aorta and in mean 16.9 s before the peak in the portal vein. CONCLUSIONS: Benign periablational enhancement is a result of primary arterial and not portalvenous hyperperfusion. In order to reduce heat sink effects, peri-ablational arterial balloon occlusion or transarterial chemoembolization may be beneficial during RFA.

Written reply: “Optimal multibipolar radiofrequency parameters should overcome heat-sink effect”

We took note of the letter to the editor by Hocquelet et al. [1] regarding our article “The vascular cooling effect in hepatic multipolar radiofrequency ablation leads to incomplete ablation ex vivo” with great interest. Hocquelet et al. showed in their large multicentre study that multipolar radiofrequency ablation (RFA) outclasses monopolar RFA, regarding primary RF success and sustained local tumour response next to hepatic vessels [1]. However, his working group also pointed out that ablations near large vessels were independent factors associated with an increased risk for RFA failure. This is in accordance with our results [2]. We observed a vascular cooling effect around an artificial vessel in our ex vivo study. We choose this setting to examine RFA in a standardised setting, which is not influenced by biological variations. However, further in vivo studies will be necessary to examine exactly the heat-sink effect, described by both working groups. An optimal selection of ablation parameters and applicator positioning, using multipolar RFA, should considerably reduce incomplete ablation rates. Nevertheless, heat-sink effects have to be considered in multipolar RFA as well. Hocquelet et al. [1] addressed several issues in their letter to the editor: Ad 1): We agree that bipolar applicators with an active length of 20mm (T-20) should not normally be used in clinical for the treatment of hepatic malignancies, since ablations are becoming small. We used applicators with an active tip length of 20mm (T-20) in our ex vivo setting to avoid artefacts at the liver border. These artefacts would occur in the absence of a normal liver perfusion, as RFA lesions tend to get large in the relatively small porcine liver. In our experimental setting we also used the recommended starting power of 1 Watt/mm (according to 60 Watt). However, it has to be distinguished between preselected starting power (manufacturer’s recommendation: 1 Watt/mm) and actual power output. The RFAgenerator chooses optimal power output according to the actual impedance of the tissue in order to avoid dehydration and carbonisation of the tissue (the so-called “Resistance Controlled Automatic Power” – RCAP mode). In our experience (experimental and clinical), the generator never uses the preselected maximal power output. We agree that energy delivery is dependent on active tip length. However, the actual power output is usually considerably lower than 1 Watt/mm. Ad 2): The authors addressed are very interesting issue here. In clinical practice, we choose output power and total energy according to the dosimetry table of the manufacturer, instead of waiting for the automatic shutdown by the generator. Impedance of the ablated tissue increases slowly by using the RCAP-mode and therefore ablations longer than 1h may arise in clinical practice (in an ex vivo setting ablations more than 120min are not uncommon without automatic shutdown). Therefore, exact dosimetry tables for each applicator size and applicator distance seem to be mandatory. Ad 3): There is some evidence that vessels <3mm in diameter and within an ablation zone occlude during ablation [3]. Therefore, these vessels do not seem to be crucial for vascular cooling effects. However, vessels next to the ablation zones take part in the diffuse cooling effect and therefore limit ablation size. Additionally, it has to be examined, which is the optimal applicator position in order to reduce vascular cooling effects as far as possible. In vivo studies would be of great interest. Ad 4): A percutaneous puncture of the portal or hepatic vein under ultrasound guidance may be a possible alternative for an experienced physician. However, an ultrasound guided puncture of the portal or hepatic vein remains demanding and is not always possible. Additionally, a considerable vascular cooling effect of the arterial perfusion persists performing a selective balloon occlusion of the portal or hepatic vein [4].