Hepatic Radiofrequency Ablation Research Articles

Fibroblast growth factors induce hepatic tumorigenesis post radiofrequency ablation

Image-guided radiofrequency ablation (RFA) is used to treat focal tumors in the liver and other organs. Despite potential advantages over surgery, hepatic RFA can promote local and distant tumor growth by activating pro-tumorigenic growth factor and cytokines. Thus, strategies to identify and suppress pro-oncogenic effects of RFA are urgently required to further improve the therapeutic effect. Here, the proliferative effect of plasma of Hepatocellular carcinoma or colorectal carcinoma patients 90 min post-RFA was tested on HCC cell lines, demonstrating significant cellular proliferation compared to baseline plasma. Multiplex ELISA screening demonstrated increased plasma pro-tumorigenic growth factors and cytokines including the FGF protein family which uniquely and selectively activated HepG2. Primary mouse and immortalized human hepatocytes were then subjected to moderate hyperthermia in-vitro, mimicking thermal stress induced during ablation in the peri-ablational normal tissue. Resultant culture medium induced proliferation of multiple cancer cell lines. Subsequent non-biased protein array revealed that these hepatocytes subjected to moderate hyperthermia also excrete a similar wide spectrum of growth factors. Recombinant FGF-2 activated multiple cell lines. FGFR inhibitor significantly reduced liver tumor load post-RFA in MDR2-KO inflammation-induced HCC mouse model. Thus, Liver RFA can induce tumorigenesis via the FGF signaling pathway, and its inhibition suppresses HCC development.

Radiofrequency Ablation–Induced Tumor Growth Is Suppressed by MicroRNA-21 Inhibition in Murine Models of Intrahepatic Colorectal Carcinoma

PurposeTo investigate the role of microRNA-21 (miR21) in radiofrequency (RF) ablation–induced tumor growth and whether miR21 inhibition suppresses tumorigenesis. Material and MethodsStandardized liver RF ablation was applied to 35 C57/BL6 mice. miR21 and target proteins pSTAT3, PDCD4, and PTEN were assayed 3 hours, 24 hours, and 3 days after ablation. Next, 53 Balb/c and 44 C57BL/6 mice received Antago-miR21 or scrambled Antago-nc control, followed by intrasplenic injection of 10,000 CT26 or MC38 colorectal tumor cells, respectively. Hepatic RF ablation or sham ablation was performed 24 hours later. Metastases were quantified and tumor microvascular density (MVD) and cellular proliferation were assessed at 14 or 21 days after the procedures, respectively. ResultsRF ablation significantly increased miR21 levels in plasma and hepatic tissue at 3 and 24 hours as well as target proteins at 3 days after ablation (P < .05, all comparisons). RF ablation nearly doubled tumor growth (CT26, 2.0 SD ± 1.0 fold change [fc]; MC38, 1.9 SD ± 0.9 fc) and increased MVD (CT26, 1.9 SD ± 1.0 fc; MC38, 1.5 ± 0.5 fc) and cellular proliferation (CT26, 1.7 SD ± 0.7 fc; MC38, 1.4 SD ± 0.5 fc) compared with sham ablation (P < .05, all comparisons). RF ablation–induced tumor growth was suppressed when Antago-miR21 was administered (CT26, 1.0 SD ± 0.7 fc; MC38, 0.9 SD ± 0.4 fc) (P < .01, both comparisons). Likewise, Antago-miR21 decreased MVD (CT26, 1.0 SD ± 0.3 fc; MC38, 1.0 SD ± 0.2 fc) and cellular proliferation (CT26, 0.9 SD ± 0.3 fc; MC38, 0.8 SD ± 0.3 fc) compared with baseline (P < .05, all comparisons). ConclusionsRF ablation upregulates protumorigenic miR21, which subsequently influences downstream tumor-promoting protein pathways. This effect can potentially be suppressed by specific inhibition of miR21, rendering this microRNA a pivotal and targetable driver of tumorigenesis after hepatic thermal ablation.

A study on the selection of electrode materials for hepatic radiofrequency ablation: A numerical approach

Radiofrequency Ablation (RFA) is one of the most extensively practiced and studied tumor ablation therapy to date. This treatment therapy is most commonly used to treat chronic pain, liver tumors, arthritis of the spine, etc. Previous studies suggest that material properties of the electrode used during RFA tend to gain comparatively larger temperature zones leading to better thermal lesions. Material properties of electrodes, especially thermal conductivity and electrical conductivity, play an essential role in achieving a larger ablation zone. In this regard, the present study has analyzed the effect of thermal and electrical conductivity of different electrode materials such as Ni-Ti, Pt-Ir, Au, and Cu used in RFA. A FEM-based numerical approach has been accounted for understanding the behavior of electrode materials and the temperature profile attained post ablation of 10 mins. The results show that with a constant power application for 10 mins of RFA, there is no significant difference in ablation volume and temperature zones for different electrode materials. Moreover, this study suggests that higher thermal and electrical conductivity of electrode materials doesn’t have a significant effect on the thermal lesions. Though it was observed that using Au and Cu electrodes resulted in a larger thermal lesion as compared to Ni-Ti and Pt-Ir, the current study suggests minor benefits in terms of improving the efficacy of the treatment process. The observed results would be highly beneficial for medical practitioners to decide when choosing the electrode for the RFA treatment process.

MR Imaging–Based In Vivo Macrophage Imaging to Monitor Immune Response after Radiofrequency Ablation of the Liver

PurposeTo establish molecular magnetic resonance (MR) imaging instruments for in vivo characterization of the immune response to hepatic radiofrequency (RF) ablation using cell-specific immunoprobes. Materials and MethodsSeventy-two C57BL/6 wild-type mice underwent standardized hepatic RF ablation (70 °C for 5 minutes) to generate a coagulation area measuring 6–7 mm in diameter. CD68+ macrophage periablational infiltration was characterized with immunohistochemistry 24 hours, 72 hours, 7 days, and 14 days after ablation (n = 24). Twenty-one mice were subjected to a dose-escalation study with either 10, 15, 30, or 60 mg/kg of rhodamine-labeled superparamagnetic iron oxide nanoparticles (SPIONs) or 2.4, 1.2, or 0.6 mg/kg of gadolinium-160 (160Gd)-labeled CD68 antibody for assessment of the optimal in vivo dose of contrast agent. MR imaging experiments included 9 mice, each receiving 10-mg/kg SPIONs to visualize phagocytes using T2∗-weighted imaging in a horizontal-bore 9.4-T MR imaging scanner, 160Gd-CD68 for T1-weighted MR imaging of macrophages, or 0.1-mmol/kg intravenous gadoterate (control group). Radiological-pathological correlation included Prussian blue staining, rhodamine immunofluorescence, imaging mass cytometry, and immunohistochemistry. ResultsRF ablation–induced periablational infiltration (206.92 μm ± 12.2) of CD68+ macrophages peaked at 7 days after ablation (P < .01) compared with the untreated lobe. T2∗-weighted MR imaging with SPION contrast demonstrated curvilinear T2∗ signal in the transitional zone (TZ) (186 μm ± 16.9), corresponsing to Iron Prussian blue staining. T1-weighted MR imaging with 160Gd-CD68 antibody showed curvilinear signal in the TZ (164 μm ± 3.6) corresponding to imaging mass cytometry. ConclusionsBoth SPION-enhanced T2∗-weighted and 160Gd-enhanced T1-weighted MR imaging allow for in vivo monitoring of macrophages after RF ablation, demonstrating the feasibility of this model to investigate local immune responses.

Tuning the Pennes Perfusion Rate to Model Large Vessel Cooling Effects in Hepatic Radiofrequency Ablation.

Radio frequency ablation (RFA) has become a popular method for the minimally invasive treatment of liver cancer. However, the success rate of these treatments depends heavily on the amount of experience the clinician possesses. Mathematical modeling can help mitigate this problem by providing an indication of the treatment outcome. Thermal lesions in RFA are affected by the cooling effect of both fine-scale and large-scale blood vessels. The exact model for large-scale blood vessels is advection-diffusion, i.e., a model capable of producing directional effects, which are known to occur in certain cases. In previous research, in situations where directional effects do not occur, the advection term in the blood vessel model has been typically replaced with the Pennes perfusion term, albeit with a higher-than-usual perfusion rate. Whether these values of the perfusion rate appearing in literature are optimal for the particular vessel radii in question, has not been investigated so far. This work aims to address this issue. An attempt has been made to determine, for values of vessel radius between 0.55 mm and 5 mm, best estimates for the perfusion rate which minimize the error in thermal lesion volumes between the perfusion-based model and the advection-based model. The results for the best estimate of the perfusion rate presented may be used in existing methods for fast estimation of RFA outcomes. Furthermore, the possible improvements to the presented methodology have been highlighted.

Validation of Software for Patient-Specific Real-Time Simulation of Hepatic Radiofrequency Ablation

Rationale and Objectives:CT-guided radiofrequency ablation (RFA) is a potentially curative minimally invasive treatment for liver cancer. Local tumor recurrence limits the success of RFA for large or irregular tumors as it is difficult to visualize the tissue destroyed. This study was designed to validate a real-time software-simulated ablation volume for intraprocedural guidance.Materials and Methods:Software that simulated RFA physics calculated ablation volumes in 17 agar-albumin phantoms (7 with a simulated vessel) and in six in-vivo (porcine) ablations. The software-modeled volumes were compared with the actual ablations (physical lesion in agar, contrast CT in the porcine model) and to the volume predicted by the manufacturer’s charts. Error was defined as the distance from evenly distributed points on the segmented true ablation volume surfaces to the closest points on the corresponding computer-generated model, and for the porcine model, to the manufacturer-specified ablation volume.Results:The average maximum error of the simulation was 2.8 mm (range to 4.9 mm) in the phantoms. The heat-sink effect from the simulated vessel was well-modeled by the simulation. In the porcine model, the average maximum error of the simulation was 5.2 mm (range to 8.1 mm) vs 7.8 mm (range to 10.0mm) for the manufacturer’s model (p = 0.009).Conclusion:A real-time computer-generated RFA model incorporated tine position, energy deposited, and large vessel proximity to predict the ablation volume in agar phantoms with less than 3mm maximum error. Although the in-vivo model had slightly higher maximum error, the software better predicted the achieved ablation volume compared to the manufacturer’s ablation maps.

Aggressive local treatment for recurrent intrahepatic cholangiocarcinoma—Stereotactic radiofrequency ablation as a valuable addition to hepatic resection

BackgroundTo evaluate the efficacy, safety and overall clinical outcome of local treatment for recurrent intrahepatic cholangiocellular carcinoma after hepatic resection.MethodsBetween 2007 and 2019 72 consecutive patients underwent hepatic resection for primary intrahepatic cholangiocellular carcinoma. If amenable, recurrent tumors were aggressively treated by HR or stereotactic radiofrequency ablation with local curative intent. Endpoints consisted of morbidity and mortality, locoregional and de novo recurrence, disease free survival, and overall survival.ResultsAfter a median follow-up of 28 months, recurrence of intrahepatic cholangiocellular carcinoma was observed in 43 of 72 patients undergoing hepatic resection (60.3%). 16 patients were subsequently treated by hepatic resection (n = 5) and stereotactic radiofrequency ablation (n = 11) with local curative intention. The remaining 27 patients underwent palliative treatment for first recurrence. Overall survival of patients who underwent repeated aggressive liver-directed therapy was comparable to patients without recurrence (p = 0.938) and was better as compared to patients receiving palliative treatment (p = 0.018). The 5-year overall survival rates for patients without recurrence, the repeated liver-directed treatment group and the palliative treatment group were 54.3%, 47.7% and 12.3%, respectively. By adding stereotactic radiofrequency ablation as an alternative treatment option, the rate of curative re-treatment increased from 11.9% to 37.2%.ConclusionRepeated hepatic resection is often precluded due to patient morbidity or anatomical and functional limitations. Due to the application of stereotactic radiofrequency ablation in case of recurrent intrahepatic cholangiocellular carcinoma, the number of patients treated with curative intent can be increased. This leads to favorable clinical outcome as compared to palliative treatment of intrahepatic cholangiocellular carcinoma recurrence.

Safeness of Simultaneous Colonic Resection and Hepatic Radiofrequency Ablation.

Previous reports showed an increased risk of infectious complications when liver radiofrequency ablation (RFA) is performed simultaneously to colorectal resection. The aim of this study was to compare early and long-term outcomes of simultaneous versus staged strategy. Data from colorectal cancer liver metastases consecutively treated by surgery of the primary tumor with an associated liver RFA procedure between January 1, 2010 and January 31, 2020. Patients were divided into two groups: RFA performed during colorectal surgery (simultaneous) or in a different moment (staged). Patients were manually matched (1:1) to minimize influence of known covariates. Seventy-two patients were included. After matching, there was no difference between the two groups in morbidity or mortality. Hospital stay was 2 days shorter in the simultaneous group. Early or long-term outcomes were identical between the two strategies. The simultaneous strategy was associated with a shorter duration of hospitalization although not significant. Simultaneous colorectal resection and liver RFA is safe and must be included in surgeons' armamentarium.

A validation study of combined resection and ablation therapy for multiple hepatocellular carcinoma

To validate the utility of hepatic resection combined with complementary radiofrequency ablation (RFA) compared with resection alone for patients with multiple hepatocellular carcinoma (HCC), and to compare these results with those of a previous report. A total of 78 HCC patients with multiple (≤5) tumours who were initially treated with hepatic resection only (Resection group) or with combined hepatic resection and RFA (Combination group) were included. Overall and disease-free survival were analysed. There were 21 women and 57 men with a median age of 72.5 (64.3-76.8) years. Fifty-three patients were treated with resection alone and 25 received combination therapy. The 3-, 5-, and 7-year cumulative overall survival rates were 81.2%, 68.2%, and 57.1%, respectively, in the Resection group, and 81.3%, 59.6%, and 42.4%%, respectively, in the Combination group (hazard ratio [HR], 1.462; 95% confidence interval [CI], 0.682-3.136; p=0.329). The 1-, 3-, and 5-year cumulative disease-free survival rates were 61.4%, 45.7%, and 39.8%, respectively, in the Resection group, and 53.1%, 18.6%, and 0%, respectively, in the Combination group (HR, 2.080; 95% CI, 1.157-3.737; p=0.014). The overall survival rate was not significantly different between the Resection and Combination groups in patients within the up-to-seven HCC criteria (n=56; HR, 2.101; 95% CI, 0.805-5.486; p=0.130) or those beyond these criteria (n=22; HR, 0.804; 95% CI, 0.197-3.286; p=0.761). The combination of hepatic resection and RFA therapy may be an effective strategy for HCC patients with multiple tumours.

Study of flow effects on temperature-controlled radiofrequency ablation using phantom experiments and forward simulations.

Blood flow is known to add variability to hepatic radiofrequency ablation (RFA) treatment outcomes. However, few studies exist on its impact on temperature-controlled RFA. Hence, we investigate large-scale blood flow effects on temperature-controlled RFA in flow channel experiments and numerical simulations. Ablation zones were induced in tissue-mimicking, thermochromic phantoms with a single flow channel, using an RF generator with temperature-controlled power delivery and a monopolar needle electrode. Channels were generated by molding the phantom around a removable rod. Channel radius and saline flow rate were varied to study the impact of flow on (i) the ablated cross-sectional area, (ii) the delivered generator power, and (iii) the occurrence of directional effects on the thermal lesion. Finite volume simulations reproducing the experimental geometry, flow conditions, and generator power input were conducted and compared to the experimental ablation outcomes. Vessels of different channel radii affected the ablation outcome in different ways. For mm, the ablated area decreased with increasing flow rate while the energy input was hardly affected. For mm and mm, the energy input increased toward larger flow rates; for these radii, the ablated area decreased and increased toward larger flow rates, respectively, while still being reduced overall as compared to the reference experiment without flow. Directional effects, that is, local shrinking of the lesion upstream of the needle and an extension thereof downstream, were observed only for the smallest radius. The simulations qualitatively confirmed these observations. As compared to performing the simulations without flow, including flow effects in the simulations reduced the mean absolute error between experimental and simulated ablated areas from 0.23 to 0.12. While the temperature control mechanism did not detect the heat sink effect in the case of the smallest channel radius, it counteracted the heat sink effect in the case of the larger channel radii with an increased energy input; this explains the increase in ablated area toward high flow rates (for mm). The experiments in a simple phantom setup, thus, contribute to a good understanding of the phenomenon and are suitable for model validation.

Effect of Portal Vein and Hepatic Artery Occlusion on Radiofrequency Ablation: Animal Experiment Comparing MR and Histology Measurements of the Ablation Zones.

This animal experimental study evaluated how hepatic artery and portal vein transient occlusion affects the ablation zone of hepatic radiofrequency ablation (RFA). Twenty-one rabbits were divided into three groups of seven each: (1) control, (2) hepatic artery occlusion, and (3) portal vein occlusion by a balloon catheter. For each rabbit, two or three RFA sessions were performed using an electrode needle. Ablation time, temperature around the tip of RFA needle at the end of RFA, ablation volume on fat-suppressed T1-weighted image in the hepatobiliary phase, and coagulative necrosis area on histopathology were measured and compared between the three groups using the Kruskal-Wallis paired Mann-Whitney U tests. In 43 RFA sessions (group 1, 15; group 2, 14; group 3, 14), mean tissue temperature in group 3 (77.0°C ± 7.7°C) was significantly higher compared to groups 1 (59.2°C ± 18.8°C; P = 0.010) and 2 (67.5°C ± 9.9°C; P = 0.010). In addition, mean ablation volume and coagulative necrosis in group 3 (2.10 ± 1.37 mm3 and 0.86 ± 0.28 mm2, respectively) were larger compared to groups 1 (0.84 ± 0.30 mm3; P < 0.001 and 0.55 ± 0.26 mm2; P = 0.020, respectively) and 2 (0.89 ± 0.59 mm3; P = 0.002 and 0.60 ± 0.22 mm2; P = 0.024, respectively). Portal vein occlusion potentially boosts tissue temperature, ablation volume, and area of histopathologically proven coagulative necrosis during hepatic RFA in the non-cirrhotic liver.

Abstract No. 99 Financial reimbursement in interventional radiology procedures: multicenter analysis within the Americas

To compare financial reimbursement costs related to interventional radiology procedures (IRP) across USA, Canada (Ontario) and Brazil Medicare Billing (based on RVU and CPT codes) obtained from a single institution was considered as the primary database for US billing. USA Procedure Reimbursement Fees (PRF) included billings in NON FAC PAR, NON FAC NON PAR, NON FAC LC, FAC PAR, FAC NON PAR and FAC LC categories. However, NON FAC PAR fees were utilized as a US Standard baseline for comparison with Ontario and Brazil. Brazilian private PRF were obtained from a single institution. Canadian billings were obtained from a single institution in Ontario (OHIP Database). Equivalency factor for standardization of PRF included the pre-COVID cost of living adjusted income (using proportionate household disposable income as a basis) and pre-COVID foreign exchange rate for each country (February 2020), relative to USA. All currency values were presented in US dollar equivalent. 32 of 45 procedures met inclusion criteria with PRF present for each country. Procedures with fees not available in 1 or more countries were excluded. Brazil-USA: 19 (59%) procedures demonstrated an average of 66% lower fees in Brazil as compared to USA. Some of these procedures include varicocele embolization, portal vein embolization, uterine fibroid embolization, Gastrojejunostomy tube placement and IVC filter placement. Only 12 (37%) procedures demonstrated an average of 219% higher fees in Brazil as compared to USA. Canada-USA: 22 (69%) procedures were underpaid in Ontario (-95% to -19%). Some of these procedures include biliary stent insertion, CT-guided visceral biopsy, port insertion, cholecystostomy tube, carotid stenting, hepatic radiofrequency ablation, thoracocentesis, mesenteric stenting and suprapubic catheter insertion. 1 (3%) procedure was similar in PRF (variance within ±5%). Variable PRF across nations has resulted in relatively low reimbursement fees in Brazil and Canada. Based on cost-of-living adjusted income and foreign exchange rate, a PRF reform is needed, in order to standardize IRP fees in Brazil, Canada and USA.

In vivo detection of distal tumor glycolytic flux stimulated by hepatic ablation in a breast cancer model using hyperpolarized 13C MRI

PurposeHepatic thermal ablation therapy can result in c-Met-mediated off-target stimulation of distal tumor growth. The purpose of this study was to determine if a similar effect on tumor metabolism could be detected in vivo with hyperpolarized 13C MRI. Materials and methodsIn this prospective study, female Fisher rats (n = 28, 120–150 g) were implanted with R3230 rat breast adenocarcinoma cells and assigned to either: sham surgery, hepatic radiofrequency ablation (RFA), or hepatic RFA + adjuvant c-Met inhibition with PHA-665752 (RFA + PHA). PHA-665752 was administered at 0.83 mg/kg at 24 h post-RFA. Tumor growth was measured daily. MRI was performed 24 h before and 72 h after treatment on 14 rats, and the conversion of 13C-pyruvate into 13C-lactate within each tumor was quantified as lactate:pyruvate ratio (LPR). Comparisons of tumor growth and LPR were performed using paired and unpaired t-tests. ResultsHepatic RFA alone resulted in increased growth of the distant tumor compared to sham treatment (0.50 ± 0.13 mm/day versus 0.11 ± 0.07 mm/day; p < 0.001), whereas RFA + PHA (0.06 ± 0.13 mm/day) resulted in no significant change from sham treatment (p = 0.28). A significant increase in LPR was seen following hepatic RFA (+0.016 ± 0.010, p = 0.02), while LPR was unchanged for sham treatment (−0.048 ± 0.051, p = 0.10) or RFA + PHA (0.003 ± 0.041, p = 0.90). ConclusionIn vivo hyperpolarized 13C MRI can detect hepatic RFA-induced increase in lactate flux within a distant R3230 tumor, which correlates with increased tumor growth. Adjuvant inhibition of c-Met suppresses these off-target effects, supporting a role for the HGF/c-Met signaling axis in these tumorigenic responses.

Hepatic Radiofrequency Ablation: Monitoring of Ablation-Induced Macrophage Recruitment in the Periablational Rim Using SPION-Enhanced Macrophage-Specific Magnetic Resonance Imaging.

Macrophages accumulating in the periablational rim play a pivotal role in initiating and sustaining the perifocal inflammatory reaction, which has been shown to be at least 1 of the mechanisms responsible for the systemic pro-oncogenic effects of focal hepatic radiofrequency ablation (RFA). Herein, we tested the hypothesis to use superparamagnetic iron oxide nanoparticle (SPION)-enhanced magnetic resonance imaging (MRI) for noninvasive quantification of iron-loaded macrophages in the periablational rim of VX2 tumor-bearing rabbits. Twelve VX2 tumor-bearing rabbits underwent MRI immediately after and up to 3 weeks after focal hepatic RFA. For noninvasive quantification of macrophage accumulation in the periablational rim, animals were scanned before and 24 hours after SPION injection. T2*-weighted images were analyzed and correlated with histopathological and immunohistochemical findings. Furthermore, correlations with quantitative measurements (ICP-MS [inductively coupled plasma-mass spectrometry] and LA-ICP-MS [laser ablation-ICP-MS]) were performed. SPION-enhanced T2*-weighted MRI scans displayed a progressive increase in the areas of signal intensity (SI) loss within the periablational rim peaking 3 weeks after RFA. Accordingly, quantitative analysis of SI changes demonstrated a significant decline in the relative SI ratio reflecting a growing accumulation of iron-loaded macrophages in the rim. Histological analyses confirmed a progressive accumulation of iron-loaded macrophages in the periablational rim. The ICP-MS and LA-ICP-MS confirmed a progressive increase of iron concentration in the periablational rim. SPION-enhanced MRI enables noninvasive monitoring and quantification of ablation-induced macrophage recruitment in the periablational rim. Given the close interplay between ablation-induced perifocal inflammation and potential unwanted tumorigenic effects of RFA, SPION-enhanced MRI may serve as a valuable tool to guide and modulate adjuvant therapies after hepatic RFA.

Elastin-specific MRI of extracellular matrix-remodelling following hepatic radiofrequency-ablation in a VX2 liver tumor model

Hepatic radiofrequency ablation (RFA) induces a drastic alteration of the biomechanical environment in the peritumoral liver tissue. The resulting increase in matrix stiffness has been shown to significantly influence carcinogenesis and cancer progression after focal RF ablation. To investigate the potential of an elastin-specific MR agent (ESMA) for the assessment of extracellular matrix (ECM) remodeling in the periablational rim following RFA in a VX2 rabbit liver tumor-model, twelve New-Zealand-White-rabbits were implanted in the left liver lobe with VX2 tumor chunks from donor animals. RFA of tumors was performed using a perfused RF needle-applicator with a mean tip temperature of 70 °C. Animals were randomized into four groups for MR imaging and scanned at four different time points following RFA (week 0 [baseline], week 1, week 2 and week 3 after RFA), followed by sacrifice and histopathological analysis. ESMA-enhanced MR imaging was used to assess ECM remodeling. Gadobutrol was used as a third-space control agent. Molecular MR imaging using an elastin-specific probe demonstrated a progressive increase in contrast-to-noise ratio (CNR) (week 3: ESMA: 28.1 ± 6.0; gadobutrol: 3.5 ± 2.0), enabling non-invasive imaging of the peritumoral zone with high spatial-resolution, and accurate assessment of elastin deposition in the periablational rim. In vivo CNR correlated with ex vivo histomorphometry (ElasticaVanGiesson-stain, y = 1.2x − 1.8, R2 = 0.89, p < 0.05) and gadolinium concentrations at inductively coupled mass spectroscopy (ICP-MS, y = 0.04x + 1.2, R2 = 0.95, p < 0.05). Laser-ICP-MS confirmed colocalization of elastin-specific probe with elastic fibers. Following thermal ablation, molecular imaging using an elastin-specific MR probe is feasible and provides a quantifiable biomarker for the assessment of the ablation-induced remodeling of the ECM in the periablational rim.

Fast calculation of 3D radiofrequency ablation zone based on a closed-form solution of heat conduction equation fitted by ex vivo measurements

Fast calculation or simulation of the ablation zone induced by radiofrequency ablation (RFA) has a critical role in hepatic RFA planning and therapy. However, it remains challenging to approximate the ablation zone in real time, especially when more than one probe is involved in one ablation session. This paper presents a novel computational technique to calculate the 3D ablation zone of one probe RFA and two-probe switching RFA. The main idea is to get an approximate solution of the temperature distribution from a simplified Pennes bioheat equation, and further fit the solution to the coagulation measurements on ex vivo porcine liver. With a closed-form solution of temperature distribution, the calculation of the ablation zone is as simple as the commonly used ellipsoidal model, but it allows a more realistic prediction of combined ablation zones with different inter-probe spacing. The new approximation technique could potentially replace the original ellipsoidal model in the intervention planning step.

Diaphragmatic Disruption Ahead of Herniation Following Hepatic Radiofrequency Ablation

Diaphragmatic Disruption Ahead of Herniation Following Hepatic Radiofrequency Ablation

Simulation study of the cooling effect of blood vessels and blood coagulation in hepatic radio-frequency ablation

Purpose Computer simulations of hepatic radio-frequency ablation (RFA) were performed to: (i) determine the dependence of the vessel wall heat transfer coefficient on geometrical parameters; (ii) study the conditions required for the occurrence of the directional effect of blood; and (iii) classify blood vessels according to their effect on the thermal lesion while considering blood coagulation. The information thus obtained supports the development of a multi-scale bio-heat model tailored for more accurate prediction of hepatic RFA outcomes in the vicinity of blood vessels. Materials and methods The simulation geometry consisted of healthy tissue, tumor tissue, a mono-polar RF-needle, and a single cylindrical blood vessel. The geometrical parameters of interest were the RF-needle active length and those describing blood vessel configuration. A simple, novel method to incorporate the effects of blood coagulation into the simulation was developed and tested. Results A closed form expression giving the dependence of the vessel wall heat transfer coefficient on geometrical parameters was obtained. Directional effects on the thermal lesion were found to occur for blood vessel radii between 0.4 mm and 0.5 mm. Below 0.4 mm blood coagulation blocked the flow. Conclusions The closed form expression for the heat transfer coefficient can be used in models of RFA to speed up computation. The conditions on vessel radii required for the occurrence of directional effects on the thermal lesion were determined. These conditions allow the classification of blood vessels. Different approximations to the thermal equation can thus be used for these vessel classes.

Adjuvant oxaliplatin-based chemotherapy effect after treatment of colorectal hepatic metastasis.

PurposeWe aimed to investigate whether adjuvant oxaliplatin-based chemotherapy after treatment for hepatic metastasis affects recurrence or survival and to determine the risk factors for recurrence or survival.MethodsForty-six patients who underwent curative treatment for hepatic metastasis from colorectal cancer between July 2009 and December 2017 were included from a retrospectively collected patient database. Curative resection included hepatic resection, radiofrequency ablation (RFA), or a combination of both, followed by adjuvant chemotherapy with oxaliplatin-based chemotherapy.ResultsThirty-seven patients (80.4%) had colon cancer and 9 (19.6%) had rectal cancer. Twenty-six patients (56.5%) underwent hepatic resection, 7 (15.2%) RFA, and 13 (28.3%) hepatic resection and RFA. Thirty-two patients (69.6%) underwent chemotherapy after hepatic treatment. The recurrence incidence was 50% in the non-chemotherapy group and 46.9% in the chemotherapy group (P > 0.999). The incidence of death was 7.1% in the non-chemotherapy group and 18.8% in the chemotherapy group (P = 0.657). The recurrence risk factors were N stage (N0 vs. N2; P = 0.013, P = 0.005) and bilobed hepatic metastasis (P = 0.027, P = 0.009) in the univariate and multivariate analyses, respectively. However, chemotherapy after hepatic treatment was not a risk factor for disease-free survival (DFS) or overall survival (OS) in the univariate and multivariate analyses (P = 0.656 and P = 0.414, respectively; P = 0.510 and P = 0.459, respectively).ConclusionOxaliplatin-based adjuvant chemotherapy after colorectal hepatic metastasis treatment did not affect the DFS or OS. The N stage of the primary tumor and bilobed hepatic metastasis are risk factors for recurrence and death.

AC measurements and simulations of hepatic radiofrequency ablation

Introduction The radiofrequency ablation (RFA) of liver cancer is a desirable treatment option, as it is minimally invasive. An accurate numerical simulation can greatly help physicians better plan their surgical protocols. Previously, the displacement current in the RFA process was considered negligible, and therefore RFA simulation was modeled as a direct current (DC) system instead of an alternating current (AC) system. Our study investigated the hypothesis that the displacement current in the RFA process should not always be considered negligible. Methods AC measurements of ex vivo bovine liver ablation were performed, and numerical simulations were also conducted to test the hypothesis that the relative permittivity would significantly decrease after the liver tissue reached a high temperature. Results The displacement current was observed to be a sizable fraction of the conduction current, especially before the onset of the first pause. The simulation results indicated that the relative permittivity is likely to decrease to several hundred or lower at elevated temperatures. Conclusions Our study results suggest that the DC model may be inadequate, especially before the first roll-off and that additional information could be available during RFA treatment by considering the AC nature of RFA, which could lead to improved numerical simulation. Additional measurements of tissue parameters are needed to reach the full potential of the AC model for further development of ablation control.