Radiofrequency Ablation: Variability in Heat Sensitivity in Tumors and Tissues

Mertyna, Paweł; Hines-Peralta, Andrew; Liu, Zhengjun; Halpern, Elkan F.; Goldberg, Wallace; Goldberg, S. Nahum

doi:10.1016/j.jvir.2007.02.033

Cited by 63 publications

(33 citation statements)

References 18 publications

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“…The elevation of tissue temperature to a range of 50°-60°C induces irreversible cellular damage in minutes. However, different tissues have different time-specific variable threshold levels of cell death as a result of elevated temperature (21,22). With higher temperature elevations (60°-100°C), as were achieved at the center of the tumor in these experiments, the irreversible damage is essentially instantaneous (23).…”

Section: Experimental Studies: Radiofrequency Ablation and Antigen-prmentioning

confidence: 78%

Radiofrequency Ablation Induces Antigen-presenting Cell Infiltration and Amplification of Weak Tumor-induced Immunity

Dromi¹,

Walsh²,

Herby³

et al. 2009

Radiology

197

164

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Purpose:To evaluate the influence of subtotal radiofrequency (RF) ablation on a tumor-specific immune response in a murine tumor model and to explore the role of intratumoral dendritic cells (ITDCs) in mediating this effect. Materials and Methods:Animal work was performed according to an approved protocol and in compliance with the National Cancer Institute Animal Care and Use Committee guidelines and regulations. A murine urothelial carcinoma (MB49) model expressing the male minor histocompatibility (HY) antigen was inoculated subcutaneously in female mice. Fourteen days later, splenic T cells were analyzed with enzymelinked immunosorbent spot for HY immune response (n ϭ 57). In subsequent experiments, mice were randomized into control (n ϭ 7), RF ablation, ITDC (n ϭ 9), and RF ablation ϩ ITDC (n ϭ 9) groups and monitored for tumor growth. Eleven days after treatment, tumors were harvested for histologic and immunohistochemical analysis. Animals demonstrating complete tumor regression were rechallenged in the contralateral flank. Results:Animals treated with subtotal RF ablation showed significant increases in tumor-specific class I and II responses to HY antigens and tumor regression. RF ablation, ITDC, and combined groups demonstrated similar levels of antigenpresenting cell infiltration; all groups demonstrated greater levels of infiltration compared with untreated controls. ITDC injection also resulted in tumor regression. However, combination therapy did not enhance tumor regression when compared with either treatment alone. Rechallenged mice in RF ablation, ITDC, and combination groups demonstrated significant tumor growth inhibition compared with controls. Conclusion:Subtotal RF ablation treatment results in enhanced systemic antitumor T-cell immune responses and tumor regression that is associated with increased dendritic cell infiltration. ITDC injection mimics the RF ablation effect but does not increase immune responses when injected immediately after RF ablation.

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Section: Experimental Studies: Radiofrequency Ablation and Antigen-prmentioning

confidence: 78%

Radiofrequency Ablation Induces Antigen-presenting Cell Infiltration and Amplification of Weak Tumor-induced Immunity

Dromi¹,

Walsh²,

Herby³

et al. 2009

Radiology

197

164

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“…8,11,12 For many tissue types treated with hyperthermia, it is estimated that for each 1°C temperature rise above 43°C, there is a doubling of the biological effect of the hyperthermia. 8,11 For long periods of hyperthermia, lower tissue temperatures are needed to produce tissue injury. Conversely, shorter exposures to hyperthermia require higher temperatures to produce tissue damage.…”

Section: Discussionmentioning

confidence: 99%

Direct Measurement of the Lethal Isotherm for Radiofrequency Ablation of Myocardial Tissue

Wood

Goldberg

Lau

et al. 2011

Circ: Arrhythmia and Electrophysiology

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Background-The lethal isotherm for radiofrequency catheter ablation of cardiac myocardium is widely accepted to be 50°C, but this has not been directly measured. The purpose of this study was to directly measure the tissue temperature at the edge of radiofrequency lesions in real time using infrared thermal imaging. Methods and Results-Fifteen radiofrequency lesions of 6 to 240 seconds in duration were applied to the left ventricular surface of isolated perfused pig hearts. At the end of radiofrequency delivery, a thermal image of the tissue surface was acquired with an infrared camera. The lesion was then stained and an optical image of the lesion was obtained. The thermal and optical images were electronically merged to allow determination of the tissue temperature at the edge of the lesion at the end of radiofrequency delivery. By adjusting the temperature overlay display to conform with the edge of the radiofrequency lesion, the lethal isotherm was measured to be 60.6°C (interquartile ranges, 59.7°to 62.4°C; range, 58.1°to 64.2°C). The areas encompassed by the lesion border in the optical image and the lethal isotherm in the thermal image were statistically similar and highly correlated (Spearman ϭ0.99, PϽ0.001). The lethal isotherm temperature was not related to the duration of radiofrequency delivery or to lesion size (both PϾ0.64). The areas circumscribed by 50°C isotherms were significantly larger than the areas of the lesions on optical imaging (Pϭ0.002). Conclusions-By direct measurement, the lethal isotherm for cardiac myocardium is near 61°C for radiofrequency energy deliveries Ͻ240 seconds in duration. A 50°C isotherm overestimates lesion size. Accurate knowledge of the lethal isotherm for radiofrequency ablation is important to clinical practice as well as mathematical modeling of radiofrequency lesions. (Circ Arrhythm Electrophysiol. 2011;4:373-378.)

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“…In essence, we are producing an infi nite spectrum of thermal doses ( 50 ), which underscores the importance of understanding the spatial distribution of a myriad of different mechanisms of cell death and the varied physiologic responses to different levels of thermal insult. On the other hand, it can be argued that rather than resorting to a common strategy of reducing the study of hyperthermia to a single or a set of limited thermal doses ( 50,51 ), our model helps us understand what occurs across a wide range of temperatures and thermal doses, a situation which undoubtedly occurs not only in high-temperature ablation, but also more often than not for lowertemperature hyperthermia regimens ( 52 ). Regardless, our data support the contention that conceptual models such as the concentric zones highlighted in Figure 2 will be needed to best understand current and future thermal ablation paradigms.…”

Section: Experimental Studies: Increasing Stress and Apoptosis At Ablmentioning

confidence: 99%

“…These fi ndings also encourage exploration of combined treatment for other methods of tumor ablation. Finally, some of these modifications may be necessary for other tumor types which are likely to show both variable thermal dosimetry ( 50,51 ) and varied sensitivity to different adjuvants.…”

Section: Experimental Studies: Increasing Stress and Apoptosis At Ablmentioning

confidence: 99%

Liposomal Doxorubicin Increases Radiofrequency Ablation–induced Tumor Destruction by Increasing Cellular Oxidative and Nitrative Stress and Accelerating Apoptotic Pathways

Solazzo

Ahmed²,

Schor-Bardach³

et al. 2010

Radiology

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Purpose:To determine if oxidative and nitrative stress and/or apoptosis contribute to increased coagulation when combining radiofrequency (RF) ablation with liposomal doxorubicin. Materials and Methods:Animal care committee approval was obtained. R3230 mammary adenocarcinomas in Fischer rats were treated with either RF ablation ( n = 43), 1 mg of intravenously injected liposomal doxorubicin ( n = 26), or combined therapy ( n = 30) and were compared with control subjects ( n = 11). A subset of animals receiving combination therapy ( n = 24) were treated in the presence or absence of N -acetylcysteine (NAC) administered 24 hours and 1 hour before RF ablation. Tumors were analyzed 2 minutes to 72 hours after treatment to determine the temporal range of response by using immunohistochemical staining of the apoptosis marker cleaved caspase-3, phosphorylated g H2AX , and Results:By 4 hours after RF ablation alone, a 0.48-mm 6 0.13 (standard deviation ) peripheral band with 57.0% 6 7.3 cleaved caspase-3 positive cells was noted at the ablation margin, whereas a 0.73-mm 6 0.18 band with 77.7% 6 6.3 positivity was seen for combination therapy ( P , .03 for both comparisons). Combination therapy caused increased and earlier staining for 4-HNE-modifi ed proteins, 8-OHdG, NT, and g H2AX with colocalization to cleaved caspase-3 staining. A rim of increased HSP70 was identifi ed peripheral to the area of cleaved caspase-3. Parameters of oxidative and nitrative stress were signifi cantly inhibited by NAC 1 hour following RF ablation, resulting in decreased cleaved caspase-3 positivity (0.28-mm 6 0.09 band of 25.9% 6 7.4 positivity vs 0.59-mm 6 0.11 band of 62.9% 6 6.0 positivity, P , .001 for both comparisons). Conclusion:Combining RF ablation with liposomal doxorubicin increases cell injury and apoptosis in the zone of increased coagulation by using a mechanism that involves oxidative and nitrative stress that leads to accelerated apoptosis.q RSNA, 2010

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Radiofrequency Ablation: Variability in Heat Sensitivity in Tumors and Tissues

Cited by 63 publications

References 18 publications

Radiofrequency Ablation Induces Antigen-presenting Cell Infiltration and Amplification of Weak Tumor-induced Immunity

Radiofrequency Ablation Induces Antigen-presenting Cell Infiltration and Amplification of Weak Tumor-induced Immunity

Direct Measurement of the Lethal Isotherm for Radiofrequency Ablation of Myocardial Tissue

Liposomal Doxorubicin Increases Radiofrequency Ablation–induced Tumor Destruction by Increasing Cellular Oxidative and Nitrative Stress and Accelerating Apoptotic Pathways

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