Rationale and Objectives
Inflammatory reaction surrounding the ablated area is a major confounding factor in the early detection of viable tumor after radiofrequency (RF) ablation. A difference in the responsiveness of normal and tumor blood vessels to vasoactive agents may be used to distinguish these regions in post-ablation follow-up. The goal of this study was to examine longitudinal perfusion changes in untreated viable tumor and the peripheral hyperemic rim of RF-ablated tumor in response to a vasoconstrictor (phenylephrine) or vasodilator (hydralazine) in a subcutaneous rat tumor model.
Materials and Methods
Bilateral subcutaneous shoulder tumors were inoculated in 24 BDIX rats and evenly divided into two groups (phenylephrine and hydralazine groups). One tumor in each animal was completely treated with RF ablation (at 90 ± 2°C for 3 minutes), and the other remained untreated. Computed tomographic perfusion scans before and after phenylephrine (10 μg/kg) or hydralazine (5 mg/kg) administration were performed 2, 7, and 14 days after ablation. Four rats per group were euthanized on each scan day, and pathologic evaluation was performed. The changes of blood flow in the peripheral rim of ablated tumor and untreated viable tumor in response to phenylephrine or hydralazine at each time point were compared. The diagnostic accuracy of viable tumor using the percentage change of blood flow in response to phenylephrine and hydralazine was compared using receiver-operating characteristic analysis.
Results
The peripheral rim of ablated tumor presented with a hyperemic reaction with dilated vessels and congestion on day 2 after ablation, numerous inflammatory vessels on day 7, and granulation tissue formation on day 14. Phenylephrine significantly decreased the blood flow in the peripheral hyperemic rim of ablated tumor on days 2, 7, and 14 by 16.3 ± 9.7% ( P = .001), 24.0 ± 22.6% ( P = .007), and 31.1 ± 25.4% ( P = .045), respectively. In untreated viable tumor, the change in blood flow after phenylephrine was irregular and insignificant. Hydralazine decreased the blood flow in the peripheral rim of both ablated tumor and untreated viable tumor. Receiver-operating characteristic analysis showed that reliable tumor diagnosis using the percentage change of blood flow in response to phenylephrine was noted on days 2 and 7, for which the areas under the curve were 0.82 (95% confidence interval, 0.64–1.00) and 0.81 (95% confidence interval, 0.56–1.00), respectively. However, tumor diagnosis using the blood flow change in response to hydralazine was unreliable.
Conclusion
Phenylephrine markedly decreased blood flow in the peripheral hyperemic rim of ablated tumor but had little effect on the untreated viable tumor. Computed tomographic perfusion with phenylephrine may be useful in the long-term treatment assessment of RF ablation.
Interventional oncologic procedures such as chemical ablation, laser ablation, radiofrequency (RF) ablation, and microwave ablation have been widely used in unresectable solid tumor treatment. These techniques can provide efficacious, cost-effective management of localized cancer sites . However, local recurrence due to factors such as large tumor size (>3 cm), irregular contours, and affluent blood supply continues to be a main cause of treatment failure . The early detection of residual or locally recurrent tumor after interventional treatment is critical and can facilitate successful retreatment at an early stage.
Contrast-enhanced computed tomography and magnetic resonance (MR) are currently used to evaluate RF ablation efficacy. However, an inflammatory peripheral rim induced by ablation, which presents as enhancement surrounding the coagulated zone, can obscure viable residual tumor. The histologic examination of ablated tumors has shown that the sensitivity of computed tomography or MR for the detection of viable tumor after ablation ranges from 36% to 86% . Recent reports that positron emission tomography/computed tomography can increase the sensitivity and accuracy for the detection of residual tumor are promising , but this modality may not be sufficiently cost effective to become a routine follow-up method. New imaging methods are needed for the successful and accurate follow-up of local tumor ablation therapy.
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Materials and methods
Overall Experimental Design
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Animal Model
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RF Ablation
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CT Perfusion
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Image Analysis
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Histopathologic Examination
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Statistical Analysis
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Results
CT Perfusion Findings and Corresponding Histologic Correlation
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![Figure 1, Correlation of perfusion images ( [a] maximum-intensity projection, [b] blood flow) with histology ( [c] 4×, [d] 200× [hematoxylin and eosin]) in an untreated tumor. The central zone ( asterisks ) of the tumor presents hyperdense on the maximum-intensity projection image (a) , shows no perfusion (b) , and appears necrotic on the corresponding histologic image (c) . The tumor rim consists of densely packed viable tumor cells encased by a hypervascular fibrous capsule (d) .](https://storage.googleapis.com/dl.dentistrykey.com/clinical/RadiofrequencyAblation/0_1s20S1076633208005394.jpg)
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![Figure 2, Representative hematoxylin and eosin histology ( [a,c,e] 4×, [b,d,f] 200×) of tumor progression after radiofrequency ablation on days 2 (a,b) , 7 (c,d) , and 14 (e,f) . (a) On day 2, coagulative necrosis was seen in the ablation zone. In the peripheral rim (b) (white square) , a hyperemic reaction zone with dilated vessels and red blood cell infiltration is present. (c) On day 7, numerous blood vessels were found in the peripheral rim of the ablation zone (d) (white square) . The lumen of these vessels shrank to normal. (e) On day 14, granulation tissue formed in the margin of the ablation zone (f) (white square) , and the quantity of blood vessels decreased.](https://storage.googleapis.com/dl.dentistrykey.com/clinical/RadiofrequencyAblation/1_1s20S1076633208005394.jpg)
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Blood Flow Changes in the Peripheral Rim of Ablated Tumor and Untreated Viable Tumor in Response to Phenylephrine
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Table 1
Changes in Blood Flow (mL/100 mL/min) in the Peripheral Rim of Ablated Tumor, Untreated Viable Tumor, and Muscle in Response to Phenylephrine
Peripheral Rim of Ablated Tumor Untreated Viable Tumor Muscle Day_n_ Pre Post % Change Pre Post % Change Pre Post % Change 2 12 52.8 ± 19.5 44.1 ± 18.2 ∗ −16.3 ± 9.7 46.9 ± 12.9 52.2 ± 24.0 11.0 ± 32.7 4.7 ± 3.3 2.9 ± 2.3 −36.8 ± 54.7 7 8 69.2 ± 26.3 52.2 ± 25.1 ∗ −24.0 ± 22.6 51.4 ± 8.2 49.0 ± 8.4 −4.5 ± 9.0 4.8 ± 4.7 3.7 ± 3.7 −1.6 ± 56.8 14 4 73.5 ± 14.5 49.5 ± 17.3 † −31.1 ± 25.4 46.9 ± 10.0 46.5 ± 16.9 1.8 ± 35.0 5.1 ± 5.3 2.1 ± 1.9 −61.2 ± 17.8
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Perfusion Changes in the Peripheral Rim of Ablated Tumor and Untreated Viable Tumor in Response to Hydralazine
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Table 2
Changes in Blood Flow (mL/100 mL/min) in the Peripheral Rim of Ablated Tumor, Untreated Viable Tumor, and Muscle in Response to Hydralazine
Peripheral Rim of Ablated Tumor Untreated Viable Tumor Muscle Day_n_ Pre Post % Change Pre Post % Change Pre Post % Change 2 12 47.2 ± 20.1 38.1 ± 12.8 ∗ −15.0 ± 25.9 40.9 ± 11.1 28.8 ± 9.1 † −27.5 ± 19.1 5.6 ± 2.3 3.6 ± 2.0 † −23.3 ± 52.7 7 8 71.6 ± 17.0 58.1 ± 14.5 ∗ −17.7 ± 16.8 50.6 ± 13.4 36.2 ± 10.5 ∗ −24.4 ± 32.1 3.4 ± 1.9 2.5 ± 1.7 −16.9 ± 58.5 14 4 64.4 ± 20.6 58.3 ± 31.2 −10.3 ± 30.7 43.7 ± 8.9 30.6 ± 8.7 † −30.6 ± 5.1 6.6 ± 3.1 2.5 ± 2.1 † −66.2 ± 15.7
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ROC Analysis
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Table 3
AUCs and 95% CIs of the Receiver-operating Characteristic Curves of Percentage Changes of Blood Flow in Response to Phenylephrine and Hydralazine
Phenylephrine Hydralazine AUC 95% CI AUC 95% CI Day 2 0.82 0.64–1.00 0.58 0.33–0.82 Day 7 0.81 0.56–1.00 0.66 0.37–0.95 Day 14 0.81 0.46–1.00 0.75 0.26–1.00 Pooled data 0.83 0.71–0.95 0.63 0.46–0.80
AUC, area under the curve; CI, confidence interval.
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Discussion
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Conclusion
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