| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Clinical Observations |
1 Department of Radiology, Osaka City University Graduate School of Medicine,
1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan.
2 Department of Pathology, Osaka City University Graduate School of Medicine,
Abeno-ku, Osaka 545-8585, Japan.
Received June 18, 2004;
accepted after revision November 10, 2004.
Address correspondence to A. Yamamoto.
Abstract
 Top Abstract IntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
CONCLUSION. Ground-glass attenuation on CT led to overestimation of the size of necrotic lesions. The layered structural findings on CT were consistent with the histopathologic findings. Although CT findings reflect the histopathologic findings, attention should be paid to the dissociation of ablated lesions and high-density areas in clinical interpretation of CT images.
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
For all procedures, anesthesia was induced with midazolam (40 mg/kg), medetomidine hydrochloride (0.2 mg/kg), ketamine hydrochloride (10-20 mg/kg), and atropine sulfate (0.5 mg/kg). Pentobarbital sodium (50-150 mg) was used to maintain anesthesia. We used 15-gauge needles that have four retractable hooks with a maximum diameter of 3.0 cm (Model 30, RITA Medical Systems). After a swine was prepared without tracheal intubation and was placed in the left or right lateral position on a CT table, grounding pads were placed on the thighs. Percutaneous radiofrequency ablation was performed under CT guidance (ProSpeed, GE Healthcare) at four to eight random points per animal so that they did not overlap with each other. A 50-W radiofrequency ablation generator was used in the Power Control mode. The emission power was initially set at 10 W and was increased by 5 W every 2 min. Radiofrequency energy was applied until the generator automatically stopped due to the increased resistance caused by tissue dehydration. After a cooling period of 30 sec, the second session was performed in a similar manner to the first. However, the second session was started with 75% of the maximum power of the first session and was allowed to be terminated by automatic power adjustment.
|
|
|
|
The swine in each group were sacrificed immediately after the final CT examination. After heparinization, the animals were sacrificed with an overdose of IV-injected pentobarbital sodium (60-120 mg). The lung specimens were fixed and inflated by Heitzman's method [25, 26] using a fixative composed of polyethylene glycol 400, 95% ethanol, 40% formaldehyde, and distilled water in proportions of 10:5:2:3. As a preliminary step, we distended and fixed the specimen with 10% formalin before proceeding to Heitzman's method. The duration of preliminary formalin distention was 3 hr. After fixation, as much formalin as possible was removed by manual compression. Afterward, the fixative was injected through the trachea at 30 cm of H2O pressure for 4 days and air was inflated for 2 or 3 days. Subsequently, each radiofrequency lesion was axially sliced at 5-mm intervals for comparison between CT and histopathologic findings.
|
|
The CT findings of all radiofrequency lesions were correlated with the histopathologic results. The maximum lesion size as measured on CT was then correlated with the histopathologically determined lesion size. The correlation between the ablated lesion on CT and that on macroscopic observation was investigated using Poisson's correlation coefficient, which was used to describe the degrees of correlation between all possible two-variable combinations. Statistical significance was established by the Student's two-tailed t test. A p value of 0.05 was considered to be statistically significant.
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
(range, 65-120 ).
Group A: Sacrificed Within 2 Hr After Radiofrequency Ablation
In group A, the ablated lesions were typically shown as areas with a
ground-glass attenuation on CT images (Fig.
1A). Macroscopically, the ablated lesions had a two-layered
structure presenting as a ring shape (Fig.
1B). The boundaries of the two layers were not clear.
Histopathologically, the ablated lesions presented as a three-layered
structure. In the outermost layer, strong congestion was seen and was
accompanied by hemorrhage, neutrophil infiltration, and fibrin deposition
(hemorrhagic rim) (Fig. 1C). The average width of the outermost layer ± SD was 2.6 ± 0.66 mm
(range, 2.0-4.1 mm). In its intermediate layer, alveolar spaces were filled
with effusion, and hyaline membrane formation was observed in the inner
surfaces of the alveolar walls. Congestion was also observed in the
intermediate layer but was milder than that seen in the outermost layer. In
the innermost portion, the alveolar structure and cell nuclei were seemingly
retained. However, the cytoplasm showed acidophilic changes and the nuclei had
condensed chromatin. Around the needled areas, the tissue structure
disappeared and only an amorphous eosinophilic matrix remained. These changes
collectively indicated that the innermost portion was necrotic lesion. Enzyme
histochemical staining for NADH (n = 12) confirmed that nonstained
cells in the innermost portion and intermediate layer completely lost cellular
integrity (ongoing necrosis) and the outermost layer contained an admixture of
stained and nonstained cells (Figs.
1D and
1E).
Group B: Sacrificed 3 Days After Radiofrequency Ablation
The ablated lesions from group B were typically observed as a two-layered
ring-shaped structure on CT images. Macroscopically, the lesions in group B
showed a three-layered structure similar to that in group A. The boundaries
between the outermost layer and nonablated portion were clearer than those in
group A. Histopathologically, the ablated lesions presented as a three-layered
structure as with group A, and almost no difference in the structure was
observed between group A and B lesions. On the other hand, the ring-shaped
lesion in the outermost layer was clear and inflammatory cell infiltration was
enhanced in group B lesions.
|
|
|
Group D: Sacrificed 4 Weeks After Radiofrequency Ablation
On CT images, the overall size of group D lesions had decreased compared
with the overall size of group C lesions and the lesions were typically
recognized as high-density masslike lesions. Histopathologically, a two-layer
structure was seen. Hyperplasia of granulation tissues in the outer layer and
necrotic tissues in the inner layer were observed. The decreased area of the
inner layer resulted in a decrease in the overall size (Figs.
3A,
3B, and
3C).
|
|
|
For all the imaging techniques we used, the average maximum lesion sizes are summarized in Figure 4. The diameters of the high-density areas observed on CT and those of the ablated lesions microscopically observed were significantly correlated in groups A, B, and C. However, the correlation in group D was not significant.
|
During the follow-up period, among the 52 lesions in all groups except those in group A, 21 (40.4%) showed a wedge-shaped high-density area to the periphery that was found in only the periphery of the ablated areas on CT (Fig. 3B). Histopathologically, in the ablated lesions of the bronchus, stenosis or obstruction by granulation tissues or a polyplike formation of granulation tissues, which originated from organization of the necrotic layers (Fig. 3C), was found. This was considered because of bronchial stenosis or obstruction, wedge-shaped occlusive pneumonitis, and lowered pneumatization were observed in the peripheral lung parenchyma (Fig. 3A).
For all the lesions excluding those in group A, a cavity that was similar to pulmonary abscesses on CT was found (Fig. 5A) (18 cases in 52 nodes [34.6%]). Histopathologically, the border of this cavity was covered with granulation tissues in the outer layer, which was found in groups C and D, and the inner layers were necrotic tissue or completely empty of tissue (Fig. 5B). This was considered to be due to draining of internal necrotic tissues into bronchus.
|
|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
The first characteristic is that unlike radiofrequency ablation used against liver tumors in which the ablated lesions can be monitored by sonography and the postoperative ablated areas can be determined by dual CT, radiofrequency ablation of lung tumors has no appropriate technique for follow-up. There is no uniform view about the image findings that indicate effective ablation areas in cases receiving radiofrequency ablation for lung tumors because the lung is not satisfactorily visible on sonograms or enhanced CT. In this study, the ablated lesions showed as areas with a ground-glass attenuation on CT immediately after ablation. The maximum diameters of the ablated lesions were significantly correlated with the size of the areas showing ground-glass attenuation on CT.
Histopathologically, the areas with a ground-glass attenuation consisted of three-layered structure (innermost portion, intermediate layer, and outermost layer). The ground-glass attenuation was observed mainly because the alveolar spaces were filled with effusion in the intermediate layer. Effusion in the intermediate layer was considered to reflect the increased permeability of blood vessels due to a defect of functional endothelial cells. Are all three-layered structures necrotic lesion? In H and E staining performed immediately after radiofrequency ablation, nuclei are still present and histopathologic changes are slight, so it is difficult to determine which areas are necrotic. A method to make up the deficit of H and E staining is NADH staining. This staining method permits evaluation of tissue ablation based on cell viability rather than on histologic characteristics [26-29].
The complete absence of NADH stain indicates a lack of cellular viability. In our study, the innermost portion and intermediate layer showed a complete absence of NADH stain, but the outermost layer contained an admixture of viable lung parenchyma. The ground-glass attenuation on CT corresponded to the inner necrotic lesion plus the hemorrhagic rim (Figs. 6A and 6B). The ground-glass attenuation on CT led to overestimation of the size of the completely necrotic lesion. The average width of the outermost layer was 2.6 mm, and the maximum width was 4.1 mm. These results suggest that the edge of tumors should be identified in the ablated lesion (i.e., areas surrounded by ground-glass attenuation) and that an adequate safety margin (at least 4.1 mm from the edge of the tumor to the edge of the ablated lesion) should be obtained on CT immediately after radiofrequency ablation in the ablation for lung tumors.
|
|
The second characteristic is that in the tissues after ablation the inflammatory cells infiltrated from the border where congestion was observed in the early stage (0-3 days after radiofrequency ablation). During that period, CT showed mainly areas with a ground-glass attenuation. The layer of granulation tissues that was gradually replaced by collagen fibers was observed in the chronic stage (10-28 days after radiofrequency ablation). CT reflected such histopathologic changes primarily on the outer layer as a ring-shaped high-density area.
As the follow-up examinations progressed, the difference between the maximum diameter measured on CT images and that measured macroscopically became larger (group D). This was thought to be because the areas including the obstructive pneumonitis region and the real lesion of ablation were regarded as the ablated lesions on CT. Attention should be paid to the dissociation of ablated lesions and high-density areas in clinical interpretation of CT images. The high-density areas were revealed to differ from the actual ablated areas as follow-up examinations progressed.
Clinically, tumors after ablation are often detected as larger on CT than before ablation [13, 14, 18]. This is because normal lung parenchyma and tumors are ablated together and the tumor and outer layer (granulation tissue) are recognized as an ablated lesion. We have to interpret the follow-up CT examinations to account for the influence of the ablated change of normal lung parenchyma on follow-up CT.
During the follow-up examinations, cavitation was observed in about one third of the samples. This cavitation has also been reported clinically [11, 13, 14, 18]. In our study, the lesion presented an image finding that was similar to that of a lung abscess. The results of this study suggest that this change is caused by completely necrotized tissues being drained into the bronchus and the remaining rigid outermost layer. Because this finding was relatively prevalent, we believe that this can be treated as a normal change in images after radiofrequency ablation as long as there are no clinical issues such as fever or increased inflammation.
The changes in layer structures were similar to those in the liver generated by radiofrequency ablation [30-32]. Goldberg et al. [22] and Miao et al. [23] also found the similar layer structures using their unique radiofrequency needles in rabbits' lungs. Goldberg et al. investigated the feasibility and safety of performing percutaneous radiofrequency ablation for the lung in eight rabbits and used CT to assess the tissue 24 hr, 3 days, 10 days, 21 days, and 28 days after radiofrequency ablation. Miao et al. performed radiofrequency ablation for VX2 tumors in 18 rabbits and confirmed the layer appearance of ablated lesion. Our histopathologic findings support their results. However, in their study, the number of ablated lesions was low, quantitation of lesion size was not based on CT, histopathology studies were not performed and there was no circumstantial histopathologic report. Because they relied only on H and E staining, they did not discuss the completely necrotic lesion. Moreover, in their report, such cavitations or obstructive pneumonitis was not reported. This is because their number of ablated lesions was low or they used their unique radiofrequency needle.
The limitations of this study are as follows: First, the number and flow of respirations in the swine under general anesthesia differed from those in patients under local anesthesia. Second, in the case of a tumor, the image findings in our model could be different from those in clinical cases containing lung cells and tumors. Third, the potential differences in lung tissues between humans and swine might influence the extrapolation of data from swine to humans. Fourth, a 50-W radiofrequency ablation generator is old technology. The effects of higher wattage in the modern equipment may influence our results. In their study, de Baere et al. [33] reported that the cooled-tip needle by a 200-W generator induced significantly larger lesions than the expandable needle by a 50-W generator. However, there was no difference in histopathologic findings between the two. We believed that the same results could be obtained from the high-power generator.
In conclusion, in this study using a porcine lung model, NADH staining suggested that the area with a ground-glass attenuation on CT performed immediately after radiofrequency ablation overestimates the size of completely necrotic lesions. In the ablation of lung tumors, the edge of tumors should be identified in the ablated lesion (surrounded by ground-glass attenuation), and an adequate safety margin should be obtained on CT immediately after radiofrequency ablation. The lesions after radiofrequency ablation presented a layer structure that exhibited pathologic changes chronologically. The layered structural findings on CT reflected the histopathologic findings. As the follow-up examinations progressed, the difference between the diameter measured on CT images and on macroscopic examination became larger. Attention should be paid to the dissociation of ablated lesions and high-density areas in clinical interpretation of CT images. We believed the information obtained would be useful for designing tumor ablation protocols and understanding the changes in images at the time of follow-ups.
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  C. L. Brace, J. L. Hinshaw, P. F. Laeseke, L. A. Sampson, and F. T. Lee Jr Pulmonary Thermal Ablation: Comparison of Radiofrequency and Microwave Devices by Using Gross Pathologic and CT Findings in a Swine Model Radiology, June 1, 2009; 251(3): 705 - 711. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Lanuti, A. Sharma, S. R. Digumarthy, C. D. Wright, D. M. Donahue, J. C. Wain, D. J. Mathisen, and J.-A. O. Shepard Radiofrequency ablation for treatment of medically inoperable stage I non-small cell lung cancer. J. Thorac. Cardiovasc. Surg., January 1, 2009; 137(1): 160 - 166. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. A. Durick, P. F. Laeseke, L. S. Broderick, F. T. Lee Jr, L. A. Sampson, T. M. Frey, T. F. Warner, J. P. Fine, D. W. van der Weide, and C. L. Brace Microwave Ablation with Triaxial Antennas Tuned for Lung: Results in an in Vivo Porcine Model Radiology, April 1, 2008; 247(1): 80 - 87. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Hiraki, H. Gobara, T. Iishi, Y. Sano, T. Iguchi, H. Fujiwara, N. Tajiri, J. Sakurai, H. Date, H. Mimura, et al. Percutaneous radiofrequency ablation for clinical stage I non-small cell lung cancer: results in 20 nonsurgical candidates. J. Thorac. Cardiovasc. Surg., November 1, 2007; 134(5): 1306 - 1312. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Avril 18F-FDG PET After Radiofrequency Ablation: Is Timing Everything? J. Nucl. Med., August 1, 2006; 47(8): 1235 - 1237. [Full Text] [PDF]
|
|
|
|
|
|
T. Okuma, T. Matsuoka, T. Okamura, Y. Wada, A. Yamamoto, Y. Oyama, K. Koyama, K. Nakamura, Y. Watanabe, and Y. Inoue 18F-FDG Small-Animal PET for Monitoring the Therapeutic Effect of CT-Guided Radiofrequency Ablation on Implanted VX2 Lung Tumors in Rabbits J. Nucl. Med., August 1, 2006; 47(8): 1351 - 1358. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
