twenty - eight male new zealand white rabbits weighing 2.5 - 3 kg were anesthetized by intramuscular injection of 50 mg / kg ketamine hydrochloride ( ketamine ; yuhan , seoul , korea ) and 5 mg / kg xylazine ( rumpun ; bayer korea , ansan , korea ) prior to rfa and other procedures . booster injections of up to one - half of the initial dose were administered as needed . the upper back and lower abdominal areas
were shaved and sterilized , and each animal was placed in the prone position on the ct table . to assess the feasibility and safety of saline - enhanced rfa of normal lung parenchyma compared to conventional rfa
, rabbits were allocated to either the rfa group ( n=10 ) or the saline - enhanced rfa ( srfa ) group ( n=18 ) .
in addition , to compare the histopathologic change in lung parenchyma following srfa and the occurrence of delayed complications , the rabbits in the srfa group were allocated to either an acute ( n=10 ) or subacute subgroup ( n=8 ) , and sacrificed at different time intervals after the procedure . in the rfa group ( n=10 ) and the acute subgroup of the srfa group ( n=10 ) ,
unilateral lung rfa was performed in 20 rabbits and all were sacrificed on the day of the procedure . during the subacute phase ,
eight rabbits were sacrificed on day 7 ( n=2 ) , or day 10 ( n=2 ) , and at two ( n=2 ) or three weeks ( n=2 ) after rfa .
a somatom plus-4 ct scanner ( siemens , erlangen , germany ) was used to obtain axial scans ( 2-mm slice thickness and 1.0 - 1.5 pitch ) of the entire lung field , and the target portion and appropriate approach route for saline infusion and rfa were thus determined . in the saline infusion group , a polyteflon - coated 21-gauge chiba needle ( m.i.tech , seoul , korea ) was used for 0.9% saline infusion before and during the application of rf energy . an internally cooled , 17-gauge electrode ( radionics ; burlington , mass . , u.s.a . ) with a 1- or 2-cm active tip was placed in the target area of the lung under ct guidance , and the chiba needle was inserted using the tandem technique ( 20 ) . to maximize the effects of saline instillation ,
the tip of the needle was placed 3 mm posterior to the tip of the rf electrode . to confirm the position of the needle and the electrode in the target area , ct scanning was performed .
saline ( 0.5 ml ) was then infused at a rate of 0.1 ml / sec prior to the application of rf energy , and to avoid bronchial aspiration , 1 ml saline at a rate of 0.05 ml / sec was also infused during rfa after frequent pulsing began .
an electrode with a 1-cm active tip was used in rabbits in the rfa and srfa groups to evaluate the immediate effects of rfa , while the electrode used in the subacute subgroup to evaluate histopathologic change and delayed complications had a 2-cm active tip .
lesions were created using a 500-khz rf generator ( cc-3 ; radionics ) capable of producing 200 w of power . for analyzing the adverse effects of rf energy on lung parenchyma , ablated lesions were induced in the central portion of the lung in 14 rabbits and in its peripheral portion in the other 14 . during the procedure
, a thermocouple embedded within the electrode tip continuously measured the local tissue temperature , and tissue impedance was monitored by circuitry incorporated within the generator . a peristaltic pump ( watson - marlow ; medford , mass . , u.s.a . ) was used to infuse normal saline solution at 0 into the lumen of the electrode at a rate of 10 - 25 ml / min , and this was sufficient to maintain a tip temperature of 20 - 25. when the desired current could not be applied due to a rapid elevation of impedance suggestive of tissue boiling , the generator automatically switched to the pulsed - rf technique ( 21 ) .
power output was set at 30 w , and rf energy was applied for approximately five minutes on the basis of our earlier study findings ( 22 ) . using the same scanner and starting two hours after rfa ( day 0 ) , spiral ct scans were obtained to monitor the effects of ablation and to observe morphological change in the lesions at weeks 1 , 2 , and 3 after rfa .
axial scans ( 2-mm slice thickness and 1.0 - 1.5 pitch ) of both the lung and upper abdomen , including the kidneys , were obtained before and after the injection of contrast medium ( 6 - 9 ml , ultravist 370 ; schering , berlin , germany ) at a rate of 1 ml / sec through the ear vein .
the diameters of the ablated lesions were measured on pacs images by one radiologist using an electric caliper .
imaging analysis : two radiologists experienced in body imaging reviewed pre- and post - ablation ct images of all animals .
each rfa lesion was evaluated in terms of its location , size and shape , attenuation change , and the presence of hemorrhage or air in the pleural cavity , and then classified as either central ( inner 2/3 ) or peripheral ( outer 1/3 ) , depending on its location . to ensure that the changes noted were not present before rfa
histopathologic examination : after spiral ct examination , rabbits were sacrificed at various points in time by injection of an overdose of ketamine and xylazine , and their lungs were harvested .
the gross specimens obtained were dissected in planes similar to those of the spiral ct scans , and were examined . for macroscopic examination ,
two observers , who reached a consensus , used calipers to measure the central discolored region of coagulation necrosis in each pathologic specimen .
tissues were then fixed in 10% formalin for routine histologic examination , and final processing for light microscopic study involved paraffin sectioning and hematoxylin - eosin ( he ) staining .
tissues obtained from all treatment areas were analyzed for nonviability , their histologic appearance , and demarcation from surrounding viable tissue .
a surgical pathologist and a radiologist evaluated the gross and microscopic findings at each rfa site , and reached a consensus .
the technical aspects of rfa ( namely , total time needed for the procedure and current or impedance changes occurring ) and complications arising were compared for both techniques . for all statistical analysis , spss 9.0 computer software ( spss inc . ,
the size of the acute rf lesions in the two groups was compared using an unpaired student 's t test .
all contingency data were analyzed using the chi - square test , or fisher 's exact test for fewer than five observed events .
for all statistical analysis , a p value of less than 0.05 was considered statistically significant .
twenty - eight male new zealand white rabbits weighing 2.5 - 3 kg were anesthetized by intramuscular injection of 50 mg / kg ketamine hydrochloride ( ketamine ; yuhan , seoul , korea ) and 5 mg / kg xylazine ( rumpun ; bayer korea , ansan , korea ) prior to rfa and other procedures . booster injections of up to one - half of the initial dose were administered as needed . the upper back and lower abdominal areas
were shaved and sterilized , and each animal was placed in the prone position on the ct table . to assess the feasibility and safety of saline - enhanced rfa of normal lung parenchyma compared to conventional rfa
, rabbits were allocated to either the rfa group ( n=10 ) or the saline - enhanced rfa ( srfa ) group ( n=18 ) .
in addition , to compare the histopathologic change in lung parenchyma following srfa and the occurrence of delayed complications , the rabbits in the srfa group were allocated to either an acute ( n=10 ) or subacute subgroup ( n=8 ) , and sacrificed at different time intervals after the procedure . in the rfa group ( n=10 ) and the acute subgroup of the srfa group ( n=10 ) ,
unilateral lung rfa was performed in 20 rabbits and all were sacrificed on the day of the procedure . during the subacute phase ,
eight rabbits were sacrificed on day 7 ( n=2 ) , or day 10 ( n=2 ) , and at two ( n=2 ) or three weeks ( n=2 ) after rfa .
a somatom plus-4 ct scanner ( siemens , erlangen , germany ) was used to obtain axial scans ( 2-mm slice thickness and 1.0 - 1.5 pitch ) of the entire lung field , and the target portion and appropriate approach route for saline infusion and rfa were thus determined . in the saline infusion group , a polyteflon - coated 21-gauge chiba needle ( m.i.tech , seoul , korea ) was used for 0.9% saline infusion before and during the application of rf energy . an internally cooled , 17-gauge electrode ( radionics ; burlington , mass . , u.s.a . ) with a 1- or 2-cm active tip was placed in the target area of the lung under ct guidance , and the chiba needle was inserted using the tandem technique ( 20 ) . to maximize the effects of saline instillation ,
the tip of the needle was placed 3 mm posterior to the tip of the rf electrode . to confirm the position of the needle and the electrode in the target area , ct scanning was performed .
saline ( 0.5 ml ) was then infused at a rate of 0.1 ml / sec prior to the application of rf energy , and to avoid bronchial aspiration , 1 ml saline at a rate of 0.05 ml / sec was also infused during rfa after frequent pulsing began .
an electrode with a 1-cm active tip was used in rabbits in the rfa and srfa groups to evaluate the immediate effects of rfa , while the electrode used in the subacute subgroup to evaluate histopathologic change and delayed complications had a 2-cm active tip .
lesions were created using a 500-khz rf generator ( cc-3 ; radionics ) capable of producing 200 w of power . for analyzing the adverse effects of rf energy on lung parenchyma , ablated lesions were induced in the central portion of the lung in 14 rabbits and in its peripheral portion in the other 14 . during the procedure
, a thermocouple embedded within the electrode tip continuously measured the local tissue temperature , and tissue impedance was monitored by circuitry incorporated within the generator . a peristaltic pump ( watson - marlow ; medford , mass . , u.s.a . ) was used to infuse normal saline solution at 0 into the lumen of the electrode at a rate of 10 - 25 ml / min , and this was sufficient to maintain a tip temperature of 20 - 25. when the desired current could not be applied due to a rapid elevation of impedance suggestive of tissue boiling , the generator automatically switched to the pulsed - rf technique ( 21 ) .
power output was set at 30 w , and rf energy was applied for approximately five minutes on the basis of our earlier study findings ( 22 ) .
using the same scanner and starting two hours after rfa ( day 0 ) , spiral ct scans were obtained to monitor the effects of ablation and to observe morphological change in the lesions at weeks 1 , 2 , and 3 after rfa .
axial scans ( 2-mm slice thickness and 1.0 - 1.5 pitch ) of both the lung and upper abdomen , including the kidneys , were obtained before and after the injection of contrast medium ( 6 - 9 ml , ultravist 370 ; schering , berlin , germany ) at a rate of 1 ml / sec through the ear vein .
the diameters of the ablated lesions were measured on pacs images by one radiologist using an electric caliper .
imaging analysis : two radiologists experienced in body imaging reviewed pre- and post - ablation ct images of all animals .
each rfa lesion was evaluated in terms of its location , size and shape , attenuation change , and the presence of hemorrhage or air in the pleural cavity , and then classified as either central ( inner 2/3 ) or peripheral ( outer 1/3 ) , depending on its location . to ensure that
the changes noted were not present before rfa , the post- and preprocedural ct findings were compared .
histopathologic examination : after spiral ct examination , rabbits were sacrificed at various points in time by injection of an overdose of ketamine and xylazine , and their lungs were harvested .
the gross specimens obtained were dissected in planes similar to those of the spiral ct scans , and were examined . for macroscopic examination , two observers , who reached a consensus , used calipers to measure the central discolored region of coagulation necrosis in each pathologic specimen .
tissues were then fixed in 10% formalin for routine histologic examination , and final processing for light microscopic study involved paraffin sectioning and hematoxylin - eosin ( he ) staining .
tissues obtained from all treatment areas were analyzed for nonviability , their histologic appearance , and demarcation from surrounding viable tissue . a surgical pathologist and
a radiologist evaluated the gross and microscopic findings at each rfa site , and reached a consensus .
the technical aspects of rfa ( namely , total time needed for the procedure and current or impedance changes occurring ) and complications arising were compared for both techniques . for all statistical analysis ,
the size of the acute rf lesions in the two groups was compared using an unpaired student 's t test .
all contingency data were analyzed using the chi - square test , or fisher 's exact test for fewer than five observed events .
for all statistical analysis , a p value of less than 0.05 was considered statistically significant .
rfa was technically successful in all instances , and 28 lesions were created with or without saline infusion .
since the tip of the rf electrode or chiba needle was easily localized at ct , its positioning was not difficult .
the time required for correct needle placement ranged from 1.5 to 3.5 ( mean , 2.3  0.6 ) minutes for rfa and from 2.7 to 4.5 ( mean , 3.4  1.5 ) minutes for srfa ( p = .04 ) . in the rfa group , mean initial tissue impedance was 187  24,and in the srfa group , after instillation of 0.5 ml of normal saline , the reading decreased to 134  24 ( p < .05 ) .
in the rfa group , tissue impedance changed markedly ( from 200 to 1000 ) during the procedure and frequently induced activation of the pulsing technique , whereas in the srfa group , impedance showed no notable change ( range , 100 - 500 ) . without saline infusion , as in the rfa group , impedance rose abruptly within a mean period of 20  4.5 seconds .
this automatically initiated rf pulsing , which was followed by alternating 5 - 10-second periods of high - energy deposition and approximately 15-second periods of low energy deposition . with saline infusion
prior to and during rfa ( srfa group ) , impedance remained constantly low ( at approximately 100 ) during the first 1 - 2 minutes of rf energy instillation , but an abrupt rise which induced rf pulsing occurred during the second half of the procedure ( at mean 107  54 seconds ) .
additional infusion of saline after the initiation of rf pulsing led to a lower rise in impedance and extended the time of continuous rf energy application .
differences between the two groups in the duration of rf energy instillation before pulsing were statistically significant : 20  4.5 vs. 107  54 seconds ( p < .05 ) . in the srfa and rfa groups ,
the mean maximum diameters of acute lesions induced by a 1-cm active tip , as measured in gross specimens , were 12.5  1.6 and 8.5  1.4 mm , respectively ; this difference between the two groups was statistically significant ( p < .05 ) ( table 1 ) . in the srfa group ,
the mean maximum diameter of subacute lesions induced by a 2-cm active tip was 21.3  5.8 cm ( p < .05 ) . the complications occurring after rfa are summarized in table 2 , and were as follows : pneumothorax ( n=8 ) ; thermal injury to the chest wall ( n=2 ) ; hemothorax ( n=1 ) ; and lung abscess ( n=1 ) .
three pneumothoraces were large ( with lung volume decrease due to pleural air collection and clinically visible respiratory distress ) and five were small ( perilesional small air collection , with no evidence of respiratory distress ) .
complications tended to occur more frequently in the srfa group ( 55.6% , 10/18 ) than in the rfa group ( 20% , 2/10 ) , though the difference was not statistically significant ( p = .11 ) .
however , complication rates varied between the two groups , depending on the location of the lesions . among central lesions ,
large pneumothorax occurred in two rabbits in the rfa group ( 20% , 2/10 ) and in one in the srfa group ( 5.6% , 1/18 ) ( p = .28 ) . among peripheral lesions , on the other hand ,
the complication rate was much higher in the srfa group ( 77.8% ) than in the rfa group ( p = .02 ) .
the complications involved included thermal injury to the chest wall , and one lung abscess .
the incidence rates of complications , namely 35.7% ( 5/14 ) for centrally located lesions and 50% ( 7/14 ) for peripherally located lesions , did not differ significantly ( p = .72 ) , though the type of complication involved depended on the location of the ablated lesion .
although the incidence rate of pneumothorax ( 28.6% , 4/14 ) was not different between centrally and peripherally located lesions , large pneumothoraces ( n=3 ) or hemothorax ( n=1 ) occurred only in four central lesions ( 28.6% ) adjacent to hilar vessels or bronchi .
major hemorrhage due to electrode penetration of vessels did not occur even where the lesion was located directly on a vessel .
after rfa , unenhanced ct scanning revealed circumscribed hyperattenuated regions extending 5 - 8 mm from the portion of the inserted electrode ( fig .
1 ) , while contrast - enhanced ct showed no enhancement in the region of altered pulmonary attenuation .
greater conspicuity of coagulated tissues was observed at wide window settings ( level=500 hu , width = 2000 hu ) . at ct imaging ,
thermal lesions appeared as hazy opacity in the soft tissue window ( level=50 hu , width=350 hu ) and ranged in diameter from 8 to 19 ( mean , 12.6  4.3 ) mm ( figs . 1 , 2 ) . at ct imaging at a soft - tissue window setting , acute lesions were round or oval - shaped except in regions abutting pulmonary vessels , and there was no significant difference in the shape of acute lesions between the rfa and the srfa group .
however , because of the opacity related to saline infusion in rabbits in the srfa group , the appearance of lesions in the lung window was not well matched with that of gross specimens .
gross examination showed that the diameter of an acute lesion , measured as a central discolored region , was 7 - 14 ( mean , 10.9  1.8)mm , and the thickness of the peripheral rim was 1 - 2 mm .
the mean difference in lesion size , as determined by ct scanning and pathologic examination , was 3 mm , which was not statistically significant ( p > .05 ) .
histological examination of an acute lesion revealed a central charred zone with complete destruction of the parenchyma , including a small central cavity where tissue had been lost .
surrounding this were two zones of eosinophilic coagulative necrosis and a peripheral hemorrhagic rim ( figs . 1 , 2 )
one to two weeks following rfa , surrounding tissue was becoming organized into granulation tissue , with an increase of fibroblasts and macrophages and dilatation of blood vessels at the perimeter of the lesion ( fig .
3 ) . in a lesion 's central zone , typical findings of coagulation necrosis were observed . in centrally located lesions ,
, granulation tissue had achieved progressive ingrowth into the original area of necrosis , and was replacing it , and there was sharp cut - off between the lesion and normal tissue .
the final appearance was of a nodule comprised of central coagulation necrosis surrounded by a fibrous capsule .
since the tip of the rf electrode or chiba needle was easily localized at ct , its positioning was not difficult .
the time required for correct needle placement ranged from 1.5 to 3.5 ( mean , 2.3  0.6 ) minutes for rfa and from 2.7 to 4.5 ( mean , 3.4  1.5 ) minutes for srfa ( p = .04 ) . in the rfa group , mean initial tissue impedance was 187  24,and in the srfa group , after instillation of 0.5 ml of normal saline , the reading decreased to 134  24 ( p < .05 ) .
in the rfa group , tissue impedance changed markedly ( from 200 to 1000 ) during the procedure and frequently induced activation of the pulsing technique , whereas in the srfa group , impedance showed no notable change ( range , 100 - 500 ) . without saline infusion , as in the rfa group , impedance rose abruptly within a mean period of 20  4.5 seconds .
this automatically initiated rf pulsing , which was followed by alternating 5 - 10-second periods of high - energy deposition and approximately 15-second periods of low energy deposition . with saline infusion
prior to and during rfa ( srfa group ) , impedance remained constantly low ( at approximately 100 ) during the first 1 - 2 minutes of rf energy instillation , but an abrupt rise which induced rf pulsing occurred during the second half of the procedure ( at mean 107  54 seconds ) .
additional infusion of saline after the initiation of rf pulsing led to a lower rise in impedance and extended the time of continuous rf energy application .
differences between the two groups in the duration of rf energy instillation before pulsing were statistically significant : 20  4.5 vs. 107  54 seconds ( p < .05 ) .
in the srfa and rfa groups , the mean maximum diameters of acute lesions induced by a 1-cm active tip , as measured in gross specimens , were 12.5  1.6 and 8.5  1.4 mm , respectively ; this difference between the two groups was statistically significant ( p < .05 ) ( table 1 ) . in the srfa group ,
the mean maximum diameter of subacute lesions induced by a 2-cm active tip was 21.3  5.8 cm ( p < .05 ) . the complications occurring after rfa are summarized in table 2 , and were as follows : pneumothorax ( n=8 ) ; thermal injury to the chest wall ( n=2 ) ; hemothorax ( n=1 ) ; and lung abscess ( n=1 ) .
three pneumothoraces were large ( with lung volume decrease due to pleural air collection and clinically visible respiratory distress ) and five were small ( perilesional small air collection , with no evidence of respiratory distress ) .
complications tended to occur more frequently in the srfa group ( 55.6% , 10/18 ) than in the rfa group ( 20% , 2/10 ) , though the difference was not statistically significant ( p = .11 ) . however , complication rates varied between the two groups , depending on the location of the lesions . among central lesions ,
large pneumothorax occurred in two rabbits in the rfa group ( 20% , 2/10 ) and in one in the srfa group ( 5.6% , 1/18 ) ( p = .28 ) . among peripheral lesions , on the other hand , the complication rate was much higher in the srfa group ( 77.8% ) than in the rfa group ( p = .02 ) .
the complications involved included thermal injury to the chest wall , and one lung abscess .
the incidence rates of complications , namely 35.7% ( 5/14 ) for centrally located lesions and 50% ( 7/14 ) for peripherally located lesions , did not differ significantly ( p = .72 ) , though the type of complication involved depended on the location of the ablated lesion .
although the incidence rate of pneumothorax ( 28.6% , 4/14 ) was not different between centrally and peripherally located lesions , large pneumothoraces ( n=3 ) or hemothorax ( n=1 ) occurred only in four central lesions ( 28.6% ) adjacent to hilar vessels or bronchi .
major hemorrhage due to electrode penetration of vessels did not occur even where the lesion was located directly on a vessel .
after rfa , unenhanced ct scanning revealed circumscribed hyperattenuated regions extending 5 - 8 mm from the portion of the inserted electrode ( fig .
1 ) , while contrast - enhanced ct showed no enhancement in the region of altered pulmonary attenuation .
greater conspicuity of coagulated tissues was observed at wide window settings ( level=500 hu , width = 2000 hu ) . at ct imaging
, thermal lesions appeared as hazy opacity in the soft tissue window ( level=50 hu , width=350 hu ) and ranged in diameter from 8 to 19 ( mean , 12.6  4.3 ) mm ( figs . 1 , 2 ) . at ct imaging at a soft - tissue window setting , acute lesions were round or oval - shaped except in regions abutting pulmonary vessels , and there was no significant difference in the shape of acute lesions between the rfa and the srfa group .
however , because of the opacity related to saline infusion in rabbits in the srfa group , the appearance of lesions in the lung window was not well matched with that of gross specimens .
gross examination showed that the diameter of an acute lesion , measured as a central discolored region , was 7 - 14 ( mean , 10.9  1.8)mm , and the thickness of the peripheral rim was 1 - 2 mm .
the mean difference in lesion size , as determined by ct scanning and pathologic examination , was 3 mm , which was not statistically significant ( p > .05 ) .
histological examination of an acute lesion revealed a central charred zone with complete destruction of the parenchyma , including a small central cavity where tissue had been lost .
surrounding this were two zones of eosinophilic coagulative necrosis and a peripheral hemorrhagic rim ( figs . 1 , 2 ) .
there was sharp cut - off between ablated lesions and normal lung . outside this area ,
one to two weeks following rfa , surrounding tissue was becoming organized into granulation tissue , with an increase of fibroblasts and macrophages and dilatation of blood vessels at the perimeter of the lesion ( fig .
3 ) . in a lesion 's central zone , typical findings of coagulation necrosis were observed . in centrally located lesions ,
, granulation tissue had achieved progressive ingrowth into the original area of necrosis , and was replacing it , and there was sharp cut - off between the lesion and normal tissue .
the final appearance was of a nodule comprised of central coagulation necrosis surrounded by a fibrous capsule .
lung cancer is among the most commonly occurring malignancies in the world and is one of the few that continues to show an increasing incidence ( 23 , 24 ) . although surgical resection is acknowledged to be the treatment of choice and the only therapy with any prospect of cure or long - term survival , in practice a considerable percentage of patients with lung cancer are not eligible for surgical intervention due to the advanced stage of the disease , their limited pulmonary functional reserve , co - morbidities or advanced age ( 25 ) . those who are not candidates for surgery can undergo radiation treatment and/or chemotherapy , but survival prospects increase only modestly and gains are often accompanied by substantial toxicity , especially in patients suffering from other co - morbidities ( 26 ) .
nevertheless , the development of nonsurgical and minimally invasive percutaneous techniques for the treatment of lung cancer would be advantageous .
effective options might prove useful for patients with multiple medical problems , co - morbid disease , or concomitant tumor , or for whom surgery carries high risks .
after encouraging results of rfa in the liver , some researchers have suggested that the procedure could be used for the treatment of lung malignancies ( 13 - 17 ) .
the main advantage of rfa is that it is simple , easy to perform and offers the option of an indefinite number of repeated applications .
a drawback , however , is that it is often necessary to overlap ablations by multiple repositioning of the electrode in order to decrease marginal recurrence after rfa ( 6 ) .
furthermore , if lung tumors are to be treated by rfa , the naturally high impedance of air - containing lung tissue and the risk of pneumothorax related to multiple passes through the pleura during rfa might be an obstacle to induction of complete tumor necrosis .
if these inherent problems of rfa of lung tumors are to be solved , ablation must produce a larger coagulation area that could include focal lung malignancies and some safety margin .
several investigators have demonstrated the possibility of increasing rf tissue heating and coagulation during rf ablation by altering electrical and/or thermal conduction through the injection of saline into the tissues during rf application ( 18 , 19 ) .
the present study was conducted to assess the actual effect of simultaneous infusion of saline during rfa , and possible resultant complications . in our study , the mean diameter of rfa lesions in the saline infusion group was significantly greater than in the control group : 12.5 mm vs. 8.5 mm ( p < .05 ) .
in addition , initial impedance in the srfa group was significantly lower than in the rfa group ( p < .05 ) , and tissue impedance did not change markedly . thus , in the srfa group , high - rf energy instillation over a long period was possible , but in the rfa group , impedance changed rapidly during the procedure , frequently inducing activation of the pulsing technique .
furthermore , impedance was decreased by additional infusion of saline during the application of rf energy .
this increases tissue ionicity and decreases tissue impedance , thereby permitting greater current flow , and the heated liquid spreads thermal energy further and faster through the tissue than does heat conduction ( 28 , 29 ) . in this study ,
an internally cooled electrode was used for rfa , together with the pulsing technique , and the resultant lesion was larges than that made by the conventional electrode used in previous studies ( 21 , 27 , 30 ) .
nonetheless , even with an internal cooling mechanism and pulsing technique , impedance rose rapidly and uncontrollably during rf energy instillation , inducing frequent pulsing and leading to restrictions in the size of lesions .
after saline infusion , however , the period of rf energy instillation increased , and with it , lesion size .
our results agreed with those of previous studies of saline - enhanced rfa of the liver and retroperitoneum ( 31 - 33 ) .
as demonstrated in this investigation , an extended volume of coagulation necrosis due to saline infusion may increase the clinical utility of rfa therapy by permitting successful treatment of larger lung tumors or reducing the number of sessions needed for the treatment of a given tumor .
this finding is of particular importance in the application of rfa to the treatment of lung cancer , since in order to decrease the occurrence of pneumothoraces , electrodes should pass through the pleura as infrequently as possible .
if the incidence of pneumothorax can be reduced , more patients may benefit from this potentially curative therapy , with its reduced medical and social costs .
procedure - related complications arose in 12 cases , comprising eight pneumothoraces , two thermal injuries to the chest wall , one hemothorax , and one lung abscess ( table 2 ) .
their incidence tended to be higher in the srfa group ( 55.6% ) than the rfa group ( 20% ) , though the difference was not statistically significant ( p = .11 ) . for the peripheral lesions , however , the complication rates among rabbits in the srfa group ( 77.8% , 7/9 ) was higher than among those in the rfa group ( 0% ) ( p < .05 ) .
the relatively high incidence rates ( 28.6% , 8/28 ) of pneumothorax in this study were related to the small size of rabbit lung , the relatively large size of the electrodes , and the additional use of a chiba needle with an electrode in the srfa group .
we believe that if the electrode used during rfa is adequate , permitting simultaneous instillation of saline during rfa in large animals or in clinical trials , the incidence rates of pneumothorax could decrease markedly .
according to earlier reports of saline - enhanced rfa ( 18 , 19 , 31 , 32 ) , direct and uncontrollable thermal damage to both adjacent and remote structures was observed more frequently in the saline infusion group than in the conventional rfa group . to decrease this damage
, we used a very small amount of saline ( 1.5 ml ) at a slow infusion rate ( approximately 0.05 ml / sec ) , and it is possible that the two cases of unexpected thermal injury to the chest wall and diaphragm resulted from drainage of steam or saline through low - resistance tissue .
a further possible drawback of saline - enhanced rfa , also involving this steam or saline drainage , is that the lesions produced may be somewhat irregular in shape , rather than spherical .
however , most ablated lesions in the present study were spherical , and we believe that instillation of a larger amount of saline than we used could be related to the formation of irregularly shaped lesions
. the clinical role of rfa in the treatment of lung tumors is still not clear but will undoubtedly evolve .
for example , in patients with hemoptysis or cough in whom radiotherapy has not controlled the symptoms or can not be undertaken due to poor lung function or co - morbidity , this technique might play a primarily palliative role .
we believe that in lung cancer patients , rf ablation possesses several potential benefits compared with systemic chemotherapy or radiotherapy .
first , because the therapy is local in nature , it is likely to minimize damage to lung parenchyma and reduce adverse systemic affects on a patient 's general health , and for this same reason , rf ablation therapy can be utilized in patients with limited pulmonary reserve .
it is less likely to have a curative role for stage - i tumors because many patients with peripheral tumors who have poor lung function can be offered limited resection , such as wedge resection or segmentectomy by video - assisted thoracoscopic surgery ( 34 - 36 ) .
however , a randomized trial of lobectomy versus limited resection for stage - i lung cancer showed that the latter did not confer improved perioperative morbidity or mortality .
furthermore , even if less invasive than open surgery , limited resection also requires general anesthesia ( 35 ) .
there could , therefore , be a role for rfa as a less invasive alternative to metastasectomy , but for the present , the greatest clinical utility of rfa may be in patients with small peripheral lung cancers who are poor candidates for surgery .
first , the results obtained in healthy rabbit lung may differ from those obtained with non - small - cell human lung carcinoma .
however , aspects of the process of cell degeneration caused by the effect of heat on tissue lead us to believe that the results might well be the same with either normal lung tissue in rabbits or human lung cancer cells .
second , rabbit lungs are smaller than the size of the rf ablation zone that can be produced with the currently available rf electrode system , and the effectiveness of saline infusion during rfa may thus not be entirely comparable between the two groups .
in addition , since the 17-gauge electrode used in this study is too large for rabbits , with their relatively smaller lungs , the complication rates of rfa might be overestimated . in conclusion , ct - guided percutaneous transthoracic rfa with simultaneous hypertonic saline infusion is feasible , and more effectively produces coagulation necrosis than rfa without saline infusion .
saline - enhanced rfa might be a promising technique for the management of inoperable lung malignancies and has the potential for use as a minimally invasive approach . to determine whether the technique can be feasibly and safely used to produce a sufficiently large volume of necrosis to be of value in the treatment of small peripheral lung tumors in patients for whom surgery or palliative radiotherapy is unsuitable , further study using a larger animal model is warranted
 objectiveto assess the feasibility and safety of ct - guided percutaneous transthoracic radiofrequency ablation ( rfa ) with saline infusion of pulmonary tissue in rabbits.materials and methodstwenty - eight new zealand white rabbits were divided into two groups : an rfa group ( n=10 ) and a saline - enhanced rfa ( srfa ) group ( n=18 ) . in the rfa group , 
 percutaneous rfa of the lung was performed under ct guidance and using a 17-gauge internally cooled electrode . in the srfa group , 1.5 ml of 0.9% saline 
 was infused slowly through a 21-gauge , polyteflon - coated chiba needle prior to and during rfa . 
 lesion size and the healing process were studied in rabbits sacrificed at times from the day following treatment to three weeks after , and any complications were noted.resultsin the srfa group , the mean diameter ( 12.5  1.6 mm ) of acute rf lesions was greater than that of rfa lesions ( 8.5  1.4 mm ) ( p < .05 ) . the complications arising in 12 cases were pneumothorax ( n=8 ) , thermal injury to the chest wall ( n=2 ) , hemothorax ( n=1 ) , and lung abscess ( n=1 ) . 
 although procedure - related complications tended to occur more frequently in the srfa group ( 55.6% ) than in the rfa group ( 20% ) , the difference was not statistically significant ( p = .11).conclusionsaline - enhanced rfa of pulmonary tissue in rabbits produces more extensive coagulation necrosis than conventional rfa procedures , without adding substantial risk of serious complications . 