a pure ground - glass nodule ( ggn ) in the lung may represent an early lung malignancy , such as adenocarcinoma in situ ( ais ) or minimally invasive adenocarcinoma ( mia ) ( 1 ) .
approximately 20 - 30% of patients with adenocarcinoma and a predominantly pure ggn who undergo surgery have additional ggn lesions , either in the same or different lung lobes ( 2 ) . in such cases , multiple limited resection may be an appropriate treatment if a few pure ggn lesions are scattered in multiple lobes or peripherally in one lobe , and the patient has sufficient pulmonary functional reserve ( 3 ) .
however , alternative options should be considered if several ggn lesions are scattered in both lungs with multiple lobes involved , and there is a risk for insufficient pulmonary functional reserve after resection .
chemotherapy has been suggested as an additional therapeutic option , if surgery is not possible due to a lack of pulmonary functional reserve ( 4 ) .
another strategy is to rely on serial computed tomography ( ct ) scans until the nodule develops a definite solid portion .
if curative therapy is not performed , there remains a significant chance for progression ( 1 ) .
cryoablation has been explored as an option for treating metastatic lesions in patients with non - small cell lung cancer who can not undergo surgery or chemotherapy ( 5 ) . however , no clinical reports of cryoablation techniques applied to multiple ggns in the lung have been published . here
, we describe a patient with lung cancer and a pure ggn in the left lower lung lobe that persisted after several limited resections and was successfully treated with cryoablation .
a 59-year - old woman visited our hospital due to abnormal chest radiography findings on a health maintenance exam at another hospital .
all pre- and post - procedural ct scans were performed using a multi - detector ct scanner ( somatom definition flash , enlargen siemens , forchheim , germany ) .
the scanning parameters were : 120 kvp , 200 mas , 0.75-mm collimation , 2-mm reconstruction intervals , smooth algorithm , and pitch of 1 .
several ggns were detected by ct scan : a 12-mm - sized , partially solid nodule in the right middle lobe ( fig .
1a ) , a 7-mm - sized pure ggn in the right upper lobe , and two 5-mm - sized pure ggns in each of the lower lobes ( fig .
the patient underwent a right middle lobectomy and wedge resection of the right upper lobe using video - assisted thoracoscopic surgery .
the partially solid nodule in the right middle lobe was diagnosed as adenocarcinoma , and the pure ggn in the right upper lobe was diagnosed as a mia .
the two pure ggns in both lower lobes remained without significant change on a 10-month follow - up ct scan .
an additional wedge resection was performed for the pure ggn in the right lower lobe , and this nodule was diagnosed as ais .
after these surgeries , the patient did not have sufficient pulmonary functional reserve to tolerate any additional surgery .
thus , we decided to perform cryoablation on the pure ggn in the left lower lobe .
the patient fasted for 6 hours before the procedure , and her blood coagulation parameters were checked .
we used an argon and helium gas - based system ( seednet , galil medical , yokneam , israel ) , a 1.5-mm 17-g cryoprobe , and a thermal sensor .
the procedure was performed in a fluoroscopy room by an interventional radiologist . after placing the patient in the prone position on the table ,
a cross - shaped radio - opaque skin marker was applied to determine the needle insertion site under fluoroscopy .
subsequently , a c - arm cone - beam ct ( cbct ) scan ( dynact , enlargen siemens ) was taken ( fig .
1d - f ) to obtain 1.5-mm thick axial , coronal , and sagittal images . based on these images
, we measured the distance from the center of the skin marker to the target ggn .
the area of the skin marker was draped , and a 1% lidocaine solution was injected into the skin down to the pleural surface . after localizing the needle tip , a cbct scan was performed to confirm the probe insertion site . a 17-g cryoprobe (
seednet , galil medical ) was carefully introduced into the pure ggn under fluoroscopic guidance .
we used a fluoroscope and cbct to visualize the size of the ice ball during the procedure .
we took a ct scan to confirm that the ice ball had reached sufficient size , as indicated by a low attenuation region with an envelope of ground - glass opacity and a margin of 1 cm beyond the ggn .
a small pneumothorax was noted after removing the cryoprobe ; however , the patient was asymptomatic with stable vital signs .
we performed a follow - up ct scan 1 day after cryoablation to assess any initial changes in the ablated lesion and procedural - related side effects ( fig .
the scan showed a 3-cm sized ablated zone in the left lower lobe with no major procedure - related complications , such as hemothorax .
the size of the ablated zone had decreased markedly on a follow - up ct scan 2 months later .
the pure ggn in the left lower lobe was judged to have been successfully ablated without recurrence on a 6-month follow - up ct scan ( fig .
our results show the potential of cryoablation as a new treatment method for ggn , particularly in patients in whom surgery is contraindicated .
some controversy exists as to whether some nodules should be resected or followed by serial ct scans .
kim et al . ( 6 ) noted that several pure ggn lesions detected in patients undergoing surgery for bronchioloalveolar carcinoma did not change in size or features during follow - up .
they suggested that surgical resection should be considered in selected cases in which nodules exhibit significant changes in size or appearance during follow - up .
( 7 ) found that all ggn lesions > 10 mm were carcinomas and insisted that these lesions should be resected rather than followed .
partially solid ggn lesions should be resected regardless of size because they represent more invasive lesions than pure ggns .
thus , a non - surgical alternative is needed for patients with insufficient pulmonary functional reserve or in patients in whom surgery is technically not feasible .
minimally invasive ablation techniques , such as radiofrequency ablation ( rfa ) and cryoablation , may be useful adjunctive treatment options for lung cancer or metastatic lesions and preserve pulmonary function ( 5 , 9 , 10 ) .
minimally invasive ablation techniques for lung cancer have several advantages , including selective damage , minimal morbidity and mortality , minimal loss of lung function , repeatability , low cost , excellent monitoring during treatment , less pain , and shorter hospital stay ( 11 ) . ablating lung tumors is currently used for curative treatment of primary lung cancer and metastatic lung malignancies or cytoreduction ( 12 ) .
ablation is also an option in patients with lung metastases from colorectal and renal cell carcinoma , melanoma , hepatocellular carcinoma , or primary sarcoma ( 13 ) .
although rfa is a contemporary tumor ablation technique , it may cause serious complications , such as air embolism or uncontrolled pain ( 9 , 14 ) .
cryoablation is a thermoablational technique that consists of alternating cycles of decreasing ( freezing ) and increasing ( thawing ) temperatures , leading to direct cellular and vascular injury .
cryoablation works by forming an ice ball , which causes increased extracellular osmolarity and , as a consequence , water diffuses from the intracellular space into the extracellular space .
thus , cryoablation may be a better option for patients with extensive emphysema ( 10 ) .
however , percutaneous or surgical biopsy was difficult due to the small size and multiplicity of the ggn lesions .
nevertheless , localized ggns can include invasive disease , such as ais or mia ( 1 ) . in our case ,
two similar nodules in the right upper and right lower lobes were identified during surgery as mia and ais , respectively .
cryoablation may reduce the likelihood that a remnant ggn will progress to advanced cancer and does not require additional surgery .
thus , long - term follow - up may be necessary to determine the outcome of cryoablation for treating pure ggns . in conclusion
 treatments for pure ground - glass nodules ( ggns ) include limited resection ; however , surgery is not always possible in patients with limited pulmonary functional reserve . in such patients 
 , cryoablation may be a suitable alternative to treat a pure ggn . here , we report our initial experience with cryoablation of a pure ggn that remained after repeated surgical resection in a patient with multiple ggns . 
 a 5-mm - sized pure ggn in the left lower lobe was cryoablated successfully without recurrence at the 6-month follow - up . 