- Email: [email protected]
Percutaneous Cryoablation for Pulmonary Nodules in the Residual Lung After Pneumonectomy
CHEST
Selected Report
Percutaneous Cryoablation for Pulmonary Nodules in the Residual Lung After Pneumonectomy
nectomies. Application of percutaneous cryoablation may represent a new treatment option for lung tumors in patients who have previously undergone pneumonectomies. CHEST 2011; 140(6):1633–1637
Report of Two Cases
S
Yoshikane Yamauchi, MD; Yotaro Izumi, MD; Hideki Yashiro, MD; Masanori Inoue, MD; Seishi Nakatsuka, MD; Masafumi Kawamura, MD; and Hiroaki Nomori, MD
Lung cancers in the residual lungs of patients who have undergone pneumonectomies are often unresectable, primarily because of the risks of overt pulmonary function losses. Percutaneous cryoablation of lung tumors is a potentially minimally invasive technique that has recently been used in the treatment of lung cancers and metastatic lung tumors. Here, we present two patients who had previously undergone pneumonectomies, in whom lung cancers in the residual lungs were treated by cryoablation. In both patients, the procedures were performed safely without any complications, such as airway bleeding, hemothoraces, or pneumothoraces. The changes in pulmonary functions after the procedures were minimal: % vital capacity (21% and 24%), and %FEV1 (21% and 110%) in the first and second patients, respectively. The performance statuses were maintained at zero in both patients after cryoablation. In the first patient, local control has been maintained for 4 years. In the second patient, local control was maintained for 2 years until the patient died of distant metastases. This is, to our knowledge, the first reported case of lung cryoablation in residual lungs of patients who have previously undergone pneumoManuscript received February 22, 2011; revision accepted April 1, 2011. Affiliations: From the Department of Surgery (Drs Yamauchi, Izumi, and Nomori), and the Department of Diagnostic Radiology (Drs Inoue and Nakatsuka), School of Medicine, Keio University, Tokyo; the Department of Radiology (Dr Yashiro), Hiratsuka City Hospital, Kanagawa; and the Department of Surgery (Dr Kawamura), Teikyo University School of Medicine, Tokyo, Japan. Correspondence to: Yotaro Izumi, MD, Department of Surgery, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan; e-mail: [email protected] © 2011 American College of Chest Physicians. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/ site/misc/reprints.xhtml). DOI: 10.1378/chest.11-0459 www.chestpubs.org
Abbreviations: SRT 5 stereotactic radiotherapy; VC 5 vital capacity
urgical resections of recurrent or primary lung cancers in the residual lungs after pneumonectomies are not always feasible and are reported to have high rates of postoperative morbidities (21%-44%) and/or mortalities (0%-8.3%).1-3 Percutaneous cryoablation is currently evolving as a minimally invasive, and potentially effective, local treatment of lung tumors.4-6 Following a report of percutaneous radiofrequency ablation for a lung nodule in a patient after pneumonectomy,7 percutaneous cryoablation was attempted in two patients with pulmonary nodules in the residual lungs after pneumonectomies. To our knowledge, this study describes the first reported cases of lung cryoablation in residual lungs postpneumonectomy. The cryoablation protocol was approved by the institutional review board in October 2002. Written consent was obtained from both patients.
Case 1 In September 2004, a 55-year-old woman underwent a left pneumonectomy for lung adenocarcinoma at another institution. Pathologic stage was pT3 (separate nodule in primary lobe) N0M0, stage IIB. Four cycles of cisplatin/gemcitabine were administered as adjuvant chemotherapy. Eighteen months after surgery, CT scan of the chest showed two solitary pulmonary nodules, one in the right upper lobe (Fig 1A) and the other in the right lower lobe (Fig 1B). Systemic examinations, such as whole-body contrastenhanced CT scan, PET scan, bronchoscopy, and serum examinations of tumor markers, did not reveal any other evidence of disease. Histologic diagnoses of the two lesions could not be obtained by transbronchial biopsy. At 30 months after surgery, both of these lesions had increased in size from 8 mm and 10 mm to 13 mm and 16 mm in diameter, respectively. Although histologic diagnoses were not obtained for the nodules, CT scan-guided needle biopsies were not performed because of the potential risks of airway bleeding, pneumothoraces, and/or hemothoraces. Since the lesions existed in different lobes of the right lung after left pneumonectomy, from the criteria of Martini and Melamed8 the nodules were both assumed to be second primary lung cancers, although the possibility of pulmonary metastases could not be ruled out. The mixed groundglass opacity appearances of the nodules on CT scan also supported this assumption. CHEST / 140 / 6 / DECEMBER, 2011
Downloaded from chestjournal.chestpubs.org by Kimberly Henricks on December 7, 2011 © 2011 American College of Chest Physicians
1633
Figure 1. A, CT scan of case 1 showing a nodule in the right upper lobe. B, CT scan of case 1 showing a nodule in the right lower lobe.
The patient could have been considered as a candidate for partial lung resections, but it was thought that partial resections of both nodules could still result in substantial loss of lung function. Therefore, the patient was referred to us for percutaneous cryoablation. Percutaneous cryoablations were performed sequentially for the two nodules for safety. The lower lobe nodule, which was slightly larger, was done in February 2007, and the upper lobe nodule was done in April 2007. The procedure of percutaneous cryoablation was performed as previously described.4 Under a multidetector-row CT scanner with multislice CT scan fluoroscopy functions (Aquilion 64; Toshiba Medical Co Ltd; Tokyo, Japan), using an outer insertion sheath, a 1.7-mm-diameter cryoprobe (CRYOcare Cryosurgical Unit; Endocare; Irvine, California) was inserted into the targeted nodule under fluoroscopic CT scan guidance. Two cryoprobes were inserted for the treatment of the nodule in the lower lobe (Figs 2A, 2B), since the ablation margin was considered to be insufficient with just one probe. One cryoprobe was inserted for the treatment of the nodule in the upper lobe (Fig 2C). The cryoprobe uses high-pressure argon and helium gases for freezing and thawing, respectively, based on the JouleThompson principle. For both nodules, cryoablation consisted of two cycles of freezing, 5 min each. The tip of the
cryoprobe reaches approximately 2130°C during freezing. This was followed by thawing until the temperature of the cryoprobe reached 20°C, and then a third cycle of freezing (10 min) followed by thawing. Fibrin glue was infused into the outer sheath at the time of cryoprobe removal to reduce the risks of hemothoraces and pneumothoraces. Whole-lung CT scans were taken at the end of each of the procedures. Chest radiographs were also checked 2 h after, the next day, and the day after each of the procedures. The CT scan and chest radiographs showed no evidence of complications such as hemothoraces or pneumothoraces after any of the procedures. The patient was discharged on the second postoperative day on both treatment occasions. Performance status was maintained at zero after cryoablation. Changes in respiratory functions were minimal at 3 months after the second cryoablation; vital capacity (VC) was 1.82 L (68% VC) vs 1.81 L (67% VC), and FEV1 was 1.31 L (72% FEV1) vs 1.26 L (71% FEV1), before and after cryoablations, respectively. Follow-up CT scan was taken every 6 months after cryoablation. Infiltrative shadows persisted in the vicinity of the ablated sites, but they were considered to be scar formations since they never increased in size during follow-up. Local control was considered to be maintained in both lesions for 4 years after cryoablations (Figs 3A, 3B).
Figure 2. A and B, CT scans of case 1 showing placement of two cryoprobes into the nodule in right lower lobe. C, Two months later, placement of one cryoprobe into the nodule in the right upper lobe. 1634
Selected Report
Downloaded from chestjournal.chestpubs.org by Kimberly Henricks on December 7, 2011 © 2011 American College of Chest Physicians
Figure 3. A, CT scan of the right lower lobe 4 years after treatment of case 1. B, CT scan of the right upper lobe 4 years after treatment of case 1. The ablated nodules are both locally controlled, with only treatment-related scar formation (arrows).
Case 2 In June 2004, a 60-year-old man underwent a right pneumonectomy at another institution for four multiple synchronous lung cancers. Pathologic study indicated that the nodules were three lung adenocarcinomas and one lung squamous cell carcinoma. The lesions were considered to be all primary lung cancers. One adenocarcinoma lesion in the right middle lobe had metastasis to the bronchial lymph node and was considered to be pT1bN1M0, stage IIA. The other three lesions were considered as pT2aN0M0, stage IB. No adjuvant treatment was given. At follow-up 2 years later, chest CT scan showed the appearance of two pulmonary nodules; one nodule was 12 mm in diameter, in the upper lobe of the residual left lung (Fig 4A), and the other nodule, 15 mm in diameter, was in the left lower lobe (Fig 4B). Whole-body contrast-enhanced CT scan did not reveal any other evidence of disease. PET scan was not performed. Histologic diagnosis of the two lesions could not be obtained by transbronchial biopsy. Surgical wedge resection of left lower lobe lesion was performed in January 2007, and the pathologic findings suggested that the nodule was considered to be more likely metastasis of lung cancer rather than metachronous primary lung cancer, because the pathologic finding of this nodule was quite similar to that of the lung cancer in the right middle lobe resected 2 years previously. From the clinical course and the radiologic appearance, the upper lobe nodule was also speculated to be pulmonary metastasis rather than metachronous primary lung cancer. It was considered that surgical removal of the nodule might involve removal of too much lung parenchyma because the nodule was not located peripherally. Therefore, the patient was referred to us for percutaneous cryoablation. The procedure was performed for the nodule in March 2007, as described in case 1, using one cryoprobe (Fig 5A). No complications occurred after the procedure and the patient was discharged on the second postoperative day. Performance status was maintained at zero after cryoablation. Changes in respiratory functions were minimal at 3 months after cryoablation; VC was 2.28 L (68% VC) vs 2.15 L (64% VC), and FEV1 was 1.47 L (68% FEV1) vs 1.64 L (78% FEV1) before and after cryoablation, respectively. www.chestpubs.org
Follow-up CT was taken every 6 months after cryoablation. A nodular shadow persisted in the vicinity of the ablated site but it was considered to be scar formation since it never increased in size during follow-up. Local control was maintained for 2 years after cryoablation, until the patient died of progressive lung metastases and pleural disseminations (Fig 5B).
Discussion Cryoablation is a relatively new procedure that potentially permits local treatment of lung tumors with minimal loss of lung parenchyma. This procedure, used when surgical resection is contraindicated, is currently under evaluation as a potential complementary therapy for patients with primary lung cancers as well as metastatic lung tumors. In our institution, we have been performing percutaneous cryoablation of lung tumors as a clinical study since 2002.4 We have, to date, treated . 300 lung tumors in . 200 patients. As for the perioperative complications, pneumothoraces occurred in 50% of cases, which were mostly categorized as grade 1 according to the Common Terminology Criteria for Adverse Events, version 4.0. The insertion of a chest tube was required in only 4.5% of the pneumothoraces cases. A small amount of pleural effusion and transient hemoptysis also occurred in about 30% of cases, but these cases were also categorized as grade 1 according to the Common Terminology Criteria for Adverse Events, version 4.0, and all resolved spontaneously. There were neither treatment-related deaths nor conversions to surgical interventions. As for local disease control, radiologically determined response rate of 54% was achieved with lesions , 3 cm in diameter.4 Although further data collections are necessary, particularly in terms of local disease control rates, the data so far suggest that cryoablation could be a feasible option in patients who are deemed unable to tolerate surgical resection, with the aim of local control of lung tumors. In view of these feasibility and efficacy results, we attempted cryoablation in the reported two patients who have previously undergone pneumonectomies. In these two patients, we experienced no apparent complications, CHEST / 140 / 6 / DECEMBER, 2011
Downloaded from chestjournal.chestpubs.org by Kimberly Henricks on December 7, 2011 © 2011 American College of Chest Physicians
1635
Figure 4. A, CT scan of case 2 showing the nodule in the left upper lobe, which was cryoablated. B, CT scan of case 2 showing the nodule in the left lower lobe, which was resected.
the decrease in respiratory function was minimal, and the local control was also considered to be satisfactory. Recently, results of radiofrequency ablation in single-lung patients after pneumonectomies have been reported with good feasibility.9 Although the radiofrequency procedures were done under general anesthesia, as opposed to local anesthesia for cryoablation, the data support the concept that needle ablation procedures, including cryoablation, may be safely applicable in single-lung patients. In terms of safety, there is a statement from the US Food and Drug Administration that discourages the use of radiofrequency ablation in lung tumors because of reports of serious complications, but it is difficult to find definitive support for this statement in the published literature. In fact, the majority of reports indicate that radiofrequency ablation for lung tumors is safe.10 In terms of efficacy, there is evidence to suggest that cryoablation may result in improved local control in renal tumors,11 but, to our knowledge, there are no studies comparing the two modalities in lung tumors. Hence, we consider that a retrospective study comparing the two modalities is a minimum requirement to evaluate any comparative strengths or weaknesses of each of the procedures in terms of safety and
efficacy. Animal experiments comparing the differential effects of the two modalities on the lung tissue may also be necessary. Stereotactic radiotherapy (SRT) would have been another treatment option for these patients. Although we could not find reports of SRT in single-lung patients per se, there is accumulating evidence that the changes in pulmonary function tests after SRT are minimal.12-14 Hence, SRT may be another option for the treatment of single-lung patients, although radiation-associated pneumonitis could have fatal consequences in these patients. A limitation of the present report is that histologic diagnoses were not obtained for the nodules, particularly in case 1. Acquisition of specimens for on-site cytology and/or frozen pathology through the outer sheath during the cryoablation procedure may have been an option, but the optimal route of cryoprobe insertion for tumor treatment is not always the optimal route for specimen acquisition. Also, the procedure needs to be interrupted, with the outer sheath placed in the lung, until the pathologic results arrive, which may increase the risks of bleeding and/or pneumothoraces. Therefore, diagnoses based on just the clinical courses and the clinical findings may be unavoidable,
Figure 5. A, CT scan of case 2 showing placement of one cryoprobe into the nodule in the left upper lobe (arrow). Pulmonary hemorrhage is seen around the nodule after placement of the outer sheath. B, On CT scan 2 years after the treatment of case 2, the ablated nodule in the left upper lobe is locally controlled, with only treatment-related scar formation (arrow). 1636
Selected Report
Downloaded from chestjournal.chestpubs.org by Kimberly Henricks on December 7, 2011 © 2011 American College of Chest Physicians
particularly in single-lung patients. To this end, PET scans should have been performed in both patients. PET scan was negative for the two nodules in case 1, but the nodules may have been too small and their opacities too low to be detectable on PET scan. PET scan may have provided additional support of malignancy for the nodule in case 2, but was not performed. In conclusion, percutaneous cryoablation may represent a potentially new treatment option for lung tumors in cases wherein surgical resections may be difficult, such as in single-lung patients who have previously undergone pneumonectomies.
Acknowledgments Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.
References 1. Donington JS, Miller DL, Rowland CC, et al. Subsequent pulmonary resection for bronchogenic carcinoma after pneumonectomy. Ann Thorac Surg. 2002;74(1):154-159. 2. Spaggiari L, Grunenwald D, Girard P, et al. Cancer resection on the residual lung after pneumonectomy for bronchogenic carcinoma. Ann Thorac Surg. 1996;62(6):1598-1602. 3. Terzi A, Lonardoni A, Scanagatta P, Pergher S, Bonadiman C, Calabrò F. Lung resection for bronchogenic carcinoma after pneumonectomy: a safe and worthwhile procedure. Eur J Cardiothorac Surg. 2004;25(3):456-459. 4. Kawamura M, Izumi Y, Tsukada N, et al. Percutaneous cryoablation of small pulmonary malignant tumors under computed tomographic guidance with local anesthesia for nonsurgical candidates. J Thorac Cardiovasc Surg. 2006;131(5): 1007-1013.
www.chestpubs.org
5. Wang H, Littrup PJ, Duan Y, Zhang Y, Feng H, Nie Z. Thoracic masses treated with percutaneous cryotherapy: initial experience with more than 200 procedures. Radiology. 2005;235(1):289-298. 6. Yamauchi Y, Kawamura M. Cryoablation for metastatic lung tumor derived from colorectal cancer [in Japanese]. Gan To Kagaku Ryoho. 2009;36(8):1259-1262. 7. Ambrogi MC, Fanucchi O, Lencioni R, Cioni R, Mussi A. Pulmonary radiofrequency ablation in a single lung patient. Thorax. 2006;61(9):828-829. 8. Martini N, Melamed MR. Multiple primary lung cancers. J Thorac Cardiovasc Surg. 1975;70(4):606-612. 9. Hess A, Palussière J, Goyers JF, Guth A, Aupérin A, de Baère T. Pulmonary radiofrequency ablation in patients with a single lung: feasibility, efficacy, and tolerance. Radiology. 2011;258(2):635-642. 10. Zhu JC, Yan TD, Morris DL. A systematic review of radiofrequency ablation for lung tumors. Ann Surg Oncol. 2008; 15(6):1765-1774. 11. Kunkle DA, Uzzo RG. Cryoablation or radiofrequency ablation of the small renal mass: a meta-analysis. Cancer. 2008;113(10):2671-2680. 12. Henderson M, McGarry R, Yiannoutsos C, et al. Baseline pulmonary function as a predictor for survival and decline in pulmonary function over time in patients undergoing stereotactic body radiotherapy for the treatment of stage I nonsmall-cell lung cancer. Int J Radiat Oncol Biol Phys. 2008; 72(2):404-409. 13. Ohashi T, Takeda A, Shigematsu N, et al. Differences in pulmonary function before vs. 1 year after hypofractionated stereotactic radiotherapy for small peripheral lung tumors. Int J Radiat Oncol Biol Phys. 2005;62(4):1003-1008. 14. Stephans KL, Djemil T, Reddy CA, et al. Comprehensive analysis of pulmonary function Test (PFT) changes after stereotactic body radiotherapy (SBRT) for stage I lung cancer in medically inoperable patients. J Thorac Oncol. 2009;4(7): 838-844.
CHEST / 140 / 6 / DECEMBER, 2011
Downloaded from chestjournal.chestpubs.org by Kimberly Henricks on December 7, 2011 © 2011 American College of Chest Physicians
1637
Selected Report
Percutaneous Cryoablation for Pulmonary Nodules in the Residual Lung After Pneumonectomy
nectomies. Application of percutaneous cryoablation may represent a new treatment option for lung tumors in patients who have previously undergone pneumonectomies. CHEST 2011; 140(6):1633–1637
Report of Two Cases
S
Yoshikane Yamauchi, MD; Yotaro Izumi, MD; Hideki Yashiro, MD; Masanori Inoue, MD; Seishi Nakatsuka, MD; Masafumi Kawamura, MD; and Hiroaki Nomori, MD
Lung cancers in the residual lungs of patients who have undergone pneumonectomies are often unresectable, primarily because of the risks of overt pulmonary function losses. Percutaneous cryoablation of lung tumors is a potentially minimally invasive technique that has recently been used in the treatment of lung cancers and metastatic lung tumors. Here, we present two patients who had previously undergone pneumonectomies, in whom lung cancers in the residual lungs were treated by cryoablation. In both patients, the procedures were performed safely without any complications, such as airway bleeding, hemothoraces, or pneumothoraces. The changes in pulmonary functions after the procedures were minimal: % vital capacity (21% and 24%), and %FEV1 (21% and 110%) in the first and second patients, respectively. The performance statuses were maintained at zero in both patients after cryoablation. In the first patient, local control has been maintained for 4 years. In the second patient, local control was maintained for 2 years until the patient died of distant metastases. This is, to our knowledge, the first reported case of lung cryoablation in residual lungs of patients who have previously undergone pneumoManuscript received February 22, 2011; revision accepted April 1, 2011. Affiliations: From the Department of Surgery (Drs Yamauchi, Izumi, and Nomori), and the Department of Diagnostic Radiology (Drs Inoue and Nakatsuka), School of Medicine, Keio University, Tokyo; the Department of Radiology (Dr Yashiro), Hiratsuka City Hospital, Kanagawa; and the Department of Surgery (Dr Kawamura), Teikyo University School of Medicine, Tokyo, Japan. Correspondence to: Yotaro Izumi, MD, Department of Surgery, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan; e-mail: [email protected] © 2011 American College of Chest Physicians. Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/ site/misc/reprints.xhtml). DOI: 10.1378/chest.11-0459 www.chestpubs.org
Abbreviations: SRT 5 stereotactic radiotherapy; VC 5 vital capacity
urgical resections of recurrent or primary lung cancers in the residual lungs after pneumonectomies are not always feasible and are reported to have high rates of postoperative morbidities (21%-44%) and/or mortalities (0%-8.3%).1-3 Percutaneous cryoablation is currently evolving as a minimally invasive, and potentially effective, local treatment of lung tumors.4-6 Following a report of percutaneous radiofrequency ablation for a lung nodule in a patient after pneumonectomy,7 percutaneous cryoablation was attempted in two patients with pulmonary nodules in the residual lungs after pneumonectomies. To our knowledge, this study describes the first reported cases of lung cryoablation in residual lungs postpneumonectomy. The cryoablation protocol was approved by the institutional review board in October 2002. Written consent was obtained from both patients.
Case 1 In September 2004, a 55-year-old woman underwent a left pneumonectomy for lung adenocarcinoma at another institution. Pathologic stage was pT3 (separate nodule in primary lobe) N0M0, stage IIB. Four cycles of cisplatin/gemcitabine were administered as adjuvant chemotherapy. Eighteen months after surgery, CT scan of the chest showed two solitary pulmonary nodules, one in the right upper lobe (Fig 1A) and the other in the right lower lobe (Fig 1B). Systemic examinations, such as whole-body contrastenhanced CT scan, PET scan, bronchoscopy, and serum examinations of tumor markers, did not reveal any other evidence of disease. Histologic diagnoses of the two lesions could not be obtained by transbronchial biopsy. At 30 months after surgery, both of these lesions had increased in size from 8 mm and 10 mm to 13 mm and 16 mm in diameter, respectively. Although histologic diagnoses were not obtained for the nodules, CT scan-guided needle biopsies were not performed because of the potential risks of airway bleeding, pneumothoraces, and/or hemothoraces. Since the lesions existed in different lobes of the right lung after left pneumonectomy, from the criteria of Martini and Melamed8 the nodules were both assumed to be second primary lung cancers, although the possibility of pulmonary metastases could not be ruled out. The mixed groundglass opacity appearances of the nodules on CT scan also supported this assumption. CHEST / 140 / 6 / DECEMBER, 2011
Downloaded from chestjournal.chestpubs.org by Kimberly Henricks on December 7, 2011 © 2011 American College of Chest Physicians
1633
Figure 1. A, CT scan of case 1 showing a nodule in the right upper lobe. B, CT scan of case 1 showing a nodule in the right lower lobe.
The patient could have been considered as a candidate for partial lung resections, but it was thought that partial resections of both nodules could still result in substantial loss of lung function. Therefore, the patient was referred to us for percutaneous cryoablation. Percutaneous cryoablations were performed sequentially for the two nodules for safety. The lower lobe nodule, which was slightly larger, was done in February 2007, and the upper lobe nodule was done in April 2007. The procedure of percutaneous cryoablation was performed as previously described.4 Under a multidetector-row CT scanner with multislice CT scan fluoroscopy functions (Aquilion 64; Toshiba Medical Co Ltd; Tokyo, Japan), using an outer insertion sheath, a 1.7-mm-diameter cryoprobe (CRYOcare Cryosurgical Unit; Endocare; Irvine, California) was inserted into the targeted nodule under fluoroscopic CT scan guidance. Two cryoprobes were inserted for the treatment of the nodule in the lower lobe (Figs 2A, 2B), since the ablation margin was considered to be insufficient with just one probe. One cryoprobe was inserted for the treatment of the nodule in the upper lobe (Fig 2C). The cryoprobe uses high-pressure argon and helium gases for freezing and thawing, respectively, based on the JouleThompson principle. For both nodules, cryoablation consisted of two cycles of freezing, 5 min each. The tip of the
cryoprobe reaches approximately 2130°C during freezing. This was followed by thawing until the temperature of the cryoprobe reached 20°C, and then a third cycle of freezing (10 min) followed by thawing. Fibrin glue was infused into the outer sheath at the time of cryoprobe removal to reduce the risks of hemothoraces and pneumothoraces. Whole-lung CT scans were taken at the end of each of the procedures. Chest radiographs were also checked 2 h after, the next day, and the day after each of the procedures. The CT scan and chest radiographs showed no evidence of complications such as hemothoraces or pneumothoraces after any of the procedures. The patient was discharged on the second postoperative day on both treatment occasions. Performance status was maintained at zero after cryoablation. Changes in respiratory functions were minimal at 3 months after the second cryoablation; vital capacity (VC) was 1.82 L (68% VC) vs 1.81 L (67% VC), and FEV1 was 1.31 L (72% FEV1) vs 1.26 L (71% FEV1), before and after cryoablations, respectively. Follow-up CT scan was taken every 6 months after cryoablation. Infiltrative shadows persisted in the vicinity of the ablated sites, but they were considered to be scar formations since they never increased in size during follow-up. Local control was considered to be maintained in both lesions for 4 years after cryoablations (Figs 3A, 3B).
Figure 2. A and B, CT scans of case 1 showing placement of two cryoprobes into the nodule in right lower lobe. C, Two months later, placement of one cryoprobe into the nodule in the right upper lobe. 1634
Selected Report
Downloaded from chestjournal.chestpubs.org by Kimberly Henricks on December 7, 2011 © 2011 American College of Chest Physicians
Figure 3. A, CT scan of the right lower lobe 4 years after treatment of case 1. B, CT scan of the right upper lobe 4 years after treatment of case 1. The ablated nodules are both locally controlled, with only treatment-related scar formation (arrows).
Case 2 In June 2004, a 60-year-old man underwent a right pneumonectomy at another institution for four multiple synchronous lung cancers. Pathologic study indicated that the nodules were three lung adenocarcinomas and one lung squamous cell carcinoma. The lesions were considered to be all primary lung cancers. One adenocarcinoma lesion in the right middle lobe had metastasis to the bronchial lymph node and was considered to be pT1bN1M0, stage IIA. The other three lesions were considered as pT2aN0M0, stage IB. No adjuvant treatment was given. At follow-up 2 years later, chest CT scan showed the appearance of two pulmonary nodules; one nodule was 12 mm in diameter, in the upper lobe of the residual left lung (Fig 4A), and the other nodule, 15 mm in diameter, was in the left lower lobe (Fig 4B). Whole-body contrast-enhanced CT scan did not reveal any other evidence of disease. PET scan was not performed. Histologic diagnosis of the two lesions could not be obtained by transbronchial biopsy. Surgical wedge resection of left lower lobe lesion was performed in January 2007, and the pathologic findings suggested that the nodule was considered to be more likely metastasis of lung cancer rather than metachronous primary lung cancer, because the pathologic finding of this nodule was quite similar to that of the lung cancer in the right middle lobe resected 2 years previously. From the clinical course and the radiologic appearance, the upper lobe nodule was also speculated to be pulmonary metastasis rather than metachronous primary lung cancer. It was considered that surgical removal of the nodule might involve removal of too much lung parenchyma because the nodule was not located peripherally. Therefore, the patient was referred to us for percutaneous cryoablation. The procedure was performed for the nodule in March 2007, as described in case 1, using one cryoprobe (Fig 5A). No complications occurred after the procedure and the patient was discharged on the second postoperative day. Performance status was maintained at zero after cryoablation. Changes in respiratory functions were minimal at 3 months after cryoablation; VC was 2.28 L (68% VC) vs 2.15 L (64% VC), and FEV1 was 1.47 L (68% FEV1) vs 1.64 L (78% FEV1) before and after cryoablation, respectively. www.chestpubs.org
Follow-up CT was taken every 6 months after cryoablation. A nodular shadow persisted in the vicinity of the ablated site but it was considered to be scar formation since it never increased in size during follow-up. Local control was maintained for 2 years after cryoablation, until the patient died of progressive lung metastases and pleural disseminations (Fig 5B).
Discussion Cryoablation is a relatively new procedure that potentially permits local treatment of lung tumors with minimal loss of lung parenchyma. This procedure, used when surgical resection is contraindicated, is currently under evaluation as a potential complementary therapy for patients with primary lung cancers as well as metastatic lung tumors. In our institution, we have been performing percutaneous cryoablation of lung tumors as a clinical study since 2002.4 We have, to date, treated . 300 lung tumors in . 200 patients. As for the perioperative complications, pneumothoraces occurred in 50% of cases, which were mostly categorized as grade 1 according to the Common Terminology Criteria for Adverse Events, version 4.0. The insertion of a chest tube was required in only 4.5% of the pneumothoraces cases. A small amount of pleural effusion and transient hemoptysis also occurred in about 30% of cases, but these cases were also categorized as grade 1 according to the Common Terminology Criteria for Adverse Events, version 4.0, and all resolved spontaneously. There were neither treatment-related deaths nor conversions to surgical interventions. As for local disease control, radiologically determined response rate of 54% was achieved with lesions , 3 cm in diameter.4 Although further data collections are necessary, particularly in terms of local disease control rates, the data so far suggest that cryoablation could be a feasible option in patients who are deemed unable to tolerate surgical resection, with the aim of local control of lung tumors. In view of these feasibility and efficacy results, we attempted cryoablation in the reported two patients who have previously undergone pneumonectomies. In these two patients, we experienced no apparent complications, CHEST / 140 / 6 / DECEMBER, 2011
Downloaded from chestjournal.chestpubs.org by Kimberly Henricks on December 7, 2011 © 2011 American College of Chest Physicians
1635
Figure 4. A, CT scan of case 2 showing the nodule in the left upper lobe, which was cryoablated. B, CT scan of case 2 showing the nodule in the left lower lobe, which was resected.
the decrease in respiratory function was minimal, and the local control was also considered to be satisfactory. Recently, results of radiofrequency ablation in single-lung patients after pneumonectomies have been reported with good feasibility.9 Although the radiofrequency procedures were done under general anesthesia, as opposed to local anesthesia for cryoablation, the data support the concept that needle ablation procedures, including cryoablation, may be safely applicable in single-lung patients. In terms of safety, there is a statement from the US Food and Drug Administration that discourages the use of radiofrequency ablation in lung tumors because of reports of serious complications, but it is difficult to find definitive support for this statement in the published literature. In fact, the majority of reports indicate that radiofrequency ablation for lung tumors is safe.10 In terms of efficacy, there is evidence to suggest that cryoablation may result in improved local control in renal tumors,11 but, to our knowledge, there are no studies comparing the two modalities in lung tumors. Hence, we consider that a retrospective study comparing the two modalities is a minimum requirement to evaluate any comparative strengths or weaknesses of each of the procedures in terms of safety and
efficacy. Animal experiments comparing the differential effects of the two modalities on the lung tissue may also be necessary. Stereotactic radiotherapy (SRT) would have been another treatment option for these patients. Although we could not find reports of SRT in single-lung patients per se, there is accumulating evidence that the changes in pulmonary function tests after SRT are minimal.12-14 Hence, SRT may be another option for the treatment of single-lung patients, although radiation-associated pneumonitis could have fatal consequences in these patients. A limitation of the present report is that histologic diagnoses were not obtained for the nodules, particularly in case 1. Acquisition of specimens for on-site cytology and/or frozen pathology through the outer sheath during the cryoablation procedure may have been an option, but the optimal route of cryoprobe insertion for tumor treatment is not always the optimal route for specimen acquisition. Also, the procedure needs to be interrupted, with the outer sheath placed in the lung, until the pathologic results arrive, which may increase the risks of bleeding and/or pneumothoraces. Therefore, diagnoses based on just the clinical courses and the clinical findings may be unavoidable,
Figure 5. A, CT scan of case 2 showing placement of one cryoprobe into the nodule in the left upper lobe (arrow). Pulmonary hemorrhage is seen around the nodule after placement of the outer sheath. B, On CT scan 2 years after the treatment of case 2, the ablated nodule in the left upper lobe is locally controlled, with only treatment-related scar formation (arrow). 1636
Selected Report
Downloaded from chestjournal.chestpubs.org by Kimberly Henricks on December 7, 2011 © 2011 American College of Chest Physicians
particularly in single-lung patients. To this end, PET scans should have been performed in both patients. PET scan was negative for the two nodules in case 1, but the nodules may have been too small and their opacities too low to be detectable on PET scan. PET scan may have provided additional support of malignancy for the nodule in case 2, but was not performed. In conclusion, percutaneous cryoablation may represent a potentially new treatment option for lung tumors in cases wherein surgical resections may be difficult, such as in single-lung patients who have previously undergone pneumonectomies.
Acknowledgments Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.
References 1. Donington JS, Miller DL, Rowland CC, et al. Subsequent pulmonary resection for bronchogenic carcinoma after pneumonectomy. Ann Thorac Surg. 2002;74(1):154-159. 2. Spaggiari L, Grunenwald D, Girard P, et al. Cancer resection on the residual lung after pneumonectomy for bronchogenic carcinoma. Ann Thorac Surg. 1996;62(6):1598-1602. 3. Terzi A, Lonardoni A, Scanagatta P, Pergher S, Bonadiman C, Calabrò F. Lung resection for bronchogenic carcinoma after pneumonectomy: a safe and worthwhile procedure. Eur J Cardiothorac Surg. 2004;25(3):456-459. 4. Kawamura M, Izumi Y, Tsukada N, et al. Percutaneous cryoablation of small pulmonary malignant tumors under computed tomographic guidance with local anesthesia for nonsurgical candidates. J Thorac Cardiovasc Surg. 2006;131(5): 1007-1013.
www.chestpubs.org
5. Wang H, Littrup PJ, Duan Y, Zhang Y, Feng H, Nie Z. Thoracic masses treated with percutaneous cryotherapy: initial experience with more than 200 procedures. Radiology. 2005;235(1):289-298. 6. Yamauchi Y, Kawamura M. Cryoablation for metastatic lung tumor derived from colorectal cancer [in Japanese]. Gan To Kagaku Ryoho. 2009;36(8):1259-1262. 7. Ambrogi MC, Fanucchi O, Lencioni R, Cioni R, Mussi A. Pulmonary radiofrequency ablation in a single lung patient. Thorax. 2006;61(9):828-829. 8. Martini N, Melamed MR. Multiple primary lung cancers. J Thorac Cardiovasc Surg. 1975;70(4):606-612. 9. Hess A, Palussière J, Goyers JF, Guth A, Aupérin A, de Baère T. Pulmonary radiofrequency ablation in patients with a single lung: feasibility, efficacy, and tolerance. Radiology. 2011;258(2):635-642. 10. Zhu JC, Yan TD, Morris DL. A systematic review of radiofrequency ablation for lung tumors. Ann Surg Oncol. 2008; 15(6):1765-1774. 11. Kunkle DA, Uzzo RG. Cryoablation or radiofrequency ablation of the small renal mass: a meta-analysis. Cancer. 2008;113(10):2671-2680. 12. Henderson M, McGarry R, Yiannoutsos C, et al. Baseline pulmonary function as a predictor for survival and decline in pulmonary function over time in patients undergoing stereotactic body radiotherapy for the treatment of stage I nonsmall-cell lung cancer. Int J Radiat Oncol Biol Phys. 2008; 72(2):404-409. 13. Ohashi T, Takeda A, Shigematsu N, et al. Differences in pulmonary function before vs. 1 year after hypofractionated stereotactic radiotherapy for small peripheral lung tumors. Int J Radiat Oncol Biol Phys. 2005;62(4):1003-1008. 14. Stephans KL, Djemil T, Reddy CA, et al. Comprehensive analysis of pulmonary function Test (PFT) changes after stereotactic body radiotherapy (SBRT) for stage I lung cancer in medically inoperable patients. J Thorac Oncol. 2009;4(7): 838-844.
CHEST / 140 / 6 / DECEMBER, 2011
Downloaded from chestjournal.chestpubs.org by Kimberly Henricks on December 7, 2011 © 2011 American College of Chest Physicians
1637