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DOI:10.2214/AJR.04.1068
AJR 2006; 186:1703-1706
© American Roentgen Ray Society

Technical Innovation

Percutaneous Cryotherapy of the Thorax: Safety Considerations for Complex Cases

Abraham Ahmed1 and Peter Littrup2

1 Wayne State University School of Medicine, 540 East Canfield, Detroit, MI 48202.
2 Department of Radiology, Karmanos Cancer Institute and Wayne State University, Detroit, MI 48201.

Received July 6, 2004; accepted after revision August 8, 2005.

 
Address correspondence to A. Ahmed (aahmed{at}med.wayne.edu).

Keywords: ablation • chest • CT technique • percutaneous • safety


Introduction
Top
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
Percutaneous cryotherapy may have a wide range of anatomic and tumor treatment options because of its low pain, good ice visualization, and preservation of collagenous tissue architecture. Cryoablation was performed in the liver, prostate, kidney, and breast with good outcomes [1-4]. More recently, we showed it to be safe and feasible in the thorax [5] with basic CT and cryotherapy equipment. Reports involving endobronchial cryotherapy followed by external beam radiation also suggest better local tumor control than radiation alone [6]. We used current cryotechnology with angled probes (Fig. 1A) that allow CT fluoroscopy, including novel safety techniques. Five successful cryotherapy procedures were performed in two complex patients with sarcoma metastases to the lung.


Figure 1
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  		Fig. 1A —28-year-old woman with two metastatic foci from synovial cell sarcoma. Angled cryoprobe (A) was used during all procedures. Unenhanced CT images before cryotherapy show paraesophageal mass (perpendicular bidimensional measurement calipers coinciding with numbers 1 and 2, B) abutting posterior aspect of trachea (white arrow) and esophagus (black arrow). Locally recurrent mass is seen (C) in right posterior costophrenic angle (arrows).

 

Materials and Methods
Top
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
The first patient was a 28-year-old woman diagnosed with thoracic metastases from high-grade synovial sarcoma. Two separate masses involved the left upper lobe adjacent to the esophagus and the right posterior chest wall-diaphragmatic junction. One year after surgical resection, chemotherapy, external radiation, and brachytherapy, the primary mass in the right posterior hemithorax had recurred. Chest CT showed a 6.5 x 3-cm mass abutting the reconstructed diaphragm, which involved the adjacent ribs and dome of the liver (Fig. 1C). Both this and the other 3-cm tumor in the left posterior paraesophageal region (Fig. 1B) were positive on FDG PET and were confirmed to be metastatic synovial sarcoma with a CT-guided 18-gauge core biopsy.


Figure 3
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  		Fig. 1C —28-year-old woman with two metastatic foci from synovial cell sarcoma. Angled cryoprobe (A) was used during all procedures. Unenhanced CT images before cryotherapy show paraesophageal mass (perpendicular bidimensional measurement calipers coinciding with numbers 1 and 2, B) abutting posterior aspect of trachea (white arrow) and esophagus (black arrow). Locally recurrent mass is seen (C) in right posterior costophrenic angle (arrows).

 

Figure 2
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  		Fig. 1B —28-year-old woman with two metastatic foci from synovial cell sarcoma. Angled cryoprobe (A) was used during all procedures. Unenhanced CT images before cryotherapy show paraesophageal mass (perpendicular bidimensional measurement calipers coinciding with numbers 1 and 2, B) abutting posterior aspect of trachea (white arrow) and esophagus (black arrow). Locally recurrent mass is seen (C) in right posterior costophrenic angle (arrows).

 
The second patient was a 39-year-old woman diagnosed with bilateral pulmonary metastases from alveolar soft part sarcoma (ASPS). Initially a 3 x 3-cm right hilar mass showed faster progression than approximately seven other tiny (< 1-cm) nodules. Five months after cryotherapy of her first mass, a 3.5 x 3-cm left aortopulmonary window tumor and another 3 x 3-cm right lower lobe mass had distinctly increased in follow-up. External beam radiation was not considered, and bilateral surgical resection was declined. Two additional cryotherapy sessions were then performed.

All procedures and associated chart reviews were performed with approval by our university's institutional review board, including patient informed consent. A CT scanner (Somatom Plus 4, Siemens Medical Solutions) with the CARE Vision fluoroscopy package was used for all five procedures. The cryosurgical unit for all procedures was an argon gas-based system (Cryocare, Endocare). General endotracheal anesthesia was used only for the procedure involving the paraesophageal mass, and all other procedures used IV midazolam and morphine sedation titrated to patient comfort. After liberal injection of Xylocaine (2%), a 20-gauge 15-cm needle was first inserted in the center of each mass using CT fluoroscopy. Two angled 2.4-mm (outer diameter) cryoprobes with sharp tips were spaced no more than 2 cm apart (Figs. 2A, 2B, and 2C) and placed directly along a course tandem to the 20-gauge needle in the periphery of the masses. (This "bracketing" approach allows for approximately 1-cm freeze ablation margins beyond all visible tumor margins) [5]. Freezing cycles generally lasted 10 min (15 min in the larger chest wall tumor to ensure adequate tumor margin coverage) for the first freeze cycle, followed by a 10-min passive thaw and a 10-min refreeze. An additional probe was placed during the thaw phase of two procedures because visible ice could not be verified to cover all tumor margins (Fig. 1F).


Figure 7
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  		Fig. 2A —39-year-old woman with three metastatic foci from alveolar soft part sarcoma. Cryotherapy CT images show right hilar mass being treated (A) from anterior approach with cryoprobes bracketing mass (arrows) to avoid posterior vascular structures. Aortopulmonary window (B) mass is being treated from an anterior approach. Two cryoprobes (C) are seen bracketing second right lower lobe mass (arrow) from posterolateral approach.

 

Figure 8
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  		Fig. 2B —39-year-old woman with three metastatic foci from alveolar soft part sarcoma. Cryotherapy CT images show right hilar mass being treated (A) from anterior approach with cryoprobes bracketing mass (arrows) to avoid posterior vascular structures. Aortopulmonary window (B) mass is being treated from an anterior approach. Two cryoprobes (C) are seen bracketing second right lower lobe mass (arrow) from posterolateral approach.

 

Figure 9
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  		Fig. 2C —39-year-old woman with three metastatic foci from alveolar soft part sarcoma. Cryotherapy CT images show right hilar mass being treated (A) from anterior approach with cryoprobes bracketing mass (arrows) to avoid posterior vascular structures. Aortopulmonary window (B) mass is being treated from an anterior approach. Two cryoprobes (C) are seen bracketing second right lower lobe mass (arrow) from posterolateral approach.

 

Figure 6
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  		Fig. 1F —28-year-old woman with two metastatic foci from synovial cell sarcoma. One of two urethral warming catheters (D) used for esophageal protection. Postcryotherapy CT images are at same levels as in Figures 1A, 1B, 1C. Four hours after cryotherapy (E) shows no enhancement of paraesophageal mass (black arrowheads) (note margin of tumor "ghost") with surrounding area of approximately 1-cm thick border of cryotherapy effect. Posterior wall of trachea (white arrow) and esophagus (black arrow) are seen. Immediate removal of cryotherapy probes (F) with air density is seen in five tracks. Track is shown (white arrow) where additional probe was placed during thaw cycle to assure thorough lateral coverage of low-density ice (black arrows) extending well beyond underlying tumor ghost (white arrowheads).

 
Novel safety techniques included a vasoconstriction cocktail for all procedures consisting of 2-3 mL of unlabeled macroaggregated albumin with dilute (1:50,000-100,000) epinephrine, followed by 3-10 mL (i.e., depending on mass size) of 7.5% hypertonic saline with dilute epinephrine. For esophageal protection in the first patient, two 1-cm coaxial urethral warming catheters (Urethral Warmer, Endocare) (Fig. 1D) [7] were placed in the esophagus beyond the level of the adjacent mass. The freeze protocol was also modified during one procedure in the ASPS patient to protect the recurrent laryngeal nerve coursing near the left anteroposterior window mass. She was instructed to hum (vocalize) until she noted some hoarseness, then the flow rate of the cryoprobes was reduced to 50% and stopped after 6 min during the first freeze. She experienced similar increased hoarseness during the second freeze but tolerated a full 8-min third freeze at 100% flow without significant voice changes.


Figure 4
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  		Fig. 1D —28-year-old woman with two metastatic foci from synovial cell sarcoma. One of two urethral warming catheters (D) used for esophageal protection. Postcryotherapy CT images are at same levels as in Figures 1A, 1B, 1C. Four hours after cryotherapy (E) shows no enhancement of paraesophageal mass (black arrowheads) (note margin of tumor "ghost") with surrounding area of approximately 1-cm thick border of cryotherapy effect. Posterior wall of trachea (white arrow) and esophagus (black arrow) are seen. Immediate removal of cryotherapy probes (F) with air density is seen in five tracks. Track is shown (white arrow) where additional probe was placed during thaw cycle to assure thorough lateral coverage of low-density ice (black arrows) extending well beyond underlying tumor ghost (white arrowheads).

 


Figure 5
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  		Fig. 1E —28-year-old woman with two metastatic foci from synovial cell sarcoma. One of two urethral warming catheters (D) used for esophageal protection. Postcryotherapy CT images are at same levels as in Figures 1A, 1B, 1C. Four hours after cryotherapy (E) shows no enhancement of paraesophageal mass (black arrowheads) (note margin of tumor "ghost") with surrounding area of approximately 1-cm thick border of cryotherapy effect. Posterior wall of trachea (white arrow) and esophagus (black arrow) are seen. Immediate removal of cryotherapy probes (F) with air density is seen in five tracks. Track is shown (white arrow) where additional probe was placed during thaw cycle to assure thorough lateral coverage of low-density ice (black arrows) extending well beyond underlying tumor ghost (white arrowheads).

 


Figure 10
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  		Fig. 2D —39-year-old woman with three metastatic foci from alveolar soft part sarcoma. Postcryotherapy CT images are at same levels as in Figures 2A, 2B, 2C. Near complete resolution (D) of previous right hilar mass (arrow) is seen 9 months postprocedure. Four-hour postcryotherapy CT (E) is seen with minimal enhancement of hypervascular anteroposterior window mass (white arrow) and minimal effusion (black arrow). Four hours after cryotherapy (F) shows minimal lateral pneumothorax (arrowheads), and perpendicular bidimensional calipers (i.e., coinciding with numbers 1 and 2) denote estimated margins of cryotherapy effect approximately 1 cm beyond right lower lobe tumor margins (i.e., hazy consolidation surrounding underlying smaller white mass, arrows).

 


Figure 11
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  		Fig. 2E —39-year-old woman with three metastatic foci from alveolar soft part sarcoma. Postcryotherapy CT images are at same levels as in Figures 2A, 2B, 2C. Near complete resolution (D) of previous right hilar mass (arrow) is seen 9 months postprocedure. Four-hour postcryotherapy CT (E) is seen with minimal enhancement of hypervascular anteroposterior window mass (white arrow) and minimal effusion (black arrow). Four hours after cryotherapy (F) shows minimal lateral pneumothorax (arrowheads), and perpendicular bidimensional calipers (i.e., coinciding with numbers 1 and 2) denote estimated margins of cryotherapy effect approximately 1 cm beyond right lower lobe tumor margins (i.e., hazy consolidation surrounding underlying smaller white mass, arrows).

 


Figure 12
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  		Fig. 2F —39-year-old woman with three metastatic foci from alveolar soft part sarcoma. Postcryotherapy CT images are at same levels as in Figures 2A, 2B, 2C. Near complete resolution (D) of previous right hilar mass (arrow) is seen 9 months postprocedure. Four-hour postcryotherapy CT (E) is seen with minimal enhancement of hypervascular anteroposterior window mass (white arrow) and minimal effusion (black arrow). Four hours after cryotherapy (F) shows minimal lateral pneumothorax (arrowheads), and perpendicular bidimensional calipers (i.e., coinciding with numbers 1 and 2) denote estimated margins of cryotherapy effect approximately 1 cm beyond right lower lobe tumor margins (i.e., hazy consolidation surrounding underlying smaller white mass, arrows).

 
Helical CT scans were performed immediately after an active thaw allowed removal of cryoprobes less than 2 min after completion of the second freeze. Follow-up chest CT scans were also performed approximately 4 hr after the procedures to document any complications immediately before discharge. Patients were called daily by a nurse coordinator to assess symptoms during the first week postprocedure. Subsequent CT scans were scheduled at 1, 3, 6, and 12 months after cryotherapy.


Results
Top
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
All procedures were well tolerated without significant complications (i.e., tiny pneumothorax and pleural effusion not requiring intervention). Minor discomfort at the procedure site generally resolved within 48 hr. Follow-up of the first patient is at over 1 year for both procedures, and the second patient is over 3 months after her second procedure. The first patient's chest CT 4 hr after both procedures showed thorough hypovascular cryotherapy effect beyond the paraesophageal and chest wall mass margins (Figs. 1E and 1F).

The hoarseness the second patient experienced during the anteroposterior window mass procedure persisted 1 week after the procedure and resolved at 1 month. During cryotherapy of the hilar and mediastinal tumors, back bleeding from the 20-gauge placement needle occurred immediately after removal of the stylet but stopped after the vasoconstriction cocktail. Follow-up CT in this patient showed areas of cryotherapy effect extending beyond previous tumor margins (Figs. 2E and 2F). Neither nodular enhancement nor tissue vascularity was seen, suggesting complete ablation and longer follow-up. The right lower lobe mass showed progressive resorption to approximately 1 x 1.5 cm 9 months postprocedure without significant adjacent parenchymal scarring (Fig. 2D).


Discussion
Top
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
Percutaneous cryotherapy of lung masses is technically feasible and may be a valuable treatment alternative when other treatments do not result in sufficient local tumor control. We achieved our major treatment goals of near real-time procedure visualization, patient acceptance with minimal sedation, and preservation of underlying tissue architecture with minimal complications. Use of angled probes allowed for CT gantry clearance and real-time imaging during probe placement to minimize procedural morbidity near major vasculature. In our first patient, urethral warming catheters [7] most likely preserved the endoluminal mucosa of the esophagus, preventing native mucosal bacteria from spreading to the necrotic cryoablation zone and causing perforation and possibly abscess. Our vasoconstrictive cocktail also appeared to assist hemostasis, particularly in the highly vascular ASPS tumor. The cocktail used macroaggregated albumin to create a gel-like matrix [8] to better contain the subsequent injection of a hypertonic saline-epinephrine solution, which is reported to minimize bleeding in polypectomies [9]. As an established safe adjunct for highly vascular tumors, we believe this cocktail is helpful, but routine use requires further evaluation. In summary, complex cryotherapy procedures are possible for nearly any location in the thorax if the appropriate safety precautions embodied in our suggested techniques are used.


References
Top
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

  1. Lee FT Jr, Chosy SG, Littrup PJ, Warner TF, Kuhlman JE, Mahvi DM. CT-monitored percutaneous cryoablation in a pig liver model: pilot study. Radiology 1999;211 : 687-692[Abstract/Free Full Text]
  2. Bahn DK, Lee F, Badalament R, Kumar A, Greski J, Chernick M. Targeted cryoablation of the prostate: 7-year outcomes in the primary treatment of prostate cancer. Urology2002; 60 [suppl 1]:3 -11[CrossRef][Medline]
  3. Collyer WC, Landman J, Olweny EO, et al. Comparison of renal ablation with cryotherapy, dry radiofrequency, and saline augmented radiofrequency in a porcine model. J Am Coll Surgery2001; 193:505 -513
  4. Littrup PJ, Freeman-Gibb L, Andea A, et al. Cryotherapy for breast fibroadenomas. Radiology 2005;234 : 63-72[Abstract/Free Full Text]
  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 : 289-298[Abstract/Free Full Text]
  6. Vergnon JM, Schmitt T, Alamartine E, Barthelemy JC, Fournel P, Emonot A. Initial combined cryotherapy and irradiation for unresectable non-small cell lung cancer: preliminary results. Chest1992; 102:1436 -1440[Abstract/Free Full Text]
  7. Cohen JK, Miller RJ. Thermal protection of urethra during cryosurgery of the prostate. Cryobiology1994; 31:313 -316[Medline]
  8. Order SE, Siegel JA, Principato R, et al. Selective tumor irradiation by infusional brachytherapy in nonresectable pancreatic cancer: a phase I study. Int J Radiat Oncol Biol Phys1996; 36:1117 -1126[CrossRef][Medline]
  9. Shirai M, Nakamura T, Matsuura A, Ito Y, Kobayashi S. Safer colonoscopic polypectomy with local submucosal injection of hypertonic saline-epinephrine solution. Am J Gastroenterol1994; 89:334 -338[Medline]

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