Ann Thorac Surg 2006;81:718-721
© 2006 The Society of Thoracic Surgeons
Case report
Direct Cryosurgery for Inoperable Metastatic Disease of the Lung
Omar Maiwand, MD
a
,
*
,
Robert Glynne-Jones, MD
b
,
Jane Chambers, MD
a
,
George Asimakopoulos, MD
a
a Department of Thoracic Surgery, Harefield Hospital, Middlesex, United Kingdom
b Department of Oncology, Mount Vernon Hospital, Middlesex, United Kingdom
Accepted for publication November 11, 2004.
* Address correspondence to Dr Maiwand, Department of Cryosurgery, Harefield Hospital, Middlesex UB9 6JH, United Kingdom (Email: cryotherapy{at}rbh.nthames.nhs.uk).
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Abstract
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A 50-year-old woman presented with dyspnea associated with two isolated metastases in the right lung, which was 1 year after the resection of a primary pleomorphic fibrous histiocytoma from her left thigh. At a planned thoracotomy, the tumor was found to be advanced, contraindicating lobectomy. We aimed to completely destroy the tumor by applying cryosurgery.
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Introduction
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Metastatic disease in the lung is common. Tumors such as sarcomas metastasize almost exclusively to the lung parenchyma and occasionally can be cured by treatment of the primary site and resection of the lung metastasis. However, in most cases the management of lung metastasis relies on systemic treatment. For patients with inoperable intraluminal obstructive tumors, endobronchial cryosurgery can provide symptomatic relief by local destruction of the intraluminal tumor. Nitrous oxide is the most commonly used cooling agent and achieves a local temperature of about –70°C [1, 2].
In patients where the lung tumor is inaccessible through the tracheobronchial tree, and surgical resection is not indicated, oncological treatment of large tumors are often of limited benefit, and therefore, treatment options are severely restricted. Nitrous oxide as a cooling agent has been used for some years for the destruction of intraluminal tumors [1, 2]. Based on the knowledge of the biological effect of extreme cold, a lethal temperature of about –100°C at tumor level is required to achieve total destruction of the tumor mass of 2 cm or larger in diameter. Direct intraoperative cryosurgery using liquid nitrogen, which can achieve these temperatures is a novel treatment option, which was recently pioneered at our institution. Liquid nitrogen (boiling point –196°C) is significantly more powerful as a coolant than nitrous oxide and has a greater destructive effect over larger tissue mass. Direct liquid nitrogen cryoablation therapy has been successfully applied to tumors involving liver, prostate, skin, and bone [3]. Our extensive experience with endobronchial cryotherapy and recent work with direct intraoperative nitrous oxide cryosurgery [4] provided the stimulus to develop a new treatment of direct intraoperative cryosurgery of lung tumors with liquid nitrogen as the coolant through thoracotomy. We believe this is the first reported case of direct intraoperative cryosurgery with liquid nitrogen for inoperable lung metastasis.
A 50-year-old woman had a complete local excision of a pleomorphic sarcoma from her left thigh in June 2002. This was followed by postoperative adjuvant radiotherapy at a dose of 60 Gy in 30 fractions over 6 weeks. In July 2003, she presented with shortness of breath on moderate exertion. A routine chest roentgenogram revealed two circular well circumscribed opacities in the upper and mid zones of the right lung suspected to be metastases from the sarcoma (Fig 1A). Computed tomography revealed two lesions merging with each other (one 5.5 cm in maximum diameter located in the posterior segment of the right upper lobe and another one 3 cm in maximum diameter situated in the apex of the lower lobe with no lymphadenopathy) (Fig 2A). An Fluoro-2-deoxy-D-glucose positron-emission tomographic scan showed intense hypermetabolism in the right lung masses corresponding to the opacities seen on computed tomography (Fig 3A). Bronchoscopy revealed that the posterior segment of the right upper lobe bronchus was blocked by tumor and histology of the reported biopsy strands of pleomorphic spindle cells separated by an expanse of amorphous collagenous stroma compatible with pleomorphic sarcoma.
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Fig 1. (A) Chest roentgenogram revealing two circular well circumscribed opacities in the right upper and mid zones. (B) Both lesions almost completely resolved with residual linear opacities only.
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Fig 2. (A) Computed tomographic scan of the thorax (axial view with contrast) demonstrates a large parenchymal mass with rim enhancement. (B) Computed tomographic scan 12 months later shows complete resolution of mass with residual linear markings only.
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Fig 3. (A) Fluoro-2-deoxy-D-glucose positron-emission tomographic scan showing intense hypermetabolism in the right lung mass. (B) Fluoro-2-deoxy-D-glucose positron-emission tomographic scan 12 months after surgery shows complete absence of hypermetabolism.
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After a multidisciplinary case discussion, a right upper lobectomy plus a wedge resection or direct cryosurgery was offered. Informed consent was obtained after full explanation of risks and benefits. A standard right posterolateral thoracotomy was performed through the sixth intercostal space. The tumor was found to be more extensive than expected invading all three lobes. A 6-cm diameter tumor was found in the upper lobe, a 4-cm tumor was identified in the lower lobe, and a small lesion was identified in the middle lobe. It was apparent that the lobectomy would not achieve tumor clearance, and a pneumonectomy, although possible with good exercise tolerance and respiratory function (forced vital capacity of 3.08 L, 123% of predicted value; forced expiratory volume in 1 second of 2.51 L, 118% of predicted value) was not appropriate for metastatic disease. Therefore, the decision was taken to ablate the tumor masses with direct cryosurgery using a liquid nitrogen cooled probe from the Cryotech LCS 2000 unit (Spembly Medical Ltd, Andover, UK). A full assessment of the relationship to vital structures was made before cryoprobe insertion, and needle aspiration was performed to confirm the position of the major blood vessels. A 5-mm probe was introduced into the center of the largest lesion in the right upper lobe through a stab incision for a period of 10 minutes, and an ice ball of about 7.5 cm was achieved. This was repeated for the lower lobe lesion to the middle lobe. It was ensured that the resultant ice ball included the whole tumor area, and this was allowed to thaw spontaneously. A 5-mm margin of normal lung tissue was included within the ice-ball mass. The chest was then closed routinely with two chest tubes in position.
The patient made an uncomplicated postoperative recovery and remains asymptomatic. A chest roentgenogram taken 12 months later showed that both lesions had almost completely resolved with residual linear opacities (Fig 1B). A follow-up computed tomographic scan taken at 12 months showed complete resolution of the mass with only residual linear markings (Fig 2B).
The FDG18 positron-emission tomographic scan showed complete absence of hypermetabolism related to the residual opacity in the right upper lobe consistent with benign residual fibrosis and no evidence of any other metastatic focus in the right lung or elsewhere in the body (Fig 3B).
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Comment
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Cryosurgery causes coagulation necrosis confined to the tissues within the region of probe application and ice-ball formation as a result of the dehydration caused by the intracellular ice crystals that form at very low temperatures. This leads to protein denaturation and solute toxicity within the cell [5, 6]. The extent and degree of tissue destruction correlates with the size of the ice ball and temperatures within it. Liquid nitrogen has a lower freezing point (–196°C) compared with nitrous oxide (–89°C) [7], and therefore it is a more effective coolant. Argon has a faster rate of freezing, but it produces a smaller ice-ball diameter compared with liquid nitrogen. Experimental studies show that cryo-toxicity of tissues correlates with the freezing rate, and in some cases freezing different areas of a tumor for shorter periods of time may achieve greater destruction than one prolonged freeze [8].
Direct cryosurgery of lung lesions requires large probes (5 to 10 mm) able to deliver a low temperature in order to maximize the destruction of large lesions. The device used consists of the console, a container with the cooling agent, and the cryoprobe. Ideally, consoles should be portable and of small size and should be compatible with all types of probes, and also useable within the complex equipment settings of an operating room. The device used for our work is relatively large in size, but it can be used for operations comfortably. Devices being development will be smaller and will provide even more flexibility with regard to the choice of probes.
Sarcomas, such as malignant fibrous histiocytoma, with lung metastases can occasionally be cured by resection of primary and secondary lesions. However, in this particular patient the secondary deposits, although confined to the right lung, extended across the fissures. A pneumonectomy could have achieved adequate clearance but was not appropriate for metastatic disease. Malignant fibrous histiocytoma is the most common soft tissue sarcoma of late adult life [9], with the pleomorphic subtype being the commonest. The 5-year survival rate after appropriate treatment for low-grade, large, soft-tissue sarcomas is 82% to 98%, for intermediate-grade tumors it is 80%, and for high-grade tumors it is 52% to 60% [10].
As a palliative procedure, endobronchial cryosurgery reduces tumor load and helps to maintain airway patency. However, at thoracotomy for planned resection, a significant number of patients have inoperable, obstructing lung carcinoma inaccessible through the tracheobronchial tree. A series of 17 such patients received direct intraoperative cryosurgery using nitrous oxide as the coolant for primary nonsmall cell carcinoma with encouraging results [4]. With this experience and the success of liquid nitrogen cryoablation in other tumors, such as colorectal liver metastases [4], we believe that this case was suitable for direct freezing of the tumors with liquid nitrogen at thoracotomy.
In this particular patient, there was a very significant reduction in tumor mass 12 months post-cryosurgery, and the FDG18 positron-emission tomographic scan showed no evidence of active tumor at the site of cryosurgery, nor any evidence of metastatic disease elsewhere in the body. One of the main problems encountered in cryosurgery of organs such as the liver, kidney and prostate is the limiting, potential irreversible destruction of nearby healthy tissues and organs during cooling. With endobronchial and direct lung cryosurgery, air in the alveoli being a very poor thermal conductor provides a natural insulation hence protection of the adjacent healthy lung tissue during freezing.
The outcome of this case suggests that direct liquid nitrogen cryosurgery may offer symptomatic benefit and potential curative treatment of metastatic malignant fibrous histiocytoma of the lung, especially when resection and endobronchial ablation is not possible, or both are not possible, and chemoradiotherapy is of limited value. Further research is being conducted to assess the possible contribution of cryosurgery to patients with other metastatic lung disease and unresectable primary lung tumors.
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Acknowledgments
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The authors gratefully acknowledge the assistance of Julia Beeson in the preparation of this article.
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References
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- Maiwand MO. Cryotherapy for advanced carcinoma of the trachea and bronchi BMJ 1986;293:181-182.[Abstract/Free Full Text]
- Maiwand MO, Evans JM, Beeson JE. The application of cryosurgery in the treatment of lung cancer Cryobiology 2004;1:55-61.
- Ruers TJM, Joosten J, Jager GJ, Wobbes T. Long-term results of treating hepatic colorectal metastases with cryosurgery Br J Surg 2001;88:844-849.[Medline]
- Maiwand MO, Asimakopoulos G. Cryosurgery for lung cancerclinical results and technical aspects. Technol Cancer Res Treat 2004;3:143-150.[Medline]
- Maiwand MO, Homasson JP. Cryotherapy for tracheobronchial disorders Clin Chest Med 1995;16:427-443.[Medline]
- Rubinsky B. Cryosurgery Ann Rev Biomed Eng 2000;02:157-187.
- Hewitt PM, Zhao J, Akhter J, Morris DL. A comparative study of liquid nitrogen and argon gas cryosurgery systems Cryobiology 1997;35:303-308.[Medline]
- Gage AA, Baust JG. Cryosurgery – a review of recent advances and current issues CryoLetters 2002;23:69-78.[Medline]
- Wang BY, Boag AH, Idrees M, Young ID, Unger PD. Malignant fibrous histiocytomaa case report and review of the literature. Arch Pathol Lab Med 2004;128(4):456-460.[Medline]
- Damron TA, Beauchamp CP, Rougraff BT, Ward WG. Soft tissue lumps and bumps J Bone Joint Surg Am 2003;6:1142-1156.
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Abstract
Introduction
