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Original Report |
1 All authors: Department of Diagnostic Imaging, Brown Medical School, Rhode Island Hospital, 593 Eddy St., Providence, RI 02903.
Received March 4, 2004;
accepted after revision June 14, 2004.
Address correspondence to D. E. Dupuy
(ddupuy{at}lifespan.org).
Abstract
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CONCLUSION. Preliminary results suggest that percutaneous cryoablation may offer a minimally invasive alternative for relief of symptomatic metastatic disease in patients for whom conventional therapy failed.
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Recurrent local or metastatic disease to extraabdominal sites is a source of significant morbidity. Symptoms include local pain and mass effect on adjacent structures. Surgical resection of locally invasive disease is often not an option because of poorly defined margins, involvement of adjacent critical structures, inaccessible location, and comorbid conditions. Long recovery time and complications may also follow complicated surgical resections. Percutaneous therapy potentially offers these patients palliation and improved quality of life with minimal recovery time.
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Cryoablation
Cryoablation was performed using an argon-based cryoablation system
(Endocare, Mountainview) and 2.4-mm percutaneous applicators. The applicators
have a 5-cm active tip and create a freeze zone of approximately 5 x
1.52.0 cm (length x width). Up to eight applicators were placed
simultaneously (range, 58 applicators) 2 cm apart in the patient.
Temperatures were measured during the procedure with an attached thermocoupler
(range, -94°C to -136°C). Placement was planned according to the size
of the tumor and margin of the tumor and of destroyed bone to achieve pain
palliation. Each patient underwent multiple 8- to 11-min freeze cycles, each
followed by a 5-min active helium thaw. The low-density changes within the
tissue were measured to approximate the size of the ablated region. Visible
treatment margins were routinely extended 1 cm beyond the tumor during
cryoablation. The terms "freeze zone," "ice ball," and
"treatment area" are used interchangeably in the text and refer to
the area of decreased density visualized on CT after the tissue has been
frozen.
Patients and Treatment:
The first patient was a 57-year-old man diagnosed with rectal cancer who
underwent primary resection and diverting colostomy
(Table 1). Seven years later,
he was diagnosed with local recurrence in the presacral region.
Abdominoperoneal resection and placement of a right distal ureteral stent were
performed followed by local radiation therapy. CT scans obtained 1 year later
revealed an enlarging presacral mass and a chemotherapy regimen of irinotecan,
5-fluorouracil, and leucovorin was initiated. The patient subsequently
developed two pulmonary metastases; each was treated twice with percutaneous
radiofrequency ablation. Follow-up CT examination showed continued enlargement
of the presacral mass with bony invasion and increased activity on PET.
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The painful 9 x 5 x 7.5 cm mass was treated with CT-guided percutaneous cryoablation (Figs. 1A, 1B, 1C, 1D, and 1E) with the patient under conscious sedation. Eight cryoapplicators were placed into the mass, and two 10-min freezethaw cycles were performed. A 10 x 5 x 7 cm freeze zone was measured on CT performed immediately after treatment (Fig. 1B). The patient was transferred to the recovery room in stable condition and discharged after 2 hr with no immediate complications. He reported immediate improvement in preprocedure pain. Twelve months after treatment, he continues to have no pain and has not undergone follow-up imaging.
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The second patient was a 20-year-old woman with a nonosseous Ewing's sarcoma arising from the soft tissues adjacent to the pubic symphysis (Table 1). The 12-cm tumor was surgically resected with no reported evidence of metastatic disease. The patient refused chemotherapy and radiation therapy. Follow-up CT scans revealed no residual disease until 4 years later when a local recurrence in the pelvis was documented by sonographically guided percutaneous biopsy. The patient again refused chemotherapy and radiation therapy. Shortly thereafter, she developed abdominal pain; weight loss; and right hydronephrosis, which was treated with ureteral stent placement. CT examination 28 months later showed a 13 x 15 x 17 cm right pelvic mass with destructive changes in the right superior pubic ramus and pubic symphysis.
The patient was referred to our department for palliative CT-guided percutaneous cryoablation. With the patient under general anesthesia at her request, seven cryoapplicators were placed into the mass and an 11-min freezethaw cycle followed by a 5-min thaw was performed. The applicators were then repositioned, and a second 8-min freezethaw cycle was performed. The freeze zone was 8 x 12 x 6 cm on CT performed immediately after treatment. The patient was transferred to the recovery room in stable condition. After 2 hr of uneventful observation, she was transferred back to the medical floor for treatment of preexisting anemia and pain. She reported that her pain was improved, and she was discharged 3 days after the procedure. Four weeks after the procedure, she was ambulating and had further improvement in her pain. She died 1 month later.
The third patient was a 55-year-old woman diagnosed with adenocarcinoma of the left breast (Table 1). Modified radical mastectomy was performed with negative resection margins, and three of 10 axillary lymph nodes were positive for malignancy. She then completed six cycles of chemotherapy with cyclophosphamide, methotrexate, and 5-fluorouracil and was placed on tamoxifen. She did well until 4 years later when she developed a palpable lump in the left supraclavicular region. Biopsy was positive for metastatic adenocarcinoma, consistent with breast origin. Surgical excision was performed followed by postoperative external beam radiation (total dose, 60 Gy). Ten months later, she developed left arm pain from a brachial plexopathy. Gadolinium-enhanced MRI depicted a 3 x 3 x 3 cm enhancing soft-tissue mass deep in relation to the pectoralis muscle in the region of the left brachial plexus in the area of recent radiation therapy (Fig. 2C). CT-guided biopsy confirmed metastatic adenocarcinoma.
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Patient 3 was referred for palliative treatment with CT-guided percutaneous cryoablation (Figs. 2A, 2B, 2C, and 2D), which was performed while she was under conscious sedation. The patient was advised that damage to the brachial plexus during treatment was highly likely, but she agreed to undergo the treatment because of the severe pain. Six cryoapplicators were placed into the mass, and two consecutive 8-min freezethaw cycles were performed. The applicators were repositioned, and a third 8-min freezethaw cycle was performed. A freeze zone of 7 x 5 x 6 cm was obtained (Fig. 2B). She was observed in the recovery area for 2 hr after the procedure. Before she was discharged, she reported an improvement in her left arm pain and some improvement in motor function. At a follow-up office visit, she had subsequently lost most motor function and sensation in that arm but was essentially pain-free. She was aware of this possibility before the procedure and was pleased with the treatment outcome. Follow-up MRI performed 7 weeks after treatment showed no change in tumor size with a persistent 1-cm area of enhancement surrounding the left subclavian artery (Fig. 2D). She continues to report no pain 13 months after cryoablation.
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The fourth patient was a 49-year-old man with colon cancer (Table 1). He underwent right hemicolectomy and intraoperative radiofrequency ablation of a single 9-mm liver metastasis. He received five cycles of chemotherapy with 5-fluorouracil, leucovorin, and irinotecan. One year later, he developed pain in the medial posterior mid back and CT revealed a 4 x 7 x 8 cm soft-tissue mass causing bony destruction of the posterior right 10th and 11th ribs. Biopsy results indicated the mass was metastatic colon carcinoma. He was treated with radiation therapy (total dose, 50 Gy) and placed on a chemotherapy regimen of five cycles of 5-fluorouracil, leucovorin, and oxaliplatin. CT-guided percutaneous radiofrequency ablation of the chest wall mass was performed 1 month later. He experienced a moderate amount of procedural pain, and the treatment was terminated prematurely. Follow-up CT examination 6 months later showed an increase in size of the mass, now measuring 9 x 7.5 x 6 cm.
Because of the size of the lesion and the pain associated with the previous radiofrequency ablation, the patient was treated with CT-guided percutaneous cryoablation under laryngeal mask anesthesia. Five cryoapplicators were placed into the anterolateral component of the mass, and two 8-min freezethaw cycles were performed. The probes were then repositioned into the medial aspect of the mass, and two 8-min freezethaw cycles were repeated. A freeze zone of 9 x 8 x 8 cm was obtained. The patient was transferred to the recovery room after the procedure and observed for 2 hr. He was discharged from the hospital with no immediate complications. One week after the procedure, he reported improved tolerance of his pain, but he experienced a change in the quality of the preprocedure pain that required the addition of the analgesic gabapentin to his medical therapy for neuropathic pain. Despite improvement in pain tolerance, follow-up CT examination 3.5 months after treatment showed an increase in the craniocaudal dimension to approximately 12 cm with no change in the transverse or anteroposterior extent. The patient underwent emergency thoracic laminectomy for decompression of metastatic disease 8 months after treatment.
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All patients tolerated the procedure well. None of the patients developed significant bleeding or vascular injury. Nerve damage to the brachial plexus did occur during treatment of the third patient. While this damage may be considered a complication, it was an expected outcome and was acceptable to the patient.
All patients had follow-up office visits or telephone contact (range, 213 months; median, 12.5 months) and imaging as described previously.
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Percutaneous radiofrequency ablation of both intra- and extraabdominal primary and metastatic lesions has been described using both CT and sonographic guidance [1013]. Radiofrequency ablation offers a minimally invasive local treatment option but can be limited by local procedural pain, poor real-time visualization of treatment effects under CT guidance, and limited ablation volumes. Cryoablation offers a few specific advantages over radiofrequency ablation, such as probable decreased procedure-associated pain [17] and real-time visualization of the treatment area. Although the cryoablation applicators are slightly less expensive than the radiofrequency ablation electrodes, depending on tumor size, more applicators are used in cryoablation offsetting the cost advantage. In addition, the start-up costs of a cryoablation system are slightly higher because argon gas is required.
The ability to observe the treatment margins in real-time is an essential attribute of an effective imaging-guided treatment technique. Multiple prior articles have described the appearance of frozen tissue on sonography, CT, and MRI [3, 9, 1820]. The use of sonographic guidance is limited because only the near edge of frozen tissue is adequately visualized given that sound waves do not adequately penetrate frozen tissue. This problem is not a significant one intraoperatively because the probe can be moved into other planes, but it poses significant difficulty when the percutaneous approach is used. Conversely, CT guidance with CT fluoroscopy offers clear visualization of the entire treatment margin in real-time, which is critical when treating lesions near vital organs, hollow viscera, and the biliary tree and urinary tract where posttreatment strictures can occur. The margins of the frozen tissue seen on CT do not represent the true margins of tumor necrosis because temperatures at the advancing outer edge of the ice ball are sublethal [21]. Therefore, we attempted to extend the margin of frozen tissue 1 cm beyond the tumor margins seen on CT.
The use of multiple small (2.4-mm) tip applicators allows substantial control over the size and shape of the treatment area. This is especially important when treating lesions with irregular margins. We placed applicators at a distance of approximately 2 cm apart within the lesion and attempted to place applicators within 1 cm of the edge of visible tumor to achieve adequate treatment margins. The freeze zones blended smoothly between applicators giving the area of frozen tissue a homogeneous appearance on posttreatment CT. We did have difficulty achieving adequate freezing of a tumor adjacent to a large vessel in the third patient. This is thought to be secondary to what we refer to as the "cold sink" effect where the continuous inflow of blood at body temperature does not allow adequate freezing of the adjacent tissue. This was confirmed on follow-up imaging where there was residual enhancing tumor adjacent to the left subclavian artery (Fig. 2D).
Our study is limited by a small patient population and limited imaging follow-up. Further investigation with larger treatment groups, longterm follow-up, and the use of a standardized pain-reporting scale is necessary for proof of efficacy. The patients in our report had already failed conventional therapy and had very advanced disease with large locally aggressive lesions. Our preliminary results suggest that percutaneous imaging-guided cryoablation is well tolerated and may play a role in the treatment of symptomatic local metastases.
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