Va s c u l a r a n d I n t e r ve n t i o n a l R a d i o l o g y • O r i g i n a l R e s e a r c h Bing et al. Cryoablation of Bone and Soft-Tissue Tumors
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Vascular and Interventional Radiology Original Research
Imaging-Guided Percutaneous Cryotherapy of Bone and Soft-Tissue Tumors: What Is the Impact on the Muscles Around the Ablation Site? Fabrice Bing1 Julien Garnon1 Georgia Tsoumakidou1 Iulian Enescu1 Nitin Ramamurthy 2 Afshin Gangi1 Bing F, Garnon J, Tsoumakidou G, Enescu I, Ramamurthy N, Gangi A
Keywords: cryotherapy, MRI, myositis, tumoral ablation DOI:10.2214/AJR.13.11430 Received June 24, 2013; accepted after revision October 10, 2013. 1 Service d’Imagerie Interventionnelle, Hôpital Universitaire de Strasbourg, 1 Place de l’Hôpital, Strasbourg, Alsace 67000, France. Address correspondence to F. Bing ([email protected]). 2 Department of Radiology, University Hospital South Manchester, Wythenshawe Hospital, Wythenshawe, Manchester, United Kingdom.
AJR 2014; 202:1361–1365 0361–803X/14/2026–1361 © American Roentgen Ray Society
OBJECTIVE. The objectives of our study were to evaluate the incidence of muscular injury after cryoablation of bone and soft-tissue tumors, to relate MRI findings to the size of the intramuscular ice ball, and to determine the clinical significance of postcryotherapy myositis. MATERIALS AND METHODS. Between January 2010 and October 2012, 24 bone and soft-tissue lesions (16 pelvic lesions, three shoulder lesions, and five paravertebral lesions) in 21 patients treated by imaging-guided percutaneous cryoablation and followed up with MRI were retrospectively analyzed. Muscular hyperintensity on T2 STIR images was graded as follows: grade 0, no myositis; grade 1, local myositis; grade 2, myositis in less than half of the volume of the muscle; or grade 3, myositis in half of the volume of the muscle or more. The presence of T2 STIR hyperintensity in the muscles surrounding the cryoablation site was correlated with the volume of the intramuscular ice ball. RESULTS. Muscular T2 STIR hyperintensity was observed in 87.5% of cases (grade 0 in 12.5%, grade 1 in 45.8%, grade 2 in 20.8%, and grade 3 in 20.8%). The volume of the intramuscular ice ball and grade of myositis (mean volume: grade 0, 2.8 cm3; grade 1, 9.2 cm3; grade 2, 17.1 cm3; grade 3, 42.9 cm3) were positively correlated in the 24 lesions in the study cohort (r = 0.64, p < 0.001). Only two cases of myositis (grade 3) were symptomatic, and antiinflammatory drugs promoted pain resolution in both cases. CONCLUSION. Muscular injury around the cryoablation site is commonly observed and is correlated with the volume of the ice ball. When muscular injury around the cryoablation site causes pain, the symptoms differ from the initial tumoral pain and can be treated with antiinflammatory drugs.
I
maging-guided percutaneous thermal ablation techniques consist of destroying tumoral cells through heating (radiofrequency, laser, microwave ablation) or freezing (cryoablation) and are increasingly used to treat focal malignancies or benign tumors in a wide range of tissues [1]. The effectiveness of radiofrequency ablation and cryoablation for the treatment of painful bone tumoral lesions has been reported [2–4]. Cryoablation offers potential advantages over radiofrequency ablation, including the ability to continuously monitor the extension of the freezing zone on CT or MRI, and some evidence indicates postprocedural analgesic requirements and hospital stays are reduced [5]. One of the main complications of thermal ablation is collateral damage to the surrounding structures. Despite the use of protective measures, significant local complications—principally in-
volving damage to hollow organs, nervous structures, skin, and treated bone—have been reported [3, 4, 6]. To our knowledge, the effect of cryoablation on surrounding muscle involved in the ice ball has not been described. The purpose of this study was to evaluate the incidence of thermal muscular injury after bone and soft-tissue tumor cryoablation and correlate the severity of follow-up MRI appearances with the final size of the intramuscular ice ball. Possible mechanisms and the key clinical significance of this relatively common finding are discussed. Materials and Methods Between January 2010 and October 2012, 24 bone and soft-tissue tumoral lesions (16 pelvic lesions, three shoulder lesions, and five paravertebral lesions) in 21 patients (mean age ± SD, 53.8 ± 18.6 years) treated by imaging-guided percutaneous cryoablation and followed up with MRI
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Bing et al.
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TABLE 1: Characteristics of the Bone Tumoral Lesions Treated With Cryoablation Lesion No.
Patient Age (y)
Ice-Ball Volume (cm3)
Myositis Gradea
No. of Needles
1
61
Metastasis (rectum)
Sacrum
1.5
0
2
CO2 dissectionb
2
59
3
71
Metastasis (lung)
Thoracic paravertebral
25.2
1
5
None
Metastasis (lung)
Iliac bone
7.0
0
1
None
4 5
26
Aneurysmal cyst
Thoracic paravertebral
7.0
1
2
None
22
Desmoid tumor
Lumbar paravertebral
2.8
1
5
6
None
34
Metastasis (breast)
Iliac bone
4.6
1
1
None
7
54
Metastasis (uterus)
Ischium
5.9
2
3
CO2 dissectionb
8
55
Metastasis (thyroid)
Sacrum
10.0
2
3
None
Type of Lesion
Location of Lesion
Thermoprotective Technique
9
66
Metastasis (thyroid)
Iliac bone
5.7
1
2
None
10
51
Desmoid tumor
Shoulder
0.7
1
3
None
11
69
Desmoid tumor
Iliac bone
48.0
3
13
Open surgery
12
74
Metastasis (thyroid)
Iliac bone
58.0
3
8
CO2 dissectionb
13
43
No diagnosis
Iliac bone
0.0
0
1
None
14
18
Aneurysmal cyst
Lumbar paravertebral
50.2
2
8
CO2 dissectionb
15
77
Metastasis (lung)
Iliac bone
15.5
3
4
None
16
37
Metastasis (uterus)
Pubis
9.4
1
5
None
17
63
Metastasis (thyroid)
Sacrum
36.1
1
3
None
18
63
Metastasis (thyroid)
Ischium
75.2
3
7
CO2 dissectionb
19
84
Metastasis (thyroid)
Sacrum
5.2
1
3
CO2 dissectionb
20
74
Metastasis (bladder)
Iliac bone
17.7
3
4
None
21
51
Desmoid tumor
Shoulder
0.5
1
3
None
22
28
Desmoid tumor
Shoulder
17.5
2
6
CO2 dissectionb
23
64
Metastasis (thyroid)
Lumbar paravertebral
2.1
2
2
None
24
64
Metastasis (thyroid)
Iliac bone
3.6
1
2
None
aMuscular hyperintensity was graded on T2 STIR images as follows: grade 0, no myositis; grade 1, local myositis; grade 2, myositis in less than half of the volume of the
muscle; or grade 3, myositis in half of the volume of the muscle or more.
bInjection of medical carbonic gas through a 22-gauge needle placed adjacent to the lesion.
were retrospectively analyzed (Table 1). Of the 24 lesions, two were considered nonaggressive (aneurysmal cysts), no histologic diagnosis was possible in one case, five lesions were soft-tissue desmoid tumors, and the remaining lesions were bony metastases (Table 1). Informed consent was obtained from all patients, but no approval was required in our hospital for this study. Patients were hospitalized for 48 hours for the cryoablation. Cryoablation was performed with the patient under general anesthesia in the CT (n = 21 lesions) or MRI (n = 3 lesions) interventional suite. After sterile skin preparation was performed, cryoprobes were inserted through a skin nick into the tumoral lesion under CT or MRI guidance and positioned close to the tumor margin 1.5–2 cm apart. The number and type of probes used depended on preoperative tumor volume, but overall we used a mean of 4 ± 2.8 (SD) needles to obtain complete tumor coverage in all cases. In seven cases (29.2%), CO2 dissec-
1362
tion (injection of medical carbonic gas through a 22-gauge needle placed adjacent to the lesion) was used to protect surrounding nervous, vascular, and hollow visceral structures. One additional case necessitated cryoablation under open surgery to avoid internal organ damage around a pelvic desmoid tumor. A single cycle of alternating freezing (10 minutes), thawing (10 minutes), and freezing (10 minutes) was performed, with minor modifications to freezing times and gas flow depending on the rate of ice-ball extension. Ice-ball growth was serially monitored every 2–3 minutes on CT or MRI to guide this process. After the procedure, patients were transferred to a recovery ward and discharged when fit. No antiinflammatory medication was given during or after the treatment.
Calculation of the Intramuscular Ice-Ball Volume The final volume of the ice ball was measured on CT or MR images acquired immediately before retrieval of the cryoprobes. Two formulas were
used to calculate the volume of the intramuscular component depending on the shape of the ice ball. Spherical cap shape (section of a sphere cut off by a plane)—The volume of the intramuscular ice ball, Vim , was calculated as follows if the ice ball had a spherical cap shape: Vim = πh / 6 (3a2 + h2), where h is the height of the cut sphere and a is the radius of the cut sphere (Fig. 1). Triaxial ellipsoid shape (3D representation of a planar ellipse) —The volume of the intramuscular ice ball, Vim , was calculated as follows if the ice ball had an ellipsoid shape: Vim = V − Vit = 4/3 × π× (a × b × c − ait × bit × cit), where V corresponds to the total volume of the ice ball; Vit, to the intratumoral ice ball; a, b, and c, to the total dimensions of the ice ball; and ait, bit, and cit, to the dimensions of the intratumoral iceball component (Fig. 2).
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Cryoablation of Bone and Soft-Tissue Tumors
All patients were admitted for observation after the procedure and discharged within 48 hours according to institutional practice. Clinical follow-up of all patients was undertaken by the treating interventional radiologist or referring physician at an interval of less than 4 weeks after the procedure. Patients presenting with ongoing pain at follow-up were assessed using a visual analog scale to rate the severity of pain from 1 to 10, with 10 being the most severe pain, and functional limitation was classified according to Common Terminology Criteria for Adverse Events (CTCAE) guidelines [7].
MRI-Based Myositis Grading All patients included in this study underwent MRI before the procedure. Preprocedural MRI showed normal intramuscular signal intensity in all cases. A control MRI examination was performed in all patients with an average delay of 28.5 ± 15 (SD) days after cryoablation. Muscular hyperintensity seen on postprocedural T2 STIR studies was interpreted to represent inflammatory myositis and was graded as follows: grade 0, no myositis; grade 1, local myositis (< 1 cm around the ablation site); grade 2, myositis in less than half of the volume of the muscle; or grade 3, myositis in half of the volume of the muscle or more. For each case, the MRI-based myositis grade in the muscles surrounding the cryoablation site was then correlated with the volume of the intramuscular ice ball using the Pearson correlation coefficient (XLSTAT statistical software, version 2012.1; Addinsoft SARL).
Results On T2 STIR imaging, muscular hyperintensity was observed around the cryoablation site in 87.5% of cases (grade 1 in 45.8%, grade 2 in 20.8%, and grade 3 in 20.8%). There was a positive correlation (r = 0.64) between the final volume of the intramuscular ice ball and the myositis grade (mean volume [± SD]: grade 0, 2.8 ± 3.7 cm3; grade 1, 9.2 ± 11.2 cm3; grade 2, 17.1 ± 19.3 cm3; grade 3, 42.9 ± 29.7 cm3) (Fig. 3). Clinically, only two patients (9.5%) were symptomatic. They presented with pain (score on 1- to 10-point visual analog scale: 7 and 8, respectively) that limited their activities (CTCAE grade 2 [1]) and was distinct from the pain that was originally induced by the tumoral lesion. In both cases, grade 3 myositis was observed (Figs. 4 and 5). One patient had to be hospitalized for 6 days more after the cryoablation because of the pain induced by the myositis. Antiinflammatory drugs promoted good pain resolution in both
Fig. 1—Axial CT image obtained during cryoablation of left iliac lung metastasis in 77-year-old man shows measurements for calculation of volume of intramuscular ice ball (Vim ) with spherical cap shape (arrows): Vim = πh / 6(3a2 + h2), where h (white line) is height of cut sphere and a (black line) is radius of cut sphere.
Fig. 2—Axial CT image obtained during cryoablation of right L4 transverse process aneurysmal cyst in 18-year-old man shows measurements for calculation of volume of intramuscular ice ball (Vim ) with triaxial ellipsoid shape. If V corresponds to total volume of ice ball and Vit to volume of intratumoral ice ball, then intramuscular ice-ball volume, Vim , is calculated as follows: Vim = V – Vit = 4/3 × π × (a × b × c – ait × bit × cit ), where a, b, and c correspond to total dimensions of ice ball and ait , bit , and cit correspond to dimensions of intratumoral ice ball; distances between a and b (black line) and between ait and bit (white line) are measured in axial plane; c and cit correspond to heights of ice ball and tumor, respectively, and are not visible on this axial view.
80 70 Ice-Ball Volume (cm3)
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Clinical Follow-Up
60 50 40 30 20 10 0 −10
0
2
1
3
Myositis Grade
Fig. 3—Bar graph shows myositis grades and mean final ice-ball volume for 24 lesions in study group. Muscular hyperintensity on T2 STIR images was graded as follows: grade 0, no myositis; grade 1, local myositis; grade 2, myositis in less than half of volume of muscle; or grade 3, myositis in half of volume of muscle or more. Vertical black bars correspond to SDs. Positive and significant correlation (r = 0.64, p < 0.001) is observed.
patients even though one patient had a poor response to treatment with an opioid analgesia. In that patient, muscular hyperintensity was shown to persist on T2 STIR imaging 1 month after cryoablation. Discussion Imaging-guided percutaneous thermal ablation therapies are effective, increasingly used techniques for the palliative and curative management of a variety of primary and secondary musculoskeletal neoplasms [2–4]. The goal of therapy is to completely encom-
pass the tumor and destroy tumoral cells by heating or freezing without injuring surrounding critical structures. Cryoablation is particularly useful for the management of bone tumoral lesions, where the intraosseous ablative zone is poorly visualized. Clear realtime visualization of the leading edge of the ice ball permits fine control of extraosseous (intramuscular) extension, allowing a 5-mm extraosseous ablative margin to be achieved without endangering adjacent structures. Both CT and MRI may be used for imaging guidance, but the superior soft-tissue contrast res-
AJR:202, June 2014 1363
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Bing et al. olution of MRI makes MRI a particularly complementary modality to use to monitor ice-ball volume and extension [8, 9]. One of the major complications of thermal ablative therapies is unintended damage to surrounding nontarget tissues. Most reported complications have involved hollow visceral, neural, and vascular structures; skin; and treated bone [3, 4, 6, 10]. Clearly, avoiding injury to these structures is of critical importance, and a variety of thermoprotective techniques have been recommended to avoid collateral injury including hydrodissection, CO2 dissection, and continuous temperature monitoring using thermocouples [11, 12]. In contrast, the incidence and significance of muscular injury around the cryoablation site have been considered negligible. Some authors have suggested that cooling of the muscles is not considered a clinical problem because patients are usually asymptomatic [13], whereas others have adopted a less aggressive approach to displacing muscle and soft tissues because of a low associated complication rate [14]. However, to our knowledge, the impact of percutaneous cryoablation on the muscles surrounding the operative site has not been reported. The results of our study show that an inflammatory reaction in the muscles adjacent to the treated bone lesion was commonly observed (87.5% of cases). Moreover, there was a positive correlation between the severity of muscular inflammation and the volume of the intramuscular ice ball present at the end of the procedure. In most cases, patients were asymptomatic. However, after cryo-
A
B
Fig. 4—74-year-old man treated for iliac bone metastasis of thyroid carcinoma (lesion 12 in Table 1). A, On axial CT scan, final volume of ice ball (arrows) measured 58.0 cm 3. B, After cryotherapy, patient described new pain in pelvis. Coronal STIR MR image obtained 5 days after treatment shows diffuse intramuscular edema.
therapy, two patients (9.5%) described new pain in the region of the lesion that was distinct from the pain induced by the original tumor; one patient responded poorly to opioid analgesia. The pain was very severe and lasted 3–6 weeks before the administration of oral antiinflammatory medications (nonsteroidal antiinflammatory drugs [NSAIDs]) was considered. On follow-up MRI, both patients had severe muscular edema involving muscles that were not originally in contact with the ice ball (grade 3 myositis of the proposed classification). In both cases, oral NSAIDs promoted good resolution of symptoms despite the fact that muscle edema persisted on subsequent MRI.
Local complications after thermal ablation of bone and soft-tissue tumors have previously been reported and comprise much-feared neurologic injuries [15] and pathologic fractures of treated bones [4, 6]. Interestingly, neurologic injuries have also been reported after cryocompression therapy in the treatment of athletic trauma [8, 9]. The likely mechanism of local injury to nerves and probably to muscles, as seen in our study, is a direct local thermotoxic effect of the ice ball. Similar to the tumor ablative effect, the thermotoxic effect of the ice ball on muscle may involve intra- and extracellular ice crystal formation, direct damage to cell membranes and organelles, osmotic
A
B
Fig. 5—74-year-old man treated for iliac bone metastasis of vesical carcinoma (lesion 20 in Table 1). A, On axial CT scan obtained with patient in prone position, final volume of ice ball (arrows) measured 17.7 cm 3. B, Patient presented 27 days after cryoablation with intense pain different from pain induced by bone metastasis. Axial STIR MR image obtained with patient in supine position again shows diffuse intramuscular edema that crosses midline.
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Cryoablation of Bone and Soft-Tissue Tumors shifts during the thawing phase, and delayed ischemic effects [16]. However, it is also possible that a component of the observed changes may be systemic or at least locoregional, thus accounting for the changes observed in muscles distant from the cryoablation site. For example, systemic inflammatory reactions have been described in the lung after liver cryoablation and seem to be associated with activation of hepatic nuclear factor–kB protein, ultrastructural changes in the parenchyma, and the release of inflammatory mediators during the thawing phase [17]. Similarly, the “cryoshock phenomenon” (i.e., a complex cytokine-mediated multisystem injury including disseminated intravascular coagulation, renal insufficiency, hepatic failure, and acute respiratory distress syndrome) has also been described after large-volume hepatic ablation [18–20]. Finally, a variety of biochemical derangements have been described after cryotherapy—including transient myoglobinuria in the absence of muscular collateral damage—that suggest that systemic mediators may cause muscular injury [21]. In comparison, radiofrequency ablation is not associated with such systemic deleterious effects probably because radiofrequency ablation destroys intracellular structures, whereas cryoablation disrupts cellular membranes and may permit dispersion of intracellular substances into the affected organ [22]. There are several limitations to this study. First, the proposed MRI-based classification of myositis is an arbitrary grading system to assess intramuscular hyperintensity on T2 STIR imaging. We have not studied intraobserver or interobserver variability. Second, only patients who underwent follow-up MRI after cryoablation were included in this study, limiting the sample size and potentially biasing the incidence of muscular injury. The delay between cryoablation and follow-up MRI was also variable. Third, patient analgesia was not controlled after the procedure, so postprocedural symptoms could potentially have been confounded by variable analgesic therapy. Finally, this analysis is retrospective and a prospective study must be performed to confirm these results. Conclusion We report a high frequency of modifications in muscle signal intensity on MRI
around the cryoablation site of bone and soft-tissue tumors that we interpreted as inflammatory myositis. Our results indicate that muscular injury may be more common than previously thought and that the severity of the injury appears to be related to the final size of the intramuscular ice ball during the procedure. Although most patients with inflammatory myositis after cryoablation are asymptomatic, a minority may experience significant pain that is distinct from the original tumoral pain. Interventional radiologists should try to minimize extension of the ice ball into the muscles; consider the possibility of inflammatory myositis in patients presenting with pain after cryoablation of bone and soft-tissue tumors; and be aware that the administration of NSAIDS may promote good pain resolution even in cases that do not respond to opioid analgesia and that show persistent muscular signal-intensity modifications on MRI. References 1. Ahmed M, Brace CL, Lee FT Jr, Goldberg SN. Principles of and advances in percutaneous ablation. Radiology 2011; 258:351–369 2. Callstrom MR, Atwell TD, Charboneau JW, et al. Painful metastases involving bone: percutaneous image-guided cryoablation—prospective trial interim analysis. Radiology 2006; 241:572–580 3. Dupuy DE, Liu D, Hartfeil D, et al. Percutaneous radiofrequency ablation of painful osseous metastases: a multicenter American College of Radiology Imaging Network trial. Cancer 2010; 116:989–997 4. Goetz MP, Callstrom MR, Charboneau JW, et al. Percutaneous image-guided radiofrequency ablation of painful metastases involving bone: a multicenter study. J Clin Oncol 2004; 22:300–306 5. Thacker PG, Callstrom MR, Curry TB, et al. Palliation of painful metastatic disease involving bone with imaging-guided treatment: comparison of patients’ immediate response to radiofrequency ablation and cryoablation. AJR 2011; 197:510–515 6. Nakatsuka A, Yamakado K, Maeda M, et al. Radiofrequency ablation combined with bone cement injection for the treatment of bone malignancies. J Vasc Interv Radiol 2004; 15:707–712 7. National Cancer Institute website. Common terminology criteria for adverse events, version 4.0. evs. nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-1 4_QuickReference_5x7.pdf. Published May 29, 2009. Accessed February 23, 2014 8. Bassett FH 3rd, Kirkpatrick JS, Engelhardt DL, Malone TR. Cryotherapy-induced nerve injury.
Am J Sports Med 1992; 20:516–518 9. Drez D, Faust DC, Evans JP. Cryotherapy and nerve palsy. Am J Sports Med 1981; 9:256–257 10. Nemcek AA. Complications of radiofrequency ablation of neoplasms. Semin Intervent Radiol 2006; 23:177–187 11. Tsoumakidou G, Buy X, Garnon J, Enescu J, Gangi A. Percutaneous thermal ablation: how to protect the surrounding organs. Tech Vasc Interv Radiol 2011; 14:170–176 12. Buy X, Tok CH, Szwarc D, Bierry G, Gangi A. Thermal protection during percutaneous thermal ablation procedures: interest of carbon dioxide dissection and temperature monitoring. Cardiovasc Intervent Radiol 2009; 32:529–534 13. Silverman SG, Tuncali K, Morrison PR. MR imaging–guided percutaneous tumor ablation. Acad Radiol 2005; 12:1100–1109 14. Bodily KD, Atwell TD, Mandrekar JN, et al. Hydrodisplacement in the percutaneous cryoablation of 50 renal tumors. AJR 2010; 194:779–783 15. Philip A, Gupta S, Ahrar K, Tam AL. A spectrum of nerve injury after thermal ablation: a report of four cases and review of the literature. Cardiovasc Intervent Radiol 2013; 36:1427–1435 16. Weber SM, Lee FT Jr. Cryoablation: history, mechanism of action, and guidance modalities. In: Van Sonnenberg E, MacMullen W, Solbiati L, eds. Tumor ablation: principles and practice. New York, NY: Springer-Verlag, 2005:250–265 17. Chapman WC, Debelak JP, Blackwell TS, et al. Hepatic cryoablation-induced acute lung injury: pulmonary hemodynamic and permeability effects in a sheep model. Arch Surg 2000; 135:667– 672; discussion, 672–673 18. Haddad FF, Chapman WC, Wright JK, Blair TK, Pinson CW. Clinical experience with cryosurgery for advanced hepatobiliary tumors. J Surg Res 1998; 75:103–108 19. Sarantou T, Bilchik A, Ramming KP. Complications of hepatic cryosurgery. Semin Surg Oncol 1998; 14:156–162 20. Stewart GJ, Preketes A, Horton M, Ross WB, Morris DL. Hepatic cryotherapy: double-freeze cycles achieve greater hepatocellular injury in man. Cryobiology 1995; 32:215–219 21. Nair RT, Silverman SG, Tuncali K, Obuchowski NA, vanSonnenberg E, Shankar S. Biochemical and hematologic alterations following percutaneous cryoablation of liver tumors: experience in 48 procedures. Radiology 2008; 248:303–311 22. Chapman WC, Debelak JP, Wright Pinson C, et al. Hepatic cryoablation, but not radiofrequency ablation: results in lung inflammation. Ann Surg 2000; 231:752–761
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Vascular and Interventional Radiology Original Research
Imaging-Guided Percutaneous Cryotherapy of Bone and Soft-Tissue Tumors: What Is the Impact on the Muscles Around the Ablation Site? Fabrice Bing1 Julien Garnon1 Georgia Tsoumakidou1 Iulian Enescu1 Nitin Ramamurthy 2 Afshin Gangi1 Bing F, Garnon J, Tsoumakidou G, Enescu I, Ramamurthy N, Gangi A
Keywords: cryotherapy, MRI, myositis, tumoral ablation DOI:10.2214/AJR.13.11430 Received June 24, 2013; accepted after revision October 10, 2013. 1 Service d’Imagerie Interventionnelle, Hôpital Universitaire de Strasbourg, 1 Place de l’Hôpital, Strasbourg, Alsace 67000, France. Address correspondence to F. Bing ([email protected]). 2 Department of Radiology, University Hospital South Manchester, Wythenshawe Hospital, Wythenshawe, Manchester, United Kingdom.
AJR 2014; 202:1361–1365 0361–803X/14/2026–1361 © American Roentgen Ray Society
OBJECTIVE. The objectives of our study were to evaluate the incidence of muscular injury after cryoablation of bone and soft-tissue tumors, to relate MRI findings to the size of the intramuscular ice ball, and to determine the clinical significance of postcryotherapy myositis. MATERIALS AND METHODS. Between January 2010 and October 2012, 24 bone and soft-tissue lesions (16 pelvic lesions, three shoulder lesions, and five paravertebral lesions) in 21 patients treated by imaging-guided percutaneous cryoablation and followed up with MRI were retrospectively analyzed. Muscular hyperintensity on T2 STIR images was graded as follows: grade 0, no myositis; grade 1, local myositis; grade 2, myositis in less than half of the volume of the muscle; or grade 3, myositis in half of the volume of the muscle or more. The presence of T2 STIR hyperintensity in the muscles surrounding the cryoablation site was correlated with the volume of the intramuscular ice ball. RESULTS. Muscular T2 STIR hyperintensity was observed in 87.5% of cases (grade 0 in 12.5%, grade 1 in 45.8%, grade 2 in 20.8%, and grade 3 in 20.8%). The volume of the intramuscular ice ball and grade of myositis (mean volume: grade 0, 2.8 cm3; grade 1, 9.2 cm3; grade 2, 17.1 cm3; grade 3, 42.9 cm3) were positively correlated in the 24 lesions in the study cohort (r = 0.64, p < 0.001). Only two cases of myositis (grade 3) were symptomatic, and antiinflammatory drugs promoted pain resolution in both cases. CONCLUSION. Muscular injury around the cryoablation site is commonly observed and is correlated with the volume of the ice ball. When muscular injury around the cryoablation site causes pain, the symptoms differ from the initial tumoral pain and can be treated with antiinflammatory drugs.
I
maging-guided percutaneous thermal ablation techniques consist of destroying tumoral cells through heating (radiofrequency, laser, microwave ablation) or freezing (cryoablation) and are increasingly used to treat focal malignancies or benign tumors in a wide range of tissues [1]. The effectiveness of radiofrequency ablation and cryoablation for the treatment of painful bone tumoral lesions has been reported [2–4]. Cryoablation offers potential advantages over radiofrequency ablation, including the ability to continuously monitor the extension of the freezing zone on CT or MRI, and some evidence indicates postprocedural analgesic requirements and hospital stays are reduced [5]. One of the main complications of thermal ablation is collateral damage to the surrounding structures. Despite the use of protective measures, significant local complications—principally in-
volving damage to hollow organs, nervous structures, skin, and treated bone—have been reported [3, 4, 6]. To our knowledge, the effect of cryoablation on surrounding muscle involved in the ice ball has not been described. The purpose of this study was to evaluate the incidence of thermal muscular injury after bone and soft-tissue tumor cryoablation and correlate the severity of follow-up MRI appearances with the final size of the intramuscular ice ball. Possible mechanisms and the key clinical significance of this relatively common finding are discussed. Materials and Methods Between January 2010 and October 2012, 24 bone and soft-tissue tumoral lesions (16 pelvic lesions, three shoulder lesions, and five paravertebral lesions) in 21 patients (mean age ± SD, 53.8 ± 18.6 years) treated by imaging-guided percutaneous cryoablation and followed up with MRI
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TABLE 1: Characteristics of the Bone Tumoral Lesions Treated With Cryoablation Lesion No.
Patient Age (y)
Ice-Ball Volume (cm3)
Myositis Gradea
No. of Needles
1
61
Metastasis (rectum)
Sacrum
1.5
0
2
CO2 dissectionb
2
59
3
71
Metastasis (lung)
Thoracic paravertebral
25.2
1
5
None
Metastasis (lung)
Iliac bone
7.0
0
1
None
4 5
26
Aneurysmal cyst
Thoracic paravertebral
7.0
1
2
None
22
Desmoid tumor
Lumbar paravertebral
2.8
1
5
6
None
34
Metastasis (breast)
Iliac bone
4.6
1
1
None
7
54
Metastasis (uterus)
Ischium
5.9
2
3
CO2 dissectionb
8
55
Metastasis (thyroid)
Sacrum
10.0
2
3
None
Type of Lesion
Location of Lesion
Thermoprotective Technique
9
66
Metastasis (thyroid)
Iliac bone
5.7
1
2
None
10
51
Desmoid tumor
Shoulder
0.7
1
3
None
11
69
Desmoid tumor
Iliac bone
48.0
3
13
Open surgery
12
74
Metastasis (thyroid)
Iliac bone
58.0
3
8
CO2 dissectionb
13
43
No diagnosis
Iliac bone
0.0
0
1
None
14
18
Aneurysmal cyst
Lumbar paravertebral
50.2
2
8
CO2 dissectionb
15
77
Metastasis (lung)
Iliac bone
15.5
3
4
None
16
37
Metastasis (uterus)
Pubis
9.4
1
5
None
17
63
Metastasis (thyroid)
Sacrum
36.1
1
3
None
18
63
Metastasis (thyroid)
Ischium
75.2
3
7
CO2 dissectionb
19
84
Metastasis (thyroid)
Sacrum
5.2
1
3
CO2 dissectionb
20
74
Metastasis (bladder)
Iliac bone
17.7
3
4
None
21
51
Desmoid tumor
Shoulder
0.5
1
3
None
22
28
Desmoid tumor
Shoulder
17.5
2
6
CO2 dissectionb
23
64
Metastasis (thyroid)
Lumbar paravertebral
2.1
2
2
None
24
64
Metastasis (thyroid)
Iliac bone
3.6
1
2
None
aMuscular hyperintensity was graded on T2 STIR images as follows: grade 0, no myositis; grade 1, local myositis; grade 2, myositis in less than half of the volume of the
muscle; or grade 3, myositis in half of the volume of the muscle or more.
bInjection of medical carbonic gas through a 22-gauge needle placed adjacent to the lesion.
were retrospectively analyzed (Table 1). Of the 24 lesions, two were considered nonaggressive (aneurysmal cysts), no histologic diagnosis was possible in one case, five lesions were soft-tissue desmoid tumors, and the remaining lesions were bony metastases (Table 1). Informed consent was obtained from all patients, but no approval was required in our hospital for this study. Patients were hospitalized for 48 hours for the cryoablation. Cryoablation was performed with the patient under general anesthesia in the CT (n = 21 lesions) or MRI (n = 3 lesions) interventional suite. After sterile skin preparation was performed, cryoprobes were inserted through a skin nick into the tumoral lesion under CT or MRI guidance and positioned close to the tumor margin 1.5–2 cm apart. The number and type of probes used depended on preoperative tumor volume, but overall we used a mean of 4 ± 2.8 (SD) needles to obtain complete tumor coverage in all cases. In seven cases (29.2%), CO2 dissec-
1362
tion (injection of medical carbonic gas through a 22-gauge needle placed adjacent to the lesion) was used to protect surrounding nervous, vascular, and hollow visceral structures. One additional case necessitated cryoablation under open surgery to avoid internal organ damage around a pelvic desmoid tumor. A single cycle of alternating freezing (10 minutes), thawing (10 minutes), and freezing (10 minutes) was performed, with minor modifications to freezing times and gas flow depending on the rate of ice-ball extension. Ice-ball growth was serially monitored every 2–3 minutes on CT or MRI to guide this process. After the procedure, patients were transferred to a recovery ward and discharged when fit. No antiinflammatory medication was given during or after the treatment.
Calculation of the Intramuscular Ice-Ball Volume The final volume of the ice ball was measured on CT or MR images acquired immediately before retrieval of the cryoprobes. Two formulas were
used to calculate the volume of the intramuscular component depending on the shape of the ice ball. Spherical cap shape (section of a sphere cut off by a plane)—The volume of the intramuscular ice ball, Vim , was calculated as follows if the ice ball had a spherical cap shape: Vim = πh / 6 (3a2 + h2), where h is the height of the cut sphere and a is the radius of the cut sphere (Fig. 1). Triaxial ellipsoid shape (3D representation of a planar ellipse) —The volume of the intramuscular ice ball, Vim , was calculated as follows if the ice ball had an ellipsoid shape: Vim = V − Vit = 4/3 × π× (a × b × c − ait × bit × cit), where V corresponds to the total volume of the ice ball; Vit, to the intratumoral ice ball; a, b, and c, to the total dimensions of the ice ball; and ait, bit, and cit, to the dimensions of the intratumoral iceball component (Fig. 2).
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Cryoablation of Bone and Soft-Tissue Tumors
All patients were admitted for observation after the procedure and discharged within 48 hours according to institutional practice. Clinical follow-up of all patients was undertaken by the treating interventional radiologist or referring physician at an interval of less than 4 weeks after the procedure. Patients presenting with ongoing pain at follow-up were assessed using a visual analog scale to rate the severity of pain from 1 to 10, with 10 being the most severe pain, and functional limitation was classified according to Common Terminology Criteria for Adverse Events (CTCAE) guidelines [7].
MRI-Based Myositis Grading All patients included in this study underwent MRI before the procedure. Preprocedural MRI showed normal intramuscular signal intensity in all cases. A control MRI examination was performed in all patients with an average delay of 28.5 ± 15 (SD) days after cryoablation. Muscular hyperintensity seen on postprocedural T2 STIR studies was interpreted to represent inflammatory myositis and was graded as follows: grade 0, no myositis; grade 1, local myositis (< 1 cm around the ablation site); grade 2, myositis in less than half of the volume of the muscle; or grade 3, myositis in half of the volume of the muscle or more. For each case, the MRI-based myositis grade in the muscles surrounding the cryoablation site was then correlated with the volume of the intramuscular ice ball using the Pearson correlation coefficient (XLSTAT statistical software, version 2012.1; Addinsoft SARL).
Results On T2 STIR imaging, muscular hyperintensity was observed around the cryoablation site in 87.5% of cases (grade 1 in 45.8%, grade 2 in 20.8%, and grade 3 in 20.8%). There was a positive correlation (r = 0.64) between the final volume of the intramuscular ice ball and the myositis grade (mean volume [± SD]: grade 0, 2.8 ± 3.7 cm3; grade 1, 9.2 ± 11.2 cm3; grade 2, 17.1 ± 19.3 cm3; grade 3, 42.9 ± 29.7 cm3) (Fig. 3). Clinically, only two patients (9.5%) were symptomatic. They presented with pain (score on 1- to 10-point visual analog scale: 7 and 8, respectively) that limited their activities (CTCAE grade 2 [1]) and was distinct from the pain that was originally induced by the tumoral lesion. In both cases, grade 3 myositis was observed (Figs. 4 and 5). One patient had to be hospitalized for 6 days more after the cryoablation because of the pain induced by the myositis. Antiinflammatory drugs promoted good pain resolution in both
Fig. 1—Axial CT image obtained during cryoablation of left iliac lung metastasis in 77-year-old man shows measurements for calculation of volume of intramuscular ice ball (Vim ) with spherical cap shape (arrows): Vim = πh / 6(3a2 + h2), where h (white line) is height of cut sphere and a (black line) is radius of cut sphere.
Fig. 2—Axial CT image obtained during cryoablation of right L4 transverse process aneurysmal cyst in 18-year-old man shows measurements for calculation of volume of intramuscular ice ball (Vim ) with triaxial ellipsoid shape. If V corresponds to total volume of ice ball and Vit to volume of intratumoral ice ball, then intramuscular ice-ball volume, Vim , is calculated as follows: Vim = V – Vit = 4/3 × π × (a × b × c – ait × bit × cit ), where a, b, and c correspond to total dimensions of ice ball and ait , bit , and cit correspond to dimensions of intratumoral ice ball; distances between a and b (black line) and between ait and bit (white line) are measured in axial plane; c and cit correspond to heights of ice ball and tumor, respectively, and are not visible on this axial view.
80 70 Ice-Ball Volume (cm3)
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Clinical Follow-Up
60 50 40 30 20 10 0 −10
0
2
1
3
Myositis Grade
Fig. 3—Bar graph shows myositis grades and mean final ice-ball volume for 24 lesions in study group. Muscular hyperintensity on T2 STIR images was graded as follows: grade 0, no myositis; grade 1, local myositis; grade 2, myositis in less than half of volume of muscle; or grade 3, myositis in half of volume of muscle or more. Vertical black bars correspond to SDs. Positive and significant correlation (r = 0.64, p < 0.001) is observed.
patients even though one patient had a poor response to treatment with an opioid analgesia. In that patient, muscular hyperintensity was shown to persist on T2 STIR imaging 1 month after cryoablation. Discussion Imaging-guided percutaneous thermal ablation therapies are effective, increasingly used techniques for the palliative and curative management of a variety of primary and secondary musculoskeletal neoplasms [2–4]. The goal of therapy is to completely encom-
pass the tumor and destroy tumoral cells by heating or freezing without injuring surrounding critical structures. Cryoablation is particularly useful for the management of bone tumoral lesions, where the intraosseous ablative zone is poorly visualized. Clear realtime visualization of the leading edge of the ice ball permits fine control of extraosseous (intramuscular) extension, allowing a 5-mm extraosseous ablative margin to be achieved without endangering adjacent structures. Both CT and MRI may be used for imaging guidance, but the superior soft-tissue contrast res-
AJR:202, June 2014 1363
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Bing et al. olution of MRI makes MRI a particularly complementary modality to use to monitor ice-ball volume and extension [8, 9]. One of the major complications of thermal ablative therapies is unintended damage to surrounding nontarget tissues. Most reported complications have involved hollow visceral, neural, and vascular structures; skin; and treated bone [3, 4, 6, 10]. Clearly, avoiding injury to these structures is of critical importance, and a variety of thermoprotective techniques have been recommended to avoid collateral injury including hydrodissection, CO2 dissection, and continuous temperature monitoring using thermocouples [11, 12]. In contrast, the incidence and significance of muscular injury around the cryoablation site have been considered negligible. Some authors have suggested that cooling of the muscles is not considered a clinical problem because patients are usually asymptomatic [13], whereas others have adopted a less aggressive approach to displacing muscle and soft tissues because of a low associated complication rate [14]. However, to our knowledge, the impact of percutaneous cryoablation on the muscles surrounding the operative site has not been reported. The results of our study show that an inflammatory reaction in the muscles adjacent to the treated bone lesion was commonly observed (87.5% of cases). Moreover, there was a positive correlation between the severity of muscular inflammation and the volume of the intramuscular ice ball present at the end of the procedure. In most cases, patients were asymptomatic. However, after cryo-
A
B
Fig. 4—74-year-old man treated for iliac bone metastasis of thyroid carcinoma (lesion 12 in Table 1). A, On axial CT scan, final volume of ice ball (arrows) measured 58.0 cm 3. B, After cryotherapy, patient described new pain in pelvis. Coronal STIR MR image obtained 5 days after treatment shows diffuse intramuscular edema.
therapy, two patients (9.5%) described new pain in the region of the lesion that was distinct from the pain induced by the original tumor; one patient responded poorly to opioid analgesia. The pain was very severe and lasted 3–6 weeks before the administration of oral antiinflammatory medications (nonsteroidal antiinflammatory drugs [NSAIDs]) was considered. On follow-up MRI, both patients had severe muscular edema involving muscles that were not originally in contact with the ice ball (grade 3 myositis of the proposed classification). In both cases, oral NSAIDs promoted good resolution of symptoms despite the fact that muscle edema persisted on subsequent MRI.
Local complications after thermal ablation of bone and soft-tissue tumors have previously been reported and comprise much-feared neurologic injuries [15] and pathologic fractures of treated bones [4, 6]. Interestingly, neurologic injuries have also been reported after cryocompression therapy in the treatment of athletic trauma [8, 9]. The likely mechanism of local injury to nerves and probably to muscles, as seen in our study, is a direct local thermotoxic effect of the ice ball. Similar to the tumor ablative effect, the thermotoxic effect of the ice ball on muscle may involve intra- and extracellular ice crystal formation, direct damage to cell membranes and organelles, osmotic
A
B
Fig. 5—74-year-old man treated for iliac bone metastasis of vesical carcinoma (lesion 20 in Table 1). A, On axial CT scan obtained with patient in prone position, final volume of ice ball (arrows) measured 17.7 cm 3. B, Patient presented 27 days after cryoablation with intense pain different from pain induced by bone metastasis. Axial STIR MR image obtained with patient in supine position again shows diffuse intramuscular edema that crosses midline.
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Cryoablation of Bone and Soft-Tissue Tumors shifts during the thawing phase, and delayed ischemic effects [16]. However, it is also possible that a component of the observed changes may be systemic or at least locoregional, thus accounting for the changes observed in muscles distant from the cryoablation site. For example, systemic inflammatory reactions have been described in the lung after liver cryoablation and seem to be associated with activation of hepatic nuclear factor–kB protein, ultrastructural changes in the parenchyma, and the release of inflammatory mediators during the thawing phase [17]. Similarly, the “cryoshock phenomenon” (i.e., a complex cytokine-mediated multisystem injury including disseminated intravascular coagulation, renal insufficiency, hepatic failure, and acute respiratory distress syndrome) has also been described after large-volume hepatic ablation [18–20]. Finally, a variety of biochemical derangements have been described after cryotherapy—including transient myoglobinuria in the absence of muscular collateral damage—that suggest that systemic mediators may cause muscular injury [21]. In comparison, radiofrequency ablation is not associated with such systemic deleterious effects probably because radiofrequency ablation destroys intracellular structures, whereas cryoablation disrupts cellular membranes and may permit dispersion of intracellular substances into the affected organ [22]. There are several limitations to this study. First, the proposed MRI-based classification of myositis is an arbitrary grading system to assess intramuscular hyperintensity on T2 STIR imaging. We have not studied intraobserver or interobserver variability. Second, only patients who underwent follow-up MRI after cryoablation were included in this study, limiting the sample size and potentially biasing the incidence of muscular injury. The delay between cryoablation and follow-up MRI was also variable. Third, patient analgesia was not controlled after the procedure, so postprocedural symptoms could potentially have been confounded by variable analgesic therapy. Finally, this analysis is retrospective and a prospective study must be performed to confirm these results. Conclusion We report a high frequency of modifications in muscle signal intensity on MRI
around the cryoablation site of bone and soft-tissue tumors that we interpreted as inflammatory myositis. Our results indicate that muscular injury may be more common than previously thought and that the severity of the injury appears to be related to the final size of the intramuscular ice ball during the procedure. Although most patients with inflammatory myositis after cryoablation are asymptomatic, a minority may experience significant pain that is distinct from the original tumoral pain. Interventional radiologists should try to minimize extension of the ice ball into the muscles; consider the possibility of inflammatory myositis in patients presenting with pain after cryoablation of bone and soft-tissue tumors; and be aware that the administration of NSAIDS may promote good pain resolution even in cases that do not respond to opioid analgesia and that show persistent muscular signal-intensity modifications on MRI. References 1. Ahmed M, Brace CL, Lee FT Jr, Goldberg SN. Principles of and advances in percutaneous ablation. Radiology 2011; 258:351–369 2. Callstrom MR, Atwell TD, Charboneau JW, et al. Painful metastases involving bone: percutaneous image-guided cryoablation—prospective trial interim analysis. Radiology 2006; 241:572–580 3. Dupuy DE, Liu D, Hartfeil D, et al. Percutaneous radiofrequency ablation of painful osseous metastases: a multicenter American College of Radiology Imaging Network trial. Cancer 2010; 116:989–997 4. Goetz MP, Callstrom MR, Charboneau JW, et al. Percutaneous image-guided radiofrequency ablation of painful metastases involving bone: a multicenter study. J Clin Oncol 2004; 22:300–306 5. Thacker PG, Callstrom MR, Curry TB, et al. Palliation of painful metastatic disease involving bone with imaging-guided treatment: comparison of patients’ immediate response to radiofrequency ablation and cryoablation. AJR 2011; 197:510–515 6. Nakatsuka A, Yamakado K, Maeda M, et al. Radiofrequency ablation combined with bone cement injection for the treatment of bone malignancies. J Vasc Interv Radiol 2004; 15:707–712 7. National Cancer Institute website. Common terminology criteria for adverse events, version 4.0. evs. nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-1 4_QuickReference_5x7.pdf. Published May 29, 2009. Accessed February 23, 2014 8. Bassett FH 3rd, Kirkpatrick JS, Engelhardt DL, Malone TR. Cryotherapy-induced nerve injury.
Am J Sports Med 1992; 20:516–518 9. Drez D, Faust DC, Evans JP. Cryotherapy and nerve palsy. Am J Sports Med 1981; 9:256–257 10. Nemcek AA. Complications of radiofrequency ablation of neoplasms. Semin Intervent Radiol 2006; 23:177–187 11. Tsoumakidou G, Buy X, Garnon J, Enescu J, Gangi A. Percutaneous thermal ablation: how to protect the surrounding organs. Tech Vasc Interv Radiol 2011; 14:170–176 12. Buy X, Tok CH, Szwarc D, Bierry G, Gangi A. Thermal protection during percutaneous thermal ablation procedures: interest of carbon dioxide dissection and temperature monitoring. Cardiovasc Intervent Radiol 2009; 32:529–534 13. Silverman SG, Tuncali K, Morrison PR. MR imaging–guided percutaneous tumor ablation. Acad Radiol 2005; 12:1100–1109 14. Bodily KD, Atwell TD, Mandrekar JN, et al. Hydrodisplacement in the percutaneous cryoablation of 50 renal tumors. AJR 2010; 194:779–783 15. Philip A, Gupta S, Ahrar K, Tam AL. A spectrum of nerve injury after thermal ablation: a report of four cases and review of the literature. Cardiovasc Intervent Radiol 2013; 36:1427–1435 16. Weber SM, Lee FT Jr. Cryoablation: history, mechanism of action, and guidance modalities. In: Van Sonnenberg E, MacMullen W, Solbiati L, eds. Tumor ablation: principles and practice. New York, NY: Springer-Verlag, 2005:250–265 17. Chapman WC, Debelak JP, Blackwell TS, et al. Hepatic cryoablation-induced acute lung injury: pulmonary hemodynamic and permeability effects in a sheep model. Arch Surg 2000; 135:667– 672; discussion, 672–673 18. Haddad FF, Chapman WC, Wright JK, Blair TK, Pinson CW. Clinical experience with cryosurgery for advanced hepatobiliary tumors. J Surg Res 1998; 75:103–108 19. Sarantou T, Bilchik A, Ramming KP. Complications of hepatic cryosurgery. Semin Surg Oncol 1998; 14:156–162 20. Stewart GJ, Preketes A, Horton M, Ross WB, Morris DL. Hepatic cryotherapy: double-freeze cycles achieve greater hepatocellular injury in man. Cryobiology 1995; 32:215–219 21. Nair RT, Silverman SG, Tuncali K, Obuchowski NA, vanSonnenberg E, Shankar S. Biochemical and hematologic alterations following percutaneous cryoablation of liver tumors: experience in 48 procedures. Radiology 2008; 248:303–311 22. Chapman WC, Debelak JP, Wright Pinson C, et al. Hepatic cryoablation, but not radiofrequency ablation: results in lung inflammation. Ann Surg 2000; 231:752–761
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