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The role of embolization in reducing the complications of cryoablation in renal cell carcinoma
Clinical Radiology 69 (2014) 1045e1049
Contents lists available at ScienceDirect
Clinical Radiology journal homepage: www.clinicalradiologyonline.net
The role of embolization in reducing the complications of cryoablation in renal cell carcinoma J.M. Miller*, P. Julien, A. Wachsman, R.J. Van Allan, M.L. Friedman Department of Imaging, Cedars-Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA 90048, USA
art icl e i nformat ion Article history: Received 9 December 2013 Received in revised form 3 May 2014 Accepted 23 May 2014
AIM: To investigate whether embolization prior to cryoablation would decrease morbidity without negative effects on tissue pathology, renal function, or recurrence. MATERIAL AND METHODS: The electronic medical records of all patients undergoing cryoablation for renal cell carcinomas were reviewed for lesion size, pre-ablative renal function, post-ablative renal function, post-ablative complications, recurrence, and quality of biopsy specimen. Comparisons were made between patients who underwent cryoablation (the CryoOnly group) and those who underwent cryoablation after same-day coil embolization of their lesion (the Cryo-Embo group). Further comparison was made between the Cryo-Embo lesions and the subset of larger Cryo-Only lesions (3 cm), which were expected to have a higher natural complication rate. RESULTS: A total of 21 lesions in 19 patients were treated by percutaneous cryoablation (17 Cryo-Only, four Cryo-Embo). Complications were seen in 83% of the large Cryo-Only lesions (average size 3.6 cm), whereas no complication was seen amongst Cryo-Embo lesions (average size 4 cm). Embolization significantly decreased complications between size-matched lesions (p ¼ 0.048) without impacting renal function (p ¼ 1), biopsy quality (p ¼ 1), or recurrence (p ¼ 1). CONCLUSION: Performance of trans-arterial embolization prior to cryoablation of large renal cell carcinomas significantly decreases complications, such as haemorrhage, without a discernible effect on biopsy quality, renal function, or recurrence rate. Ó 2014 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
Introduction Percutaneous ablative therapies, including radiofrequency ablation (RFA), microwave ablation (MWA), and cryoablation, have become the standard method for treatment of renal malignancies in patients unable to undergo operative intervention.1 Recent studies have discussed the * Guarantor and correspondent: J. Miller, Department of Imaging, CedarsSinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA 90048, USA. Tel.: þ1 (310) 423 8000. E-mail address: [email protected] (J.M. Miller).
role of percutaneous ablation as preoperative adjuvants for downsizing renal cancers,2 and shown that ablation has similar effectiveness to that of nephron-sparing surgery.3 Percutaneous therapies may soon become the preferred alternative in the treatment of renal cell carcinomas, even in patients able to tolerate surgical intervention.4 Although RFA and MWA induce coagulative necrosis through heat deposition,5 cryoablation causes osmotic lysis via repeated freeze and thaw cycles.6 These mechanistic differences have become differences in application, as the significant thermal heat sink effects of large vessels near the renal hilum7 have been thought to limit the effectiveness of
0009-9260/$ e see front matter Ó 2014 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.crad.2014.05.110
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J.M. Miller et al. / Clinical Radiology 69 (2014) 1045e1049
heat-based ablative techniques to the treatment of small and more peripheral renal lesions.8 Recent studies in porcine models have sought to reduce this heat sink effect by interruption of renal vasculature, and have reported significant increases in the size and regularity of the ablation zone after arterial occlusion.9,10 Initial trials in humans have shown both a reasonable safety profile and at least equivalent efficacy with RFA and peri-operative embolization compared to RFA alone.11 Higher morbidity is associated with the larger, more peripheral lesions often targeted with cryoablation.12 Significant haemorrhage requiring transfusion is a known complication of percutaneous cryoablation that is likely to increase in frequency as the procedure is more widely adopted.13 Given the proven feasibility of such a process with RFA and MWA, it was postulated that the complication-free success of percutaneous cryoablation could be enhanced by pre-ablative embolization of renal malignancies. Large case series have included incidental reports of subjectively decreased bleeding in the small subsets of patients who underwent pre-ablation embolization,14 and indeed, the procedures are already paired in some centres on a case-by-case basis when anti-coagulation must be restarted soon after ablation.15 The aim of the present study was to investigate whether same-day embolization prior to percutaneous cryoablation would prove technically and logistically feasible, and would demonstrate improved outcomes when treating renal malignancies without negative effects on tissue pathology or safety profile.
Materials and methods Approval for this retrospective analysis of patient treatment records was obtained from the institutional review board, along with a waiver of informed consent. The first percutaneous cryoablation procedures were performed by the Department of Radiology at Cedars-Sinai Medical Center in February 2010 following 4 years of experience with percutaneous RFA. All percutaneous cryoablation procedures were performed with computed tomographic (CT) guidance, with a pre-ablation percutaneous biopsy. Patients in the Cryo-Embo group underwent unilateral diagnostic renal angiogram with transarterial coil embolization of their renal mass(es) immediately prior to biopsy and ablation. Angiography was performed in a standard fashion in order to demonstrate the lesion’s arterial feeder vessel or vessels. Coil embolization was performed within the distal aspect of the feeder vessel in order to spare as much nephron mass as possible and preserve renal function. A completion angiogram was performed, and the patient was then transferred from the angiography suite to the CT procedural suite while under sedation and monitored by an anaesthesiologist. Patients from both groups were monitored post-ablation and discharged if they met standardized discharge criteria. Of note, lesions requiring multiple cryoablation probes were ablated in a simultaneous fashion: cryoablation was only initiated once all probes were correctly positioned.
The electronic medical records (EMRs) of all patients undergoing this procedure for treatment of one or more suspected renal cell carcinomas were included in the study. In circumstances where no pre-ablation serum creatinine value was available, values were obtained from office notes referencing known creatinine values obtained at referring hospitals. Patients were categorized into one of two groups: those that underwent cryoablation therapy alone (“CryoOnly”), and those that were embolized prior to cryoablation (“Cryo-Embo”). EMRs were reviewed for pre-ablative lesion size; pre-ablative renal function (as assessed by most recent preablative serum creatinine level); post-ablative renal function (as assessed by serum creatinine level at follow-up); post-ablative complications; evidence of recurrence; and quality of biopsy specimen. The number of cryoablation probes utilized was recorded. Ablative complication data were treated as a categorical variable and follow-up imaging studies were reviewed. Individual interventions were classified solely on the presence or absence of any complication to indicate damage to healthy renal parenchyma or adjacent organs due to ice-ball formation, including: non-target organ injury, haemorrhage, haematoma, or haematuria. Pre- and post-ablative renal function were compared and an intervention was classified as having caused an acute kidney injury if serum creatinine increased by an absolute value 0.3 mg/dl or greater, an easily assessed threshold utilized in the Acute Kidney Injury Network (AKIN) recommendations,16 which was expected to reflect renal injury from ablation, embolization, and iodinated contrast medium exposure. Comparisons were made between the Cryo-Embo and Cryo-Only groups, as well as between the Cryo-Embo lesions and the subset of larger Cryo-Only lesions (3 cm), which were expected to have a higher natural complication rate. Two-tailed Fisher’s exact probability test was used to compare for the presence or absence of ablative complications, non-diagnostic biopsy, and acute kidney injury; a p-value of 0.05 was considered significant. Two-tailed unpaired t-test was used to compare pre-procedural lesion size with a p-value of 0.05 considered significant. Correlation between presence of complications and number of probes used for therapy was calculated by linear regression. All statistical analysis was performed with Microsoft Excel 2007. Patients 85 years old are referred to as such in order to maintain patient privacy in accordance with HIPAA.
Results A total of 19 patients underwent percutaneous cryoablation of suspected renal cell carcinoma between February 2010 and March 2013. Two separate radiologists performed these ablations (P.J., A.W.). A total of 21 lesions were treated by percutaneous cryoablation. Of this total, 17 lesions in 16 patients were classified Cryo-Only, whereas the remaining four lesions in three patients were classified Cryo-Embo. Two radiologists performed these embolizations (M.F., R.V.A.). The Cryo-Only group averaged 75 years old with 12 male and four female patients; the Cryo-Embo group
J.M. Miller et al. / Clinical Radiology 69 (2014) 1045e1049
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Figure 1 Embolization. (a) Renal artery angiogram demonstrates a large exophytic midpole renal mass. (b) Subselective angiogram of feeder vessel demonstrates isolation of renal mass vasculature. (c) Radiograph demonstrates coil embolization of feeder vessel. (d) Post-embolization renal artery angiogram demonstrates successful embolization with non-perfusion of renal mass.
averaged 71 years old with three male and no female patients. Fig 1 shows serial images from one of the included embolization procedures, showing successful tumour embolization. Fig 2 shows subsequent cryoablation in this same patient, showing confinement of ablational zone to the target lesion once the probes have been removed. Of the 19 total patients, four did not have quantitative preablative serum creatinine levels on record, but were noted in peri-procedural office notes to have “normal” renal function; these values were considered to represent values of serum creatinine no higher than 1.2 mg/dl. One patient (Cryo-Only) was lost to follow-up after the immediate post-procedural period and did not have follow-up laboratory values drawn. Imaging-based follow-up was performed using contrastenhanced CT or magnetic resonance imaging (MRI) at 3 months, 6 months, 1 year, and 2 years after ablation. Two additional patients were lost to follow-up after the initial post-procedural period, but before follow-up imaging could be obtained (one from each group). The average period of follow-up was 15.6 months for the Cryo-Only group, and 7 months for the Cryo-Embo group. No patient from either group was found to have recurrent disease. Two patients had MWA performed on an additional renal lesion concurrent with cryoablation. Two patients did not undergo immediate pre-procedural renal biopsy as lesions
had been successfully biopsied previously; of the lesions that underwent biopsy, all tissue specimens were found to be of diagnostic quality without evidence of necrosis produced by embolization and all were ultimately found to represent renal cell carcinoma or oncocytoma. Results are listed as Table 1. Correlation between the number of probes utilized in therapy and presence or absence of complications was weak (r2 ¼ 0.009). Table 2 compares the complete Cryo-Embo and CryoOnly groups, where average (mean) pre-procedural lesion size was significantly different (Cryo-Only: 2.6 cm, standard deviation: 0.9; Cryo-Embo: 4 cm, standard deviation: 0.88; p ¼ 0.011). No significant difference between the two groups was seen in complication rate (p ¼ 0.090), or rate of acute kidney injury (p ¼ 1). Table 3 compares the Cryo-Embo lesions against the subset of six Cryo-Only lesions measuring at least 3 cm, and average pre-procedural lesion size was comparable (CryoOnly: 3.6 cm, standard deviation: 0.56; Cryo-Embo: 4 cm, p ¼ 0.341). No significant difference in rate of acute kidney injury (p ¼ 1) was seen between the size-matched groups; however, complication rates were seen to differ significantly (p ¼ 0.048), with complications present after cryoablation in 83% of the large lesions treated with cryoablation alone, and no complications seen when treating these large lesions with cryoablation after embolization.
Figure 2 Cryoablation. (a) Pre-ablation axial CT image demonstrates large exophytic midpole renal mass status post-coil embolization. (b) Axial CT image for probe placement demonstrates correct positioning of cryoablation probe within the renal mass. (c) Post-ablation axial CT image demonstrates successful cryoablation of renal mass without apparent damage to surrounding abdominal structures.
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Table 1 Raw data from patients who underwent cryoablation (the Cryo-Only group) and those who underwent cryoablation after same-day coil embolization of their renal cell carcinoma (the Cryo-Embo group). Patient #
Cryo-Only 1 2 3 4 5 6 7 8 9 10c 11 12 13 14c 15 16 Cryo-Embo 17 18 19 a b c
Age
M/F
85þ 59
M M
67 84 61 72 67 84 74 80 85þ 57 85þ 81 78 78
F M M F M M F M F M M M M M
66 77 71
M M M
Size (cm)
3.2 2.5 1.5 3.5 2.3 1.9 2.0 4.7 2.7 2.0 2.9 2.4 1.5 1.7 3.4 3.5 3.2 5.1 4.2 3.0 3.7
Serum creatinine (mg/dl) Pre-ablation
Post-ablation
1.6 “Normal”
2.2 1.3
1.1 1.1 1.0 0.7 “Normal” 1.0 “Normal” 1.2 0.7 4.6 “Normal” 1.0 1.0 1.2
1.2 0.9 0.8 1.2 1.5 0.9 1.2 0.7 5.7 1.3 1.1 1.4 2.0
1.3 2.3 1.1
1.4 2.7 1.2
b
Biopsy qualitya
No. of probes
Complication
þ þ þ þ þ þ þ þ þ þ þ þ þ
3 2 1 2 2 2 2 3 2 1 2 2 1 2 2 2 3
Haemorrhage, haematoma, haematuria None None Haemorrhage Haemorrhage Haemorrhage None Haemorrhage Non-target organ injury None None Haemorrhage, non-target organ injury Haemorrhage None Haematuria Haematoma None
þ þ þ þ
3 2 2 2
None None None None
Biopsy quality: , Did not undergo biopsy at time of cryoablation; þ, successful biopsy. Lost to follow-up. Underwent microwave ablation of additional ipsilateral renal lesion concurrent with cryoablation.
Table 2 Outcome comparisons between patients who underwent cryoablation (the Cryo-Only group) and those who underwent cryoablation after same-day coil embolization of their renal cell carcinoma (the Cryo-Embo group). Patient # Cryo-Only 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 Average Cryo-Embo 17 18 19 Average p-Value
Pre-ablation size
AKI
Complication
3.2 2.5 1.5 3.5 2.3 1.9 2.0 4.7 2.7 2.0 2.9 2.4 1.5 1.7 3.4 3.5 3.2 2.6
Y N N N N N N N Y N N N Y N N Y Y
Y N N Y Y Y N Y Y N N Y Y N Y Y N
5.1 4.2 3.0 3.7 4.0 0.011
N Y N
N N N N
1
0.090
AKI, acute kidney injury.
Discussion Percutaneous cryoablation is a minimally invasive way to treat renal malignancies in patients unable to tolerate surgical intervention. Although the procedure offers a limited risk profile compared to nephrectomy, complications due to bleeding and non-target organ injury do occur. Recent studies Table 3 Outcome comparisons between size-matched renal cell carcinomas in patients who underwent cryoablation (the Cryo-Only group) and those who underwent cryoablation after same-day coil embolization (the Cryo-Embo group). Patient # Cryo-Only 1 3 7 14 15 16 Average Cryo-Embo 17 18 19 Average p-Value
Pre-ablation size
AKI
Complication
3.2 3.5 4.7 3.4 3.5 3.2 3.6
Y N N N Y Y
Y Y Y Y Y N
5.1 4.2 3.0 3.7 4.0 0.341
N Y N
N N N N
1
0.048
AKI, acute kidney injury.
J.M. Miller et al. / Clinical Radiology 69 (2014) 1045e1049
have shown improved ablation effects by pairing other percutaneous therapies with targeted embolization.8e10 The aim of the present retrospective study was to see whether such an approach was also feasible for percutaneous cryoablation. The data show a significant (p ¼ 0.048) decrease in post-cryoablation complications, such as haemorrhage and organ injury, when performed after embolization of large renal lesions (3 cm). An improved complication profile was suggested across all lesion sizes; however, it was less than statistically significant (p ¼ 0.09). Given that cryoablation complications are more likely with larger lesions, the retrospective nature of the study may have resulted in a selection bias. The significant size differences between all lesions receiving cryoablation (Cryo-Only) versus those embolized before ablation (Cryo-Embo) may be indicative of a predisposition to treat larger and seemingly more complex lesions with both embolization and cryoablation therapies. From that perspective, the lack of haemorrhage or haematoma in the embolized lesions is notable, even with the small sample size, as larger lesions may be more likely to bleed after cryoablation. Of the patients undergoing embolization prior to biopsy and cryoablation, there was no effect on biopsy quality or the duration of the patient’s visit: both procedures were able to be performed on the same day. Importantly, there was no evidence of increased incidence of acute kidney injury due to the added step of coil embolization. Performance of trans-arterial embolization prior to cryoablation of large renal cell carcinomas significantly decreases post-procedural complications without a discernible effect on biopsy quality, renal function, or duration of treatment. Given the small sample size of this retrospective review and in light of the increased cost and resources involved in pre-procedural embolization, larger prospective studies are needed before consideration is given to widespread adoption of this practice. Studies beginning to report the results of medium- and long-term follow-up for cryoablation of renal cell carcinoma have detailed recurrence-free survival approaching that of partial nephrectomy.17,18 If these trends can be extrapolated, it seems possible that cryoablation may become the preferred method of management for renal tumours of all sizes and locations, reserving surgical intervention for special circumstances. Although the complication profile is favourable, studies lauding cryoablation are quick to point out that serious risks such as kidney injury, non-target organ injury, and life-threatening haemorrhage are not infrequently encountered. These risks are only likely to increase as cryoablation becomes more common, necessitating appropriate mitigation strategies. Certainly the
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present results indicate that there may be such a role for embolization of large renal cell carcinomas before definitive therapy with cryoablation.
References 1. Venkatesan AM, Wood BJ, Gervais DA. Percutaneous ablation in the kidney. Radiology 2011;261:375e91. 2. Bex A, Kroon BK, de Bryijn R. Is there a role for neoadjuvant targeted therapy to downsize primary tumors for organ sparing strategies in renal cell carcinomas? Int J Surg Oncol 2012;2012:250479. 3. Faddegon S, Cadeddu JA. Does renal mass ablation provide adequate long-term oncologic control? Urol Clin North Am 2012;39:181e90. vi. 4. Graversen JA, Mues AC, Landman J. Laparoscopic ablation of renal neoplasms. J Endourol 2011;25:187e94. 5. Lubner MG, Brace CL, Hinshaw JL, et al. Microwave tumor ablation: mechanism of action, clinical results, and devices. J Vasc Interv Radiol 2010;21(Suppl.):S192e203. 6. Finelli A, Rewcastle JC, Jewett MA. Cryotherapy and radiofrequency ablation: pathophysiologic basis and laboratory studies. Curr Opin Urol 2003;13:187e91. 7. Goldberg SN, Gazelle GS, Mueller PR. Thermal ablation therapy for focal malignancy: a unified approach to underlying principles, techniques, and diagnostic imaging guidance. AJR Am J Roentgenol 2000;174:323e31. 8. Gervais DA, McGovern FJ, Arellano RS, et al. Renal cell carcinoma: clinical experience and technical success with radio-frequency ablation of 42 tumors. Radiology 2003;226:417e24. 9. Sommer CM, Koch V, Pap B, et al. Effect of tissue perfusion on microwave ablation: experimental in vivo study in porcine kidneys. J Vasc Interv Radiol 2011;22:1751e7. 10. Nakasone Y, Ikeda O, Kawanaka K, et al. Radiofrequency ablation in a porcine kidney model: effect of occlusion of the arterial blood supply on ablation temperature, coagulation diameter, and histology. Acta Radiol 2012;53:852e6. 11. Nakasone Y, Kawanaka K, Ikeda O, et al. Sequential combination treatment (arterial embolization and percutaneous radiofrequency ablation) of inoperable renal cell carcinoma: single-center pilot study. Acta Radiol 2012;53:410e4. 12. Lehman DS, Hruby GW, Phillips CK, et al. Laparoscopic renal cryoablation: efficacy and complications for larger renal masses. J Endourol 2008;22:1123e7. 13. Schmit GD, Atwell TD, Callstrom MR, et al. Ice ball fractures during percutaneous renal cryoablation: risk factors and potential implications. J Vasc Interv Radiol 2010;21:1309e12. 14. Atwell TD, Farrell MA, Leibovich BC, et al. Percutaneous renal cryoablation: experience treating 115 tumors. J Urol 2008;179:2136e40. 15. Georgiades CS, Hong K. Kidney ablation. In: Hong K, Georgiades CS, editors. Percutaneous tumor ablation: strategies and techniques. Thieme; 2010. Chapter 7, pp. 132–135. 16. Mehta RL, Kellum JA, Shah SV, et al. Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury. Crit Care 2007;11:R3. 17. Georgiades CS, Rodriguez R. Efficacy and safety of percutaneous cryoablation for stage 1A/B renal cell carcinoma: results of a prospective, single-arm, 5-year study. Cardiovasc Intervent Radiol 2014 Jan 3 [Epub ahead of print]. Available at: http://link.springer.com/article/10.1007/ s00270-013-0831-8 [accessed 01.05.14]. 18. Breen DJ, Bryant TJ, Abbas A, et al. Percutaneous cryoablation of renal tumours: outcomes from 171 tumours in 147 patients. BJU Int 2013;112:758e65.
Contents lists available at ScienceDirect
Clinical Radiology journal homepage: www.clinicalradiologyonline.net
The role of embolization in reducing the complications of cryoablation in renal cell carcinoma J.M. Miller*, P. Julien, A. Wachsman, R.J. Van Allan, M.L. Friedman Department of Imaging, Cedars-Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA 90048, USA
art icl e i nformat ion Article history: Received 9 December 2013 Received in revised form 3 May 2014 Accepted 23 May 2014
AIM: To investigate whether embolization prior to cryoablation would decrease morbidity without negative effects on tissue pathology, renal function, or recurrence. MATERIAL AND METHODS: The electronic medical records of all patients undergoing cryoablation for renal cell carcinomas were reviewed for lesion size, pre-ablative renal function, post-ablative renal function, post-ablative complications, recurrence, and quality of biopsy specimen. Comparisons were made between patients who underwent cryoablation (the CryoOnly group) and those who underwent cryoablation after same-day coil embolization of their lesion (the Cryo-Embo group). Further comparison was made between the Cryo-Embo lesions and the subset of larger Cryo-Only lesions (3 cm), which were expected to have a higher natural complication rate. RESULTS: A total of 21 lesions in 19 patients were treated by percutaneous cryoablation (17 Cryo-Only, four Cryo-Embo). Complications were seen in 83% of the large Cryo-Only lesions (average size 3.6 cm), whereas no complication was seen amongst Cryo-Embo lesions (average size 4 cm). Embolization significantly decreased complications between size-matched lesions (p ¼ 0.048) without impacting renal function (p ¼ 1), biopsy quality (p ¼ 1), or recurrence (p ¼ 1). CONCLUSION: Performance of trans-arterial embolization prior to cryoablation of large renal cell carcinomas significantly decreases complications, such as haemorrhage, without a discernible effect on biopsy quality, renal function, or recurrence rate. Ó 2014 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.
Introduction Percutaneous ablative therapies, including radiofrequency ablation (RFA), microwave ablation (MWA), and cryoablation, have become the standard method for treatment of renal malignancies in patients unable to undergo operative intervention.1 Recent studies have discussed the * Guarantor and correspondent: J. Miller, Department of Imaging, CedarsSinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA 90048, USA. Tel.: þ1 (310) 423 8000. E-mail address: [email protected] (J.M. Miller).
role of percutaneous ablation as preoperative adjuvants for downsizing renal cancers,2 and shown that ablation has similar effectiveness to that of nephron-sparing surgery.3 Percutaneous therapies may soon become the preferred alternative in the treatment of renal cell carcinomas, even in patients able to tolerate surgical intervention.4 Although RFA and MWA induce coagulative necrosis through heat deposition,5 cryoablation causes osmotic lysis via repeated freeze and thaw cycles.6 These mechanistic differences have become differences in application, as the significant thermal heat sink effects of large vessels near the renal hilum7 have been thought to limit the effectiveness of
0009-9260/$ e see front matter Ó 2014 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.crad.2014.05.110
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J.M. Miller et al. / Clinical Radiology 69 (2014) 1045e1049
heat-based ablative techniques to the treatment of small and more peripheral renal lesions.8 Recent studies in porcine models have sought to reduce this heat sink effect by interruption of renal vasculature, and have reported significant increases in the size and regularity of the ablation zone after arterial occlusion.9,10 Initial trials in humans have shown both a reasonable safety profile and at least equivalent efficacy with RFA and peri-operative embolization compared to RFA alone.11 Higher morbidity is associated with the larger, more peripheral lesions often targeted with cryoablation.12 Significant haemorrhage requiring transfusion is a known complication of percutaneous cryoablation that is likely to increase in frequency as the procedure is more widely adopted.13 Given the proven feasibility of such a process with RFA and MWA, it was postulated that the complication-free success of percutaneous cryoablation could be enhanced by pre-ablative embolization of renal malignancies. Large case series have included incidental reports of subjectively decreased bleeding in the small subsets of patients who underwent pre-ablation embolization,14 and indeed, the procedures are already paired in some centres on a case-by-case basis when anti-coagulation must be restarted soon after ablation.15 The aim of the present study was to investigate whether same-day embolization prior to percutaneous cryoablation would prove technically and logistically feasible, and would demonstrate improved outcomes when treating renal malignancies without negative effects on tissue pathology or safety profile.
Materials and methods Approval for this retrospective analysis of patient treatment records was obtained from the institutional review board, along with a waiver of informed consent. The first percutaneous cryoablation procedures were performed by the Department of Radiology at Cedars-Sinai Medical Center in February 2010 following 4 years of experience with percutaneous RFA. All percutaneous cryoablation procedures were performed with computed tomographic (CT) guidance, with a pre-ablation percutaneous biopsy. Patients in the Cryo-Embo group underwent unilateral diagnostic renal angiogram with transarterial coil embolization of their renal mass(es) immediately prior to biopsy and ablation. Angiography was performed in a standard fashion in order to demonstrate the lesion’s arterial feeder vessel or vessels. Coil embolization was performed within the distal aspect of the feeder vessel in order to spare as much nephron mass as possible and preserve renal function. A completion angiogram was performed, and the patient was then transferred from the angiography suite to the CT procedural suite while under sedation and monitored by an anaesthesiologist. Patients from both groups were monitored post-ablation and discharged if they met standardized discharge criteria. Of note, lesions requiring multiple cryoablation probes were ablated in a simultaneous fashion: cryoablation was only initiated once all probes were correctly positioned.
The electronic medical records (EMRs) of all patients undergoing this procedure for treatment of one or more suspected renal cell carcinomas were included in the study. In circumstances where no pre-ablation serum creatinine value was available, values were obtained from office notes referencing known creatinine values obtained at referring hospitals. Patients were categorized into one of two groups: those that underwent cryoablation therapy alone (“CryoOnly”), and those that were embolized prior to cryoablation (“Cryo-Embo”). EMRs were reviewed for pre-ablative lesion size; pre-ablative renal function (as assessed by most recent preablative serum creatinine level); post-ablative renal function (as assessed by serum creatinine level at follow-up); post-ablative complications; evidence of recurrence; and quality of biopsy specimen. The number of cryoablation probes utilized was recorded. Ablative complication data were treated as a categorical variable and follow-up imaging studies were reviewed. Individual interventions were classified solely on the presence or absence of any complication to indicate damage to healthy renal parenchyma or adjacent organs due to ice-ball formation, including: non-target organ injury, haemorrhage, haematoma, or haematuria. Pre- and post-ablative renal function were compared and an intervention was classified as having caused an acute kidney injury if serum creatinine increased by an absolute value 0.3 mg/dl or greater, an easily assessed threshold utilized in the Acute Kidney Injury Network (AKIN) recommendations,16 which was expected to reflect renal injury from ablation, embolization, and iodinated contrast medium exposure. Comparisons were made between the Cryo-Embo and Cryo-Only groups, as well as between the Cryo-Embo lesions and the subset of larger Cryo-Only lesions (3 cm), which were expected to have a higher natural complication rate. Two-tailed Fisher’s exact probability test was used to compare for the presence or absence of ablative complications, non-diagnostic biopsy, and acute kidney injury; a p-value of 0.05 was considered significant. Two-tailed unpaired t-test was used to compare pre-procedural lesion size with a p-value of 0.05 considered significant. Correlation between presence of complications and number of probes used for therapy was calculated by linear regression. All statistical analysis was performed with Microsoft Excel 2007. Patients 85 years old are referred to as such in order to maintain patient privacy in accordance with HIPAA.
Results A total of 19 patients underwent percutaneous cryoablation of suspected renal cell carcinoma between February 2010 and March 2013. Two separate radiologists performed these ablations (P.J., A.W.). A total of 21 lesions were treated by percutaneous cryoablation. Of this total, 17 lesions in 16 patients were classified Cryo-Only, whereas the remaining four lesions in three patients were classified Cryo-Embo. Two radiologists performed these embolizations (M.F., R.V.A.). The Cryo-Only group averaged 75 years old with 12 male and four female patients; the Cryo-Embo group
J.M. Miller et al. / Clinical Radiology 69 (2014) 1045e1049
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Figure 1 Embolization. (a) Renal artery angiogram demonstrates a large exophytic midpole renal mass. (b) Subselective angiogram of feeder vessel demonstrates isolation of renal mass vasculature. (c) Radiograph demonstrates coil embolization of feeder vessel. (d) Post-embolization renal artery angiogram demonstrates successful embolization with non-perfusion of renal mass.
averaged 71 years old with three male and no female patients. Fig 1 shows serial images from one of the included embolization procedures, showing successful tumour embolization. Fig 2 shows subsequent cryoablation in this same patient, showing confinement of ablational zone to the target lesion once the probes have been removed. Of the 19 total patients, four did not have quantitative preablative serum creatinine levels on record, but were noted in peri-procedural office notes to have “normal” renal function; these values were considered to represent values of serum creatinine no higher than 1.2 mg/dl. One patient (Cryo-Only) was lost to follow-up after the immediate post-procedural period and did not have follow-up laboratory values drawn. Imaging-based follow-up was performed using contrastenhanced CT or magnetic resonance imaging (MRI) at 3 months, 6 months, 1 year, and 2 years after ablation. Two additional patients were lost to follow-up after the initial post-procedural period, but before follow-up imaging could be obtained (one from each group). The average period of follow-up was 15.6 months for the Cryo-Only group, and 7 months for the Cryo-Embo group. No patient from either group was found to have recurrent disease. Two patients had MWA performed on an additional renal lesion concurrent with cryoablation. Two patients did not undergo immediate pre-procedural renal biopsy as lesions
had been successfully biopsied previously; of the lesions that underwent biopsy, all tissue specimens were found to be of diagnostic quality without evidence of necrosis produced by embolization and all were ultimately found to represent renal cell carcinoma or oncocytoma. Results are listed as Table 1. Correlation between the number of probes utilized in therapy and presence or absence of complications was weak (r2 ¼ 0.009). Table 2 compares the complete Cryo-Embo and CryoOnly groups, where average (mean) pre-procedural lesion size was significantly different (Cryo-Only: 2.6 cm, standard deviation: 0.9; Cryo-Embo: 4 cm, standard deviation: 0.88; p ¼ 0.011). No significant difference between the two groups was seen in complication rate (p ¼ 0.090), or rate of acute kidney injury (p ¼ 1). Table 3 compares the Cryo-Embo lesions against the subset of six Cryo-Only lesions measuring at least 3 cm, and average pre-procedural lesion size was comparable (CryoOnly: 3.6 cm, standard deviation: 0.56; Cryo-Embo: 4 cm, p ¼ 0.341). No significant difference in rate of acute kidney injury (p ¼ 1) was seen between the size-matched groups; however, complication rates were seen to differ significantly (p ¼ 0.048), with complications present after cryoablation in 83% of the large lesions treated with cryoablation alone, and no complications seen when treating these large lesions with cryoablation after embolization.
Figure 2 Cryoablation. (a) Pre-ablation axial CT image demonstrates large exophytic midpole renal mass status post-coil embolization. (b) Axial CT image for probe placement demonstrates correct positioning of cryoablation probe within the renal mass. (c) Post-ablation axial CT image demonstrates successful cryoablation of renal mass without apparent damage to surrounding abdominal structures.
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Table 1 Raw data from patients who underwent cryoablation (the Cryo-Only group) and those who underwent cryoablation after same-day coil embolization of their renal cell carcinoma (the Cryo-Embo group). Patient #
Cryo-Only 1 2 3 4 5 6 7 8 9 10c 11 12 13 14c 15 16 Cryo-Embo 17 18 19 a b c
Age
M/F
85þ 59
M M
67 84 61 72 67 84 74 80 85þ 57 85þ 81 78 78
F M M F M M F M F M M M M M
66 77 71
M M M
Size (cm)
3.2 2.5 1.5 3.5 2.3 1.9 2.0 4.7 2.7 2.0 2.9 2.4 1.5 1.7 3.4 3.5 3.2 5.1 4.2 3.0 3.7
Serum creatinine (mg/dl) Pre-ablation
Post-ablation
1.6 “Normal”
2.2 1.3
1.1 1.1 1.0 0.7 “Normal” 1.0 “Normal” 1.2 0.7 4.6 “Normal” 1.0 1.0 1.2
1.2 0.9 0.8 1.2 1.5 0.9 1.2 0.7 5.7 1.3 1.1 1.4 2.0
1.3 2.3 1.1
1.4 2.7 1.2
b
Biopsy qualitya
No. of probes
Complication
þ þ þ þ þ þ þ þ þ þ þ þ þ
3 2 1 2 2 2 2 3 2 1 2 2 1 2 2 2 3
Haemorrhage, haematoma, haematuria None None Haemorrhage Haemorrhage Haemorrhage None Haemorrhage Non-target organ injury None None Haemorrhage, non-target organ injury Haemorrhage None Haematuria Haematoma None
þ þ þ þ
3 2 2 2
None None None None
Biopsy quality: , Did not undergo biopsy at time of cryoablation; þ, successful biopsy. Lost to follow-up. Underwent microwave ablation of additional ipsilateral renal lesion concurrent with cryoablation.
Table 2 Outcome comparisons between patients who underwent cryoablation (the Cryo-Only group) and those who underwent cryoablation after same-day coil embolization of their renal cell carcinoma (the Cryo-Embo group). Patient # Cryo-Only 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 Average Cryo-Embo 17 18 19 Average p-Value
Pre-ablation size
AKI
Complication
3.2 2.5 1.5 3.5 2.3 1.9 2.0 4.7 2.7 2.0 2.9 2.4 1.5 1.7 3.4 3.5 3.2 2.6
Y N N N N N N N Y N N N Y N N Y Y
Y N N Y Y Y N Y Y N N Y Y N Y Y N
5.1 4.2 3.0 3.7 4.0 0.011
N Y N
N N N N
1
0.090
AKI, acute kidney injury.
Discussion Percutaneous cryoablation is a minimally invasive way to treat renal malignancies in patients unable to tolerate surgical intervention. Although the procedure offers a limited risk profile compared to nephrectomy, complications due to bleeding and non-target organ injury do occur. Recent studies Table 3 Outcome comparisons between size-matched renal cell carcinomas in patients who underwent cryoablation (the Cryo-Only group) and those who underwent cryoablation after same-day coil embolization (the Cryo-Embo group). Patient # Cryo-Only 1 3 7 14 15 16 Average Cryo-Embo 17 18 19 Average p-Value
Pre-ablation size
AKI
Complication
3.2 3.5 4.7 3.4 3.5 3.2 3.6
Y N N N Y Y
Y Y Y Y Y N
5.1 4.2 3.0 3.7 4.0 0.341
N Y N
N N N N
1
0.048
AKI, acute kidney injury.
J.M. Miller et al. / Clinical Radiology 69 (2014) 1045e1049
have shown improved ablation effects by pairing other percutaneous therapies with targeted embolization.8e10 The aim of the present retrospective study was to see whether such an approach was also feasible for percutaneous cryoablation. The data show a significant (p ¼ 0.048) decrease in post-cryoablation complications, such as haemorrhage and organ injury, when performed after embolization of large renal lesions (3 cm). An improved complication profile was suggested across all lesion sizes; however, it was less than statistically significant (p ¼ 0.09). Given that cryoablation complications are more likely with larger lesions, the retrospective nature of the study may have resulted in a selection bias. The significant size differences between all lesions receiving cryoablation (Cryo-Only) versus those embolized before ablation (Cryo-Embo) may be indicative of a predisposition to treat larger and seemingly more complex lesions with both embolization and cryoablation therapies. From that perspective, the lack of haemorrhage or haematoma in the embolized lesions is notable, even with the small sample size, as larger lesions may be more likely to bleed after cryoablation. Of the patients undergoing embolization prior to biopsy and cryoablation, there was no effect on biopsy quality or the duration of the patient’s visit: both procedures were able to be performed on the same day. Importantly, there was no evidence of increased incidence of acute kidney injury due to the added step of coil embolization. Performance of trans-arterial embolization prior to cryoablation of large renal cell carcinomas significantly decreases post-procedural complications without a discernible effect on biopsy quality, renal function, or duration of treatment. Given the small sample size of this retrospective review and in light of the increased cost and resources involved in pre-procedural embolization, larger prospective studies are needed before consideration is given to widespread adoption of this practice. Studies beginning to report the results of medium- and long-term follow-up for cryoablation of renal cell carcinoma have detailed recurrence-free survival approaching that of partial nephrectomy.17,18 If these trends can be extrapolated, it seems possible that cryoablation may become the preferred method of management for renal tumours of all sizes and locations, reserving surgical intervention for special circumstances. Although the complication profile is favourable, studies lauding cryoablation are quick to point out that serious risks such as kidney injury, non-target organ injury, and life-threatening haemorrhage are not infrequently encountered. These risks are only likely to increase as cryoablation becomes more common, necessitating appropriate mitigation strategies. Certainly the
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present results indicate that there may be such a role for embolization of large renal cell carcinomas before definitive therapy with cryoablation.
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