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1 Note: This copy is for your personal, non-commercial use only. To order presentation-ready copies for distribution to your colleagues or clients, contact us at Brian T. Welch, BS Thomas D. Atwell, MD Douglas A. Nichols, MD C. Thomas Wass, MD Matthew R. Callstrom, MD Bradley C. Leibovich, MD Paul C. Carpenter, MD Jayawant N. Mandrekar, PhD J. William Charboneau, MD Percutaneous Image-guided Adrenal Cryoablation: Procedural Considerations and Technical Success1 Purpose: Materials and Methods: To assess safety, technical success, complications, and hemodynamic changes associated with the adrenal cryoablation procedure. This retrospective review was approved by the institutional review board, with waiver of informed consent, and was compliant with the Health Insurance Portability and Accountability Act. Adult patients with adrenal metastasis who were treated with adrenal cryoablation between May 2005 and October 2009 were eligible for this review. Twelve patients (undergoing 13 procedures) with single adrenal tumors were included in the analysis. For statistical analysis, hemodynamic data were averaged for the patient undergoing the procedure twice. Technical success, safety, and local control were analyzed according to standard criteria. Hemodynamic changes during the procedure were analyzed and compared with data from an unmatched cohort of patients who underwent kidney (not in the upper pole) cryoablation (Wilcoxon rank sum test). A further subanalysis of hemodynamic changes was performed on the basis of whether preprocedural a - or b -adrenergic blockade was used. ORIGINAL RESEARCH n VASCULAR AND INTERVENTIONAL RADIOLOGY 1 From Mayo Medical School (B.T.W.), Rochester, Minn; Departments of Radiology (T.D.A., D.A.N., M.R.C., J.W.C.), Anesthesiology (C.T.W.), Urology (B.C.L.), Endocrinology (P.C.C.), and Biostatistics (J.M.), Mayo Clinic, 200 First St SW, Rochester, MN Received April 9, 2010; revision requested June 21; fi nal revision received July 7; accepted July 27; fi nal version accepted August 2. Address correspondence to B.T.W. ( Welch.brian@mayo.edu ). q RSNA, 2010 Results: Conclusion: With adrenal cryoablation, local control was achieved following treatment in 11 (92%; 95% confidence interval: 65.1%, 99.6%) of 12 tumors. One patient with known adrenal insufficiency underwent conservative ablation and developed ipsilateral adrenal recurrence, which was retreated. Five patients developed hypertensive crisis during the final, active thaw phase of the cryoablation procedure, and one patient developed hypertensive crisis in the immediate postablation period. Patients undergoing adrenal cryoablation experienced a significant increase in systolic blood pressure ( P =.005), pulse pressure ( P =.02), and mean arterial pressure ( P =.01) when compared with the cohort of kidney cryoablation patients. Adrenal cryoablation patients who were not premedicated with an a -blocker ( n = 5) had a higher level of systolic blood pressure increase during the cryoablation procedure when compared with their counterparts who were premedicated ( n = 7) ( P =.034). Adrenal cryoablation is technically feasible with a high rate of local control. Patients premedicated with the a -blocker phenoxybenzamine appear to have a reduced risk of hypertensive crisis. q RSNA, 2010 Radiology: Volume 258: Number 1 January 2011 n radiology.rsna.org 301

2 Neoplasms of the adrenal gland occur in approximately 1% of the general population, with metastases comprising the most common malignant adrenal neoplasm ( 1 ). Lung cancer is the most common primary origin of adrenal metastasis, but renal cell carcinoma (RCC), melanoma, and gastrointestinal tumors also have a predilection for the adrenal gland ( 1 ). In selected patients with isolated metastatic disease of the adrenal gland, adrenalectomy has been associated with increased survival ( 2 5 ). Percutaneous ablation is evolving into an effective method of focal tumor treatment. In particular, radiofrequency (RF) ablation has been established as a safe and effective treatment for adrenal tumors ( 6 8 ). With RF ablation, pulses of RF waves are used to generate thermal injury and subsequent cell death, whereas with cryoablation, argon gas currently is used via the Joule- Thomson effect to create subfreezing temperatures and induction of cell lysis. An important advantage of cryoablation is the capability to allow visualization of treatment progression and tumor coverage with monitoring of the development and progression of a low-attenuation ice ball with computed tomographic (CT) imaging. Cryoablation has been effectively used to treat neoplasms of the liver, kidney, prostate, lung, and soft tissue ( 9 15 ). Cryoablation of the adrenal gland is a promising technique for percutaneous treatment of adrenal metastasis, with limited experience reported in the literature ( 5,16 ). Thus, our purpose Advances in Knowledge n Adrenal cryoablation patients who were not premedicated with an a -blocker had a higher level of systolic blood pressure increase during the cryoablation procedure compared with their counterparts who were premedicated ( P =.034). n Local control was achieved fol- lowing adrenal cryoablation in 11 (92%) of 12 tumors. was to assess safety, technical success, complications, and hemodynamic changes associated with the adrenal cryoablation procedure. Materials and Methods This retrospective review was approved by the institutional review board and was compliant with the Health Insurance Portability and Accountability Act. Although informed consent was obtained prior to each ablation procedure, consent specific for this review was waived by the institutional review board. The inclusion criterion was that the patients were adults with an adrenal metastasis who underwent percutaneous image-guided adrenal cryoablation between May 2005 and October Patients with metastatic adrenal tumors of up to 5 cm were selected to undergo cryoablation. Moreover, patients were screened for pheochromocytoma with urine or plasma metanephrine level analysis prior to consideration for treatment with cryoablation. Twelve patients (11 men, one woman; mean age, 70 years; range, years) with single adrenal tumors (total, 12 tumors) matched these criteria ( Table 1 ) and underwent a total of 13 cryoablation procedures; one patient underwent two procedures, including retreatment. In all cases, patients had imaging findings consistent with adrenal metastatic disease. Four of 12 patients underwent adrenal biopsy to achieve pathologic Implications for Patient Care n Cryoablation for the treatment of metastatic disease involving the adrenal gland can be performed safely and with high local control rates. n Patients with metastatic disease involving the adrenal gland who are undergoing ablation of the tumor should be premedicated with an a -blocker (10 60 mg oral phenoxybenzamine for days prior to ablation coupled with subsequent titration of a b -blocker). confirmation of metastatic disease. The remaining patients were suspected of having metastatic disease owing to positron emission tomographic findings positive for disease, new lesions noted on images, or distinct interval growth. The primary tumor in six of 12 patients was RCC ( Table 1 ). Other primary histologic findings included hepatocellular carcinoma, melanoma, squamous cell lung carcinoma, neuroendocrine large cell carcinoma of the lung, penile squamous cell carcinoma, and urothelial carcinoma. Seven of ten patients with available primary tumor pathologic findings had neoplasms of a high grade (grade 3 or 4) ( 17 ). Eight patients were seen by an endocrinologist prior to the procedure for discussion of the use of a - or b -adrenergic blockade. The decision to consult an endocrinologist was made by the referring physician. Initiation of such premedication (including medication choices and dosages) prior to cryoablation was left to the discretion of the individual endocrinologist. Five patients were receiving a - and b -blockers, two patients were re ceiving a -blockers alone, two patients were receiving b -blockers alone, and three patients received no a - or b -blockers ( Table 2 ). All procedures were performed with patients receiving a general anesthetic. Published online before print /radiol Radiology 2011; 258: Abbreviations: DBP = diastolic blood pressure MAP = mean arterial pressure PP = pulse pressure RCC = renal cell carcinoma RF = radiofrequency SBP = systolic blood pressure Author contributions: Guarantors of integrity of entire study, B.T.W., D.A.N.; study concepts/study design or data acquisition or data analysis/ interpretation, all authors; manuscript drafting or manuscript revision for important intellectual content, all authors; approval of final version of submitted manuscript, all authors; literature research, B.T.W., T.D.A., D.A.N., C.T.W., M.R.C., P.C.C.; clinical studies, B.T.W., T.D.A., D.A.N., M.R.C., P.C.C.; statistical analysis, B.T.W., P.C.C., J.N.M.; and manuscript editing, B.T.W., T.D.A., D.A.N., C.T.W., M.R.C., B.C.L., P.C.C., J.N.M. Potential conflicts of interest are listed at the end of this article. 302 radiology.rsna.org n Radiology: Volume 258: Number 1 January 2011

3 Table 1 Primary Characteristics for 12 Adrenal Cryoablation Patients Patient No./ Age (y)/sex Primary Location Grade Original Treatment Adrenal Location No. of Probes Used Adrenal Lesion Size (cm) * Follow-up (mo) 1/85/M RCC (clear cell) 2 Left partial nephrectomy Left /66/M Melanoma Unknown Surgery, chemotherapy Right /68/M Hepatocellular carcinoma 3 Right hepatectomy Left /63/M RCC 1 Right radical nephrectomy Left /67/M RCC 3 Right radical nephrectomy Left /65/M RCC 3 Right radical nephrectomy Left /64/M RCC 4 Right radical nephrectomy Right /71/F Squamous cell carcinoma of lung 3 Chemotherapy, radiation therapy Right /71/F Squamous cell carcinoma of lung Right /69/M RCC 2 Right radical nephrectomy Left /71/M Urothelial carcinoma 3 Radical cystectomy Left /70/M Penile squamous cell carcinoma 3 Partial penectomy Right /75/M Neuroendocrine large cell carcinoma of lung Unknown Chemotherapy Right * Anteroposterior dimension. Table 2 a - and b -Adrenergic Blockade and Intraprocedural Hemodynamics Patient No. a - or b-blocker Used * Consultation with Endocrinologist Intraprocedural Blood Pressure (mm Hg) Baseline Maximum 1 Metoprolol, 75 mg twice a day; long term per home regimen No 121/66 300/170 2 Labetalol, 200 mg twice a day for 4 days; labetalol, 400 mg on the morning of procedure Yes 118/61 240/125 3 Phenoxybenzamine, 40 mg daily for 7 days No 93/55 168/81 4 Phenoxybenzamine, 30 mg twice a day for 7 days; metoprolol, 75 mg daily; long term Yes 101/61 167/102 per home regimen 5 No a - or b-blocker used No 85/52 162/91 6 Phenoxybenzamine, 30 mg daily for 6 days; metoprolol, 50 mg on the night before and Yes 105/80 144/78 the morning of procedure 7 No a - or b-blocker used Yes 94/65 216/122 8 No a - or b-blocker used Yes 124/64 191/88 8 No a - or b-blocker used Yes 106/53 186/81 9 Phenoxybenzamine, 10 mg twice a day for 7 days Yes 98/60 136/84 10 Metoprolol, 50 mg daily; long term per home regimen No 104/59 218/ Phenoxybenzamine, 10 mg twice a day for 5 days; atenolol, 50 mg daily; long term Yes 90/61 157/84 per home regimen 12 Phenoxybenzamine, 10 mg twice a day for 7 days; metoprolol, 50 mg on the night before and the morning of procedure Yes 95/58 168/64 * Trade and manufacturers names for the drugs are as follows: metoprolol, NovaPlus, Irving, Tex; labetalol, Hospira, Lake Forest, Ill; phenoxybenzamine, WellSpring Pharmaceutical, Sarasota, Fla; and atenolol, AstraZeneca, Wilmington, Del. For patient 8 who underwent two procedures (one as retreatment), the average baseline intraprocedural blood pressure was 115/58.5 mm Hg, and the average maximum intraprocedural blood pressure was 188.5/84.5 mm Hg. Continuous radial arterial blood pressure monitoring was performed, with values pertaining to hemodynamics recorded. Direct, arterial blood pressure monitoring enabled prompt detection of a change in hemodynamics by the anesthesia care team. The same cryoablation system (Healthtronics/Endocare, Irvine, Calif) was used in all treatments. CT guidance was used to place the cryoprobes in the adrenal tumor. The total number of probes placed was Radiology: Volume 258: Number 1 January 2011 n radiology.rsna.org 303

4 Grade 2 clear cell RCC in an 85-year-old man who underwent partial left nephrectomy. (a) Transverse contrast-enhanced CT demonstrates a normal appearance to the left adrenal 1 year after surgery. (b) Transverse contrast-enhanced CT 2 years after surgery shows a new 2.8-cm left adrenal mass, consistent with RCC metastasis. (c) Unenhanced CT during ablation procedure demonstrates the ice ball encompassing the lesion 10 minutes into the ablation procedure. (d) Transverse contrast-enhanced CT 37 months after ablation reveals no evidence of residual tumor in the left adrenal. based on tumor size, with a goal to provide an ice ball that would completely encompass the tumor by 5 mm or more beyond the tumor margin. CT monitor ing was used during the procedure with an open 40-section CT system (Somatom Sensation; Siemens, Munich, Germany). Limited CT images without contrast material were obtained every 2 minutes during the freezing portions of the cycle to monitor the ice ball growth; the specific CT technique was governed by automated exposure control (typically, 120 kvp and approximately 240 ma). Each lesion received a single treatment cycle of freezing, thawing, and freezing again. Duration of the freezing was based on the growth of the ice ball relative to the tumor; the goal was to extend the ice ball 5 mm beyond the tumor margin during the freezing cycle. The first, passive thaw occurs when the temperature of the probe is held just below freezing by using intermittent pulses of argon gas. Following the ablation treatment, the probes were actively thawed by using helium gas and were withdrawn. Routine imaging with either contrast material enhanced CT or magnetic resonance (MR) imaging was performed within 24 hours of the cryoablation treatment to assess for potential complications (Figure ). Additional follow-up imaging with contrast-enhanced (Omnipaque; GE Healthcare, Milwaukee, Wis) CT or MR imaging was performed at 3 6-month intervals, as deemed appropriate by the primary clinician. The specific imaging protocol was defined by the radiologist responsible for the imaging but was typically tailored to the general malignancy diagnosis. Technical success was defined as coverage of the tumor by the ice ball during CT monitoring ( 18 ). If incomplete ablation occurred for any reason, this was deemed a technical failure, and the patient was considered for further treatment, including surgical resection. A retrospective review of blood pressure changes during the cryoablation procedure was performed. Two specific measurements were recorded for the purpose of this study: the patient s blood pressure immediately before placement of the cryoprobes and the maximum systolic blood pressure (SBP) and corresponding diastolic blood pressure (DBP) during the remainder of the procedure, including the immediate postablation period. An unmatched (unmatched for age, tumor size, and tumor location) cohort of 13 patients (nine men, four women; mean age, 71 years; range, years) who underwent percutaneous image-guided cryoablation of the kidney served as a control group (kidney cohort) for statistical analysis of these hemodynamic changes. Hemodynamic monitoring in these patients was performed by using an automatic blood pressure cuff, with recordings taken every minute. These patients were selected on the basis of similarity of tumor size (anteroposterior) relative to the tumor size in patients in the adrenal co hort (mean, 2.3 cm; range, cm); only cases in which ablation of the lower pole of the kidney was performed were used to avoid possible confounding owing to adrenal injury. A further subanalysis of blood pressure changes was performed on the basis of whether an a - or a b -blocker was administered; patients who were premedicated with an a -blocker ( n = 7) were compared with those who had received no a -blocker ( n = 5). One patient underwent two cryoablation procedures. This patient had known adrenal insufficiency at the time of the initial ablation treatment and was treated conservatively, with greater emphasis on adrenal preservation over tumor margins to preserve underlying adrenal function. To avoid biasing the hemodynamic data pool, the hemodynamic changes for the two procedures in this patient were averaged. 304 radiology.rsna.org n Radiology: Volume 258: Number 1 January 2011

5 Classification of hemodynamic changes during the cryoablation procedure was done in accordance with Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure version 7 guidelines. Specifically, patients were designated as having a hypertensive crisis if they had an increase of SBP to greater than 180 mm Hg or of DBP to greater than 120 mm Hg ( 19 ). Moreover, procedural complications were evaluated on the basis of accepted standardized criteria set forth in the Common Terminology Criteria for Adverse Events, version 3.0, guidelines ( 20 ). Routine clinical follow-up was maintained by the patient s primary clinician, as documented in our electronic medical record. Patients were also asked to send pertinent cross-sectional images obtained outside our facility to us for our review. Changes, relative to baseline values, in SBP, DBP, pulse pressure (PP), and mean arterial pressure (MAP) were calculated. SBP was continuously monitored via the radial arterial catheter. PP was calculated by using the following formula: PP = SBP 2 DBP. MAP was calculated by using the following formula: MAP = [(2 DBP)+SBP]/3. Comparison of these changes between the kidney cohort and those of the adrenal cohort and between patients with a -adrenergic blockade and patients with no a -adrenergic blockade were made by using the Wilcoxon rank sum test owing to the smaller sample size and the non-gaussian nature of the data. P values less than.05 were considered to indicate a significant difference. Statistical analysis was performed by using software (SAS version 9.0; SAS, Cary, NC). In light of the small sample size, the Blyth-Still-Casella procedure was used to generate a 95% confidence interval for local control achieved with cryoablation. Results Twelve patients with 12 adrenal tumors underwent 13 cryoablation procedures. Adrenal metastases ranged in size (anteroposterior) from 1.2 to 4.5 cm (mean, 2.7 cm). One patient with a 1.8-cm right adrenal metastasis developed ipsilateral adrenal recurrence of disease and was retreated with cryoablation 7 months after the original procedure ( Table 1 ). The number of probes used for the ablation procedure ranged from one to three, with a mean of 1.8. Overall, local control was achieved following the treatment of 11 (92%; 95% confidence interval: 65.1%, 99.6%) of 12 tumors. In none of the other patients was subsequent adrenal tumor treatment necessitated, and the mean follow-up time was 18 months (range, 3 55 months). Six (46%) of 13 cryoablation procedures were complication free. During six (46%) of the 13 cryoablation procedures in five patients, patients experienced hypertensive crisis, with the patient undergoing two procedures having hypertensive crisis during each procedure. More important, although an increase in blood pressure was seen during the initial passive thaw, five episodes of hypertensive crisis occurred during the final, active thaw cycle (with the patient undergoing two procedures experiencing one episode of hypertensive crisis during the active thaw and one episode during the immediate postablation time period in the recovery area). Each episode of hypertensive crisis was successfully managed by the anesthesia team with normalization of hemodynamic status. Five of six patients who experienced hypertensive crisis had received no a -blockers prior to the cryoablation procedure; the patient who underwent two procedures had received no a -blockers during either procedure ( Table 2 ). The sixth patient received dual a - and b -blockers, with labetalol as opposed to phenoxybenzamine, owing to close proximity to the procedure date (less than 5 7 days). None of the patients who received pretreatment with phenoxybenzamine experienced a hypertensive crisis during adrenal cryoablation. One (8%) additional procedure of 13 was complicated by a pleural effusion with delayed-onset pneumonia requiring a six-day hospitalization at an outside hospital. This complication was defined as a grade 2 complication because it was symptomatic but required less than two sessions of therapeutic thoracentesis, according to Common Terminology Criteria for Adverse Events, version 3.0 ( 20 ). There were no cardiac rhythm changes in any of the patients. Patients who underwent adrenal cryoablation experienced a significant increase in SBP ( P =.005), PP ( P =.02), and MAP ( P =.01) when they were compared with the cohort of patients who underwent kidney cryoablation ( Table 3 ). The adrenal cryoablation cohort also had an increase in DBP, but this difference was not significant ( P =.07). Adrenal cryoablation patients who were not premedicated with an a -blocker had a higher level of SBP increase during the cryoablation procedure when compared with their counterparts who were premedicated with an a -blocker ( P =.034) ( Table 4 ). Although changes in DBP, PP, and MAP were not significant, patients without a -blocker premedication had a relatively higher increase in these hemodynamic factors during the procedure compared with those with a -blocker premedication ( P =.07,.17,.06, respectively) ( Table 4 ). Discussion Improvements in technique and technology for percutaneous ablation of neoplastic lesions have resulted in an expanding frontier of potential roles in tumor treatment. This expansion has included treatment of adrenal tumors. Wood et al ( 7 ) have shown that RF ablation of adrenal neoplasms was effective, with complete ablation achieved in eight (67%) of 12 tumors of 5 cm or smaller. Mayo-Smith and Dupuy ( 8 ) successfully treated 11 of 13 adrenal tumors by using single-session RF ablation. To the best of our knowledge, only case reports describing adrenal tumor cryoablation exist ( 21,22 ). A noteworthy attribute of cryoablation when compared with other methods of percutaneous ablation is the capability for monitoring the ablation procedure with either CT or MR imaging. For our study, limited nonenhanced CT imaging was used to visualize ice ball progression. The capability to accurately monitor cryoablation progression may diminish the likelihood of collateral Radiology: Volume 258: Number 1 January 2011 n radiology.rsna.org 305

6 Table 3 Comparison of Change in Hemodynamic Status during Adrenal and Kidney Cryoablation Variable Kidney Cohort ( n = 13) * Adrenal Cohort ( n = 12) * P Value Baseline SBP 117 (100, 143) 100 (85, 121)... Baseline DBP 66 (50, 91) 61 (52, 80)... Maximum SBP 155 (145, 209) 168 (136, 300)... Maximum DBP 82 (55, 115) 88 (64, 170)... Baseline PP 51 (26, 76) 38 (25, 57)... Maximum PP 82 (30, 121) 91 (52, 130)... Baseline MAP 83 (66, 99) 74 (63, 88)... Maximum MAP 109 (86, 128) 117 (99, 213)... D SBP 42 (12, 78) 74 (38, 179).005 D DBP 18 ( 217, 54) 33 ( 22, 104).07 D PP 29 ( 214, 56) 48 (14, 75).02 D MAP 27 ( 27, 50) 46 (12, 129).01 * Numbers are medians, and numbers in parentheses are minimum and maximum values. Table 4 Comparison of Hemodynamic Change in Adrenal Cryoablation Patients with and without a -Blocker Premedication Variable With a -Blocker Premedication ( n = 7) * Without a -Blocker Premedication ( n = 5) * P Value D SBP 67 (38, 122) 114 (74, 179).034 D DBP 24 ( ) 45 (26, 104).07 D PP 44 (14, 67) 65 (38, 75).17 D MAP 38 (12, 83) 68 (42, 129).06 * Numbers are medians, and numbers in parentheses are minimum and maximum values. thermal injury and adjacent organ damage. This contrasts with RF ablation, where the ablation procedure can be monitored with MR imaging, although monitoring with this modality can be technically challenging. As a result, most centers use CT or ultrasonography for electrode placement and use experience to predict tissue coverage, which can be difficult. Our case series is the first, to our knowledge, to include analysis of hemodynamic change during percutaneous adrenal cryoablation. Our results illustrate a significant increase in change in SBP, PP, and MAP in patients undergoing adrenal cryoablation when compared with their kidney cryoablation counterparts. Given the catecholamine-secreting nature of the adrenal gland, these results are not unexpected. Six patients in our study experienced hypertensive crisis during the cryoablation procedure, a complication observed by others ( 21 ). Five of the six cases of hypertensive crisis occurred during the final, active thaw cycle, with the remaining episode occurring during the immediate postablation period. During the first, passive thaw, mild blood pressure changes may be observed, and other researchers ( 21 ) have noted episodes of hypertensive crisis during this period. However, during the final, active thaw, helium gas is passed within the cryoprobe, resulting in increased temperatures to thaw the tumor to allow probe removal. With active thawing of the treated tumor, we hypothesize that there is greater release of catecholamines from lysed cells. Increased vigilance and coordination with the anesthesia team is important during this time of the procedure. We use direct, arterial blood pressure monitoring in all adrenal ablation procedures. Direct, arterial blood pressure monitoring enables prompt detection of hemodynamic changes. Although the method of hemodynamic monitoring may differ on the basis of institutional preference, close communication with the anesthesia care team during adrenal cryoablation is vital to ensure patient safety. Our analysis of the hemodynamic changes in patients with metastatic disease involving the adrenal gland who were premedicated with a -blockers suggests that these patients should be pharmacologically pretreated in a way similar to that for the pretreatment of patients undergoing adrenalectomy for pheochromocytoma. More specifically, pretreatment with 10 to 60 mg of oral phenoxybenzamine for days prior to ablation coupled with subsequent titration of b -blocker is suggested. a -Blockers are used be cause of their capability to mitigate or prevent catecholaminemediated vasoconstriction during or following tumor manipulation. b -Blockers also have a role in the treatment of these patients; however, it deserves mention that b -blockers are not administered independent of a -adrenergic blockade because the former decrease myocardial contractility, which in the face of increased systemic vascular resistance may result in heart failure. Administration of both classes of medications should be guided by one with expertise in such medical treatment (eg, an endocrinologist). Should breakthrough hypertension occur during the procedure, management of the acute crisis necessitates close coordination between the anesthesia and radiology care teams, with diligent monitoring, as well as aggressive management of the patient s hemodynamic status ( 22 ). These recommendations may also extend to ablation of lesions in the posterior aspect of the right lobe of the liver owing to the risk of adjacent right adrenal injury and subsequent hypertensive crisis ( 23 ). Cryoablation for the treatment of metastatic disease involving the adrenal gland can be performed safely and with high local control rates. However, cryoablation is not without limitations. Primarily, the cryoablation technique precludes the capability to obtain tissue 306 radiology.rsna.org n Radiology: Volume 258: Number 1 January 2011

7 margins for pathologic analysis. Therefore, treatment success is ultimately determined by using serial follow-up imaging without pathologic confirmation. Although complication rates are low with the use of cryoablation, hemorrhage and collateral tissue injury are the most common risks associated with this treatment ( 24 ). There were also several limitations to this specific study. The primary study limitation was our small sample size ( n = 12). Another limitation of the study was possible bias in the selection of patients for consultation with an endocrinologist prior to ablation. Patients in this study were seen by an endocrinologist at the discretion of the referring physician. Although our mean follow-up period was 18 months, further investigation with long-term follow-up is necessary to show durability of treatment. Disclosures of Potential Conflicts of Interest: B.T.W. No potential conflicts of interest to disclose. T.D.A. No potential conflicts of interest to disclose. D.A.N. No potential conflicts of interest to disclose. C.T.W. No potential conflicts of interest to disclose. M.R.C. Financial activities related to the present article: none to disclose. Financial activities not related to the present article: received funding for a separate research study from Endocare and research grants from Siemens Medical Systems. Other relationships: none to disclose. B.C.L. No potential conflicts of interest to disclose. P.C.C. No potential conflicts of interest to disclose. J.N.M. No potential conflicts of interest to disclose. J.W.C. No potential conflicts of interest to disclose. References 1. Beland MD, Mayo-Smith WW. Ablation of adrenal neoplasms. Abdom Imaging 2009 ; 34 ( 5 ): Paul CA, Virgo KS, Wade TP, Audisio RA, Johnson FE. Adrenalectomy for isolated adrenal metastases from non-adrenal cancer. Int J Oncol 2000 ; 17 ( 1 ): Lo CY, van Heerden JA, Soreide JA, et al. Adrenalectomy for metastatic disease to the adrenal glands. Br J Surg 1996 ; 83 ( 4 ): Kim SH, Brennan MF, Russo P, Burt ME, Coit DG. The role of surgery in the treatment of clinically isolated adrenal metastasis. Cancer 1998 ; 82 ( 2 ): Uberoi J, Munver R. Surgical management of metastases to the adrenal gland: open, laparoscopic, and ablative approaches. Curr Urol Rep 2009 ; 10 ( 1 ): Nahum Goldberg S, Dupuy DE. Image-guided radiofrequency tumor ablation: challenges and opportunities. I. J Vasc Interv Radiol 2001 ; 12 ( 9 ): Wood BJ, Abraham J, Hvizda JL, Alexander HR, Fojo T. Radiofrequency ablation of adrenal tumors and adrenocortical carcinoma metastases. Cancer 2003 ; 97 ( 3 ): Mayo-Smith WW, Dupuy DE. Adrenal neoplasms: CT-guided radiofrequency ablation preliminary results. Radiology 2004 ; 231 ( 1 ): Onik G. Image-guided prostate cryosurgery: state of the art. Cancer Contr 2001 ; 8 ( 6 ): Sewell PE Jr, Jackson MS, Dhillon GS. Percutaneous MRI guided cryosurgery of bone tumors [abstr]. Radiology 2002 ; 225 ( P ): Shingleton WB, Sewell PE Jr. Percutaneous renal tumor cryoablation with magnetic resonance imaging guidance. J Urol 2001 ; 165 ( 3 ): Sewell PE, Howard JC, Shingleton WB, Harrison RB. Interventional magnetic resonance image-guided percutaneous cryoablation of renal tumors. South Med J 2003 ; 96 ( 7 ): Beland MD, Dupuy DE, Mayo-Smith WW. Percutaneous cryoablation of symptomatic extraabdominal metastatic disease: preliminary results. AJR Am J Roentgenol 2005 ; 184 ( 3 ): Wang H, Littrup PJ, Duan Y, Zhang Y, Feng H, Nie Z. Thoracic masses treated with percutaneous cryotherapy: initial experience with more than 200 procedures. Radiology 2005 ; 235 ( 1 ): Shafir M, Shapiro R, Sung M, Warner R, Sicular A, Klipfel A. Cryoablation of unresectable malignant liver tumors. Am J Surg 1996 ; 171 ( 1 ): Schulsinger DA, Sosa RE, Perlmutter AA, Vaughan ED Jr. Acute and chronic interstitial cryotherapy of the adrenal gland as a treatment modality. J Endourol 1999 ; 13 ( 4 ): American Joint Committee on Cancer. AJCC Cancer Staging Manual. 6th ed. New York, NY : Springer, Goldberg SN, Grassi CJ, Cardella JF, et al. Image-guided tumor ablation: standardization of terminology and reporting criteria. J Vasc Interv Radiol 2005 ; 16 ( 6 ): Varon J. Treatment of acute severe hypertension: current and newer agents. Drugs 2008 ; 68 ( 3 ): Trotti A, Colevas A, Setser A, et al. CTCAE v3.0: development of a comprehensive grading system for the adverse effects of cancer treatment. Semin Radiat Oncol 2003 ; 13 ( 3 ): Tsoumakidou G, Buy X, Zickler P, Zupan M, Douchet MP, Gangi A. Life-threatening complication during percutaneous ablation of adrenal gland metastasis: Takotsubo syndrome. Cardiovasc Intervent Radiol 2010 ; 33 ( 3 ): Atwell TD, Wass CT, Charboneau JW, Callstrom MR, Farrell MA, Sengupta S. Malignant hypertension during cryoablation of an adrenal gland tumor. J Vasc Interv Radiol 2006 ; 17 ( 3 ): Onik G, Onik C, Medary I, et al. Life-threatening hypertensive crises in two patients undergoing hepatic radiofrequency ablation. AJR Am J Roentgenol 2003 ; 181 ( 2 ): Seifert JK, Morris DL. World survey on the complications of hepatic and prostate cryotherapy. World J Surg 1999 ; 23 ( 2 ): ; discussion Radiology: Volume 258: Number 1 January 2011 n radiology.rsna.org 307

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